PA27.8-17 | Renal Pathology II: Tubulointerstitial, Vascular & Neoplastic — PBL Case

CLINICAL SETTING

Kamala Devi, a 38-year-old mother of three from a farming village in Rajasthan, presents to a district hospital with acute severe left flank pain radiating to the groin, associated with nausea and vomiting. She has had two similar episodes in the past 3 years, each resolving spontaneously. She reports recurrent urinary tract infections (3 treated courses of antibiotics in the past year). Urine: turbid, foul-smelling. On direct questioning, she reports mild burning on urination and incomplete bladder emptying for months. She is not hypertensive and is not diabetic. There is no family history of kidney disease that she is aware of. Her 12-year-old son, Arjun, was recently noted at school to have consistently high blood pressure (145/94 mmHg on two readings), and has been sent for further evaluation along with his mother today. On examination of Kamala: mild distress, tender over the left costovertebral angle. Temp 38.4 °C, pulse 96, BP 132/84 mmHg. Abdomen: both flanks are visibly full, and bilateral firm flank masses are palpable — right larger than left, irregular and bosselated. Urine dipstick: protein 1+, blood 3+, leucocytes 3+, nitrite positive. Serum creatinine 1.8 mg/dL (elevated), BUN 42 mg/dL. Ultrasound abdomen: both kidneys grossly enlarged; the right kidney measures 22 cm and the left 18 cm; multiple bilateral cysts of varying sizes (0.5–8 cm) replace most of the parenchyma; no obvious solid mass; bilateral renal pelves dilated.

Trigger 1: Initial Workup — Mother and Son

Plain X-ray of Kamala's abdomen (KUB): bilateral large renal shadows; a radio-opaque calculus (1.8 cm) in the left renal pelvis. CT urogram confirms: autosomal dominant polycystic kidney disease (ADPKD) — bilateral massively enlarged kidneys with innumerable cysts; multiple hepatic cysts; the left-sided stone is a staghorn calculus partially filling the left renal pelvis. Culture of midstream urine: Escherichia coli > 10⁵ CFU/mL. Genetic counselling is arranged. Arjun (12 years) undergoes ultrasound: both his kidneys are normal in size but 2–3 small cortical cysts (<1 cm) are noted. BP 148/96 mmHg. Serum creatinine normal (0.6 mg/dL). His grandfather (Kamala's father, deceased at age 48) had died of a 'brain bleed', reportedly after complaining of the 'worst headache of his life'.

Group Task Assignments

Learning Issues

Research these questions and bring your findings to the discussion.

1. [PA27.8] Classify tubulointerstitial nephritis by cause (ischaemic, toxic, infective, immune/allergic, metabolic, obstructive). Describe the morphological features distinguishing each category and the predominant tubular segment affected by each type of injury.
2. [PA27.9] Define and describe the pathogenesis of acute tubular necrosis. Compare ischaemic ATN (patchy, non-contiguous PCT necrosis) and nephrotoxic ATN (contiguous PCT necrosis). Describe the three clinical phases of ATN, the role of tubular back-leak and cast formation in oliguria, and the gross/microscopic morphological features.
3. [PA27.10] Describe the aetiology, route of infection, pathological diagnostic triad, and complications of acute pyelonephritis. Describe chronic pyelonephritis/reflux nephropathy — its characteristic gross appearance (coarse irregular scarring + calyceal clubbing) and how it is distinguished from hypertensive nephrosclerosis. Describe papillary necrosis.
4. [PA27.11] Classify vascular diseases of the kidney by vessel calibre. Describe benign nephrosclerosis (hyaline arteriolosclerosis, finely granular shrunken kidney) and malignant nephrosclerosis (fibrinoid necrosis, onion-skin hyperplasia, flea-bitten kidney). Describe renal artery stenosis as a cause of renovascular hypertension — compare atherosclerotic and fibromuscular dysplasia types.
5. [PA27.12] Classify cystic kidney diseases. Describe ADPKD — genetics (PKD1/PKD2, two-hit, polycystin/cilia dysfunction), gross and microscopic morphology, extrarenal manifestations (berry aneurysm, hepatic cysts, MVP), ESRD risk, and comparison with ARPKD and acquired cystic disease.
6. [PA27.13] Classify renal stones by composition and radio-opacity. Explain the pathogenesis of calcium oxalate, struvite (staghorn/infection), uric acid, and cystine stones — metabolic/infective triggers, urine pH dependence, and stone appearance. Describe obstructive uropathy and hydronephrosis — pathogenesis, morphological grades, and metabolic complications.
7. [PA27.14] Classify renal tumours. Describe clear cell RCC — VHL two-hit pathogenesis, gross yellow-orange appearance, microscopic clear cytoplasm with sinusoidal vessels, pattern of spread (renal vein, IVC, cannonball metastases), paraneoplastic syndromes, and Fuhrman grading. Describe Wilms tumour — age, triphasic histology, WT1 genetics, and prognosis.
8. [PA27.15] Describe thrombotic microangiopathy (TMA) as a pathological syndrome — endothelial injury, platelet-fibrin microthrombi, microangiopathic haemolytic anaemia with schistocytes. Compare HUS (Shiga toxin, children, kidney predominant, normal ADAMTS13) and TTP (ADAMTS13 deficiency, adults, neurological predominant). Describe the gross and microscopic renal changes in TMA.
9. [PA27.16] Classify urothelial tumours — papillary (low/high grade) vs flat (CIS). Describe the occupational carcinogens (aromatic amines — 2-naphthylamine, benzidine) and the field cancerisation concept. Describe the pathological features (papillary fronds, invasion depth), staging (Ta, T1, T2, T3), and the clinical significance of painless haematuria in urothelial carcinoma.
10. [PA27.17] Using a systematic reading framework (gross size/surface/cysts/mass → microscopic compartment → pattern → diagnosis), identify the gross and microscopic features of ADPKD kidneys, end-stage contracted kidneys, hydronephrotic kidneys, ccRCC, Wilms tumour, and chronic pyelonephritis in pathology specimens.