Update on Innate Immunity in Acute Kidney Injury-Lessons Taken from COVID-19.

The serious clinical course of SARS-CoV-2 infection is usually accompanied by acute kidney injury (AKI), worsening prognosis and increasing mortality. AKI in COVID-19 is above all a consequence of systemic dysregulations leading to inflammation, thrombosis, vascular endothelial damage and necrosis. All these processes rely on the interactions between innate immunity elements, including circulating blood cells, resident renal cells, their cytokine products, complement systems, coagulation cascades and contact systems. Numerous simultaneous pathways of innate immunity should secure an effective host defense. Since they all form a network of cross-linked auto-amplification loops, uncontrolled activation is possible. When the actions of selected pathways amplify, cascade activation evades control and the propagation of inflammation and necrosis worsens, accompanied by complement overactivity and immunothrombosis. The systemic activation of innate immunity reaches the kidney, where the damage affecting single tubular cells spreads through tissue collateral damage and triggers AKI. This review is an attempt to synthetize the connections between innate immunity components engaged in COVID-19-related AKI and to summarize the knowledge on the pathophysiological background of processes responsible for renal damage.

Optimising transitions of care for acute kidney injury survivors: protocol for a mixed-methods study of nephrologist and primary care provider recommendations.

INTRODUCTION: Acute kidney injury (AKI) affects nearly 20% of all hospitalised patients and is associated with poor outcomes. Long-term complications can be partially attributed to gaps in kidney-focused care and education during transitions. Building capacity across the healthcare spectrum by engaging a broad network of multidisciplinary providers to facilitate optimal follow-up care represents an important mechanism to address this existing care gap. Key participants include nephrologists and primary care providers and in-depth study of each specialty's approach to post-AKI care is essential to optimise care processes and healthcare delivery for AKI survivors. METHODS AND ANALYSIS: This explanatory sequential mixed-methods study uses survey and interview methodology to assess nephrologist and primary care provider recommendations for post-AKI care, including KAMPS (kidney function assessment, awareness and education, medication review, blood pressure monitoring and sick day education) elements of follow-up, the role of multispecialty collaboration, and views on care process-specific and patient-specific factors influencing healthcare delivery. Nephrologists and primary care providers will be surveyed to assess recommendations and clinical decision-making in the context of post-AKI care. Descriptive statistics and the Pearson's χ2 or Fisher's exact test will be used to compare results between groups. This will be followed by semistructured interviews to gather rich, qualitative data that explains and/or connects results from the quantitative survey. Both deductive analysis and inductive analysis will occur to identify and compare themes. ETHICS AND DISSEMINATION: This study has been reviewed and deemed exempt by the Institutional Review Board at Mayo Clinic (IRB 20-0 08 793). The study was deemed exempt due to the sole use of survey and interview methodology. Results will be disseminated in presentations and manuscript form through peer-reviewed publication.

Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait.

Importance: Sickle cell trait (SCT), defined as the presence of 1 hemoglobin beta sickle allele (rs334-T) and 1 normal beta allele, is prevalent in millions of people in the US, particularly in individuals of African and Hispanic ancestry. However, the association of SCT with COVID-19 is unclear. Objective: To assess the association of SCT with the prepandemic health conditions in participants of the Million Veteran Program (MVP) and to assess the severity and sequelae of COVID-19. Design, Setting, and Participants: COVID-19 clinical data include 2729 persons with SCT, of whom 353 had COVID-19, and 129 848 SCT-negative individuals, of whom 13 488 had COVID-19. Associations between SCT and COVID-19 outcomes were examined using firth regression. Analyses were performed by ancestry and adjusted for sex, age, age squared, and ancestral principal components to account for population stratification. Data for the study were collected between March 2020 and February 2021. Exposures: The hemoglobin beta S (HbS) allele (rs334-T). Main Outcomes and Measures: This study evaluated 4 COVID-19 outcomes derived from the World Health Organization severity scale and phenotypes derived from International Classification of Diseases codes in the electronic health records. Results: Of the 132 577 MVP participants with COVID-19 data, mean (SD) age at the index date was 64.8 (13.1) years. Sickle cell trait was present in 7.8% of individuals of African ancestry and associated with a history of chronic kidney disease, diabetic kidney disease, hypertensive kidney disease, pulmonary embolism, and cerebrovascular disease. Among the 4 clinical outcomes of COVID-19, SCT was associated with an increased COVID-19 mortality in individuals of African ancestry (n = 3749; odds ratio, 1.77; 95% CI, 1.13 to 2.77; P = .01). In the 60 days following COVID-19, SCT was associated with an increased incidence of acute kidney failure. A counterfactual mediation framework estimated that on average, 20.7% (95% CI, -3.8% to 56.0%) of the total effect of SCT on COVID-19 fatalities was due to acute kidney failure. Conclusions and Relevance: In this genetic association study, SCT was associated with preexisting kidney comorbidities, increased COVID-19 mortality, and kidney morbidity.

The Triad of Legionnaires' Disease, Rhabdomyolysis, and Acute Kidney Injury: A Case Report.

BACKGROUND Legionella infection is a common cause of atypical pneumonia, known as Legionnaires' disease when infection extends to extrapulmonary involvement, which often leads to hospitalization. The triad of Legionella pneumonia, rhabdomyolysis, and renal failure displays a rare yet fatal complication without prompt management. CASE REPORT Our patient was a 62-year-old man with no significant medical history who developed Legionnaires' disease with severely elevated creatinine phosphokinase (CPK) of 9614 mcg/L, consistent with rhabdomyolysis. He experienced severe headache, anorexia, and hematuria, which prompted him to seek medical care. Pertinent social history included recent flooding in his neighborhood, which surrounded the outer perimeter of his home. His clinical manifestations and laboratory findings were consistent with Legionella infection, with concomitant acute kidney injury. A chest X-ray revealed hazy left perihilar opacities concerning for atypical pneumonia. Immediate interventions of hydration and antigen-directed azithromycin were initiated to prevent rapid decompensation. His clinical symptoms resolved without further complications, and he was not transferred to the Intensive Care Unit (ICU). CONCLUSIONS Legionella-induced rhabdomyolysis is an uncommon association that can lead to acute kidney failure and rapid clinical deterioration. Early and aggressive management with fluid repletion and appropriate antibiotics can improve clinical manifestations and hospital length of stay. Our patient's reduction in CPK levels and clinical improvement confirmed that extrapulmonary involvement in Legionella infection can lead to rhabdomyolysis. It is important for healthcare providers to recognize the clinical triad of Legionella pneumonia, rhabdomyolysis, and renal failure as prompt and timely management to reduce associated morbidity.

Predictive Values of Procalcitonin and Presepsin for Acute Kidney Injury and 30-Day Hospital Mortality in Patients with COVID-19.

Background and Objectives: Acute kidney injury (AKI) is a common complication in patients with coronavirus disease 2019 (COVID-19). We investigated the values of procalcitonin (PCT) and presepsin (PSS) for predicting AKI and 30-day hospital mortality in patients with COVID-19. Materials and Methods: We retrospectively evaluated 151 patients with COVID-19 who were admitted to the hospital via the emergency department. The diagnosis of AKI was based on the Kidney Disease: Improving Global Outcomes clinical practice guidelines. Results: The median patient age was 77 years, and 86 patients (57%) were male. Fifty-six patients (37.1%) developed AKI, and 19 patients (12.6%) died within 30 days of hospital admission. PCT and PSS levels were significantly higher in patients with AKI and non-survivors. The cutoff values of PCT levels for predicting AKI and mortality were 2.26 ng/mL (sensitivity, 64.3%; specificity, 89.5%) and 2.67 ng/mL (sensitivity, 68.4%; specificity, 77.3%), respectively. The cutoff values of PSS levels for predicting AKI and mortality were 572 pg/mL (sensitivity, 66.0%; specificity, 69.1%) and 865 pg/mL (sensitivity, 84.6%; specificity, 76.0%), respectively. Conclusion: PCT and PSS are valuable biomarkers for predicting AKI and 30-day hospital mortality in patients with COVID-19.

[Clinical Characteristics and outcomes of adults with COVID-19 admitted to a Pediatric Intensive Care Unit]. / Características y resultados clínicos de adultos graves hospitalizados por COVID-19 en una Unidad de Cuidados Intensivos Pediátricos.

OBJECTIVE: To describe a cohort of critically ill adult patients suffering from COVID-19, admitted to a pediatric intensive care unit managed by a pediatric intensive care team (ICU-MP). PATIENTS AND METHOD: Retrospective observational study of adults admitted to the ICU-MP due to COVID-19 from May 11 to July 26, 2020. Demographic, clinical, biochemical, ventilatory support characteris tics, and complications were recorded. Disease severity was characterized by Acute Physiology and Chronic Health Evaluation II score (APACHE II) using data from the first 24 hours of admission to the ICU-MP. RESULTS: Ninety-three patients over 18 years with suspected or confirmed COVID-19 were admitted to the ICU-MP. The median age was 60.3 years (SD 13.9), and 59 (63.4%) patients were male. Eighty-two (88.1%) patients had at least 1 medical comorbidity. The median APACHE II score was 9.4 points (SD 5.6). Fifty-one (54.8%) patients were invasively ventilated, for a median of 13.7 days (SD 17.9). Inotropic support was used in 45 (48%) patients. Thirty-three (35.5%) patients presented acute kidney injury (AKI) and 14 (15.1%) patients received continuous renal replacement therapy. Twenty-nine (31.2%) patients had healthcare-associated infections. The median ICU-MP stay was 10.8 days (SD 11.8). 25 (26.9%) patients died, ten of them (40%) had adequacy of thera peutic effort. CONCLUSIONS: The mortality rate of critically ill patients with COVID-19 is high. Older patients (> 70 years), those who require invasive mechanical ventilation and who develop AKI are at increased risk of death. Although this is not a comparative study, our mortality rate and complica tions seem to be similar to those reported in adult case series.

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.

COVID-19 in Patients with Glomerular Disease: Follow-Up Results from the IRoc-GN International Registry.

Background: The acute and long-term effects of severe acute respiratory syndrome coronavirus 2 infection in individuals with GN are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in GN. Methods: We collected serial information on kidney-related and -unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with coronavirus disease 2019 (COVID-19) and a median follow-up period of 6.4 (interquartile range 2.3-9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple regression models were adjusted for age, sex, ethnicity, and renin-angiotensin-aldosterone system inhibitor use. Results: After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio for AKI=1.28; 95% confidence interval [CI], 0.46 to 3.60; P=0.64). The main predictor of AKI was pre-COVID-19 eGFR (adjusted odds ratio per 1 SD unit decrease in eGFR=3.04; 95% CI, 1.76 to 5.28; P<0.001). GN patients developing AKI were less likely to recover pre-COVID-19 eGFR compared with controls (adjusted 6-month post-COVID-19 eGFR=0.41; 95% CI, 0.25 to 0.56; times pre-COVID-19 eGFR). Shorter duration of GN diagnosis, higher pre-COVID-19 proteinuria, and diagnosis of focal segmental glomerulosclerosis or minimal change disease were associated with a lower post-COVID-19 eGFR. Conclusions: Pre-COVID-19 eGFR is the main risk factor for AKI regardless of GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or a diagnosis of focal segmental glomerulosclerosis or minimal change disease) should be closely monitored not only during the acute phases of COVID-19 but also after its resolution.

Sickle Cell Trait and SARS-CoV-2-Induced Rhabdomyolysis: A Case Report.

BACKGROUND Rhabdomyolysis is a syndrome characterized by muscle necrosis and the subsequent release of intracellular muscle constituents into the bloodstream. Although the specific cause is frequently evident from the history or from the immediate events, such as a trauma, extraordinary physical exertion, or a recent infection, sometimes there are hidden risk factors that have to be identified. For instance, individuals with sickle cell trait (SCT) have been reported to be at increased risk for rare conditions, including rhabdomyolysis. Moreover, there have been a few case reports of SARS-CoV-2 infection-related rhabdomyolysis. CASE REPORT We present a case of a patient affected by unknown SCT and admitted with SARS-CoV-2 pneumonia, who suffered non-traumatic non-exertional rhabdomyolysis leading to acute kidney injury (AKI), requiring acute hemodialysis (HD). The patients underwent 13 dialysis session, of which 12 were carried out using an HFR-Supra H dialyzer. He underwent kidney biopsy, where rhabdomyolysis injury was ascertained. No viral traces were found on kidney biopsy samples. The muscle biopsy showed the presence of an "open nucleolus" in the muscle cell, which was consistent with virus-infected cells. After 40 days in the hospital, his serum creatinine was 1.62 mg/dL and CPK and Myoglobin were 188 U/L and 168 ng/mL, respectively; therefore, the patient was discharged. CONCLUSIONS SARS-CoV-2 infection resulted in severe rhabdomyolysis with AKI requiring acute HD. Since SARS-CoV-2 infection can trigger sickle-related complications like rhabdomyolysis, the presence of SCT needs to be ascertained in African patients.

Risk assessment for acute kidney injury and death among new COVID-19 positive adult patients without chronic kidney disease: retrospective cohort study among three US hospitals.

OBJECTIVE: To develop simple but clinically informative risk stratification tools using a few top demographic factors and biomarkers at COVID-19 diagnosis to predict acute kidney injury (AKI) and death. DESIGN: Retrospective cohort analysis, follow-up from 1 February through 28 May 2020. SETTING: 3 teaching hospitals, 2 urban and 1 community-based in the Boston area. PARTICIPANTS: Eligible patients were at least 18 years old, tested COVID-19 positive from 1 February through 28 May 2020, and had at least two serum creatinine measurements within 30 days of a new COVID-19 diagnosis. Exclusion criteria were having chronic kidney disease or having a previous AKI within 3 months of a new COVID-19 diagnosis. MAIN OUTCOMES AND MEASURES: Time from new COVID-19 diagnosis until AKI event, time until death event. RESULTS: Among 3716 patients, there were 1855 (49.9%) males and the average age was 58.6 years (SD 19.2 years). Age, sex, white blood cell, haemoglobin, platelet, C reactive protein (CRP) and D-dimer levels were most strongly associated with AKI and/or death. We created risk scores using these variables predicting AKI within 3 days and death within 30 days of a new COVID-19 diagnosis. Area under the curve (AUC) for predicting AKI within 3 days was 0.785 (95% CI 0.758 to 0.813) and AUC for death within 30 days was 0.861 (95% CI 0.843 to 0.878). Haemoglobin was the most predictive component for AKI, and age the most predictive for death. Predictive accuracies using all study variables were similar to using the simplified scores. CONCLUSION: Simple risk scores using age, sex, a complete blood cell count, CRP and D-dimer were highly predictive of AKI and death and can help simplify and better inform clinical decision making.

The mechanism underlying extrapulmonary complications of the coronavirus disease 2019 and its therapeutic implication.

The coronavirus disease 2019 (COVID-19) is a highly transmissible disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that poses a major threat to global public health. Although COVID-19 primarily affects the respiratory system, causing severe pneumonia and acute respiratory distress syndrome in severe cases, it can also result in multiple extrapulmonary complications. The pathogenesis of extrapulmonary damage in patients with COVID-19 is probably multifactorial, involving both the direct effects of SARS-CoV-2 and the indirect mechanisms associated with the host inflammatory response. Recognition of features and pathogenesis of extrapulmonary complications has clinical implications for identifying disease progression and designing therapeutic strategies. This review provides an overview of the extrapulmonary complications of COVID-19 from immunological and pathophysiologic perspectives and focuses on the pathogenesis and potential therapeutic targets for the management of COVID-19.

Role of Urinary Kidney Stress Biomarkers for Early Recognition of Subclinical Acute Kidney Injury in Critically Ill COVID-19 Patients.

A high proportion of critically ill patients with COVID-19 develop acute kidney injury (AKI) and die. The early recognition of subclinical AKI could contribute to AKI prevention. Therefore, this study was aimed at exploring the role of the urinary biomarkers NGAL and [TIMP-2] × [IGFBP7] for the early detection of AKI in this population. This prospective, longitudinal cohort study included critically ill COVID-19 patients without AKI at study entry. Urine samples were collected on admission to critical care areas for determination of NGAL and [TIMP-2] × [IGFBP7] concentrations. The demographic information, comorbidities, clinical, and laboratory data were recorded. The study outcomes were the development of AKI and mortality during hospitalization. Of the 51 individuals that were studied, 25 developed AKI during hospitalization (49%). Of those, 12 had persistent AKI (23.5%). The risk factors for AKI were male gender (HR = 7.57, 95% CI: 1.28-44.8; p = 0.026) and [TIMP-2] × [IGFBP7] ≥ 0.2 (ng/mL)2/1000 (HR = 7.23, 95% CI: 0.99-52.4; p = 0.050). Mortality during hospitalization was significantly higher in the group with AKI than in the group without AKI (p = 0.004). Persistent AKI was a risk factor for mortality (HR = 7.42, 95% CI: 1.04-53.04; p = 0.046). AKI was frequent in critically ill COVID-19 patients. The combination of [TIMP-2] × [IGFBP7] together with clinical information, were useful for the identification of subclinical AKI in critically ill COVID-19 patients. The role of additional biomarkers and their possible combinations for detection of AKI in ritically ill COVID-19 patients remains to be explored in large clinical trials.

Brief Report: Acute Kidney Injury in People Living With HIV Hospitalized With Coronavirus Disease 2019: Clinical Characteristics and Outcomes.

BACKGROUND: Data on clinical characteristics and outcomes of people living with HIV (PLWH) hospitalized with coronavirus disease 2019 (COVID-19) who develop acute kidney injury (AKI) are limited. SETTING: Large tertiary health care system in the Bronx, NY. METHODS: We performed a retrospective cohort study of 83 PLWH and 4151 patients without HIV hospitalized with COVID-19 from March 10, 2020, to May 11, 2020. We compared the clinical characteristics and outcomes associated with AKI by HIV serostatus and evaluated HIV-related factors for AKI among PLWH. AKI was defined and staged using Kidney Disease Improving Global Outcomes criteria. RESULTS: The incidence of AKI in hospitalized patients with COVID-19 did not differ significantly by HIV serostatus (54.2% in PLWH vs 49.5% in patients without HIV, P = 0.6). Despite a higher incidence of stage 3 AKI (28.9% vs 17.1% P = 0.05) in PLWH compared with those without HIV, there was no significant difference in the need for renal replacement therapy (22.2% vs 13.4% P = 0.12), renal recovery (76.9% vs 82.5% P = 0.61), or dependence on renal replacement therapy (7.7% vs 3.8% P = 0.27). CD4 T-cell count, HIV-1 RNA viral suppression, and antiretroviral therapy use were not associated with AKI. AKI was associated with increased need for invasive ventilation and in-hospital death, but HIV was not an independent risk factor of in-hospital death after AKI [adjusted hazard ratio 1.01 (95% CI: 0.59 to 1.72), P = 0.98]. CONCLUSIONS: HIV-related factors were not associated with increased risk of AKI in PLWH hospitalized with COVID-19. PLWH hospitalized with COVID-19 had more stage 3 AKI, but outcomes after AKI were similar to those without HIV.

Prophylactic versus therapeutic dose anticoagulation effects on survival among critically ill patients with COVID-19.

INTRODUCTION: Although patients with severe COVID-19 are known to be at high risk of developing thrombotic events, the effects of anticoagulation (AC) dose and duration on in-hospital mortality in critically ill patients remain poorly understood and controversial. The goal of this study was to investigate survival of critically ill COVID-19 patients who received prophylactic or therapeutic dose AC and analyze the mortality rate with respect to detailed demographic and clinical characteristics. MATERIALS AND METHODS: We conducted a retrospective, observational study of critically ill COVID-19 patients admitted to the ICU at Stony Brook University Hospital in New York who received either prophylactic (n = 158) or therapeutic dose AC (n = 153). Primary outcome was in-hospital death assessed by survival analysis and covariate-adjusted Cox proportional hazard model. RESULTS: For the first 3 weeks of ICU stay, we observed similar survival curves for prophylactic and therapeutic AC groups. However, after 3 or more weeks of ICU stay, the therapeutic AC group, characterized by high incidence of acute kidney injury (AKI), had markedly higher death incidence rates with 8.6 deaths (95% CI = 6.2-11.9 deaths) per 1,000 person-days and about 5 times higher risk of death (adj. HR = 4.89, 95% CI = 1.71-14.0, p = 0.003) than the prophylactic group (2.4 deaths [95% CI = 0.9-6.3 deaths] per 1,000 person-days). Among therapeutic AC users with prolonged ICU admission, non-survivors were characterized by older males with depressed lymphocyte counts and cardiovascular disease. CONCLUSIONS: Our findings raise the possibility that prolonged use of high dose AC, independent of thrombotic events or clinical background, might be associated with higher risk of in-hospital mortality. Moreover, AKI, age, lymphocyte count, and cardiovascular disease may represent important risk factors that could help identify at-risk patients who require long-term hospitalization with therapeutic dose AC treatment.

COVID-19-associated acute kidney injury patients treated with renal replacement therapy in the intensive care unit: A multicenter study in São Paulo, Brazil.

INTRODUCTION: Multicenter studies involving patients with acute kidney injury (AKI) associated with the disease caused by the new coronavirus (COVID-19) and treated with renal replacement therapy (RRT) in developing countries are scarce. The objectives of this study were to evaluate the demographic profile, clinical picture, risk factors for mortality, and outcomes of critically ill patients with AKI requiring dialysis (AKI-RRT) and with COVID-19 in the megalopolis of São Paulo, Brazil. METHODS: This multicenter, retrospective, observational study was conducted in the intensive care units of 13 public and private hospitals in the metropolitan region of the municipality of São Paulo. Patients hospitalized in an intensive care unit, aged ≥ 18 years, and treated with RRT due to COVID-19-associated AKI were included. RESULTS: The study group consisted of 375 patients (age 64.1 years, 68.8% male). Most (62.1%) had two or more comorbidities: 68.8%, arterial hypertension; 45.3%, diabetes; 36.3%, anemia; 30.9%, obesity; 18.7%, chronic kidney disease; 15.7%, coronary artery disease; 10.4%, heart failure; and 8.5%, chronic obstructive pulmonary disease. Death occurred in 72.5% of the study population (272 patients). Among the 103 survivors, 22.3% (23 patients) were discharged on RRT. In a multiple regression analysis, the independent factors associated with death were the number of organ dysfunctions at admission and RRT efficiency. CONCLUSION: AKI-RRT associated with COVID-19 occurred in patients with an elevated burden of comorbidities and was associated with high mortality (72.5%). The number of organ dysfunctions during hospitalization and RRT efficiency were independent factors associated with mortality. A meaningful portion of survivors was discharged while dependent on RRT (22.3%).

COVID-19: a trigger for severe thrombotic microangiopathy in a patient with complement gene variant.

The evidence regarding thrombotic microangiopathy (TMA) related to Coronavirus Infectious Disease 2019 (COVID-19) in patients with complement gene mutations as a cause of acute kidney injury (AKI) are limited. We presented the case of a 23-year-old male patient admitted with an asymptomatic form of COVID-19, but with uncontrolled hypertension and AKI. Kidney biopsy showed severe lesions of TMA. In evolution patient had persistent microangiopathic hemolytic anemia, decreased level of haptoglobin and increased LDH level. Decreased complement C3 level and the presence of schistocytes were found for the first time after biopsy. Kidney function progressively decreased and the patient remained hemodialysis dependent. Complement work-up showed a heterozygous variant with unknown significance in complement factor I (CFI) c.-13G>A, affecting the 5' UTR region of the gene. In addition, the patient was found to be heterozygous for the complement factor H (CFH) H3 haplotype (involving the rare alleles of c.-331C>T, Q672Q and E936D polymorphisms) reported as a risk factor of atypical hemolytic uremic syndrome. This case of AKI associated with severe TMA and secondary hemolytic uremic syndrome highlights the importance of genetic risk modifiers in the alternative pathway dysregulation of the complement in the setting of COVID-19, even in asymptomatic forms.

Overweight and Obesity Are Associated With Acute Kidney Injury and Acute Respiratory Distress Syndrome, but Not With Increased Mortality in Hospitalized COVID-19 Patients: A Retrospective Cohort Study.

Objective: To evaluate the association between overweight and obesity on the clinical course and outcomes in patients hospitalized with COVID-19. Design: Retrospective, observational cohort study. Methods: We performed a multicenter, retrospective, observational cohort study of hospitalized COVID-19 patients to evaluate the associations between overweight and obesity on the clinical course and outcomes. Results: Out of 1634 hospitalized COVID-19 patients, 473 (28.9%) had normal weight, 669 (40.9%) were overweight, and 492 (30.1%) were obese. Patients who were overweight or had obesity were younger, and there were more women in the obese group. Normal-weight patients more often had pre-existing conditions such as malignancy, or were organ recipients. During admission, patients who were overweight or had obesity had an increased probability of acute respiratory distress syndrome [OR 1.70 (1.26-2.30) and 1.40 (1.01-1.96)], respectively and acute kidney failure [OR 2.29 (1.28-3.76) and 1.92 (1.06-3.48)], respectively. Length of hospital stay was similar between groups. The overall in-hospital mortality rate was 27.7%, and multivariate logistic regression analyses showed that overweight and obesity were not associated with increased mortality compared to normal-weight patients. Conclusion: In this study, overweight and obesity were associated with acute respiratory distress syndrome and acute kidney injury, but not with in-hospital mortality nor length of hospital stay.