Evaluation of Plasma Biomarkers to Predict Major Adverse Kidney Events in Hospitalized Patients With COVID-19.

RATIONALE & OBJECTIVE: Patients hospitalized with COVID-19 are at increased risk for major adverse kidney events (MAKE). We sought to identify plasma biomarkers predictive of MAKE in patients hospitalized with COVID-19. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 576 patients hospitalized with COVID-19 between March 2020 and January 2021 across 3 academic medical centers. EXPOSURE: Twenty-six plasma biomarkers of injury, inflammation, and repair from first available blood samples collected during hospitalization. OUTCOME: MAKE, defined as KDIGO stage 3 acute kidney injury (AKI), dialysis-requiring AKI, or mortality up to 60 days. ANALYTICAL APPROACH: Cox proportional hazards regression to associate biomarker level with MAKE. We additionally applied the least absolute shrinkage and selection operator (LASSO) and random forest regression for prediction modeling and estimated model discrimination with time-varying C index. RESULTS: The median length of stay for COVID-19 hospitalization was 9 (IQR, 5-16) days. In total, 95 patients (16%) experienced MAKE. Each 1 SD increase in soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 was significantly associated with an increased risk of MAKE (adjusted HR [AHR], 2.30 [95% CI, 1.86-2.85], and AHR, 2.26 [95% CI, 1.73-2.95], respectively). The C index of sTNFR1 alone was 0.80 (95% CI, 0.78-0.84), and the C index of sTNFR2 was 0.81 (95% CI, 0.77-0.84). LASSO and random forest regression modeling using all biomarkers yielded C indexes of 0.86 (95% CI, 0.83-0.89) and 0.84 (95% CI, 0.78-0.91), respectively. LIMITATIONS: No control group of hospitalized patients without COVID-19. CONCLUSIONS: We found that sTNFR1 and sTNFR2 are independently associated with MAKE in patients hospitalized with COVID-19 and can both also serve as predictors for adverse kidney outcomes. PLAIN-LANGUAGE SUMMARY: Patients hospitalized with COVID-19 are at increased risk for long-term adverse health outcomes, but not all patients suffer long-term kidney dysfunction. Identification of patients with COVID-19 who are at high risk for adverse kidney events may have important implications in terms of nephrology follow-up and patient counseling. In this study, we found that the plasma biomarkers soluble tumor necrosis factor receptor 1 (sTNFR1) and sTNFR2 measured in hospitalized patients with COVID-19 were associated with a greater risk of adverse kidney outcomes. Along with clinical variables previously shown to predict adverse kidney events in patients with COVID-19, both sTNFR1 and sTNFR2 are also strong predictors of adverse kidney outcomes.

Urine Output and Mortality in Patients Resuscitated from out of Hospital Cardiac Arrest.

BACKGROUND: Limited data exist regarding urine output (UO) as a prognostic marker in out-of-hospital-cardiac-arrest (OHCA) survivors undergoing targeted temperature management (TTM). METHODS: We included 247 comatose adult patients who underwent TTM after OHCA between 2007 and 2017, excluding patients with end-stage renal disease. Three groups were defined based on mean hourly UO during the first 24 h: Group 1 (<0.5 mL/kg/h, n = 73), Group 2 (0.5-1 mL/kg/h, n = 81) and Group 3 (>1 mL/kg/h, n = 93). Serum creatinine was used to classify acute kidney injury (AKI). The primary and secondary outcomes respectively were in-hospital mortality and favorable neurological outcome at hospital discharge (modified Rankin Scale [mRS]<3). RESULTS: In-hospital mortality decreased incrementally as UO increased (adjusted OR 0.9 per 0.1 mL/kg/h higher; p = 0.002). UO < 0.5 mL/kg/h was strongly associated with higher in-hospital mortality (adjusted OR 4.2 [1.6-10.8], p = 0.003) and less favorable neurological outcomes (adjusted OR 0.4 [0.2-0.8], p = 0.007). Even among patients without AKI, lower UO portended higher mortality (40% vs 15% vs 9% for UO groups 1, 2, and 3 respectively, p < 0.001). CONCLUSION: Higher UO is incrementally associated with lower in-hospital mortality and better neurological outcomes. Oliguria may be a more sensitive early prognostic marker than creatinine-based AKI after OHCA.

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. © 2022 Società Italiana di Nefrologia - Anno 39 Volume 6 n° 4.

Urinary liver-type fatty acid binding protein is increased in the early stages of the disease with a risk of acute kidney injury induced by histone.

AIM: Urinary liver-type fatty acid binding protein (L-FABP) has potential utility as an early prognostic biomarker ahead of traditional severity scores in coronavirus disease 2019 and sepsis, however, the mechanism of elevated urinary L-FABP in the disease has not been clearly elucidated. We investigated the background mechanisms of urinary L-FABP excretion through non-clinical animal model focusing on histone, which is one of the aggravating factors in these infectious diseases. METHODS: Male Sprague-Dawley rats were placed in central intravenous catheters, and these rats were given a continuous intravenous infusion of 0.25 or 0.5 mg/kg/min calf thymus histones for 240 min from caudal vena cava. RESULTS: After the administration of histone, urinary L-FABP and gene expression of an oxidative stress marker in the kidney increased in a histone dose-dependent manner before increased serum creatinine. Upon further investigation, fibrin deposition in the glomerulus was observed and it tended to be remarkable in the high dose administrated groups. The levels of coagulation factor were significantly changed after the administration of histone, and these were significantly correlated with the levels of urinary L-FABP. CONCLUSIONS: Firstly, it was suggested that histone is one of the causative agents for the urinary L-FABP increase at an early stage of the disease with a risk of acute kidney injury. Secondly, urinary L-FABP could be a marker reflecting the changes of coagulation system and microthrombus caused by histone in the early stage of acute kidney injury before becoming severely ill and maybe a guide to early treatment initiation.

Renal Thrombotic Microangiopathy: A Review.

Thrombotic microangiopathy (TMA), a pathological lesion observed in a wide spectrum of diseases, is triggered by endothelial injury and/or dysfunction. Although TMA lesions are often accompanied by clinical features of microangiopathic hemolytic anemia, thrombocytopenia, and ischemic end-organ injury, renal-limited forms of TMA are not infrequently encountered in clinical practice. The presence of renal-limited manifestations can be diagnostically challenging, often delaying the initiation of targeted therapy. Prompt investigation and empirical treatment of TMA is warranted to reduce associated morbidity and mortality. Major advances have been made with respect to the pathophysiology of primary TMA entities, with the subsequent development of novel diagnostic tools and lifesaving therapies for diseases like thrombotic thrombocytopenic purpura and complement-mediated TMA. This article will review the clinical presentation and pathologic hallmarks of TMA involving the kidney, and the disease-specific mechanisms that contribute to the endothelial injury that characterizes TMA lesions. Diagnostic approach and both empirical and disease-specific treatment strategies will be discussed, along with the potential role for emerging targeted disease-specific therapies.

Acute kidney injury (AKI) post-mRNA SARS-CoV-2 vaccine in patients with cancer, treated with immune check point inhibitor (ICPi): An immune double whammy!

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.

Outcomes, Healthcare Resource Utilization, and Costs of Overall, Community-Acquired, and Hospital-Acquired Acute Kidney Injury in COVID-19 Patients.

Background: In hospitalized patients with COVID-19, acute kidney injury (AKI) is associated with higher mortality, but data are lacking on healthcare resource utilization (HRU) and costs related to AKI, community-acquired AKI (CA-AKI), and hospital-acquired AKI (HA-AKI). Objectives: To quantify the burden of AKI, CA-AKI, and HA-AKI among inpatients with COVID-19. Methods: This retrospective cohort study included inpatients with COVID-19 discharged from US hospitals in the Premier PINC AI™ Healthcare Database April 1-October 31, 2020, categorized as AKI, CA-AKI, HA-AKI, or no AKI by ICD-10-CM diagnosis codes. Outcomes were assessed during index (initial) hospitalization and 30 days postdischarge. Results: Among 208 583 COVID-19 inpatients, 30%, 25%, and 5% had AKI, CA-AKI, and HA-AKI, of whom 10%, 7%, and 23% received dialysis, respectively. Excess mortality, HRU, and costs were greater for HA-AKI than CA-AKI. In adjusted models, for patients with AKI vs no AKI and HA-AKI vs CA-AKI, odds ratios (ORs) (95% CI) were 3.70 (3.61-3.79) and 4.11 (3.92-4.31) for intensive care unit use and 3.52 (3.41-3.63) and 2.64 (2.52-2.78) for in-hospital mortality; mean length of stay (LOS) differences and LOS ratios (95% CI) were 1.8 days and 1.24 (1.23-1.25) and 5.1 days and 1.57 (1.54-1.59); and mean cost differences and cost ratios were $7163 and 1.35 (1.34-1.36) and $19 127 and 1.78 (1.75-1.81) (all P < .001). During the 30 days postdischarge, readmission LOS was ≥6% longer for AKI vs no AKI and HA-AKI vs CA-AKI; outpatient costs were ≥41% higher for HA-AKI vs CA-AKI or no AKI. Only 30-day new dialysis (among patients without index hospitalization dialysis) had similar odds for HA-AKI vs CA-AKI (2.37-2.8 times higher for AKI, HA-AKI, or CA-AKI vs no AKI). Discussion: Among inpatients with COVID-19, HA-AKI had higher excess mortality, HRU, and costs than CA-AKI. Other studies suggest that interventions to prevent HA-AKI could decrease excess morbidity, HRU, and costs among inpatients with COVID-19. Conclusions: In adjusted models among COVID-19 inpatients, AKI, especially HA-AKI, was associated with significantly higher mortality, HRU, and costs during index admission, and higher dialysis and longer readmission LOS during the 30 days postdischarge. These findings support implementation of interventions to prevent HA-AKI in COVID-19 patients.

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.

Early Patient-Triggered Pressure Support Breathing in Mechanically Ventilated Patients with COVID-19 May Be Associated with Lower Rates of Acute Kidney Injury.

BACKGROUND: Acute respiratory distress syndrome (ARDS) in COVID-19 patients often necessitates mechanical ventilation. Although much has been written regarding intensive care admission and treatment for COVID-19, evidence on specific ventilation strategies for ARDS is limited. Support mode during invasive mechanical ventilation offers potential benefits such as conserving diaphragmatic motility, sidestepping the negative consequences of the longer usage of neuromuscular blockers, and limiting the occurrence of ventilator-induced lung injury (VILI). METHODS: In this retrospective cohort study of mechanically ventilated and confirmed non-hyperdynamic SARS-CoV-2 patients, we studied the relation between the occurrence of kidney injury and the decreased ratio of support to controlled ventilation. RESULTS: Total AKI incidence in this cohort was low (5/41). In total, 16 of 41 patients underwent patient-triggered pressure support breathing at least 80% of the time. In this group we observed a lower percentage of AKI (0/16 vs. 5/25), determined as a creatinine level above 177 µmol/L in the first 200 h. There was a negative correlation between time spent on support ventilation and peak creatinine levels (r = -0.35 (-0.6-0.1)). The group predominantly on control ventilation showed significantly higher disease severity scores. CONCLUSIONS: Early patient-triggered ventilation in patients with COVID-19 may be associated with lower rates of acute kidney injury.

Incidence, predictors, clinical outcomes, and economic burden of recurrent acute kidney injury: a retrospective cohort study.

OBJECTIVE: This study aimed to assess the incidence, predictors, mortality, and economic outcomes of recurrent Acute kidney injury (AKI) in Jordan. METHODS: This was a retrospective cohort study that included adult patients who were admitted with AKI to university hospitals in the country from 2010-2019. Recurrent episodes of AKI, laboratory data, baseline medication list, and death dates were retrieved from patient's medical records. The incidence rate of recurrent AKI was estimated. Predictors of recurrent AKI and mortality during the five years post-discharge was evaluated. Total admission charges were described and evaluated in total and by service provided. RESULTS: Among 1162 AKI patients, 57 patients (4.9%) died during the index admission (first admission during the study period), and among the survivors, 220 patients were re-hospitalized with a recurrent AKI during five years of follow-up. Patients with higher discharge serum creatinine level (SCr) at index admission had higher odds of AKI recurrence (OR = 1.001). Patients who were on respiratory, antineoplastic, or anticoagulant medications were also more susceptible to recurrence; ORs were 1.69, 2.77, and 4.16, respectively. Patients who were elderly, with recurrent AKI episodes, or with a more extended hospital stay at index admission were more likely to die during the five years post discharge. The median charge of recurrent admissions was higher than the median charge of the index admissions; 1519.17 JOD ($2142.7) versus 1362.85 JOD ($1922.2), respectively. CONCLUSIONS: Recurrent AKI is associated with increased mortality and health expenditures. Higher discharge SCr levels at index admission, and chronic comorbidities are associated with a higher likelihood of AKI recurrence.

Atypical Hemolytic Uremic Syndrome Occurring After Receipt of mRNA-1273 COVID-19 Vaccine Booster: A Case Report.

Atypical hemolytic uremic syndrome (aHUS) is a subtype of thrombotic microangiopathy (TMA) characterized by a dysregulation of the alternative complement pathway. Here, we report a previously healthy 38-year-old woman in whom aHUS developed after a COVID-19 vaccine booster. One day after receipt of a booster dose of mRNA-1273 vaccine, she felt ill. Because of persistent headache, nausea, and general malaise, she went to her general practitioner, who referred her to the hospital after detecting hypertension and acute kidney injury. A diagnosis of TMA was made. Her treatment consisted of blood pressure control, hemodialysis, plasma exchange, and respiratory support. Kidney biopsy confirmed the diagnosis of acute TMA. The patient was referred for treatment with eculizumab, and kidney function improved after initiation of this therapy. Genetic analysis revealed a pathogenic C3 variant. SARS-CoV-2 infection as a trigger for complement activation and development of aHUS has been described previously. In addition, there is one reported case of aHUS occurring after receipt of the adenovirus-based COVID-19 vaccine ChAdOx1 nCoV-19, but, to our knowledge, this is the first case of aHUS occurring after a booster dose of an mRNA COVID-19 vaccine in a patient with an underlying pathogenic variant in complement C3. Given the time frame, we hypothesize that the vaccine probably was the trigger for development of aHUS in this patient.

Acute kidney injury following multisystem inflammatory syndrome associated with SARS-CoV-2 infection in children: a systematic review and meta-analysis.

INTRODUCTION: Multisystem inflammatory syndrome (MIS-C) is a rare paediatric hyper-inflammatory disorder that occurs following SARS-CoV-2 infection. Acute kidney injury (AKI) occurs in approximately one-quarter to one-third of the patients with MIS-C and is associated with poor prognosis in critically ill children. This systematic review is aimed to evaluate the incidence of AKI, mortality, and the need for kidney replacement therapy (KRT) in patients with MIS-C. METHODS: We searched databases from Medline, EMBASE, Cochrane Register, and Google Scholar from December 2019 to December 2021 with our search strategy. Studies meeting the following criteria were included in this systematic review: (1) articles on AKI in MIS-C; (2) studies providing AKI in MIS-C and COVID-19 infection separately; (3) studies reporting outcomes such as mortality, KRT, serum creatinine; length of hospital/ICU stay. QUALITY ASSESSMENT: The quality of the included studies was independently assessed by using the National Heart Lung and Blood Institute (NHLBI) quality assessment tool for cohort studies and case series. STATISTICAL ANALYSIS: Outcomes and their 95% confidence intervals (CI) were reported if a meta-analysis of these outcomes was conducted. Heterogeneity was reported using I2 statistics, and heterogeneity ≥ 50% was considered high. We used Baujat's plot for the contribution of each study toward overall heterogeneity. In sensitivity analysis, the summary estimates were assessed by repeating meta-analysis after omitting one study at a time. Forest plots were used for reporting outcomes in each study and with their 95% CI. All statistical tests were performed using R software version 4.0.3. RESULTS:  A total of 24 studies were included in this systematic review and of these, 11 were included in the meta-analysis. The pooled proportion of patients with MIS-C developing AKI was 20% (95% CI: 14-28%, I2 = 80%). Pooled proportion of death in children with MIS-C was 4% (95% CI: 1-14%; I2 = 93%). The odds of death in patients with AKI were 4.68 times higher than in patients without AKI (95% CI: 1.06-20.7%; I2 = 17%). The overall pooled proportion of MIS-C-induced AKI patients requiring KRT was 15% (95% CI: 4-42%; I2 = 91%). CONCLUSION: Approximately one-fifth of children with MIS-C develop AKI which is associated with higher odds of death. PROSPERO registration: CRD42022306170 A higher resolution version of the Graphical abstract is available as Supplementary information.

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.

Acute kidney injury (AKI) post-mRNA SARS-CoV-2 vaccine in patients with cancer, treated with immune check point inhibitor (ICPi): An immune double whammy!

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.

Clinical utility of tubular markers in kidney disease: a narrative review

Background and Objective: Various tubular markers have been established for the diagnosis of kidney diseases and evaluation of treatment efficacy. Currently, there are limited treatments available for advanced kidney disease. Therefore, early identification of patients at high risk of progression to end-stage renal disease (ESRD) is necessary for the provision of appropriate treatment at an early phase. The present review focuses on newly established urinary tubular markers, i.e., urinary [tissue inhibitor of metalloproteinases-2 (TIMP-2)]*[insulin-like growth factor binding protein-7 (IGFBP7)] and L-type fatty acid binding protein (L-FABP). Methods: A literature search of the electronic databases MEDLINE (January 2014 to February 2022) was conducted using search terms of “urinary [TIMP-2]*[IGFBP7]”, “urinary L-FABP”, “kidney disease”, and “COVID-19”. Original articles, which were written in English and show clinical usefulness of urinary [TIMP-2]*[IGFBP7] or urinary L-FABP, were mainly reviewed. Key Content and Findings: These proteins are expressed in human tubules and are reported to have renoprotective functions against kidney disease. In 2014, the U.S. Food and Drug Administration approved the clinical application of NephroCheck, measuring urinary [TIMP-2]*[IGFBP7], for the diagnosis of acute kidney injury (AKI). Notably, the usefulness of urinary L-FABP in AKI, chronic kidney disease (CKD), diabetic kidney disease, aging, and coronavirus disease 2019 (COVID-19) has been widely reported. Furthermore, various methods have been established for the easy, rapid, and highly sensitive measurements of c in various situations. In 2011, urinary L-FABP was approved by the Ministry of Health, Labor and Welfare in Japan. Conclusions: Early utilization of an accurate marker may improve the prognosis of kidney disease and patient survival. © Journal of Laboratory and Precision Medicine. All rights reserved.

The Supporting Role of Combined and Sequential Extracorporeal Blood Purification Therapies in COVID-19 Patients in Intensive Care Unit.

Critical clinical forms of COVID-19 infection often include Acute Kidney Injury (AKI), requiring kidney replacement therapy (KRT) in up to 20% of patients, further worsening the outcome of the disease. No specific medical therapies are available for the treatment of COVID-19, while supportive care remains the standard treatment with the control of systemic inflammation playing a pivotal role, avoiding the disease progression and improving organ function. Extracorporeal blood purification (EBP) has been proposed for cytokines removal in sepsis and could be beneficial in COVID-19, preventing the cytokines release syndrome (CRS) and providing Extra-corporeal organ support (ECOS) in critical patients. Different EBP procedures for COVID-19 patients have been proposed including hemoperfusion (HP) on sorbent, continuous kidney replacement therapy (CRRT) with adsorbing capacity, or the use of high cut-off (HCO) membranes. Depending on the local experience, the multidisciplinary capabilities, the hardware, and the available devices, EBP can be combined sequentially or in parallel. The purpose of this paper is to illustrate how to perform EBPs, providing practical support to extracorporeal therapies in COVID-19 patients with AKI.

ACUTE KIDNEY INJURY AFTER COVID-19 IN A PATIENT WITH NEUROGENIC LOWER URINARY TRACT DYSFUNCTION: A CLINICAL CASE OBSERVATION.

Complications after COVID-19, even in mild and moderate form, can be detected in children. Patients with chronic diseases are the most susceptible to the development of complications. The impact of COVID-19 on exacerbation of pyelonephritis and acute kidney injury (AKI) in children is not studied enough as yet. The authors present a clinical case observation of a COVID-19 complication in a 6 years old male patient with spinal neurogenic lower urinary tract dysfunction in a form of areflex maladaptive bladder. Two weeks after the coronavirus infection the patient developed an exacerbation of chronic pyelonephritis and AKI with an increase in creatinine, urea, and microalbuminuria levels. Continuous catheterization of the bladder, crystalloid infusions and antibiotic therapy coupled with Dipyridamole made it possible to stop the AKI manifestations within 10 days. (English) [ FROM AUTHOR] После перенесенной инфекции СОVID-19, даже в легкой и среднетяжелой форме, у детей могут выявляться осложнения. Развитию осложнений наиболее подвержены пациенты с хроническими заболеваниями. Влияние инфекции СОVID-19 на обострение пиелонефрита и острого повреждения почек (ОПП) у детей еще не до конца изучено. Авторы предлагают вниманию коллег клиническое наблюдение осложнения после перенесенной инфекции СОVID-19 у мальчика 6 лет с нейрогенным спинальным арефлекторно-неадаптированным мочевым пузырем. Через 2 недели после перенесенной коронавирусной инфекции у ребенка развились обострение хронического пиелонефрита и ОПП с повышением показателей креатинина, мочевины и уровня микроальбуминурии. Постоянная катетеризация мочевого пузыря, инфузии кристаллоидов, антибактериальная терапия и назначение дипиридамола позволили в течение 10 дней купировать проявления ОПП. (Russian) [ FROM AUTHOR] Copyright of Pediatriya named after G. N. Speransky is the property of Pediatria, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Targeting ACE2 as a potential prophylactic strategy against COVID-19-induced exacerbation of chronic kidney disease.

Patients with chronic kidney disease (CKD) are at higher risk for severe coronavirus disease 2019 (COVID-19). Such patients are more likely to develop "COVID-19-induced acute kidney injury (AKI)", which exacerbates the pre-existing CKD and increases the mortality rate of the patients. COVID-19-induced AKI is pathologically characterized by acute tubular necrosis and the interstitial infiltration of proinflammatory leukocytes. In our rat model with advanced CKD, immunohistochemistry for angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) demonstrated their strong expression in the cytoplasm of damaged proximal tubular cells and the infiltrating leukocytes within the cortical interstitium, which overlapped with the lesions of COVID-19-induced AKI. Since ACE2 and TMPRSS2 are enzymes that facilitate the viral entry into the cells and trigger the onset of cytokine storm, the renal distribution of these proteins in advanced CKD was thought to be responsible for the development of COVID-19-induced AKI. Concerning such mechanisms, the pharmacological blockade of ACE2 or the use of soluble forms of the ACE2 protein may halt the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells. This would protect against the COVID-19-induced exacerbation of pre-existing CKD by preventing the development of AKI.

Case Report: Role of Ketone Monitoring in Diabetic Ketoacidosis With Acute Kidney Injury: Better Safe Than Sorry.

Background: Type 1 Diabetes (T1D) is a well-known endocrinological disease in children and adolescents that is characterized by immune-mediated destruction of pancreatic ß-cells, leading to partial or total insulin deficiency, with an onset that can be subtle (polydipsia, polyuria, weight loss) or abrupt (Diabetic Keto-Acidosis, hereafter DKA, or, although rarely, Hyperosmolar Hyperglycemic State, hereafter HHS). Severe DKA risk at the onset of T1D has recently significantly increased during the SARS-CoV-2 pandemic with life-threatening complications often due to its management. DKA is marked by low pH (<7.3) and bicarbonates (<15 mmol/L) in the presence of ketone bodies in plasma or urine, while HHS has normal pH (>7.3) and bicarbonates (>15 mmol/L) with no or very low ketone bodies. Despite this, ketone monitoring is not universally available, and DKA diagnosis is mainly based on pH and bicarbonates. A proper diagnosis of the right form with main elements (pH, bicarbonates, ketones) is essential to begin the right treatment and to identify organ damage (such as acute kidney injury). Case Presentations: In this series, we describe 3 case reports in which the onset of T1D was abrupt with severe acidosis (pH < 7.1) in the absence of both DKA and HHS. In a further evaluation, all 3 patients showed acute kidney injury, which caused low bicarbonates and severe acidosis without increasing ketone bodies. Conclusion: Even if it is not routinely recommended, a proper treatment that included bicarbonates was then started, with a good response in terms of clinical and laboratory values. With this case series, we would like to encourage emergency physicians to monitor ketones, which are diriment for a proper diagnosis and treatment of DKA.

Study of Acute Kidney Injury in Patients Hospitalized with COVID-19: A Single Center Study in Bangladesh

Introduction: The incidence of acute kidney injury (AKI) associated with hospitalized corona virus disease -19(Covid-19) patients and associated outcomes are not well determined. This study describes the presentation, risk factors and outcomes of AKI in patients hospitalized with Covid-19. Material & Methods: In this cross sectional study, we reviewed the health records for all conveniently selected patients hospitalized with Covid-19 irrespective of co morbidity from 1st May to 31st July, 2020, at combined military hospital Dhaka, Bangladesh. Patients younger than 18 years, end stage kidney disease or with a kidney transplant recipient were excluded from the study. AKI was deûned according to kidney disease improving global outcome (KDIGO) criteria. Results: A total of 470 Covid-19 patients were recruited in this current study, out of them 67.02% were male and 32.98% of were female;with male to female ratio was 2:1. The mean age of the study population was 54.71(±14.31) years. AKI developed among 106 (22.55%) patients of whom 50 patients had CKD. The peak stages of AKI were stage 3 in 58(12.34%), followed by stage 1 in 37(7.87%), and stage 2 in 11(2.34%) patients. Renal replacement therapy was required (RRT) for 37(7.87%) patients. Risk factors included older age, hypertension, diabetes mellitus, cardiovascular disease, and chronic kidney disease and those who presented with prolong fever and breathlessness.AKI was commonly seen in patients with severe disease. Considerable number of patient had proteinuria 222(47.23%) and haematuria in 63 (13.40%) and were significantly associated with AKI. Elevated level of ferritin, D-dimer and procalcitonin were observed among 249(52.98%), 179(38.08%) and 138(35, 88%) patients respectively which were substantially correlated with AKI. COVID-19 patients complicated to acute kidney injury were strongly associated with higher mortality19 of 23 (82.60%). Conclusion: Renal involvement in COVID-19 (Corona virus-nephropathy) has a complex etiology. It is closely associated with severity of disease and indicating poor prognosis. Further study will be needed for better understanding the causes of AKI and patient outcomes. [ FROM AUTHOR] Copyright of Journal of Bangladesh College of Physicians & Surgeons is the property of Bangladesh College of Physicians & Surgeons and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)