Background Data on renal replacement therapy (RRT) for end-stage renal disease (ESRD) was collected by the European Renal Association (ERA) Registry via national and regional renal registries in Europe and countries bordering the Mediterranean Sea. This paper provides a summary of the 2019 ERA Registry Annual Report, including data from 34 countries and additional age comparisons. Methods Individual patient data for 2019 was provided by 35 registries and aggregated data by 17 registries. Using this data, the incidence and prevalence of RRT, the kidney transplantation activity and the survival probabilities were calculated. Results In 2019, a general population of 680.8 million people was covered by the ERA Registry. Overall, the incidence of RRT was 132 per million population (p.m.p.). Of these patients, 62% were men, 54% were ≥ 65 years of age, 21% had diabetes mellitus as primary renal disease, and 84% had haemodialysis (HD), 11% had peritoneal dialysis (PD) and 5% had pre-emptive kidney transplantation as initial treatment modality. The overall prevalence of RRT on 31 December 2019 was 893 p.m.p., with 58% of patients on HD, 5% on PD, and 37% living with a kidney transplant. The overall kidney transplant rate was 35 p.m.p. and 29% of the kidney grafts were from a living donor. The unadjusted 5-year survival probability was 42.3% for patients commencing dialysis, 86.6% for recipients of deceased donor grafts and 94.4% for recipients of living donor grafts in the period 2010–2014. When comparing age categories, there were substantial differences in the distribution of primary renal disease, treatment modality, kidney donor type, and in the survival probabilities.

Background Dialysis confers the highest risk of COVID-19 death among comorbidities predisposing to severe COVID-19. However, reports of COVID-19-associated mortality frequently refer to mortality during the initial hospitalization or first month after diagnosis. Methods In a prospective, observational study, we have analyzed the long-term (one year follow-up) serological and clinical outcomes of 56 hemodialysis patients that were infected by SARS-CoV-2 during the first pandemic wave. COVID-19 was diagnosed by a positive PCR test (n = 37) or by the development of anti-SARS-CoV-2 antibodies (n = 19). Results After over one year of follow-up, 35.7% of hemodialysis patients infected by SARS-COV-2 during the first pandemic wave had died, 6 (11%) during the initial admission, and 14 (25%) died in the following months, mainly within the first 3 months after diagnosis. Overall, 30% of patients died from vascular causes, and 40% from respiratory causes. In adjusted analysis, positive SARS-CoV-2 PCR test for diagnosis (HR 5.18 [1.30–20.65] p = 0.020), higher baseline C reactive protein levels (HR 1.10 [1.03–1.16] p = 0.002) and lower hemoglobin levels (HR 0.62 [0.45–0.86] p = 0.005) were associated with higher one-year mortality. Mortality in the 144 patients that did not have COVID-19 was 21 (14.6%) over 12 months [hazard ratio for death for COVID-19 patients 3.00 (1.62–5.53), log-rank p = 0.00023]. Over the first year, the percentage of patients having anti-SARS-CoV-2 IgG decreased from 36/49 (73.4%) initially to 27/44 (61.3%) at 6 months, and 14/36 (38.8%) at 12 months. Conclusions The high mortality of hemodialysis patients with COVID-19 is not limited to the initial hospitalization. Defining COVID-19 deaths as those occurring within 3 months of a COVID-19 diagnosis may better represent the burden of COVID-19. In hemodialysis patients, the anti-SARS-CoV-2 IgG response was suboptimal and short-lived.

Phenols are uremic toxins of intestinal origin formed by bacteria during protein metabolism. Of these molecules, p-cresol is the most studied and has been associated with renal function impairment and vascular damage. Bisphenol A (BPA) is a molecule with structural similarity with phenols found in plastic food and beverage containers as well as in some dialyzers. BPA is considered an environmental toxicant based on animal and cell culture studies. Japanese authorities recently banned BPA use in baby bottles based on observational association studies in newborns. BPA is excreted in urine and uremic patients present higher serum levels, but there is insufficient evidence to set cut-off levels or to link BPA to any harmful effect in CKD. However, the renal elimination and potential exposure during dialysis warrant the monitoring of BPA exposure and the design of observational studies in which the potential health risks of BPA for end-stage renal disease patients are evaluated.

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 β-hydroxybutyrate, a molecule that generates a specific histone modification, β-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.

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Mammalian kidney emerges from metanephric mesenchyme following the insertion of a migrating ureteric bud. The pattern morphology of mesenchymal speation during tubular segmentation s remarkably complex, and the relative contribution ofpattern gradients from the microenvironment versus the instructive role of Individual cells is not known. We have started to exami the differentiation of metanephrlc mesenchyme using cultures of metanephric ridge (MMR) cells from day 13.5 mouse embryos to investigate the conversion of mesenchyme toward kidney epithelium in vitro. One of our mesenchymal clones, MMR1, expresses little Pax2, uvomorulin, or cytokeratin but does express neural cell adhesion molecule, bcl2, and desmin; these are properties c ent with an early stem cell. Coculture of MMR1 cells with embryonic spinal cord leads to the induction of a more differentiated cell phenotype characterized by decreased expresson of neural cell adhesion molecule, the appearance of uvomorulin, and the emergence of cytokeratin, all consistent with an evolution toward epithelium. We were also able to detect the hepatocyte growth factor receptor c-met on MMR1 cells by indt Immuwnofuorescence. When MMR1 cells were stimuinted with hepatocyte growth factor, neural cell adhesion molecule expresion decreased and uvomorulin appeared. This effect of hepatocyte growth factor, as a single cytokine, may be important in the early assemblage of kidney, since we were able to detect mRNA tnscrip enIng c-met from mouse embryo metanephric kidneys.The metanephric kidney emerges from condensing mesenchyme as organized tubules lined by renal epithelium differentiating toward maturity. The ureteric bud, an epithelial outgrowth of the Wolffian duct, contacts and transforms this metanephros along pathways of epithelial divergence and specialization starting as early as embryonic day 11.5 (Ei1.5) in the mouse (1-3). Loose metanephric mesenchyme first condenses around the ureteric bud; comma-shaped bodies then form and elongate into S-shaped bodies. Tubules become segmented over the next 1-2 days, and one pole of the S-shaped body is vascularized by invading endothelial cells to form a glomerulus (4). Nephron segmentation by progenitor cells probably occurs in some kind of ordered cascade (5). During this process of induction, the early-stage neural cell adhesion molecule (NCAM) disappears (6), and the production of collagen types I and III decreases, while new collagen type IV emerges as part of the tubular basement membrane (7). Epithelial cell proteins including uvomorulin (Ecadherin), laminin A chain (8), and cytokeratin also become evident (9), and apoptosis thins unwanted anlage from the organizing parenchymal mass (10). Attempts to study this process in vitro have met with some limited success, and although the metanephros in organ culture can be induced to form tubules using embryonic spinal cord separated by filters (11, 12), similar events have not been reported from work in single origin cell cultures.The specific transducing agents that ...

A prospective observational study for justification, safety, and efficacy of a third dose of mRNA vaccine in patients receiving maintenance hemodialysis. Kidney Int 101: [390][391][392][393][394][395][396][397][398][399][400][401][402] 2022