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Virtual home dialysis physician mentorship is feasible. In total, 53% of participants perceived the program would change the perspective of participants on prescribing home dialysis. More research is needed to ascertain the effect of virtual mentorship on home dialysis incidence and attrition rates in a wider audience.

Home dialysis therapies are flexible kidney replacement strategies with documented clinical benefits. While the incidence of end-stage kidney disease continues to increase globally, the use of home dialysis remains low in most developed countries. Multiple barriers to providing home dialysis have been noted in the published literature. Among known challenges, gaps in clinician knowledge are potentially addressable with a focused education strategy. Recent national surveys in the United States and Australia have highlighted the need for enhanced home dialysis knowledge especially among nephrologists who have recently completed training. Traditional in-person continuing professional educational programmes have had modest success in promoting home dialysis and are limited by scale and the present global COVID-19 pandemic. We hypothesize that the use of a ‘Hub and Spoke’ model of virtual home dialysis mentorship for nephrologists based on project ECHO would support home dialysis growth. We review the home dialysis literature, known educational gaps and plausible educational interventions to address current limitations in physician education Refereed/Peer-reviewed

BACKGROUND: AKI is a significant complication of coronavirus disease 2019 (COVID-19), with no effective therapy. Niacinamide, a vitamin B3 analogue, has some evidence of efficacy in non-COVID-19-related AKI. The objective of this study is to evaluate the association between niacinamide therapy and outcomes in patients with COVID-19-related AKI. METHODS: We implemented a quasi-experimental design with nonrandom, prospective allocation of niacinamide in 201 hospitalized adult patients, excluding those with baseline eGFR

As nephrologists, we have early on recognized the current coronavirus disease 2019 (COVID-19) pandemic to be particularly threatening to the patients we care for in our clinics. Many observations have shown older patients and those with chronic medical comorbidities to be disproportionately at risk for excess morbidity and mortality due to COVID-19 infection (1,2). As a medical subspecialty, nephrologists not only see the most substantial proportion of patients age ≥80 years but also care for the most complex patient population with the highest number of comorbidities (3). Therefore, extensive discussions have been carried out in our community about the potential fallout of COVID-19 infection and the observed or anticipated adverse outcomes. These adverse outcomes include hospitalizations, critical care admission, ESKD, and death in patient’s kidney disorder (4⇓–6). Further, several reports have shown that a high number of patients with COVID-19 infection experience AKI and may require dialysis, potentially increasing demand for available resources beyond capacity (7⇓–9). Several surge-mitigation protocols and COVID-19–related best practice guidelines are now available to nephrologists (10,11). Moving beyond the surge, however, there is substantial uncertainty about the chronic management of patients with kidney disease in the near-term future. When should we time dialysis access placement? Do we place patients at unnecessary risk for “nosocomial” COVID-19 infection by requiring routine laboratory assessment or dialysis access surveillance for primary prevention? Or do we risk a rise in preventable adverse outcomes by dialing back on care considered not essential and thus, failing to identify early signs of medical complications? Answers to some of these questions were already hotly debated before. The COVID-19 pandemic has considerably increased their complexity and uncertainty. Here, we share the Kaiser Permanente Northern California (KPNC) strategy for population-wide management strategies of patients with kidney …

International audience; BACKGROUND:CSL112 (apolipoprotein A-I [human]) is a plasma-derived apolipoprotein A-I developed for early reduction of cardiovascular risk following an acute myocardial infarction (AMI). The safety of CSL112 among AMI subjects with moderate, stage 3 chronic kidney disease (CKD) is unknown.METHODS:CSL112_2001, a multicenter, placebo-controlled, parallel-group, double-blind, randomized phase 2 trial, enrolled patients with moderate CKD within 7 days following AMI. Enrollment was stratified on the basis of estimated glomerular filtration rate and presence of diabetes requiring treatment. Patients were randomized in a 2:1 ratio to receive 4 weekly infusions of CSL112 6 g or placebo. The co-primary safety end points were renal serious adverse events (SAEs) and acute kidney injury, defined as an increase ≥26.5 μmol/L in baseline serum creatinine for more than 24 hours, during the treatment period.RESULTS:A total of 83 patients were randomized (55 CSL112 vs 28 placebo). No increase in renal SAEs was observed in the CSL112 group compared with placebo (CSL112 = 1 [1.9%], placebo = 4 [14.3%]). Similarly, no increase in acute kidney injury events was observed (CSL112 = 2 [4.0%], placebo = 4 [14.3%]). Rates of other SAEs were similar between groups. CSL112 administration resulted in increases in ApoA-I and cholesterol efflux similar to those observed in patients with AMI and normal renal function or stage 2 CKD enrolled in the ApoA-I Event Reducing in Ischemic Syndromes I trial.CONCLUSIONS:These results demonstrate the acceptable safety of the 6-g dose of CSL112 among AMI subjects with moderate stage 3 CKD and support inclusion of these patients in a phase 3 cardiovascular outcomes trial powered to assess efficacy.

Nicotinamide adenine dinucleotide (NAD+) extends longevity in experimental organisms, raising interest in its impact on human health. De novo NAD+ biosynthesis from tryptophan is evolutionarily conserved yet considered supplanted among higher species by biosynthesis from nicotinamide (NAM). Here we show that a bottleneck enzyme in de novo biosynthesis, quinolinate phosphoribosyltransferase (QPRT), defends renal NAD+ and mediates resistance to acute kidney injury (AKI). Following murine AKI, renal NAD+ fell, quinolinate rose, and QPRT declined. QPRT+/− mice exhibited higher quinolinate, lower NAD+, and higher AKI susceptibility. Metabolomics suggested an elevated urinary quinolinate/tryptophan ratio (uQ/T) as an indicator of reduced QPRT. Elevated uQ/T predicted AKI and other adverse outcomes in critically ill patients. A phase 1 placebo-controlled study of oral NAM demonstrated a dose-related increase in circulating NAD+ metabolites. NAM was well tolerated and was associated with less AKI. Therefore, impaired NAD+ biosynthesis may be a feature of high-risk hospitalizations for which NAD+ augmentation could be beneficial. Impaired NAD+ biosynthesis may be a common feature of high-risk hospitalizations for which NAD+ augmentation could improve therapeutic outcome.

In the shark rectal gland (SRG), apical chloride secretion through CFTR channels is electrically coupled to a basolateral K+ conductance whose type and molecular identity are unknown. We performed studies in the perfused SRG with 17 K+ channel inhibitors to begin this search. Maximal chloride secretion was markedly inhibited by low-perfusate pH, bupivicaine, anandamide, zinc, quinidine, and quinine, consistent with the properties of an acid-sensitive, four-transmembrane, two-pore-domain K+ channel (4TM-K2P). Using PCR with degenerate primers to this family, we identified a TASK-1 fragment in shark rectal gland, brain, gill, and kidney. Using 5′ and 3′ rapid amplification of cDNA ends PCR and genomic walking, we cloned the full-length shark gene (1,282 bp), whose open reading frame encodes a protein of 375 amino acids that was 80% identical to the human TASK-1 protein. We expressed shark and human TASK-1 cRNA in Xenopus oocytes and characterized these channels using two-electrode voltage clamping. Both channels had identical current-voltage relationships (outward rectifying) and a reversal potential of −90 mV. Both were inhibited by quinine, bupivicaine, and acidic pH. The pKa for current inhibition was 7.75 for shark TASK-1 vs. 7.37 for human TASK-1, values similar to the arterial pH for each species. We identified this protein in SRG by Western blot and confocal immunofluorescent microscopy and detected the protein in SRG and human airway cells. Shark TASK-1 is the major K+ channel coupled to chloride secretion in the SRG, is the oldest 4TM 2P family member identified, and is the first TASK-1 channel identified to play a role in setting the driving force for chloride secretion in epithelia. The detection of this potassium channel in mammalian lung tissue has implications for human biology and disease.

With one of the highest mitochondrial densities in the body, the kidneys consume approximately 10% of total oxygen while constituting 0.5% of body mass. Renal respiration is linear to solute extraction, linking oxidative metabolism directly to tubular function. This fundamental role of mitochondria in renal health may become an “Achilles heel” under duress. Acute kidney injury (AKI) related to each major class of stressor - inflammation, ischemia, and toxins - exhibits early and prominent mitochondrial injury. The mitochondrial biogenesis regulator, PPARγ-coactivator-1α (PGC1α), may confer tubular protection against these stressors. Recent work proposes that renal PGC1α directly increases levels of nicotinamide adenine dinucleotide (NAD+), an essential co-factor for energy metabolism that has lately been proposed as an anti-aging factor. This mini-review summarizes recent studies on AKI, PGC1α, and NAD+ that identify a direct mechanism between the regulation of metabolic health and the ability to resist renal stressors.

Long term outcomes of biodegradable polymer drug-eluting stents (BP-DES) compared to durable polymer drug-eluting stents (DP-DES), are not well described. A comprehensive search in clinicalTrials.gov, PubMed, EBSCO, Web of Science, google scholar and Ovid was performed for RCTs comparing BP-DES and

Since the first identification of renin by Tigerstedt and Bergmann in 1898, the renin-angiotensin system (RAS) has been extensively studied. The current view of the system is characterized by an increased complexity, as evidenced by the discovery of new functional components and pathways of the RAS. In recent years, the pathophysiological implications of the system have been the main focus of attention, and inhibitors of the RAS such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin (ANG) II receptor blockers have become important clinical tools in the treatment of cardiovascular and renal diseases such as hypertension, heart failure, and diabetic nephropathy. Nevertheless, the tissue RAS also plays an important role in mediating diverse physiological functions. These focus not only on the classical actions of ANG on the cardiovascular system, namely, the maintenance of cardiovascular homeostasis, but also on other functions. Recently, the research efforts studying these noncardiovascular effects of the RAS have intensified, and a large body of data are now available to support the existence of numerous organ-based RAS exerting diverse physiological effects. ANG II has direct effects at the cellular level and can influence, for example, cell growth and differentiation, but also may play a role as a mediator of apoptosis. These universal paracrine and autocrine actions may be important in many organ systems and can mediate important physiological stimuli. Transgenic overexpression and knock-out strategies of RAS genes in animals have also shown a central functional role of the RAS in prenatal development. Taken together, these findings may become increasingly important in the study of organ physiology but also for a fresh look at the implications of these findings for organ pathophysiology.

Objective— The salt-sensitive Dahl rat and the spontaneously hypertensive rat develop comparable spontaneous hypertension on a low-salt diet, whereas only the salt-sensitive Dahl rat strain develops a striking increase in blood pressure and cardiovascular hypertrophy on a high-salt diet. We set out to identify quantitative trait loci (QTLs) contributing to the progression of salt-induced organ damage in hypertension by studying an F 2 population derived from both strains. Methods and Results— We determined systolic blood pressure (SBP), vascular aortic hypertrophy (AH), cardiac left ventricular (LV) hypertrophy (LVH), and LV fibrosis in 230 male F 2 -animals on a high-salt diet. A strong correlation between AH and LVH was found ( r =0.58, P Conclusions— This study demonstrates a strong correlation between AH and LVH in salt-sensitive hypertension and identifies QTLs contributing to the progression of cardiovascular hypertrophy in this condition.

CSL112 is plasma-derived apolipoprotein A-I (apoA-I), currently in development for early reduction of cardiovascular risk after acute myocardial infarction (AMI). The AEGIS-I trial demonstrated renal and hepatic safety and elevations in cholesterol efflux with 4 weekly intravenous infusions of 2g or

Kidney toxicity is one of the most frequent adverse events reported during drug development. The lack of accurate predictive cell culture models and the unreliability of animal studies have created a need for better approaches to recapitulate kidney function in vitro. Here, we describe a microfluidic device lined by living human kidney epithelial cells exposed to fluidic flow that mimics key functions of the human kidney proximal tubule. Primary kidney epithelial cells isolated from human proximal tubule are cultured on the upper surface of an extracellular matrix-coated, porous, polyester membrane that splits the main channel of the device into two adjacent channels, thereby creating an apical 'luminal' channel and a basal 'interstitial' space. Exposure of the epithelial monolayer to an apical fluid shear stress (0.2 dyne cm(-2)) that mimics that found in living kidney tubules results in enhanced epithelial cell polarization and primary cilia formation compared to traditional Transwell culture systems. The cells also exhibited significantly greater albumin transport, glucose reabsorption, and brush border alkaline phosphatase activity. Importantly, cisplatin toxicity and Pgp efflux transporter activity measured on-chip more closely mimic the in vivo responses than results obtained with cells maintained under conventional culture conditions. While past studies have analyzed kidney tubular cells cultured under flow conditions in vitro, this is the first report of a toxicity study using primary human kidney proximal tubular epithelial cells in a microfluidic 'organ-on-a-chip' microdevice. The in vivo-like pathophysiology observed in this system suggests that it might serve as a useful tool for evaluating human-relevant renal toxicity in preclinical safety studies.

The aim of the study was to characterize the genetic basis for the early onset of increased urinary albumin excretion (UAE) observed in the salt-sensitive Dahl rat (SS). We first characterized blood pressures and UAE values in adult SS compared with the spontaneously hypertensive rat (SHR) strain. Blood pressure measurements by radiotelemetry at 14 wk demonstrated similar spontaneous hypertension in both strains on a low-sodium diet containing 0.2% NaCl by weight, whereas UAE was markedly increased in SS compared with SHR (253.07 ± 68.39 vs. 1.65 ± 1.09 mg/24 h, P < 0.0001). Analysis of UAE in young animals of both strains fed a low-sodium diet demonstrated that UAE is elevated in SS as early as 4 wk of age ( P < 0.0001), when ultrastructural evaluation of glomeruli by electron microscopy appears still normal. At 8 wk SS demonstrated a 280-fold elevated UAE compared with SHR ( P < 0.0001). Consequently, to identify quantitative trait loci (QTLs) contributing to salt-independent early manifestation of increased UAE in the SS rat, we performed genome-wide linkage and QTL mapping analysis in a young F2population derived from the two contrasting strains. UAE was determined in 539 F2animals at 8 wk. We identified seven suggestive or significant UAE QTLs on rat chromosomes (RNO) RNO2, RNO6, RNO8, RNO9, RNO10, RNO11, and RNO19, accounting together for 34% of the overall variance of UAE in this F2population. Thus early onset albuminuria in the SS rat is under polygenetic influence and independent from salt loading.