The Injury Atlas Does the kidney recover? Cross-drug outcomes
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.
12agents
Agents’ overall severity
Each agent’s whole-drug severity grade, not the severity of this lesion specifically — an agent whose signature injury is elsewhere can still be graded severe here.
Severe· 1Moderate· 10Mild· 1
Agents’ overall reversibility
Often irreversible· 3Partially reversible· 8Variable· 1
Agents’ onset window
How soon each agent’s kidney toxicity typically appears — a whole-drug tempo, not specific to this lesion.
Subacute (weeks)· 1Delayed (weeks–months)· 10Variable· 1
Management approach
Full framework →Largely preventive — cumulative-dose limits; established chronic interstitial fibrosis is often irreversible.
Drug-level levers
- Respect cumulative-dose thresholds (e.g., the nitrosoureas) and monitor for the delayed, creeping creatinine.
- Hold or avoid further exposure once progressive CKD appears.
Pharmacologic toolkit
- Supportive CKD care — Blood-pressure and proteinuria control, avoid added nephrotoxins; no specific reversal therapy exists.
When to biopsy
Consider to confirm chronic interstitial nephropathy and exclude treatable alternatives when the cause of progressive CKD is unclear.
Monitoring
- · Long-term creatinine / eGFR (months to years)
- · Blood pressure and proteinuria
Educational use only. Educational synthesis of the published literature — not a treatment protocol, dosing guide, or medical advice. Regimens and agents shown are illustrative of what the literature describes; verify against current guidelines (ASON / KDIGO / ASCO / NCCN) and individualize to the patient. Using this site creates no clinician–patient relationship.
Offending agents
Signature offenders
7Agents for which chronic interstitial nephropathy is the defining renal lesion.
PemetrexedDelayed / cumulative; risk rises after ~10 cycles.Clinically relevant eGFR decline (≥25%) in ~21%; ~8% discontinue for nephrotoxicity. Cumulative-dose dependent.ModerateCarmustine (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). In a 74-patient single-agent 177Lu-octreotate cohort with dedicated long-term follow-up, CTCAE grade >=3 nephrotoxicity occurred in one patient (1.3%) — who also had arterial hypertension and prior chemotherapy — while a slower GFR decline was more common; 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. Reported rate: grade >=3 ctcae nephrotoxicity worsening to grade 3 in 9.4% — 32 consecutive heavily pre-treated mCRPC patients selected by 68Ga-PSMA-11 PET/CT and given 177Lu-PSMA-617 monotherapy… (Maffey-Steffan 2020, PMID 31776632).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 is hematologic (delayed myelosuppression).Moderate
Also associated
5Agents that cause chronic interstitial nephropathy as a secondary pattern alongside a different signature lesion.
IpilimumabDelayed and variable: typically weeks to several months after initiation. Median time to AKI in biopsy cohorts was roughly 3 months (about 91 days; ~4 cycles); combination ipilimumab/nivolumab nephritis can appear after only one or two doses, and onset after drug discontinuation has been described.Clinically significant kidney injury from ipilimumab monotherapy is uncommon; renal immune-related adverse events are reported in roughly 1-2% of patients on single-agent checkpoint blockade. The dominant driver of elevated incidence is combination therapy: in real-world ICI cohorts any-cause AKI reaches about 16-17%, but only a minority is true immune-mediated nephritis. The combination of ipilimumab plus nivolumab carries a substantially higher and more severe AKI risk than either single agent. In a pooled analysis of biopsy-proven ICI-related acute tubulointerstitial nephritis, all patients on dual ICI blockade developed stage 3 AKI versus about half on a single agent, and complete renal recovery was less likely with dual blockade.SevereNivolumabCharacteristically delayed compared with other drug-induced AIN: median time from ICI initiation to AKI was about 14 weeks (IQR 6-37) in a 138-patient multicenter cohort, and 91 days in the original series; onset ranges from weeks to many months and can follow drug discontinuation.Clinically significant ICI-attributed AKI is uncommon but not rare. A 2023 systematic review/meta-analysis of real-world data (18 studies, ~12,000 ICI-treated patients) found a pooled incidence of all-cause AKI during ICI therapy of about 16%, but AKI specifically attributed to the ICI of roughly 3.5%. Risk is higher with combination ICI regimens (e.g., nivolumab-ipilimumab) than with PD-1 monotherapy. Among biopsied ICI-AKI, acute tubulointerstitial nephritis is the dominant lesion (>90%); glomerular lesions and thrombotic microangiopathy are reported but uncommon.ModeratePembrolizumabDelayed and highly variable, typically weeks to months after initiation; multicenter cohorts reported median onsets around 14-16 weeks. Can occur after a single dose or after many months, and may recur on rechallenge.In real-world cohorts of patients receiving immune checkpoint inhibitors, any AKI is common (roughly 16-18%), but AKI attributable to the checkpoint inhibitor itself (ICPi-AKI) is less frequent. A single-center cohort reported AKI in 16.5% of ICI-treated patients with checkpoint-attributable nephrotoxicity in a minority, while a larger real-world study found ICPi-AKI in about 3.6%. Acute interstitial nephritis is the dominant biopsy lesion (>80% in the largest multicenter series). These figures are pooled across PD-1/PD-L1/CTLA-4 agents rather than pembrolizumab-specific.ModerateVemurafenibEarly — most cases arise within the first weeks to three months of therapy (all AKI events in the Teuma cohort occurred in the first trimester of treatment); later onset is uncommon.Clinically meaningful AKI is a recognized but variably quantified effect, and vemurafenib is the strongest renal offender of the BRAF/MEK class. Small serum-creatinine rises are common and usually low-grade; overt AKI produced the first case series of 8 patients with significant-to-severe renal insufficiency (Launay-Vacher, Cancer 2014) and 132 vemurafenib AKI reports to FDA FAERS over 3 years, far exceeding dabrafenib's 13 (Jhaveri, JAMA Oncol 2015). The monotherapy denominator comes from a retrospective single-center cohort of 74 patients with BRAF-V600-mutant metastatic melanoma, with creatinine measured before treatment, monthly on treatment and 3 months after stopping: 44 of 74 (59.5%) met the KDIGO threshold of a 1.5-fold creatinine rise, and 40 of those 44 (91%) were stage 1. Read that figure with its definition attached — it is creatinine-based, and BRAF/MEK inhibitors also blunt tubular creatinine secretion, so a share of any such cohort is pseudo-AKI rather than tubular injury; the authors biopsied two stage-1 patients to demonstrate real tissue damage. Men were over-represented among the AKI-positive patients (75% versus 40%). Adding a MEK inhibitor lowers it substantially: in the companion cobimetinib cohort 9 of 38 (24%) developed AKI, all within three months and mostly stage 1-2, about a 60% reduction versus monotherapy.ModerateIobenguane I-131Biphasic — modest, often transient creatinine changes within weeks of a therapeutic dose; the characteristic radiation nephropathy is delayed, typically appearing 6-12 months or later after cumulative renal irradiation, sometimes years out.Reported renal toxicity is uncommon and usually low-grade. In a dosimetry-guided high-activity 131I-MIBG cohort, 3 of 14 patients (21%) had transient grade 1 renal toxicity (Maric 2023, small single-center series using conventional 131I-MIBG). In the registrational high-specific-activity trial (Azedra, n=68 dosed), renal failure was not among the most common treatment-emergent events — nausea, myelosuppression and fatigue dominated — and clinically significant (grade >=3) nephrotoxicity was rare. The kidney concern is driven less by acute events than by the delayed, cumulative absorbed radiation dose, so headline incidence figures come from small cohorts and should be read as low-grade signal rather than a robust rate.Mild