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Interstitial Nephritis

BASICS

Description

  • Acute Interstitial Nephritis (AIN) and Chronic Interstitial Nephritis (CIN) are tubulointerstitial diseases characterized by:
  • Inflammation and immune-mediated injury of renal interstitium and tubules.
  • AIN → typically acute kidney injury (AKI).
  • CIN → progressive scarring and chronic kidney disease (CKD).
  • AIN is mostly due to hypersensitivity to drugs, leading to inflammatory infiltration and tubular dysfunction.

EPIDEMIOLOGY

  • AIN accounts for 15–20% of AKI cases.
  • Peak incidence: Women aged 60–70 years.
  • Pediatric: TINU syndrome in adolescent females.
  • Geriatric:
  • Drug-induced AIN more common (87% vs 64%).
  • PPI-induced AIN higher (18% vs 6%).
  • Autoimmune AIN less common in elderly.

ETIOLOGY & PATHOPHYSIOLOGY

Acute Interstitial Nephritis (AIN)

Category Cause
Drugs (75%) PPIs (omeprazole), antibiotics (amoxicillin, ciprofloxacin), NSAIDs, diuretics, antivirals, anticonvulsants, allopurinol
Infections (10–15%) Legionella, Leptospira, E. coli, CMV, EBV, TB, SARS-CoV-2
Autoimmune (10–15%) Sarcoidosis, SLE, Sjögren’s, GPA, cryoglobulinemia
Toxins Snake venom
Idiopathic TINU syndrome, anti-TBM disease

🔍 T-cell–mediated delayed hypersensitivity with inflammatory infiltrate in renal interstitium.

Chronic Interstitial Nephritis (CIN)

  • Long-term OFA exposure → fibrosis, tubular atrophy, progressive CKD.
  • Lead exposure in childhood → adult CIN.
  • May be silent; often discovered via routine labs.

ASSOCIATED CONDITIONS

  • Chronic pyelonephritis
  • Analgesic nephropathy
  • Lithium use
  • Gout
  • Sarcoidosis, lymphoma, myeloma, amyloidosis
  • Uveitis, TINU syndrome
  • Heavy metal exposure

CLINICAL FEATURES

AIN

  • Symptoms: Fatigue, malaise, fever (27%), rash (15%), nausea, vomiting, arthralgia (45%)
  • Signs: Hypertension, volume overload, rash, pericardial rub, lung crepitations
  • Urine: Hematuria (95%), sterile pyuria, WBC casts, proteinuria (<1g/day unless NSAID-induced)
  • Lab: Elevated creatinine/BUN, eosinophilia (23%, lower in NSAID-AIN), anemia
  • Course: Onset may be delayed; latency from drug exposure = 3 days to months

CIN

  • Polyuria, polydipsia, HTN
  • Electrolyte issues: hyperkalemia, hyponatremia
  • Non-anion gap metabolic acidosis
  • Anemia, low concentrating ability
  • Fanconi syndrome

DIAGNOSIS

Initial Labs

  • CBC: Eosinophilia, anemia
  • Serum chemistry: ↑ creatinine, acidosis, hyperkalemia
  • Urine: WBCs, RBCs, white cell casts; low-grade proteinuria
  • Urine biomarkers: α1- and β2-microglobulin, IL-9, TNF-α (experimental)

Imaging

  • Renal ultrasound: normal or increased echogenicity
  • CXR: if suspect TB or sarcoidosis

Serologic Workup (Autoimmune/Infectious Causes)

  • ANA, anti-dsDNA, ANCA, ACE, C3/C4, IgG4, CRP, RF
  • Urinary Legionella antigen, TB screening
  • SPEP, LFTs (in drug-induced hepatitis)

❌ Eosinophiluria: poor specificity—not recommended for routine diagnosis.

Renal Biopsy (Gold Standard)

Indications: - Persistent AKI post-OFA withdrawal - Diagnostic uncertainty - Planning immunosuppressive therapy - High-grade proteinuria - Suspected CIN

Findings: - AIN: interstitial infiltration (T cells, monocytes ± eosinophils), tubulitis - CIN: interstitial fibrosis, tubular atrophy, mononuclear cell infiltrates

TREATMENT

GENERAL MEASURES

  • Stop all offending agents (systemic/topical)
  • Hydration, control BP
  • Correct electrolytes and acidosis
  • Anemia management
  • Avoid nephrotoxic contrast
  • Renally dose medications

AIN – Steroid Use

Indication Protocol
Persistent AKI IV methylprednisolone 125–250 mg/day × 3 days, then oral prednisone 0.5–1 mg/kg/day (max 40–60 mg/day) tapered over 4–6 weeks

📌 Best outcomes when steroids are started within 7 days of OFA withdrawal
❌ NSAID-induced AIN does not respond well to steroids.

SECOND-LINE THERAPY

  • Mycophenolate mofetil: for steroid-dependent AIN
  • Lead toxicity: succimer or EDTA chelation
  • SLE nephritis: corticosteroids + cyclophosphamide or azathioprine
  • Urate nephropathy: allopurinol (with renal dosing)
  • Lithium nephropathy: amiloride
  • Indinavir: consider probenecid

ONGOING CARE

Monitoring

  • Serum creatinine, electrolytes, urine output
  • Follow-up for drug rechallenge or recurrence
  • Monitor BP, acid-base status

Diet

  • Low potassium, sodium, and protein
  • High fiber, consider DASH diet

PROGNOSIS

Feature Outcome
AIN (early detection + OFA withdrawal) Favorable; recovery in 65%
NSAID-induced AIN Often incomplete recovery
AKI with delayed diagnosis May require dialysis; ESRD in 12%
CIN Chronic progression to ESRD

CLINICAL PEARLS

  • Always check for drug history—PPIs, NSAIDs, and antibiotics are common culprits.
  • Renal biopsy is gold standard for diagnosis and guides therapy.
  • Early steroid use improves outcomes, especially if biopsy-confirmed.
  • Consider nephrology referral for all patients with AKI + electrolyte/acid-base issues.

CODES

  • N10 — Acute tubulo-interstitial nephritis
  • N11.9 — Chronic tubulo-interstitial nephritis, unspecified
  • N12 — Tubulo-interstitial nephritis, not specified as acute or chronic

REFERENCES

  1. Muriithi AK, et al. Kidney Int. 2015;87(2):458–64.
  2. Muriithi AK, et al. Am J Kidney Dis. 2014;64(4):558–66.
  3. Ng JH, et al. Clin Kidney J. 2021;14(10):2151–57.
  4. Caravaca-Fontán F, et al. Curr Opin Crit Care. 2019;25(6):558–64.
  5. Preddie DC, et al. Clin J Am Soc Nephrol. 2006;1(4):718–22.