Although the patient declined kidney biopsy or transplant nephrectomy, acute rejection due to ICI therapy was clinically suspected, steroids were initiated, and the patients pain and hematuria resolved

Although the patient declined kidney biopsy or transplant nephrectomy, acute rejection due to ICI therapy was clinically suspected, steroids were initiated, and the patients pain and hematuria resolved. ICI, immune checkpoint inhibitor; irAE, immune-related adverse events; HD, hemodialysis; PD, peritoneal dialysis. Two patients are highlighted because their clinical courses appear exceptional. The first, a 65-year-old male with a history of renal transplantation (2010) and subsequent allograft failure (2016), was on HD for 3 years and weaned off maintenance transplant immunosuppression by 2018. He subsequently developed hepatocellular carcinoma in 2018 and was initiated on nivolumab. Several cycles into therapy, he developed abdominal pain at the graft site and acute gross hematuria. Although the patient declined kidney biopsy or transplant nephrectomy, acute rejection due to ICI therapy was clinically suspected, steroids were initiated, and the patients pain and hematuria resolved. Further ICI was held due to progression of disease and he was transitioned to hospice care. The second patient, PR22 a 79-year-old male with cholangiocarcinoma and known CKD stage 4 was treated with pembrolizumab, which was complicated by AKI after the second cycle. A kidney biopsy confirmed oxalate nephropathy, with the cause being attributed to prior gastric surgeries. Given the progressive renal failure, he was initiated on HD. ICI therapy was continued without any adverse events. This case was included to illustrate an alternate cause of renal failure unrelated to acute interstitial nephritis from ICI therapy, underscoring the importance of a kidney biopsy in the diagnosis of AKI during ICI therapy. Three additional patients developed dialysis-dependent ESKD as a result of ICI therapy (Table 2). All three patients were on proton pump inhibitors. Two of the patients had ICI-associated amyloid A amyloidosis (based on kidney biopsy); the detailed report has been published separately (4). The other patient developed ESKD after the initiation of atezolizumab, however, a kidney biopsy was not performed. His long-term outcome was unclear because he was lost to follow-up. Table 2. Clinical summary of patients who developed ESKD from ELQ-300 immune checkpoint inhibitors thead Case No.AgeGender (M/F)Cancer DiagnosisTime to ESKD after ICI (mo)Kidney Biopsy FindingsMonths to Dialysis after ICI Was StartedICI GivenCancer StatusDeath (yes/no) /thead 142MColorectal cancer3AA amyloidosis4PembrolizumabIn remissionNo281MMelanoma10AA amyloidosis11NivolumabIn remissionYes371MBladder cancer4No kidney biopsy done5AtezolizumabProgressedLost to follow-up Open in a separate window M, male; F, female; ICI, immune check point inhibitor; AA amyloidosis, amyloid A amyloidosis. Review of the Literature Table 3 summarizes all currently published cases and outcomes of using ICIs in patients with ESKD. A total of 26 patients have previously been described in the literature (5C,18), with the majority of them ELQ-300 from two centers, (2,3) and mostly receiving HD (92%). A variety of malignancies were treated (35% for melanoma; 54% for renal cell carcinoma; with the remainder composed of squamous cell skin cancer, urothelial cancer, and nonsmall cell lung cancer). Interestingly, 27% of these patients were on dialysis as a result of a rejected kidney transplant due to ICI therapy, and then continued to receive ICI. Over 80% of the patients had either partial or complete response to treatment. Aside from the kidney transplant rejection preceding dialysis, a minimal number of patients had a grade 2, 3, or 4 adverse immunotherapy-related event (15%). Table 3. Summary of patient data from 26 published cases of the use of immunotherapy in dialysis patients thead No. of PatientsAgeICI TypeCancerDialysis ModalityCancer Response (full, partial, none)irAEsReference No. /thead 1a74NivolumabMelanomaHDFullRejected transplant on dialysis(6)1a76NivolumabMelanomaHDFullRejected transplant on dialysis(7)1a57PembrolizumabSkin SCCHDFullRejected transplant on dialysis(10)1a48Ipilimumab+nivolumabMelanomaHDFullRejected transplant on dialysis(11)1a68Ipilimumab+pembrolizumabMelanomaHDFullRejected transplant on dialysis(12)1a40IpilimumabMelanomaHD/PDNoneRejected transplant on dialysis(13)1a57NivolumabMelanomaHDFullRejected transplant on dialysis(15)177NivolumabRCCHDFullNone(8)1NAPembrolizumabMelanomaHDFullNone(9)149NivolumabRCCHDFullNone(14)256,69Ipilimumab (2)MelanomaHDFull, partialOne patient had dermatitis(5)166PembrolizumabNSCLCHDPartialNone(16)172NivolumabRCCHDPartialNone(17)364,65,68Nivolumab (2), AtezolizumabRCC (2); urothelial cancer (1)HDFull, partial, nonePneumonitis in ELQ-300 one patient(2)851C77NivolumabRCC7 HD, br / 1 PDSix with partial response, two with noneTwo patients with grade three toxicities(3)1NAAtezolizumabRCCHDPartial responseNone(18) Open in a separate window ICI, immune check point inhibitor; irAEs, immune-related adverse events; HD, hemodialysis; SCC, squamous cell cancer; PD, peritoneal dialysis; RCC, renal cell cancer; NSCLC, nonsmall cell lung cancer; NA, not available. aThe patient had a transplant rejection due to immunotherapy leading to dialysis-dependent kidney failure; immunotherapy was continued while the patient was on dialysis. Conclusion Immunotherapy has changed the paradigm of treatment in several solid malignancies. The incidence and type of irAEs vary with the immunotherapeutic agent and duration of therapy (19). The reported incidence of any grade irAEs ranges from 60% to 70% in patients treated with ipilimumab as compared with 39%C41% on programmed cell death protein 1 inhibitors, and the incidence of grade 3C4 irAEs is higher with.