The Injury Atlas
AIN
Acute Interstitial Nephritis
Immune-mediated inflammation of the renal interstitium — the signature kidney injury of checkpoint inhibitors.
17agents
Severity mix
Moderate· 11Mild· 6
Reversibility
Partially reversible· 6Variable· 4Reversible· 7
Signature offenders
9Agents for which acute interstitial nephritis is the defining renal lesion.
Immune Checkpoint InhibitorsDelayed — median ~14 weeks after starting therapy.ICI-associated AKI ~2–5% (higher with combination therapy); ~93% of biopsies show interstitial nephritis.ModerateAtezolizumabTypically weeks to a few months after initiation (median time to checkpoint-inhibitor AKI is on the order of 3-4 months, characteristically later than classic drug AIN).Across the checkpoint-inhibitor class, any acute kidney injury occurs in roughly 15-17% of treated patients in cohort studies, while clinically significant immune-related AKI (most often acute interstitial nephritis) affects a smaller subset (commonly a few percent). Meta-analysis suggests anti-PD-L1 agents like atezolizumab carry somewhat lower AKI risk than anti-PD-1 agents; PD-L1-specific rates are not precisely separated.ModerateDurvalumabWeeks to several months after starting therapy.As with the PD-1/PD-L1 class, any AKI occurs in roughly 15-17% of treated patients, with immune-related AIN representing a smaller, clinically significant fraction (a few percent). Anti-PD-L1 agents trend toward lower AKI risk than anti-PD-1 agents; durvalumab-specific rates are not separately well quantified.ModerateAvelumabWeeks to months after initiation.Immune-related nephritis follows the PD-1/PD-L1 class pattern: any AKI in roughly 15-17% of patients and clinically significant immune-related AIN in a smaller subset. Anti-PD-L1 agents trend toward lower AKI risk than anti-PD-1 agents; avelumab-specific renal incidence is not separately quantified and rests on class-level pharmacovigilance and meta-analysis data.ModerateCemiplimabWeeks to months after initiation.Follows the PD-1/PD-L1 class profile: any AKI in roughly 15-17% of patients, with immune-related AIN in a smaller clinically significant subset. As an anti-PD-1 agent it may carry somewhat higher AKI risk than anti-PD-L1 agents, and pharmacovigilance data show an immune-nephropathy signal; cemiplimab-specific renal incidence is not separately quantified.ModerateDostarlimabWeeks to months after initiation.Consistent with the PD-1/PD-L1 class: any AKI in roughly 15-17% of treated patients, with immune-related AIN in a smaller clinically significant subset. As a newer anti-PD-1 agent, dostarlimab-specific renal incidence is not separately quantified.ModerateAmivantamabElectrolyte changes during therapy and cumulative; AIN timing not well characterized (subacute, days–weeks after a triggering exposure by analogy to drug AIN).In CHRYSALIS, electrolyte disturbance — notably hypokalemia (grade 3–4 in ~5%) and hypomagnesemia/hypocalcemia — was among the notable laboratory adverse events, consistent with EGFR-pathway inhibition. Acute interstitial nephritis is an emerging, clinician-flagged signal that is not yet quantified in the published renal literature.ModerateRelatlimabDelayed — typically weeks to months after initiation (long latency is characteristic of ICI-AIN).LAG-3-specific renal literature is thin: dedicated searches return no relatlimab AKI cohort or case series, and the pivotal RELATIVITY-047 trial reported aggregate grade 3/4 treatment-related adverse events (about 18.9% with the combination vs 9.7% with nivolumab alone) without an isolated nephritis rate. The renal signal is therefore class-based — immune checkpoint inhibitors cause acute interstitial nephritis, the dominant lesion in 80–90%+ of biopsied ICI-AKI cases, with combination immunotherapy a recognized risk factor.ModerateBicalutamideIf AIN occurs, typically subacute over weeks of exposure (idiosyncratic).Bicalutamide is largely kidney-neutral. Pharmacokinetics are unaffected by renal impairment and no renal dose adjustment is required. Acute interstitial nephritis is, at most, a rare idiosyncratic case-report-level event; no meaningful incidence rate is established.Mild
Also associated
8Agents that cause acute interstitial nephritis as a secondary pattern alongside a different signature lesion.
Sacituzumab govitecanVariable; prerenal AKI tracks with GI toxicity during treatment cycles.AKI is mainly prerenal, driven by the severe diarrhea/nausea and neutropenia that dominate the ASCENT safety profile; renal-specific incidence is not well quantified. A biopsy-proven severe acute tubulointerstitial nephritis requiring hemodialysis has also been reported (case-level).ModerateIbrutinibHypertension develops over weeks–months (can be early); tumor lysis is early (first cycle); glomerular/interstitial lesions are case-level over weeks to months.New or worsened hypertension is common (~26% in a real-world CLL cohort comparing it with acalabrutinib; higher with longer follow-up). AKI at CLL presentation and with tumor lysis is well described. Drug-attributable AKI from interstitial nephritis or glomerular endotheliosis is case-level.ModerateProcarbazineVariable; tumor-lysis-related AKI within days of starting in bulky disease, hypersensitivity-type injury after re-exposure.Not well quantified at the drug-specific level. Procarbazine appears in classic onconephrology reviews of the renal complications of cytotoxic therapy as an agent with recognized renal/urological complications, and it is part of multi-agent lymphoma regimens in which acute renal failure (often multifactorial — tumor lysis, volume depletion, combined nephrotoxins) is described. Discrete procarbazine-attributable nephrotoxicity is largely case-/review-level rather than quantified.ModerateBRAF / MEK InhibitorsAcute–subacute during therapy.No denominator-based rate; pharmacovigilance shows vemurafenib > dabrafenib. Mild creatinine elevation common, serious AKI uncommon.MildEncorafenibWeeks into therapy when it occurs.Renal injury with BRAF/MEK therapy is uncommon and largely case-level (tubular injury and acute interstitial nephritis reported); usually mild and reversible with drug interruption. In COLUMBUS, grade 3-4 creatine-phosphokinase elevation (7%) and hypertension (6%) were the renally relevant grade 3-4 events with encorafenib plus binimetinib.MildCobimetinibWeeks into therapy.AKI with BRAF/MEK therapy is uncommon and mostly mild; notably, a pharmacovigilance analysis found that adding a MEK inhibitor to vemurafenib was associated with a ~60% reduction in acute kidney injury versus vemurafenib alone.MildIdelalisibDiarrhea/colitis often delayed — a median of several months into therapy; transaminitis is typically earlier (first weeks).Severe immune-mediated diarrhea/colitis occurs in roughly 14-20% (grade 3+) and transaminitis is common; secondary prerenal AKI from volume loss is not separately quantified. Direct renal lesions are rare.MildDuvelisibDiarrhea/colitis often after several months; rash and transaminitis can appear earlier.Diarrhea/colitis is common (any-grade ~50%, grade 3+ roughly 15-20% in DUO); the resulting volume-depletion prerenal AKI is not separately tabulated. Direct nephrotoxicity is uncommon.Mild