CKD MNT Module 3: Complications

Module 3: Complications

Complications May Increase as Kidney Function Declines

1. Use laboratory parameters to assess anemia in

chronic kidney disease (CKD)

2. Associate increased risk for hyperkalemia with

hyperglycemia and metabolic acidosis in CKD

3. Use and interpret laboratory parameters to assess

hypoalbuminemia in CKD


metabolic acidosis in CKD


CKD bone disorders

Participants will be able to:

Fewer functioning nephrons may mean:

− Inadequate erythropoietin (anemia)

− Accumulation of potassium (K)

− Accumulation of hydrogen ion (metabolic acidosis)

− Inadequate activation of vitamin D (bone disease)

− Accumulation of phosphorus (P)

− Accumulation of pro-inflammatory cytokines

Toxins build up in the blood.

Complications increase as kidney function declines

Complications may increase as estimated glomerular filtration rate (eGFR) decreases

Reference: Adapted from USRDS 2010 Annual Data Report (NIDDK, 2010)

Joseph is a 40-year-old man with numerous medical

issues, including morbid obesity and type 2

diabetes.

His eGFR is 21 mL/min/1.73 m2 at initial visit.

His urine protein-to-creatinine ratio (Up/Uc) is 6.6

grams/day.

Let’s meet Joseph

Date Weight (lb) Blood pressure A1C Urine protein/urine creatinine (g/day)

2/16 310 140/82 10.5 6.6

4/6 306 128/80 9.0

5/20 299 135/80 8.0 5.6

6/22 296 128/83

7/29 293 127/80 7.7 3.0

Test Reference 2/16 4/6 6/22 7/29WBC 4.8-10.8 10.6 10.2 12.6 H 11.8 HRBC 4.7-6.1 3.83 L 3.7 L 3.82 L 3.93 LHGB 14-18 10.5 L 10.3 L 10.6 L 10.9 LHCT 42-52 30.3 L 29.9 L 30.8 L 31.6 LMCV 80-94 80.6 80.9 80.7 80.2MCH 28-32 27.8 L 27.9 L 27.8 L 27.8 LMCHC 32-36 34.6 34.5 34.5 34.6RDW 11.5-14.5 14.5 14.8 H 14.6 H 15.1 HPLT 140-440 398 335 332 377

Joseph: The man with many complications

Joseph: The man with many complications

Test Reference 2/16 4/6 5/20 6/22 7/29Glucose 70. -100 301 174 H 103 H 174 H 157 HBUN 7-18 72 H 58 H 69 H 88 H 87 HCreatinine 0.8-1.3 3.5 H 3.4 H 3.5 H 4.0 H 4.6 HeGFR > 60 21 22 21 18 15Sodium 135-145 136 140 139 136 138Potassium 3.5- 5.0 5.0 4.7 5.3 H 5.5 H 4.9 Chloride 101-111 108 110 111 104 108CO2 21-32 20.2 L 23.8 18.0 L 16.2 L 18.5 LPhosphorus 2.5-4.9 4.8 4.2 5.2 H 5.3 HCalcium 8.5-10.0 7.4 L 8.3 L 8.1 L 8.0 L 8.1 LAlbumin 3.5-5.0 3.1 L 3.0 L 3.2 L 3.3 L 3.5 Cholesterol 0-200 155 - - - -Triglyceride 30-200 214 - - - -HDL 35 26 - - - -LDL 0-170 86.2 - - - -

Anemia

Hyperkalemia

Hypoalbuminemia

− Marker for malnutrition and/or inflammation

Metabolic acidosis

Mineral and bone disorders

Topics

You may want to download this PDF to use with this module.

Reference: http://www.nkdep.nih.gov/resources/nkdep-kidney-test-results-508.pdf

ANEMIA

Anemia may start early in the course of CKD due to inadequate erythropoietin synthesis

Anemia may develop as eGFR declines

Reference: Adapted from USRDS Annual Data Report (NIDDK, 2009)

Anemia may develop as a result of inadequate

erythropoietin synthesis.

May develop early and worsens as CKD progresses.

May develop earlier in people with diabetes.

May involve inadequate iron intake or impaired iron

absorption as well.

Anemia is a complication of CKD

Joseph’s anemia worsened as eGFR declined; treatment improved Hgb levels

Decreased responsiveness to erythropoietin

Uremia

Chronic inflammation

Severe hyperparathyroidism

Folate deficiency

Additional factors for anemia in CKD

Observational data show association with:

Coronary artery disease

Hospitalization for cardiac disease

Death from congestive heart failure

All-cause mortality

Left ventricular hypertrophy

Anemia in CKD is associated with morbidity and mortality

Reference: Toto. Kidney Int 2003; 64(suppl 87):S20–S23.

Renal tissue hypoxia triggers erythropoietin

production.

Erythropoietin stimulates erythrocyte (red blood cell)

synthesis in bone marrow.

Hemoglobin is the primary iron-containing protein in

erythrocytes that transports and delivers oxygen to

tissues.

Both erythropoietin and iron are required to produce

hemoglobin (Hgb) and correct hypoxia.

Kidneys act as oxygen sensors in the body

Iron transport and storage

Reference: http://www.cdc.gov/ncbddd/hemochromatosis/training/pathophysiology/iron_cycle_popup.htm

Increased absorption with:

− Decreased iron stores (ferritin)

− Increased erythropoiesis

− Anemia (low hemoglobin)

− Hypoxia

− Absence of inflammatory cytokines

Reduced absorption with:

− Inflammation or infection

Many factors influence iron absorption

Both a spontaneous decrease in intake and aversion

to foods with protein may occur as eGFR declines.

Hepcidin may accumulate in CKD.

− Hepcidin is the hormone that controls iron levels.

− This hormone regulates iron absorption in the gut and

mobilization of stored iron.

Inflammation may reduce absorption of iron.

Additional factors for inadequate iron in CKD

References: Kopple et al. Kidney Int 2000; 57(4):1688–1703; Young et al. Clin J Am Soc Nephrol 2009;4(8):1384–1387.

Serum iron

− Measures ferric iron (Fe+3)

− Decreases with iron deficiency and inflammation

Total iron-binding capacity (TIBC)

− TIBC measures serum transferrin after saturation of all

available binding sites with iron.

Tends to be increased with iron deficiency

Tends to be decreased with chronic inflammation

− More than 400 g/dL indicates storage iron depletion.

Assessing iron status

Reference: http://www.cdc.gov/nutritionreport/report.html

Transferrin saturation (TSAT)

− Transferrin transports iron

− Ratio of serum iron/TIBC x 100 = TSAT

− Early functional iron deficiency: < 16% may indicate

iron-deficiency anemia in general population (IOM)

Ferritin

− Storage iron

− Acute phase reactant (acute & chronic inflammation)

− Depleted stores: < 12 ng/mL may indicate iron

depletion in general population (Institute of Medicine)

Assessing iron status

Reference: http://www.cdc.gov/nutritionreport/pdf/nutrition_report.pdf

Complete blood count (CBC)

− Hemoglobin (Hgb)

Iron indices

− Transferrin saturation

Iron available for erythropoiesis

− Ferritin

Storage iron

Anemia of CKD is usually normochromic and

normocytic.

Laboratory assessment for anemia in CKD

Iron supplementation

− Oral

− Intravenous (parenteral)

Possible oxidant

Erythropoiesis-stimulating agents (ESAs)

− Injectable

Possible interventions to treat anemia in CKD

A 325 mg dose of:

− Ferrous fumarate has 108 mg elemental iron.

− Ferrous sulfate has 65 mg elemental iron.

− Ferrous gluconate has 35 mg elemental iron.

Absorption: Ferrous+2 iron > ferric+3 iron

Amount of elemental iron differs between oral iron supplements

Reference: http://www.anemia.org A Physician’s Guide to Oral Iron Supplementation. Nov 2008.

Food reduces iron absorption by 40–66%.

Amount absorbed decreases as dose increases.

Multiple doses may be needed.

CDC recommends 50–60 mg elemental iron twice

daily for nonpregnant adults.

Fewer side effects occur with extended release

forms, but less is absorbed.

Oral iron supplements are poorly absorbed


More than 25% of people experience side effects:

− Nausea

− Vomiting

− Constipation

− Diarrhea

− Dark-colored stools

− Abdominal distress

About 20% of people discontinue supplements due

to side effects.

Oral iron supplements have gastrointestinal side effects


Tips on oral iron supplements


Calcium supplements may be prescribed with meals

to bind dietary phosphorus.

− Calcium may interfere with iron absorption.

Indications of when to take iron supplements:

− Iron absorption is increased when supplement is taken

between meals and separate from phosphate binders.

− If person is already taking multiple medications,

supplement increases complexity of regimen.

Take iron supplement separate from calcium-based phosphate binders

Free iron is toxic.

Parenteral iron is transported on iron-carbohydrate

complexes:

− Dextran (may increase risk of anaphylaxis)

− Sucrose

− Gluconate

− Oligosaccharide

Carbohydrates may “shield” body from oxidation,

allowing safe delivery of the iron.

Parenteral iron may be used, more common in dialysis

Reference: Zager, Clin J Am Soc Nephrol 2006; 1(suppl 1):S24–S31.

Iron is a potent oxidant.

Parenteral iron may injure renal tubules.

Iron may increase risk of infection.

Parenteral iron may suppress phagocytosis of

bacteria.

Risks with parenteral iron

References: Zager et al. Kidney Int 2004; 66(1):144–156; Zager, Clin J Am Soc Nephrol 2006; 1(suppl 1):S24–S31;

Hörl, J Am Soc Nephrol 2007; 18(2):382–393.

Genetically engineered forms of erythropoietin

Injectable medication

Approved in 1989 to treat anemia in end-stage renal

disease (ESRD)

Must advise patient of risks and benefits

Erythropoiesis-stimulating agents (ESAs) are available

Reference:http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm200297.htm

Therapy may include ESAs to increase red blood cell

production and prevent need for transfusion. ESAs may be

beneficial, although their exact role is still being defined.

FDA black box warning for ESAs was released as a result of

recent trials which showed an increased risk for stroke,

blood clot, heart attack, and death when ESAs were

prescribed to achieve higher Hgb goals (> 12 g/dL).

FDA requires a Medication Guide explaining the risks and

benefits of ESAs be provided to all patients receiving ESAs.

Treating the anemia of CKD with ESAs

40-year-old male with DM 2 since 1997

His eGFR is 21 at initial visit

Severe kidney damage

− Heavy proteinuria

Urine protein/urine creatinine ratio = 6.6 g/day

All protein lost in the urine, not just albumin

Morbidly obese

− BMI 45.8 (initial), height 69”

− Going to weight-loss classes at endocrinologist’s office

Referred due to history of hyperkalemia

− Instructed at nephrologist’s office on potassium restriction

Joseph is trying to lose weight to get on kidney transplant list, wants to walk more

Food and beverage intake

Two meals/day. Working on eating lower potassium foods. Breakfast: 3 eggs, 1–2 slices dry toast, sugar-free beverage. Supper: fast foods. Cut out iced tea, added regular lemon-lime pop or diet cola. Eating more rice, noodles, and fewer potatoes. Snacks on salted jerky or corn chips.

Medications FeSO4 325 mg BID ordered, not taking, on “too many medications”; lisinopril 80 mg, knows this makes potassium higher. Endocrinologist stopped pioglitazone and glyburide; now 50 units glargine at bedtime. Reports postprandials < 150, were 200–300. Started 0.25 mcg calcitriol last month.

Diet order/ experience

1,700–2,000 Kcal, 96 g protein (per endocrinologist where he attends weight-loss classes); potassium restriction instruction at nephrologist’s office. No sodium restriction per patient and wife.

Physical activity Played football in high school. Not active now. Lives at high altitude. Short of breath when walked down hall to office. Very fatigued, wants to walk more.

Height & weight Height 69”, weight 310#, down 25 # since Sept. BMI = 45.8.

Assessment (2/16)

Biochemical data

eGFR 21, Up/Uc 6.6, K 5.0, Hgb 10.5, TSAT 19, ferritin 134. A1C 10.5. 25(OH)D 9, intact parathyroid hormone (iPTH) 207, Ca 7.4 (corrected 8.1), P 4.8, Alb 3.1.

Personal history

40-year-old male, studying criminology at the university. No tobacco or alcohol use.

Patient history Patient’s chief nutrition complaint: “Miserable” due to too few calories in current diet. Dislikes limiting potassium. DM 2 for over 13 years. Blood pressure 142/80 today.

Social history Wife is trying to lose weight too. Both attend university; up late with homework. Easier to grab fast food. Wife is struggling with potassium restriction; she tries to eat what he eats.

Assessment (2/16) Continued

Inadequate iron intake is related to non-

adherence to iron supplementation, as evidenced by

not taking FeSO4 and TSAT level.

Nutrition-related knowledge deficit is related to

lack of knowledge about need for sodium restriction

evidenced by fast food intake, salted snacks.

Diagnoses

Nutrition education: Role of kidney disease in anemia;

why treating anemia may help with ability to exercise for

weight loss; need for FeSO4; may be prescribed ESAs in

the future; role of sodium in controlling blood pressure

and CKD. Gave him NKDEP’s Sodium handout and used

Your Kidney Test Results to show lab results.

Goal: Take 325 mg FeSO4 with breakfast and supper as

prescribed. Begin reading Nutrition Facts for sodium

information. Choose foods with less sodium.

Collaborate with other providers in regard to his CKD.

Intervention

Joseph developed anemia; he was treated with oral iron and ESAs

Iron Studies

Reference Anemia 2/16 5/22

% Sat > 20% < 16% 19 20

Ferritin 80–270mcg/L

< 12 mcg/L

134 134

Monitor hemoglobin levels (CBC)

Assess iron status prior to use of supplements

− Transferrin saturation

− Ferritin

May need iron supplementation

− May be most effective between meals

May receive ESAs

May receive parenteral iron

Summary: Anemia of CKD

HYPERKALEMIA

Potassium excretion is regulated by the renin-angiotensin-aldosterone system

Serum potassium may increase as eGFR decreases


Potassium balance

− Transcellular shifts

Hyperkalemia

− Serum K ≥ 5.0 mEq/L

− Interventions

Topics

Joseph’s diet and medications play a role in his hyperkalemia, but it’s not the entire story

Serum potassium levels affect muscle functioning

Hypokalemia

− Cardiac arrhythmias

− Muscle weakness

− Glucose intolerance

Hyperkalemia

− Cardiac arrhythmias

− Muscle weakness

The reference range for serum potassium level is

3.5–5.0 mEq/L.

Susceptibility to hyperkalemia depends on calcium

level and other factors determining transmembrane

potential.

Cardiac arrhythmias and cardiac arrest are possible

if severe hyperkalemia is not recognized and

treated.

Hyperkalemia is potentially life threatening

About 85% of dietary potassium is absorbed.

Proximal tubules reabsorb 70–80% of K.

Potassium secretion occurs in distal tubule and

collecting duct and may be an “adaptation” to high

intake.

A small amount may be excreted in the feces.

Potassium balance involves the kidneys

Reference: Gennari & Segal, Kidney Int 2002; 62(1):1–9.

Activation of RAAS increases potassium excretion via

aldosterone.

Medications that inhibit RAAS increase risk for

hyperkalemia.

Renin-angiotensin-aldosterone system (RAAS) affects potassium excretion

98% of potassium is intracellular.

− 75% in muscles

2% is extracellular (65–70 mEq).

Transcellular electrical potential generated by

sodium-potassium exchange is responsible for

voltage gradient across cell membranes.

Gradient difference is needed for muscle and nerve

function.

K shifts between intracellular and extracellular compartments

Insulin concentration and hyperglycemia

− Insulin moves potassium into cells.

− Insulin deficiency may lead to hyperkalemia.

Acid-base status

− Metabolic acidosis (excessive hydrogen ion in plasma)

may drive potassium out of cells, as hydrogen ion is

buffered intracellularly.

Factors affecting potassium shifts between compartments

Control hyperglycemia with adequate insulin.

− Potassium follows glucose into the cells.

Treating acidosis may lower serum potassium.

− Treatment may allow continued use of blood pressure

medications that help lower urine albumin.

− Dietary protein may play a role here.

Treating hyperglycemia and acidemia may lower serum potassium

Reference: Palmer, N Engl J Med 2004; 351(6):585–592

Impaired K excretion

− ACEi

− ARBs

− K+-sparing diuretics

− Nonsteroidal anti-inflammatory drugs

− Tacrolimus or cyclosporine (anti-rejection medication

for transplant)

Medication-induced hyperkalemia is a concern in CKD

Specific level of eGFR does not determine need for

potassium restriction.

Restrict dietary potassium to help achieve and

maintain safe level.

Level of potassium restriction should be

individualized.

Potassium restriction is not indicated in the absence of hyperkalemia

Metabolic acidosis may result in K moving out of the

cells to maintain electroneutrality.

His nephrologist changed medications:

− Stopped the angiotensin-converting enzyme inhibitor

(ACEi), and is trying an angiotensin receptor blocker (ARB)

− Added loop diuretic

− Added sodium bicarbonate as base to treat the low serum

bicarbonate

Joseph’s potassium may be elevated due to transcellular shifts

Treating metabolic acidosis may have helped lower Joseph’s serum potassium

Food/beverage intake

Still eating 3 eggs, 1–2 slices of dry white toast. Added “small” lunch―regular burger, apple. Dinner: green beans, rice, small piece of meat. Fewer fast foods and salted snacks. Drinking diet beverage with potassium acesulfame in office.

Diet experience Using recipes from cooking classes. Still hard to follow K restriction. Very happy weight < 300#. Wife is helping with Na restriction.

Physical activity Walking 10–15 minutes/day with wife; less shortness of breath

Height & weight Height 69”, weight 296#

Biochemical data eGFR 18 (stable), Up/Ucr 5.6 (), K 5.5 (), CO2 16.2 (), Hgb 10.6 (improved), iron studies next month. Ca 8.0 (corrected 8.5), P 5.2. Vitamin D and intact parathyroid hormone (iPTH) drawn today.

Patient history Darbopoeitin injections continue. Saw nephrologist last week. Lisinopril discontinued; added losartan 50 mg, furosemide 80 mg and sodium bicarbonate 650 mg BID. Blood pressure 138/85 today. Has dental appointment tomorrow for tooth extraction.

Reassessment (6/30) Met goals: Taking FeSO4 BID. No GI upset. Feels less fatigue, trying to walk more. Iron studies pending. Choosing foods with less sodium.

Altered nutrition-related laboratory value:

elevated K due to reduced renal excretion,

medication, and acidosis.

Decreased need for dietary phosphorus related

to reduced renal excretion and enhanced absorption

with use of active vitamin D (calcitriol) evidenced by

elevated serum level.

Diagnosis

Used Your Kidney Test Results to show improved

hemoglobin.

Reviewed dietary potassium; sodium bicarbonate may help

lower serum level.

Started discussing phosphorus, binders and calcitriol.

Gave him Phosphorus and How to Read a Food Label

handouts.

Goals: Read ingredient lists for added phosphorus and

potassium. Choose foods without added P and K. Take new

medications as prescribed.

Intervention: Nutrition education

HYPOALBUMINEMIA

Serum albumin is a marker for nutritional status and inflammation

Serum albumin

Hypoalbuminemia

− Inflammation

− Poor oral intake

Metabolic acidosis and hypoalbuminemia

Topics

Joseph’s hypoalbuminemia improved with various interventions

Very little albumin crosses glomerular basement

membrane normally.

Most is reabsorbed by the tubule.

Damaged kidneys allow albumin to cross the

filtration barrier into the urine.

The level of albumin in the urine may exceed

tubule’s capacity to reabsorb the protein.

Review: Renal handling of albumin

Maintains oncotic pressure and blood volume

Acts as buffer

Binds (some examples):

− Calcium, magnesium

− Hormones

− Vitamins (e.g., A, riboflavin, B6, C, and folate)

− Medications (e.g., furosemide)

Serum albumin is a marker for nutritional status and

inflammation

Serum albumin

Serum albumin ≥ 4.0 g/dL at initiation of dialysis is

associated with reduced mortality risk.

Only 11% of new dialysis patients had serum

albumin ≥ 4.0 g/dL (1999–2005).

Serum albumin level at dialysis initiation is an independent risk factor for mortality

Reference: Adapted from Kaysen et al. J Renal Nutr 2008; 18(4):323–331.

Inflammation

− Acute or chronic, e.g., foot ulcer, infected tooth

Albuminuria

Metabolic acidosis

Insulin resistance

Spontaneous decrease in intake in CKD, particularly

for foods high in protein

Hypoalbuminemia in CKD is multifactorial

Low serum albumin in CKD is associated with inflammation

Reference: Eustace et al. Kidney Int 2004; 65(3):1031–1040.

Joseph’s weight loss and lower sodium intake may have helped improve albumin

Dental extraction and treating metabolic acidosis may have helped improve

Joseph’s albumin

Reassessment (7/29)Met goal: Reading labels for phosphorus and potassium. Dislikes diuretic, plans when to take; if he has class, takes later in the day.

Note: Improved fluid balance with diuretic also may have affected albumin level.

Diet experience Feeling more confident with sodium, potassium, and calorie restrictions. Surprised about all the added phosphorus in foods.

Medications Nephrologist added calcium acetate 667 mg with meals 2 weeks ago. Glad he knew why he had to take it.

Physical activity

Not walking as often (summer term).

Height & weight Height 69”, weight 293#, down 3# since last month.

Labs eGFR 18 (stable), K 4.9 (improved), CO2 18.5 (low but improved), P 5.3 (), Ca 8.1, (corrected 8.5), 25(OH)D 25, iPTH 130; Alb 3.5, was 3.3 last month.

Patient history Dentist extracted 2 teeth last month, no problems chewing. Blood pressure 136/85. Tearful when discussing eGFR, possible need for dialysis before getting on transplant list. Still not ready to make decision about dialysis option.

Altered nutrient-related laboratory value:

Elevated phosphorus; just started phosphorus-

binding medication 2 weeks ago.

NCP diagnosis

Nutrition education: Used Your Kidney Test Results to

re-explain why nephrologist is discussing dialysis

options. Discussed diet requirements for different

treatment options.

Goals: Continue sodium, potassium, phosphorus

restrictions. Continue medications as prescribed,

including calcium acetate with meals (phosphorus

binder).

Intervention

Reduce inflammation, treat infections

Serum albumin ≥ 4.0 g/dL at initiation of dialysis

associated with lower risk of mortality

Control blood pressure to slow progression

Provide adequate protein and calories

Treat metabolic acidosis

− Eating less protein may reduce acid load.

− Physician may prescribe medication to treat.

Summary: Hypoalbuminemia in CKD

METABOLIC ACIDOSIS

A serum bicarbonate level < 22 mEq/L may indicate metabolic acidosis

Serum bicarbonate may decrease as eGFR decreases


Metabolic acidosis (chronic)

Possible adverse effects of metabolic acidosis

Interventions

Topics

Acid production exceeds acid loss

CO2 + H2O HCO3 + H+

The reference range for serum HCO3 is

21–28 mEq/L.

Maintaining normal serum HCO3 may be beneficial.

Metabolic acidosis = excessive hydrogen ions in the blood

Tubules reabsorb filtered HCO3 and synthesize HCO3

to neutralize acid load.

− About 80–85% is reabsorbed within the proximal

tubules.

Patients with CKD have fewer functioning nephrons.

− Less hydrogen ion (acid) is excreted.

− Capacity to reabsorb and synthesize HCO3 is reduced.

− Condition may lead to chronic metabolic acidosis.

Kidney tubules help maintain normal acid-base balance

Accelerates muscle degradation

Reduces albumin synthesis

Exacerbates pre-existing bone disease

May impair glucose tolerance due to interference

with insulin actions

May accelerate CKD progression

May stimulate inflammation

Chronic metabolic acidosis

Endogenous acid production correlates to animal

protein intake, primarily due to the catabolism of

sulfur-containing amino acids.

Fruit and vegetables are not sources of acid load.

Reducing dietary protein may result in increasing

bicarbonate levels.

Animal protein may be a source of acid load

References: Remer & Manz, J Am Diet Assoc 1995; 95(7):791–797; Gennari et al. Clin J Am Soc Nephrol 2006; 1(1):52–57

Adequate, not excessive, intake of animal protein

Supplemental base may be prescribed to balance

the acid

Sodium bicarbonate may be prescribed,

650 mg tablet has 179 mg sodium

Re-emphasize dietary salt restriction, if used

May require higher dose of diuretic

Interventions for chronic metabolic acidosis

Reference: Kraut & Madias, Nat Rev Nephrol 2010; 6(5):274–285

Treating metabolic acidosis may have helped improve Joseph’s albumin

Serum bicarbonate (HCO3) level < 22 mEq/L may

indicate metabolic acidosis.

Animal protein may increase acid load.

Reducing protein may increase serum HCO3.

Supplemental base may be prescribed to treat.

Sodium bicarbonate will increase sodium intake.

Review salt restriction, if prescribed.

Treatment may improve serum albumin levels.

Summary: Metabolic acidosis

CKD MINERAL AND BONE DISORDERS

Kidneys fail to maintain serum calcium and phosphorus levels

CKD bone disorders

Vitamin D

Phosphorus

Calcium

Parathyroid hormone (PTH)

Fibroblastic growth factor-23 (FGF-23)

Topics

Lower serum calcium, higher serum phosphorus may be seen as eGFR declines


Systemic disorder of mineral and bone metabolism

due to CKD is identified by:

− Abnormalities of calcium, phosphorus, PTH, or vitamin

D metabolism

− Abnormalities in bone turnover, mineralization,

volume, linear growth, or strength

− Vascular or other soft-tissue calcification

CKD mineral and bone disorders

Reference: Kidney International (suppl 113), 2009

Joseph’s kidneys failed to maintain serum calcium and phosphorus levels

High bone turnover disease

− Also known as secondary hyperparathyroidism

Low bone turnover disease

− Adynamic

May be seen more frequently with diabetes

− Osteomalacia

Mixed bone disease

− Features of both high and low types

A range of bone disorders occur in CKD

Bone biopsy is the gold standard for diagnosing bone disease in CKD

Serum levels of calcium, phosphorus, intact

parathyroid hormone (iPTH), and alkaline phosphatase

(alk phos) vary by type of bone disease.

− Secondary hyperparathyroidism may see:

Elevated Ca, P, iPTH, alk phos

− Adynamic bone disease may see:

Normal or elevated Ca and P; normal to low iPTH and

alk phos

− Osteomalacia may see:

Elevated Ca; normal or elevated P, iPTH, alk phos

Laboratory indicators in bone disease

Reference: Martin & Gozalez, J Am Soc Nephrol 2007; 18(3):875–885.

1,25(OH)2 D

Calcium

Phosphorus

Parathyroid hormone (PTH)

Fibroblastic growth factor-23 (FGF-23)

Bone disease results from complex interactions

7-dehydrocholesterol

D2

Ergocalciferol(plants)

D3

Cholecalciferol (animals)

Ultraviolet B

D3

Liver

25(OH)D

Kidneys

1,25(OH)2 D(Calcitriol)

1-alpha-hydroxylase

25-hydroxylase

Major form in circulation, used to assess status

The kidneys activate vitamin D

The major circulating form of vitamin D is 25(OH)D.

The “adequate” level is > 20 ng/mL

(> 50 nmol/L).

Levels for CKD have not been established.

25(OH)D is used to assess vitamin D status

Reference: Institute of Medicine (November 2010)

Kidneys

− 1-alpha-hydroxylase enzyme in tubules stimulates

conversion of 25(OH)D to 1,25 (OH)2 D

− 1,25 (OH)2 D enhances tubular calcium reabsorption

Intestines

− 1,25 (OH)2 D increases calcium absorption and

increases phosphorus absorption

Bone formation

− 1,25 (OH)2 D increases calcium deposition

Calcitriol helps maintain serum calcium levels

Calcium-sensing receptors are located in the

parathyroid gland.

Low serum calcium stimulates PTH secretion from

the parathyroid.

PTH stimulates the 1-alpha-hydroxylase enzyme in

the tubule increasing 1,25(OH)2D which enhances

calcium absorption.

PTH increases calcium resorption from bone.

Parathyroid hormone helps maintain serum calcium levels

PTH reduces phosphorus reabsorption and increases

phosphorus excretion by tubule.

Serum phosphorus may remain in the normal range

as a result of higher PTH levels.

PTH stimulates phosphorus excretion

Normal serum level is thought to be < 65 pg/dL.

Levels vary by kidney function and type of bone

disease.

iPTH is not standardized, and levels may not be

comparable.

Intact PTH (iPTH) may be used to monitor PTH levels

Reference: Martin & Gozalez, J Am Soc Nephrol 2007; 18(3):875–885.

FGF-23 is produced by bone osteoclasts and

osteoblasts and is stimulated by high serum

phosphorus levels.

FGF-23 inhibits 1,25(OH)2D formation, which

decreases intestinal P absorption.

FGF-23 increases urinary phosphorus excretion.

Serum phosphorus is within “normal range.”

FGF-23 may maintain serum phosphorus levels

Reference: Ramon et al. Eur J Endocrinol 2010; 162(1):1–10.

CKD-MBD: Complex interactions involving numerous systems

Normal serum level: 8.5–10.2 mg/dL

40% transported on albumin

If hypoalbuminemia, use corrected calcium

Corrected calcium (mg/dL) =

serum calcium (mg/d) + 0.8(4.0 – serum albumin g/dL)

Correct calcium for albumin level

Reference: http://www.mdcalc.com/calcium-correction-for-hypoalbuminemia

Serum Ca 8.0

Serum albumin 3.0

Corrected calcium (mg/dL) = serum calcium (mg/dL)

+ 0.8(4.0 – serum albumin g/dL)

Corrected calcium = 8.0 + 0.8 (4.0 – 3.0) = 8.8

Example of calculation to correct calcium

Activity: Corrected calcium

Serum calcium

Serum albumin

Corrected calcium

7.4 2.3 -

8.1 2.9 -

8.3 3.0 -

Corrected calcium (mg/dL) =

serum calcium (mg/dL) + 0.8(4.0 – serum albumin g/dL)

Phosphorus restriction

Adequate, not excessive protein

Phosphorus-binding medication

− Usually calcium-based salts in CKD

Vitamin D (CKD) and vitamin D analogs

Interventions for bone disease in CKD

Phosphorus absorption differs between food sources.

− Food additives > animal sources > plant sources

Reducing dietary protein reduces phosphorus.

Phosphorus food additives can be identified by

reading ingredient list for phosphorus.

− Limit or avoid these foods.

Phosphorus in plants is not well absorbed due to

phytates (last ones to limit).

Dietary phosphorus restriction may be beneficial

Calcium carbonate

− 40% elemental calcium

− 1,250 mg tablet = 500 mg elemental calcium

Calcium acetate

− 25% elemental calcium

− 667 mg capsule = 169 mg elemental calcium

Calcium citrate

− NOT RECOMMENDED for CKD because of risk for

increased aluminum absorption.

Calcium-based phosphorus binders

Sevalemer bicarbonate

− Resin

− May also help lower low-density lipoprotein (LDL), increase

HCO3 level

− Expensive

Lanthanum carbonate

− Rare earth metal

− Expensive

Aluminum hydroxide

− Not recommended, used rarely

Other phosphorus binders are commonly used in dialysis

CKD

− Ergocalciferol

50,000 IU weekly

− Cholecalciferol

End-stage renal disease (ESRD)

− Calcitriol (risk for hypercalcemia and

hyperphosphatemia)

− Vitamin D analogs

Alfacalcidol (1-hydroxyvitamin D3)

Doxercalciferol (1-hydroxyvitamin D2)

Paricalcitol (19-nor-1,25-dihydroxyvitamin D3)

Vitamin D supplements

Reference: Palmer et al. Cochrane Database Syst Rev 2009; October 7(4);CD008175.

- Normal Levels Notes

Calcium 8.5–10.2 mg/dL If hypoalbuminemia, use corrected calcium Corrected Ca = serum Ca + 0.8(4.0 – serum albumin)

Phosphorus 2.7–4.6 mg/dL Phosphorus restriction• Adequate protein, not excessive intake

Phosphorus-binding medication with meals• Calcium based • Non-calcium based

25(OH)D > 20 ng/mL Ergocalciferol (D2)Cholecalficerol (D3)

iPTH < 65 pg/dL Assess levelVitamin D suppresses PTHPhosphorus restriction

Bone disease results from complex interactions

Using corrected calcium makes a difference when assessing Joseph’s Ca levels

As vitamin D increased, iPTH decreased

Supplemental vitamin D may increase phosphorus absorption

Vitamin D may lower iPTH.

Vitamin D increases calcium absorption and may be

discontinued with hypercalcemia.

Vitamin D increases phosphorus absorption and may

be discontinued with hyperphosphatemia.

Active vitamin D increases risk for hypercalcemia and hyperphosphatemia

Different types of renal bone diseases

− High turnover, low turnover, mixed

25(OH)D and iPTH levels

− Inversely related to each other

Serum phosphorus normal until advanced CKD

− May need dietary phosphorus restriction

− May need phosphate binders with meals

Summary: Bone disease in CKD

Anemia (inadequate erythropoietin)

− Monitor hemoglobin, transferrin saturation, ferritin

− May be treated with oral or parenteral iron;

erythropoietic-stimulating agents

− Take oral iron supplements at different times than

phosphate-binding medications

Hyperkalemia

− May involve dietary intake, use of medications that

block the RAAS, and transcellular shifts

− Limit dietary potassium when serum level elevated

Take-home messages: Complications increase as kidney function declines

Hypoalbuminemia

− Marker indicates nutritional status and inflammation.

− Serum albumin > 4.0 g/dL at times of initiation of dialysis

reduces risk of mortality.

− Treating metabolic acidosis may improve serum albumin.

Metabolic acidosis

− Maintaining normal serum HCO3 > 22 mEq/L may be

beneficial.

− Animal protein may be a source of metabolic acid.

− Condition may be treated with base such as sodium

bicarbonate.


Mineral and bone disorders

− Inadequate activation of Vitamin D

Check 25(OH)D

May be treated with supplemental vitamin D

− Increases both calcium and phosphorus absorption

− May be discontinued with hypercalcemia,

hyperphosphatemia

− Accumulation of phosphorus

iPTH and FGF-23 enhance excretion

May need phosphorus restriction

May need phosphate binders with meals


You may find this helpful when you counsel patients

Reference: http://nkdep.nih.gov/resources/nkdep-kidney-test-results-508.pdf

You may find this guide helpful

Reference: http://www.nkdep.nih.gov/resources/nkdep-ckd-amt-guide-508.pdf

If you think you are overwhelmed…consider the

person with CKD!

This professional development opportunity was created by the National Kidney Disease Education Program (NKDEP), an initiative of the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. With the goal of reducing the burden of chronic kidney disease (CKD), especially among communities most impacted by the disease, NKDEP works in collaboration with a range of government, nonprofit, and health care organizations to:

• raise awareness among people at risk for CKD about the need for testing;

• educate people with CKD about how to manage their disease;

• provide information, training, and tools to help health care providers better detect and treat CKD; and

• support changes in the laboratory community that yield more accurate, reliable, and accessible test results.

To learn more about NKDEP, please visit: http://www.nkdep.nih.gov. For additional materials from NIDDK, please visit: http://www.niddk.nih.gov.

Theresa A. Kuracina, M.S., R.D., C.D.E., L.N.

Ms. Kuracina is the lead author of the American Dietetic Association’s CKD Nutrition Management Training Certificate Program and NKDEP’s nutrition resources for managing patients with CKD.Ms. Kuracina has more than 20 years of experience in clinical dietetics with the Indian Health Service (IHS). She is a senior clinical consultant with the National Kidney Disease Education Program (NKDEP) at the National Institutes of Health. She also serves as a diabetes dietitian and coordinator for a diabetes self-management education program at the IHS Albuquerque Indian Health Center in New Mexico, a role in which she routinely counsels patients who have CKD.

Meet our Presenters

Andrew S. Narva, M.D., F.A.C.P.

Dr. Narva is the director of the National Kidney Disease Education Program (NKDEP) at the National Institutes of Health (NIH). Prior to joining NIH in 2006, he served for 15 years as the Chief Clinical Consultant for Nephrology for the Indian Health Service (IHS). Via telemedicine from NIH, he continues to provide care for IHS patients who have chronic kidney disease. A highly recognized nephrologist and public servant, Dr. Narva has served as a member of the Medical Review Board of ESRD Network 15 and as chair of the Minority Outreach Committee of the National Kidney Foundation (NKF). He serves on the NKF Kidney Disease Outcomes Quality Initiative Work Group on Diabetes in Chronic Diabetes and is a member of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 8 Expert Panel.

Meet our Presenters

American Dietetic Association. International Dietetics and Nutrition Terminology (IDNT) Reference Manual. Standardized Language for the Nutrition Care Process. 3rd ed. Chicago, IL: American Dietetic Association; 2011.

A physician’s guide to oral iron supplements. National Anemia Action Council website. http://www.anemia.org/professionals/feature-articles/content.php?contentid=306&sectionid=15 November 2008. Accessed June 14, 2011.

Besarab A, Coyne DW. Iron supplementation to treat anemia in patients with chronic kidney disease. Nature Reviews Nephrology. 2010;6(12):699–710.

Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin levels in patients with chronic kidney disease and anemia. New England Journal of Medicine. 2006;355(20):2071–2084.

References: Anemia

FDA Drug Safety Communication: Erythropoiesis-stimulating agents (ESAs): Procrit, Epogen and Aranesp. U.S. Food and Drug Administration website. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm200297.htm . February 26, 2010. Accessed September 8, 2011.

FDA Drug Safety Communication: Modified dosing recommendations to improve the safe use of erythropoiesis-stimulating agents (ESAs) in chronic kidney disease. U.S. Food and Drug Administration website. http://www.fda.gov/Drugs/DrugSafety/ucm259639.htm . June 24, 2011. Accessed September 7, 2011.

Fleming RE, Bacon BR. Orchestration of iron homeostasis. New England Journal of Medicine. 2005;352(17):1741–1744.

Ganz, T. Molecular control of iron transport. Journal of the American Society of Nephrology. 2007;18(2):394–400.

References: Anemia

Ganz T, Nemeth E. Iron imports. IV. Hepcidin and regulation of body iron metabolism. American Journal of Physiology Gastrointestinal and Liver Physiology. 2006;290(2):G199–G203.

Hörl WH. Clinical aspects of iron use in the anemia of kidney disease. Journal of the American Society of Nephrology. 2007;18(2):382–393.

Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, D.C.: National Academy Press; 2001. Institute of Medicine website. http://iom.edu/Reports/2001/Dietary-Reference-Intakes-for-Vitamin-A-Vitamin-K-Arsenic-Boron-Chromium-Copper-Iodine-Iron-Manganese-Molybdenum-Nickel-Silicon-Vanadium-and-Zinc.aspx. Accessed August 31, 2011.

References: Anemia

Kopple JD, Greene T, Chumlea WC, et al. Relationship between nutritional status and the glomerular filtration rate: results from the MDRD Study. Kidney International. 2000;57(4):1688–1703.

Kovedsky CP. Iron and clinical outcomes in dialysis and non-dialysis-dependent chronic kidney disease patients. Advances in Chronic Kidney Disease. 2009;16(2):109–116.

National Kidney Disease Education Program. Your kidney test results. Revised September 2011. NIH publication 11–7407. National Kidney Disease Education Program website. http://nkdep.nih.gov/resources/nkdep-kidney-test-results-508.pdf. Accessed September 8, 2011.

National report on biochemical indicators of diet and nutrition in the U.S. population 1999–2002. U.S. Centers for Disease Control and Prevention website. http://www.cdc.gov/nutritionreport/part_3.html. July 2008. Accessed June 14, 2011.

References: Anemia

Normal iron absorption and storage. Centers for Disease Control and Prevention website. http://www.cdc.gov/ncbddd/hemochromatosis/training/pathophysiology/iron_cycle_popup.htm . Updated September 23, 2010. Accessed June 14, 2011.

Singh AK. Does TREAT give the boot to ESAs in the treatment of CKD anemia? Journal of the American Society of Nephrology. 2010;21(1):2–6.

Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. New England Journal of Medicine. 2006;355(20):2085–2098.

Strippoli GFM, Craig JC, Manno C, Schena FP. Hemoglobin targets for the anemia of chronic kidney disease: a meta-analysis of randomized, control trials. Journal of the American Society of Nephrology. 2004;15(12):3154–3165.

References: Anemia

Toto RD. Anemia of chronic disease: past, present, future. Kidney International. 2003;64(suppl 87):S20–S23.

U.S. Renal Data System. USRDS 2010 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2010. United States Renal Data System website. http://www.usrds.org/adr.htm. Accessed August 31, 2011.

U.S. Renal Data System. USRDS 2009 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2009. United States Renal Data System website. http://www.usrds.org/adr.htm. Accessed August 31, 2011.

References: Anemia

Young B, Zaritsky J. Hepcidin for clinicians. Clinical Journal of the American Society of Nephrology. 2009;4(8):1384–1387.

Zager RA, Johnson ACM, Hanson SY. Parenteral iron nephrotoxicity: potential mechanisms and consequences. Kidney International. 2004;66(1):144–156.

Zager RA. Parenteral iron compounds: potent oxidants but mainstays of anemia management in chronic renal disease. Clinical Journal of the American Society of Nephrology. 2006;1(suppl 1):S24–S31.

References: Anemia

Gennari FJ, Segal AS. Hyperkalemia: an adaptive response in chronic renal insufficiency. Kidney International. 2002;62(1):1–9.

Institute of Medicine. Dietary Reference Intakes for Water, Potassium, Sodium, Chloride, and Sulfate. Washington, D.C.: National Academy Press; 2004. Institute of Medicine website. http://iom.edu/Reports/2004/Dietary-Reference-Intakes-Water-Potassium-Sodium-Chloride-and-Sulfate.aspx. Accessed June 13, 2011.

Palmer BF. Managing hyperkalemia caused by inhibitors of the renin-angiotensin-aldosterone system. New England Journal of Medicine. 2004; 351(6):585–592.

Schaefer TJ, Wolford RW. Disorders of potassium. Emergency Medicine Clinics of North America. 2005;23(3):723–747.

References: Hyperkalemia

U.S. Renal Data System. USRDS 2009 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2009. United States Renal Data System website. http://www.usrds.org/adr.htm . Accessed August 31, 2011.

References: Hyperkalemia

Bailey JL. Metabolic acidosis: an unrecognized cause of morbidity in the patient with chronic kidney disease. Kidney International. 2005;68(suppl 96):S15–S23.

Birn H, Christensen EI. Renal albumin absorption in physiology and pathology. Kidney International. 2006;69(3):440–449.

Eustace JA, Astor B, Muntner PM, Ikizler TA, Coresh J. Prevalence of acidosis and inflammation and their association with low serum albumin in chronic kidney disease. Kidney International. 2004;65(3):1031–1040.

Kaysen GA, Johansen KL, Cheng S, Jin C, Chertow GM. Trends and outcomes associated with serum albumin concentration among incident dialysis patients in the United States. Journal of Renal Nutrition. 2008;18(4):323–331.

References: Hypoalbuminemia

Kopple JD, Kalantar-Zadeh K, Mehrotra R. Risks of chronic metabolic acidosis in patients with chronic kidney disease. Kidney International. 2005;67(suppl 95):S21–S27.

References: Hypoalbuminemia

Bailey JL. Metabolic acidosis: an unrecognized cause of morbidity in the patient with chronic kidney disease. Kidney International. 2005;68(suppl 96):S15–S23.

de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM. Bicarbonate supplementation slows progression of CKD and improves nutritional status. Journal of the American Society of Nephrology. 2009;20(9):2075–2084.

Gennari FJ, Hood VL, Greene T, Wang X, Levey AS. Effect of dietary protein intake on total serum CO2 concentration in chronic kidney disease: Modification of Diet in Renal Disease study findings. Clinical Journal of the American Society of Nephrology. 2006;1(1):52–57.

Kraut JA, Madias NE. Metabolic acidosis: pathophysiology, diagnosis and management. Nature Reviews Nephrology. 2010;6(5):274–285.

References: Metabolic Acidosis

Remer T, Manz F. Potential renal acid load of foods and its influence on urine pH. Journal of the American Dietetic Association. 1995; 95(7):791–797.


References: Metabolic Acidosis

Dietary supplements fact sheet: vitamin D. Office of Dietary Supplements, National Institutes of Health website. http://ods.od.nih.gov/factsheets/VitaminD/. Reviewed June 24, 2011. Accessed August 31, 2011.

Doorenbos CRC, van den Born J, Navis G, de Borst MH. Possible renoprotection by vitamin D in chronic renal disease: beyond mineral metabolism. Nature Reviews Nephrology. 2009;5(12):691–700.

Emmett M. A comparison of clinically useful phosphorus binders for patients with chronic kidney failure. Kidney International. 2004;66(suppl 90):S25–S32.

Fadem SZ, Moe SM. Management of chronic kidney disease mineral-bone disorder. Advances in Chronic Kidney Disease. 2007;14(1):44–53.

References: Mineral and Bone Disorders

Felsenfeld AJ, Rodriguez M, Aguilera-Tejero, E. Dynamics of parathyroid hormone secretion in health and secondary hyperparathyroidism. Clinical Journal of the American Society of Nephrology. 2007;2(6):1283–1305.

Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, D.C.: National Academies Press; 2010. Institute of Medicine website. http://www.iom.edu/Reports/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D.aspx. November 2010; updated May 9, 2011. Accessed June 14, 2011

Kalantar-Zadeh K, Gutekunst L, Mehrotra R, et al. Understanding sources of dietary phosphorus in the treatment of patients with chronic kidney disease. Clinical Journal of the American Society of Nephrology. 2010;5(3):519–530.


Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney International. 2009;76(suppl 113):S1–S130. Kidney Disease Improving Global Outcomes website. http://www.kdigo.org/guidelines/mbd/index.html . Accessed August 31, 2011.

Liu S, Quarles LD. How fibroblastic growth factor 23 works. Journal of the American Society of Nephrology. 2007;18(6):1637–1647.

Martin KJ, Gonzalez EA. Metabolic bone disease in chronic kidney disease. Journal of the American Society of Nephrology. 2007;18(3):875–885.


National Kidney and Urologic Diseases Information Clearinghouse. Chronic kidney disease—Mineral and bone disorder. February 2009. NIH publication 09–4630. National Kidney and Urological Diseases Information Clearinghouse website. http://www.kidney.niddk.nih.gov/kudiseases/pubs/CKD_Mineral_Bone . Accessed June 14, 2011.

National Kidney Disease Education Program. Chronic kidney disease (CKD) and diet: assessment, management and treatment. Treating CKD patients who are not on dialysis. An overview guide for dietitians. Revised September 2011. National Kidney Disease Education Program website. http://nkdep.nih.gov/resources/nkdep-ckd-amt-guide-508.pdf. Accessed September 8, 2011.

Palmer SC, McGregor DO, Craig JC, Elder G, Macaskill P, Strippoli GF. Vitamin D compounds for people with chronic kidney disease not requiring dialysis. Cochrane Database of Systematic Reviews. 2009;October 7(4);CD008175.


Palmer SC, Hayen A, Macaskill P, et al. Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: a systematic review and meta-analysis. Journal of the American Medical Association. 2011;305(11):1119–1127.

Prentice A, Goldberg GR, Schoenmakers I. Vitamin D across the lifecycle: physiology and biomarkers. American Journal of Clinical Nutrition. 2008;88(2):500S–506S.

Ramon I, Kleynen P, Body J, Karmali R. Fibroblastic growth factor 23 and its role in phosphate homeostasis. European Journal of Endocrinology. 2010;162(1):1–10.

Seiler S, Heine GH, Fliser D. Clinical relevance of FGF-23 in chronic kidney disease. Kidney International. 2009;76(suppl 114):S34–S42.




Health & Medicine

CKD MNT Module 3: Complications