Renal Tubular & Interstitial Disease (SELFNOTES)

Acute Tubular Injury / Necrosis (ATI / ATN)

Classification

• Ischaemic ATI
  • Global or regional renal hypoperfusion.
  • Typical precipitants: prolonged hypotension/shock (sepsis, severe bleeding, burns), advanced heart failure, massive trauma, pancreatitis, obstetric catastrophes.
• Nephrotoxic ATI
  • Direct tubular poisons.
  • Endogenous: haemoglobin, myoglobin, free light-chains, bilirubin.
  • Exogenous: aminoglycosides, radiocontrast, cisplatin, amphotericin-B, heavy metals, ethylene glycol.

Pathogenesis (shared, with contrasts)

• Ischaemic type
  • Patchy necrosis & detachment of tubular epithelium—maximal in proximal straight tubule (PST) & thick ascending limb (TAL).
  • Cast formation → luminal obstruction → ↑ intratubular pressure → $\downarrow\,\text{GFR}$.
  • Filtrate back-leak across ruptured basement membrane.
  • Intrarenal vasoconstriction perpetuates ischaemia.
• Nephrotoxic type
  • Diffuse, dose-related epithelial necrosis; basement membrane usually spared → good potential for regeneration if patient survives.
  • Prototype site: proximal convoluted tubule (PCT).

Clinical Course

• Initiation (hours): subtle $\downarrow\, \text{UO}$, mild azotaemia.
• Maintenance (days – 3 weeks): oliguria (<400\,\text{mL/day}), rising $\text{Cr}$ & $K^+$, metabolic acidosis, fluid overload, uraemic manifestations.
• Recovery: polyuric phase with high loss of water/$Na^+$/$K^+$ → risk of hypokalaemia & dehydration before full renal recovery.

Morphology

• Focal epithelial flattening, loss of brush border.
• Granular “muddy-brown” casts in lumen (tubular cell debris + Tamm-Horsfall protein).
• Interstitial oedema; leukocytes in vasa recta.
• Regenerating epithelium shows mitoses in recovery phase.

Electro-Metabolic Sequelae (classic AKI profile)

• Hyponatraemia (\text{serum Na}^+ <135\,\text{mEq/L}) due to impaired free-water clearance.
• Hyperkalaemia (\text{K}^+ >5.5\,\text{mEq/L}) from reduced excretion + tissue breakdown.
• Metabolic acidosis $(\downarrow\, \text{HCO}_3^- ,\; \uparrow\, \text{H}^+ )$ via ↓ acid excretion & ↓ bicarbonate reabsorption.
• Hyperphosphataemia & hypocalcaemia—phosphate retention inhibits $1\alpha$-hydroxylase → ↓ calcitriol → skeletal resistance to PTH.
• Hypermagnesaemia when \text{GFR} <30\,\text{mL/min}.

Tubulointerstitial Nephritis (TIN)

Pyelonephritis

Acute Pyelonephritis

• >$90\%$ ascending infection (vesicoureteral reflux ± obstruction); <$10\%$ haematogenous.
• Common bacteria: E. coli ≫ Proteus, Klebsiella, Enterobacter, Enterococcus.
• Neutrophilic interstitial suppuration → abscess formation, tubular necrosis; glomeruli usually spared.

Presentation

• Sudden flank pain, high fever, chills, N/V, costovertebral angle tenderness.
• Urinary symptoms if cystitis present: dysuria, frequency, urgency.
• Labs: pyuria, bacteriuria, WBC casts, blood cultures + in $20\text{–}30\%$.

Chronic Pyelonephritis

• Recurrent/persistent infection on background of VUR or obstruction.
• Produces irregular cortical scars overlying deformed blunted calyces; polar & corticomedullary in reflux nephropathy.
• Histology: patchy interstitial fibrosis, chronic inflammatory infiltrate, tubular thyroidisation, arteriolosclerosis.

Clinical Picture

• Often silent: polyuria/nocturia from concentrating defect, flank pain, HTN, progressive CKD; acute flares mimic acute pyelo.

Obstructive Uropathy & Urolithiasis

Obstructive Uropathy

• Mechanical block anywhere urethra ←→ renal pelvis (stones, tumours, strictures, congenital PUJ obstruction, BPH).
• Back-pressure → hydronephrosis → ischaemia, tubular apoptosis, interstitial fibrosis.
• Bilateral acute blockage ⇒ post-renal AKI; partial chronic obstruction ⇒ progressive CKD.
• Removal can restore function if fibrosis limited.

Features & Morphology

• Flank pain/fullness; anuria when bilateral & acute.
• Recurrent UTIs, haematuria; late: polyuria/nocturia, HTN.
• Grossly: dilated pelvis/calyces, cortical thinning; microscopically: interstitial fibrosis, tubular atrophy, glomerulosclerosis.

Urolithiasis (Renal Stones)

• Key requirement: urine supersaturation with calculogenic solutes ± ↓ inhibitors (citrate, Mg$^{2+}$), favourable pH, organic matrix for nucleation.
• Types & associations
  • Calcium oxalate ± phosphate (70–80 %) — hypercalciuria, hyperoxaluria, hypocitraturia.
  • Struvite (magnesium–ammonium–phosphate) — urease-positive bacteria; may form staghorn calculi.
  • Uric acid — acidic urine, gout, tumour lysis.
  • Cystine — autosomal-recessive tubular transport defect.

Clinical Pearls

• Renal/ureteric colic: abrupt severe flank → groin pain, haematuria, restlessness.
• Infection superimposes risk of sepsis.
• Non-obstructing stones may be silent.
• Stones are hard, multifaceted; struvite stones can cast the entire collecting system.

Cystic Renal Diseases (Selected High-Yield Forms)

Integrative & Ethical Considerations

• Early recognition of reversible causes (ischaemia, toxins, obstruction) prevents progression to CKD/ESRD.
• Judicious drug use (aminoglycosides, NSAIDs, PPIs) and monitoring serum creatinine can avoid TIN & ATI.
• Antibiotic stewardship minimises resistant pathogens causing pyelonephritis & struvite stones.
• Genetic counselling for ADPKD families—screening of relatives, discussions on transplant options.

High-Yield Numbers & Equations

• Oliguria: \text{UO} <400\,\text{mL/day}.
• Post-void residual for significant obstruction: >100\,\text{mL}.
• Stone supersaturation threshold for calcium oxalate: \text{[Ca]} \times \text{[Ox]} >\ K_s (solubility product).
• Risk of RCC in dialysis cystic disease: $12\text{–}18\times$ general population.

Key Take-Home Points

• ATI/ATN = most common intrinsic AKI; prognosis hinges on basement-membrane integrity & removal of insult.
• TIN is usually drug-induced; look for delayed AKI with systemic allergic signs.
• Pyelonephritis is overwhelmingly ascending; VUR/obstruction convert acute episodes into chronic scarred kidneys.
• Any degree of obstruction can silently and irreversibly damage renal parenchyma—intervene early.
• Stone formation is a physicochemical event modulated by urine pH & inhibitors; prevention targets supersaturation.
• Cystic diseases span harmless simple cysts to ADPKD with systemic complications—recognise patterns for timely referral.