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Oxalate is a metabolite promoting the formation of calcium oxalate crystals in urine. Hyperoxaluria is a feature of genetic diseases, known as primary hyperoxaluria, leading to chronic kidney disease. Ethylene glycol poisoning induces the crystallization of calcium oxalate crystals in renal tubules, promoting acute renal failure. Urine oxalate results from glyoxylate transformation to oxalate in the liver, due to lactate dehydrogenase (LDH) activity, especially the LDH-5 isoenzyme. Genetic RNA interference therapy targeting lactate dehydrogenase lowers urine oxalate excretion in murine models. Stiripentol is a drug inhibiting neuronal LDH-5 isoenzyme activity. We hypothesized that stiripentol would also reduce hepatic oxalate production and urine oxalate excretion. In vitro Stiripentol decreases oxalate synthesis by hepatocytes. In vivo, stiripentol decreases urine oxalate excretion in rats and protects kidney tissue and function against ethylene glycol intoxication and hydroxyproline-induced calcium oxalate crystalline nephropathy. The use of stiripentol in clinical practice deserves further clinical studies.Kidney stone disease comprising nephrolithiasis and nephrocalcinosis is a clinical syndrome of increasing prevalence with remarkable heterogeneity. Stone composition, age of manifestation, rate of recurrence, and impairment of kidney function varies with underlying etiologies. While calcium-based kidney stones account for the vast majority their etiology is still poorly understood. Recent studies underline the notion that genetic susceptibility together with dietary habits constitutes the major driver of kidney stone formation. In addition to single gene (Mendelian) disorders, which are most likely underestimated in the adult population, common risk alleles explain part of the observed heritability. Interestingly, identified GWAS loci often match those of Mendelian disease genes and vice versa (CASR, SLC34A1, CYP24A1). These findings provide mechanistic links related to renal calcium homeostasis, vitamin D metabolism, and CaSR-signaling regulated by the CaSR-CLDN14-CLDN16/19 axis (paracellular Ca2+ reabsorption) and TRPV5 (transcellular Ca2+ reabsorption). Recent identification of new single gene disorders of calcium-oxalate-nephrolithiasis (SLC26A1, CLDN2) and distal renal tubular acidosis with nephrocalcinosis (FOXI1, WDR72, ATP6V1C2) enabled additional insights into the kidney-gut axis and molecular prerequisites of proper urinary acidification. Implementation of centralized patient registries on hereditary kidney stone diseases are necessary to build up well characterized cohorts for urgently needed clinical studies.In kidney transplantation, the assessment of individual risks remains highly imperfect and highlights the need for robust noninvasive biomarkers with the overall goal to improve patient and graft outcomes. In the field of noninvasive biomarkers discovery, urinary biomarkers are promising tools which use easily accessible biological fluid. During the past decades, the technical revolution in the fields of genetics and molecular biology, and advances in chemistry and data analysis have led to a wealth of studies using urinary cell pellets or supernatants from kidney transplant recipients. Transcriptomic, proteomic and metabonomic analyses have suggested numerous signatures for the diagnoses of acute rejection, delayed-graft function or interstitial fibrosis. Nevertheless, the translation and validation of exploratory findings and their implementation into standard clinical practice remain challenging. This requires dedicated prospective interventional trials demonstrating that the use of these biomarkers avoids invasive procedures and improves patient or transplant outcomes.In the last decade, a plenitude of potential molecular peripheral blood biomarkers has been developed. In assessing the utility of these markers for clinical practice, it is important to evaluate their diagnostic performance in different clinical scenarios. The higher probability of diagnosing rejection in indication compared to protocol biopsies illustrates that kidney functional parameters (estimated glomerular filtration rate evolution, proteinuria) are inherently already non-invasive biomarkers for rejection, with evident clinical utility. However, by definition, graft functional assessment will miss subclinical rejection. In this paper, we review how some of the most promising peripheral blood molecular biomarkers, like blood transcriptomic markers and donor-derived cell-free DNA measurement, perform in relation to graft functional evaluation. Since the definition of graft dysfunction is relatively arbitrary, we propose using a standardized clinical model for non-invasive diagnosis of allograft rejection, as benchmark and for integration with novel molecular biomarkers.In France, long nocturnal dialyses, eight hours three-times a week, are sparsely proposed. However, numerous studies reported that this specific type of dialysis is associated to better blood pressure control, better cardiac remodeling, better mineral and nutritional balance as well as better life quality and survival rate. MATERIAL AND METHODS In this study, we aimed at quantifying the benefits, risks and obstacles of developing night dialysis and at describing the results of a program that took place in Rennes from 2002 to 2019. Data were collected between 2008 and 2014 for eighteen case-patients and were compared to thirty-six controls that underwent conventional dialysis. Patients were paired according sex, age and year of dialysis start. RESULTS The median age for dialysis start was 47.5 years [27-60] with a male prevalence (5/1). After six months, a significant difference was reported for postdialytic, systolic and diastolic pressure (respectively 126±15 vs 139±21 [P=0.04] and 72±9 vs 81±14 [P=0.02]) despite an antihypertensive reduction ranging from 2.4±1.4 to 1.3±0.9 per day at six months and 0.7±0.9 at one year (P=0.02). An increase of nPCR was evidenced at 6 and 9 months (P=0.02). At the end of the study, the phosphate level was maintained for both cohorts at the expense of an increased consumption of phosphate binder for the long nocturnal dialysis group (P=0.025). As a whole, 61% of the patients that pursued long night dialysis maintained a professional activity compared to only 30% for the controls (P=0.04). This highlights the advantages of night dialysis for maintaining employment but also the bias that represents the employment status in observational study on this specific topic.A number of studies have compared relative survival for home hemodialysis patients (including longer hours/more frequent schedules) and other forms of renal replacement therapy. While informative, many of these studies have been limited by issues pertaining to their observational design including selection bias and residual confounding. Furthermore the few randomized controlled trials that have been conducted have been underpowered to detect a survival difference. Finally, in the face of a growing recognition of the value of patient-important outcomes beyond survival, the focus of comparisons between dialysis modalities may be changing. see more In this review, we will discuss the determinants of survival for patients receiving home hemodialysis and address the various studies that have compared relative survival for differing home hemodialysis schedules to each of in-center hemodialysis, peritoneal dialysis and transplantation. We will conclude this review by discussing whether there is an ongoing role for survival analyses in home hemodialysis.There has been a resurgence in home haemodialysis over the last decade and interest in its implementation in gaining momentum with advances in technology and healthcare policy initiatives. Both increasing haemodialysis frequency and treatment time have several potential benefits in improving dialysis efficiency and are ideally placed in the home setting. The paper describes the rationale, current status, controversies, challenges and future avenues for home haemodialysis.The development of new high-throughput technologies in genomics and then in transcriptomics has modified clinical approach in nephrology. At the interface between high-throughput technologies (microarray, new generation sequencing «NGS») and few mRNA analysis (reverse transcriptase quantitative PCR [RT-qPCR]), the nCounter® of NanoString® offers a new and complementary approach. Capable of analyzing formalin-fixed paraffin-embedded samples, this technology is a credible candidate for implanting transcriptomics in clinical routine.The usage of artificial intelligence to evaluate histological images was recently explored in many different areas of pathology. Studies focusing on nephropathology demonstrated that algorithms could be trained to identify various structures of the kidney, like glomeruli and interstitium, as well as performing a classification task just as good as highly experienced pathologists. It is conceivable that further development of digitalized pathology in combination with all opportunities that artificial intelligence and machine learning have to offer, will rapidly change the work of the clinical pathologist in a substantial way.Chronic interstitial nephritis in agricultural communities is a devastating kidney disease with a globally increasing prevalence. Its cause is unknown. Two predominant etiologies are hypothesised recurrent episodes of dehydration and exposure to environmental toxins, such as agrochemicals and metals. In this review, we summarise arguments on 1) why heat stress/dehydration is an unlikely cause of this disease and 2) why chronic interstitial nephritis in agricultural communities is to be considered a toxin-induced nephropathy. Mechanistically, we provide arguments for a putative role of pesticides on the one hand, and the calcineurin pathway on the other hand, both of which require further investigation. Finally, we summarise several important perspectives for research on chronic interstitial nephritis in agricultural communities.Nephrology was a relatively poorly known specialty in sub-Saharan Africa until the early 1980s, because of low awareness and lack of access to diagnosis and renal replacement therapies. Nephrology has seen progress on the continent despite an unfavourable economic and geopolitical environment. With a prevalence of fewer than five nephrologists per million inhabitants, the training of nephrologists, now carried out on the continent, allowed to have more than 200 specialists trained in the last decade in French-speaking sub-Saharan Africa. Clinical and basic research is developing with quality work published from the continent in major international journals. The population receiving haemodialysis remains small, between 0 and 200 per million inhabitants. Kidney transplantation, with a prevalence between 0 and 5 per million inhabitants, is only well structured in South Africa. In this context of scarce resources, a strategy based on the prevention of non-communicable diseases in general, and chronic kidney disease in particular, should be prioritised.Mass disasters, particularly earthquakes, cause many medical problems, including kidney problems, but an organized approach to cope with them was initiated only at the end of previous century, subsequent to the Armenian Spitak earthquake in 1988. Originally, interventions were focused on acute kidney injury (AKI) following crush injury and rhabdomyolysis in victims who had been trapped under the debris of collapsed buildings. However, similar problems were also registered in the context of other catastrophic events, especially man-made disasters like wars and torture. Other kidney-related problems, such as the preservation of treatment continuity in chronic kidney disease (CKD), especially in maintenance dialysis patients, deserved attention as well. Specific therapeutic principles apply to disaster-related kidney problems and these may differ from usual day-to-day clinical practice. Those approaches have been formulated in global and specific country-related guidelines and recommendations. It is clear that a well-conceived and organized management of kidney diseases in disasters benefits outcomes.
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