Association of Acute Interstitial Nephritis With Programmed Cell Death 1 Inhibitor Therapy in Lung Cancer Patients.
Immune checkpoint inhibitors that target the programmed death 1 (PD-1) signaling pathway have recently been approved for use in advanced pretreated non-small cell lung cancer and melanoma. Clinical trial data suggest that these drugs may have adverse effects on the kidney, but these effects have not been well described. We present 6 cases of acute kidney injury in patients with lung cancer who received anti-PD-1 antibodies, with each case displaying evidence of acute interstitial nephritis (AIN) on kidney biopsy. All patients were also treated with other drugs (proton pump inhibitors and nonsteroidal anti-inflammatory drugs) linked to AIN, but in most cases, use of these drugs long preceded PD-1 inhibitor therapy. The association of AIN with these drugs in our patients raises the possibility that PD-1 inhibitor therapy may release suppression of T-cell immunity that normally permits renal tolerance of drugs known to be associated with AIN.
Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT. Electronic address: anushree.shirali@yale.edu.
Anushree C
AC
Shirali
Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
Mark A
MA
Perazella
Section of Oncology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.
Scott
S
Gettinger
D000208:Acute Disease; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D016923:Cell Death / Q000187:drug effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000139:chemically induced*; D000077594:Nivolumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D000077594:Nivolumab; C582435:pembrolizumab
PD-1; PD-1 inhibitor; PDCD1; Programmed cell death 1; acute interstitial nephritis (AIN); acute kidney injury (AKI); advanced melanoma; anti–PD-1 antibody; immune checkpoint inhibitor; ipilimumab; nephrotoxicity; nivolumab; non-small cell lung cancer (NSCLC); pembrolizumab; renal biopsy