Kidney Biopsy Should Be Performed to Document the Cause of Immune Checkpoint Inhibitor–Associated Acute Kidney Injury: Commentary

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

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Immune Checkpoint Inhibitor (ICPI) induced Nephrotoxicity – An Insight.

JMS SKIMS ◽

10.33883/jms.v23i3.774 ◽

2020 ◽

Vol 23 (3) ◽

Author(s):

Mohmad Hussian Mir ◽

Tariq Ahmad Bhat ◽

Khalid Parvez Sofi ◽

Imtiyaz Ahmad Wani ◽

Muzafar Maqsood Wani

Keyword(s):

Acute Kidney Injury ◽

Immune Checkpoint Inhibitor ◽

Checkpoint Inhibitor ◽

Kidney Injury ◽

Check Point ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

New Class ◽

Transplant Patients ◽

Check Point Inhibitors

Immune check point inhibitors (ICPIs) are a new class of anti-neoplastic agents being increasingly used by oncologists to treat various malignancies. These drugs have been associated with varied side effects and have a nephrotoxic potential. Many cases of ICPI induced acute kidney injury are increasingly being reported. Their use in CKD patients on dialysis as well as in kidney transplant recipients is associated with various challenges. This review discusses the use of ICPIs in CKD, dialysis and renal transplant patients and their nephrotoxic potential

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Immune checkpoint inhibitor (nivolumab)-associated kidney injury and the importance of recognizing concomitant medications known to cause acute tubulointerstitial nephritis: a case report

BMC Nephrology ◽

10.1186/s12882-018-0848-y ◽

2018 ◽

Vol 19 (1) ◽

Cited By ~ 24

Author(s):

Ryo Koda ◽

Hirofumi Watanabe ◽

Masafumi Tsuchida ◽

Noriaki Iino ◽

Kazuo Suzuki ◽

...

Keyword(s):

Case Report ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Tubulointerstitial Nephritis ◽

Checkpoint Inhibitor ◽

Kidney Injury ◽

Acute Tubulointerstitial Nephritis ◽

Concomitant Medications

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Acute kidney injury from immune checkpoint inhibitor use

BMJ Case Reports ◽

10.1136/bcr-2019-231211 ◽

2019 ◽

Vol 12 (10) ◽

pp. e231211 ◽

Cited By ~ 1

Author(s):

Lexis Gordon ◽

Pouneh Dokouhaki ◽

Kimberly Hagel ◽

Bhanu Prasad

Keyword(s):

Acute Kidney Injury ◽

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitor ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Kidney Injury ◽

Acute Interstitial Nephritis ◽

Programmed Death ◽

Programmed Death 1

Immune checkpoint inhibitors are novel oncological medications, current classes of which include monoclonal antibodies that target inhibitory receptors cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death 1 protein (PD-1) and programmed death-ligand 1. While they are novel in their ability to treat cancer, they also have a unique spectrum of immune-related adverse events. Renal-related immune adverse events, though rare, are an increasingly recognised clinical entity. We present the case of a 67-year-old man with acute kidney injury (AKI) after the second cycle of combination anti-CTLA-4 and anti-PD-1 antibodies for metastatic cutaneous melanoma. He presented with vomiting and diarrhoea, and AKI secondary to dehydration was treated with aggressive rehydration. After failing to recover biochemically, a renal biopsy was performed, which demonstrated severe acute interstitial nephritis. The culprit medications were held and he was treated with steroids. With immunosuppression, creatinine improved to pretreatment values.

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A new expression of immune checkpoint inhibitors’ renal toxicity: when distal tubular acidosis precedes creatinine elevation

Clinical Kidney Journal ◽

10.1093/ckj/sfz051 ◽

2019 ◽

Vol 13 (1) ◽

pp. 42-45

Author(s):

Xavier Charmetant ◽

Cécile Teuma ◽

Jennifer Lake ◽

Frédérique Dijoud ◽

Vincent Frochot ◽

...

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Immune Checkpoint Inhibitor ◽

Renal Toxicity ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Kidney Injury ◽

Acute Interstitial Nephritis ◽

Tubular Dysfunction ◽

Distal Tubular Acidosis

Abstract The main manifestation of acute interstitial nephritis (AIN) due to immune checkpoint inhibitors is acute kidney injury. We report here a biopsy-proven AIN revealed by tubular acidosis. This case highlights that immune checkpoint inhibitor prescribers must be aware of electrolytic disorders since tubular dysfunction can precede serum creatinine increase and reveal renal toxicity.

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Immune checkpoint inhibitor-associated acute kidney injury and mortality: An observational study

PLoS ONE ◽

10.1371/journal.pone.0252978 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0252978

Author(s):

Marije S. Koks ◽

Gurbey Ocak ◽

Britt B. M. Suelmann ◽

Cornelia A. R. Hulsbergen-Veelken ◽

Saskia Haitjema ◽

...

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Serum Creatinine ◽

Renal Dysfunction ◽

Immune Checkpoint ◽

Enzyme Inhibitor ◽

Checkpoint Inhibitor ◽

Checkpoint Inhibitors ◽

Kidney Injury ◽

Low Grade

Background Immune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of side effects, including acute kidney injury (AKI). The aim of this study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI in patients receiving checkpoint inhibitors. Methods Patients receiving checkpoint inhibitors between January 2013 and May 2020 at the University Medical Center Utrecht, the Netherlands, were identified using the Utrecht Patient Oriented Database. AKI was defined as an increase in serum creatinine of ≥1.5 times the baseline value, based on the Kidney Disease: Improving Global Outcomes criteria. Cox proportional hazard regression analysis was used to assess risk factors for AKI and to evaluate the relationship between AKI and mortality. Persistent renal dysfunction was diagnosed in AKI patients with a final serum creatinine measurement of >1.3 times the baseline value. Results Among 676 patients receiving checkpoint inhibitors, the overall incidence of AKI was 14.2%. Baseline variables independently associated with AKI were a gynecologic malignancy, monotherapy with ipilimumab, and the use of a diuretic, angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, or proton pump inhibitor at baseline. AKI was checkpoint inhibitor-associated in one third of all patients with AKI. Checkpoint inhibitor-associated AKI was mostly low-grade, occurred a median of 15 weeks after checkpoint inhibitor initiation, and resulted in persistent renal dysfunction in approximately 40% of the patients. Patients with all-cause AKI had a twofold increased mortality risk, but checkpoint inhibitor-associated AKI was not associated with increased mortality. Conclusions In this study, patients receiving checkpoint inhibitors frequently developed AKI due to various etiologies. AKI directly related to the effect of checkpoint inhibitor toxicity did not increase mortality. However, AKI not related to the effect of checkpoint inhibitor toxicity was associated with increased mortality.

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