Tubulointerstitial Nephritis (TIN)
Summary
Tubulointerstitial Nephritis (TIN), also known as Acute Interstitial Nephritis (AIN), is a common cause of Acute Kidney Injury resulting from inflammation of the renal tubules and the interstitium (the space between tubules), typically sparing the glomeruli. It is an Immunologic Hypersensitivity Reaction (Type IV), most commonly triggered by drugs. Early recognition and withdrawal of the offending agent are critical to prevent permanent renal scarring. [1,2]
Key Facts
- The Culprits: Medications account for 70-75% of cases. The "Big 5" are:
- Antibiotics (Penicillins, Cephalosporins, Cipro, Rifampicin).
- NSAIDs (Ibuprofen, Naproxen, COX-2 inhibitors).
- PPIs (Omeprazole, Lansoprazole - increasingly common).
- Diuretics (Furosemide, Thiazides).
- Allopurinol.
- The "Classic Triad": Fever + Rash + Eosinophilia. However, this full triad is only seen in 10-15% of patients. Do not exclude TIN just because there is no rash.
- Sterile Pyuria: A key diagnostic clue. The urine dipstick shows Leukocytes (+++) but Culture is negative (because the inflammation is chemical/allergic, not bacterial).
Clinical Pearls
PPI Nephritis: Proton Pump Inhibitors are now a leading cause of AIN, especially in the elderly. The onset is insidious (weeks to months), unlike antibiotics (days). It is often asymptomatic AKI found on routine bloods.
NSAID Difference: NSAID-induced TIN often presents with significant Proteinuria (Nephrotic range) because NSAIDs can cause a specific Minimal Change Disease-like lesion alongside the interstitial nephritis.
Urine Eosinophils: Historically taught as a good test (Hansel stain). Modern studies show it has poor sensitivity and specificity. Do NOT rely on it.
Demographics
- Prevalence: Causes 15-27% of hospital AKI cases.
- Age: Any age, but higher risk in elderly (polypharmacy).
Mechanisms
- Hapten Model: The drug (or its metabolite) binds to the tubular basement membrane, acting as a hapten.
- Immune Attack: This complex is recognised as foreign -> T-cell activation and Eosinophil recruitment.
- Oedema: The interstitium swells, compressing the tubules -> AKI.
- Fibrosis: If unchecked, inflammation turns to scar tissue -> Chronic Kidney Disease (CKD).
History
Extra-Renal Signs (Sjögren's/Sarcoid)
- Skin: Maculopapular rash (drug exanthem).
- Temperature: Low grade fever.
- Fluid Status: Usually Euvolaemic (unlike Pre-renal AKI/Dehydration).
Urine
- Dipstick: Leukocytes +++, Blood +, Protein + (usually less than 1g, unless NSAIDs).
- Microscopy: White Cell Casts (pathognomonic of tubular inflammation, vs Red Cell Casts in Glomerulonephritis).
- Culture: Negative.
Bloods
- U&E: Elevated Creatinine, Urea.
- FBC: Eosinophilia (>0.5).
- Autoantibodies: ANA, Anti-Ro/La (Sjögren's), ACE (Sarcoid).
Imaging
- Ultrasound: Kidneys are often normal size or enlarged/echogenic (swollen). Excludes obstruction.
- Gallium Scan: Shows uptake in kidneys (inflammation) - rarely used now.
Biopsy (Gold Standard)
- Indications:
- Diagnosis unclear (e.g. suspect vasculitis).
- Failure to improve after stopping drug.
- Considering prolonged steroid course.
- Finding: Interstitial oedema + Lymphocytic/Eosinophilic infiltration.
Management Algorithm
UNEXPLAINED AKI + DRUG HISTORY
(Sterile Pyuria +/- Rash)
↓
STOP OFFENDING DRUG(S)
(The most important step. Stop "all but essential")
↓
SUPPORTIVE CARE
- Monitor Creatinine daily
- Maintain fluid balance
↓
IMPROVEMENT IN 3-7 DAYS?
┌───────────┴───────────┐
YES NO
↓ ↓
OBSERVE CONSIDER BIOPSY
(Document allergy) (Confirm diagnosis)
↓
START STEROIDS
(Prednisolone 1mg/kg for 2-4w)
(Taper slowly)
1. Discontinuation
- Stop the drug. Recovery usually begins within days.
- List as an Allergy to prevent re-challenge.
2. Immunosuppression
- Corticosteroids: Used if bio-proven AIN or strong clinical suspicion with no recovery after washout.
- Evidence suggests earlier steroid use (less than 1 week of diagnosis) leads to better renal recovery and less chronic fibrosis compared to delayed treatment.
3. Renal Replacement Therapy
- Dialysis may be needed temporarily if AKI is severe (Oliguria/Hyperkalaemia).
- Acute -> Chronic: 40% of patients have some degree of permanent renal impairment.
- Papillary Necrosis: Specific complication of chronic NSAID use (sloughing of papillae -> colic/obstruction).
- Renal Tubular Acidosis (RTA): Type 1 (Distal) or Type 4.
- Prognosis: Good if offending agent removed early.
- Poor Factors: Prolonged exposure (>3 weeks), Older age, Interstitial fibrosis on biopsy.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Renal Association | UK Kidney (2019) | Biopsy for non-recovering AKI. Early steroid consideration. |
Landmark Papers
1. Gonzalez et al (Kidney Int 2008)
- Showed that early steroid treatment results in better recovery of baseline renal function compared to delayed treatment in drug-induced AIN.
What is TIN?
It is an allergic reaction occurring inside the kidneys.
What caused it?
It is usually caused by a reaction to a medication. Common culprits include painkillers (ibuprofen), antibiotics, and stomach acid tablets (omeprazole). Even drugs you have taken for a while can suddenly trigger it.
What happens to the kidneys?
The reaction causes the kidneys to become swollen and inflamed, preventing them from filtering waste properly.
How do we treat it?
The most important thing is to identify and stop the drug causing the problem. In most cases, the kidneys will heal themselves once the drug is gone. Sometimes, we need to give a course of steroid tablets to calm down the inflammation faster.
Primary Sources
- Praga M, et al. Acute interstitial nephritis. Kidney Int. 2010;77:956-961.
- Baker RJ, et al. Renal Association Clinical Practice Guideline on the management of acute kidney injury. BMC Nephrol. 2017.
- Perazella MA. Diagnosing acute interstitial nephritis: time for a shift in mindset? Kidney Int. 2015.
Common Exam Questions
- Diagnosis: "AKI + Fever + Rash + Eosinophilia?"
- Answer: Acute Interstitial Nephritis.
- Investigations: "What casts are seen?"
- Answer: White Cell Casts.
- Drugs: "Common PPI cause?"
- Answer: Omeprazole / Lansoprazole.
- Pathology: "Sterile Pyuria definition?"
- Answer: White cells in urine but negative culture.
Viva Points
- TINU Syndrome: A rare autoimmune condition affecting young women (Tubulointerstitial Nephritis + Uveitis). Always ask about red eyes.
- Analgesic Nephropathy: Chronic TIN from years of aspirin/NSAID/paracetamol abuse. Causes "small indented kidneys" and Papillary Necrosis.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.