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Design and Methods of the Chronic Kidney Disease in Children (CKiD) Prospective Cohort Study 1. Susan L. Furth * , 2. Stephen R. Cole , 3. Marva Moxey-Mims § , 4. Frederick Kaskel , 5. Robert Mak , 6. George Schwartz ** , 7. Craig Wong †† , 8. Alvaro Muñoz , 9. Bradley A. Warady ‡‡ + Author Affiliations 1. * Department of Pediatrics, Johns Hopkins Children’s Center, Baltimore, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, and The Welch Center for Prevention, Epidemiology & Clinical Research, Baltimore, Maryland; § National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; Montefiore Medical Center, Bronx, New York; Oregon Health & Science University, Portland, Oregon; ** University of Rochester, Rochester, New York; †† University of New Mexico, Albuquerque, New Mexico; and ‡‡ Children’s Mercy Hospital, Kansas City, Missouri 1. Address correspondence to: Dr. Susan L. Furth, The Johns Hopkins Medical Institutions, Departments of Pediatrics and Epidemiology, The Welch Center for Prevention, Epidemiology & Clinical Research, 2024 E. Monument Street, Baltimore MD, 21287. Phone: 410- 502-7964; Fax: 410-614-3680; E-mail: [email protected] Next Section Abstract An estimated 650,000 Americans will have ESRD by 2010. Young adults with kidney failure often develop progressive chronic kidney disease (CKD) in childhood and adolescence. The Chronic Kidney Disease in Children (CKiD) prospective cohort study of 540 children aged 1 to 16 yr and have estimated GFR between 30 and 75 ml/min per 1.73 m 2 was established to identify novel risk factors for CKD progression; the impact of kidney function decline on growth, cognition, and behavior; and the evolution of cardiovascular disease risk factors. Annually, a physical examination documenting height, weight, Tanner stage, and standardized BP is conducted, and cognitive function, quality of life, nutritional, and behavioral questionnaires are completed by the parent or the child. Samples of serum, plasma, urine, hair, and fingernail clippings are stored in biosamples and genetics repositories. GFR is measured

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Page 1: Renal Cohort

Design and Methods of the Chronic Kidney Disease in Children (CKiD) Prospective Cohort Study

1. Susan L. Furth *  † ‡ , 2. Stephen R. Cole  † , 3. Marva Moxey-Mims  § ,4. Frederick Kaskel  ‖ , 5. Robert Mak  ¶ , 6. George Schwartz ** , 7. Craig Wong  †† ,8. Alvaro Muñoz  † , 9. Bradley A. Warady  ‡‡

+Author Affiliations1. *Department of Pediatrics, Johns Hopkins Children’s Center,

Baltimore, †Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, and ‡The Welch Center for Prevention, Epidemiology & Clinical Research, Baltimore, Maryland; §National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland; ‖Montefiore Medical Center, Bronx, New York; ¶Oregon Health & Science University, Portland, Oregon; **University of Rochester, Rochester, New York; ††University of New Mexico, Albuquerque, New Mexico; and ‡‡Children’s Mercy Hospital, Kansas City, Missouri

1. Address correspondence to:Dr. Susan L. Furth, The Johns Hopkins Medical Institutions, Departments of Pediatrics and Epidemiology, The Welch Center for Prevention, Epidemiology & Clinical Research, 2024 E. Monument Street, Baltimore MD, 21287. Phone: 410-502-7964; Fax: 410-614-3680; E-mail: [email protected] Next Section

Abstract

An estimated 650,000 Americans will have ESRD by 2010. Young adults with kidney failure often develop progressive chronic kidney disease (CKD) in childhood and adolescence. The Chronic Kidney Disease in Children (CKiD) prospective cohort study of 540 children aged 1 to 16 yr and have estimated GFR between 30 and 75 ml/min per 1.73 m2 was established to identify novel risk factors for CKD progression; the impact of kidney function decline on growth, cognition, and behavior; and the evolution of cardiovascular disease risk factors. Annually, a physical examination documenting height, weight, Tanner stage, and standardized BP is conducted, and cognitive function, quality of life, nutritional, and behavioral questionnaires are completed by the parent or the child. Samples of serum, plasma, urine, hair, and fingernail clippings are stored in biosamples and genetics repositories. GFR is measured annually for 2 yr, then every other year using iohexol, HPLC creatinine, and cystatin C. Using age, gender, and serial measurements of Tanner stage, height, and creatinine, compared with iohexol GFR, a formula to estimate GFR that will improve on traditional pediatric GFR estimating equations when applied longitudinally is expected to be developed. Every other year, echocardiography and ambulatory BP monitoring will assess risk for cardiovascular disease. The primary outcome is the rate of decline of GFR. The CKiD study will be the largest North American multicenter study of pediatric CKD.It has been estimated that 650,000 Americans will have ESRD by 2010 with an annual cost of $28 billion per year (1,2). Although alarming increases in ESRD rates have occurred in older Americans, young adults with ESRD bear a sizable burden of the disease. For example,

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in 2001, 37% of prevalent US transplant patients were between 20 and 44 yr of age (1). In addition, many of the 12,753 young adults who presented with kidney failure (incident patients with ESRD) in 2001 likely developed early stages of chronic kidney disease (CKD) in childhood (1). Identification of modifiable risk factors to slow progression of CKD in children will aid in decreasing the burden of CKD and may yield further insights into risk factors for progression in adults before the onset of multiple comorbidities (3).CKD in children carries a significant impact. The mortality that is associated with ESRD in children who receive dialysis is estimated to be at least 30 times higher than that in the general pediatric population (4). Unlike adults, who have completed their physiologic and intellectual maturation, children are in formative stages of development and therefore are particularly vulnerable to the adverse effects of CKD. Early detection and aggressive management have the potential to improve outcomes in young patients with CKD. Few sizable prospective studies of CKD in children have been performed (5,6), and relatively little is known about the natural history of early stages of CKD in this population.With funding from the National Institute of Diabetes and Digestive and Kidney Diseases, in collaboration with the National Institute of Neurologic Disorders and Stroke, the National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute, we have established a prospective cohort study of children with CKD, called the Chronic Kidney Disease in Children (CKiD) study. The specific aims of the CKiD study are to (1) identify novel and traditional risk factors for the progression of CKD; (2) characterize the impact of a decline in kidney function on neurodevelopment, cognitive abilities, and behavior; (3) identify the prevalence and the evolution of cardiovascular (CV) disease risk factors in children with CKD; and (4) examine the effects of declining GFR on growth and assess the consequences of growth failure on morbidity in children with CKD.Previous Section Next Section

Materials and Methods

Study OrganizationThe CKiD study consists of two clinical coordinating centers in Baltimore, MD, and Kansas City, MO, which include 57 clinical sites (locations and principal investigators are listed in the Appendix); a data coordinating center in Baltimore, MD; a central laboratory in Rochester, NY; a laboratory for cystatin C (Kansas City, MO); central reading centers for echocardiograms and carotid intima-media thickness (Cincinnati, OH), magnetic resonance imaging (MRI; Bronx, NY), ambulatory BP monitoring (ABPM; Houston, TX), and neurocognitive testing (Chapel Hill, NC); and central repositories for biologic (Rockville, MD) and genetic material (New Brunswick, NJ). A study web site for CKiD is located athttp://www.statepi.jhsph.edu/ckid. An External Advisory Committee meets annually to evaluate study progress, and the Steering Committee has semimonthly conference calls, including review of any adverse events related to study measurements (see Figure 1 for study organization chart).

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Figure 1.

Chronic Kidney Disease in Children (CKiD) study organization.

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Study PopulationThe CKiD study is a prospective, observational cohort of 540 children who have CKD and are enrolled during a 24-mo period. Inclusion and exclusion criteria are presented in Table 1. For eligibility, GFR is estimated by the Schwartz formula (7) on the basis of height and two measurements of serum creatinine obtained within 18 mo before enrollment.

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Table 1.Inclusion and exclusion criteriaa

Table 2 describes the expected number of children in each stratum of age and estimated GFR (eGFR). The expected age distribution is based on data from the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) (8) registry and surveys of participating sites. The lower age limit of 1 yr was chosen to facilitate testing for CKD progression, as well as CV and neurocognitive measurements. The upper age limit of 16 yr was chosen to optimize follow-up, because 16-yr-old participants likely would remain under the care of the enrolling pediatric nephrology center for 2 to 5 yr.

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Table 2.

Expected number of children by age and eGFR categories

On the basis of surveys of the participating sites and NAPRTCS data, we anticipate that 40% of the cohort will be female, 62% will be white, 18% will be black, 4% will be Asian or Pacific Islander, 2% will be Native American, and 14% will be other (8). To ensure heterogeneity in the racial/ethnic distribution, the CKiD study will limit enrollment of non-Hispanic white participants to no more than 65% of the cohort.Multicenter Study CoordinationTo facilitate standardized data collection with a large number of active clinical sites and a complex study design with age- and gender-dependent measurements (e.g., ABPM cuff-size, intelligence tests, Tanner stage), we use interactive web-based visit schedules. These interactive visit schedules detail the questionnaires, examinations, and biologic samples that are required for a given child at a given study visit. In addition, training DVDs detailing study procedures are sent to study coordinators, and training meetings are held annually.Study Follow-UpParticipants will be scheduled to return between 3 and 6 mo after study entry and on the anniversary of study enrollment thereafter. Participants will cease study visits after documented initiation of renal replacement therapy but will continue to be followed for clinical events and mortality by telephone contacts. Children with a high probability for ESRD (initiation of dialysis or transplantation) within the calendar year after a study visit ( i.e., GFR <15 ml/min per 1.73 m2 or stage 5 CKD) will have their subsequent study visit accelerated to within 3 mo of the documentation of GFR <15 ml/min per 1.73 m2 to capture data before onset of ESRD and will have telephone follow-up every 6 mo to document the date of initiation of renal replacement therapy.Table 3 depicts information to be obtained at baseline (i.e., follow-up month 0) and at each subsequent study visit. Tests are to be conducted on all cohort members, except when specifically targeted to a subcohort as noted in Table 3. Annually, study investigators conduct a physical examination and collect biologic specimens, and clinical site personnel assist the parent and the child to complete a set of questionnaires. For future studies, CKiD stores samples of serum, plasma, and urine as well as hair and fingernail clippings in a

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biosamples repository. In addition, to empower the study with a virtually inexhaustible supply of DNA, CKiD has requested that the National Institute of Diabetes and Digestive and Kidney Disease genetics repository create lymphocyte cell lines based on a sample of whole blood taken at the 6-mo visit. From annual blood and urine collection, we obtain centrally determined HPLC serum creatinine, renal panel, urine creatinine and protein, and local complete blood count and pregnancy tests.

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Table 3.Study measurements by visita

The physical examination consists of height or length, weight, head (age < 3 yr) and mid-upper arm circumferences, Tanner stage, edema classification, clinical BP, and resting pulse measured at each study visit. Tanner staging is standardized at annual training meetings, and medical illustrations of male and female Tanner stages are included on the study forms. The collection of annual questionnaires elicits information from the parent and the child about medical history, medication use, symptoms, quality of life, dietary intake, and environmental exposures (e.g., smoking, alcohol). Medication use includes prescription and over-the-counter medicines, dietary supplements, nutritional aids, and alternative medicines. Quality of life is measured with the parent and child versions of the Pediatrics Quality of Life Scale, a 23-item generic health status instrument that assesses five domains of health (Physical Functioning, Emotional Functioning, Psychosocial Functioning, Social Functioning, and School Functioning) in children and adolescents ages 2 yr and older (9,10). To assess physical activity, smoking, and alcohol and drug use in participants who are 12 yr old and older, questions from the 2005 Youth Risk Behavior Survey will be used (11,12).Three-day diet records and a child version of the Willett food frequency questionnaire (13) will be obtained on a yearly basis beginning at the second visit at 3 to 6 months (V1b). Children and parents are instructed on how to complete a consecutive 3-d 24-h recall food diary by study coordinators who have undergone training to standardize instructions.Clinical BP is measured three times at one sitting during the study visit, and the mean of the systolic and diastolic BP will be used. Hypertension will be defined as outlined in “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High BP in Children and Adolescents” (14). Other CV measurements, including echocardiography, ABPM (SpaceLabs 90217 device, Issaquah, WA), and carotid artery intima-media thickness, will be taken at the same visits as the iohexol GFR beginning in month 12. A battery of neurocognitive tests (Table 4) and measures of nutrition and bone health (e.g., intact parathyroid hormone) will be taken at the 3- to 6-mo follow-up visit and then in alternate years between iohexol-based GFR measurements. The parathyroid hormone assay that will be used is the Elecsys System 2010 (Roche Diagnostics, Mannheim, Germany), a one-step sandwich electrochemiluminescence immunoassay that is based on the streptavidin-biotin technology (15).

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Table 4.

CKiD neurocognitive battery by age

Measurement of GFRGFR will be measured at baseline, 12 mo, and biannually thereafter. GFR measurements will be based on blood disappearance curves with four time points at 10, 30, 120, and 300 min after infusion of 5 ml of iohexol (Omnipaque; GE Healthcare [formerly Amersham Health], Princeton, NJ). The timing of these four points was determined on the basis of pilot data (16).

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Concurrent with the iohexol-based measurement of GFR will be a cystatin C–based GFR measurement.Primary Outcomes

The primary outcome is the rate of decline of the biomarker GFR, which is measured repeatedly over time in cohort participants. Specifically, iohexol-based GFR will be measured every 2 yr, and Schwartz-based GFR will be assessed every year. A secondary outcome is the time to ESRD, defined by transplantation, dialysis, or a 50% decrease in GFR.

Statistical AnalysesThe repeated assessment of growth and development (e.g., physical measures of height, weight, and Tanner staging), cognitive and behavioral function, and health-related quality of life will allow us to assess the trajectories of these measures in children with stable kidney function and in those with declining kidney function in this cohort. The prospective nature of the cohort design will allow us to analyze properly the effect of the exposure (i.e., decline in GFR) on growth rates, sexual development, gain in cognitive and developmental function,etc. This will allow the identification of the effect of progressive kidney disease on slowing growth and development trajectories in children with CKD.Previous Section Next Section

Results

Longitudinal Data Analysis of Biomarkers

The longitudinal data analysis methods described in this section apply with equal force to the analysis of the rate of decline in kidney function as measured by GFR, to the level and rate of changes in standardized neurocognitive function, to the level and rates of change of BP (obtained either by ABPM or in the clinical setting) and fasting lipids, and to the level and rates of growth as measured by changes in height or weight. For analyses that examine risk factors for decline in GFR, the outcome is continuous and may be analyzed as measured, or transformed to the log scale.

An important issue of longitudinal data is the intrinsic dependence of the observations measured over time within individuals (17–19). One approach to handle this dependence is to use generalized estimating equations (20). Alternatively, mixed-effects approaches (21) model the correlation of the repeated observations that are obtained over time for each individual. A key feature of such methods for longitudinal data is the ability to incorporate incomplete and unbalanced data (22). Classical methods of longitudinal analyses that weight individuals according to the number of data points contributed over time can be misleading. In particular, if we censor patients who progress quickly and proceed rapidly to ESRD, then it is possible that those who contribute the most data points would be those who decline the least, and, in turn, fast progressors may be underrepresented. Missing data methods may be tailored to account for such informative censoring (23,24).Analysis of Time-to-Event DataIn the CKiD study, some time-to-event outcomes of potential interest are (1) stage 5 CKD (ESRD), (2) initiation of renal replacement therapy with dialysis or transplant, (3) a prespecified reduction (e.g., 50%) in GFR, and (4) incident hypertension. To study the natural history of CKD rather than anchor the analysis time scale as zero at the date of enrollment, we will anchor the time scale using birth or date of diagnosis of CKD obtained from medical records. Although children may be enrolled during roughly the same calendar period, construction of risk sets would account explicitly for the time since birth (i.e., age) or CKD diagnosis. Statistical methods to handle late entries will be used (25,26). Semiparametric survival methods, such as Cox proportional hazards regression, will be used to compare groups. However, parametric survival methods (27–29) will be used to provide clinical insight about the underlying disease process.

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For a cohort of children with CKD, time to transplantation and time to dialysis may act as competing risks. Common methods for handling competing risks are to (1) construct a combined end point (e.g., ESRD), (2) censor one type of risk while modeling the second type of risk, or (3) fit an explicit model for the competing risks. Although some key analyses will use a combined ESRD end point (option 1), use of competing risk models (option 3) likely will yield insight that is not gleaned from the analysis of the combined end point (30,31). For example, race may have differing effects on the time to transplantation and time to dialysis.Analytic Methods of Nested StudiesIt is anticipated that many hypotheses will involve highly expensive or time-consuming laboratory assays, such that it will not be possible to investigate these hypotheses in the full cohort. In such cases, it will be necessary to either (1) identify case patients and match them to control subjects on the basis of specific characteristics to perform nested case-control analysis or (2) select a subcohort in which to perform a case-cohort analysis (32). An example of a nested case-control study in CKiD would assess a novel biomarker for CKD progression among all case patients who develop ESRD with biosamples that previously were obtained in this cohort compared with a set of age- and gender-matched children who are free of ESRD. The nested design will allow efficient estimation of the association between the novel biomarker and development of ESRD by requiring the biomarker to be measured only in the case patients and a subset of, rather than all, control subjects.Statistical Power

The primary scientific goal of the study is to determine risk factors for rapid decline of GFR. Combining the measured GFR with the eGFR on the basis of an internally derived formula will result in a database with yearly GFR measurements. Assuming a uniform enrollment rate over the course of 24 mo, we will expect to have 270 children with four visits and 270 with three visits. We assume 10, 5, and 5% will exit follow-up before visits 2, 3, and 4, respectively, as a result of dropout and incident ESRD.

The slope of GFR decline in a group with a particular risk factor, for example hypertension (the exposed group; i.e. Δ1), will be compared with the slope of GFR decline in the unexposed group without hypertension, for example (i.e., Δ0). This ratio Δ1/Δ0 is the primary parameter for which the study is powered. Therefore, the primary hypothesis is whether Δ1/Δ0 = 1 (i.e., there is no risk for an accelerated decline associated with a putative exposure). We present statistical power curves for Δ1/Δ0 to be between 1.1 and 1.5 (i.e., an increase in the rate of decline as a result of the exposure from 10 to 50%), with a two-sided significance level of 5% (Figure 2). We assume that the SD of the baseline GFR is 12 ml/min per 1.73 m2 on the basis of data from the Modification of Diet in Renal Disease (MDRD) and the African American Study of Kidney Disease (AASK). An overall rate of decline of 5 ml/min per 1.73 m2 per year was assumed on the basis of NAPRTCS data (8). The three power curves in Figure 2 depict 20, 30, and 40% of the cohort being exposed. For a risk factor to which 40% are exposed, the study will have 80% power to detect an increase of 24% among the exposed (i.e., ratio of slopes = 1.24) when the overall rate of decline is 5 ml/min per 1.73 m2 per year.

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Figure 2.Statistical power for decline in GFR at 5% two-sided significance level with N = 540 and overall rate of GFR decline of 5 ml/min per 1.73 m2 per year.

Alternative analytical methods will use the time to event, in which the event may be ESRD. Table 5 shows the rate ratios that will be detectable with 80% statistical power at a 5% two-sided significance level according to three possible rates of progression per 100 person-years among the unexposed—3, 6, and 9 per 100 person-years—and by three levels of the prevalence of exposures of interest: 20, 30, and 40%. The total number of person-years will be 1350 (270 × 3 + 270 × 2), and allowing for an attrition of 20%, we use 1080 person-years in these power calculations. Specifically, reading from the center of Table 5, if the incidence is 6 per 100 person-years among the unexposed and 30% are exposed, then we will have 80% power to detect a rate ratio of approximately 1.9. However, if the event were to be defined, as in the AASK study (33), as (1) ESRD, (2) ≥50% decline in GFR, or (3) decline of at least 25 ml/min per 1.73 m2, then a rate of 9 per 100 person-years among the unexposed may be more appropriate and greater statistical power will result under such a composite end point.

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Table 5.Detectable rate ratios for ESRD with 80% statistical power at 5% two-sided significance level (N = 540)

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Appendix: CKiD Investigators by Clinical Site

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Discussion

CKD is a growing problem in the United States. Previous longitudinal studies of renal disease progression in adults (33,34) have suggested that the annual rate of decline in GFR in patients with CKD is approximately 3 to 5 ml/min per 1.73 m2. Therefore, many young adults who present with ESRD likely developed early stages of CKD in childhood or adolescence. In addition, CKD and its metabolic derangements substantially affect the well-being of children. The CKiD study will focus on risk factors for CKD progression. The study will obtain longitudinal data on 540 children who are aged 1 to 16 yr at study entry and have mildly to moderately impaired kidney function to determine the heterogeneity of rates of decline of renal function.The CKiD study has several design elements that are unique. Kidney function will be measured by blood clearance of iohexol annually for the first 2 yr and then every other year. The first two iohexol-based GFR measurements will provide a precise baseline value from which to assess decline in biannual iohexol-based GFR measurements. Because it forgoes the intrinsic variability and limitations of urinary clearances of inulin, iothalamate, and indirect measures of kidney function that are based on serum creatinine, the use of iohexol

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GFR measurement, as proposed in CKiD, has the potential to become the standard for a precise measurement of kidney function in large population studies (35).Furthermore, every year, we have the standard creatinine-based GFR estimates that allow for developing equations between iohexol- and creatinine-based GFR measurements. Through comparison with iohexol GFR measurement, the CKiD cohort study will provide a unique opportunity to improve on the current limitations of creatinine-based estimates of GFR in longitudinal follow-up of children with increasing muscle mass as a result of growth and puberty. Currently, creatinine-based estimates of GFR using the Schwartz formula use a different coefficient for pubertal boys; however, this alternative coefficient frequently is applied at a chronologic age cutoff, rather than more specifically associated with pubertal development and muscle mass. Delayed puberty, which is common in adolescents with CKD, may result in striking differences in eGFR depending on which Schwartz coefficient is applied. With the incorporation of age, gender, Tanner staging, height, and creatinine, compared with iohexol GFR in the CKiD study, we expect to find a continuous formula to estimate GFR from a combination of these parameters. Such an equation will be the essential means to complete the iohexol-based GFR data every year. For such purposes, we apply standard statistical procedures of imputation of missing data. Our design of collecting data on all participants every other year is stronger than alternative designs of selecting subsets of the cohort to be measured every year.

There are a number of unique challenges in conducting a multicenter cohort study of children. In contrast to studies of adults, one must obtain consent from parents as proxies for their children, as well as obtain the participating child’s assent. Obtaining consent for banking biologic and genetic materials from children and their parents is complex; for these specimens to remain in the repository, we may have to obtain consent for participation from children and adolescents when they turn 18 yr old.

In children, few large prospective cohort studies have addressed risk factors for CKD progression. High serum cholesterol (5), hyperlipidemia (36–38), hypertension (39), proteinuria (40), and race and ethnicity (41) each have been associated with CKD progression. This cohort study, with standardized prospective measurements and precise measures of GFR, will allow refined assessment of the risk that is associated with these clinical findings in children.The effects of CKD on neurodevelopment and cognitive function of children remain largely unknown, but age of CKD onset (42,43), duration of kidney failure (44,45), hypertension (46), anemia (47–50), and depression (51–53) have been associated with impairments in cognition and neurodevelopment. Furthermore, systematic assessment of nutritional status by measurement of growth parameters (height, weight, mid-upper arm circumference, pubertal development, and nutritional intake via 3 d diet history) and food frequency questionnaire will be collected to define further the influence of CKD on these parameters and the influence of these parameters on cognition and development.A key strength of the CKiD study is the measurement of GFR in the entire cohort. Currently, the best clinical estimate of GFR used in children is the Schwartz formula. However, studies that describe the precision of the Schwartz formula show that only approximately 75% of estimates are within 30% of the GFR measured by inulin clearance (54). Formulas such as the Cockcroft-Gault equation (55) and the more recent MDRD equation (56), which are used to estimate GFR in adults, do not generalize to children (57). The study intends to develop a novel estimating equation for GFR in children.

The proposed infrastructure for the CKiD study can serve as a platform for ancillary research grants and career development awards to enhance the scientific output of the study. Serum, plasma, and urine will be collected so that future ancillary studies potentially can examine the role of cytokines and chemokines in CV disease, malnutrition, growth failure, and CKD progression. Lymphocyte cell lines will be generated to facilitate study of genetic predisposition to CKD progression. Successful study implementation will improve

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understanding of the physiologic, genetic, environmental, and socioeconomic factors that are associated with CKD progression and with the impact of neurocognitive and CV sequelae on the overall well-being of children. Finally, identification of modifiable risk factors for progressive CKD, neurocognitive deficits, and CV disease may lead to intervention trials to improve the health outcomes of children and adolescents with CKD.

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Acknowledgments

The CKiD is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the National Institute of Neurologic Disorders and Stroke, National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (UO1-DK-66143, UO1-DK-66174, and UO1-DK-66116).

The CKiD prospective cohort study has clinical coordinating centers (principal investigators) at Children’s Mercy Hospital and the University of Missouri–Kansas City (Bradley Warady, MD) and Johns Hopkins School of Medicine (Susan Furth, MD, PhD), and data coordinating center (principal investigator) at the Johns Hopkins Bloomberg School of Public Health (Alvaro Muñoz, PhD).

We acknowledge the tireless efforts of the CKiD study coordinators: Judith Jerry-Fluker, MPH, Anne Carlson, MHS, Julie Starr, RN, Wendy Wantland, RN, Jacqueline Ndirangu, MPH, and Alicia Wentz, BS.

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Footnotes

Published online ahead of print. Publication date available at www.cjasn.org. Received December 2, 2005. Accepted May 16, 2006.

Copyright © 2006 by the American Society of NephrologyPrevious Section 

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Home : Kidney & Urologic Diseases A-Z List of Topics and Titles : Kidney Disease in Children : Overview of Kidney Diseases in Children

Overview of Kidney Diseases in Children

On this page:

What are the kidneys, and what do they do?

Who is at risk?

What are the causes of kidney failure in children?

What are the treatments for kidney failure?

Hope through Research

For More Information

What are the kidneys, and what do they do?The kidneys are two bean-shaped organs located near the middle of the back, just below the rib cage.

When blood flows through the kidneys, waste products and extra water are removed from the blood and

sent to the bladder as urine. The kidneys also regulate blood pressure, balance chemicals like sodium

and potassium, and make hormones to help bones grow and keep the blood healthy by making new red

blood cells.

[Top]

Who is at risk?In the general population, slightly more than 30 people in every 100,000 develop kidney failure each year.

In the pediatric population-age 19 and under-the annual rate is only 1 or 2 new cases in every 100,000

children. In other words, adults are about 20 times more likely to develop kidney failure than children. The

risk increases steadily with age.

African Americans in their late teens are three times more likely than Caucasians in the same age group

to develop kidney failure. Diseases that damage the tiny blood vessels in the kidney are also more

common in children of color. Moreover, boys are nearly twice as likely as girls to develop kidney failure

from birth defects, polycystic kidney disease, or other hereditary diseases.

[Top]

What are the causes of kidney failure in children?

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Kidney failure may be acute or chronic. Acute diseases develop quickly and can be very serious.

Although an acute disease may have long-lasting consequences, it usually lasts for only a short time and

then goes away once the underlying cause has been treated. Chronic diseases, however, do not go away

and tend to get worse over time. When the kidneys stop working, doctors use a treatment called dialysis

to remove waste products and extra water from patients with chronic kidney failure.

Acute Kidney Diseases

Acute kidney disease may result from an injury or from poisoning. Any injury that results in loss of blood

may reduce kidney function temporarily, but once the blood supply is replenished, the kidneys usually

return to normal. Other kinds of acute kidney disease in children are

Hemolytic uremic syndrome. This rare disease affects mostly children under 10 years of age and

can result in kidney failure. Eating foods contaminated by bacteria leads to an infection in the

digestive system, which in the first stages causes vomiting and diarrhea. When these symptoms

subside, the child is still listless and pale. Poisons produced by the bacteria can damage the kidneys,

causing acute kidney failure. Children with hemolytic uremic syndrome may need blood transfusion

or dialysis for a short time. Most children, however, return to normal after a few weeks. Only a small

percentage of children (mostly those who have severe acute kidney disease) will develop chronic

kidney disease.

Nephrotic syndrome. A child with this syndrome will urinate less often, so the water left in the body

causes swelling around the eyes, legs, and belly. The small amount of urine the body makes

contains high levels of protein. Healthy kidneys keep protein in the blood, but damaged kidneys let it

leak from the blood into the urine. Nephrotic syndrome can usually be treated with prednisone to stop

protein leakage, and sometimes a diuretic is used to help the child urinate and reduce the swelling.

Usually, the child can take smaller and smaller doses of prednisone and eventually return to normal

with no lasting kidney damage. This temporary condition is called minimal change disease. Relapses

are common but usually respond to prednisone treatment.

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New cases, by age, per million population, adjusted for gender and race.

Source: United States Renal Data System. 

2005 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. 2005.

Chronic Kidney Diseases

Unfortunately, the conditions that lead to chronic kidney failure in children cannot be easily fixed. Often,

the condition will develop so slowly that it goes unnoticed until the kidneys have been permanently

damaged. Treatment may slow down the progression of some diseases, but in many cases the child will

eventually need dialysis or transplantation.

Birth defects. Some babies are born without kidneys or with abnormally formed kidneys. The kidney

abnormality is sometimes part of a syndrome that affects many parts of the body.

Blocked urine flow and reflux. If blockage develops between the kidneys and the opening where

urine leaves the body, the urine can back up and damage the kidney.

Hereditary diseases. In polycystic kidney disease (PKD), children inherit defective genes that cause

the kidneys to develop many cysts, sacs of fluid that replace healthy tissue and keep the kidneys

from doing their job. In Alport syndrome, the defective gene that causes kidney disease may also

cause hearing or vision loss.

Glomerular diseases. Some diseases attack the individual filtering units in the kidney. When

damaged, these filters-which are called glomeruli-leak blood and protein into the urine. If the damage

to the glomeruli is severe, kidney failure may develop.

Systemic diseases. Diabetes and lupus can affect many parts of the body, including the kidneys in

some people. In lupus, the immune system becomes overactive and attacks the body's own tissues.

Diabetes leads to high levels of blood glucose that damage the glomeruli. Diabetes is the leading

cause of kidney failure in adults. In children, however, diabetes is low on the list of causes because it

Page 23: Renal Cohort

usually takes many years of high blood glucose for the kidney disease of diabetes to develop.

However, an increasing number of children have type 2 diabetes, which is usually associated with

adults. As a result, we may see more children with chronic kidney failure caused by diabetes in the

future.

From birth to age 4 years, birth defects and hereditary diseases are by far the leading causes of kidney

failure. Between ages 5 and 14 years, hereditary diseases continue to be the most common causes,

followed closely by glomerular diseases. In the 15- to 19-year-old age group, glomerular diseases are the

leading cause, and hereditary diseases become rarer.

CJASN(clinical journal of American Society of Nephrology) May 2008 vol. 3, no. 3 881-886

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Epidemiology of Acute Kidney Injury

1. Jorge Cerdá*, 2. Norbert Lameire†, 3. Paul Eggers‡, 4. Neesh Pannu§, 5. Sigehiko Uchino‖, 6. Haiyan Wang¶, 7. Arvind Bagga**, 8. Adeera Levin††

+ Author Affiliations

1. *Division of Nephrology, Albany Medical College, Albany, New York; †Department of Internal Medicine, University Hospital Ghent, Ghent, Belgium; ‡Kidney and Urology Epidemiology, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland; §Division of Nephrology, University of Alberta, Edmonton, Alberta, Canada; ‖Department of Emergency and Critical Care Medicine, Saitama Medical Center, Saitama, Japan; ¶The First Hospital Institute of Nephrology, Beijing University, Beijing, China; **Division of Pediatric Nephrology, All India Institute of Medical Sciences, New Delhi, India; and ††Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada

1. Correspondence:Dr. Jorge Cerdá, Division of Nephrology, Albany Medical College and Capital District Renal Physicians, 62 Hackett Boulevard, Albany, NY 12209. Phone: 518-434-2244; Fax: 518-434-4659; E-mail: [email protected]

Next Section

Abstract

Background and objectives: The worldwide incidence of acute kidney injury is poorly known because of underreporting, regional disparities, and differences in definition and case mix. New definitions call for revision of the problem with unified criteria.

Design, setting, participants, & measurements: This article reports on the research recommendations of an international multidisciplinary committee, assembled to define a research agenda on acute kidney injury epidemiology using a modified three-step Delphi process.

Results: Knowledge of incidence and risk factors is crucial because it drives local and international efforts on detection and treatment. Also, notable differences exist between developing and developed countries: Incidence seems higher in the former, but underreporting compounded by age and gender disparities makes available data unreliable. In developing countries, incidence varies seasonally; incidence peaks cause critical shortages in medical and nursing personnel. Finally, in developing countries, lack of systematic evaluation of the role of falciparum malaria, obstetric mechanisms, and hemolytic uremic syndrome on acute kidney injury hampers efforts to prevent acute kidney injury.

Conclusions: The committee concluded that epidemiologic studies should include (1) prospective out- and inpatient studies that measure incidence of community and hospital acute kidney injury and post–acute kidney injury chronic kidney disease; (2) incidence measurements during seasonal peaks in developing and developed countries; and (3) whenever available, use of reliable existing administrative or institutional databases. Epidemiologic studies using

Page 25: Renal Cohort

standardized definitions in community and institutional settings in developing and underdeveloped countries are essential first steps to achieving early detection and intervention and improved patient outcomes.

The incidence rate of acute kidney injury (AKI) around the world is not well known (1–3). Recent studies in the United States (4,5) and Spain (6) have shown incidences varying between an average of 23.8 cases per 1000 discharges (4) with an 11% yearly increase between 1992 and 2001, to an increase from 61 to 288 per 100,000 population between 1988 and 2002 (5). More recently, Ali et al. (7) reported a high incidence of 1811 cases of AKI per million population during 2003. The relatively wide disparity in reported incidence rates and the increasing frequency of the condition raise concerns as to the real magnitude of the problem. In addition to a real increase in worldwide incidence, large differences in the definition of AKI and case mix likely underlie such differences.

It is recognized that the epidemiology of AKI in developing countries differs from that of the developed world in many important ways (8–16). Whereas in developed regions elderly patients predominate (4,5), in developing countries, AKI is a disease of the young (14,17,18) and children (19,20), in whom volume-responsive “prerenal” mechanisms are common (21–24). Although overall mortality seems to be lower than in developed countries (25–28), this finding is not true across all age groups: In these regions, AKI affects predominantly the young and children and mortality is high (29,30).

The difficulties of defining the incidence of AKI are especially notable when one searches for data on developing countries (8,13,15,16,25,31–33), the place of residence of more than 50% of the world 's population. No nationwide collection systems are available, and data from isolated centers are not based on the current AKI definition. Reports from Kuwait (8) reported an incidence of 4.1 per 100,000 population per year; Anochie et al. (31) in Nigeria reported an incidence of 11.7 cases of AKI per year in children in a hospital that serves more than 1 million children; in a tertiary care center in north India, the reported incidence was 20 cases per 1000 pediatric admissions (29). Among adult patients from South Africa, Seedat (25,34) reported an incidence of 20 cases per year per million population; in Brazil, Noronha et al. (10) reported an incidence of 7.9 cases per 1000 hospital admissions, and in North India, Jha and Chugh (33) reported a yearly incidence of 6.4 per 1000 admissions.

New definitions of AKI (35–37) make it again necessary to revisit this issue with unified criteria. Such new measurements will help us to understand the magnitude of the problem and enable meaningful comparisons between different centers and geographic regions. Previous articles have reviewed the status of this rapidly changing field (1–3). A recent systematic review described the similarities and differences in incidence, cause, pathophysiology, and public health implications of AKI in developed and developing regions (16). This article aims to build on such a review of existing knowledge and present a research agenda to begin to address the multiple areas of uncertainty in the epidemiology of AKI. This is the first time a multidisciplinary group including representatives from the main national and international societies of nephrology and critical care gathers to elaborate such a research agenda. The group understands that only by obtaining accurate knowledge on the epidemiology of AKI using contemporary diagnostic criteria can the problem acquire the necessary visibility that will enable the development of new initiatives. Such initiatives will be essential to move us forward in the field, decrease the worldwide incidence of AKI, and improve patient outcomes (36,38).

As long as AKI remains underreported, it will not be addressed properly. In developing countries, the most common causes of AKI are frequently associated with volume-responsive “prerenal”

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(39,40), obstetric (41), infectious (42,43), or toxic (25,44) mechanisms; thus, inexpensive, simple interventions such as education on oral rehydration (29,45), improved cross-cultural interaction with traditional healers (46), change in obstetric management policies (47,48), or management of infection (49) may result in a dramatic reduction in the incidence and severity of AKI (29,42,45–49). Given that in developing countries the costs of renal replacement therapies are prohibitively high (17,50–52), prevention is often the only realistic way to decrease its severe impact on morbidity and mortality. Although inexpensive, such interventions will not be carried on until the problem reaches political visibility and achieves institutional and organizational support (16).

Previous SectionNext Section

Materials and Methods

For the purposes of defining a research agenda in the context of the epidemiology of AKI, we used a modified Delphi process. This is described in detail by Kellum et al. (53) in this issue. Briefly, the three-step modified Delphi procedure included a literature review phase, focused group interactions with presentations to the entire committee, and a final ranking phase during which the research agenda was developed.

Literature Review and Synthesis

We conducted a systematic review of the literature using the following databases: Medline (1966 through August 2006), EMBASE (1980 through 2006, week 36), CINAHL (1982 through August 2006), and PubMed. Articles in any language were considered. The purpose of the review was to identify key unanswered questions. A secure internet Web site was set up with FTP capability; group members were able to upload and download full-text articles, and through a number of iterative steps, a series of clinical questions were developed.

Work Group Deliberations

After reviewing the literature and establishing a global perspective on the problem, discussions were undertaken within the work group regarding key knowledge gaps and recommendations for research that would improve the understanding of AKI worldwide. An organizational framework for AKI was introduced and discussed (Figure 1). In addition, recognizing that AKI commonly precedes or aggravates chronic kidney disease (CKD) (20,54–60), a schematic view of the natural history of AKI was developed (Figure 2).

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Figure 1.

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Conceptual model of acute kidney injury (AKI).

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Figure 2.

Natural history of AKI. Patients who develop AKI may experience (1) complete recovery of renal function, (2) development of progressive chronic kidney disease (CKD), (3) exacerbation of the rate of progression of preexisting CKD; or (4) irreversible loss of kidney function and evolve into ESRD.

Previous SectionNext Section

Results

Global Perspectives

Local conditions in developing countries make underreporting an important problem (1,16). It is improbable that incidence rates are so much lower in these regions than in developed countries. The most likely explanation for the seemingly lower incidence of AKI is that the majority of patients who develop AKI never make it to large reporting centers: The condition is underrecognized, distances are enormous, and the costs of transportation and lost wages are prohibitive (3). Delayed referral as a result of transportation difficulties and traditional cultural mores is still a formidable problem in many regions of the world (61) associated with significantly worse outcomes, as seen among children with hemolytic uremic syndrome in India (30).

Gender disparities in seeking medical attention make available reports even more unreliable. Thus, in certain regions in Africa and India, boys are more than twice as likely as girls to be taken by their parents to see medical personnel (62–66). Gender disparity is also expressed in the development of AKI after septic abortion (41,67). In some African countries, the problem has unfortunately worsened (41) despite nationwide efforts.

In developing countries—even at large centers—the availability of medical and nursing personnel is limited. This limitation becomes even more critical during seasonal variations in incidence (10,68–70). For example, during the monsoon season in Southeast Asia, the incidence of AKI may increase by 18 to 24% as a result of the increase in new cases of malaria, leptospirosis, acute gastroenteritis, and dysentery (71).

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The causes and risk factors for AKI in developing countries may be different from those in developed countries. Although prerenal or toxic mechanisms predominate, specific etiologies are important.

The incidence of acute glomerulonephritis, both primary and secondary to infectious diseases appears to be higher than in developed countries. Thus, in south-east Anatolia, Turkey, acute glomerulonephritis causes more than 60% of childhood cases of AKI (72), and is an important cause of AKI in northern Africa (73–75) Potential reasons are multiple, including access to care (leading to late and therefore severe presentation), diagnostic testing capabilities and perhaps a true incidence difference. This is an important research question that warrants further study.

Malaria represents an especially important problem (16). There is an upsurge in worldwide malarial incidence (76,77). In India, for example, the overall yearly incidence is 13 to 17.8% of malarial cases (43). Incidence is increasing in Africa, India, Thailand, and New Guinea (42). As its worldwide incidence increases, so are the complications of severe falciparum malaria, including AKI (78). Each year, 300 million people contract the disease, which will be responsible for more than 1 million yearly deaths in Africa alone (49,77). It is estimated that in 1% of cases (3000,000/yr), a combination of parasite and host factors will lead to severe malaria, jaundice, and AKI (42,78), a complication associated with 45% mortality (78); in areas of endemic malaria, the incidence of AKI may be >4% of malarial cases (42). Worldwide, the incidence of AKI as a result of malaria varies between 0.6 and 60% of malarial cases, depending on the region (43). Early intervention, including appropriate antimalarial treatment and renal replacement therapy, is associated with improved survival and recovery of kidney function among patients with AKI as a result of severe falciparum malaria (79,80).

Specific Problems in Children

Although the majority of causes of AKI in children around the world are secondary to volume-responsive mechanisms, including acute diarrheal losses and renal hypoperfusion after major surgery and secondary to systemic sepsis (81–83), other conditions have shown an increased frequency in certain regions of the world. Thus, hemolytic uremic syndrome (HUS) is the chief cause of CKD and ESRD in children in Argentina (84) and in northern India (85), where it has increased in frequency in comparison with previous surveys (45). Whereas in Argentina the mortality associated with HUS has decreased from 10 to 3% (84), in India, it remains high (up to 59% [29]), attributed often to late referral of patients (30). An additional complication to longitudinal incidence comparisons is that some diseases virtually did not exist a few years ago; thus, HUS was very uncommon in south and southeast Asia before the 1970s but has since then become one of the most important causes of AKI in children of that region (29). Follow-up studies of patients suggest that of the patients who have AKI and are successfully discharged from the hospital, a significant proportion may show features of CKD, including low GFR, hypertension, and proteinuria (20,84).

The Elderly and Complex Patients

Although it is widely known that the elderly and those with multiple medical conditions are at increased risk for AKI (4,5,86), the measurement of this risk is inaccurate, especially in outpatient situations. It remains unclear whether the underlying condition(s) increases susceptibility or whether those patients are more likely to be exposed to important initiating factors for AKI.

Previous SectionNext Section

Research Recommendations

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Key research studies to evaluate incidence and risk factors are crucial. Knowledge of the magnitude of the problem will drive local and international efforts to detect and treat the problem as early as possible. The scarcity or absence of data makes it unlikely that the problem will be addressed by local, regional, and worldwide organizations such as the Pan American Health Organization and the World Health Organization in a strong, consistent manner. Accurate knowledge of the epidemiology of AKI in developing countries will have powerful preventive and treatment effects (18,29,30,45,80,87); conversely, complex technical questions on renal replacement therapies may, for the time being, largely remain less relevant to this population (51,52).

Epidemiology of AKI in Developing and Developed Countries

There is a need for a variety of epidemiologic studies to acquire new knowledge about the incidence of AKI. Although data collected from surveys, administrative data sets, post hoc analysis of clinical trials, or review of existing laboratory or clinical databases have important methodologic limitations, it is clear that without attempts to quantify the true burden of illness using standardized definitions, improved understanding and outcomes will not be possible.

Establishing the True Incidence in Different Locations.

Studies using the new definition of AKI can be instrumented in a prospective manner, such as measuring the incidence of AKI in emergency departments to measure community-acquired AKI and among hospital inpatients to measure hospital and intensive care unit–acquired AKI. Such measurements can then be followed up longitudinally for 3, 6, and 12 mo to ascertain the natural history of the problem and to measure the importance of AKI as a cause of CKD (see Figure 2). In developing countries, where community-acquired AKI occurs in the rural setting and rarely reaches the hospital, different regional data collection techniques will be necessary to ensure accurate measurement of incidence.

Unique situations that may facilitate knowledge acquisition include data collection during periods of presumed increased incidence, such as during monsoon season in Southeast Asia (68,70) or the rainy season in South America (10,88). If local resources are used, then such studies would not be costly and could be obtained in a short period of time. Local innovations in this regard would enable acquisition of data at small cost.

Establishing True Incidence in Different Locations/Situations.

In developed countries, use of currently existing administrative or institution databases whenever available will help to establish the prevalence of abnormal kidney function at the time of admission to hospitals or emergency departments and the occurrence of changes in renal function during hospitalization. Collecting information about populations at risk (e.g., elderly patients in nursing homes during influenza season or before and after vaccination) would also enable more precise estimates of the burden of illness. Such databases are rarely available (32,41,89) in developing countries.

Previous SectionNext Section

Conclusions

AKI is a worsening problem, but its true incidence is unknown. From a worldwide perspective, there is a clear need to understand the epidemiology of AKI more accurately. Use of standardized definitions and descriptions of existing at-risk and high-risk populations, both in community and

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institutional settings in developing and underdeveloped countries, are the first steps to improve outcomes

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Chronic kidney diseaseFrom Wikipedia, the free encyclopedia

Chronic kidney disease

Classification and external resources

ICD-10 N   03   

ICD-9 585 403

DiseasesDB 11288

MedlinePlus 000471

eMedicine article/238798

MeSH D007676

Chronic kidney disease (CKD), also known as chronic renal disease, is a progressive loss in renal

function over a period of months or years. The symptoms of worsening kidney function are unspecific, and

might include feeling generally unwell and experiencing a reduced appetite. Often, chronic kidney disease is

diagnosed as a result of screening of people known to be at risk of kidney problems, such as those with high

blood pressure or diabetesand those with a blood relative with chronic kidney disease. Chronic kidney disease

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may also be identified when it leads to one of its recognized complications, such as cardiovascular

disease, anemia or pericarditis.[1]

Chronic kidney disease is identified by a blood test for creatinine. Higher levels of creatinine indicate a

falling glomerular filtration rate and as a result a decreased capability of the kidneys to excrete waste products.

Creatinine levels may be normal in the early stages of CKD, and the condition is discovered if urinalysis (testing

of a urine sample) shows that the kidney is allowing the loss of protein or red blood cells into the urine. To fully

investigate the underlying cause of kidney damage, various forms of medical imaging, blood tests and often

renal biopsy (removing a small sample of kidney tissue) are employed to find out if there is a reversible cause

for the kidney malfunction.[1] Recent professional guidelines classify the severity of chronic kidney disease in

five stages, with stage 1 being the mildest and usually causing few symptoms and stage 5 being a severe

illness with poor life expectancy if untreated. Stage 5 CKD is also called established chronic kidney

disease and is synonymous with the now outdated terms end-stage renal disease (ESRD), chronic kidney

failure (CKF) or chronic renal failure (CRF).[1]

There is no specific treatment unequivocally shown to slow the worsening of chronic kidney disease. If there is

an underlying cause to CKD, such as vasculitis, this may be treated directly with treatments aimed to slow the

damage. In more advanced stages, treatments may be required for anemia and bone disease. Severe CKD

requires one of the forms of renal replacement therapy; this may be a form of dialysis, but ideally constitutes

a kidney transplant.[1]

Contents

  [hide] 

1     Signs and symptoms   

2     Causes   

3     Diagnosis   

o 3.1      Stages   

o 3.2      NDD-CKD vs. ESRD   

4     Screening and Referral   

5     Treatment   

6     Prognosis   

7     Epidemiology   

8     Organizations   

9     See also   

10      References   

11      External links   

Page 43: Renal Cohort

[edit]Signs and symptoms

CKD is initially without specific symptoms and can only be detected as an increase in serum creatinine or

protein in the urine. As the kidney function decreases:

Blood pressure  is increased due to fluid overload and production of vasoactive hormones created by the

kidney via the RAS (renin-angiotensin system), increasing one's risk of developinghypertension and/or

suffering from congestive heart failure

Urea  accumulates, leading to azotemia and ultimately uremia (symptoms ranging from lethargy

to pericarditis and encephalopathy). Urea is excreted by sweating and crystallizes on skin ("uremic frost").

Potassium  accumulates in the blood (known as hyperkalemia with a range of symptoms

including malaise and potentially fatal cardiac arrhythmias)

Erythropoietin  synthesis is decreased (potentially leading to anemia, which causes fatigue)

Fluid volume overload  — symptoms may range from mild edema to life-threatening pulmonary edema

Hyperphosphatemia  — due to reduced phosphate excretion, associated with hypocalcemia (due to 1,25

dihydroxyvitamin D3 deficiency). The 1,25 dihydroxyvitamin D3 deficiency is due to stimulation of fibroblast

growth factor-23.[citation needed]

Later this progresses to secondary hyperparathyroidism, renal osteodystrophy and vascular

calcification that further impairs cardiac function.

Metabolic acidosis , due to accumulation of sulfates, phosphates, uric acid etc. This may cause altered

enzyme activity by excess acid acting on enzymes and also increased excitability of cardiac and neuronal

membranes by the promotion of hyperkalemia due to excess acid (acidemia)[2]

People with chronic kidney disease suffer from accelerated atherosclerosis and are more likely to

develop cardiovascular disease than the general population. Patients afflicted with chronic kidney disease and

cardiovascular disease tend to have significantly worse prognoses than those suffering only from the latter.

[edit]Causes

The most common causes of CKD are diabetes mellitus, hypertension, and glomerulonephritis.[3] Together,

these cause approximately 75% of all adult cases. Certain geographic areas have a high incidence of HIV

nephropathy.

Historically, kidney disease has been classified according to the part of the renal anatomy that is involved, to

wit:[citation needed]

Vascular , includes large vessel disease such as bilateral renal artery stenosis and small vessel disease

such as ischemic nephropathy, hemolytic-uremic syndrome and vasculitis

Page 44: Renal Cohort

Glomerular, comprising a diverse group and subclassified into

Primary Glomerular disease such as focal segmental glomerulosclerosis and IgA nephritis

Secondary Glomerular disease such as diabetic nephropathy and lupus nephritis

Tubulointerstitial including polycystic kidney disease, drug and toxin-induced chronic tubulointerstitial

nephritis and reflux nephropathy

Obstructive such as with bilateral kidney stones and diseases of the prostate

On rare cases, pin worms infecting the kidney can also cause nephropathy.

[edit]Diagnosis

In many CKD patients, previous renal disease or other underlying diseases are already known. A small number

present with CKD of unknown cause. In these patients, a cause is occasionally identified retrospectively.[citation

needed]

It is important to differentiate CKD from acute renal failure (ARF) because ARF can be reversible.

Abdominal ultrasound, in which the size of the kidneys is measured, is commonly performed. Kidneys with CKD

are usually smaller (< 9 cm) than normal kidneys, with notable exceptions such as in diabetic

nephropathy and polycystic kidney disease. Another diagnostic clue that helps differentiate CKD from ARF is a

gradual rise in serum creatinine (over several months or years) as opposed to a sudden increase in the serum

creatinine (several days to weeks). If these levels are unavailable (because the patient has been well and has

had no blood tests), it is occasionally necessary to treat a patient briefly as having ARF until it has been

established that the renal impairment is irreversible.[citation needed]

Additional tests may include nuclear medicine MAG3 scan to confirm blood flows and establish the differential

function between the two kidneys. DMSA scans are also used in renal imaging; with both MAG3 and DMSA

being used chelated with the radioactive element Technetium-99.[citation needed]

In chronic renal failure treated with standard dialysis, numerous uremic toxins accumulate. These toxins show

various cytotoxic activities in the serum, have different molecular weights and some of them are bound to other

proteins, primarily to albumin. Such toxic protein bound substances are receiving the attention of scientists who

are interested in improving the standard chronic dialysis procedures used today.[citation needed]

[edit]Stages

All individuals with a glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for 3 months are classified as having

chronic kidney disease, irrespective of the presence or absence of kidney damage. The rationale for including

these individuals is that reduction in kidney function to this level or lower represents loss of half or more of the

adult level of normal kidney function, which may be associated with a number of complications.[1]

All individuals with kidney damage are classified as having chronic kidney disease, irrespective of the level of

GFR. The rationale for including individuals with GFR > 60 mL/min/1.73 m2 is that GFR may be sustained at

Page 45: Renal Cohort

normal or increased levels despite substantial kidney damage and that patients with kidney damage are at

increased risk of the two major outcomes of chronic kidney disease: loss of kidney function and development of

cardiovascular disease.[1]

The loss of protein in the urine is regarded as an independent marker for worsening of renal function and

cardiovascular disease. Hence, British guidelines append the letter "P" to the stage of chronic kidney disease if

there is significant protein loss.[4]

Stage 1

Slightly diminished function; kidney damage with normal or relatively high GFR (≥90 mL/min/1.73 m2). Kidney

damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or

urine test or imaging studies.[1]

Stage 2

Mild reduction in GFR (60–89 mL/min/1.73 m2) with kidney damage. Kidney damage is defined as pathological

abnormalities or markers of damage, including abnormalities in blood or urine test or imaging studies.[1]

Stage 3

Moderate reduction in GFR (30–59 mL/min/1.73 m2).[1] British guidelines distinguish between stage 3A (GFR

45–59) and stage 3B (GFR 30–44) for purposes of screening and referral.[4]

Stage 4

Severe reduction in GFR (15–29 mL/min/1.73 m2)[1] Preparation for renal replacement therapy

Stage 5

Established kidney failure (GFR <15 mL/min/1.73 m2, or permanent renal replacement therapy (RRT)[1]

[edit]NDD-CKD vs. ESRD

The term non-dialysis dependent CKD, also abbreviated as NDD-CKD, is a designation used to encompass

the status of those persons with an established CKD who do not yet require the life-supporting treatments

for renal failure known as renal replacement therapy (including maintenance dialysis or renal transplantation).

The condition of individuals with CKD, who require either of the 2 types of renal replacement

therapy (dialysis or transplantation), is referred to as the end-stage renal disease (ESRD). Hence, the start of

the ESRD is practically the irreversible conclusion of the NDD-CKD. Even though the non-dialysis

dependent status refers to the status of persons with earlier stages of CKD (stages 1 to 4), patients with

advanced stage of CKD (Stage 5), who have not yet started renal replacement therapy are also referred to as

NDD-CKD.

[edit]Screening and Referral

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Early identification of patients with kidney disease is recommended, as measures may be instituted to slow

progression and mitigate cardiovascular risk. Among those who should be screened are subjects with

hypertension or history of cardiovascular disease, those with diabetes or marked obesity, those aged > 60

years, subjects with indigenous (native American Indian, First Nations) racial origin, those with a history of renal

disease in the past, as well as subjects who have relatives who had kidney disease requiring dialysis.

Screening should include calculation of estimated GFR/1.73 m2 from the serum creatinine level, and

measurement of urine-to-albumin creatinine ratio in a first-morning urine specimen as well as dipstick screen

for hematuria. [5] Guidelines for nephrologist referral vary among different countries. Nephrology referral is

useful when eGFR/1.73m2 is less than 30 or decreasing by more than 3 mL/min/year, when urine albumin-to-

creatinine ratio is more than 300 mg/g, when blood pressure is difficult to control, or when hematuria or other

findings suggest either a primarily glomerular disorder or secondary disease amenable to specific treatment.

Other benefits of early nephrology referral include proper patient education regarding options for renal

replacement therapy as well as pre-emptive transplantation, and timely workup and placement of an

arteriovenous fistula in those patients opting for future hemodialysis.

[edit]Treatment

The neutrality of this section is disputed. Please see the discussion on the talk page. Please do not remove this message until the dispute is resolved. (August 2009)

The goal of therapy is to slow down or halt the progression of CKD to stage 5. Control of blood pressure and

treatment of the original disease, whenever feasible, are the broad principles of management.

Generally, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARBs) are

used, as they have been found to slow the progression of CKD to stage 5.[6][7] Although the use of ACE

inhibitors and ARBs represents the current standard of care for patients with CKD, patients progressively lose

kidney function while on these medications, as seen in the IDNT[8] and RENAAL[9] studies, which reported a

decrease over time in estimated glomerular filtration rate (an accurate measure of CKD progression, as

detailed in the K/DOQI guidelines[1]) in patients treated by these conventional methods.

Currently, several compounds are in development for CKD. These include, but are not limited to, bardoxolone

methyl,[10] olmesartan medoxomil, sulodexide, and avosentan.[11]

Replacement of erythropoietin and calcitriol, two hormones processed by the kidney, is often necessary in

patients with advanced CKD. Phosphate binders are also used to control the serumphosphate levels, which are

usually elevated in advanced chronic kidney disease.

When one reaches stage 5 CKD, renal replacement therapy is required, in the form of either dialysis or

a transplant.

Page 47: Renal Cohort

The normalization of hemoglobin has not been found to be of any benefit.[12]

People with CKD are at a markedly increased risk of cardiovascular disease, and often have other risk factors

for heart disease, such as hyperlipidemia. The most common cause of death in people with CKD is therefore

cardiovascular disease rather than renal failure. Aggressive treatment of hyperlipidemia is warranted.[13]

[edit]Prognosis

The prognosis of patients with chronic kidney disease is guarded as epidemiological data has shown that all

cause mortality (the overall death rate) increases as kidney function decreases.[14] The leading cause of death

in patients with chronic kidney disease is cardiovascular disease, regardless of whether there is progression to

stage 5.[14][15][16]

While renal replacement therapies can maintain patients indefinitely and prolong life, the quality of life is

severely affected.[17][18] Renal transplantation increases the survival of patients with stage 5 CKD significantly

when compared to other therapeutic options;[19][20] however, it is associated with an increased short-term

mortality (due to complications of the surgery). Transplantation aside, high intensity home

hemodialysis appears to be associated with improved survival and a greater quality of life, when compared to

the conventional three times a week hemodialysis and peritoneal dialysis.[21]

[edit]Epidemiology

In Canada 1.9 to 2.3 million people have chronic kidney disease.[12]

In the US, the Centers for Disease Control and Prevention found that CKD affected an estimated 16.8% of

adults aged 20 years and older, during 1999 to 2004.[22]

UK estimates suggest that 8.8% of the population of Great Britain and Northern Ireland have symptomatic

CKD.[23]

Chronic kidney disease (CKD) is a major concern in African Americans, mostly due to increased prevalence of

hypertension. As an example, 37% of end-stage renal disease cases in African Americans can be attributed to

high blood pressure, compared with 19% among caucasians.[24] Treatment efficacy also differs between racial

groups. Administration of anti-hypertensive drugs generally halts disease progression in white populations, but

has little effect in slowing renal disease among blacks, and additional treatment such as bicarbonate therapy is

often required.[24] While lower socioeconomic status contributes to prevalence of CKD, there are still significant

differences in CKD prevalence between African Americans and whites when controlling for environmental

factors.[24]Studies have shown that there is a true association between history of chronic renal failure in first or

second-degree relatives, and risk of disease.[25] In addition, African Americans may have higher serum levels of

human leukocyte antigens (HLA).[25] High HLA concentrations can contribute to increased systemic

inflammation, which indirectly may lead to heightened susceptibility for developing kidney disease. Lack of

Page 48: Renal Cohort

nocturnal reduction in blood pressure among groups of African Americans is also offered as an explanation,

[25] which lends further credence to a genetic etiology of CKD racial disparities.

[edit]Organizations

In the USA, the National Kidney Foundation is a national organization representing patients and professionals

who treat kidney diseases. The American Kidney Fund (AKF) is a national non-profit organization providing

treatment-related financial assistance to 1 out of every 5 dialysis patients each year. The Renal Support

Network (RSN) is a nonprofit, patient-focused, patient-run organization that provides non-medical services to

those affected by CKD. The American Association of Kidney Patients (AAKP) is a non-profit, patient-centric

group focused on improving the health and well-being of CKD and dialysis patients. The Renal Physicians

Association (RPA) is an association representing nephrology professionals.

In the United Kingdom, the UK National Kidney Federation represents patients, and the Renal

Association represents renal physicians and works closely with the National Service Framework for kidney

disease.

Kidney Health Australia serves that country.

The International Society of Nephrology is an international body representing specialists in kidney diseases.

[edit]See also

Acute renal failure

Dialysis

Hepatorenal syndrome

Renal failure

Artificial kidney

Nephropathy

[edit]References

1. ^ a b c d e f g h i j k l National Kidney Foundation (2002). "K/DOQI clinical practice guidelines for chronic kidney

disease". Retrieved 2008-06-29.

2. ̂  Adrogué HJ, Madias NE (September 1981). "Changes in plasma potassium concentration during acute

acid-base disturbances". Am. J. Med. 71 (3): 456–67. doi:10.1016/0002-9343(81)90182-0.PMID 7025622.

3. ̂  http://www.usrds.org/

4. ^ a b National Institute for Health and Clinical Excellence. Clinical guideline 73: Chronic kidney disease.

London, 2008.

Page 49: Renal Cohort

5. ̂  Johnson, David (2011-05-02). "Chapter 4: CKD Screening and Management: Overview". In Daugirdas,

John. Handbook of Chronic Kidney Disease Management. Lippincott Williams and Wilkins. pp. 32–

43. ISBN 1582558930.

6. ̂  Ruggenenti P, Perna A, Gherardi G, Gaspari F, Benini R, Remuzzi G (October 1998). "Renal function and

requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo

Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in

Nephropathy". Lancet 352 (9136): 1252–6. doi:10.1016/S0140-6736(98)04433-X. PMID 9788454.

7. ̂  Ruggenenti P, Perna A, Gherardi G et al. (July 1999). "Renoprotective properties of ACE-inhibition in non-

diabetic nephropathies with non-nephrotic proteinuria". Lancet 354 (9176): 359–64.doi:10.1016/S0140-

6736(98)10363-X. PMID 10437863.

8. ̂  Lewis EJ, Hunsicker LG, Clarke WR et al. (2001). "Renoprotective effect of the angiotensin-receptor

antagonist irbesartan in patients with nephropathy due to type 2 diabetes". N Engl J Med 345 (12): 851–

60. doi:10.1056/NEJMoa011303. PMID 11565517.

9. ̂  Brenner BM, Cooper ME, de ZD et al. (2001). "Effects of losartan on renal and cardiovascular outcomes

in patients with type 2 diabetes and nephropathy". N Engl J Med 345 (12): 861–

9.doi:10.1056/NEJMoa011161. PMID 11565518.

10. ̂  Roehr, Bob (April 6, 2009). "NKF 2009: Bardoxolone May Improve Renal Function Through Inflammatory

Pathways". Medscape Medical News.

11. ̂  "Avosentan May Slow Progression Of Diabetic Kidney Disease". Medical News Today. 14 February 2009.

12. ^ a b Levin A, Hemmelgarn B, Culleton B et al. (November 2008). "Guidelines for the management of chronic

kidney disease". CMAJ 179 (11): 1154–62. doi:10.1503/cmaj.080351. PMC 2582781.PMID 19015566.

13. ̂  Chauhan V, Vaid M (November 2009). "Dyslipidemia in chronic kidney disease: managing a high-risk

combination". Postgrad Med 121 (6): 54–61. doi:10.3810/pgm.2009.11.2077. PMID 19940417.

14. ^ a b Perazella MA, Khan S (March 2006). "Increased mortality in chronic kidney disease: a call to

action". Am. J. Med. Sci. 331 (3): 150–3. doi:10.1097/00000441-200603000-00007. PMID 16538076.

15. ̂  Sarnak MJ, Levey AS, Schoolwerth AC et al. (October 2003). "Kidney disease as a risk factor for

development of cardiovascular disease: a statement from the American Heart Association Councils on

Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology

and Prevention". Circulation 108 (17): 2154–

69. doi:10.1161/01.CIR.0000095676.90936.80.PMID 14581387.

16. ̂  Tonelli M, Wiebe N, Culleton B et al. (July 2006). "Chronic kidney disease and mortality risk: a systematic

review". J. Am. Soc. Nephrol. 17 (7): 2034–47. doi:10.1681/ASN.2005101085.PMID 16738019.

17. ̂  Heidenheim AP, Kooistra MP, Lindsay RM (2004). "Quality of life". Contrib Nephrol. Contributions to

Nephrology 145: 99–105. doi:10.1159/000081673. ISBN 3-8055-7808-3. PMID 15496796.

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18. ̂  de Francisco AL, Piñera C (January 2006). "Challenges and future of renal replacement

therapy". Hemodial Int 10 (Suppl 1): S19–23. doi:10.1111/j.1542-4758.2006.01185.x. PMID 16441862.

19. ̂  Groothoff JW (July 2005). "Long-term outcomes of children with end-stage renal disease". Pediatr.

Nephrol. 20 (7): 849–53. doi:10.1007/s00467-005-1878-9. PMID 15834618.

20. ̂  Giri M (2004). "Choice of renal replacement therapy in patients with diabetic end stage renal

disease". Edtna Erca J 30 (3): 138–42. PMID 15715116.

21. ̂  Pierratos A, McFarlane P, Chan CT (March 2005). "Quotidian dialysis--update 2005". Curr. Opin. Nephrol.

Hypertens. 14 (2): 119–24. doi:10.1097/00041552-200503000-00006. PMID 15687837.

22. ̂  "Prevalence of chronic kidney disease and associated risk factors—United States, 1999–2004". MMWR

Morb. Mortal. Wkly. Rep. 56 (8): 161–5. March 2007. PMID 17332726.

23. ̂  The Association of Public Health Observatories – Chronic Kidney Disease Prevalence Estimates. 2007

[cited 1/3/2010]; Available from: http://www.apho.org.uk/resource/item.aspx?RID=63798.

24. ^ a b c Appel LJ, Wright JT, Greene T, et al. (April 2008). "Long-term effects of renin-angiotensin system-

blocking therapy and a low blood pressure goal on progression of hypertensive chronic kidney disease in

African Americans". Arch. Intern. Med. 168 (8): 832–9. doi:10.1001/archinte.168.8.832. PMID 18443258.

25. ^ a b c Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Stamler J (1997). "End-stage renal

disease in African-American and white men. 16-year MRFIT findings". JAMA 277 (16): 1293–

8.PMID 9109467.

Acute kidney injuryFrom Wikipedia, the free encyclopedia

Acute kidney injury

Classification and external resources

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Pathologic kidney specimen showing marked pallor of the cortex, 

contrasting to the darker areas of surviving medullary tissue. The patient 

died with acute kidney injury.

ICD-10 N   17   

ICD-9 584

DiseasesDB 11263

MedlinePlus 000501

eMedicine med/1595

MeSH D007675

Acute kidney injury (AKI), previously called acute renal failure (ARF),[1] is a rapid loss of kidney function. Its

causes are numerous and include low blood volume from any cause, exposure to substances harmful to the

kidney, and obstruction of the urinary tract. AKI is diagnosed on the basis of characteristic laboratory findings,

such as elevated blood urea nitrogen and creatinine, or inability of the kidneys to produce sufficient amounts of

urine. AKI may lead to a number of complications, including metabolic acidosis, high potassium levels, uremia,

changes in body fluid balance, and effects to otherorgan systems. Management includes supportive care, such

as renal replacement therapy, as well as treatment of the underlying disorder.

Contents

  [hide] 

1     Signs and symptoms   

2     Causes   

o 2.1      Prerenal   

Page 52: Renal Cohort

o 2.2      Intrinsic   

o 2.3      Postrenal   

3     Diagnosis   

o 3.1      Detection   

o 3.2      Further testing   

4     Classification   

o 4.1      Definition   

o 4.2      Staging   

5     Treatment   

o 5.1      Specific therapies   

o 5.2      Diuretic agents   

o 5.3      Renal replacement therapy   

o 5.4      Complications   

6     Prognosis   

7     Epidemiology   

8     History   

9     See also   

10      References   

[edit]Signs and symptoms

The symptoms of acute kidney injury result from the various disturbances of kidney function that are associated

with the disease. Accumulation of urea and other nitrogen-containing substances in the bloodstream lead to a

number of symptoms, such as fatigue, loss of appetite, headache, nausea and vomiting.[2] Marked increases in

the potassium level can lead to irregularities in the heartbeat, which can be severe and life-threatening.

[3] Fluid balance is frequently affected, though hypertension is rare.[4]

Pain in the flanks may be encountered in some conditions (such as thrombosis of the renal blood vessels or

inflammation of the kidney); this is the result of stretching of the fibrous tissue capsule surrounding the kidney.

[5] If the kidney injury is the result of dehydration, there may be thirst as well as evidence of fluid depletion

on physical examination.[5] Physical examination may also provide other clues as to the underlying cause of the

kidney problem, such as a rash in interstitial nephritis and a palpable bladder.[5]

Finally, inability to excrete sufficient fluid from the body can cause accumulation of fluid in the limbs (peripheral

edema) and the lungs (pulmonary edema),[2] as well as cardial tamponade as a result of fluid effusions.[4]

[edit]Causes

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This section does not cite any references or sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (April 2011)

The one cause of acute kidney injury are commonly categorised into prerenal, intrinsic, and postrenal.

Classic laboratory findings in AKI

Type UOsm UNa FeNa BUN/Cr

Prerenal >500 <10<1%

>20

Intrinsic <350 >20>2%

<15

Postrenal <350 >40>4%

>15

[edit]Prerenal

Prerenal causes of AKI ("pre-renal azotemia") are those that decrease effective blood flow to the kidney. These

include systemic causes, such as low blood volume, low blood pressure, and heart failure, as well as local

changes to the blood vessels supplying the kidney. The latter include renal artery stenosis, which is a

narrowing of the renal artery that supplies the kidney, and renal vein thrombosis, which is the formation of

a blood clot in the renal vein that drains blood from the kidney.

Renal ischaemia ultimately results in functional disorder, depression of GFR, or both. These causes the

inadequate cardiac output and hypovolemia or vascular diseases causing reduced perfusion of both kidneys.

[edit]Intrinsic

Sources of damage to the kidney itself are dubbed intrinsic. Intrinsic AKI can be due to damage to

the glomeruli, renal tubules, or interstitium. Common causes of each are glomerulonephritis, acute tubular

necrosis (ATN), and acute interstitial nephritis (AIN), respectively.

[edit]Postrenal

Postrenal AKI is a consequence of urinary tract obstruction. This may be related to benign prostatic

hyperplasia, kidney stones, obstructed urinary catheter, bladder stone, bladder, ureteral or renal malignancy. It

Page 54: Renal Cohort

is useful to perform a bladder scan or a post void residual to rule out urinary retention. In post void residual, a

catheter is inserted immediately after urinating to measure fluid still in the bladder. 50-100ml suggests

neurogenic bladder. A renal ultrasound will demonstrate hydronephrosis if present. A CT scan of the abdomen

will also demonstrate bladder distension or hydronephrosis, however, in case of acute renal failure, the use of

IV contrast is contraindicated. On the basic metabolic panel, the ratio of BUN to creatinine may indicate post

renal failure.

[edit]Diagnosis

[edit]Detection

The deterioration of renal function may be discovered by a measured decrease in urine output. Often, it is

diagnosed on the basis of blood tests for substances normally eliminated by the kidney: ureaand creatinine.

Both tests have their disadvantages. For instance, it takes about 24 hours for the creatinine level to rise, even if

both kidneys have ceased to function. A number of alternative markers has been proposed, but none are

currently established enough to replace creatinine as a marker of renal function.[citation needed]

Sodium and potassium, two electrolytes that are commonly deranged in people with acute kidney injury, are

typically measured together with urea and creatinine.[citation needed]

[edit]Further testing

Once the diagnosis of AKI is made, further testing is often required to determine the underlying cause. These

may include urine sediment analysis, renal ultrasound and/or kidney biopsy. Indications for renal biopsy in the

setting of AKI include:[6]

1. Unexplained AKI

2. AKI in the presence of the nephritic syndrome

3. Systemic disease associated with AKI

[edit]Classification

Acute kidney injury is diagnosed on the basis of clinical history and laboratory data. A diagnosis is made when

there is rapid reduction in kidney function, as measured by serum creatinine, or based on a rapid reduction in

urine output, termed oliguria.

[edit]Definition

Introduced by the Acute Kidney Injury Network (AKIN), specific criteria exist for the diagnosis of AKI:[7]

1. Rapid time course (less than 48 hours)

2. Reduction of kidney function

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Rise in serum creatinine

Absolute increase in serum creatinine of ≥0.3 mg/dl (≥26.4 μmol/l)

Percentage increase in serum creatinine of ≥50%

Reduction in urine output, defined as <0.5 ml/kg/hr for more than 6 hours

[edit]Staging

The RIFLE criteria, proposed by the Acute Dialysis Quality Initiative (ADQI) group, aid in the staging of patients

with AKI:[8][9]

Risk: serum creatinine increased 1.5 times or urine production of <0.5 ml/kg for 6 hours

Injury: doubling of creatinine or urine production <0.5 ml/kg for 12 hours

Failure: tripling of creatinine or creatinine >355 μmol/l (with a rise of >44) (>4 mg/dl) OR urine output below

0.3 ml/kg for 24 hours

Loss: persistent AKI or complete loss of kidney function for more than 4 weeks

End-stage renal disease : complete loss of kidney function for more than 3 months

[edit]Treatment

This section does not cite any references or sources. Please help improve this section by adding citations to reliable sources. Unsourced material may be challenged and removed. (April 2011)

The management of AKI hinges on identification and treatment of the underlying cause. In addition to treatment

of the underlying disorder, management of AKI routinely includes the avoidance of substances that are toxic to

the kidneys, called nephrotoxins. These include NSAIDs such as ibuprofen, iodinated contrasts such as those

used for CT scans, and others.[10]

Monitoring of renal function, by serial serum creatinine measurements and monitoring of urine output, is

routinely performed. In the hospital, insertion of a urinary catheter helps monitor urine output and relieves

possible bladder outlet obstruction, such as with an enlarged prostate.

[edit]Specific therapies

In prerenal AKI without fluid overload, administration of intravenous fluids is typically the first step to improve

renal function. Volume status may be monitored with the use of a central venous catheter to avoid over- or

under-replacement of fluid.

Should low blood pressure prove a persistent problem in the fluid-replete patient, inotropes such

as norepinephrine and dobutamine may be given to improve cardiac output and hence renal perfusion. While a

useful pressor, there is no evidence to suggest that dopamine is of any specific benefit,[11] and may be harmful.

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The myriad causes of intrinsic AKI require specific therapies. For example, intrinsic AKI due to Wegener's

granulomatosis may respond to steroid medication. Toxin-induced prerenal AKI often responds to

discontinuation of the offending agent, such as aminoglycoside, penicillin, NSAIDs, or acetaminophen.[5]

If the cause is obstruction of the urinary tract, relief of the obstruction (with a nephrostomy or urinary catheter)

may be necessary.

[edit]Diuretic agents

The use of diuretics such as furosemide, while widespread and sometimes convenient in ameliorating fluid

overload, does not reduce the risk of complications or death.[12]

[edit]Renal replacement therapy

Renal replacement therapy, such as with hemodialysis, may be instituted in some cases of AKI. A systematic

review of the literature in 2008 demonstrated no difference in outcomes between the use of intermittent

hemodialysis and continuous venovenous hemofiltration (CVVH).[13] Among critically ill patients, intensive renal

replacement therapy with CVVH does not appear to improve outcomes compared to less intensive intermittent

hemodialysis.[14][10]

[edit]Complications

Metabolic acidosis, hyperkalemia, and pulmonary edema [15]  may require medical treatment with sodium

bicarbonate, antihyperkalemic measures, and diuretics.

Lack of improvement with fluid resuscitation, therapy-resistant hyperkalemia, metabolic acidosis, or fluid

overload may necessitate artificial support in the form of dialysis or hemofiltration.[3]

[edit]Prognosis

Depending on the cause, a proportion of patients will never regain full renal function, thus having end-stage

renal failure requiring lifelong dialysis or a kidney transplant.[citation needed]

[edit]Epidemiology

Acute kidney injury is common among hospitalized patients. It affects some 3-7% of patients admitted to the

hospital and approximately 25-30% of patients in the intensive care unit.[16]

[edit]History

Before the advancement of modern medicine, acute kidney injury might be referred to as uremic

poisoning. Uremia was the term used to describe the contamination of the blood with urine. Starting around

1847 this term was used to describe reduced urine output, now known as oliguria, which was thought to be

caused by the urine's mixing with the blood instead of being voided through theurethra.[citation needed]

Page 57: Renal Cohort

Acute kidney injury due to acute tubular necrosis (ATN) was recognised in the 1940s in the United Kingdom,

where crush injury victims during the London Blitz developed patchy necrosis of renal tubules, leading to a

sudden decrease in renal function.[17] During the Korean and Vietnam wars, the incidence of AKI decreased

due to better acute management and administration of intravenous fluids.[18]

[edit]See also

BUN-to-creatinine ratio

Chronic kidney disease

Dialysis

Renal failure

Rhabdomyolysis

[edit]References

Find more about Acute kidney injury on 

Wikipedia's sister projects:

Definitions from Wiktionary

Images and media from Commons

Learning resources from Wikiversity

News stories from Wikinews

Quotations from Wikiquote

Source texts from Wikisource

Textbooks from Wikibooks

1. ̂  Webb S, Dobb G (December 2007). "ARF, ATN or AKI? It's now acute kidney injury". Anaesthesia and

Intensive Care 35 (6): 843–4. PMID 18084974.

2. ^ a b Skorecki K, Green J, Brenner BM (2005). "Chronic renal failure". In Kasper DL, Braunwald E, Fauci

AS, et al.. Harrison's Principles of Internal Medicine (16th ed.). New York, NY: McGraw-Hill. pp. 1653–

63. ISBN 0-071-39140-1.

3. ^ a b Weisberg LS (December 2008). "Management of severe hyperkalemia". Crit. Care Med. 36 (12): 3246–

51. doi:10.1097/CCM.0b013e31818f222b.PMID 18936701.

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4. ^ a b Tierney, Lawrence M.; Stephen J. McPhee and Maxine A. Papadakis (2004). "22". CURRENT Medical

Diagnosis and Treatment 2005 (44 ed.). McGraw-Hill. p. 871. ISBN 0071436928.

5. ^ a b c d Brady HR, Brenner BM (2005). "Chronic renal failure". In Kasper DL, Braunwald E, Fauci AS, et

al.. Harrison's Principles of Internal Medicine (16th ed.). New York, NY: McGraw-Hill. pp. 1644–53. ISBN 0-

071-39140-1.

6. ̂  Papadakis MA, McPhee SJ (2008). Current Medical Diagnosis and Treatment. McGraw-Hill

Professional. ISBN 0-07-159124-9.

7. ̂  Mehta RL, Kellum JA, Shah SV, et al. (2007). "Acute Kidney Injury Network: report of an initiative to

improve outcomes in acute kidney injury". Critical Care (London, England) 11 (2):

R31. doi:10.1186/cc5713. PMC 2206446. PMID 17331245.

8. ̂  Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P (2004). "Acute renal failure - definition, outcome

measures, animal models, fluid therapy and information technology needs: the Second International

Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group". Crit Care 8 (4): R204–

12.doi:10.1186/cc2872. PMC 522841. PMID 15312219.

9. ̂  Lameire N, Van Biesen W, Vanholder R (2005). "Acute renal failure". Lancet 365 (9457): 417–

30. doi:10.1016/S0140-6736(05)17831-3. PMID 15680458.

10. ^ a b Palevsky PM, Zhang JH, O'Connor TZ, et al. (July 2008). "Intensity of renal support in critically ill

patients with acute kidney injury". The New England Journal of Medicine 359 (1): 7–

20.doi:10.1056/NEJMoa0802639. PMC 2574780. PMID 18492867.

11. ̂  Holmes CL, Walley KR (2003). "Bad medicine: low-dose dopamine in the ICU". Chest 123 (4): 1266–

75. doi:10.1378/chest.123.4.1266. PMID 12684320.

12. ̂  Uchino S, Doig GS, Bellomo R, et al (2004). "Diuretics and mortality in acute renal failure". Crit. Care

Med. 32 (8): 1669–77. doi:10.1097/01.CCM.0000132892.51063.2F. PMID 15286542.

13. ̂  Pannu N, Klarenbach S, Wiebe N, Manns B, Tonelli M (February 2008). "Renal replacement therapy in

patients with acute renal failure: a systematic review". JAMA : the Journal of the American Medical

Association 299 (7): 793–805. doi:10.1001/jama.299.7.793. PMID 18285591.

14. ̂  Bellomo R, Cass A, Cole L, et al. (October 2009). "Intensity of continuous renal-replacement therapy in

critically ill patients". The New England Journal of Medicine 361 (17): 1627–

38.doi:10.1056/NEJMoa0902413. PMID 19846848.

15. ̂  http://beavermedic.wordpress.com/2010/01/19/the-kidneys/

16. ̂  Brenner and Rector's The Kidney. Philadelphia: Saunders. 2007. ISBN 1-4160-3110-3.

17. ̂  Bywaters EG, Beall D (1941). "Crush injuries with impairment of renal function.". Br Med J 1 (4185): 427–

32. doi:10.1136/bmj.1.4185.427. PMC 2161734. PMID 20783577.

18. ̂  Schrier RW, Wang W, Poole B, Mitra A (2004). "Acute renal failure: definitions, diagnosis, pathogenesis,

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Acute glomerulonephritis is a disease characterized by the sudden appearance of edema, hematuria, proteinuria, and hypertension. It is a representative disease of acute nephritic syndrome in which inflammation of the glomerulus is manifested by proliferation of cellular elements secondary to an immunologic mechanism (see the following image).[1, 2]

A schematic representation of the proposed mechanism for acute poststreptococcal glomerulonephritis (APSGN). C = Activated complement; Pl = Plasmin; NAPlr = Nephritis-associated plasmin receptor; SK = Streptokinase; CIC = Circulating immune complex.

Acute poststreptococcal glomerulonephritis (APSGN) results from an antecedent infection of the skin or throat caused by nephritogenic strains of group A beta-hemolytic streptococci.[3, 4, 5] The concept of nephritogenic streptococci was initially advanced by Seegal and Earl in 1941, who noted that rheumatic fever and acute poststreptococcal glomerulonephritis (both nonsuppurative complications of streptococcal infections) did not simultaneously occur in the same patient and differ in geographic location.[6]Acute poststreptococcal glomerulonephritis occurs predominantly in males and often completely heals, whereas patients with rheumatic fever often experience relapsing attacks.

The M and T proteins in the bacterial wall have been used for characterizing streptococci. Nephritogenicity is mainly restricted to certain M protein serotypes (ie, 1, 2, 4, 12, 18, 25, 49, 55, 57, and 60) that have shown nephritogenic potential. These may cause skin or throat infections, but specific M types, such as 49, 55, 57, and 60, are most commonly associated with skin infections. However, not all strains of a nephritis-associated M protein serotype are nephritogenic.[7] In addition, many M protein serotypes do not confer lifetime immunity. Group C streptococci have been responsible for recent epidemics of APSGN (eg, Streptococcus zooepidemicus). Thus, it is possible that nephritogenic antigens are present and possibly shared by streptococci from several groups.[2]

In addition, nontypeable group A streptococci are frequently isolated from the skin or throat of patients with glomerulonephritis, representing presumably unclassified nephritogenic strains.[7] The overall risk of developing acute poststreptococcal glomerulonephritis after infection by these nephritogenic strains is about 15%. The risk of nephritis may also be related to the M type and the site of infection. The risk of developing nephritis infection by M type 49 is 5% if it is present in the throat. This risk increases to 25% if infection by the same organism in the skin is present.

See also Acute Glomerulonephritis, Emergent Management of Acute Glomerulonephritis, and Rheumatic Heart Disease.

1. Avner ED, Davis ID. Acute poststreptococcal glomerulonephritis. In: Behrman RE, Kliegman RM, Jenson HB, eds. Nelson Textbook of Pediatrics. 17th ed. Philadelphia, Pa: Elsevier Science; 2004:1740-41.

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3. Blyth CC, Robertson PW, Rosenberg AR. Post-streptococcal glomerulonephritis in Sydney: a 16-year retrospective review. J Paediatr Child Health. Jun 2007;43(6):446-50. [Medline].

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5. Sagel I, Treser G, Ty A, et al. Occurrence and nature of glomerular lesions after group A streptococci infections in children. Ann Intern Med. Oct 1973;79(4):492-9. [Medline].

6. Kimmelstiel P. The hump-a lesion of glomerulonephritis. Bull Pathol. 1965;6:187.7. Nissenson AR, Baraff LJ, Fine RN, Knutson DW. Poststreptococcal acute glomerulonephritis: fact

and controversy. Ann Intern Med. Jul 1979;91(1):76-86. [Medline].8. Yoshizawa N, Yamakami K, Fujino M, et al. Nephritis-associated plasmin receptor and acute

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11. Parra G, Rodríguez-Iturbe B, Batsford S, et al. Antibody to streptococcal zymogen in the serum of patients with acute glomerulonephritis: a multicentric study. Kidney Int. Aug 1998;54(2):509-17. [Medline].

12. Cu GA, Mezzano S, Bannan JD, Zabriskie JB. Immunohistochemical and serological evidence for the role of streptococcal proteinase in acute post-streptococcal glomerulonephritis. Kidney Int. Sep 1998;54(3):819-26. [Medline].

13. García R, Rubio L, Rodríguez-Iturbe B. Long-term prognosis of epidemic poststreptococcal glomerulonephritis in Maracaibo: follow-up studies 11-12 years after the acute episode. Clin Nephrol. Jun 1981;15(6):291-8. [Medline].

14. Perlman LV, Herdman RC, Kleinman H, Vernier RL. Poststreptococcal glomerulonephritis. A ten-year follow-up of an epidemic. JAMA. Oct 4 1965;194(1):63-70. [Medline].

15. Kandoth PW, Agarwal GJ, Dharnidharka VR. Acute renal failure in children requiring dialysis therapy.Indian Pediatr. Mar 1994;31(3):305-9. [Medline].

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26. Derrick CW, Reeves MS, Dillon HC Jr. Complement in overt and asymptomatic nephritis after skin infection. J Clin Invest. Jun 1970;49(6):1178-87. [Medline]. [Full Text].

27. Levy M, Sich M, Pirotzky E, Habib R. Complement activation in acute glomerulonephritis in children. Int J Pediatr Nephrol. Jan-Mar 1985;6(1):17-24. [Medline].

28. Sjöholm AG. Complement components and complement activation in acute poststreptococcal glomerulonephritis. Int Arch Allergy Appl Immunol. 1979;58(3):274-84. [Medline].

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