Increased prevalence of Kidney cysts in individuals carrying heterozygous COL4A3 or COL4A4 pathogenic variants.

BACKGROUND: Clinical variability among individuals with heterozygous pathogenic/likely pathogenic (P/LP) variants in the COL4A3/COL4A4 genes (also called autosomal dominant Alport syndrome or COL4A3/COL4A4 related disorder) is huge; many individuals are asymptomatic or show microhematuria, while others may develop proteinuria and chronic kidney disease (CKD). The prevalence of simple kidney cysts (KC) in the general population varies according to age, and patients with advanced CKD are prone to have them. A possible association between heterozygous COL4A3, COL4A4, and COL4A5 P/LP variants and KC has been described in small cohorts. The presence of KC in a multicenter cohort of individuals with heterozygous P/LP variants in the COL4A3/COL4A4 genes is assessed in this study. METHODS: We evaluated the presence of KC by ultrasound in 157 individuals with P/LP variants in COL4A3 (40.7%) or COL4A4 (53.5%) without kidney replacement therapy. The association between presence of KC and age, proteinuria, eGFR, and causative gene was analyzed. Prevalence of KC was compared with historical case series in the general population. RESULTS: Half of the individuals with P/LP variants in COL4A3/COL4A4 showed KC, which is a significantly higher percentage than in the general population. Only 3.8% (6/157) had cystic nephromegaly. Age and eGFR showed an association with the presence of KC (p<0.001). No association was found between KC and proteinuria, sex, or causative gene. CONCLUSIONS: Individuals with COL4A3/COL4A4 P/LP variants are prone to develop KC more frequently than the general population, and their presence is related to age and to eGFR. Neither proteinuria, sex nor the causative gene influences the presence of KC in these individuals.

Tasa de ultrafiltración horaria ajustada a peso corporal y mortalidad en hemodiálisis / Ultrafiltration rate adjusted to body weight and mortality in hemodialysis patients

Antecedentes y objetivo: La mortalidad de los pacientes en hemodiálisis es alta. Una tasa de ultrafiltración horaria ajustada por peso (UFR/W) elevada se ha asociado con episodios de hipotensión arterial y con mayor riesgo de muerte y/o eventos cardiovasculares. Material y métodos: Hemos evaluado la asociación entre UFR/W y mortalidad en 215 pacientes en hemodiálisis prevalentes seguidos durante 28 ± 6,12 meses. Se estimaron características clínicas basales y UFR/W media a lo largo del seguimiento. Resultados: La UFR/W media fue 9,0 ± 2,4 y los terciles 7,1 y 10,1 mL/kg/h. Se categorizó a la población en función del tiempo que habían estado con UFR/W igual o superior a los puntos de corte descritos en la literatura como relacionados con mayor mortalidad (10,0 mL/kg/h y 13,0 mL/kg/h). Los pacientes con mayor UFR/W fueron más jóvenes, con mayor ganancia de peso interdiálisis y porcentaje de reducción de peso, pero con menor peso seco, inicial y final. Durante el seguimiento, fallecieron 46 (21,4%) personas de las cuales la mayoría eran > 70 años, diabéticas o con enfermedad cardiovascular. No hubo diferencias en la mortalidad entre los grupos de UFR/W ni en la UFR/W entre los fallecidos y no fallecidos. En comparación con estudios previos donde describieron la asociación entre UFR/W y mortalidad, en nuestra población había más prevalencia de medicación protectora cardiovascular y no se observaron UFR/W tan altas. Conclusión: En nuestro medio, la UFR/W más elevada se observó en pacientes más jóvenes y de menor peso y no se asoció con mayor mortalidad. (AU)

Background and aims: Mortality among hemodialysis patients remains high. An elevated ultrafiltration rate adjusted by weight (UFR/W) has been associated with hypotension and higher risk of death and/or cardiovascular events. Methods: We evaluated the association between UFR/W and mortality in 215 hemodialysis patients. The mean follow-up was 28 ± 6.12 months. We collected patientś baseline characteristics and mean UFR/W throughout the follow-up. Results: Mean UFR/W was 9.0 ± 2,4 and tertiles 7.1 y 10.1 mL/kg/h. We divided our population according to the percentage of sessions with UFR/W above the limits described in the literature associated with increased mortality (10.0 mL/kg/h and 13.0 mL/kg/h). Patients with higher UFR/W were younger, with higher interdialytic weight gain and weight reduction percentage but lower dry, pre and post dialysis weight. Throughout the follow-up, 46 (21.4%) patients died, the majority over 70 years old, diabetic or with cardiovascular disease. There were neither differences regarding mortality between groups nor differences in UFR/W among patients who died and those who did not. Contrary to previous studies, we did not find an association between UFR/W and mortality, maybe due to a higher prevalence in the use of cardiovascular protection drugs and lower UFR/W. Conclusions: The highest UFR/W were observed in younger patients with lower weight and were not associated with an increased mortality. (AU)

Phosphate, Microbiota and CKD.

Phosphate is a key uremic toxin associated with adverse outcomes. As chronic kidney disease (CKD) progresses, the kidney capacity to excrete excess dietary phosphate decreases, triggering compensatory endocrine responses that drive CKD-mineral and bone disorder (CKD-MBD). Eventually, hyperphosphatemia develops, and low phosphate diet and phosphate binders are prescribed. Recent data have identified a potential role of the gut microbiota in mineral bone disorders. Thus, parathyroid hormone (PTH) only caused bone loss in mice whose microbiota was enriched in the Th17 cell-inducing taxa segmented filamentous bacteria. Furthermore, the microbiota was required for PTH to stimulate bone formation and increase bone mass, and this was dependent on bacterial production of the short-chain fatty acid butyrate. We review current knowledge on the relationship between phosphate, microbiota and CKD-MBD. Topics include microbial bioactive compounds of special interest in CKD, the impact of dietary phosphate and phosphate binders on the gut microbiota, the modulation of CKD-MBD by the microbiota and the potential therapeutic use of microbiota to treat CKD-MBD through the clinical translation of concepts from other fields of science such as the optimization of phosphorus utilization and the use of phosphate-accumulating organisms.

Clinical Features of Asymptomatic SARS-CoV-2 Infection in Hemodialysis Patients.

BACKGROUND: CKD is a risk factor for severe COVID-19. However, the clinical spectrum of COVID-19 in hemodialysis patients is still poorly characterized. OBJECTIVE: To analyze the clinical spectrum of COVID-19 on hemodialysis patients. METHOD: A retrospective observational study was conducted on 66 hemodialysis patients. Nasopharyngeal swab PCR and serology for SARS-CoV-2, blood analysis, chest radiography, treatment, and outcomes were assessed. RESULTS: COVID-19 was diagnosed in 50 patients: 38 (76%) were PCR-positive and 12 (24%) were PCR-negative but developed anti-SARS-CoV-2 antibodies. By contrast, 17% of PCR-positive patients failed to develop detectable antibodies against SARS-CoV-2. Among PCR-positive patients, 5/38 (13%) were asymptomatic, while among PCR-negative patients 7/12 (58%) were asymptomatic (p = 0.005) for a total of 12/50 (24%) asymptomatic patients. No other differences were found between PCR-positive and PCR-negative patients. No differences in potential predisposing factors were found between asymptomatic and symptomatic patients except for a lower use of ACE inhibitors among asymptomatic patients. Asymptomatic patients had laboratory evidence of milder disease such as higher lymphocyte counts and oxygen saturation and lower troponin I and interleukin-6 levels than symptomatic patients. Overall mortality was 7/50 (14%) and occurred only in symptomatic PCR-positive patients in whom mortality was 7/33 (21%). CONCLUSIONS: Asymptomatic SARS-CoV-2 infection is common in hemodialysis patients, especially among patients with initial negative PCR that later seroconvert. Thus COVID-19 mortality in hemodialysis patients may be lower than previously estimated based on PCR tests alone.

Ultrafiltration rate adjusted to body weight and mortality in hemodialysis patients.

BACKGROUND AND AIMS: Mortality among hemodialysis patients remains high. An elevated ultrafiltration rate adjusted by weight (UFR/W) has been associated with hypotension and higher risk of death and/or cardiovascular events. METHODS: We evaluated the association between UFR/W and mortality in 215 hemodialysis patients. The mean follow-up was 28 ±â€¯6.12 months. We collected patients' baseline characteristics and mean UFR/W throughout the follow-up. RESULTS: Mean UFR/W was 9.0 ±â€¯2,4 and tertiles 7.1 y 10.1 mL/kg/h. We divided our population according to the percentage of sessions with UFR/W above the limits described in the literature associated with increased mortality (10.0 ml/kg/h and 13.0 mL/kg/h). Patients with higher UFR/W were younger, with higher interdialytic weight gain and weight reduction percentage but lower dry, pre and post dialysis weight. Throughout the follow-up, 46 (21.4%) patients died, the majority over 70 years old, diabetic or with cardiovascular disease. There were neither differences regarding mortality between groups nor differences in UFR/W among patients who died and those who did not. Contrary to previous studies, we did not find an association between UFR/W and mortality, maybe due to a higher prevalence in the use of cardiovascular protection drugs and lower UFR/W. CONCLUSIONS: The highest UFR/W were observed in younger patients with lower weight and were not associated with an increased mortality.

The Spectrum of Clinical and Serological Features of COVID-19 in Urban Hemodialysis Patients.

INTRODUCTION: The inherent immunosuppression of uremia increases the susceptibility of hemodialysis patients to infection. There is still limited evidence on hemodialysis patients and COVID-19. The clinical and analytical spectrum and treatment responses and mortality are poorly characterized. MATERIAL AND METHODS: Clinical and analytical features, chest X-ray, polymerase chain reaction (PCR) and antibodies for SARS-CoV-2, treatment and outcomes were analyzed in 48 patients diagnosed with COVID-19 during March and April 2020 in two coordinated Spanish hemodialysis units. RESULTS: In 200 haemodialysis patients, COVID-19 was diagnosed in 48, of whom 22 were PCR positive, eight PCR negative but seroconverted and two were diagnosed on typical clinical grounds. Despite a mean age of 72.6 years, the overall mortality rate was 5/48 (10%). Among the PCR positive patients, 21 (55%) required admission and five (13%) died. PCR positive patients were more often symptomatic and hospitalized and had higher troponin I levels than PCR negative patients, but did not differ in lymphocyte counts, D-dimer or interleukin-6 (IL-6) levels. Among PCR negative COVID-19 patients, three out of 10 (30%) required admission, and none died. The most frequent symptom among the 48 patients was fever (31%), followed by asymptomatic patients (23%). A low number of lymphocytes was the only parameter significantly different between hospitalized and ambulatory COVID-19 patients, independently of PCR status. CONCLUSIONS: COVID-19 hemodialysis patients are frequently asymptomatic, and mortality may be lower than previously reported. Diagnosis may be retrospective, based on seroconversion, as PCR may be negative. This information should guide preventive and patient isolation strategies.

Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease.

Diabetic kidney disease is one of the fastest growing causes of death worldwide. Epigenetic regulators control gene expression and are potential therapeutic targets. There is functional interventional evidence for a role of DNA methylation and the histone post-translational modifications-histone methylation, acetylation and crotonylation-in the pathogenesis of kidney disease, including diabetic kidney disease. Readers of epigenetic marks, such as bromodomain and extra terminal (BET) proteins, are also therapeutic targets. Thus, the BD2 selective BET inhibitor apabetalone was the first epigenetic regulator to undergo phase-3 clinical trials in diabetic kidney disease with an endpoint of kidney function. The direct therapeutic modulation of epigenetic features is possible through pharmacological modulators of the specific enzymes involved and through the therapeutic use of the required substrates. Of further interest is the characterization of potential indirect effects of nephroprotective drugs on epigenetic regulation. Thus, SGLT2 inhibitors increase the circulating and tissue levels of ß-hydroxybutyrate, a molecule that generates a specific histone modification, ß-hydroxybutyrylation, which has been associated with the beneficial health effects of fasting. To what extent this impact on epigenetic regulation may underlie or contribute to the so-far unclear molecular mechanisms of cardio- and nephroprotection offered by SGLT2 inhibitors merits further in-depth studies.