The Injury Atlas
CIN
Chronic Interstitial Nephropathy
Slow, cumulative tubulointerstitial scarring — fibrosis, tubular atrophy and glomerulosclerosis with no discrete acute phase. The nitrosourea (carmustine/lomustine) lesion and delayed radioligand (radiation) nephropathy; often irreversible and detected only as a creeping creatinine months to years later.
6agents
Severity mix
Moderate· 6
Reversibility
Often irreversible· 3Partially reversible· 3
Signature offenders
6Agents for which chronic interstitial nephropathy is the defining renal lesion.
Carmustine (BCNU)Delayed - months to years after cumulative exposure; conditioning-associated TMA appears within weeks.Insidious, cumulative-dose chronic nephrotoxicity; in classic high-cumulative-dose series the majority of long-term survivors develop reduced renal function, with small scarred kidneys. Acute injury is uncommon except via infusion hypotension or as part of conditioning-associated TMA/HUS.ModerateLomustine (CCNU)Delayed - months to years; dose-cumulative.Chronic, cumulative-dose nephrotoxicity analogous to carmustine; high-dose/long-duration exposure causes interstitial fibrosis and progressive CKD. Acute injury is uncommon and lomustine-specific incidence is not precisely quantified - the clinical signal is reported under the nitrosourea class.ModerateLutetium-177 DotatateDelayed — radiation nephropathy evolves over months to years after treatment; the amino-acid-related hyperkalemia is acute (during infusion).Clinically significant nephrotoxicity is uncommon when amino-acid renoprotection is used: in the NETTER-1 and large Erasmus/Rotterdam cohorts, no therapy-related long-term renal failure was attributed to lutetium-177 dotatate, and the typical long-term GFR decline is modest (~2 mL/min/year). A precise incidence of grade >=3 nephrotoxicity is not well quantified and is low; the more feared long-term toxicity is delayed MDS/AML (~1-2%).ModerateLutetium-177 PSMA-617 (vipivotide)Renal changes are delayed/gradual; xerostomia can appear early during treatment.Clinically significant nephrotoxicity is uncommon in trial populations and is not well quantified; in VISION renal adverse events were infrequent. Dosimetry consistently shows the kidney is the highest-dose internal organ, but the dose-limiting clinical toxicities are usually xerostomia (salivary/lacrimal uptake) and myelosuppression rather than renal failure.ModerateFotemustineDelayed — weeks to months, and cumulative with repeated cycles; chronic interstitial injury may appear after prolonged exposure.Renal toxicity is generally reported as mild within fotemustine regimens, but, consistent with the nitrosourea class, delayed tubulointerstitial injury/ATN can occur; in one combination study renal toxicity was mild yet possibly contributed to two deaths. Drug-specific incidence is not well quantified and is often confounded by co-administered cisplatin.ModerateNimustine (ACNU)Delayed and cumulative — typically over months of repeated cycles, mirroring the nitrosourea class.Drug-specific human renal-toxicity data for nimustine are thin; renal risk is asserted largely at the class level. Like other nitrosoureas, cumulative dosing is associated with delayed tubulointerstitial injury and CKD, but a reliable nimustine-specific incidence is not established. Dose-limiting toxicity in practice is hematologic (delayed myelosuppression).Moderate