Kidney Injury in COVID-19: Epidemiology, Molecular Mechanisms and Potential Therapeutic Targets.

As of December 2021, SARS-CoV-2 had caused over 250 million infections and 5 million deaths worldwide. Furthermore, despite the development of highly effective vaccines, novel variants of SARS-CoV-2 continue to sustain the pandemic, and the search for effective therapies for COVID-19 remains as urgent as ever. Though the primary manifestation of COVID-19 is pneumonia, the disease can affect multiple organs, including the kidneys, with acute kidney injury (AKI) being among the most common extrapulmonary manifestations of severe COVID-19. In this article, we start by reflecting on the epidemiology of kidney disease in COVID-19, which overwhelmingly demonstrates that AKI is common in COVID-19 and is strongly associated with poor outcomes. We also present emerging data showing that COVID-19 may result in long-term renal impairment and delve into the ongoing debate about whether AKI in COVID-19 is mediated by direct viral injury. Next, we focus on the molecular pathogenesis of SARS-CoV-2 infection by both reviewing previously published data and presenting some novel data on the mechanisms of cellular viral entry. Finally, we relate these molecular mechanisms to a series of therapies currently under investigation and propose additional novel therapeutic targets for COVID-19.

La infección por VHB es un factor de riesgo de enfermedad renal crónica: revisión sistemática y metaanálisis / HBV infection is a risk factor for chronic kidney disease: Systematic review and meta-analysis

Antecedentes El papel del virus de la hepatitis B (VHB) como factor de riesgo en la incidencia y progresión de la enfermedad renal crónica (ERC) no ha sido clarificado. Objetivo Evaluamos el impacto producido por la infección con el VHB sobre el riesgo de la ERC en la población general. Material y métodos Llevamos a cabo una revisión sistemática de la literatura médica publicada a fin de evaluar si existe, en la población adulta general, una relación entre la infección por el VHB y un aumento del riesgo de ERC. Adoptamos el modelo de efectos aleatorios de DerSimonian y Laird para proporcionar una estimación resumida del riesgo de ERC (definida por una tasa de filtración glomerular reducida y/o una proteinuria detectable) por infección con el VHB en los estudios publicados. También se realizaron metarregresiones y análisis estratificados. Resultados Recogimos 33 estudios (n=7.849.849 pacientes) publicados en 26 artículos y se realizó un metaanálisis por separado conforme a los resultados. La agrupación de los resultados de los estudios de cohortes (11 estudios, n=1.056.645 pacientes) demostró una relación entre un estatus serológico VHB positivo y el aumento de la incidencia de la ERC, con una estimación resumida para la HR ajustada con VHB en todas las encuestas del 1,40 (IC 95% 1,16-1,69; p<0,001). Se observó heterogeneidad entre estudios (valor Q: 49,5; p<0,0001). En el subconjunto de estudios transversales no se detectó relación entre el VHB y la prevalencia de la ERC (10 estudios; n=3.222.545 pacientes; OR ajustada 1,04; IC 95% 0,90-1,218; p=0,5). Los análisis de metarregresión informaron de una relación entre el estatus HBcAg positivo y la incidencia de ERC en la población general (p<0,015). Conclusiones Parece que la exposición a la infección por VHB está asociada con un aumento en el riesgo de desarrollar ERC en la población adulta general. Se están realizando estudios destinados a comprender los mecanismos responsables de dicha asociación (AU)

Background The activity of hepatitis B virus (HBV) as a risk factor for the incidence and progression of chronic kidney disease (CKD) has not been clarified. Aim We evaluated the impact of infection with HBV on the risk of CKD in the general population. Material and methods We carried out a systematic review of the published medical literature to assess whether a relationship between hepatitis B infection and an increased risk of CKD in the adult general population occurs. We adopted the random effects model of DerSimonian and Laird to provide a summary estimate of the risk of chronic kidney disease (defined by lowered glomerular filtration rate and/or detectable proteinuria) with HBV infection across the published studies. Meta-regression and stratified analyses were also performed. Results We retrieved 33 studies (n=7,849,849 patients) published in 26 different articles, and separate meta-analyses were performed according to the outcome. Pooling results from cohort studies (11 studies, n=1,056,645 patients) demonstrated a relationship between positive HBV serologic status and increased incidence of CKD, the summary estimate for adjusted HR with HBV across the surveys, 1.40 (95% CI, 1.16-1.69) (P<.001). Between-study heterogeneity was noted (Q value, 49.5, P<.0001). No relationship between HBV and prevalence of CKD was noted in the subset of cross-sectional studies (10 studies; n=3,222,545 patients), adjusted OR, 1.04 (95% IC 0.90-1.218; P=.5). Meta-regression analysis reported a relationship between positive HBsAg status and incidence of CKD in the general population (P<.015). Conclusions It appears that exposure to HBV infection seems to be associated with an increased risk of developing CKD in the adult general population. Studies aimed to understand the mechanisms responsible of such association are under way (AU)

Chronic kidney disease linked to SARS-CoV-2 infection: a case report.

BACKGROUND: The recent COVID-19 pandemic has raised concerns about patient diagnosis and follow-up of chronically ill patients. Patients suffering from chronic illnesses, concomitantly infected by SARS-CoV-2, globally tend to have a worse prognosis and poor outcomes. Renal tropism and acute kidney injury following SARS-CoV-2 infection has recently been described in the literature, with elevated mortality rates. Furthermore, patients with pre-existing chronic kidney disease, infected by SARS-CoV-2, should be monitored carefully. Here, we report the case of a 69-year-old patient with splenic marginal zone lymphoma, suffering from longstanding chronic kidney disease following SARS-CoV-2 infection. CASE PRESENTATION: A 69-year-old male patient previously diagnosed with pulmonary embolism and splenic marginal zone lymphoma (Splenomegaly, Matutes 2/5, CD5 negative and CD23 positive), was admitted to the hospital with shortness of breath, fever and asthenia. A nasopharyngeal swab test was performed in addition to a CT-scan, which confirmed SARS-CoV-2 infection. Blood creatinine increased following SARS-CoV-2 infection at 130 µmol/l, with usual values at 95 µmol/l. The patient was discharged at home with rest and symptomatic medical treatment (paracetamol and hydration), then readmitted to the hospital in August 2020. A kidney biopsy was therefore conducted as blood creatinine levels were abnormally elevated. Immunodetection performed in a renal biopsy specimen confirmed co-localization of SARS-CoV2 nucleocapsid and protease 3C proteins with ACE2, Lewis x and sialyl-Lewis x antigens in proximal convoluted tubules and podocytes. Co-localization of structural and non-structural viral proteins clearly demonstrated viral replication in proximal convoluted tubules in this chronically ill patient. Additionally, we observed the co-localization of sialyl-Lewis x and ACE2 receptors in the same proximal convoluted tubules. Reverse Transcriptase-Polymerase Chain Reaction test performed on the kidney biopsy was negative, with very low Ct levels (above 40). The patient was finally readmitted to the haematology department for initiation of chemotherapy, including CHOP protocol and Rituximab. CONCLUSIONS: Our case emphasizes on the importance of monitoring kidney function in immunosuppressed patients and patients suffering from cancer following SARS-CoV-2 infection, through histological screening. Further studies will be required to decipher the mechanisms underlying chronic kidney disease and the putative role of sialyl-Lewis x and HBGA during SARS-CoV-2 infection.

Potential Mechanisms of the SARS-CoV-2-induced AKI Progression to CKD: A Forward-Looking Perspective.

Coronavirus disease 2019 (COVID­19) was identified in December 2019 and is still expanding in most parts of the world. The wide variety of affected organs is likely based upon the shared expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) important entry-receptor angiotensin-converting enzyme 2 (ACE2). For this reason, the broad distribution of ACE2 receptors in different tissues plays a crucial role in the multi-organ dysfunction and fatality due to COVID-19. Because of the high prevalence of acute kidney injury (AKI) in patients with COVID-19, we review the molecular understanding into viral infection mechanisms and implications for AKI. Furthermore, mechanisms of the AKI to chronic kidney disease (CKD) progression, such as the relative contribution of immune cell reaction, fibroblasts activation, endothelial dysfunction, and subsequent hypoxia may contribute to the association of AKI with worse outcomes during this virus pandemic. We highlight the state of the knowledge on SARS-CoV-2-dependent mechanisms for AKI and list the potential management choices for the prevention of AKI aggravation and the impending possibility of CKD. Finally, we intend to provide a much better understanding of why Coronavirus induces AKI and its subsequent progression to CKD in the coming years and further discuss the acute and long-term renal consequences.

Lectin Pathway Mediates Complement Activation by SARS-CoV-2 Proteins.

Early and persistent activation of complement is considered to play a key role in the pathogenesis of COVID-19. Complement activation products orchestrate a proinflammatory environment that might be critical for the induction and maintenance of a severe inflammatory response to SARS-CoV-2 by recruiting cells of the cellular immune system to the sites of infection and shifting their state of activation towards an inflammatory phenotype. It precedes pathophysiological milestone events like the cytokine storm, progressive endothelial injury triggering microangiopathy, and further complement activation, and causes an acute respiratory distress syndrome (ARDS). To date, the application of antiviral drugs and corticosteroids have shown efficacy in the early stages of SARS-CoV-2 infection, but failed to ameliorate disease severity in patients who progressed to severe COVID-19 pathology. This report demonstrates that lectin pathway (LP) recognition molecules of the complement system, such as MBL, FCN-2 and CL-11, bind to SARS-CoV-2 S- and N-proteins, with subsequent activation of LP-mediated C3b and C4b deposition. In addition, our results confirm and underline that the N-protein of SARS-CoV-2 binds directly to the LP- effector enzyme MASP-2 and activates complement. Inhibition of the LP using an inhibitory monoclonal antibody against MASP-2 effectively blocks LP-mediated complement activation. FACS analyses using transfected HEK-293 cells expressing SARS-CoV-2 S protein confirm a robust LP-dependent C3b deposition on the cell surface which is inhibited by the MASP-2 inhibitory antibody. In light of our present results, and the encouraging performance of our clinical candidate MASP-2 inhibitor Narsoplimab in recently published clinical trials, we suggest that the targeting of MASP-2 provides an unsurpassed window of therapeutic efficacy for the treatment of severe COVID-19.

Seroprevalence of Infection with Feline Morbilliviruses Is Associated with FLUTD and Increased Blood Creatinine Concentrations in Domestic Cats.

Feline morbilliviruses (FeMV) are fairly newly discovered paramyxoviruses found in cats. The first description indicated an association with widely distributed chronic kidney disease (CKD) in the host species. In various studies, a global prevalence and a further genotype, designated FeMV-2, and the involvement of other organ systems in infected individuals were shown. Using an immunofluorescence assay, we detected an overall seroprevalence of FeMV in almost half of the cats investigated (n = 380), with a significantly increased proportion in younger animals. In comparison to European Shorthair cats, the rate of seropositivity is higher in pedigree cats. Regardless of the breed, FeMV infection was associated with increased blood creatinine concentrations, suggesting an association with CKD. Further analysis indicated that this association was the strongest in animals having high IFA titers against FeMV-2. In addition, a significant association between FeMV-positive status and the prevalence of feline lower urinary tract disease (FLUTD, or idiopathic cystitis) was detected. This association was dominated by cats having antibodies against FeMV-1 only. To further evaluate the positive correlation between FeMV seroprevalence and CKD as well as FLUTD, consideration of additional clinical characteristics and laboratory parameters is warranted, and controlled infection studies with both FeMV genotypes are necessary. Clinicians should, however, be aware of a possible link between renal and lower urinary tract disease and FeMV infections.

Multi Organ Involvement in a Kidney Transplant Recipient, A Case Report.

A 22-year old man underwent kidney transplant two years ago. Following fever and cough, epigastric pain, convulsion, vomiting and PO intolerance he had been brought to the emergency room. During evaluation in addition to pulmonary involvement with SARS-COVID-19, brain, stomach and pancreas involvements with COVID-19 infection also were detected. Hemodialysis and specific treatments were initiated. After 16 days he could be discharged ultimately.

Cross-sectional retrospective analysis of clinical characteristics of chronic hepatitis B patients with oral antiviral treatment in eastern China.

BACKGROUND: In China, more than 20 million patients with chronic hepatitis B need antiviral treatment. Side effects of antiviral treatment such as renal complications can be problematic, particularly in an aging population. METHODS: The data were retrospectively extracted from the hospital medical charts of five centers in eastern China from January 1 to December 31, 2018. RESULTS: A total of 8309 patients with CHB was enrolled in this study. The median age of the patients was 46 years. The prevalence of diabetes mellitus, hypertension, and hepatic cirrhosis was respectively 3.49%, 4.42%, and 23.72%. The prevalence of these comorbidities increased with age (P < 0.001). Of the patients with CHB, 5332 had complete renal function results. Among them, patients with an estimated glomerular filtration rate of < 60 mL/min/1.73m2 accounted for 4.14%, and those with proteinuria for 8.33%. According to the definition of chronic kidney disease, the proportion of patients with chronic kidney disease was 11.37%. The prevalence of chronic kidney disease increased with age (P < 0.001). In a multivariate analysis, age group [odds ratio (OR) = 2.387], diabetes mellitus (OR = 1.486), hypertension (OR = 2.557), hepatic cirrhosis (OR = 1.295), and a history of exposure to adefovir dipivoxil (OR = 1.644) were significantly associated with CKD (P < 0.05). Among patients with CKD, 17.66% (107/606) had a history of lamivudine exposure, and 34.65% (210/606) had a history of nucleotide analogue exposure CONCLUSION: The management of Chinese patients with CHB should take into consideration age, previous medication history, and renal impairment.

Prolonged SARS-CoV-2 viral shedding in patients with chronic kidney disease.

Recent World Health Organization guidance has aimed to provide pragmatic guidance acknowledging the role of sequential nasopharyngeal swabs taken >24 hours apart for SARS-CoV-2 in high-risk populations. Patients with chronic kidney disease (CKD) are known to have an altered immune milieu which may be associated with a delay in viral clearance. Here, a cross-sectional observational study of 138 patients admitted with SARS-CoV-2 infection at two large regional hospitals in Scotland, UK examined the median time to two consecutive negative nasopharyngeal swabs for SARS-CoV-2 in an inpatient population. The median time from admission to the first of two consecutive negative nasopharyngeal swabs was 18 days (range = 1-44) in patients with CKD, compared with 11 days (range: 1-71) in patients without CKD (P = .0007). Multivariable linear regression analysis using explanatory variables of age, sex, SARS-CoV-2 disease severity, key comorbidities and renal function showed that declining estimated glomerular filtration rate was independently associated with prolonged time to viral clearance. Our data suggest that patients with CKD who are admitted to hospital with SARS-CoV-2 take longer to achieve sequential negative nasopharyngeal swab reverse transcription-polymerase chain reaction results than those without CKD. This has implications for renal service provision, discharge planning and hospital capacity as well as a direct impact on patients due to extended hospital stay, anxiety and stigmatisation.

Hepatitis C and Treatment in Patients with Chronic Kidney Disease.

Hepatitis C virus (HCV) is associated with increased mortality and morbidity in patients with chronic kidney disease (CKD). The early detection and treatment of Hepatitis C associated with kidney disease is paramount to preventing the progressive loss of kidney function. HCV treatment until the advent of direct acting anti-viral agents (DAAs) was limited to interferon and ribavirin. Interferon and ribavirin treatment resulted in only modest success but with frequent adverse events and poor tolerability. Furthermore, interferon and ribavirin could not be used in certain patient populations including those with advanced CKD, were on dialysis, or those who have received a kidney transplant. DAAs have now made treatment possible in these sub-groups with a sustained viral response (SVR) of 90-100% and minimal side effects. DAAs have helped increase transplant rates by allowing for the use of HCV positive kidneys in recipients who are HCV negative. Although the choice of DAAs should be carefully considered and based on patient characteristics, concomitant medications, and HCV genotype.

Kidney disease and all-cause mortality in patients with COVID-19 hospitalized in Genoa, Northern Italy.

BACKGROUND: The prevalence of kidney involvement during SARS-CoV-2 infection has been reported to be high. Nevertheless, data are lacking about the determinants of acute kidney injury (AKI) and the combined effect of chronic kidney disease (CKD) and AKI in COVID-19 patients. METHODS: We collected data on patient demographics, comorbidities, chronic medications, vital signs, baseline laboratory test results and in-hospital treatment in patients with COVID-19 consecutively admitted to our Institution. Chronic kidney disease was defined as eGFR < 60 mL/min per 1.73 m2 or proteinuria at urinalysis within 180 days prior to hospital admission. AKI was defined according to KDIGO criteria. The primary and secondary outcomes were the development of AKI and death. RESULTS: Of 777 patients eligible for the study, acute kidney injury developed in 176 (22.6%). Of these, 79 (45%) showed an acute worsening of a preexisting CKD, and 21 (12%) required kidney replacement therapy. Independent associates of AKI were chronic kidney disease, C-reactive protein (CRP) and ventilation support. Among patients with acute kidney injury, 111 died (63%) and its occurrence increased the risk of death by 60% (HR 1.60 [95% IC 1.21-2.49] p = 0.002) independently of potential confounding factors including hypertension, preexisting kidney damage, and comorbidities. Patients with AKI showed a significantly higher rate of deaths attributed to bleeding compared to CKD and the whole population (7.5 vs 1.5 vs 3.5%, respectively). CONCLUSION: Awareness of kidney function, both preexisting CKD and development of acute kidney injury, may help to identify those patients at increased risk of death.

Cystatin C and Urine Albumin to Creatinine Ratio Predict 5-Year Mortality and Cardiovascular Events in People Living With HIV.

BACKGROUND: Identifying people with HIV (PWH) at risk for chronic kidney disease, cardiovascular events, and death is crucial. We evaluated biomarkers to predict all-cause mortality and cardiovascular events, and measured glomerular filtration rate (mGFR) slope. METHODS: Biomarkers were measured at enrollment. Baseline and 5-year mGFR were measured by plasma iohexol clearance. Outcomes were a composite criterion of all-cause mortality and/or cardiovascular events, and mGFR slope. RESULTS: Of 168 subjects, 146 (87.4%) had undetectable HIV load. Median follow-up was 59.1 months (interquartile range, 56.2-62.1). At baseline, mean age was 49.5 years (± 9.8) and mean mGFR 98.9 mL/min/1.73m2 (± 20.6). Seventeen deaths and 10 cardiovascular events occurred during 5-year follow-up. Baseline mGFR was not associated with mortality/cardiovascular events. In multivariable analysis, cystatin C (hazard ratio [HR], 5.978; 95% confidence interval [CI], 2.774-12.88; P < .0001) and urine albumin to creatinine ratio (uACR) at inclusion (HR, 1.002; 95% CI, 1.001-1.004; P < .001) were associated with mortality/cardiovascular events. Area under receiver operating curve of cystatin C was 0.67 (95% CI, .55-.79) for mortality/cardiovascular event prediction. Biomarkers were not associated with GFR slope. CONCLUSIONS: uACR and cystatin C predict all-cause mortality and/or cardiovascular events in PWH independently of mGFR.

Prevalence of comorbidities among individuals with COVID-19: A rapid review of current literature.

INTRODUCTION: On February 11, 2020 WHO designated the name "COVID-19" for the disease caused by "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), a novel virus that quickly turned into a global pandemic. Risks associated with acquiring the virus have been found to most significantly vary by age and presence of underlying comorbidity. In this rapid literature review we explore the prevalence of comorbidities and associated adverse outcomes among individuals with COVID-19 and summarize our findings based on information available as of May 15, 2020. METHODS: A comprehensive systematic search was performed on PubMed, Medline, Scopus, Embase, and Google Scholar to find articles published until May 15, 2020. All relevant articles providing information on PCR tested COVID-19 positive patient population with clinical characteristics and epidemiological information were selected for review and analysis. RESULTS: A total of 27 articles consisting of 22,753 patient cases from major epicenters worldwide were included in the study. Major comorbidities seen in overall population were CVD (8.9%), HTN (27.4%), Diabetes (17.4%), COPD (7.5%), Cancer (3.5%), CKD (2.6%), and other (15.5%). Major comorbidity specific to countries included in the study were China (HTN 39.5%), South Korea (CVD 25.6%), Italy (HTN 35.9%), USA (HTN 38.9%), Mexico, (Other 42.3%), UK (HTN 27.8%), Iran (Diabetes 35.0%). Within fatal cases, an estimated 84.1% had presence of one or more comorbidity. Subgroup analysis of fatality association with having comorbidity had an estimated OR 0.83, CI [0.60-0.99], p<0.05. CONCLUSIONS: Based on our findings, hypertension followed by diabetes and cardiovascular diseases were the most common comorbidity seen in COVID-19 positive patients across major epicenters world-wide. Although having one or more comorbidity is linked to increased disease severity, no clear association was found between having these risk factors and increased risk of fatality.

Clinical Characteristics and Outcomes of Patients Hospitalized for COVID-19 in Africa: Early Insights from the Democratic Republic of the Congo.

Little is known about the clinical features and outcomes of SARS-CoV-2 infection in Africa. We conducted a retrospective cohort study of patients hospitalized for COVID-19 between March 10, 2020 and July 31, 2020 at seven hospitals in Kinshasa, Democratic Republic of the Congo (DRC). Outcomes included clinical improvement within 30 days (primary) and in-hospital mortality (secondary). Of 766 confirmed COVID-19 cases, 500 (65.6%) were male, with a median (interquartile range [IQR]) age of 46 (34-58) years. One hundred ninety-one (25%) patients had severe/critical disease requiring admission in the intensive care unit (ICU). Six hundred twenty patients (80.9%) improved and were discharged within 30 days of admission. Overall in-hospital mortality was 13.2% (95% CI: 10.9-15.8), and almost 50% among those in the ICU. Independent risk factors for death were age < 20 years (adjusted hazard ratio [aHR] = 6.62, 95% CI: 1.85-23.64), 40-59 years (aHR = 4.45, 95% CI: 1.83-10.79), and ≥ 60 years (aHR = 13.63, 95% CI: 5.70-32.60) compared with those aged 20-39 years, with obesity (aHR = 2.30, 95% CI: 1.24-4.27), and with chronic kidney disease (aHR = 5.33, 95% CI: 1.85-15.35). In marginal structural model analysis, there was no statistically significant difference in odds of clinical improvement (adjusted odds ratio [aOR] = 1.53, 95% CI: 0.88-2.67, P = 0.132) nor risk of death (aOR = 0.65, 95% CI: 0.35-1.20) when comparing the use of chloroquine/azithromycin versus other treatments. In this DRC study, the high mortality among patients aged < 20 years and with severe/critical disease is of great concern, and requires further research for confirmation and targeted interventions.

Clinical features of patients with type 2 diabetes with and without Covid-19: A case control study (CoViDiab I).

AIMS: To evaluate whether subjects with diabetes hospitalized for Coronavirus disease-19 (Covid-19) represent a subgroup of patients with high-risk clinical features compared to patients with diabetes without Covid-19. METHODS: In this case-control study 79 patients with type 2 diabetes out of 354 adults hospitalized for Covid-19 and 158 controls with type 2 diabetes but without Covid-19, matched for age and gender, were enrolled. Medical history and concomitant therapies were retrieved from medical charts and compared between cases and controls, controlling for confounders. RESULTS: Fully-adjusted multivariate logistic regression model showed that previous CVD history did not differ between patients with and without Covid-19 (odds ratio 1.40, 95% confidence interval [CI]: 0.59-3.32, p = 0.45). A higher prevalence of chronic obstructive pulmonary disease (COPD) (OR 3.72, 95%CI: 1.42-9.72, p = 0.007) and of chronic kidney disease (CKD) (OR 3.08, 95%CI: 1.18-8.06, p = 0.022) and a lower prevalence of ever smokers (OR 0.30, 95%CI: 0.13-0.67, p = 0.003), of users of lipid lowering agents (OR 0.26, 95%CI: 0.12-0.54, p < 0.001), and of anti-hypertensive drugs (OR 0.39, 95%CI: 0.16-0.93, p = 0.033) were found among cases. CONCLUSIONS: CVD prevalence does not differ between people with diabetes with and without Covid-19 requiring hospitalization. An increased prevalence of COPD and of CKD in Covid-19 patients with type 2 diabetes is suggested. These findings aid to clarify the relationship between underlying conditions and SARS-CoV-2 infection in the high-risk group of patients with diabetes.

Role of SIRT1 in HIV-associated kidney disease.

Human immunodeficiency virus (HIV) infection of kidney cells can lead to HIV-associated nephropathy (HIVAN) and aggravate the progression of other chronic kidney diseases. Thus, a better understanding of the mechanisms of HIV-induced kidney cell injury is needed for effective therapy against HIV-induced kidney disease progression. We have previously shown that the acetylation and activation of key inflammatory regulators, NF-κB p65 and STAT3, were increased in HIVAN kidneys. Here, we demonstrate the key role of sirtuin 1 (SIRT1) deacetylase in the regulation of NF-κB and STAT3 activity in HIVAN. We found that SIRT1 expression was reduced in the glomeruli of human and mouse HIVAN kidneys and that HIV-1 gene expression was associated with reduced SIRT1 expression and increased acetylation of NF-κB p65 and STAT3 in cultured podocytes. Interestingly, SIRT1 overexpression, in turn, reduced the expression of negative regulatory factor in podocytes stably expressing HIV-1 proviral genes, which was associated with inactivation of NF-κB p65 and a reduction in HIV-1 long terminal repeat promoter activity. In vivo, the administration of the small-molecule SIRT1 agonist BF175 or inducible overexpression of SIRT1 specifically in podocytes markedly attenuated albuminuria, kidney lesions, and expression of inflammatory markers in Tg26 mice. Finally, we showed that the reduction in SIRT1 expression by HIV-1 is in part mediated through miR-34a expression. Together, our data provide a new mechanism of SIRT1 regulation and its downstream effects in HIV-1-infected kidney cells and indicate that SIRT1/miR-34a are potential drug targets to treat HIV-related kidney disease.

Situación de la infección por SARS-CoV-2 en pacientes en tratamiento renal sustitutivo Informe del Registro COVID-19 de la Sociedad Española de Nefrología (S.E.N.) / SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (S.E.N.)

La reciente aparición de la pandemia por el coronavirus SARS-CoV-2 ha impactado de forma muy importante en la población general. Los pacientes en tratamiento renal sustitutivo (TRS) no han sido ajenos a esta situación y por sus características resultan especialmente vulnerables. Presentamos los resultados del análisis del Registro COVID-19 de la S.E.N. MATERIAL Y MÉTODOS: EL Registro comenzó a funcionar el 18 de marzo de 2020. Recoge variables epidemiológicas, datos del contagio y diagnóstico, clínica acompañante, tratamientos y desenlace. Se trata de un registro "on line". Los pacientes fueron diagnosticados de infección por SARS-Cov-2 en base a los resultados de la PCR del virus, realizada tanto en pacientes que habían manifestado clínica compatible o tenían signos sospechosos como en aquellos a los que se había hecho como cribado tras algún contacto conocido con otro enfermo. RESULTADOS: A fecha 11 de abril el Registro disponía de datos de 868 pacientes, procedentes de todas las Comunidades Autónomas. La modalidad de TRS más representada es la hemodiálisis en centro (HDC) seguida de los pacientes trasplantados. La clínica de presentación es similar a la población general. Un porcentaje muy elevado (85%) requirió ingreso hospitalario, un 8% en unidades de cuidados intensivos. Los tratamientos más utilizados fueron hidroxicloroquina, lopinavirritonavir y esteroides. La mortalidad es elevada y alcanza el 23%: los pacientes fallecidos estaban con más frecuencia en HDC, desarrollaban más frecuentemente neumonía y recibían en menos ocasiones lopinavir-ritonavir y esteroides. La edad y la neumonía se asociaban de forma independiente al riesgo de fallecer. CONCLUSIONES: La infección por SARS-CoV-2 afecta ya a un número importante de pacientes españoles en TRS, fundamentalmente aquellos que están en HDC, las tasas de hospitalización son muy elevadas y la mortalidad es elevada; la edad y el desarrollo de neumonía son factores asociados a mortalidad

The recent appearance of the SARS-CoV-2 coronavirus pandemic has had a significant impact on the general population. Patients on renal replacement therapy (RRT) have not been unaware of this situation and due to their characteristics they are especially vulnerable. We present the results of the analysis of the COVID-19 Registry of the Spanish Society of Nephrology. MATERIAL AND METHODS: The Registry began operating on March 18th, 2020. It collects epidemiological variables, contagion and diagnosis data, signs and symptoms, treatments and outcomes. It is an "online" registry. Patients were diagnosed with SARS-Cov-2 infection based on the results of the PCR of the virus, carried out both in patients who had manifested compatible symptoms or had suspicious signs, as well as in those who had undergone screening after some contac, acquainted with another patient. RESULTS: As of April 11, the Registry had data on 868 patients, from all the Autonomous Communities. The most represented form of TRS is in-center hemodialysis (ICH) followed by transplant patients. Symptoms are similar to the general population. A very high percentage (85%) required hospital admission, 8% in intensive care units. The most used treatments were hydroxychloroquine, lopinavir-ritonavir, and steroids. Mortality is high and reaches 23%; deceased patients were more frequently on ICH, developed pneumonia more frequently, and received less frequently lopinavir-ritonavir and steroids. Age and pneumonia were independently associated with the risk of death. CONCLUSIONS: SARS-CoV-2 infection already affects a significant number of Spanish patients on RRT, mainly those on ICH, hospitalization rates are very high and mortality is high; age and the development of pneumonia are factors associated with mortality

First report of feline morbillivirus in mainland China.

Feline morbillivirus (FeMV) is an emerging member of the family Paramyxoviridae that is suspected to be involved in chronic kidney disease (CKD). FeMV was first discovered in Hong Kong in 2012 and has subsequently been detected in many countries. However, the prevalence of FeMV in mainland China is still unclear. To clarify the present status and examine the genetic diversity of FeMV in mainland China, in this study, we collected cat urine samples in veterinary hospitals in Guangdong Province in 2017 and 2018. Using reverse transcription (RT)-PCR, we found that the urine of six out of 64 cats tested positive for FeMV RNA. Sequencing and genetic analysis of the FeMV L gene showed that FeMV in mainland China is genetically diverse, and phylogenetic analysis showed that the viruses segregated into two clusters. Two isolates, GD5 and GD6, grouped in a branch that was separate from the one containing other previously reported FeMV isolates. These results will contribute to a better understanding of the evolution of FeMV in China.