HEREDITARY TUBULAR DISORDERS

X-rays may reveal severe rickets or osteopenia. serum creatinine and renal USG is usually normal. All cases should also be investigated for primary cause.

Treatment includes: (a) alkali therapy as for proximal RTA (8-14 mEq/kg/d), (b) potassium supplements (2-4 mEq/kg/d), (c) phosphate supplements (50-75 mg/kg/d) as Joule's solution or Adphos sachets (30 mg/ml), and (d) vitamin D analogues in cases with rickets; along with treatment of primary disease.

Cystinosis, an autosomal recessive disorder, is an important cause of secondary Fanconi syndrome and proximal RTA. It is characterized by generalized accumulation of cystine in various body tissues including kidneys, due to a membrane transport defect that prevents cystine excretion from cells.

Clinically, apart from features of Fanconi syndrome, diagnosis may be confirmed by detection of cystine crystals in cornea and measurement of leukocyte cystine content.

Treatment aims to correct metabolic abnormalities, along with life-long therapy with oral cysteamine that binds cystine to form excretable cysteine. Early initiation of this drug can delay the deterioration of renal function.

Idiopathic hypercalciuria is a common inherited defect of tubular calcium transport with reduced reabsorption, leading to hypercalciuria and consequent nephrocalcinosis.

Clinically, these cases present with recurrent gross or persistent microscopic hematuria, along with recurrent formation of renal calculi.

Diagnosis rests on 24-hour urinary calcium excretion (gt;4 mg/kg) or urinary calcium:creatinine ratio (gt;0.2), beyond infancy.

Treatment involves use of oral thiazide diuretics in symptomatic cases to reduce urinary calcium excretion by stimulating its reabsorption in distal tubules.

Nail-Patella syndrome is an autosomal dominant disorder with—(a) dystrophic nails, (b) absent/hypo- plastic patella, and (c) chronic renal disease, characte­rized by impaired urinary concentration/acidification capacity, microscopic hematuria and/or proteinuria. Most cases run a benign course but 10-20% develop CKD in late life.

Bartter syndrome is a rare form of renal potassium wasting due to unexplained cause (probably secondary to a chloride reabsorption defect), biochemically characterized by—(a) persistent moderate hypokalemia, (b) high urinary potassium, and (c) hypochloremic metabolic alkalosis.

Clinically, it presents since infancy with growth failure, polyuria/polydipsia, recurrent dehydration and muscle weakness/cramps. Absence of hypertension (despite elevated renin) in a case of hypochloremic metabolic acidosis is an indicator of Bartter syndrome.

Treatment includes long-term oral potassium supple­ments with a potassium sparing diuretic, e.g. triamterene. Refractory cases may be treated with prostaglandin inhibitors, e.g. indomethacin.

Nephrogenic diabetes insipidus (DI) is characterized by complete or partial tubular unresponsiveness to antidiuretic hormone (ADH), leading to severe impairment in urinary concentration capacity. It may be primary (X-linked recessive) or secondary due to loss of medullary concentration capacity in renal failure, interstitial nephritis, obstructive uropathies, nephrocalcinosis, etc.

Clinically, primary nephrogenic DI usually presents in early infancy with polyuria, polydipsia and recurrent episodes of hypernatremic dehydration. Long-term complications include growth failure, mental retardation and hydronephrosis due to excessive urine production Diagnosis is confirmed by water deprivation test, though formal test is not necessary in cases with serum osmolality of gt;290 mOsm/kg with simultaneous urine osmolality of lt;290 mOsm/kg. Further vasopressin challenge test is required to exclude central DI (Ch 22.2.4).

Management includes adequate fluid intake, low-salt diet and diuretic therapy. Paradoxical response to diuretic therapy (Hydrochlorothiazide 1-2 mg/kg/d) is probably due to sodium depletion after diuretics, which enhances absorption of sodium and water in proximal tubules.

sulfonamides and furosemide, (b) Systemic infections, e.g. diphtheria, leptospirosis, CMV, EBV, etc.

Chronic interstitial nephritis is seen in—(a) obstructive uropathy with vesicoureteric reflux, (b) prolonged analgesic abuse, and (c) systemic disorders, e.g. SLE or sickle cell disease.

Clinically, acute interstitial nephritis may present with rapidly progressive renal insufficiency with history of preceding drug/infection exposure, after 3-5 days of offending exposure.

Presentation of chronic disease is usually non-specific with progressive pallor, mild edema, headache, anorexia and recurrent abdominal pain.

Diagnosis must be suspected in any case of progressive renal insufficiency despite adequate urine output. Hypo­sthenuria and mild proteinuria is common. Presence of eosinophils in urine indicates drug-induced disease.

Renal biopsy is diagnostic and reveals focal or diffuse inflammatory reaction in interstitium, more prominent in peritubular region; with/without secondary involvement of tubules and rarely, glomeruli.

Management is non-specific and cause-related; including—(a) elimination of offending drug, (b) treat­ment of primary cause and (c) management of acute/ chronic renal failure. Corticosteroid trial (PO Prednisolone 0.5-1 mg/kg/day) may be given if disease is remitting or prolonged.

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