MO404ACUTE KIDNEY INJURY DUE TO IMMUNE CHECKPOINT INHIBITORS (CPIS) NEPHROTOXICITY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Fausta Catapano ◽  
Elisa Persici ◽  
Giulia Ubaldi ◽  
Francesca Romani ◽  
Elena Mancini
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Interstitial Nephritis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Renal Outcome ◽  
Long Term Follow Up

Abstract Background and Aims The approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding; however the immune-related toxicities associated with CPIs can limit its efficacy. Case Report. A 52 year-old female diagnosed with left ocular melanoma and treated for 14 months with nivolumab developed non-oliguric, stage 3 (KDIGO), Acute Kidney Injury (AKI) and mixed proteinuria (0.6 g/day), then was transferred in our Unit. As known causes of AKI were excluded, kidney biopsy was performed. By Optical Microscopy, there were 33 normal glomeruli; arteries and arterioles were normal. The main damage was interstitial and characterized by tubulitis, tubular necrosis, non-isometric citoplasmatic vacuolization and diffuse, acute and chronic, CD4+, inflammatory infiltrate (Figure 1, 2). By Immunofluorescence, 27 glomeruli were negative for all eight tested antibodies (IgA, IgM, IgG, F, C3, C1q, kappa and lambda light chains). On the basis of these histological findings, Nivolumab-induced Acute Tubulo-Interstitial Nephritis was diagnosed. Nivolumab was discontinuated. Patient was treated by steroids and she achieved almost complete renal function recovery (Figure 3). Conclusions. CPIs can induce a long-term Acute Kidney Injury. Histological features are characterized by Acute Tubulo-Interstitial Nephritis. Steroids can improve renal outcome. In patients treated with CPIs a multidisciplinary management between oncologists and nephrologists is desirable for monitoring renal function at basal, after drug administration and in the long-term follow-up.

scholarly journals Acute Kidney Injury after Pembrolizumab-Induced Adrenalitis and Adrenal Insufficiency

2018 ◽  
Vol 8 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Ramy M. Hanna ◽  
Umut Selamet ◽  
Patrick Bui ◽  
Shih-Fan Sun ◽  
Olivia Shenouda ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Adrenal Insufficiency ◽  
Interstitial Nephritis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Clinical Course ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Glomerular Disease ◽  
Severe Hypotension

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein 1 (PD-1) antigen and induces an immune response against tumor tissues. It has been successful in inducing remission in patients with severe metastatic disease, often refractory to other chemotherapeutic agents. The risk of injury of other organ systems has been noted with reported cases of glomerular disease and endocrine disease. In addition, hypophysitis as well as dermatological and gastroenterological side effects have been reported. Renal injury with immune checkpoint inhibitors like nivolumab and pembrolizumab is usually mediated via interstitial nephritis, though glomerular disease presentations like anti-neutrophil cytoplasmic antibody-associated vasculitis, immune complex disease, and thrombotic microangiopathy have also been reported. We report a 70-year-old Caucasian male who underwent treatment with pembrolizumab for adenocarcinoma of the lung. He developed acute adrenal insufficiency and concomitant severe hypotension upon presentation. He did not require renal replacement therapy, rather his severe acute kidney injury resolved with hydration, normalization of blood pressures with vasopressors, and treatment with high-dose corticosteroids. His urinary indices (fractional excretion of urea, FEUrea) and clinical course were highly suspicious for acute tubular necrosis that resolved quickly after treating his underlying adrenalitis. The urinary sediment, proteinuria, and clinical course were not typical for the usually expected renal lesion of interstitial nephritis in patients treated with immune checkpoint inhibitors.

scholarly journals The mechanisms of acute interstitial nephritis in the era of immune checkpoint inhibitors in melanoma

2019 ◽  
Vol 11 ◽  
pp. 175883591987554 ◽  
Author(s):  
Marco Tucci ◽  
Anna Passarelli ◽  
Annalisa Todisco ◽  
Francesco Mannavola ◽  
Luigia Stefania Stucci ◽  
...  
Keyword(s):  
Renal Function ◽  
Interstitial Nephritis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Acute Interstitial Nephritis ◽  
Clinical State ◽  
High Dose ◽  
Systemic Symptoms ◽  
The Impact

Treatment with immune checkpoint inhibitors (ICIs) has improved the prognosis of patients with a number of types of cancer, but the frequent development of immune-related adverse effects (irAEs) can worsen the outcome. The most common irAEs involve the gastrointestinal, cutaneous, and endocrine systems, but nephrotoxicity, resulting from damage to the tubule-interstitial compartment, may occur in some patients. The early phases of acute interstitial nephritis (AIN) are characterized by systemic symptoms that indicate a poor clinical state as well as a mild deterioration of renal function. Tubular injury is due to a direct effect mediated by cytotoxic CD8+ T cells, which sustain the local production of pro-inflammatory cytokines that progressively impair renal function. The treatment of AIN is mainly based on high-dose steroids, which in most instances leads to the recovery of renal function. However, the premature discontinuation of ICI therapy may prevent the impact of treatment on the clinical progression of the malignancy. Adequately addressing irAEs requires a standardized therapy that is based on the results of large clinical trials.

scholarly journals Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors

2016 ◽  
Vol 90 (3) ◽  
pp. 638-647 ◽  
Author(s):  
Frank B. Cortazar ◽  
Kristen A. Marrone ◽  
Megan L. Troxell ◽  
Kenneth M. Ralto ◽  
Melanie P. Hoenig ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Clinicopathological Features

Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia

2020 ◽  
Vol 26 (7) ◽  
pp. 1791-1794 ◽  
Author(s):  
Ali Yılmaz ◽  
Cem Mirili ◽  
Mehmet Bilici ◽  
Salim Başol Tekin
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Drug Induced ◽  
Musculoskeletal Problems ◽  
Third Line ◽  
Anti Tumor Activity

Introduction The immune checkpoint inhibitors (ICIs), which are used to activate the immune system and stimulate anti-tumor activity, are preferred in many cancers. Atezolizumab acts by blocking programmed cell death ligand (PD-L1) and may cause immune hyperstimulation in healthy tissues like other ICIs, resulting in immune-related adverse events (irAEs). Hepatitis, colitis, pneumonitis, hypophysitis, hypothyroidism, rash, musculoskeletal problems are the most common irAEs, and on the other hand, acute kidney injury (AKI) and immune thrombocytopenic purpura (ITP) are infrequent. Case report We present a case with non-small cell lung cancer (NSCLC) treated with atezolizumab 1200 mg every three weeks for third-line treatment. The patient was admitted with fatigue and back pain. The patient’s complaints started one week after the first dose of atezolizumab. The patient had renal injury and thrombocytopenia and was diagnosed with drug-induced AKI and ITP. Management and outcome After platelet replacement, intravenous immunoglobulin (IVIG), and steroid therapy, the patient whose platelet count was normalized and creatinine level regressed was discharged, and routine follow-up continues. Discussion Here, we present a case with NSCLC treated with atezolizumab and with drug-induced ITP and AKI association. Given that atezolizumab and other immune checkpoint inhibitors are being utilized in the treatment of cancers, physicians should be aware of the irAEs, including the AKI and ITP.

640 Characterizing severe acute kidney injury in patients treated with immune checkpoint inhibitors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A676-A676
Author(s):  
Chung-Jiah Chen ◽  
Lisa Kim ◽  
Ashley Weaver ◽  
Sandip Patel
Keyword(s):  
Acute Kidney Injury ◽  
Renal Biopsy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
University Of California ◽  
High Dose ◽  
Renal Ultrasound ◽  
The University

BackgroundRenal immune-related adverse events (irAEs), are relatively rare in patients treated with immune checkpoint inhibitors (ICIs). This retrospective analysis characterizes the etiology of severe acute kidney injury (AKI) in patients treated with ICIs at the University of California, San Diego.MethodsThe electronic medical record was used to identify all patients with an estimated glomerular filtration rate (eGFR) <15 mL/hr who received ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, cemiplimab between 1/2000 and 1/2019. Patients with baseline eGFR < 15 mL/hr or who experienced an eGFR decline to <15 mL/hr prior to ICI initiation were excluded. Extracted data included serum creatinine, eGFR, ICI dose, urinalysis, renal ultrasound, clinical documentation of both ICI-related nephritis and other suspected causes of AKI. These data were analyzed to determine cause of AKI and possible relation to ICI.Results46 patients who received ICI therapy and subsequently developed an AKI with eGFR <15 mL/hr were identified. Three of these 46 patients (6.5%) had AKIs partially or predominately attributed by the clinician to ICI therapy (table 1). Characteristics of ICI-related AKI for these patients are summarized in (table 2). AKI onset occurred 32–110 days after ICI initiation. All three patients exhibited proteinuria, pyuria, and hematuria on urinalysis with negative urine cultures, but none underwent confirmatory renal biopsy. Only one patient had urine eosinophils checked, which was negative. Two (66%) of these patients received high-dose corticosteroids with subsequent complete eGFR recovery. Neither of these two patients required renal replacement therapy. One patient (33%) declined corticosteroid treatment due to concomitant multiorgan failure. An additional four (8.7%) patients developed multifactorial AKIs with other concurrent IRAEs that were treated with corticosteroids, but were not formally diagnosed with ICI-related AKI.Abstract 640 Table 1AKI etiologies in ICI-treated patientsAbstract 640 Table 2Patient characteristics in ICI-related AKIConclusionsIn our cohort, 6.5% of patients who develop AKI after receiving ICI therapy experienced immune-related nephritis. A further 8.7% of patients experienced other irAEs with AKI, suggesting that the true prevalence of immune-related nephritis is likely underdiagnosed. Notably, 84.8% of patients who develop AKI after ICI therapy have a non-ICI-related etiology, and no patient in our cohort of 46 patients underwent renal biopsy, highlighting the need for blood-based biomarker development for immune-related nephritis.Ethics ApprovalThe study was approved by the University of California San Diego’s Institutional Review Board, approval number 150348.

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