Abstract BACKGROUND AND AIMS Immune checkpoint inhibitors (CPIs)—a landmark in cancer therapy—has been occasionally associated with immune-related nephropathy [1]. Acute interstitial nephritis is considered to be the most common underlying histological entity, according to recent literature [2]. METHOD We report on six patients, 58–73 years old, three women and three men who presented with acute kidney disease, while on immunotherapy with CPIs. Five of them carried the diagnosis of non-small cell lung carcinoma (NSCLC) and one the diagnosis of renal cell carcinoma. All received proton pump inhibitors and experienced one or more of immune-related adverse events (dermatitis, arthritis, colitis, hepatitis and pneumonitis), prior to nephropathy. All underwent kidney biopsy. RESULTS Two female patients, both with NSCLC, developed heavy nephrotic syndrome (serum albumin: 1.7–1.8 mg/dL and 24-h urine protein: 12–16 g), after 23–28 months on pembrolizumab monotherapy, which was withdrawn. In the first patient, kidney biopsy demonstrated histology consistent with a lupus like membranous nephropathy (Figure 1). She received corticosteroids with partial recovery. Rechallenge with pembrolizumab was attempted and well tolerated. Renal biopsy of the second patient demonstrated a secondary AA (+) amyloidosis (Figure 2). She showed increased levels of SAA (114 mg/L) and IL-1b (22.9 pg/mL). She received colchicine and moderate dose of corticosteroids with partial remission. Two other patients, with NSCLC and clear cell renal carcinoma respectively, demonstrated renal biopsy findings consistent with acute interstitial nephritis (serum creatinine 1.5–1.6 mg/dL). The first one was on pembrolizumab along with cisplatin and pemetrexed, while the second one was on pembrolizumab along with axitinib. Both received prednisolone (10–20 mg for 3 months approximately). Pembrolizumab was restarted thereafter. Their renal function remained stable. Finally, two patients with NSCLC, both men, disclosed acute renal failure (serum creatinine: 3.6- 5 mg/dL) without considerable albuminuria. Acute tubular injury (ATI) was the predominant histological finding (along with focal and mild interstitial inflammation). Both were on combined chemo- and immune- therapy. One on ipilimumab and nivolumab along with platinum and pemetrexed and the other on pembrolizumab and pemetrexed. ATI was attributed most probably to pemetrexed which was withdrawn. Corticosteroids were promptly stopped in the first patient. The second patient showed gradual improvement of his renal function without corticosteroid therapy. CONCLUSION CPIs can induce nephropathy other than acute interstitial nephritis. Renal biopsy showed diverse and unusual histological findings. Renal biopsy along with the clinical setting was helpful in choosing appropriate therapy and deciding on CPI's continuation or withdrawal.