158. Interstitial nephritis and polycystic kidney disease - classification, etiology, pathogenesis, clinical manifestations.

Interstitial nephritis

Definition

Interstitial nephritis refers to inflammatory injury predominantly affecting the renal interstitium and tubules, rather than glomeruli or vasculature.

Classification

Etiology

Acute interstitial nephritis

• Drugs (most common):
• Antibiotics (penicillins, cephalosporins, sulfonamides).
• NSAIDs.
• Diuretics.
• Proton pump inhibitors.
• Infections:
• Bacterial (pyelonephritis).
• Viral (CMV, EBV).
• Autoimmune diseases (e.g., Sjögren syndrome, SLE).

Chronic interstitial nephritis

• Long-term analgesic use (analgesic nephropathy).
• Chronic urinary tract obstruction.
• Heavy metals (lead, cadmium).
• Metabolic disorders (hyperuricemia).

Pathogenesis

1. 1 Immune-mediated hypersensitivity reaction (in AIN):

T-cell–mediated reaction → interstitial edema and inflammatory cell infiltration (lymphocytes, eosinophils).

2. Tubular cell injury → impaired concentrating and reabsorptive functions.
3. Chronic injury → interstitial fibrosis and tubular atrophy → progressive renal dysfunction.

Clinical manifestations

• Acute interstitial nephritis:
• Oliguria or non-oliguric acute kidney injury.
• Fever, rash, arthralgias (classic triad but present in minority).
• Eosinophilia (blood) and eosinophiluria (urine).
• Mild proteinuria, hematuria, pyuria.
• Chronic interstitial nephritis:
• Polyuria (impaired concentrating ability).
• Nocturia.
• Progressive azotemia.
• Hypertension.

Polycystic kidney disease (PKD)

Classification

Etiology

ADPKD

• Mutations in PKD1 gene (chromosome 16) or PKD2 gene (chromosome 4).
• Family history in most cases.

ARPKD

• Mutation in PKHD1 gene (chromosome 6).

Pathogenesis

ADPKD

1. Mutations → defective polycystin proteins → abnormal tubular epithelial proliferation and fluid secretion.
2. Progressive formation of numerous cysts throughout cortex and medulla.
3. Compression of surrounding parenchyma → interstitial fibrosis and loss of function.

ARPKD

1. Cysts mainly in collecting ducts.
2. Congenital hepatic fibrosis frequently associated.

Clinical manifestations

ADPKD

• Often asymptomatic until adulthood (30–50 years).
• Flank pain (from cyst rupture or hemorrhage).
• Hematuria.
• Hypertension (very common, early onset).
• Recurrent urinary tract infections.
• Progressive chronic kidney disease → ESRD.
• Extrarenal manifestations:
• Hepatic cysts.
• Intracranial berry aneurysms → subarachnoid hemorrhage.
• Mitral valve prolapse.

ARPKD

• Presents in infancy or early childhood.
• Enlarged, palpable kidneys.
• Pulmonary hypoplasia (due to oligohydramnios).
• Severe hypertension.
• Liver fibrosis → portal hypertension.

Summary table

Conclusion

Interstitial nephritis primarily results from immune-mediated tubulointerstitial injury, while polycystic kidney disease is a genetic disorder causing progressive cyst formation, leading to chronic kidney disease and systemic complications.

✅ Let me know if you'd also like a diagram summarizing cyst formation, or a "drug-induced AIN features" quick chart!

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