Table 1 Characteristics of the patients who developed CPI-related renal manifestations and their laboratory and microscopic findings associated with the CPI-related renal manifestations, initial therapies and the outcomes
No | Age, years | Sex | Race | Cancer type | CPI duration | Comorbidities | Potentially nephrotoxic home medication (dose; mg/day) | Baseline Cr mg/dL Prior UA | Peak Cr mg/dL Severity of AKI | Urine Sediment Cells/HPF Proteinuria | Kidney biopsy | Initial Management | Renal outcome | PFS Cancer status |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Acute tubulointerstitial nephritis | ||||||||||||||
1 | 65 | M | W | Smoldering myeloma | Pembrolizumab 6 cycles (14 weeks) | HTN, dyslipidemia, RA, GERD | Losartan, 50 Omeprazole, 20 | 0.8 N/A | 4.83 G3 | 3 WBC, 1 RBC, UPC:1 | • Acute TIN with eosinophils • Acute mild tubular epithelial injury with tubulitis • 5% IFTA | CPI discontinued Dexamethasone (0.6 mg/kg) | Partial recovery | 17 weeks progressed to MM, started on CYBORD |
2 | 74 | M | W | Urothelial bladder cancer | Nivolumab 60 cycles (24 weeks) | CKD stage 4, stable, attributed to prior chemotherapy-related nephrotoxicity | Ibuprofen, PRN | 2.5 N/A | 7.48 G3 | 11 WBC, eosinophil 0 RBC, UPC: 0.8 | • Acute TIN with neutrophils and eosinophils • Moderate hypertensive nephroscleosis • No immune complex deposition • 48% global glomerular sclerosis • 50% IFTA | CPI discontinued Prednisone (1 mg/kg) | Partial recovery followed by AKI(sepsis) dialysis-dependent | 32 months Minimal residual disease |
3 | 68 | M | W | Metastatic melanoma | Nivolumab and dabrafenib and trametinib 9 cycles (9 months) | HTN, CKD stage 2, hypophysitis; hypothyroidism and adrenal insufficiency | Fosinopril, 40 Hydralazine, 30 Hydrocortisone, 60 | 1.3 N/A | 5.38 G3 | 48 WBC, 7 RBC, UPC:0.36 | • Acute tubuloepithelial injury • Acute tubulointerstitial nephritis • Arterial and arteriolar sclerosis • IFTA 30% and global sclerosis 23% | CPI discontinued Methylprednisolone (1.1 mg/kg) Infliximab (2 doses 8 weeks apart) | Partial recovery | 15 months with no evidence of progression under observation |
4 | 77 | M | W | Papillary urothelial cancer of urinary bladder | Pembrolizumab for 10 weeks 3 doses | DM CKD stage 3 Obstructive uropathy (S/p left nephrostomy) | - | 1.5 Protein (+ 1) | 7.8 G4 | > 182 WBC 9 RBC eosinophil + 1 protein | ATIN with eosinophil and few multinucleated giant cells ATN Global sclersosis 50% and IFTA 50% | CPI discontinued. Methyprednisone 1 mg/kg BID intiated on HD and steroid dose was tapered | Persistent AKI dialysis depenedent | 2 months with no evidence of progression under observatoin |
5 | 55 | M | B | Transitional cell bladder cancer | Atezolizumab around 6 months | Obstructive uropathy s/p bilateral nephrostomy tubes CKD stage 4 GERD | Pantoprazole, 40 | 3.3 UPC 1.2 | 5.8 G3 | 27 WBC 8 RBC eosinophil UPC:2.7 | Acute and chronic tubulointerstitial nephritis with neutrophils and eosinophils Diffuse (> 95%) IFTA | CPI discontinued. | no renal recovery. CKD stage 5 | 9 months had progression of metastasis. Deceased |
Acute tubulointersitial Nephritis with Glomerulonephritis | ||||||||||||||
6 | 41 | M | W | Squamous cell cancer of the lung | Nivolumab 4 cycles (14 weeks) | Asthma | Ibuprofen daily for 2 weeks | 0.8 N/A | 4.52 G3 | 19 WBC, 320 RBC,UACR:1025 mg/g | • Acute focal segmental necrotizing pauci-immune GN (no crescents or global sclerosis): ANCA-negative • Mild interstitial nephritis without atrophy | CPI discontinued Prednisone (1 mg/kg) Rituximab (1 dose) | Complete recovery | 14 weeks patient deceased owe to progression of cancer |
7 | 75 | M | W | Metastatic RCC | Tremelimumab 2 doses (6 weeks) | HTN and CKD stage 3 | Amoxicillin/clavulanate, 500 mg daily for 5 days Hydralazine, 75 | 1.8 N/A | 4.75 G3 | 5 WBC, 67 RBC,UPC:1.43 | • Acute focal segmental pauci-immune necrotizing GN • Mild acute tubulointerestitial nephritis with eosinophils • Acute tubular epithelial injury • Arterial and arteriolar sclerosis • IFTA 5% and global sclerosis 38% | CPI discontinued Methylprednisolone (2 mg/kg) Rituximab (weekly for 4 doses) Plasmapheresis (daily for 5 sessions) | Partial recovery | 11 months with no evidence of progression under observatoin |
8 | 69 | W | W | Uveal Melanoma | Nivolumab and Ipilimumab (3 cycles) 9 weeks | HTN, DM, Stroke CKD stage 3 GERD | Omeprazole, 40 Valsartan, 80 | 1.4 No protein | 4.9 G3 | 15 WBC 7 RBC UPC:0.4 | Granulomatous necrotizing vasculitis hypertensive nephrosclerosis Patchy moderate to severe interstitial inflammation 50% global glomeulosclerosis and 30% IFTA Negative ANCA | CPI discontinued. Prednisone 1 mg/kg daily followed by rituximab x1 after one week | Complete recovery | 8 months with no evidence of progression under observatoin |
9 | 69 | M | W | Melanoma | Ipilimumab and Nivolumab 2 cycles (6 weeks) | GERD, HTN, CKD stage 3 | Olmesartan, 40 Furosemide, 20 Omeprazole, 20 | 1.4 N/A | 2.40 G2 | 7 WBC, 11 RBC, UPC: 7.7 | • IgA nephropathy with focal segmental endocapillary hypercellularity and sclerosis • Acute mild TIN with eosinophils • 40% global glomerular sclerosis, 20% IFTA • Mild arterial and arteriolar sclerosis | CPI discontinued Prednisone (0.5 mg/kg) | Complete recovery followed by relapse | 19 months with no evidence of disease on observation |
10 | 50 | F | W | Melanoma | Pembrolizumab completed 5 doses (12 weeks) | Asthma, GERD, HTN | Naproxen, 250 PRN Omeprazole, 10 HCTZ, 12.5 | 0.8 N/A | 3.08 G3 | 6 WBC, 2 RBC, negative dipstick | Done 5 weeks after AKI: • low-grade tubulointerstitial injury • IgA nephropathy (without pathologic indication of active disease) • FSGS, NOS • Very mild interstitial inflammation | CPI discontinued Prednisone (2 mg/kg) Mycophenolate Mofetil 1 g BID Infliximab (one dose) | Partial recovery followed by AKI attributed to Vemurafenib | 4 weeks progression of metastasis |
11 | 60 | F | H | RCC | Nivolumab 6 cycles (16 weeks) | GERD, and dyslipidemia | Esomeprazole, 40 | 0.8 Negative dipstick | N/A | 2 WBC, 3 RBC, UPC: 9.7 | • PLA2R negative early membranous GN • Focal T-cell–rich crescent-like inflammation • Acute tubulocentric TIN with T cells positive for CD3, CD4, CD8 | CPI discontinued Prednisone (1 mg/kg) | Complete recovery | 20 weeks then had disease progression started on axitinib |
12 | 61 | F | W | Smoldering myeloma | Pembrolizumab 2 cycles (8 weeks) | Hypothyroidism,HTN, dyslipidemia GERD | Lansoprazole, 30 | 0.6 N/A | 2.86 G3 | 32 WBC, 1 RBC, UPC: 0.3 | • Granulomatous TIN • C3 deposition (possible early GN) • Rare subepithelial deposits • 5–10% IFTA • Arterial and arteriolar sclerosis | CPI discontinued Prednisone (1 mg/kg) | Partial recovery | 12 months with no progression under observation |
13 | 74 | M | W | RCC CML | Nivolumab with Axitinib (for 14 months) and Imatinib (for 20 months) | HTN CKD stage 3 GERD | Omeprazole, 40 | 1.6 N/A | 2.73 G2 | 1 WBC, 0 RBC, UPC: 0.38 | • Acute tubuloepithelial injury • Acute tubulointerestitial nephritis with eosinophils • FSGS (preservation of foot process) likely secondary (HTN and post-nephrectomy) • Arterial and arteriolar sclerosis (moderate) • IFTA 20% and global sclerosis 9% | CPI discontinued Predisone (0.8 mg/kg) | Partial recovery | 12 months with evidence of progression |
14 | 63 | M | W | Chondroma | Pembrolizumab 6 cycles (18 weeks) | Coronary artery disease, hypothyroidism, neurogenic bladder | – | 0.5 N/A | 2.25 G3 | 21 WBC, 11 RBC, UPC: 31 | • AA type amyloidosis, • Acute tubular epithelial injury • 28%global glomerular sclerosis • 5% IFTA | CPI discontinued Methylprednisolone (1 mg/kg) Infliximab 440 mg one dose | Partial recovery followed by AKI(sepsis) | 26 weeks Patient deceased owing to bowel perforation |
Cases with suspected CPI toxicity | ||||||||||||||
15 | 38 | M | W | Hodgkin Lymphoma | Nivolumab and LAG-3 antibody 2 cycles (10 weeks) | Cardiomyopathy s/p SCT (9 months ago) | Sulfamethoxazole and trimethoprim (800/160 mg) 3 times per week Valacyclovir, 500 Pantoprazole, 40 | 0.8–0.9 N/A | 1.63 G1 | 11 WBC, 1 RBC, UPC: 0.05 | Done 4 weeks after AKI (first biopsy was inadequate): • No evidence of acute glomerular or tubular injury or inflammation • IFTA 5% and global sclerosis 5% | CPI was held then resumed after 6 weeks along with proton pump inhibitor without recurrence of AKI | Complete recovery | 13 months remains with complete response then patient declined further therapy |
16 | 58 | M | W | Non-small cell lung cancer | Carboplatin and Pemetrexed for 3 cycles (7 weeks added to Pembrolizumab (13 weeks) | HTN COPD | Amoxicillin and Clavulanate, 875–125 mg BID Lisinopril 20 | 0.5 Protein (+ 1) | 7.1 G3 | No pyuria or hematuria UPC 0.6 | ATN No Glomerulosclerosis 15% IFTA | CPI discontinued. Prednisone 1 mg/kg | Persistent AKI dialysis dependent depenedent | 9 months with no recurrence (withdrew from further therapy) |