STEPTRACKERRENAL | PATHOLOGY + PHARMACOLOGY + PHYSIOLOGY | HIGH-YIELD REVIEW

Interstitial Nephritis, Papillary Necrosis & Tubular Disorders

Injury to the space around the tubules and to the tubules' own transport — from drug allergies to sloughed papillae to renal tubular acidosis.

FOCUS ON
Acute interstitial nephritis: a drug (penicillins, NSAIDs, PPIs, sulfas, diuretics) 1–2 weeks earlier → fever, rash, eosinophilia, WBC casts, sterile pyuria → stop the drug. Papillary necrosis: sickle cell, analgesics, diabetes, pyelonephritis, obstruction → gross hematuria and flank pain. Know the three RTA types.
DISORDER
MECHANISM · CAUSE
FEATURES
CLUE
Drug-induced acute interstitial nephritis
Drug acts as hapten → type IV (± type I) hypersensitivity in the interstitium: penicillins, cephalosporins, NSAIDs, PPIs, sulfonamides, rifampin, diuretics, allopurinol
1–2 weeks after starting: fever, rash, ↑ creatinine, eosinophilia, urine eosinophils, WBC casts, sterile pyuria
Stop the drug ± steroids
Other causes of AIN
Infections (strep, Legionella, CMV); autoimmune (SLE, Sjögren, sarcoidosis, IgG4)
TINU syndrome: interstitial nephritis + uveitis
Interstitial lymphocytes, eosinophils, edema
Analgesic nephropathy
Years of combination analgesics (NSAIDs + acetaminophen ± caffeine) → medullary ischemia
Chronic interstitial nephritis, papillary necrosis, CKD
↑ urothelial carcinoma of the renal pelvis
Renal papillary necrosis
Ischemia of the papillae (end of the vasa recta)
Gross hematuria, flank pain, sloughed tissue in urine (may obstruct)
Sickle cell, analgesics, diabetes, acute pyelonephritis, obstruction
Sickle cell nephropathy
Hypoxic, hypertonic, acidic medulla promotes sickling (also in trait)
Isosthenuria (can't concentrate), painless hematuria, papillary necrosis
Renal medullary carcinoma (trait)
Myeloma cast nephropathy
Filtered light chains (Bence Jones) bind Tamm-Horsfall protein → obstructing casts; direct tubular toxicity
AKI with large waxy "fractured" casts; hypercalcemia contributes
Dipstick negative for protein; urine immunofixation positive
Fanconi syndrome
Generalized proximal tubule failure: tenofovir, ifosfamide, cisplatin, expired tetracycline, lead, Wilson, cystinosis, myeloma
Glucosuria (normal glucose), aminoaciduria, phosphaturia, bicarbonaturia, hypokalemia
Type 2 RTA; rickets/osteomalacia
Type 1 (distal) RTA
α-intercalated cells can't secrete H⁺: amphotericin B, Sjögren, SLE, lithium, obstruction
Urine pH > 5.5; hypokalemia; nonanion gap acidosis
Calcium phosphate stones (alkaline urine, ↓ citrate)
Type 2 (proximal) RTA
↓ HCO₃⁻ reabsorption: Fanconi, acetazolamide, myeloma
Urine pH < 5.5 once serum HCO₃⁻ falls; hypokalemia
Hypophosphatemic rickets
Type 4 RTA
↓ aldosterone or resistance: diabetic hyporeninemia, ACEi/ARB, NSAIDs, heparin, spironolactone, trimethoprim
Hyperkalemia; urine pH < 5.5; ↓ NH₄⁺ excretion
Most common RTA
Lithium & lead
Lithium → ↓ ADH response in collecting duct · lead → proximal injury, ↓ urate excretion
Lithium: nephrogenic DI, chronic interstitial nephritis · lead: CKD, "saturnine" gout, hypertension
Lithium DI: thiazide or amiloride

Mechanism — the medulla runs on low oxygen

Vasa rectaSlow, sparse flow
→
Papillary tipLowest O₂
→
Extra hitSickling, NSAIDs (↓ PGE₂ vasodilation), microangiopathy
→
Papillary necrosisHematuria, colic
Drug hapten
→
T cells + eosinophilsIn interstitium
→
Interstitial edema↓ GFR, WBC casts

Renal tubular acidosis at a glance

TYPE
DEFECT
URINE pH
K⁺
1 (distal)
H⁺ secretion
> 5.5
↓
2 (proximal)
HCO₃⁻ reabsorption
< 5.5 (late)
↓
4 (hyperkalemic)
Aldosterone effect
< 5.5
↑

All three are normal anion gap (hyperchloremic) metabolic acidoses.

How it's tested

COMMON CONFUSIONWBC casts mean the kidney itself is inflamed — AIN or pyelonephritis. Fever, rash and eosinophilia after a new drug point to AIN; positive urine culture points to pyelonephritis.
THE TRAPGlucose in the urine with normal blood glucose is a proximal tubule problem (Fanconi or pregnancy), not diabetes.
YOUR APPROACHNew drug? → AIN. Hematuria + flank pain + risk group → papillary necrosis. Nonanion gap acidosis → urine pH and K⁺ → RTA type → cause.

If you see… think…

Rash, fever, eosinophilia and rising creatinine 10 days after starting omeprazole → AIN
WBC casts with negative urine culture → interstitial nephritis
Sickle trait with painless gross hematuria → papillary necrosis
Chronic headache sufferer on daily combination analgesics with CKD → analgesic nephropathy
Myeloma with AKI and fractured waxy casts → cast nephropathy
Glucosuria, aminoaciduria, phosphaturia on tenofovir → Fanconi syndrome
Sjögren + urine pH 6.5 + calcium phosphate stones → type 1 RTA
Acidosis on acetazolamide → type 2 RTA
Diabetic with hyperkalemia and nonanion gap acidosis → type 4 RTA
Bipolar patient on lithium with polyuria → nephrogenic DI