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# Tubulointerstitial nephritis: acute drug-induced vs chronic forms

- Lesion

Inflammation centred on tubules and interstitium, most often a drug reaction; chronic forms come from analgesics, lithium, lead and immune diseases.

Updated Nov 12, 2026

## Key points

- Acute drug-induced interstitial nephritis: antibiotics (β-lactams), NSAIDs, proton pump inhibitors, diuretics, allopurinol.
- Classic triad (in a minority): fever, rash and eosinophilia; plus rising creatinine and sterile pyuria.
- Micro: interstitial edema, lymphocytes, macrophages and eosinophils; tubulitis; granulomas with some drugs.
- Analgesic nephropathy: papillary necrosis and chronic interstitial nephritis; also linked to urothelial carcinoma of the pelvis.
- Lithium: nephrogenic diabetes insipidus and chronic interstitial nephritis with microcysts; lead: proximal tubular inclusions and gout.

## What it is

In tubulointerstitial nephritis the primary injury is in the tubules and interstitium, not the glomeruli. Acute forms are usually hypersensitivity reactions to drugs, starting days to weeks after exposure, with interstitial edema, lymphocytes, eosinophils and sometimes granulomas. Chronic forms build slowly from long exposure to analgesics, lithium, lead or plant toxins such as aristolochic acid, or from immune diseases such as Sjögren disease, sarcoidosis and IgG4-related disease. Infection, obstruction and metabolic causes produce similar changes.

## Structure

- Acute: edematous interstitium with mixed infiltrate rich in eosinophils; leukocytes invade the tubules (tubulitis); glomeruli normal.
- NSAIDs can add minimal change disease or membranous nephropathy to the interstitial nephritis.
- Chronic: interstitial fibrosis, tubular atrophy, mononuclear infiltrate; later periglomerular fibrosis and sclerosis.
- IgG4-related disease: storiform fibrosis with IgG4-positive plasma cells.

## Causes of tubulointerstitial nephritis and their clues

| Cause | Course | Clue |
| --- | --- | --- |
| [Drugs (hypersensitivity)](https://durgical.com/en/conditions/acute-interstitial-nephritis/) | Acute, days to weeks | Eosinophils, rash, fever; recovers when the drug is stopped |
| [Analgesics and chronic NSAID use](https://durgical.com/en/conditions/renal-papillary-necrosis/) | Chronic | Papillary necrosis, small kidneys with scars over papillae |
| [Lithium](https://durgical.com/en/conditions/lithium-toxicity/) | Chronic | Polyuria from nephrogenic diabetes insipidus; tubular microcysts |
| [Lead](https://durgical.com/en/conditions/lead-poisoning/) | Chronic | Saturnine gout, hypertension, nuclear inclusions in tubular cells |
| Aristolochic acid (plant remedies, contaminated flour) | Chronic | Paucicellular fibrosis; high risk of upper-tract urothelial carcinoma |
| [Immune (sarcoidosis, Sjögren, IgG4-related)](https://durgical.com/en/conditions/sarcoidosis/) | Subacute or chronic | Granulomas, plasma cells, tubular acidosis |

## Clinical notes

- Acute kidney injury weeks after starting a new drug, with sterile pyuria and white cell casts, suggests drug-induced interstitial nephritis.
- Withdrawal of the drug is the key step; delay leaves fibrosis.
- Chronic forms present with polyuria, salt wasting and tubular acidosis before the GFR falls much.

## Memory aid

Pills, pain-killers, lithium, lead and leaves: the tubule and its interstitium pay the bill.

## Test yourself

Think of the answer, then tap the question to see it.

## What cell type is a strong clue to acute drug-induced interstitial nephritis?

Eosinophils in the interstitial infiltrate (and sometimes in the urine).

## What renal lesion is typical of long-term analgesic abuse?

Papillary necrosis with chronic tubulointerstitial nephritis.

## Why does lithium cause polyuria?

It makes collecting ducts resistant to ADH (nephrogenic diabetes insipidus).

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## Elsewhere in DurgiPedia

- [Type IV hypersensitivity (delayed, T cells)](https://durgical.com/en/immunology/type-iv-hypersensitivity/)
- [Injury by therapeutic drugs: the classic examples](https://durgical.com/en/general-pathology/injury-by-therapeutic-drugs-the-classic-examples/)
- [Heavy metals: lead, mercury, arsenic and cadmium](https://durgical.com/en/general-pathology/heavy-metals-lead-mercury-arsenic-and-cadmium/)

## Connections

## Related 5

- [Acute tubular injury (acute tubular necrosis)](https://durgical.com/en/general-pathology/acute-tubular-injury/)
- [Acute pyelonephritis](https://durgical.com/en/general-pathology/acute-pyelonephritis/)
- [Crystal nephropathies and nephrocalcinosis](https://durgical.com/en/general-pathology/crystal-nephropathies-and-nephrocalcinosis/)
- [Injury by therapeutic drugs: the classic examples](https://durgical.com/en/general-pathology/injury-by-therapeutic-drugs-the-classic-examples/)
- [Heavy metals: lead, mercury, arsenic and cadmium](https://durgical.com/en/general-pathology/heavy-metals-lead-mercury-arsenic-and-cadmium/)

## Related conditions 9

- [Acute interstitial nephritis](https://durgical.com/en/conditions/acute-interstitial-nephritis/)
- [Sarcoidosis](https://durgical.com/en/conditions/sarcoidosis/)
- [Sjögren disease](https://durgical.com/en/conditions/sjogren-disease/)
- [IgG4-related disease](https://durgical.com/en/conditions/igg4-related-disease/)
- [Lead poisoning](https://durgical.com/en/conditions/lead-poisoning/)
- [Lithium toxicity](https://durgical.com/en/conditions/lithium-toxicity/)
- [Diabetes insipidus (central and nephrogenic)](https://durgical.com/en/conditions/diabetes-insipidus/)
- [Renal papillary necrosis](https://durgical.com/en/conditions/renal-papillary-necrosis/)
- [Chronic kidney disease](https://durgical.com/en/conditions/chronic-kidney-disease/)

[← All of general pathology](https://durgical.com/en/general-pathology/)

Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Interstitial nephritis: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000464.htm) (MedlinePlus, US National Library of Medicine, 2025).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/general-pathology/tubulointerstitial-nephritis-acute-drug-induced-vs-chronic-forms/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/tubulointerstitial-nephritis-acute-drug-induced-vs-chronic-forms/