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Introduction: Etelcalcetide is an i.v. calcimimetic agent, effectively reducing parathyroid hormone levels in patients on maintenance hemodialysis (HD). The clinical impact of discontinuing etelcalcetide at the time of kidney transplantation is unknown., Methods: We retrospectively reviewed all patients on HD meeting predefined criteria who received a kidney transplant at our institution between January 1, 2015, and December 12, 2022. The incidence of parathyroidectomy and the evolution of calcium, phosphate, and intact parathyroid hormone (iPTH) levels after transplantation was analyzed according to the type of calcimimetic treatment before transplantation (cinacalcet vs. etelcalcetide vs. none)., Results: Overall, 372 patients (aged 53 years; interquartile range [IQR]: 42-62 years) were included. At the time of transplantation, 35, 75, and 262 patients were under etelcalcetide, cinacalcet, or no calcimimetic, respectively. After 1064 (IQR: 367-1658) days, the incidences of parathyroidectomy in the etelcalcetide, cinacalcet, no calcimimetic groups were 29%, 12%, and 1%, respectively ( P  < 0.001). Etelcalcetide was associated with an increased incidence of parathyroidectomy after adjustment for age, sex, and HD vintage (hazard ratio [HR]: 97.0, 95% confidence interval [CI]: 19.1-493.9, P  < 0.001). The incidence of parathyroidectomy was related to etelcalcetide dosage (6/11 [54.6%] in patients with ≥ 10 mg vs. 4/24 [16.7%] in patients with < 10 mg, P  = 0.02). Moreover, peak calcium levels were higher ( P  < 0.001) and parathyroidectomy was performed earlier (median 80 vs. 480 days, P  < 0.001) in the etelcalcetide compared with the cinacalcet group. Long-term graft function, graft loss, and mortality were similar., Conclusion: Etelcalcetide use during maintenance HD is associated with an increased incidence of early parathyroidectomy after transplantation compared to cinacalcet or no calcimimetic., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Catastrophic antiphospholipid syndrome (CAPS) is a rare and life-threatening condition characterized by the persistence of antiphospholipid antibodies and occurrence of multiple vascular occlusive events. CAPS currently remains a diagnostic challenge and requires urgent treatment. The diagnosis of CAPS is made difficult by classification criteria used as diagnostic criteria in clinical practice, knowledge derived from retrospective data and case reports, confounding clinical and biological features, and its rapid onset and mortality. The absence of prospective studies of CAPS limits the strength of evidence for guideline treatment protocols. This comprehensive review summarizes the current understanding of the disease, and discusses how the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria impact the definition and therapeutic management of CAPS, which is considered the most severe form of APS. The correct integration of 2023 ACR/EULAR APS classification criteria is poised to facilitate CAPS diagnosis, particularly in critical situations, offering a promising avenue for improved outcomes.

Background and Objective: Coronavirus Disease 2019 (COVID-19) has been associated with the onset of autoimmune conditions, but whether this relationship is causal remains unknown, partly because robust evidence based on the detection of autoantibodies is lacking. This study explored the potential impact of COVID-19 pandemic on the temporal trends of autoimmunity., Methods: Retrospective analysis of all consecutive autoimmune tests performed at one central laboratory at a University hospital, operating services for 18 other hospitals and clinical laboratories in Belgium, from January 01, 2015 to May 31, 2022. Longitudinal changes in the positivity rates of autoimmunity tests were analyzed, i.e. before and after the onset of the COVID-19 pandemic (March 11, 2020). The tests notably included the detection of autoantibodies associated with type 1 diabetes, thyroid diseases, connective tissue diseases, antiphospholipid syndrome, vasculitis and other organ-specific conditions. Kendall rank correlation test was applied to assess temporal trends., Results: Over a period of 89 months, a total of 301,720 consecutive tests for 24 different autoantibodies among 87,674 unique patients were performed (87% adults, 68% women, mean age 44 ± 20 years). Overall, 52,862 (18%) tests returned positive, with positivity rates for each test ranging between 1% and 46%. No increase in the positivity rate of autoimmunity tests was observed after the start of the pandemic., Conclusion: The onset of the COVID-19 pandemic was not associated with increased positivity rates of a large panel of autoimmune tests. Whether the higher incidence of autoimmune disorders associated with COVID-19 reflects detection bias or reverse causality, or is linked to seronegative autoimmune disorders requires further investigation., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: E. Van Regemorter reports speaker honoraria for 10.13039/100004702Baxter and 10.13039/100004325AstraZeneca and travel grants from 10.13039/501100006484Vifor Pharma, Astellas and Pharmacosmos; all outside the submitted work. J. Morelle reports consultancy for Alexion Pharmaceuticals, AstraZeneca, Bayer, GlaxoSmithKline, and Sanofi-Genzyme; research funding from 10.13039/100006396Alexion Pharmaceuticals, 10.13039/100004325AstraZeneca, and 10.13039/100007658Baxter Healthcare; advisory or leadership roles for Alexion Pharmaceuticals, AstraZeneca, Bayer, Sanofi-Genzyme, and Versantis; speaker honoraria for 10.13039/100004325AstraZeneca, 10.13039/100007658Baxter Healthcare, and 10.13039/100015699Fresenius Medical Care; funding from the 10.13039/501100002661National Fund for Scientific Research (FRS-FNRS, Brussels, Belgium), the Association pour l’Information et la Recherche sur les Maladies Rénales Génétiques (AIRG, Brussels, Belgium), and the 10.13039/501100011068Saint-Luc Foundation (Brussels, Belgium); and travel grants from 10.13039/100013995Sanofi-Genzyme and 10.13039/501100006484Vifor Pharma; all outside the submitted work. All other authors do not report any conflict of interest., (© 2023 The Authors.)

Background: The identification of complement defects as major drivers of primary atypical hemolytic uremic syndrome (HUS) has transformed the landscape of thrombotic microangiopathies (TMAs), leading to the development of targeted therapies and better patient outcomes. By contrast, little is known about the presentation, genetics, and outcomes of TMA associated with specific diseases or conditions, also referred to as secondary TMA., Methods: In this study, we assessed the relative incidence, clinical and genetic spectra, and long-term outcomes of secondary TMA versus other TMAs in consecutive patients hospitalized with a first episode of TMA from 2009 to 2019 at two European reference centers., Results: During the study period, 336 patients were hospitalized with a first episode of TMA. Etiologies included atypical HUS in 49 patients (15%), thrombotic thrombocytopenic purpura (TTP) in 29 (9%), shigatoxin-associated HUS in 70 (21%), and secondary TMA in 188 (56%). The main causes of secondary TMA were hematopoietic stem-cell transplantation ( n =56, 30%), solid-organ transplantation ( n =44, 23%), and malignant hypertension ( n =25, 13%). Rare variants in complement genes were identified in 32 of 49 patients (65%) with atypical HUS and eight of 64 patients (13%) with secondary TMA; pathogenic or likely pathogenic variants were found in 24 of 49 (49%) and two of 64 (3%) of them, respectively ( P < 0.001). After a median follow-up of 1157 days, death or kidney failure occurred in 14 (29%), eight (28%), five (7%), and 121 (64%) patients with atypical HUS, TTP, shigatoxin-associated HUS, and secondary TMA, respectively. Unadjusted and adjusted Cox regressions showed that patients with secondary TMA had the highest risk of death or kidney failure (unadjusted hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.85 to 6.07; P < 0.001; adjusted HR, 4.11; 95% CI, 2.00 to 8.46; P < 0.001; considering atypical HUS as reference)., Conclusions: Secondary TMAs represent the main cause of TMA and are independently associated with a high risk of death and progression to kidney failure., (Copyright © 2023 by the American Society of Nephrology.)

Chronic kidney disease (CKD) is a major public health problem, increasing the risk of cardiovascular events and death and potentially leading to kidney failure. Novel drugs that slow the progression of this non-communicable disease are therefore urgently needed. Initially developed as glucose-lowering drugs, inhibitors of the sodium-glucose cotransporter 2 (SGLT2) drastically reduce the overall mortality and cardiovascular events and slow the progression of CKD. Kidney protection conferred by SGLT2 inhibitors is independent from the presence of diabetes, observed on top of renin-angiotensin system inhibition and consistent across a wide range of categories of glomerular filtration rate and albuminuria. The mechanisms through which SGLT2 inhibitors improve kidney outcomes are likely multifactorial. Inhibition of SGLT2 in the kidney proximal tubule results in natriuresis and glucosuria, with beneficial effects on metabolic control, blood pressure and body weight. In addition, SGLT2 inhibitors also improve intraglomerular hemodynamics, podocyte integrity, cell metabolism, and erythropoiesis and reduce hypoxia, oxidative stress, sympathetic nervous activity, inflammation and fibrosis. The major impact of SGLT2 inhibitors on kidney outcomes, along with the excellent safety profile of this new class of drugs, open novel avenues for the treatment of CKD in patients with and without diabetes.

SARS-CoV-2 causes major disturbances in serum metabolite levels, associated with severity of the immune response. Despite the numerous advantages of urine for biomarker discovery, the potential association between urine metabolites and disease severity has not been investigated in coronavirus disease 2019 (COVID-19). In a proof-of-concept study, we performed quantitative urine metabolomics in patients hospitalized with COVID-19 and controls using LC-MS/MS. We assessed whether metabolites alterations were associated with COVID-19, disease severity, and inflammation. The study included 56 patients hospitalized with COVID-19 (26 non-critical and 30 critical disease); 16 healthy controls; and 3 controls with proximal tubule dysfunction unrelated to SARS-CoV-2. Metabolomic profiling revealed a major urinary increase of tryptophan metabolites kynurenine (P < 0.001), 3-hydroxykynurenine (P < 0.001) and 3-hydroxyanthranilate (P < 0.001) in SARS-CoV-2 infected patients. Urine levels of kynurenines were associated with disease severity and systemic inflammation (kynurenine, r 0.43, P = 0.001; 3-hydroxykynurenine, r 0.44, P < 0.001). Increased urinary levels of neutral amino acids and imino acid proline were also common in COVID-19, suggesting specific transport defects. Urine metabolomics identified major alterations in the tryptophan-kynurenine pathway, consistent with changes in host metabolism during SARS-CoV-2 infection. The association between increased urinary levels of kynurenines, inflammation and COVID-19 severity supports further evaluation of these easily available biomarkers., (© 2022. The Author(s).)

Background: Several cases of idiopathic nephrotic syndrome (INS) relapse following the administration of coronavirus disease 2019 (COVID-19) vaccines have recently been reported, raising questions about the potential relationship between the immune response to COVID-19 vaccination and INS pathogenesis., Methods: We performed a retrospective multicentre survey describing the clinical and biological characteristics of patients presenting a relapse of INS after COVID-19 vaccination, with an assessment of outcome under treatment., Results: We identified 25 patients (16 men and 9 women) presenting a relapse within 1 month of a COVID-19 vaccine injection. The glomerular disease was of childhood onset in half of the patients and most patients (21/25) had received at least one immunosuppressive drug in addition to steroids for frequently relapsing or steroid-dependent nephrotic syndrome (NS). All patients were in a stable condition at the time of injection and 11 had no specific treatment. In five patients, the last relapse was reported >5 years before vaccine injection. The Pfizer-BioNTech (BNT162b2) vaccine was used in 80% of the patients. In 18 cases, INS relapse occurred after the first injection, a mean of 17.5 days after vaccination. A second injection was nevertheless administered in 14 of these patients. Five relapses occurred after administration of the second dose and two relapses after the administration of the third dose. All but one of the patients received steroids as first-line treatment, with an additional immunosuppressive agent in nine cases. During follow-up, complete remission was achieved in 21 patients, within 1 month in 17 cases. Only one patient had not achieved at least partial remission after 3 months of follow-up., Conclusions: This case series suggests that, in rare patients, COVID-19 vaccination may trigger INS relapse that is generally easy to control. These findings should encourage physicians to persuade their patients to complete the COVID-19 vaccination schedule., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Sepsis capillary leak syndrome (SCLS) is an independent prognostic factor for poor sepsis outcome. We previously demonstrated that α1AMP-activated protein kinase (α1AMPK) prevents sepsis-induced vascular hyperpermeability by mechanisms involving VE-cadherin (VE-Cad) stabilization and activation of p38 mitogen activated protein kinase/heat shock protein of 27 kDa (p38MAPK/HSP27) pathway. Canagliflozin, a sodium-glucose co-transporter 2 inhibitor, has recently been proven to activate AMPK in endothelial cells. Therefore, we hypothesized that canagliflozin could be of therapeutic potential in patients suffering from SCLS. We herein report that canagliflozin, used at clinically relevant concentrations, counteracts lipopolysaccharide-induced vascular hyperpermeability and albumin leakage in wild-type, but not in endothelial-specific α1AMPK-knockout mice. In vitro, canagliflozin was demonstrated to activate α1AMPK/p38MAPK/HSP27 pathway and to preserve VE-Cad's integrity in human endothelial cells exposed to human septic plasma. In conclusion, our data demonstrate that canagliflozin protects against SCLS via an α1AMPK-dependent pathway, and lead us to consider novel therapeutic perspectives for this drug in SCLS.

Background: The severity of coronavirus disease 2019 (COVID-19) is highly variable between individuals, ranging from asymptomatic infection to critical disease with acute respiratory distress syndrome requiring mechanical ventilation. Such variability stresses the need for novel biomarkers associated with disease outcome. As SARS-CoV-2 infection causes a kidney proximal tubule dysfunction with urinary loss of uric acid, we hypothesized that low serum levels of uric acid (hypouricemia) may be associated with severity and outcome of COVID-19., Methods: In a retrospective study using two independent cohorts, we investigated and validated the prevalence, kinetics and clinical correlates of hypouricemia among patients hospitalized with COVID-19 to a large academic hospital in Brussels, Belgium. Survival analyses using Cox regression and a competing risk approach assessed the time to mechanical ventilation and/or death. Confocal microscopy assessed the expression of urate transporter URAT1 in kidney proximal tubule cells from patients who died from COVID-19., Results: The discovery and validation cohorts included 192 and 325 patients hospitalized with COVID-19, respectively. Out of the 517 patients, 274 (53%) had severe and 92 (18%) critical COVID-19. In both cohorts, the prevalence of hypouricemia increased from 6% upon admission to 20% within the first days of hospitalization for COVID-19, contrasting with a very rare occurrence (< 1%) before hospitalization for COVID-19. During a median (interquartile range) follow-up of 148 days (50-168), 61 (12%) patients required mechanical ventilation and 93 (18%) died. In both cohorts considered separately and in pooled analyses, low serum levels of uric acid were strongly associated with disease severity (linear trend, P < 0.001) and with progression to death and respiratory failure requiring mechanical ventilation in Cox (adjusted hazard ratio 5.3, 95% confidence interval 3.6-7.8, P < 0.001) or competing risks (adjusted hazard ratio 20.8, 95% confidence interval 10.4-41.4, P < 0.001) models. At the structural level, kidneys from patients with COVID-19 showed a major reduction in urate transporter URAT1 expression in the brush border of proximal tubules., Conclusions: Among patients with COVID-19 requiring hospitalization, low serum levels of uric acid are common and associate with disease severity and with progression to respiratory failure requiring invasive mechanical ventilation.

Background: Membranous nephropathy (MN) results from deposition of antigen-antibody complexes along the glomerular basement membrane (GBM). PLA2R, THSD7A, NELL1, and SEMA3B account for 80%-90% of target antigens in MN., Methods: We performed laser microdissection and mass spectrometry (MS/MS) in kidney biopsies from 135 individuals with PLA2R-negative MN, and used immunohistochemistry/immunofluorescence and confocal microscopy to confirm the MS/MS finding, detect additional cases, and localize the novel protein. We also performed MS/MS and immunohistochemistry on 116 controls and used immunofluorescence microscopy to screen biopsy samples from two validation cohorts. Western blot and elution studies were performed to detect antibodies in serum and biopsy tissue., Results: MS/MS studies detected a unique protein, protocadherin 7 (PCDH7), in glomeruli of ten (5.7%) PLA2R-negative MN cases, which also were negative for PLA2R, THSD7A, EXT1/EXT2, NELL1, and SEMA3B. Spectral counts ranged from six to 24 (average 13.2 [SD 6.6]). MS/MS did not detect PCDH7 in controls (which included 28 PLA2R-positive cases). In all ten PCDH7-positive cases, immunohistochemistry showed bright granular staining along the GBM, which was absent in the remaining cases of PLA2R-negative MN and control cases. Four of 69 (5.8%) cases in the validation cohorts (all of which were negative for PLA2R, THSD7A, EXT1, NELL1, and SEMA3B) were PCDH7-positive MN. Kidney biopsy showed minimal complement deposition in 12 of the 14 PCDH7-associated cases. Confocal microscopy showed colocalization of PCDH7 and IgG along the GBM. Western blot analysis using sera from six patients showed antibodies to nonreduced PCDH7. Elution of IgG from frozen tissue of PCDH7-associated MN showed reactivity against PCDH7., Conclusions: MN associated with the protocadherin PCDH7 appears to be a distinct, previously unidentified type of MN., (Copyright © 2021 by the American Society of Nephrology.)

Introduction: The syndromes of thrombotic microangiopathy (TMA) are diverse and represent severe endothelial damage caused by various mechanisms. The complement system plays a major role in a subset of patients with TMA, and its recognition is of clinical importance because it guides choice and duration of treatment., Methods: We studied a well-defined cohort of patients with TMA and hypothesized that assessment of serum-induced ex   vivo C5b9 formation on the endothelium and screening for rare variants in complement genes can better categorize TMA., Results: Massive ex vivo C5b9 formation was found in all patients with primary atypical hemolytic uremic syndrome ( n / N  = 11/11) and in 59% of patients with TMA and coexisting conditions ( n / N  = 30/51). Massive ex vivo C5b9 formation was associated with rare genetic variants (45% [ n / N  = 20/44] vs. 0% [ n / N  = 0/21] patients with normal ex vivo C5b9 formation; P  < 0.001). Massive ex vivo C5b9 formation was associated with favorable renal response to therapeutic complement inhibition in patients with TMA and coexisting conditions (86% [ n / N  = 12/14] vs. 31% [ n / N  = 5/16] of untreated patients; P  < 0.001), indicating complement-mediated TMA rather than secondary disease. Among treated patients, the odds ratio for 1-year kidney survival was 12.0 (95% confidence interval 1.2-115.4). TMA recurrence was linked to rare genetic variants in all cases. Patients with normal ex vivo C5b9 formation had an acute, nonrelapsing form of TMA., Conclusions: Ex vivo C5b9 formation and genetic testing appears to categorize TMAs into different groups because it identifies complement as a driving factor of disease, with potential therapeutic and prognostic implications., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Background : Pneumocystis jirovecii associated pneumonia is a potentially life-threatening opportunistic infection, occurring most frequently in the first year after renal transplantation, and may be associated with hypercalcemia. Clinical presentation :We report the case of a renal transplant recipient presenting with Pneumocystis jirovecii associated pneumonia and hypercalcemia due to ectopic production of 1,25-dihydroxyvitamin D, 6 years after renal transplantation. Calcemia and 1-25 hydroxyvitamin D levels normalized after our patient was treated by trimethoprim-sulfamethoxazole. Discussion : We review similar cases to delineate the clinical and biological profile of patients with Pneumocystis jirovecii pneumonia associated hypercalcemia. Conclusion :Physicians should evoke this diagnosis in renal transplant recipients presenting with pulmonary infection associated with hypercalcemia.

Current understanding of fibrosis remains incomplete despite the increasing burden of related diseases. Preclinical models are used to dissect the pathogenesis and dynamics of fibrosis, and to evaluate anti-fibrotic therapies. These studies require objective and accurate measurements of fibrosis. Existing histological quantification methods are operator-dependent, organ-specific, and/or need advanced equipment. Therefore, we developed a robust, minimally operator-dependent, and tissue-transposable digital method for fibrosis quantification. The proposed method involves a novel algorithm for more specific and more sensitive detection of collagen fibers stained by picrosirius red (PSR), a computer-assisted segmentation of histological structures, and a new automated morphological classification of fibers according to their compactness. The new algorithm proved more accurate than classical filtering using principal color component (red-green-blue; RGB) for PSR detection. We applied this new method on established mouse models of liver, lung, and kidney fibrosis and demonstrated its validity by evidencing topological collagen accumulation in relevant histological compartments. Our data also showed an overall accumulation of compact fibers concomitant with worsening fibrosis and evidenced topological changes in fiber compactness proper to each model. In conclusion, we describe here a robust digital method for fibrosis analysis allowing accurate quantification, pattern recognition, and multi-organ comparisons useful to understand fibrosis dynamics.

Coronavirus disease 2019 (COVID-19) is commonly associated with kidney damage, and the angiotensin converting enzyme 2 (ACE2) receptor for SARS-CoV-2 is highly expressed in the proximal tubule cells. Whether patients with COVID-19 present specific manifestations of proximal tubule dysfunction remains unknown. To test this, we examined a cohort of 49 patients requiring hospitalization in a large academic hospital in Brussels, Belgium. There was evidence of proximal tubule dysfunction in a subset of patients with COVID-19, as attested by low-molecular-weight proteinuria (70-80%), neutral aminoaciduria (46%), and defective handling of uric acid (46%) or phosphate (19%). None of the patients had normoglycemic glucosuria. Proximal tubule dysfunction was independent of pre-existing comorbidities, glomerular proteinuria, nephrotoxic medications or viral load. At the structural level, kidneys from patients with COVID-19 showed prominent tubular injury, including in the initial part of the proximal tubule, with brush border loss, acute tubular necrosis, intraluminal debris, and a marked decrease in the expression of megalin in the brush border. Transmission electron microscopy identified particles resembling coronaviruses in vacuoles or cisternae of the endoplasmic reticulum in proximal tubule cells. Among features of proximal tubule dysfunction, hypouricemia with inappropriate uricosuria was independently associated with disease severity and with a significant increase in the risk of respiratory failure requiring invasive mechanical ventilation using Cox (adjusted hazard ratio 6.2, 95% CI 1.9-20.1) or competing risks (adjusted sub-distribution hazard ratio 12.1, 95% CI 2.7-55.4) survival models. Thus, our data establish that SARS-CoV-2 causes specific manifestations of proximal tubule dysfunction and provide novel insights into COVID-19 severity and outcome., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: The osmotic conductance to glucose (OCG) is a crucial determinant of ultrafiltration (UF) in peritoneal dialysis (PD) patients and can be used to monitor membrane integrity in patients on long-term PD. It has been proposed that OCG can be assessed based on drained volumes in 2 consecutive 1-hour glucose dwells, usually 1.5% and 4.25% glucose, in a so-called double mini-peritoneal equilibration test (dm-PET). However, recent data indicated that the dm-PET provides a poor estimate of OCG unless the residual volume (RV) is taken into account. We introduce an easy, robust, and accurate method to measure OCG and compare it with conventional methods., Methods: In a prospective cohort of 21 PD patients, a modified version of the dm-PET was performed, along with the determination of RV before, between, and after dwells. Based on computer simulations derived from the 3-pore model (TPM) for membrane permeability, we developed and validated a novel single-dwell method to estimate OCG. We next validated the equation in an independent cohort consisting of 32 PD patients., Results: Single-dwell OCG correlated more closely with actual UF ( r  = 0.94 vs. r = 0.07 for conventional dm-PET), sodium sieving, and free water transport (FWT) compared with other methods. These findings were replicated in the validation cohort in which OCG calculated using the single-dwell method closely correlated with parameters of osmotic water transport, even when RV was not taken into account, using only drained volumes., Conclusion: We propose a novel, easy, and robust single-dwell method to determine OCG in individual patients and to monitor membrane integrity over time on PD., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Autosomal dominant tubulointerstitial kidney disease (ADTKD) is an increasingly recognized cause of end-stage kidney disease, primarily due to mutations in UMOD and MUC1. The lack of clinical recognition and the small size of cohorts have slowed the understanding of disease ontology and development of diagnostic algorithms. We analyzed two registries from Europe and the United States to define genetic and clinical characteristics of ADTKD-UMOD and ADTKD-MUC1 and develop a practical score to guide genetic testing. Our study encompassed 726 patients from 585 families with a presumptive diagnosis of ADTKD along with clinical, biochemical, genetic and radiologic data. Collectively, 106 different UMOD mutations were detected in 216/562 (38.4%) of families with ADTKD (303 patients), and 4 different MUC1 mutations in 72/205 (35.1%) of the families that are UMOD-negative (83 patients). The median kidney survival was significantly shorter in patients with ADTKD-MUC1 compared to ADTKD-UMOD (46 vs. 54 years, respectively), whereas the median gout-free survival was dramatically reduced in patients with ADTKD-UMOD compared to ADTKD-MUC1 (30 vs. 67 years, respectively). In contrast to patients with ADTKD-UMOD, patients with ADTKD-MUC1 had normal urinary excretion of uromodulin and distribution of uromodulin in tubular cells. A diagnostic algorithm based on a simple score coupled with urinary uromodulin measurements separated patients with ADTKD-UMOD from those with ADTKD-MUC1 with a sensitivity of 94.1%, a specificity of 74.3% and a positive predictive value of 84.2% for a UMOD mutation. Thus, ADTKD-UMOD is more frequently diagnosed than ADTKD-MUC1, ADTKD subtypes present with distinct clinical features, and a simple score coupled with urine uromodulin measurements may help prioritizing genetic testing., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Understanding the dynamics of microphytobenthos biomass and photosynthetic performances in intertidal ecosystems will help advance our understanding of how trophic networks function in order to optimize ecological management and restoration projects. The main objective of this study was to investigate microphytobenthic biomass and photosynthetic performances as a function of the sedimentary and environmental variabilities in the range of intertidal habitats in the downstream Seine estuary (Normandy, France). Our results highlight higher biomass associated with more stratified biofilms and better photosynthetic performances in areas characterized by a sand/mud mixture (40-60% of mud) compared to pure sand or pure mud environments. This type of sediment probably offers an efficient trade-off between the favorable characteristics of the two types of sediments (sand and mud) with respect to light penetration and nutrient accessibility. Moreover, the large quantities of exopolysaccharides produced in sand/mud mixtures emphasizes the functional role played by microphytobenthos in promoting sediment stability against erosion. This allows us to show that despite the strong increase in sand content of the downstream Seine estuary, intertidal flats are still productive since microphytobenthic biomass, photosynthetic performances and exopolysaccharides secretion are highest in sand-mud mixtures. This study also underlines the impact of ecosystem modifications due to human disturbance and climate change on the dynamics of key primary producers in estuaries., Competing Interests: The authors have declared that no competing interests exist.

Background: Oxalate nephropathy is a potentially underestimated cause of kidney failure characterized by massive deposition of calcium oxalate crystals in the renal parenchyma. The prevalence and modes of presentation of this entity are ill-defined., Methods: Here we report on the largest consecutive series of cases of adult oxalate nephropathy diagnosed on native kidney biopsies from January 2010 to December 2018 in the UCLouvain Kidney Disease Network., Results: We screened 2265 native kidney biopsies and identified 22 cases (1%) of oxalate nephropathy. Patients had a mean age at diagnosis of 61 years (±20) and presented either with acute on chronic kidney disease (CKD) (62%) or with acute kidney injury (AKI) (38%). Mean serum creatinine at biopsy was 8.0 ± 4.5 mg/dl. Kidney biopsies showed abundant calcium oxalate crystal deposits, associated with acute interstitial nephritis and tubular necrosis, and variable degrees of interstitial fibrosis and tubular atrophy. Chronic pancreatitis and gastric bypass were the most common causes of oxalate nephropathy (48%). During a mean follow-up of 29 months, half of the patients (52%) progressed to kidney failure, all within the month following diagnosis. Higher serum creatinine level at presentation and interstitial fibrosis and tubular atrophy score were associated with progression to kidney failure., Conclusion: Oxalate nephropathy is the cause of kidney disease in 1% of consecutive native kidney biopsies and typically presents as acute on CKD or AKI. The prognosis of the disease is poor, with a high rate of kidney failure within the first month after the diagnosis., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)