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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: Thrombotic Microangiopathy (TMA) after non renal solid organ transplantation is very rare. While few cases of TMA following liver and lung transplants have been published, it has been very rarely reported following orthotopic heart transplant (OHT). We report the first case of kidney biopsy proven De Novo TMA after OHT. Case Description: 58-year-old male with non ischemic cardiomyopathy undergoes OHT in Jan 2021. He had normal renal function pre transplantation. Post-operatively he had pericardial effusion and in that setting developed oliguric AKI from ATN requiring dialysis. His renal function recovered and was discharged without dialysis. He was on tacrolimus, MMF and steroid regimen. Frequent heart biopsies were negative for rejection. In March 2021 the patient was admitted for GI bleed and again noted to have AKI. However, during this episode he developed proteinuria of over 2gm, new compared to previous urine studies. He was discharged with a serum creatinine of 2.6mg/dL. By July 2021 renal function worsened and he underwent a renal biopsy on 7/30/21 which showed acute and chronic TMA, related to calcineurin inhibitor use. Viral causes and other medications were ruled out (CMV, BK, adenovirus, SARs-COV2). Tacrolimus was held and he was initiated on Everolimus. Genetic and complement testing revealed normal complement levels, an elevated SC5b-9 complex, heterozygous for the APOL1 gene mutation (c.[1024A>G;1152T>G] p.[Ser342Gly;Ile384Met] (G1 allele)), and heterozygous for the CFHR5 gene mutation, suggestive for complement mediated TMA. He was initiated on Eculizumab. After two doses of Eculizumab he was again admitted with acute respiratory failure requiring intubation secondary to mTOR induced pneumonitis. His renal function worsened and he was reinitiated on dialysis. After a multidisciplinary discussion, he was transitioned to cyclosporine for immunosuppression. He continues to be on dialysis and cyclosporine with eculizumab without other non-renal findings of TMA. He is currently being evaluated for kidney transplantation. He has no signs of OHT rejection on heart biopsies. Discussion(s): The early identification and treatment of TMA in OHT is important in preventing further complications associated with it. Although rare as compared to other solid organ transplants, it is essential to maintain TMA as a differential diagnosis for AKI following OHT.
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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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Drug- Induced Acute Interstitial Nephritis is a known cause of AKI commonly caused by NSAIDS, PPI and antibiotics which have been well documented in the literature. The hallmark presentation is fever, rash and eosinophilia, although this is only seen in a minority of cases. Half of cases do not present with AKI and therefore the clinician must have a high index of suspicion for further workup. Early detection can lead to early treatment which should result in improved outcomes. 67 Gallium renal scan Scintigraphy has been used over the last 30 years to help diagnose AIN, however no known use of Indium-111 WBC Scan has been used to in the diagnosis of AIN. A 71-year-old male presented with fevers and generalized weakness for 4 days, endorsing associated paresthesias in both lower extremities as well as visual hallucinations. After a primary care physician outpatient visit, a WBC Scan showed localization to bilateral kidneys and the colon. He was sent to the hospital for IV antibiotics as bilateral pyelonephritis was suspected. Initial labs was significant for WBC of 11.4k (without Eosinophilia), serum creatinine of 1.73 (Baseline 1.1). Urinalysis was negative for infection however with trace proteinuria. Covid test was negative. Three sets of blood cultures were negative. Imaging was negative for acute pathology. IV antibiotics were started without resolution of symptoms. Transthoracic Echo was negative for any vegetations. Patient continued to have fevers. He stated that he was started on hydralazine three weeks prior to admission. After cessation of Hydralazine he ceased to have fevers. Case was discussed with Radiology and he had a renal biopsy. Biopsy results confirmed mild AIN, 45% global sclerosis, severe arterial and arteriolar sclerosis, tubular atrophy and interstitial fibrosis. He was started on Prednisone and tapered over 2 months. Renal function returned to baseline. AIN was suspected because of recent initiation of Hydralazine even though neither rash nor eosinophilia was present. A positive Indium-111 WBC Scan in the setting of fever, AKI and elevated WBC count encouraged us to proceed with the biopsy even though the patients' AKI had “resolved.” Here we aim to show that Indium-111 WBC assisted in the diagnosis of AIN and could be used in the future for clinicians as an indication for biopsy.
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Background: Vaccine-triggered complications, including autoimmune diseases and minimal change disease (MCD), were reported during recent COVID-19 vaccine rollout. Anti-nephrin autoantibodies were described in nephrotic syndrome (NS) with kidney biopsy (Kbx)-proven MCD. Therefore, we examined patients with COVID-19 vaccineassociated NS for anti-nephrin autoantibodies. Methods: 5 patients presenting with nephrotic-range proteinuria 1-3 weeks after COVID-19 vaccine and a KBx were identified (3 Pfizer/BioNTech, 2 Moderna). Past medical history and lab tests including serum creatinine (sCr), urine protein-to-creatinine ratio (UPCR), and serological workup were recorded. KBx were routinely evaluated by light microscopy (LM), immunofluorescence microscopy (IF), and electron microscopy (EM), followed by confocal examination of relative IgG and nephrin localization in all patients;serological studies for anti-nephrin antibodies using human glomerular extract and recombinant nephrin extracellular domain were performed using plasma available on 2 patients. Results: In all patients, sCr was 0.5-1.2 mg/dl and UPCR 4.5-7.6 g/g. 1 patient had MCD in remission diagnosed 6 months prior;others had no relevant PMH. All workup was negative, except low positive ANA in 2 patients. On KBx, diagnosis of MCD was made in 4 and stage I membranous nephropathy (MN) in 1 patient(s) (serum albumin 2.0-2.4g/dl in MCD and 3.6g/dl in MN patient(s));all had mild chronic changes. All 4 MCD patients had fine granular punctate podocyte staining for polyclonal IgG colocalizing with nephrin by IF and diffuse FPE by EM;in 1 patient plasma was saved during NS and was serologically positive for anti-nephrin. The MN patient had 3+ fine granular IF staining for polyclonal IgG and PLA2r along GBMs with sparse superficial subepithelial electron-dense deposits on EM, and was serologically negative for antinephrin. All MCD patients were successfully treated with oral glucocorticoids, while the MN patient was monitored closely under RAAS blockage. Conclusions: COVID-19 mRNA vaccines can trigger de-novo or relapsing anti-nephrin-and PLA2r-mediated NS, thus adding both autoimmune-mediated podocytopathies to vaccine-induced complications. Temporal association is essential for diagnosis;prompt accurate diagnosis benefits treatment and response.
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Background: Patients with ESKD have a dysregulated immune system and a higher annual mortality rate compared with the general population. We aimed to describe the clinical characteristics and compare the outcomes of patients with and without ESKD, among those hospitalized with COVID-19 disease. Methods: We reviewed the health records for all patients hospitalized with Covid-19 between March 1, 2020 and April 27, 2020 from 13 hospitals in New York. Patients < 18 years or admitted to inpatient obstetrics service were excluded. ESKD diagnosis was defined using ICD-10 code and manual adjudication. Patients were followed up through May 27, 2020. Results: Of 10,482 patients admitted with COVID-19, 419 (4.0%) had ESKD. Among patients with ESKD, 408 (97.4%) were on hemodialysis and 11 (2.6%) were on peritoneal dialysis. When comparing baseline characteristics of the two groups, patients with ESKD were older, were predominately of Black race, and had greater proportions of comorbid conditions. The primary outcome was that patients with ESKD had a higher odds of in-hospital death than those without ESKD (rates, 31.7% vs 25.4%;OR 1.4, 95% CI 1.1 - 1.7). After adjusting for age, sex, race/ethnicity, the odds ofin-hospital death remained higher in the ESKD group (adjusted OR 1.5, 95% CI 1.2 - 1.8). The ESKD group did not have a significantly higher odds of needing mechanical ventilation than the non-ESKD group in both the crude analysis and after adjustment for age, sex, race/ ethnicity. The odds of having a length of stay of >;7 days was higher in the ESKD group compared to the non-ESKD group, in both the crude analysis and the adjusted analysis (OR 1.62, 95% CI 1.3 - 2.1;adjusted OR 1.6, 95% CI 1.3 - 2.1). The independent predictors for death for non ESKD patients were age, male gender, cancer, CHF, elevated BUN, low albumin and being on a ventilator. The independent predictors of death for ESKD patients were age, lymphopenia, low albumin and being on a ventilator. Black race was associated with lower risk of death. Conclusions: ESKD patients had a higher rate of mortality compared to non-ESKD patients hospitalized with COVID-19. Black race was associated with a lower risk of death among ESKD patients compared to white patients.
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Background: The rate of AKI associated with patients hospitalized with Covid-19, and associated outcomes are not well understood. Methods: We reviewed the health records for all patients hospitalized with Covid-19 between March 1, and April 5, 2020, at 13 hospitals in metropolitan New York. Patients younger than 18 years of age, with ESKD or with a kidney transplant were excluded. AKI was defined according to KDIGO criteria. The primary outcome was the development of AKI. Secondary outcomes included need for RRT and hospital disposition, i.e., discharge or death. The RRT modalities offered to patients with AKI in our health system were intermittent HD or CRRT. All patients were followed up through April 12th, 2020. We additionally analyzed urine results including urine electrolytes and urinalysis with automated microscopy that were obtained within 24 hours before or 48 hours after the initial development of AKI. Results: Of 5,449 patients admitted with Covid-19, AKI developed in 1,993 (36.6%). The peak stages of AKI were stage 1 in 46.5%, stage 2 in 22.4% and stage 3 in 31.1%. Of these, 14.3% required renal replacement therapy (RRT). AKI was primarily seen in Covid-19 patients with respiratory failure, with 89.7% of patients on mechanical ventilation developing AKI compared to 21.7% of non-ventilated patients. 276/285 (96.8%) of patients requiring RRT were on ventilators. Of patients who required ventilation and developed AKI, 52.2% had the onset of AKI within 24 hours of intubation(Figure and Table). Risk factors for AKI included older age, diabetes mellitus, cardiovascular disease, black race, hypertension and need for ventilation and vasopressor medications. Among patients with AKI, 1136 died (57%), 519 (26%) were discharged and 338 (17%) were still hospitalized. Conclusions: AKI occurs frequently among patients with Covid-19 disease. It occurs early and in temporal association with respiratory failure and is associated with a poor prognosis. (Figure Presented).
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Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it inflicts, coronavirus disease 2019 (COVID-19), has become a global pandemic in 2020. To date, only one case of ANCA associated vasculitis (AAV) with COVID-19 has been reported from Iran. We describe the first two cases of AAV and glomerulonephritis in the United States. Case Description: Case one: 64 year old African American male with a distant (> 10years) history of cryptogenic organizing pneumonia presented to the hospital with hypoxic respiratory failure secondary to COVID19. He had an acute kidney injury(AKI) with elevated creatinine(Cr) of 7.87mg/dL. Urinalysis revealed active sediment with 55 RBC/ hpf, 65 WBC/hpf, and nephrotic range proteinuria: 5 gm/gm of creatinine. He was initiated on renal replacement therapy and received convalescent plasma along with Tocilizumab for the treatment of COVID-19. Serologic testing revealed a positive perinuclear (p)-ANCA (1:320), myeloperoxidase (32.5). Kidney biopsy was consistent with a pauci immune glomerulonephritis;cellular crescent present in 40% of glomeruli. He received pulse dose steroids and Rituximab. The patient had a good clinical response and was able to discontinue hemodialysis and serum Cr decreased to 3.5mg/dL. Case Two: 46 year old South Asian male presented with rash from leukocytoclastic vasculitis and was diagnosed with COVID-19. He had an AKI, serum Cr peaked at 4.0mg/dL with proteinuria, leukocyturia, and microhematuria on urinalysis. Cytoplasmic(c)-ANCA and proteinase-3(PR-3) were positive. A kidney biopsy was performed which revealed a necrotizing glomerulonephritis. He was treated with steroids and Rituximab with a positive response, Cr decreased to 2.0mg/dL. Discussion: It is now well known that SARS-CoV-2 affects organs outside of the respiratory system, with the kidneys being a usual target. The most commonly reported presentation of COVID-19 and the kidneys is AKI, the etiology of which is predominantly acute tubular necrosis (ATN). Collapsing GN is by far the most described glomerular lesion. Clinicians should be aware of AAV with GN as another potential pathology, and concurrent use of immunosuppression with treatment of infection, can lead to favorable clinical outcomes.
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Introduction: We describe a patient with COVID-19 and clinically significant kidney biopsy proven TMA Case Description: 69-year-old Caucasian female with medical history of asthma came to the ED with productive cough, fever and dyspnea for 2 weeks. She was afebrile, tachypneic and hypoxic. Initial laboratories showed a normal WBC, hemoglobin level and platelet count. Inflammatory markers were elevated. SARS-CoV-2 infection was confirmed by PCR assay. CXR showed bilateral diffuse patchy opacities. Treated with hydroxychloroquine, enoxaparin and oxygen was started. Patient received anakinra and tocilizumab. On day 12, the patient developed thrombocytopenia, anemia and worsening kidney function concerning for microangiopathic hemolytic anemia. Due to worsening hypoxemia, patient received convalescent plasma. On day 17, she was intubated due to worsening respiratory failure. Findings suggestive of hemolysis were present. Urinalysis showed hematuria and proteinuria. Patient's kidney function worsened requiring initiation of CRRT. On day 20, the patient underwent a kidney biopsy that revealed severe acute TMA with cortical necrosis. Beta 2 glycoprotein-1 IgM levels were elevated, antiphospholipid antibodies were absent. A disintegrin and ADAMTS13 level were not low. C3,C4 were in normal range. Heparin induced antibody testing was negative. Coagulation parameters were normal. Kidney doppler was unremarkable. No other systemic findings of macro thrombi were found. Low factor H complement antigen, elevated plasma CBb complement and plasma SC5b-9 complement levels suggesting an activation of the alternative complement pathway were found. Genetic testing was not done. Plasma exchange was not performed, but received a single dose of eculizumab on day 21. Unfortunately, she died on day 23. Discussion: Coagulopathy associated with SARS-CoV-2 has been widely reported. Profound hypoxia, inflammation, disseminated intravascular coagulation(DIC) have all been implicated as potential causes, but were not present in our patient. To the best of our knowledge, we report the first case of TMA associated with SARS-CoV-2 with presence of diffuse cortical necrosis and widespread microthrombi in kidney biopsy. It is not clear if the virus played a direct pathogenic role or unmasked a latent complement defect leading to widespread endothelial damage and micro thrombi.
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Background: The high rate of ARF in COVID-19 hospitalized patients increased the demand for critical care renal replacement therapy 2-3 fold at Northwell Health (NW). At the 2 largest hospitals, Long Island Jewish (LIJ) and North Shore University Hospital (NSUH), bedside HD was provided by HD RNs and continuous renal replacement therapy (CRRT) by critical care (CC) RNs. RN workload in these hypercatabolic patients soared as HD treatments more than doubled and CRRT increased from 9 to 30,. Shortages of CRRT fluid and filter sets ensued. SLED, a technique utilizing standard HD dialysate and filters, combined with a collaboratiive approach between CC and HD RNs was considered. Methods: In late March, a cohort CC bedside HD program, was initiated. Based on this success, a leadership panel of CC/HD RN and Renal/CC MDs created a SLED project plan. Details were reviewed with stakeholders on Friday prior to the Tuesday “Go-Live.” 3 patients previously treated with HD or CRRT via a Shiley catheter were selected as a pilot for three 6-8 hour sessions, Fresenius 2008T, Revaclear 300 filters with dialysate flow rate 300 cc/min and blood flow rate 200-300 cc/min were ordered. HD RN initiated treatments and available throughout, while clinical stability was monitored by CC RN. Results: NSUH pilot involved 5 patients over 3 sessions. Suboptimal cohorting required remote tablet monitoring and frequent presence of several HD RNs. One patient was terminated in one session due to persistent hypotension. Clearances and UF goals were achieved throughout. A week later the LIJ pilot used the design and advantage of NSUH experience with a 3 bed “SLED Room” model. The same 3 patients participated in all 3 sessions supervised by a single HD RN with no discontinuation. CC RN satisfaction with SLED was ranked “high” at both sites and by LIJ HD RNs but “Spread SLED” rated only “fair” by NSUH HD RNs. Pilots were extended 10 days. During this period SLED was initiated at 2 other NH sites. Future SLED programs will be focused on NH hospitals lacking CRRT. Conclusions: SLED is an efficient alternative to CC HD and CRRT. The challenges of effective cohorting in a pandemic surge relegate its role to a piece of a comprehensive renal critical care program. It imay be particularly valuable for hospitals lacking CRRT options.