Checkpoint inhibitors (pembrolizumab · nivolumab · ipilimumab)
Immune checkpoint inhibitor
Acute interstitial nephritis with long latency.
AIN
ModerateOpen →
Anti-PD-1 antibody
Dostarlimab
Jemperli · DOST
An anti-PD-1 antibody that, like its class, can cause immune-mediated acute interstitial nephritis and rare glomerular disease.
ModerateImmune checkpoint inhibitor (anti-PD-1) · approved 2021
Mismatch-repair-deficient/MSI-high endometrial cancerMismatch-repair-deficient recurrent or advanced solid tumors
Signature kidney injury
Acute Interstitial Nephritis
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.
Source: Meraz-Munoz et al., J Immunother Cancer 2020 (class-level any-AKI; agent-specific AIN rate not separately quantified)
Mechanism of kidney injury
PD-1 blockade disrupts tubulointerstitial immune tolerance, producing T-cell-mediated acute interstitial nephritis, frequently potentiated by haptenizing co-medications. Immune-mediated glomerular lesions occur less frequently, with reported pulmonary-renal syndrome / crescentic (pauci-immune) glomerulonephritis broadening the phenotype.
Clinical presentation
Subacute creatinine rise with sterile pyuria, white-cell casts, and low-grade proteinuria, often alongside other immune-related adverse events. New hematuria with rapidly rising creatinine (with or without pulmonary hemorrhage) signals a crescentic glomerular variant.
Onset
Weeks to months after initiation.
Reversibility
Partially reversible
Anticancer mechanism
Humanized IgG4 monoclonal antibody blocking the PD-1 receptor, restoring antitumor T-cell function. Used in mismatch-repair-deficient/MSI-high endometrial and other solid tumors, including chemoimmunotherapy combinations.
Management
Withhold dostarlimab, exclude alternative causes, and treat immune-related AIN with corticosteroids (prednisone ~0.5-1 mg/kg/day with taper); many patients recover at least partially. A crescentic/pulmonary-renal variant requires urgent high-dose immunosuppression. Individualize rechallenge after recovery.
Risk factors
- Concurrent PPIs/NSAIDs and other AIN-associated drugs
- Combination immunotherapy/chemoimmunotherapy
- Lower baseline kidney function
- Other active immune-related adverse events
Prevention
- Serial creatinine monitoring
- Minimize concomitant AIN-associated medications
- Early nephrology input and biopsy when appropriate
Note · Renal data are largely class-derived given the drug's recency; the expected lesion is immune-related acute interstitial nephritis, but a dostarlimab-associated pulmonary-renal/crescentic glomerulonephritis has been reported, widening the phenotype.
Clinical depth
Renal dose adjustment
No baseline renal dose adjustment (fixed-dose antibody, not renally cleared). Toxicity-based modification follows irAE grading: withhold for grade 2 nephritis with steroids; permanently discontinue for grade 3-4 or recurrent severe nephritis.
Dialyzability & ESKD dosing
Not dialyzable—IgG4 monoclonal antibody cleared by reticuloendothelial catabolism; not removed by hemodialysis, no supplemental dosing, standard dosing in ESKD.
Differential diagnosis
Distinguish ICI-AIN (late, sterile pyuria, WBC casts, steroid-responsive) from prerenal azotemia, obstruction, and other drug AIN; new hematuria, red-cell casts, or pulmonary hemorrhage point to a crescentic glomerular variant demanding biopsy and urgent treatment. Cystatin C and urine AIN biomarkers help confirm AIN and exclude pseudo-AKI.
Monitoring
- Serum creatinine/eGFR before each cycle
- Urinalysis with microscopy and protein quantification if creatinine rises
- Surveillance for concurrent irAEs
Key trials & series
- Cortazar JASN 2020 multicenter ICI-AKI cohort (class)
- Gupta J Immunother Cancer 2021 multicenter ICI-AKI cohort (class)
- Esposito Front Oncol 2023 pooled biopsy-proven ICI tubulointerstitial nephritis analysis
Clinical pearls
- Default expectation is class AIN—late onset, eosinophil-poor, steroid-responsive.
- But dostarlimab can cause a crescentic/pulmonary-renal syndrome: hematuria plus rapidly rising creatinine is an emergency.
- Deprescribe co-administered PPIs/NSAIDs during the AKI workup.
- Biopsy early when the picture is atypical—evidence for this newer agent is still thin.
Where it strikes
Nephron segments
Interstitium
Supporting tissue around the tubules
Glomerulus
Filtration barrier (podocytes + endothelium)
Injury signatures
Acute Interstitial NephritisGlomerular Injury / Proteinuria
Beyond the kidney
Class-level context for the major non-renal toxicities of anti-pd-1 antibodys.
Endocrine
Thyroiditis, hypophysitis, diabetes
- Thyroiditis, hypophysitis, type-1 diabetes
Gastrointestinal
Diarrhea, colitis, mucositis, perforation
- Immune colitis
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Immune hepatitis
Pulmonary
Pneumonitis, ILD, effusions, hypertension
- Pneumonitis
Dermatologic
Rash, HFS, SJS/TEN, vitiligo
- Rash, vitiligo, rarely SJS/TEN
Evidence
7 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkClinicopathological features of acute kidney injury associated with immune checkpoint inhibitors.Cortazar FB et al. · Kidney Int 2016 · PMID 27282937Biopsy series establishing acute interstitial nephritis as the dominant checkpoint-inhibitor renal lesion.PMIDClinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.Cortazar FB et al. · J Am Soc Nephrol 2020 · PMID 31896554Multicenter cohort defining ICI-AKI features, steroid response, and outcomes.PMIDAcute kidney injury in patients treated with immune checkpoint inhibitors.Gupta S et al. · J Immunother Cancer 2021 · PMID 34625513Large multicenter ICI-AKI cohort characterizing risk factors and recovery.PMIDBiopsy-proven acute tubulointerstitial nephritis in patients treated with immune checkpoint inhibitors: a pooled analysis of case reports.Esposito P et al. · Front Oncol 2023 · PMID 37936605Pooled biopsy-proven ICI tubulointerstitial nephritis analysis with rechallenge and severity data.PMIDNephrotoxicity of Cancer Immunotherapies: Past, Present and Future.Perazella MA et al. · J Am Soc Nephrol 2018 · PMID 29959196Mechanistic review of immunotherapy nephrotoxicity including ICI-AIN.PMIDAcute kidney injury associated with immune checkpoint inhibitor therapy: incidence, risk factors and outcomes.Meraz-Munoz A et al. · J Immunother Cancer 2020 · PMID 32601079Cohort quantifying checkpoint-inhibitor AKI incidence and risk factors.PMIDSociety for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events.Brahmer JR et al. · J Immunother Cancer 2021 · PMID 34172516Consensus management guidance for renal and other immune-related adverse events.