Tubulointerstitial diseases

Acute Tubulointerstitial Nephritis - The Allergic Kidney

• Pathophysiology: An immunologically mediated, Type IV hypersensitivity reaction causing inflammation of the renal tubules and interstitium.
• Etiology: Often drug-induced, typically 1-2 weeks post-exposure.
  • 📌 The 5 P's: Pee (diuretics), Pain-free (NSAIDs), Penicillins, Proton pump inhibitors, rifamPin.
  • Infections: Legionella, Streptococcus, CMV.
  • Autoimmune: SLE, Sjögren's syndrome.
• Presentation: Classic triad of fever, maculopapular rash, and arthralgia is rare.
• Urinalysis: Key findings include sterile pyuria (WBCs without bacteria), WBC casts, and pathognomonic eosinophiluria.

⭐ The triad of fever, rash, and eosinophilia occurs in only 10-15% of cases. The most common presentation is simply acute kidney injury after exposure to an offending agent.

Acute Tubular Necrosis - Tubular Takedown

Most common cause of intrinsic acute kidney injury (AKI), resulting from direct tubular cell damage. Reversible, but has high mortality.

• Causes & Pathogenesis:
  • Ischemic: Secondary to decreased renal blood flow (e.g., shock, sepsis, surgery). Affects proximal tubules and thick ascending limbs.
  • Nephrotoxic: Direct cellular toxicity.
    • Exogenous: Aminoglycosides, contrast dye, cisplatin.
    • Endogenous: Myoglobin (rhabdomyolysis), hemoglobin, uric acid.

• Phases & Findings:
  1. Initiation: Insult occurs; GFR starts to fall.
  2. Maintenance (1-3 wks): Oliguria, uremia, electrolyte imbalance ($↑K^+$, $↑PO_4^{3-}$).
  3. Recovery: Polyuric phase; gradual return of function.

⭐ Urinalysis Hallmark: Muddy brown granular casts and renal tubular epithelial cells/casts are pathognomonic.

Chronic Tubulointerstitial Nephritis - Slow-Burn Scars

• Pathophysiology: Irreversible, prolonged inflammation leading to interstitial fibrosis and tubular atrophy. Results in small, shrunken kidneys with cortical scarring.
• Key Etiologies:
  • Analgesic nephropathy: Chronic use of phenacetin or NSAIDs; classically causes renal papillary necrosis.
  • Reflux nephropathy: Chronic vesicoureteral reflux (VUR), typically in children, leading to polar scarring.
  • Lead nephropathy: Chronic exposure to lead.
  • Others: Gout, sickle cell disease, myeloma kidney.
• Urinalysis: May show sterile pyuria and broad, waxy casts.

⭐ Analgesic abuse nephropathy is a classic cause of renal papillary necrosis, which can present acutely with flank pain and hematuria as papillae slough off.

Pyelonephritis & Myeloma Kidney - Infections & Intruders

• Acute Pyelonephritis:
  • Cause: Ascending UTI, most commonly E. coli.
  • Clinical: Fever, chills, costovertebral angle (CVA) tenderness.
  • Diagnosis: Hallmark WBC casts in urine, distinguishing it from cystitis.
• Chronic Pyelonephritis:
  • Cause: Recurrent infections, often from vesicoureteral reflux (VUR) or obstruction.
  • Pathology: Coarse cortical scarring, blunted calyces, and "thyroidization" of the kidney (atrophic tubules containing eosinophilic proteinaceous material).
• Myeloma Kidney (Cast Nephropathy):
  • Cause: Excess monoclonal light chains (Bence-Jones protein) form obstructive casts.
  • Pathology: Large, glassy, eosinophilic, and often "fractured" casts in distal tubules.

⭐ In myeloma cast nephropathy, the filtered light chains are directly toxic to tubular epithelial cells, precipitating with Tamm-Horsfall protein to form casts that cause obstruction and interstitial inflammation.

High‑Yield Points - ⚡ Biggest Takeaways

• Acute Interstitial Nephritis (AIN) is a key cause of AKI, often drug-induced (NSAIDs, penicillins, PPIs), with a classic triad of fever, rash, and eosinophilia.
• Urinalysis in AIN may show sterile pyuria, WBC casts, and eosinophiluria, but these findings are often absent.
• Chronic tubulointerstitial nephritis is defined by interstitial fibrosis and tubular atrophy, leading to progressive CKD.
• Analgesic nephropathy from chronic NSAID use is a classic cause of chronic interstitial nephritis and papillary necrosis.
• Myeloma kidney results from light chain casts obstructing the distal tubules, causing renal failure.