HEREDITARY NEPHROPATHIES

Hereditary nephropathies include a large number of glomerular and tubulointerstitial disorders (Table 21.4) with known inheritance pattern or strong family history. Although rare, these disorders are an important causes of chronic renal failure in young children.

Important hereditary nephropathies may be broadly divided into three categories: (a) renal malformations, e.g. polycystic disease, (b) glomerulopathies, and (c) tubular disorders, discussed in respective chapters. Polycystic kidney disease, nephronophthisis and Alport syndrome are commonest hereditary nephropathies in children.

21.5 HEMATURIA

Hematuria is defined as 'presence of gt; 5 RBCs/high power field in centrifuged sample or gt;10 RBCs/mm³ in uncentrifuged urine sample.

TABLE 21.4: Important hereditary nephropathies

Polycystic renal disease

Predominantly glomerular disorders

• Congenital nephrotic syndrome

• Glomerular basement membrane defects

- Alport syndrome

- Familial benign hematuria

- Nail-patella syndrome

Predominantly tubular disorders

• Renal tubular acidosis

• Generalized transport defects

- Fanconi syndrome

- Lowe syndrome

• Isolated transport defects

- Idiopathic hypercalciuria

- Bartter syndrome

- Cystinosis

• Urinary concentration defects

- Nephrogenic diabetes insipidus

- Nephronophthisis

TABLE 21.5: Causes of hematuria in childhood

Glomerular

• Acute post-infectious GN (APIGN)

- Acute post-streptococcal GN (APSGN)

- Other infections

Bact: Staphylococci, Pneumococci, Salmonella

Viral: HBV, HCV, CMV, EBV

Others: Leptospira, malaria, filariasis, candidiasis Shunt nephritis, infective endocarditis

• Rapidly progressive GN

• Chronic GN: Membranoproliferative GN

• Hemolytic-uremic syndrome

• IgA nephropathy (Berger disease)

• Vasculitis syndromes: SLE, HSP

• Hereditary: Benign familial hematuria

Extra-glomerular

• Infections: UTI, tuberculosis, leptospirosis, HIV

• Congenital: Polycystic kidney, A-V malformations

• Urolithiasis: Stones, idiopathic hypercalciuria

• Neoplasms: Wilms' tumor, bladder tumors

• Trauma: Injury, surgery/biopsy, exercise

• Bleeding disorders: Purpura, DIC, coagulopathies

• Vascular: Renal vein thrombosis, sickle cell disease

• Drugs: NSAIDs, cyclophosphamide penicillamine

• Others: Acute interstitial nephritis

GN: Glomerulonephritis

Transient asymptomatic microscopic hematuria is not uncommon, seen in 0.5-2.0% of school children and does not require elaborate investigations.

Etiology: Hematuria may be glomerular or extra- glomerular in origin (Table 21.5). Acute post-streptococcal glomerulonephritis (APSGN) is the commonest cause of glomerular hematuria in childhood, while

Fig. 21.2: Diagnostic approach in hematuria.

extrarglomerular hematuria is usually due to, urinary tract infections, hypercalciuria or stones.

Diagnostic evaluation: An algorithm to evaluate pathoญlogical hematuria is given in Fig. 21.2, based on following steps:

Step I. To differentiate hematuria from other causes of Red-colored urine, e.g.-(a) hemoglobinuria due to severe intravascular hemolysis, (b) myoglobinuria due to rhabdomyolysis after major trauma or strenuous exercise, (c) porphyria, and (d) drugs, e.g. rifampicin or sugar beet.

A positive Benzidine test indicates hematuria, hemoglobinuria or myoglobinuria, excluding other causes of red urine. Presence of fresh RBCs on microscopy generally excludes hemoglobinuria and myoglobinuria.

Step II. To differentiate between glomerular vs non- glomerular hematuria, on the basis of fresh-urine examination, as given in Table 21.6.

Step III. Clinical evaluation, based on:

• Age of presentation:

- Newborn: Congenital anomalies, bleeding diathesis, renal vein thrombosis, acute cortical necrosis.

- Infancy: Congenital anomalies, Wilms' tumor, Hereditary nephropathies.

- Older children: APSGN, UTI, renal trauma.

• Past history:

- Throat/skin infection in APSGN.

TABLE 21.6: D/D glomerular vs non-glomerular hematuria

* due to acid hematin formation ** On phase contrast microscopy

- Recurrent hematuria in IgA nephropathy, benign familial hematuria, Alport syndrome, idiopathic hypercalciuria, etc.

• Family history:

- Congenital anomalies,

- Hereditary nephropathies.

• Magnitude of hematuria:

- Gross: APSGN, IgA nephropathy, Wilms' tumor, bleeding disorders, renal vein thrombosis

- Microscopic: UTI, chronic glomerulonephritis, collagen disorders, urolithiasis.

• Presence of pain/dysuria:

- Painless: APSGN, IgA nephropathy, Wilms' tumor, renal tuberculosis, congenital anomalies.

- Painful: UTI, urolithiasis.

• Co-existing features, e.g.

- Gross edema: Nephrotic syndrome

- Renal mass: Wilms' tumor, hydronephrosis, etc.

- Urinary calculi: Hypercalcemia, cystinosis, etc.

Step IV. Laboratory evaluation includes:

• Baseline investigations:

- Routine urine examination and culture

- Radioimaging, e.g. USG

- Serology: ASO titres, Serum C3 levels

- Renal function tests: BUN, S. Creatinine, Urinary calcium: creatinine ratio

- Others: CBC, X-ray chest, Mantoux test

• Selective investigations:

- Anti-nuclear antibodies (SLE, HSP)

- Coagulation profile (bleeding disorders)

- Sickling test (in endemic region)

- Cystoscopy

• Renal biopsy is indicated in all cases of recurrent gross hematuria or persistent microscopic hematuria for gt;2 years and presence of—(a) significant proteinuria (gt;1 gm/1.73 m²/day) or hypertension, (b) persistently low C₃ levels, (c) unexplained kidney failure, (d) family history of significant renal disease.

21.6