341.1 🎓 醫孞生版

341.1.0.1 📌 䞀頁重點

341.1.0.1.1 Acute Interstitial Nephritis (AIN)
341.1.0.1.1.1 Etiology

Drug-Induced (Most Common): - NSAIDs: ibuprofen, naproxen, COX-2 - Proton Pump Inhibitors (PPIs): omeprazole, esomeprazole, pantoprazole — increasingly recognized - Antibiotics: penicillins, cephalosporins, sulfonamides, rifampin, ciprofloxacin - Anticonvulsants: phenytoin - Diuretics: furosemide, thiazides - Allopurinol - Immune Checkpoint Inhibitors (ICIs): pembrolizumab, nivolumab, ipilimumab, atezolizumab — 2-5% - 5-ASA (mesalamine, sulfasalazine) - Antivirals: acyclovir, indinavir - Vancomycin

Infections: - Acute pyelonephritis - Hantavirus - Leptospirosis - HIV - EBV, CMV - Legionella - TB (chronic)

Autoimmune / Granulomatous: - Sjögren syndrome - IgG4-related disease - Sarcoidosis - SLE - Tubulointerstitial nephritis with uveitis (TINU) - Vasculitis (small vessel)

Idiopathic (some unclear)

341.1.0.1.1.2 Clinical Features
  • AKI (rising Cr)
  • Sterile pyuria
  • WBC casts
  • Urine eosinophils (Hansel stain — low sensitivity, ~ 25%)
  • Hypersensitivity features: fever, rash, eosinophilia (classic with penicillins; less so with PPIs, ICIs)
  • Variable proteinuria (sub-nephrotic typically; NSAIDs can cause nephrotic + MCD overlap)
  • Hematuria variable
  • Onset days-weeks after exposure (or earlier with re-exposure)
341.1.0.1.1.3 Diagnosis
  • Clinical context + lab findings
  • Gallium-67 scan: positive in AIN (rarely used now)
  • Renal biopsy definitive
    • Interstitial inflammation (lymphocytes, monocytes, eosinophils, plasma cells)
    • Tubular damage (tubulitis)
    • Sparing of glomeruli initially
  • Granulomas in: sarcoid, TB, drugs, IgG4
341.1.0.1.1.4 Treatment
  1. Stop offending drug (most important)
  2. Corticosteroids:
    • Indications: severe / persistent / biopsy-proven / autoimmune
    • Prednisone 0.5-1 mg/kg/d × 4-6 weeks → taper
    • Earlier initiation may improve recovery
  3. Supportive: hydration, electrolytes
  4. Avoid re-exposure to causative drug
341.1.0.1.1.5 Outcomes
  • 50-70% renal recovery with prompt treatment
  • Some progress to CKD
  • Recovery improved if drug discontinued early
  • ICI-related: often re-challenge possible after recovery (cautiously)
341.1.0.1.2 Chronic Interstitial Nephritis (CIN)
341.1.0.1.2.1 Etiology

Drugs / Toxins: - Lithium: nephrogenic DI + CKD - Analgesics (phenacetin, NSAIDs): “analgesic nephropathy” - Calcineurin inhibitors (cyclosporine, tacrolimus): chronic CNI nephrotoxicity - Cisplatin, ifosfamide: long-term - Aristolochic acid (䞭草藥, herbal): especially Asian / Balkan - Cadmium, lead, mercury - Tenofovir

Endemic: - Balkan Endemic Nephropathy (BEN): aristolochic acid in flour - Mesoamerican Nephropathy: agricultural workers, heat stress + dehydration

Hereditary: - Polycystic kidney disease (ADPKD, ARPKD) — see Ch341 - Nephronophthisis - Tuberous sclerosis - Alport syndrome

Anatomic / Reflux: - Reflux nephropathy: pediatric origin; vesicoureteral reflux + scarring - Obstructive uropathy: chronic - Solitary kidney

Metabolic: - Hyperuricemia (chronic gout) - Hypercalcemia - Oxaluria - Cystinuria - Sjögren (chronic)

Vascular: - Ischemic (atherosclerosis, thromboembolism)

341.1.0.1.2.2 Clinical Features
  • Slow CKD progression
  • Often modest proteinuria (< 1-2 g/d typically)
  • May have anemia (chronic)
  • HTN variable
  • Specific features per cause
341.1.0.1.2.3 Diagnosis
  • History (drug exposures, occupational, family)
  • Renal biopsy if uncertain
  • Imaging (CT, US)
341.1.0.1.2.4 Treatment
  • Remove offending agent (when possible)
  • Supportive CKD management (Ch335)
  • Specific therapies:
    • Tolvaptan for ADPKD (TEMPO 3:4)
    • Cysteamine for cystinosis
    • Specific genetic counseling
341.1.0.1.3 Renal Tubular Acidosis (RTA)
341.1.0.1.3.1 Type 1 (Distal RTA)

Mechanism: impaired distal H+ secretion → can’t acidify urine Causes: - Sjögren syndrome (most common) - Autoimmune - Hypercalciuria - Drug-induced (lithium, amphotericin) - Hereditary (SLC4A1, etc.) - Sickle cell

Lab: - Hypokalemia - Non-anion gap metabolic acidosis - Urine pH > 5.5 (cannot acidify) - Positive urine anion gap (impaired NH4 excretion)

Treatment: - Bicarbonate replacement - Potassium replacement - Treat underlying

341.1.0.1.3.2 Type 2 (Proximal RTA)

Mechanism: impaired proximal bicarbonate reabsorption Causes: - Multiple myeloma (light chains) - Drug-induced (tenofovir, acetazolamide, ifosfamide, topiramate) - Cystinosis - Wilson disease - Lead poisoning - Heavy metals - Fanconi syndrome (often)

Lab: - Hypokalemia - Non-anion gap metabolic acidosis - Urine pH can vary (acidify when bicarbonate depleted) - Glucosuria + aminoaciduria + phosphaturia (Fanconi)

Treatment: - Bicarbonate (higher doses needed than type 1) - Potassium replacement - Treat underlying

341.1.0.1.3.3 Type 4 (Hyperkalemic / Hypoaldosterone)

Mechanism: aldosterone deficiency or resistance → impaired distal Na reabsorption + K excretion Causes: - Diabetic nephropathy (common) - Drug-induced: K-sparing diuretics, ACE/ARB, MRA, trimethoprim, pentamidine, NSAIDs, calcineurin inhibitors - Addison disease (primary adrenal insufficiency) - Hyporeninemic hypoaldosteronism - Tubular damage (interstitial nephritis) - HIV

Lab: - Hyperkalemia (paradoxical for “RTA”) - Mild non-anion gap metabolic acidosis - Urine pH variable - ↓ Aldosterone + low/normal renin

Treatment: - Address cause - Mineralocorticoid (fludrocortisone) for true hypoaldosteronism - Restrict K - Loop diuretic (kaliuresis) - Sodium bicarbonate - K binders

341.1.0.1.4 Fanconi Syndrome
341.1.0.1.4.1 Definition
  • Proximal tubular dysfunction with multiple defects:
    • Glucosuria (with normal serum glucose)
    • Aminoaciduria
    • Phosphaturia (hypophosphatemia)
    • Bicarbonaturia (type 2 RTA)
    • Uricosuria (hypouricemia)
    • β2-microglobulinuria
341.1.0.1.4.2 Causes
  • Hereditary: cystinosis (most common pediatric), Wilson disease, tyrosinemia, galactosemia, Lowe syndrome
  • Multiple myeloma (light chain proximal tubulopathy)
  • Drugs: tenofovir, ifosfamide, cisplatin, valproate, gentamicin, ranitidine
  • Heavy metals: lead, cadmium, mercury, copper
341.1.0.1.4.3 Treatment
  • Address underlying
  • Phosphate, bicarbonate, potassium replacement
  • Vitamin D (1,25-OH)
341.1.0.1.5 Nephrogenic Diabetes Insipidus (NDI)
341.1.0.1.5.1 Mechanism
  • Resistance to ADH at collecting duct
  • Polyuria + dilute urine despite ADH
341.1.0.1.5.2 Causes
  • Lithium (chronic — most common acquired cause)
  • Hypercalcemia
  • Hypokalemia
  • Hereditary (AVPR2, AQP2 mutations)
  • Tubulointerstitial disease (chronic)
341.1.0.1.5.3 Diagnosis
  • Polyuria > 3 L/day
  • Dilute urine (osmolality < 300)
  • Water deprivation test: urine doesn’t concentrate adequately
  • Desmopressin test: distinguishes central (responds) vs nephrogenic (doesn’t)
341.1.0.1.5.4 Treatment
  • Address cause (hold lithium if possible, correct Ca/K)
  • Thiazide diuretic (paradoxical effect)
  • Amiloride (especially for lithium-induced)
  • Low-Na diet
  • NSAIDs (limited; nephrotoxic counterproductive)
341.1.0.1.6 Specific Diseases

341.1.1 Sjögren Syndrome Renal

  • Type 1 (distal) RTA + tubulointerstitial nephritis
  • Sometimes glomerular
  • Treatment: steroids, IS

341.1.3 Sarcoidosis Renal

  • Granulomatous interstitial nephritis
  • Hypercalcemia (1α-hydroxylase in granulomas)
  • Glomerular involvement rare
  • Treatment: steroids; HCQ adjunct

341.1.4 Cisplatin Nephrotoxicity

  • ATN initially
  • Chronic interstitial nephritis
  • Hypomagnesemia
  • Fanconi-like

341.1.5 Vancomycin AKI

  • Increasingly recognized
  • Dose-related + duration
  • Trough monitoring crucial
  • TDM-guided dosing

341.1.6 Aminoglycoside Nephrotoxicity

  • ATN
  • Extended-interval dosing reduces
  • Monitor levels

341.1.7 Aristolochic Acid Nephropathy (AAN)

  • Herbal medicine (“䞭草藥”) — banned in many countries
  • Chinese herb nephropathy (CHN)
  • Balkan endemic nephropathy
  • Progressive interstitial fibrosis
  • Increased urothelial cancer risk
  • Important in Taiwan (history)

341.1.8 Lithium Nephropathy

  • Long-term lithium use
  • Chronic interstitial nephritis
  • Nephrogenic DI
  • Acute toxicity at high levels
  • Monitor renal function
  • Amiloride may help NDI

341.1.9 COVID-19 + Tubulointerstitial

  • AKI
  • Collapsing GN
  • ATN
  • Pigment (rhabdo)
  • Tubular damage

341.1.9.1 🩺 床邊速查

  • AIN: WBC casts, eosinophils, AKI; drug-induced most (PPI, NSAID, ICI, antibiotic)
  • CIN: chronic; lithium, analgesics, aristolochic acid, reflux, hereditary, heavy metals
  • RTA Type 1 distal: urine pH > 5.5, hypoK, Sjögren most common
  • RTA Type 2 proximal: Fanconi often, multiple myeloma, drugs
  • RTA Type 4: hyperK + DKD + hypoaldosterone + drugs (K-sparing, ACE)
  • Fanconi: glucosuria + aminoaciduria + phosphaturia + RTA 2; cystinosis, MM, tenofovir
  • Nephrogenic DI: lithium, hyperCa, hypoK; thiazide + amiloride