Acute renal failure and cardiac arrhythmias associated with remdesivir use in patients with COVID-19 infections: Analysis using the US FDA adverse event reporting system.

BACKGROUND: Recently, antivirals, including remdesivir, have been repurposed to treat COVID-19 infections. Initial concerns have been raised about the adverse renal and cardiac events associated with remdesivir. OBJECTIVE: This study aimed to analyse the adverse renal and cardiac events associated with remdesivir in patients with COVID-19 infections using the US FDA adverse event reporting system. METHOD: A case/non-case method was used to determine adverse drug events associated with remdesivir as the primary suspect drug between January 1, 2020, and November 11, 2021, for patients with COVID-19 infections. Cases were reports for remdesivir with ≥1 ADEs as preferred terms included in the Medical Dictionary of Regulatory Activities (MedDRA) system organ classes 'Renal and urinary disorders' or 'cardiac' disorders. To measure disproportionality in reporting of ADEs, frequentist approaches, including the proportional reporting ratio (PRR) and reporting odds ratio (ROR), were used. The empirical Bayesian Geometric Mean (EBGM) score and information component (IC) value were calculated using a Bayesian approach. A signal was defined as the lower limit of 95% confidence intervals of ROR ≥ 2, PRR ≥ 2, IC > 0, and EBGM > 1 for ADEs with ≥4 reports. Sensitivity analyses were undertaken by excluding reports for non-Covid indications and medications strongly associated with AKI and cardiac arrhythmias. RESULTS: In the main analysis for remdesivir use in patients with COVID-19 infections, we identified 315 adverse cardiac events comprising 31 different MeDRA PTs and 844 adverse renal events comprising 13 different MeDRA PTs. Regarding adverse renal events, disproportionality signals were noted for "renal failure" (ROR = 2.8 (2.03-3.86); EBGM = 1.92 (1.58-2.31), "acute kidney injury" (ROR = 16.11 (12.52-20.73); EBGM = 2.81 (2.57-3.07), "renal impairment" (ROR = 3.45 (2.68-4.45); EBGM = 2.02 (1.74-2.33). Regarding adverse cardiac events, strong disproportionality signals were noted for "electrocardiogram QT prolonged" (ROR = 6.45 (2.54-16.36); EBGM = 2.04 (1.65-2.51), "pulseless electrical activity" (ROR = 43.57 (13.64-139.20); EBGM = 2.44 (1.74-3.33), "sinus bradycardia" (ROR = 35.86 (11.16-115.26); EBGM = 2.82 (2.23-3.53), "ventricular tachycardia" (ROR = 8.73 (3.55-21.45); EBGM = 2.52 (1.89-3.31). The risk of AKI and cardiac arrythmias were confirmed by sensitivity analyses. CONCLUSION: This hypothesis-generating study identified AKI and cardiac arrhythmias associated with remdesivir use in patients with COVID-19 infections. The relationship between AKI and cardiac arrhythmias should be further investigated using registries or large clinical data to assess the impact of age, genetics, comorbidity, and the severity of Covid infections as potential confounders.

Remdesivir for COVID-19 and acute kidney injury: disproportionality analysis of data from the U.S. Food and Drug Administration Adverse Event Reporting System.

BACKGROUND: Evidence about remdesivir-associated acute kidney injury (AKI) among patients with novel coronavirus disease 2019 (COVID-19) was controversial. AIM: To investigate the signal of disproportionate reporting of remdesivir-related AKI in COVID-19 patients over time with data from US Food and Drug Administration Adverse Event Reporting System. METHOD: Adverse events in COVID-19 patients reported between April 2020 and September 2022 were included. Reporting odds ratios (RORs) of AKI and renal disorders (a more sensitive definition for AKI) were estimated to compare remdesivir with other medications prescribed in comparable situations of COVID-19. RESULTS: During the entire study period, significant signals were identified for remdesivir-related AKI (ROR 2.00, 95% CI: 1.83-2.18) and renal disorder (ROR 2.35, 95% CI: 2.17-2.54) when compared to all comparable drugs. However, in the third quarter of 2022 (the most recent quarter) signals disappeared as the ROR of AKI was 1.50 (95% CI 0.91-2.45) and ROR of renal disorder was 1.69 (95% CI 1.06-2.70). Number of signals in sensitivity analyses and the proportion of AKI in remdesivir-associated events decreased over time. CONCLUSION: In COVID-19 patients, we observed diminishing signals of remdesivir-associated AKI over time and no significant signal in the most recent quarter, suggesting remdesivir might not be nephrotoxic.

Remdesivir Use in Pediatric Patients for SARS-CoV-2 Treatment: Single Academic Center Study.

BACKGROUND: Millions of children in the United States have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with many infections leading to hospitalization. For pediatric patients, especially younger children, treatment options are limited. Remdesivir has demonstrated a positive safety and efficacy profile in adults, but little data is published regarding remdesivir use in pediatric patients. Additional data for SARS-CoV-2 treatments in pediatric patients is required to prevent further SARS-CoV-2-related morbidity and mortality. At a single pediatric academic medical center, the safety and efficacy of remdesivir was evaluated. METHODS: A retrospective review of patients admitted to a pediatric academic medical center who received remdesivir over a 17-month period was completed. All pediatric patients who received at least 1 dose of remdesivir were included. Safety and efficacy were assessed using national organization's definitions of clinical improvement, bradycardia, hypertension, acute kidney injury and drug-induced liver injury. RESULTS: There were 48 pediatric patients included in this study with 29% of patients admitted to the pediatric intensive care unit. Less than one-third of patients received the full treatment course of remdesivir, with over half of patients not completing therapy due to symptomatic improvement or hospital discharge. Majority of patients required some level of supplemental oxygen support. The median World Health Organization score was consistent throughout all 5 days of therapy. No patients experienced significant bradycardia, hypertension, acute kidney injury, or drug-induced liver injury. CONCLUSIONS: Remdesivir may correlate with clinical stability or improvement and demonstrates safety when used in pediatric patients. A randomized controlled trial is needed to confirm these findings.

Differential renal proteomics analysis in a novel rat model of iodinated contrast-induced acute kidney injury.

Contrast-induced acute kidney injury (CI-AKI), which occurs after the use of iodinated contrast media, has become the third leading cause of hospital-acquired acute kidney injury (AKI). It is associated with prolonged hospitalization and increased risks of end-stage renal disease and mortality. The pathogenesis of CI-AKI is unclear and effective treatments are lacking. By comparing different post-nephrectomy times and dehydration times, we constructed a new, short-course CI-AKI model using dehydration for 24 h two weeks after unilateral nephrectomy. We found that the low-osmolality contrast media iohexol caused more severe renal function decline, renal morphological damage, and mitochondrial ultrastructural alterations compared to the iso-osmolality contrast media iodixanol. The shotgun proteomics based on Tandem Mass Tag (TMT) was used to conduct proteomics research on renal tissue in the new CI-AKI model, and 604 distinct proteins were identified, mainly involving complement and coagulation cascade, COVID-19, PPAR signalling pathway, mineral absorption, cholesterol metabolism, ferroptosis, staphylococcus aureus infection, systemic lupus erythematosus, folate biosynthesis, and proximal tubule bicarbonate reclamation. Then, using parallel reaction monitoring (PRM), we validate 16 candidate proteins, of which five were novel candidates (Serpina1, Apoa1, F2, Plg, Hrg) previously unrelated to AKI and associated with an acute response as well as fibrinolysis. The pathway analysis and 16 candidate proteins may help to discover new mechanisms in the pathogenesis of CI-AKI, allowing for early diagnosis and outcome prediction.

Application of logistic regression, support vector machine and random forest on the effects of titanium dioxide nanoparticles using macroalgae in treatment of certain risk factors associated with kidney injuries.

The use of titanium dioxide (TiO2) nanoparticles in many biological and technical domains is on the rise. There hasn't been much research on the toxicity of titanium dioxide nanoparticles in biological systems, despite their ubiquitous usage. In the current investigation, samples were exposed to various dosages of TiO2 nanoparticles for 4 days, 1 month, and 2 months following treatment. ICP-AES was used to dose TiO2 into the tissues, and the results showed that the kidney had a significant TiO2 buildup. On the other hand, apoptosis of renal tubular cells is one of the most frequent cellular processes contributing to kidney disease (KD). Nevertheless, the impact of macroalgal seaweed extract on KD remains undetermined. In this work, machine learning (ML) approaches have been applied to develop prediction algorithms for acute kidney injury (AKI) by use of titanium dioxide and macroalgae in hospitalized patients. Fifty patients with (AKI) and 50 patients (non-AKI group) have been admitted and considered. Regarding demographic data, and laboratory test data as input parameters, support vector machine (SVM), and random forest (RF) are utilized to build models of AKI prediction and compared to the predictive performance of logistic regression (LR). Due to its strong antioxidant and anti-inflammatory powers, the current research ruled out the potential of using G. oblongata red macro algae as a source for a variety of products for medicinal uses. Despite a high and fast processing of algorithms, logistic regression showed lower overfitting in comparison to SVM, and Random Forest. The dataset is subjected to algorithms, and the categorization of potential risk variables yields the best results. AKI samples showed significant organ defects than non-AKI ones. Multivariate LR indicated that lymphocyte, and myoglobin (MB) ≥ 1000 ng/ml were independent risk parameters for AKI samples. Also, GCS score (95% CI 1.4-8.3 P = 0.014) were the risk parameters for 60-day mortality in samples with AKI. Also, 90-day mortality in AKI patients was significantly high (P < 0.0001). In compared to the control group, there were no appreciable changes in the kidney/body weight ratio or body weight increases. Total thiol levels in kidney homogenate significantly decreased, and histopathological analysis confirmed these biochemical alterations. According to the results, oral TiO2 NP treatment may cause kidney damage in experimental samples.

Melatonin for prevention of acute kidney injury in patients treated with intravenous polymyxin B: a double-blind, placebo-controlled randomized clinical trial.

OBJECTIVES: To evaluate the effect of melatonin versus placebo on the incidence of acute kidney injury (AKI) in patients treated with polymyxin B. METHODS: We performed a single-centre, double-blind, randomized clinical trial (NCT03725267) of 30-mg oral melatonin versus placebo for patients treated with intravenous polymyxin B. Patients aged ≥18 years receiving polymyxin B for ≤48 hours were eligible. Melatonin or placebo pills were administered until the end of polymyxin B treatment or for a maximum of 14 days. The main outcome was any level of AKI. RESULTS: Eighty-eight patients were randomized: 44 in the melatonin group and 44 in the placebo group. The study ended prematurely because of polymyxin B shortage during the COVID-19 pandemic. The patients' mean age was 63.6 ± 17.3 years, and 60.2% of the patients were men. Forty-six (52.3%, 23 in each group) patients developed AKI during the follow-up period. The incidence rate of AKI was 81.9/1000 and 77.4/1000 patients per day in melatonin and placebo groups, respectively (hazard ratio, 1.09; 95% CI, 0.61-1.94; p 0.78). Renal failure and 30-day mortality were similar between the groups. Moreover, the incidence of AKI was not different in pre-specified sub-groups. DISCUSSION: Melatonin initiated in the first 48 hours of therapy did not reduce the incidence of AKI in patients treated with polymyxin B.

Pediatric Minimal Change Disease and AKI following the Pfizer-BioNTech COVID-19 Vaccine: causal or incidental correlation?

The global coronavirus 2019 (COVID-19) pandemic required vaccination even in children to reduce infection. We report on the development of acute kidney injury (AKI) and minimal change disease (MCD) nephrotic syndrome (NS), shortly after the first injection BNT162b2 COVID-19 vaccine (Pfizer-BioNTech). A 12-year-old previously healthy boy was referred to our hospital with complaints of peripheral edema and nephrotic range proteinuria. Nine days earlier he had received his first injection BNT162b2 COVID-19 vaccine (Pfizer-BioNTech). Seven days after injection, he developed leg edema, which rapidly progressed to anasarca with significant weight gain. On admission, serum creatinine was 1.3 mg/dL and 24-hour urinary protein excretion was 4 grams with fluid overload. As kidney function continued to decline over the next days, empirical steroid treatment and renal replacement therapy with ultrafiltration were started and kidney biopsy was performed. Seven days after steroid therapy, kidney function began to improve, gradually returning to normal. The association of MCD, nephrotic syndrome and AKI hasn't been previously described following the Pfizer-BioNTech COVID-19 vaccine in pediatric population, but this triad has been reported in adults. We need further similar case reports to establish the real incidence of this possible vaccine side effect.

COVID-19 vaccination and Atypical hemolytic uremic syndrome.

Introduction: COVID-19 vaccination has been associated with rare but severe complications characterized by thrombosis and thrombocytopenia. Methods and Results: Here we present three patients who developed de novo or relapse atypical hemolytic uremic syndrome (aHUS) in native kidneys, a median of 3 days (range 2-15) after mRNA-based (Pfizer/BioNTech's, BNT162b2) or adenoviral (AstraZeneca, ChAdOx1 nCoV-19) COVID-19 vaccination. All three patients presented with evident hematological signs of TMA and AKI, and other aHUS triggering or explanatory events were absent. After eculizumab treatment, kidney function fully recovered in 2/3 patients. In addition, we describe two patients with dubious aHUS relapse after COVID-19 vaccination. To assess the risks of vaccination, we retrospectively evaluated 29 aHUS patients (n=8 with native kidneys) without complement-inhibitory treatment, who received a total of 73 COVID-19 vaccinations. None developed aHUS relapse after vaccination. Conclusion: In conclusion, aHUS should be included in the differential diagnosis of patients with vaccine-induced thrombocytopenia, especially if co-occuring with mechanical hemolytic anemia (MAHA) and acute kidney injury (AKI). Still, the overall risk is limited and we clearly advise continuation of COVID-19 vaccination in patients with a previous episode of aHUS, yet conditional upon clear patient instruction on how to recognize symptoms of recurrence. At last, we suggest monitoring serum creatinine (sCr), proteinuria, MAHA parameters, and blood pressure days after vaccination.

Renin-Angiotensin System Inhibitors in Patients With COVID-19: A Meta-Analysis of Randomized Controlled Trials Led by the International Society of Hypertension.

Background Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin-angiotensin system inhibitors (RASi) in adults with COVID-19. We therefore performed a meta-analysis to assess the safety and efficacy of RASi in adults with COVID-19. Methods and Results MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID-19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all-cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow-up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all-cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69-1.30]) either overall or in subgroups defined by COVID-19 severity or trial type. Network meta-analysis identified no difference between angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33-1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05-3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation. Conclusions This meta-analysis of randomized controlled trials evaluating angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers versus control in patients with COVID-19 found no difference in all-cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID-19.

Acute Kidney Injury after First Dose of AstraZeneca COVID-19 Vaccine Managed in a Nigerian Hospital.

INTRODUCTION: The association of kidney disease and COVID-19 vaccination has been reported with minimal change disease being a common presentation. CASE REPORT: Index patient is a 54-year-old female who presented with a history of reduction in urine output within 3 weeks of receiving the Oxford-AztraZeneca COVID-19 vaccine. Her serum creatinine on admission was 1,057 µmol/L with a premorbid serum creatinine of 78 µmol/L. Her vital signs were stable. She was on antihypertensive and antidiabetic medications for hypertension and diabetes mellitus, respectively. Renal biopsy was precluded by her morbid obesity and she was commenced on oral prednisolone. She had 5 sessions of hemodialysis and her serum creatinine gradually reduced to 106 µmol/L, and she is being followed up on an outpatient basis. CONCLUSION: We report a case of a female patient with acute kidney injury following COVID-19 Oxford-AztraZeneca vaccination. Further studies are required to better understand the pathogenesis of the renal affectation post-vaccination.

INTRODUCTION: L'association de la maladie rénale et de la vaccination COVID-19 a été signalée, la maladie à changement minimal est une présentation courante. RAPPORT DE CAS: La patiente à l'étude est une femme de 54 ans qui a présenté des antécédents de réduction du débit urinaire dans les 3 semaines après avoir reçu le vaccin COVID-19 d'Oxford-AztraZeneca. Sa créatinine sérique à l'admission était de 1 057 µmol/L avec une créatinine sérique prémorbide de 78 µmol/L. Ses signes vitaux étaient stables. Elle prenait des médicaments antihypertenseurs et antidiabétiques pour l'hypertension et le diabète sucré, respectivement. Une biopsie rénale était impossible à cause de son obésité morbide et elle a été mise sous prednisolone par voie orale. Elle a subi 5 sessions d'hémodialyse et son taux de créatinine sérique a progressivement à 106 µmol/L, et elle est suivie en ambulatoire. CONCLUSION: Nous rapportons le cas d'une patiente souffrant d'une lésion rénale aiguë après la vaccination par le COVID-19 Oxford-AztraZeneca. D'autres études sont nécessaires pour mieux comprendre la pathogenèse de l'affectation rénale post-vaccination. Mots-clés: Vaccin COVID-19, Événement Indésirable, Lésion Rénale Aiguë.

Case Reports: Exposure to SARS-CoV-2, Acute Kidney Injury, and Lithium Toxicity.

PURPOSES: The aims of the study were to review 3 cases of lithium toxicity among individuals with bipolar disorder who were diagnosed with COVID-19 and to review the literature discussing the implications of COVID-19 and exposure to SARS-CoV-2 relative to medical use of lithium in management of bipolar disorder. METHODS: This is a case review of medical and psychiatric notes of 3 individuals with bipolar disorder, managed with lithium, who developed COVID-19. This study discussed these cases in context of previous case reports and relevant literature pertaining to lithium and exposure to SARS-CoV-2. FINDINGS: Infection with SARS-CoV-2 along with symptoms of COVID-19 and mental state changes in three individuals were temporally associated with lithium levels in the toxic range. IMPLICATIONS: Exposure to SARS-CoV-2 or symptoms suggestive of COVID-19 should result in increased clinical monitoring of individuals taking lithium. Those taking lithium and providers are advised to have a low clinical threshold for requesting lithium levels and kidney function estimates for the duration of the COVD-19 pandemic.

Incidence of Contrast-Associated Acute Kidney Injury in Renal-Competent COVID-19 Patients Undergoing Computed Chest Angiography.

PURPOSE: COVID-19 infection poses a significant risk of both renal injury and pulmonary embolism, producing a clinical challenge, as the criterion standard examination for pulmonary embolism, computed tomography angiography (CTA), requires the use of nephrotoxic iodinated contrast agents.Our investigation evaluated whether symptomatic COVID-19-positive patients without laboratory evidence of renal impairment are at increased risk for developing contrast-associated acute kidney injury (CA-AKI). METHOD: All COVID-19-positive patients undergoing noncontrast chest computed tomography and CTA at an apex tertiary medical center between March 1 and December 10, 2020, were retrospectively evaluated. A total of 258 renal-competent (estimated glomerular filtration rate >30) patients with baseline and 48- to 72-hour postexamination creatinine measurements were identified and analyzed for incidence of acute kidney injury (AKI) meeting the criteria for CA-AKI. RESULTS: Twenty-five of 191 patients undergoing CTA (13.1%) and 9 of the 67 undergoing noncontrast computed tomography (13.4%) experienced creatinine increases meeting the criteria for CA-AKI. Univariate and multivariate analyses accounting for known AKI risk factors revealed no correlation between iodinated contrast administration and the incidence AKI meeting the criteria for CA-AKI (univariable odds ratio, 0.97 [95% confidence interval, 0.43-2.20]; multivariable odds ratio, 0.97 [95% confidence interval, 0.40-2.36]). CONCLUSIONS: Renal-competent COVID-19 patients undergoing chest CTA may not have an increased risk of AKI. Additional studies are needed to confirm this preliminary finding.

Acute kidney injury after COVID-19 vaccines: a real-world study.

BACKGROUND: Acute kidney injury (AKI), a rare adverse event, cannot be ignored as millions of doses of coronavirus disease 2019 (COVID-19) vaccinations. We aimed to investigate the occurrence of post-vaccine AKI reported to the Vaccine Adverse Event Reporting System (VAERS). METHODS: After data mapping from December 2020 to June 2021, we summarized demographic and clinical features and outcomes of reported cases from three vaccines (Pfizer-BNT, MODERNA, and JANSSEN). The Bayesian and nonproportional analyses explored the correlations between COVID-19 vaccines and AKI. RESULTS: We identified 1133 AKI cases. Pfizer-BNT appeared to have a stronger AKI correlation than MODERNA and JANSSEN, based on the highest reporting odds ratio (ROR = 2.15, 95% confidence interval = 1.97, 2.36). We observed the differences in ages, comorbidities, current illnesses, post-vaccine AKI causes, and time to AKI onset (all p＜.05) among three vaccines. Most patients are elderly, with the highest age in MODERNA (68.41 years) and lowest in JANSSEN (59.75 years). Comorbidities were noticed in 58.83% of the cases and active infections in over 20% of cases. The leading cause of post-vaccine AKI was volume depletion (40.78%), followed by sepsis (11.74%). Patients in Pfizer-BNT had the worst outcome with 19.78% deaths, following 17.78% in MODERNA and 12.36% in JANSSEN (p = .217). The proportion of patients on dialysis was higher in JANSSEN than in Pfizer-BNT and MODERNA (14.61% vs. 6.54%, 10.62%, p = .008). CONCLUSION: AKI could occur after the COVID-19 vaccines, predominantly in elderly patients. However, the causality needs further identification.

Paxlovid (Nirmatelvir/Ritonavir) and Tacrolimus Drug-Drug Interaction in a Kidney Transplant Patient with SARS-2-CoV infection: A Case Report.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a significant impact on communities and health systems. New antiviral medications against this disease have not been properly tested yet, and their efficiency, side effects, and drug-drug interactions are not entirely known. Organ transplant recipients receive immunosuppressive medications such as tacrolimus to prevent graft rejection. Tacrolimus is metabolized by the cytochrome P450 3A4 enzyme system. Many medications can either induce or inhibit this enzyme and affect the level. Awareness of possible drug-drug interactions is vital because tacrolimus levels should be kept within a specific narrow range determined by the recipient's immunologic risk. Underexposure increases the risk of graft rejection, whereas overexposure may lead to adverse effects. Paxlovid, a novel antiviral medication approved for emergency use to treat SARS-CoV-2, is a combination of nirmatrelvir and ritonavir, a cytochrome P450 34A inhibitor. In this case report, we present a case of a kidney transplant patient receiving tacrolimus treated with Paxlovid, leading to an abruptly high tacrolimus level, significant symptoms, treatment interruption, and acute kidney injury. We conclude that the drug-drug interaction between Paxlovid and tacrolimus is indeed robust and noteworthy and leads to high tacrolimus levels and its metabolites, adverse effects, and acute kidney injury. Physicians managing immunocompromised patients receiving tacrolimus should be aware of this significant drug-drug interaction and consider other options or reduction of daily tacrolimus dose during treatment in addition to timely monitoring of both tacrolimus levels and serum creatinine. Consulting with the transplant pharmacist is foremost in alerting for these interactions.

IgA nephropathy relapse following COVID-19 vaccination treated with corticosteroid therapy: case report.

BACKGROUND: The flare of immune-mediated disease following coronavirus disease of 2019 (COVID-19) vaccination is a rare adverse event following immunization. De novo, as well as relapsing IgA nephropathy (IgAN) cases, have been reported following either mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) vaccination. To our knowledge, the majority of IgAN relapses did not result in severe acute kidney injury (AKI) and resolved spontaneously. CASE PRESENTATION: This is a case of a 54-year-old female with a previous diagnosis of IgAN who developed IgAN relapse following the second dose of Moderna vaccine. Gross hematuria developed 2 days after vaccination, which was accompanied by significant AKI. Kidney biopsy showed mild tubular atrophy and IgA staining in mesangium without crescent formation. Significant improvement in serum creatinine (Cr) was observed on day 10 after initiating prednisone. Cr came back to normal within 3 months after initiating corticosteroid. CONCLUSION: COVID-19 vaccination is associated with a flare of IgAN that may cause significant AKI. Steroid therapy is associated with recovery. IgAN flare after COVID-19 vaccination should be closely monitored to elucidate any adverse effect associated with the novel vaccine.

Remdesivir use and risks of acute kidney injury and acute liver injury among patients hospitalised with COVID-19: a self-controlled case series study.

BACKGROUND AND AIM: To investigate and quantify the risks of AKI and ALI associated with remdesivir use, given the underlying diseases of SARS-CoV-2 infection. METHODS: This self-controlled case series (SCCS) study was conducted using electronic hospital records between 23 January 2020 and 31 January 2021 as retrieved from the Hong Kong Hospital Authority which manages all laboratory-confirmed COVID-19 cases in Hong Kong. Outcomes of AKI and ALI were defined using the KDIGO Guideline and Asia Pacific Association of Study of Liver consensus guidelines. Incidence rate ratios (IRR) for AKI and ALI following the administration of remdesivir (exposure) in comparison to a non-exposure period were estimated using the conditional Poisson regression models. RESULTS: Of 860 COVID-19 patients administered remdesivir during hospitalisation, 334 (38.8%) and 137 (15.9%) had incident ALI and AKI, respectively. Compared with the baseline period, both ALI and AKI risks were increased significantly during the pre-exposure period (ALI: IRR = 6.169, 95% CI = 4.549-8.365; AKI: IRR = 7.074, 95% CI = 3.763-13.298) and remained elevated during remdesivir treatment. Compared to the pre-exposure period, risks of ALI and AKI were not significantly higher in the first 2 days of remdesivir initiation (ALI: IRR = 1.261, 95% CI = 0.915-1.737; AKI: IRR = 1.261, 95% CI = 0.889-1.789) and between days 2 and 5 of remdesivir treatment (ALI: IRR = 1.087, 95% CI = 0.793-1.489; AKI: IRR = 1.152, 95% CI = 0.821-1.616). CONCLUSION: The increased risks of AKI and ALI associated with intravenous remdesivir treatment for COVID-19 may be due to the underlying SARS-CoV-2 infection. The risks of AKI and ALI were elevated in the pre-exposure period, yet no such increased risks were observed following remdesivir initiation when compared to the pre-exposure period.

Hydroxychloroquine/chloroquine and the risk of acute kidney injury in COVID-19 patients: a systematic review and meta-analysis.

OBJECTIVES: Hydroxychloroquine/chloroquine has been widely used as part of the standard treatment for patients with coronavirus disease 2019 (COVID-19). We conducted a systematic review and meta-analysis to determine whether hydroxychloroquine/chloroquine increases the risk of acute kidney injury (AKI) in COVID-19 patients. METHODS: PubMed and Embase were searched for related publications from inception to Dec 31, 2021, including randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSIs) comparing the risk of AKI and/or increased creatinine in COVID-19 patients receiving hydroxychloroquine/chloroquine and other controls (active treatment and placebo). We conducted separate meta-analyses for RCTs and NRSIs based on fixed-effect model, with odds ratios (ORs) being considered as effect sizes. RESULTS: We included 21 studies in the analysis, with 12 were RCTs. Based on the RCTs, compared to placebo, the OR was 1.19 (95% confidence interval [CI]: 0.86, 1.64; p = .30, n = 4, moderate quality) for AKI and 1.00 (95%CI: 0.64, 1.56; p = .99, n = 5, moderate quality) for increased creatinine for patients received hydroxychloroquine/chloroquine treatment; compared to active treatment, the odds was 1.28 (95%CI: 0.65, 2.53; p = .47, n = 2, low quality) for AKI and 0.64 (95%CI: 0.13, 3.20; p = .59, n = 1, low quality) for increased creatine. Evidence from NRSIs showed slightly increased odds of AKI, with low quality. CONCLUSION: Based on current available studies which were graded as low to moderate quality, there is insufficient evidence to conclude that hydroxychloroquine/chloroquine use is associated with increased risk of AKI or raised creatinine. Abbreviations: AKI: acute kidney injury; COVID-19: Coronavirus Disease 2019; RCT: randomized controlled trials; NRSI: non-randomized studies of interventions; OR: odds ratios; ROBIS-I: Risk Of Bias In Non-randomized Studies - of Interventions.

Renal and Hepatic Outcomes after Remdesivir Therapy in Coronavirus Disease-2019-Positive Patients with Renal Dysfunction at Baseline or after Starting Therapy.

We aimed to study the effect of remdesivir therapy on renal and hepatic function in coronavirus disease-2019 (COVID-19) patients with renal dysfunction at baseline or after starting therapy and identify the factors, if any, related to the efficacy of remdesivir therapy on patient outcome. Patients included in the study were those who met all the following criteria irrespective of baseline glomerular filtration rate [including those already on maintenance hemodialysis (HD)] or baseline deranged liver function test. (1) Age >18 years, (2) COVID-19 reverse transcriptase-polymerase chain reaction positive, (3) Meeting criteria for administration of remdesivir - [any one of the following: (a) COVID-19 pneumonia with respiratory rate >30/min or SPO2<94% on room air, (b) Acute respiratory distress syndrome (ARDS)]. (4) Renal dysfunction at baseline, during or within 48 h of completion of therapy. Thirty-four patients had renal dysfunction at baseline or developed it after remdesivir therapy - 16 were acute kidney injury (AKI), 10 chronic kidney diseases (CKD), four CKD stage 5D, and four were postrenal transplant. The overall mortality was 18/34 (52.9%). Eight out of 30 (26.66%) needed HD during or after therapy and of these, 15 died and among 15 survivors, 14 returned to their baseline renal function after cessation of therapy, one patient is still dialysis dependent. In the dialysis-dependent CKD (n = 4) subgroup, three died and one was discharged. In the postrenal transplant (n = 4) group, all developed AKI during or after the completion of therapy. None required HD, two returned to their baseline renal function, and two died. Only five had alanine aminotransferase elevation (×1 upper limit of normal) during or within 48 h of completion of therapy - three died and two returned to baseline. Lower PaO2/FiO2 (severe ARDS) (P = 0.0001), higher C-reactive protein (P = 0.022), higher serum lactate dehydrogenase (P = 0.038), and duration of symptoms before starting therapy (P = 0.05) were statistically significant variables at baseline associated with higher mortality. Remdesivir can be tried in moderate-to-severe COVID-19 cases with renal dysfunction as a complete recovery of renal function was noted in survivors. However, larger and well-controlled studies evaluating its safety and efficacy in patients with AKI and CKD are needed.

Pembrolizumab-Related Side Effects: Acute Renal Failure and Severe Neurological Toxicity.

Immunotherapy with immune checkpoint inhibitors represents nowadays a marked improvement in cancer treatment. Nevertheless, they can cause severe toxicities that put the patient at high risk, often requiring aggressive treatment. We present the case of a female patient who developed a severe immune-related adverse reaction to Pembrolizumab prescribed for melanoma treatment. Her array of symptoms, which presented a few days after last drug administration, consisted of severe neurological deficit, severe renal failure, polymyositis, and hyperthyroidism. Treatment required the immediate interruption of the trigger drug, infusion of high dose steroids, renal replacement therapy, plasmapheresis, and methimazole, as will be further discussed.