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Background: Immune check point inhibitors (ICPi) have become the first line treatment for most of the cancers and have shown promising results. However, they can provoke reactions, the most feared being immune related adverse events (irAE). Case presentation: We present a series of three cases, of patients recieving ICPi. All three patients developed AKI after administration of SARS-CoV-2 mRNA vaccine. Two patients had kidney-biopsy-proven acute interstitial nephritis (AIN) which responded to ICPi discontinuation and treatment with steroids. One had presumed AIN based on the high levels of CRP and urine retinol binding protein to creatinine ratio and responded to cessation of ICPi alone. Conclusion(s): These three cases demonstrate that a strong immune response from the SARS-CoV-2 mRNA vaccine combined with an uninhibited immune system under influence of ICPi led to an amplification of autoimmunity leading to AKI presenting as AIN.Copyright © The Author(s) 2022.
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Background: Immune check point inhibitors (ICPi) have become the first line treatment for most of the cancers and have shown promising results. However, they can provoke reactions, the most feared being immune related adverse events (irAE). Case presentation: We present a series of three cases, of patients recieving ICPi. All three patients developed AKI after administration of SARS-CoV-2 mRNA vaccine. Two patients had kidney-biopsy-proven acute interstitial nephritis (AIN) which responded to ICPi discontinuation and treatment with steroids. One had presumed AIN based on the high levels of CRP and urine retinol binding protein to creatinine ratio and responded to cessation of ICPi alone. Conclusion(s): These three cases demonstrate that a strong immune response from the SARS-CoV-2 mRNA vaccine combined with an uninhibited immune system under influence of ICPi led to an amplification of autoimmunity leading to AKI presenting as AIN. Copyright © The Author(s) 2022.
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Introduction: Immune check point inhibitors (ICPi) have become the first line treatment for most of the cancers and have shown promising results. Vaccine has mitigated the spread of COVID-19 infection, however there are no reported cases in literature of precipitation of AKI in patients treated with ICPi. We describe 3 cases of vaccine induiced AIN in patients treated with ICPi. The plausible explanation is amplification of autoimmunity from SARS-CoV-2 vaacine under the influence of ICPi. Case Description: Pt 1: 55 year old man on pembrolizumab for lung adenocarcinoma (b/l SCr 1.1 mg/dL) came with AKI (SCr 7.65 mg/dL) after he received first dose of Pfizer SARS-CoV-2 vaccine a week prior to admission. COVID19 PCR was negative. Kidney biopsy showed AIN. ICPi was stopped and oral prednisone (1 mg/kg) was started. SCr declined sharply. Steroid was tapered over 7 months, SCr improved to 1.7 mg/dL. Rechallenge with ICPi was defered. Pt 2: 68 year old female was on ipilimumab for metatstaitc melanoma.10 days after her first dose of Pfizer SARS-CoV-2 vaccine she developed AKI, SCr 3.4 mg/dL (b/l 1.3 mg/dL). COVID19 PCR was negative. Kidney biopsy showed AIN. ICPi was stopped and oral prednisone (1mg/kg) was started. At 5 months her SCr was 1.6 mg/dL on prednisone 5 mg qd, however she died from sepsis and multiorgan failure. Pt 3: 65 year old female with h/o bladder cancer on pemborlizumab developed AKI, SCr 2.18 mg/dL (b/l 0.8 mg/dL). 3 weeks prior she got a booster dose of Pfizer SARS-CoV-2 vaccine. COVID19 PCR was negative. ICPi was discontinued. CRP was 40 mg/dL (was < 3mg/dL prior) and urine retinol binding protein to creatinine (uRBP/ Cr) ratio was 3797 mcg/g Cr (normal < 190). Pateint declined kidney biopsy. Kidney function returned to baseline in 6 weeks without steroids. The cause of AKI was presumed to be AIN based on the elvated uRBP/Cr ratio. Discussion(s): A strong immune response from SARS-CoV-2 vaccine combined with an uninhibited immune system from ICPi may have led to an amplification of autoimmunity leading to AIN. We suggest, extra surveillance in patients receiving ICPi after SARSCoV-2 vaccination is justified, and investigation into the amplification of T-lymphocyte response from highly immunogenic vaccines in patients receiving ICPi will throw more light on the immunopathogenesis.
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Background: Up to 1-in-3 cases of severe COVID-19 infection can cause respiratory failure sometimes necessitating extracorporeal membrane oxygenation (ECMO) support. Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is a common complication, yet risk factors & outcomes in these patients are not well studied. Methods: A retrospective single-center study included 40 patients who received ECMO support for severe COVID-19 infection from Jan 20 to April 21. We extracted demographic, clinical, & laboratory variables on all patients. Primary outcome was hospital mortality;other recorded outcomes were total length of stay, ventilator, ECMO, & CRRT days, dialysis dependence at discharge. Group comparisons with & without CRRT were made by 2-sample Wilcoxon test for continuous variables & Fisher's exact test for categorical variables. Association of CRRT use & primary outcome was assessed by multivariable logistic regression (odds ratio (OR), 95% confidence interval (CI)). Results: Overall cohort was 62.5% male, 32.5% black, with a median age of 51 years & BMI of 39.4. Thirty percent were diabetic & 42.5% were hypertensive. Of the 40 ECMO patients, 36 were on veno-venous, 2 on arterio-venous, & 2 utilized both venoand arterio-venous circuits. 19/40 (47.5%) of ECMO patients required CRRT for AKI (3/19 patients CRRT was connected through the ECMO circuit). The median CRRT days were 20. Compared to those without CRRT, ECMO with CRRT patients needed a median of 19 ventilation days vs 15, 19 ECMO days vs 11, & 28 hospital days vs 32. Overall mortality was 50% (68.4% ECMO+CRRT vs 33.3% in others;p-value 0.0562). Logistic regression indicated that CRRT use in ECMO was associated with increased adjusted odds of death (6.37 OR, 1.12-36.19 95% CI). Of those who did not experience hospital mortality in the ECMO+CRRT group, 83% were dialysis-dependent at discharge. Conclusions: Overall, extracorporeal support offers a meaningful bridge until organ recovery in severe COVID-19 infection. Despite necessitating ECMO, 50% of patients were able to be liberated from ECMO & survived. However once renal failure ensued, all patients required CRRT, which in turn predicted poor outcomes.