A case of immune-complex mediated glomerulonephritis associated with pembrolizumab

2021 ◽  
pp. 239936932110646
Author(s):  
Marco Bonilla ◽  
Vanesa Bijol ◽  
Antonio Gabriel De Leon Corona ◽  
Kevin M. Sullivan ◽  
Kenar D. Jhaveri
Keyword(s):  
Acute Kidney Injury ◽  
Immune Complex ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
High Dose ◽  
Dramatic Improvement ◽  
Pathologic Finding ◽  
Glomerular Injury ◽  
Metastatic Lung ◽  
Dose Prednisone

Introduction: Immune checkpoint inhibitors (ICI) are changing the way we treat cancer. However, these novel agents have various systemic adverse events that may preclude its use and cause poor patient outcomes. ICI-associated acute kidney injury is an emerging complication of this treatment. While tubulointerstitial disease is the most common pathologic finding of patients with ICI-associated AKI, there is sparse data in medical literature describing its association with glomerular disease. Case report: Here, we present a patient with metastatic lung adenocarcinoma who developed acute kidney injury and significant proteinuria after receiving pembrolizumab. The kidney biopsy revealed a membranoproliferative and diffuse segmental endocapillary proliferative pattern of glomerular injury. Management and outcome: Pembrolizumab was then held and high-dose prednisone was initiated, resulting in a rapid and dramatic improvement in kidney function and proteinuria. Discussion: We highlight a report of a patient diagnosed with immune-complex mediated glomerulonephritis associated with the use of pembrolizumab, who was successfully treated with drug withdrawal and corticosteroids.

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.

Acute kidney injury and nephrotic syndrome associated with eltrombopag therapy in chronic idiopathic thrombocytopenic purpura

2021 ◽  
Vol 14 (4) ◽  
pp. e241462
Author(s):  
Suchi Anindita Ghosh ◽  
Jean Patrick ◽  
Kyaw Zin Maw
Keyword(s):  
Acute Kidney Injury ◽  
Renal Failure ◽  
Nephrotic Syndrome ◽  
Idiopathic Thrombocytopenic Purpura ◽  
Kidney Injury ◽  
High Dose ◽  
Chronic Idiopathic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Antibody Screen ◽  
Auto Antibody

A 77-year-old man was admitted with severe acute kidney injury and nephrotic syndrome. He was started on eltrombopag for chronic idiopathic thrombocytopenic purpura 6 weeks earlier. An ultrasound of the kidneys was normal and an auto-antibody screen was negative. The use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient’s development of acute renal failure and eltrombopag therapy. Literature review identified only one other case of nephrotic syndrome and acute kidney injury associated with eltrombopag therapy in which a kidney biopsy revealed focal segmental glomerulosclerosis. Due to the challenges faced during the prevailing SARS-CoV-2 pandemic and persistent low platelet counts a renal biopsy was not undertaken. On stopping eltrombopag, the patients renal function stabilised and he successfully went into remission following treatment with high dose corticosteroids and diuretics. This report of a serious case of reversible renal failure and nephrotic syndrome after treatment with eltrombopag may serve to inform clinicians about the possible severe renal adverse effects of eltrombopag before its commencement for future use.

An unusual case of anuric acute kidney injury in a patient with metastatic lung cancer

2022 ◽  
Vol 101 (1) ◽  
pp. 191
Author(s):  
Cédric Aglae ◽  
Olivier Moranne ◽  
Pedram Ahmadpoor ◽  
Laurent Daniel ◽  
Florian Garo
Keyword(s):  
Lung Cancer ◽  
Acute Kidney Injury ◽  
Unusual Case ◽  
Kidney Injury ◽  
Metastatic Lung Cancer ◽  
Metastatic Lung

scholarly journals Nivolumab-associated DRESS in a genetic susceptible individual

2021 ◽  
Vol 9 (10) ◽  
pp. e002879
Author(s):  
Luoyan Ai ◽  
Jie Gao ◽  
Shihai Zhao ◽  
Qian Li ◽  
Yue-Hong Cui ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Human Leukocyte ◽  
Hla Typing ◽  
High Dose ◽  
Dress Syndrome ◽  
Th2 Response ◽  
Risk Alleles ◽  
Type Iv ◽  
Target Effect

The use of immune checkpoint inhibitors (ICIs) is rising exponentially in numerous cancers, but immune-related adverse events can occur. We report a rare case of high-grade drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome developed stepwise in a patient with gastric cancer after nivolumab treatment. Subclinical myocarditis was sensitively detected by cardiovascular magnetic resonance 3 weeks after initiating nivolumab. Eruption, eosinophilia, and interstitial pneumonitis occurred 1 week later. Corticosteroids were started and his condition improved. Four months later, when he was still on steroids tapering off, acute kidney injury and sequential herpes zoster virus activation developed. Severe acute tubulointerstitial nephritis (ATN) with an intense infiltration of lymphocytes was observed on renal biopsy. In blood, a substantial shift to Th2 response, an increase of Th17 cells, and strikingly enriched granzyme B+ and perforin+ CD8+ T cells were detected at ATN onset. Serum interleukin (IL)-5, IL-17, interferon gamma, and IL-6 levels were consistently elevated. Further molecular profiling identified a DRESS risk allele human leukocyte antigen (HLA)-A*31:01 in this patient. His ATN responded favorably to a high dose of corticosteroids. In parallel, complete antitumor response was observed during the clinical course of DRESS. This is the first ever case report of nivolumab-associated DRESS syndrome with exploration of the mechanisms from the histopathological, cellular and molecular aspects. Nivolumab-induced DRESS may result from type IV hypersensitivity-related ‘off-target effect’ and PD-1 block-mediated ‘on-target effect’. HLA risk alleles may constitute the genetic susceptible basis. HLA typing assay has the potential to screen susceptible individuals to avoid ICI-induced DRESS.

Tubulitis in a patient treated with nivolumab: Case report and literature review

2018 ◽  
Vol 2 (2-3) ◽  
pp. 107-112
Author(s):  
Viral Vakil ◽  
Mark Birkenbach ◽  
Katti Woerner ◽  
Lihong Bu
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint Inhibitors ◽  
Kidney Biopsy ◽  
Tubulointerstitial Nephritis ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Metastatic Urothelial Carcinoma ◽  
Programmed Death 1

Kidney injury associated with use of immune checkpoint inhibitors that target the programmed death-1 molecule commonly manifests as acute tubulointerstitial nephritis on kidney biopsy. We present a case of a 66-year-old man who developed acute kidney injury at 6 months after initiation of treatment with anti-programmed death-1 antibody, nivolumab, for treatment of metastatic urothelial carcinoma. A renal biopsy showed focal moderate-to-severe lymphocytic tubulitis with minimal interstitial inflammation. Programmed death ligand-1 immunopositivity was detected only in tubules exhibiting lymphocytic tubulitis. The patient’s renal function improved to baseline with conservative management consisting of discontinuation of nivolumab followed by prednisone treatment.

scholarly journals Concentration of meropenem in patients with sepsis and acute kidney injury before and after initiation of continuous renal replacement therapy: a prospective observational trial

2020 ◽  
Vol 72 (1) ◽  
pp. 147-155 ◽  
Author(s):  
Ilona Nowak-Kózka ◽  
Kamil J. Polok ◽  
Jacek Górka ◽  
Jakub Fronczek ◽  
Anna Gielicz ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Renal Replacement Therapy ◽  
Replacement Therapy ◽  
Kidney Injury ◽  
Regional Citrate Anticoagulation ◽  
High Dose ◽  
Prolonged Infusion ◽  
Time Points ◽  
Drug Concentrations ◽  
Before And After

Abstract Background The effect of renal replacement therapy on drug concentrations in patients with sepsis has not been fully elucidated because the pharmacokinetic properties of many antimicrobials are influenced by both pathophysiological and treatment-related factors. The aim of this study was to determine meropenem concentrations in patients with sepsis before and after the initiation of continuous venovenous hemodialysis with regional citrate anticoagulation (RCA-CVVHD). Methods The study included 15 critically ill patients undergoing RCA-CVVHD due to sepsis-induced acute kidney injury. All participants received 2 g of meropenem every 8 h in a prolonged infusion lasting 3 h. Meropenem concentrations were measured in blood plasma using high-performance liquid chromatography coupled with tandem mass spectrometry. Blood samples were obtained at six-time points prior to and at six-time points after introducing RCA-CVVHD. Results The median APACHE IV and SOFA scores on admission were 118 points (interquartile range [IQR] 97–134 points) and 19.5 points (IQR 18–21 points), respectively. There were no significant differences in the plasma concentrations of meropenem measured directly before RCA-CVVHD and during the first 450 min of the procedure. The drug concentration reached its peak 2 h after initiating the infusion and then steadily declined. Conclusions The concentration of high-dose meropenem (2 g every 8 h) administered in a prolonged infusion was similar before and after the introduction of RCA-CVVHD in patients with sepsis who developed acute kidney injury.

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