Approach to Renal Diseases

Outline

•Types of renal syndromes

•Causes

•Diagnostic approach to each syndrome

•Approach to renal allograft

Types of renal syndromes

Hematuria

Proteinuria

Nephrotic syndrome

Nephritic syndrome

Acute renal failure

Chronic renal failure

Urinary tract infections

Nephrolithiasis

HEMATURIA

• Red or brown urine

• Substances other than RBCs can also produce red or

brown urine.

• Urine test strip or dipstick (dark green)

color change in a chromogen (to blue)

hemoglobin peroxidase-like activityfree

In RBCs

microscopic examination of the urine

Causes of Red or Brown Urine Endogenous Substances Foods Drugs

Red blood cells Hemoglobin Myoglobin Bilirubin Porphyrins Melanin

Artificial food coloring Beets Blackberries Blueberries Fava beans Paprika Rhubarb

Adriamycin Chloroquine Deferoxamine Levodopa Methyldopa Metronidazole Nitrofurantoin PhenazopyridinePhenolphthalein Phenytoin Prochlorperazine Quinine Rifampin Sulfonamides

Differentiation of Glomerular from Urologic Bleeding Feature Glomerular Hematuria Urothelial

Hematuria

Urine color Dark red, brown, cola-colored, smoky

Bright red

Clots - +Proteinuria + -Red blood cell morphology

Dysmorphic (especially acanthocytes)

Isomorphic

Hypertension + -Edema + -Urinary voiding symptoms

- +

Back pain, flank pain + +Renal function Reduced normalFamily history + +Trauma - +Upper RTI + -

Fever, rash + -

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Hematuria

Causes of hematuriaGlomerular Lesions

Thin basement membrane nephropathyIgA glomerulonephritis

FSGSLupus glomerulonephritis

Crescentic glomerulonephritis Membranous glomerulonephritis

Mesangiocapillary glomerulonephritisDense deposit disease

PSGN

Nonglomerular HematuriaUrinary tract infectionUrinary tract calculi

Hypercalciuria and hyperuricosuriaAutosomal dominant polycystic kidney

diseaseBenign prostatic hypertrophyTransitional cell carcinoma

Nonglomerular HematuriaRenal cell carcinomaProstatic carcinomaExercise hematuria

TraumaBleeding diathesis and anticoagulants

Renal papillary necrosisSickle cell diseas

PROTEINURIA

• The dipstick is based on color change induced by the

presence of proteins at a given pH.

• Albumin> other proteins (light chains of Bence Jones

protein)

• 1+ protein ~ 30 mg/dL of proteinuria

• 3+ protein ~ 500 mg/dL of proteinuria.

Types of proteinuria

tubular

overflow

glomerular

Loss of charge and size selectivity>1gm/day

Mostly LMW proteins

Small or +vely charged proteins(Myeloma)

PROTEINURIA

• Microalbuminuria : excretion of abnormal quantities of

albumin below the level detectable by the urine dipstick.

• Radioimmunoassay or enzyme immunoassay.

• Earliest clinically detectable stage of diabetic

nephropathy

• Normal albumin excretion <30 mg/day

NEPHROTIC SYNDROME

1) High-grade, albumin-dominant proteinuria (generally

>3000 mg/day or spot urine protein/creatinine ratio of

>3000 mg of protein/gm of creatinine)

2) Hypoalbuminemia

3) Edema

4) Hyperlipidemia

5) Lipiduria

Diagnostic Evaluation in Adults with Nephrotic Syndrome• Patient history : medication or toxin exposure; risk factors for HIV or viral

hepatitis

• H/O diabetes, systemic lupus erythematosus, or other systemic illness

• Urine dipstick : Confirm proteinuria

• Random urine protein/creatinine ratio

• Quantify degree of proteinuria (ratio greater than 3 to 3.5)

• Serum creatinine

• Rule out acute renal failure, assess glomerular filtration rate

• Serum albumin : hypoalbuminemia

• Lipid panel : hyperlipidemia

• Serum or urine protein electrophoresis : amyloidosis or multiple myelomaNephrotic Syndrome in Adults: Diagnosis and ManagementAm Fam Physician. 2009 Nov 15;80(10):1129-1134

Approach to nephrotic syndrome in children

Diagnostic studies for nephrotic syndrome in children

• Establish whether nephrotic syndrome is present, because hypoalbuminemia

can occur in the absence of proteinuria and edema can occur in the absence

of hypoalbuminemia

• Laboratory tests should confirm (1) nephrotic-range proteinuria (2)

hypoalbuminemia, and (3) hyperlipidemia.

• Urinalysis

• Urine protein quantification (by first-morning urine protein/creatinine or 24-

hour urine protein)

• Serum albumin

• Lipid panel

Diagnostic studies for nephrotic syndrome in children

• First morning urine protein/creatinine is more easily

obtained than 24-hour urine studies (more reliable) and

excludes orthostatic proteinuria.

• Nephrotic-range proteinuria :

Urine protein/creatinine ratio > 2-3 mg/mg

24-hour urine protein level > 40 mg/m2/h

>1000 mg/m2/d

Diagnostic studies for nephrotic syndrome

• Lipid panel findings are typically as follows:

• Elevated total cholesterol, LDL cholesterol

• Elevated triglycerides with severe hypoalbuminemia

• HDL cholesterol (normal or low)

Diagnostic studies for nephrotic syndrome in children• Other tests and procedures in selected patients may include the following:

• < 1 year of age should be evaluated for congenital/infantile nephrotic

syndrome.

• Congenital infection (syphilis, rubella, toxoplasmosis, CMV, HIV)

• NPHS1, NPHS2, WT1, and PLCE1 as guided by biopsy findings and clinical

presentation

• Kidney ultrasonography

• Chest radiography

• Mantoux test

• Kidney biopsy

Diagnostic studies for nephrotic syndrome in children• The patient with INS can present with acute kidney failure due to

intravascular volume depletion and/or bilateral renal vein thrombosis.

• In the absence of the above, elevated BUN and creatinine levels and

signs of chronic kidney failure suggest a chronic glomerular disease

other than MCNS, such as:

• Focal segmental glomerulosclerosis (FSGS)

• Membranous nephropathy (MN)

• MPGN

• IgA nephropathy

Indications of kidney biopsy

1) Age younger than 1 year or older than 8 years

2) Presence of recurrent gross hematuria

3) Relevant family history of kidney disease

4) Symptoms of systemic disease

5) Positive viral screens

NEPHRITIC SYNDROME

• Glomerular hematuria; active urine sediment

• Dysmorphic RBCs (especially acanthocytes) and RBC

casts; often WBCs and WBC casts

• Result of an inflammatory process in the glomerulus

• GFR reduced

• Variable degrees of hypertension, oliguria, and edema

NEPHRITIC SYNDROME

• Proteinuria -low magnitude

• In many cases, the degree of proteinuria is limited by the

accompanying reduction in GFR.

• High-grade proteinuria and even full-blown nephrotic

syndrome can coexist with nephritic syndrome in some

patients.

• Hematuria can be sporadic, intermittent, or persistent.

• It can be microscopic or gross

NEPHRITIC SYNDROME

• The character of the glomerular hematuria does not

always predict the underlying cause of the disorder, nor

does it predict the long-term renal outcome of the

process.

• Glomerular hematuria due to nephritic syndrome must

be distinguished from bleeding caused by other kidney,

interstitial, or lower GU tract pathology.

NEPHRITIC SYNDROMES

Synpharyngitic hematuria IgA nephropathy

Fever, skin rash, joint symptoms Systemic disease causing glomerular hematuria

Hearing loss and visual symptoms related to lens

Alport’s disease

Hemoptysis Vasculitis or anti–glomerular basement membrane disease

Serologies

Antinuclear antibody (ANA) lupus nephritis Lower titres (1:80 or 1:40 are non-specific)

Rheumatoid factor titer rheumatoid arthritis, cryoglobulinemia (type II, III)

Complement components C3 and C4Serum immunoelectrophoresis IgA nephropathy, HSP

Myeloma kidney, lymphomas, amyloidosis, LCDD, HCDD, immunotactoid glomerulonephritis, cryoglobulinemia

Urine electrophoresis, serum free light chains, kappa-lambda ratio

Complement serum electrophoresis

ANCA Rapidly progressive GN

Serologies

Anti-GBM antibodies (IF, western blot)

Anti-GBM disease

Cryoglobulins I: waldenstrom macroglobulinemia, myelomaII: Hepatitis C, SLE, Sjogren syndrome, lymphoma

Hepatitis B Membranous nephropathy

Hepatitis C MPGN, Membranous nephropathy, cryoglobulinemia

HIV Nephrotic syndrome, acute kidney injury

Anti-DNAse/Antistreptolysin titre PIGN

ESR Systemic vasculitis, multiple myeloma, malignancy, nephrotic syndrome [DM]

Complement Levels in Acute Nephritic Syndromes

• Low Serum Complement Levels

Systemic Diseases

SLE

Cryoglobulinemia (hepatitis C)

Bacterial endocarditis

Shunt nephritis

Renal Localized Diseases

Acute PSGN (low C3, normal C4)

MPGN

Type I (low C3 and C4)

Type II (dense deposit disease)

(low C3, normal C4)

Complement Levels in Acute Nephritic Syndromes

• Normal Serum Complement Levels

Systemic Diseases

PAN

ANCA–positive granulomatosis

with polyangiitis (Wegener’s)

Hypersensitivity vasculitis

HSP

Renal Localized Diseases

IgA nephropathy

RPGN

Anti–GBM disease

Pauci-immune GN

(kidney-localized)

Acute Renal Failure

MAKING THE DIAGNOSIS

• Characteristic Signs

• Decrease in GFR over a period of hours to days

• Failure to excrete nitrogenous waste products

• Failure to maintain fluid and electrolyte homeostasis

RIFLE Criteria for Acute Kidney Injury (AKI)

Risk Creatinine increase × 1.5 or GFR decrease > 25%

<0.5 mL/kg/hr for >6 hr

Injury Creatinine increase × 2 or GFR decrease > 50%

<0.5 mL/kg/hr for >12 hr

Failure Creatinine increase × 3 or GFR decrease > 75% orCreatinine ≥ 4 mg% (acute increase ≥ 0.5 mg%)

<0.3 mL/kg/hr for >24 hr or Anuria > 12 hr

Loss Persistent AKI = complete loss of renal function >4 wk

End-stage End-stage renal disease > 3 months

Acute Kidney Injury Network (AKIN) Criteria

Stage Creatinine Criteria Urine Output Criteria

1 Increase in serum creatinine ≥ 3 mg/dL (≥26.4 μmol/L) or increase ≥ 150%-200% (1.5-2 fold) above baseline

<0.5 mL/kg/hr for >6 hr

2 Increase in serum creatinine > 200%-300% (>twofold or threefold) above baseline

<0.5 mL/kg/hr for >12 hr

3 Increase in serum creatinine > 300% (>threefold) above baseline or serum

creatinine ≥ 4 mg/dL (≥354 μmol/L) with an acute rise ≥ 0.5mg/dL (≥44 μmol/L)

Prerenal Azotemia

• Intravascular volume depletion: Hemorrhage, renal fluid

loss, gastrointestinal losses, skin loss of sweat, third-

space losses

• Reduced cardiac output: Congestive heart failure,

cardiogenic shock, pericardial effusion with tamponad,

massive pulmonary embolism

• Increased renal vascular resistance: anesthesia,

hepatorenal syndrome, prostaglandin inhibitors, aspirin,

NSAIDs

Prerenal Azotemia

• Vasoconstricting drugs: cyclosporine, tacrolimus,

radiocontrast

• Decreased intraglomerular pressure : angiotensin-

converting enzyme inhibitors, angiotensin II receptor

blockers

Intrarenal or Intrinsic ARF

• Vascular causes :

• Bilateral renal artery:

• Stenosis

• Thrombosis

• Embolism

• Operative arterial cross

clamping

• Bilateral renal vein thrombosis

• Small vessel :

• Atheroembolic disease

• TMA

• Hemolytic uremic

syndrome/thrombotic

thrombocytopenic purpura

• Scleroderma renal crisis

• Malignant hypertension

• HELLP

• Postpartum ARF

Intrarenal or Intrinsic ARF

• Glomerular :E Goodpasture’s syndrome Granular immune complex deposition:E PostinfectiousE Infective endocarditisE Lupus nephritisE Immunoglobulin A (IgA) nephropathyE Henoch-Schönlein purpuraE Membranoproliferative GN No immune deposits:E Wegener’s granulomatosisE Polyarteritis nodosaE Churg Strauss

Postrenal Azotemia

• Bilateral ureteral obstruction or unilateral obstruction in a solitary

kidney:

• Intraureteral: Stones, blood clots, papillary necrosis

• Extraureteral: Bladder, Prostatic cancer, Cervical cancer,

retroperitoneal fibrosis

• Bladder neck obstruction : Prostatic hypertrophy, Prostatic cancer,

Bladder cancer, Autonomic neuropathy, urethral obstruction, Valves,

Strictures

Evaluation of patient

• Thorough history and physical examination

• Urine Sediment

• Rise in blood urea nitrogen, serum creatinine, or both

• Renal hypoperfusion

• Bland urine sediment

• Fractional excretion of sodium 1%

• Return of renal function to normal within 24 to 72 hours of correction

of the hypoperfused state

Urine biochemical parameters in ARF

Evaluation of patient

• Radiology

• Renal ultrasonography

• Computed tomography

• Cystoscopy and retrograde or anterograde pyelography

• Indications of renal Biopsy in ARF :

• 1) ARF of unknown cause

• 2) Suspicion of GN, systemic disease (eg, vasculitis), or AIN

• 3) ATN not recovering after 4 to 6 weeks of dialysis with no more

recurrent insults

Clinical Diagnosis

• Oliguria, 400 mL urine per day

• Serum markers of renal function (future): Cystatin C

• Urine biomarkers of tubular injury (future):

Interleukin 18

Kidney injury molecule 1

• Neutophil gelatinase associated lipocalin

Chronic Renal Failure

Chronic kidney disease

End-stage

renal

disease

Kidney failure

Kidney

damag

e

GFR < 60 mL/min/1.73 m2 for >3 months

abnormalities or markers of kidney damage abnormalities in the composition of blood or urineabnormalities on imaging tests

GFR< 15mL/ min/1.73m2S/S of uremia kidney replacement therapy for t/t of complications of decreased GFR

dialysis or transplantation regardless of the level of GFR

Estimation of Kidney Function

• GFR can be measured directly using parenteral inulin,

iohexol, or iothalamate

• In clinical practice, GFR is estimated by creatinine clearance

(Ccr), which is directly proportional to creatinine generation

from muscle and inversely proportional to serum creatinine

concentration

• GFR is dependent on age, body mass, nutritional status,

and laboratory measurement of creatinine

Estimation of Kidney Function

• Methods for Estimation of GFR:

• 24-hour urine for Ccr

• Patient instructed about collection of urine for 24 hours

Estimation of GFR

v

Estimation of Kidney Function

• Urea clearance: Ccr exceeds the GFR because of tubular secretion

whereas urea clearance is usually lower than GFR because of

tubular absorption

• Cystatin C: LMW protein produced by all human nucleated cells

• A serum marker of kidney insufficiency, may improve detection of

early CKD

Superior estimation of GFR by cystatin C in children, transplant

patients and cirrhotics

> sensitive for detection of early CKD than serum creatinine

Complications of CKD: bone/mineral,heart, anemia, acidosis, malnutrition

• Elevations of phosphorus occur with decrease in Ccr

around 50 to 60 mL/min

• Determination of vitamin D (including measurement of

25- and 1,25- vitamin D levels) and PTH status

Complications of CKD: bone/mineral,heart, anemia, acidosis, malnutrition

• Lipid profile in CKD : Hypercholesterolemia

• Lipid profile in nonproteinuric CKD, especially advanced

CKD, is frequently characterized by normal to low total

cholesterol levels, low HDL levels, relatively elevated serum

LDL levels, and elevated TGs

• Elevated levels of lipoprotein a

• Elevated levels of homocysteine, AGEs, and C-reactive

protein

• Q.1) Identify the urinary casts:

Fatty cast

Waxy cast Fatty cast

• Q.2) Idiopathic membranous nephropathy

is a/w which of the following?

Hepatitis B

Hepatitis C

NSAIDs

Antibodies to M-type phospholipase receptor

All of the above

• Q.3)Estimation of GFR in pediatric population is done

by?

Schwartz formula

Cockroft gault formula

MDRD equation

CKD-EPI equation

Any of the above

Cr Cl = k. Height (cms) serum Cr (mg/dl)

• Q.4) Identify the urinary crystals:

Cystine crystalsTriple phosphate crystals

Thank you