Most instances occurred in the setting of nivolumab (anti-PD-1) and pembrolizumab (anti-PD-1) use (6 instances each), a combination of nivolumab and ipilimumab (anti-CTLA-4) (2 instances), tremelimumab(anti-CTLA-4) (1 case), and atezolizumab (anti-PD-L1) (1 case)
Most instances occurred in the setting of nivolumab (anti-PD-1) and pembrolizumab (anti-PD-1) use (6 instances each), a combination of nivolumab and ipilimumab (anti-CTLA-4) (2 instances), tremelimumab(anti-CTLA-4) (1 case), and atezolizumab (anti-PD-L1) (1 case). with advanced solid or hematologic malignancy; 12 individuals were male, and the median age was 64 (range 38 to 77?years). The median time to developing acute kidney injury (AKI) from starting CPIs was 14?weeks (range 6C56?weeks). The average time from AKI analysis to obtaining renal biopsy was 16?days (range from 1 to 46?days). Fifteen instances occurred post anti-PD-1centered therapy. ATIN was the most common pathologic getting on biopsy (14 of 16) and offered in almost all instances as either the major microscopic getting or like a mild form of interstitial swelling in association with LY 222306 additional glomerular pathologies (pauci-immune glomerulonephritis, membranous glomerulonephritis, C3 glomerulonephritis, immunoglobulin LY 222306 A (IgA) nephropathy, or amyloid A (AA) amyloidosis). CPIs were discontinued in 15 out of 16 instances. Steroids and further immunosuppression were used in most instances as indicated for treatment of ATIN and glomerulonephritis (14 of 16), with the majority achieving total to partial renal recovery. Conclusions Our data demonstrate that CPI related AKI happens relatively late after CPI therapy. Our biopsy data demonstrate that ATIN is the most IL8 common pathological getting; however it can regularly co-occur with additional glomerular pathologies, which may require immune suppressive therapy beyond corticosteroids. In the lack of predictive blood or urine biomarker, we recommend obtaining kidney biopsy for CPI related AKI. progression-free survival, male, female, white, black, lymphocyte activation gene 3, hypertension, gastroesophageal reflux disease, multiple myeloma, rheumatoid arthritis, diabetes mellitus, chronic obstructive pulmonary diseases, stem cell transplant, chronic kidney disease, white blood cells, red blood cells, urinalysis, urine protein to creatinine percentage, within normal limit, anti-nuclear antibody, antineutrophil cytoplasmic antibody, rheumatoid element, cyclic citrullinated peptide, myeloperoxidase, creatine kinase, not available, double-stranded DNA, glomerulonephritis, tubulointerstitial nephritis, interstitial fibrosis/tubular atrophy, amyloid A, urine albumin to creatinine percentage, positron emission tomography, focal segmental glomerulosclerosis, immune checkpoint inhibitor, twice daily, creatinine, renal alternative therapy Most instances identified were white males (1 case was a Hispanic man, and 4 instances were ladies), having a median age of 64?years (range, 38C77?years). Renal cell carcinoma, urothelial bladder malignancy and melanoma were the most common malignancies (3 instances of RCC and 3 urothelial bladder malignancy and 4 instances of melanoma), followed by multiple myeloma (2 instances) and 1 case each of chondroma, squamous cell malignancy of the lung, adenocarcinoma of the lung, and Hodgkin lymphoma. Most instances occurred in the establishing of nivolumab (anti-PD-1) and pembrolizumab (anti-PD-1) use (6 instances each), a combination of nivolumab and ipilimumab (anti-CTLA-4) (2 instances), tremelimumab(anti-CTLA-4) (1 case), and atezolizumab (anti-PD-L1) (1 case). 7 individuals had chronic kidney disease (CKD) at baseline:5 experienced CKD stage 3, and 2 experienced CKD stage 4. Clinical features The median time to development of AKI after starting a CPI was 14?weeks (range: 6C56?weeks). However, AKI occurred within 9?weeks with the LY 222306 use of the CTLA-4 inhibitor tremelimumab or the combination of the CTLA-4 inhibitor ipilimumab and the PD-1 inhibitor nivolumab. All other individuals on PD-1 inhibitors experienced longer durations to development of AKI: a median of 20?weeks (range, 10C56?weeks) with nivolumab alone and 13.5?weeks LY 222306 (range: 8C18?weeks) with pembrolizumab alone. The most common urine getting was sub-nephrotic proteinuria at time of acute kidney injury analysis (urine studies were carried out within 48?h of analysis in 13 out of 16 instances). The median urine protein-to-creatinine (UPC) percentage was 0.8?g/g with a range of 0C31. 3 instances experienced 0.3?g/g protein in the urine. 10 instances had proteinuria ranging from 0.3 to 3?g/g, and 3 instances had nephrotic-range proteinuria and hypoalbuminemia consistent with nephrotic syndrome and associated with renal pathologies of AA amyloidosis, membranous glomerulonephritis, or IgA.