Is health-related quality of life trajectory associated with dialysis modality choice in advanced chronic kidney disease?

BACKGROUND: Patients with advanced chronic kidney disease have lower health-related quality of life (HRQOL) than the general population. There is uncertainty regarding patterns of HRQOL changes before dialysis initiation. This study aimed to characterise HRQOL trajectory and assess its potential association with intended dialysis modality. METHODS: This prospective single-centre cohort study followed adults with an estimated glomerular filtration rate ≤15 mL/min/1.73 m2 for one year. Patients were allocated into one of two groups based on their intended treatment modality, 'home dialysis' (peritoneal dialysis or home haemodialysis (HD)) and 'other' (in-centre HD or conservative care). Follow-up was for up to 1 year or earlier if initiated on kidney replacement therapy or died. Kidney Disease Quality of Life - Short Form (KDQOL-SF) was completed every 6 months. Predictors of changes in KDQOL-SF components were modelled using mixed effect multivariable linear regressions. RESULTS: One hundred and nine patients were included. At baseline, crude physical composite summary (PCS) (45 ± 10 vs. 39 ± 8) was higher in patients choosing home dialysis (n = 41), while mental composite summary (MCS) was similar in both groups. After adjustment, patients choosing home dialysis had an increase in MCS (B = 8.4 per year, p = 0.007) compared to those selecting in-centre HD/conservative care. This translates into an annual increase in MSC by 3 points for the 'home dialysis' group, compared to an annual decline by 5.4 points in the 'other' group. There was no difference in PCS trajectory through time. CONCLUSIONS: Patients choosing home dialysis had improved MCS over time compared to those not selecting home dialysis. More work is needed to determine how differences in processes of care and/or unmeasured patient characteristics modulate this association.

Identification of inflammatory biomarkers in IgA nephropathy using the NanoString technology: a validation study in Caucasians.

OBJECTIVE AND DESIGN: Immunoglobulin A nephropathy (IgAN) is a kidney disease characterized by the accumulation of IgA deposits in the glomeruli of the kidney, leading to inflammation and damage to the kidney. The inflammatory markers involved in IgAN remain to be defined. Gene expression analysis platforms, such as the NanoString nCounter system, are promising screening and diagnostic tools, especially in oncology. Still, their role as a diagnostic and prognostic tool in IgAN remains scarce. In this study, we aimed to validate the use of NanoString technology to identify potential inflammatory biomarkers involved in the progression of IgAN. SUBJECTS: A total of 30 patients with biopsy-proven IgAN and 7 cases of antineutrophil cytoplasmic antibody (ANCA)-associated pauci-immune glomerulonephritis were included for gene expression measurement. For the immunofluorescence validation experiments, a total of 6 IgAN patients and 3 controls were included. METHODS: Total RNA was extracted from formalin-fixed paraffin-embedded kidney biopsy specimens, and a customized 48-plex human gene CodeSet was used to study 29 genes implicated in different biological pathways. Comparisons in gene expression were made between IgAN and ANCA-associated pauci-immune glomerulonephritis patients to delineate an expression profile specific to IgAN. Gene expression was compared between patients with low and moderate risk of progression. Genes for which RNA expression was associated with disease progression were analyzed for protein expression by immunofluorescence and compared with controls. RESULTS: IgAN patients had a distinct gene expression profile with decreased expression in genes IL-6, INFG, and C1QB compared to ANCA patients. C3 and TNFRSF1B were identified as potential biomarkers for IgAN progression in patients early in their disease course. Protein expression for those 2 candidate genes was upregulated in IgAN patients compared to controls. Expression of genes implicated in fibrosis (PTEN, CASPASE 3, TGM2, TGFB1, IL2, and TNFRSF1B) was more pronounced in IgAN patients with severe fibrosis compared to those with none. CONCLUSIONS: Our findings validate our NanoString mRNA profiling by examining protein expression levels of two candidate genes, C3 and TNFRSF1B, in IgAN patients and controls. We also identified several upregulated mRNA transcripts implicated in the development of fibrosis that may be considered fibrotic markers within IgAN patients.

CureGN-Diabetes Study: Rationale, Design, and Methods of a Prospective Observational Study of Glomerular Disease Patients with Diabetes.

Glomerular diseases (GDs) represent the third leading cause of end-stage kidney disease (ESKD) in the US Diabetes was excluded from the CureGN Study, an NIH/NIDDK-sponsored observational cohort study of four leading primary GDs: IgA nephropathy (IgAN), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and minimal change disease (MCD). CureGN-Diabetes, an ancillary study to CureGN, seeks to understand how diabetes influences the diagnosis, treatment, and outcomes of GD. It is a multicenter, prospective cohort study, targeting an enrollment of 300 adults with prevalent type 1 or type 2 diabetes and MCD, FSGS, MN, or IgAN, with first kidney biopsy obtained within 5 years of enrollment in 80% (20% allowed if biopsy after 2010). CureGN and Transformative Research in DiabEtic NephropaThy (TRIDENT) provide comparator cohorts. Retrospective and prospective clinical data and patient-reported outcomes are obtained. Blood and urine specimens are collected at study visits annually. Kidney biopsy reports and digital images are obtained, and standardized pathologic evaluations performed. Light microscopy images are uploaded to the NIH pathology repository. Outcomes include relapse and remission rates, changes in proteinuria and estimated glomerular filtration rate, infections, cardiovascular events, malignancy, ESKD, and death. Multiple analytical approaches will be used leveraging the baseline and longitudinal data to compare disease presentation and progression across subgroups of interest. With 300 patients and an average of 3 years of follow-up, the study has 80% power to detect a HR of 1.4-1.8 for time to complete remission of proteinuria, a rate ratio for hospitalizations of 1.18-1.56 and difference in eGFR slope of 6.0-8.6 mL/min/year between two groups of 300 participants each. CureGN-Diabetes will enhance our understanding of diabetes as a modifying factor of the pathology and outcomes of GDs and support studies to identify disease mechanisms and improve patient outcomes in this understudied patient population.

Focused Jurisdictional Scan of Glomerulonephritis Medication Access in Canada: A Program Report.

Purpose of Program: Glomerulonephritis (GN) is a group of rare kidney diseases that is increasingly being managed with higher cost immunosuppressive (IS) agents in Canada. Ontario Health's Ontario Renal Network (ORN) oversees the management and delivery of GN services in the province. Stakeholder surveys previously conducted by ORN identified that both clinicians and patients do not perceive access to GN medications as comprehensive or timely. The program conducted a focused jurisdictional scan among 7 provinces to inform ORN initiatives to improve access to GN medications. Specifically, the program examined clinician experience with GN access, public drug coverage criteria, and timelines for public coverage for select IS agents (ie, tacrolimus, cyclosporine, mycophenolate mofetil [MMF], mycophenolate sodium, rituximab, and eculizumab) used to manage GN in adults who live in Canada. Methods: For the selected IS agents, a focused jurisdictional scan on medication access was conducted by ORN in 2018 and updated in July 2022. Information was obtained by searching the gray literature and/or credible online sources for public funding policies and eligibility criteria. Findings were supplemented by personal communications with provincial drug programs and consulting GN clinical experts from 7 provinces (ie, Alberta, British Columbia, Saskatchewan, Manitoba, Ontario, Nova Scotia, and Quebec). Key Findings: Clinicians from different provinces prescribe IS agents similarly for GN indications, despite distinctions in public drug funding policies. While patients can obtain public funding for many IS agents, for GN, most provinces rely on case-by-case review processes. In addition, provinces can vary in their funding criteria and which IS agents are listed on the public formulary. For IS agents that require prior authorization or case-by-case review, timelines vary by province with decisions taking a few days to weeks. British Columbia, with a GN-specific drug formulary, had the most integrated and efficient system for patients and prescribers. Limitations: This scan primarily relied on publicly available information for drug coverage criteria and clinician experience with access in their province. Since this scan was conducted, public drug coverage criteria and/or application processes may have changed. Implications: While patients in most provinces have similar needs and nephrologists similar prescribing patterns, gaps still exist for publicly funded GN medications. Interprovincial differences in the drugs funded, funding criteria, and application process may affect timely and equitable access to GN medications across Canada. Given the rarity of GN, a pan-Canadian funding approach may be warranted to improve the current state.

Objectif du programme: Les glomérulonéphrites (GN) sont un groupe de néphropathies rares qui sont de plus en plus fréquemment traitées avec les agents immunosuppresseurs (IS) coûteux au Canada. Le Réseau rénal de l'Ontario (ORN­Ontario Renal Network) de Santé Ontario supervise la gestion et la prestation des services liés à la GN dans cette province. Des enquêtes menées précédemment par l'ORN auprès des parties prenantes ont révélé que tant les cliniciens que les patients ne percevaient pas l'accès aux médicaments pour traiter la GN comme complet ou opportun. Le programme a mené une analyse ciblée des territoires de compétences dans sept provinces afin d'orienter les initiatives de l'ORN ayant pour objectif d'améliorer l'accès aux médicaments pour traiter la GN. Plus précisément, le programme a examiné l'expérience des cliniciens en matière d'accès aux médicaments pour traiter la GN, les critères d'admissibilité au régime public d'assurance-médicaments et les délais de couverture publique de certains agents IS (p. ex., tacrolimus, cyclosporine, mycophénolate mofétil [MMF], mycophénolate sodique, Rituximab, éculizumab) utilisés pour traiter la GN chez les adultes canadiens. Méthodologie: Une analyse ciblée des territoires de compétences quant à l'accès aux médicaments a été réalisée par l'ORN en 2018 et mise à jour en juillet 2022. L'information quant aux politiques de financement public et aux critères d'admissibilité a été obtenue en effectuant une recherche dans la littérature grise et des sources crédibles en ligne. Les résultats ont été complétés par des communications directes avec les régimes provinciaux d'assurance-médicaments et des experts cliniques de la GN de sept provinces (Alberta, Colombie-Britannique, Saskatchewan, Manitoba, Ontario, Nouvelle-Écosse et Québec). Principaux résultats: Les cliniciens des différentes provinces prescrivent des agents IS de façon similaire pour les indications liées à la GN, malgré des distinctions dans les politiques publiques de financement des médicaments. Bien que les patients bénéficient d'une couverture publique pour de nombreux agents IS, pour le traitement de la GN, la plupart des provinces s'appuient sur des processus d'examen au cas par cas. De plus, il peut exister des différences entre les provinces en ce qui concerne les critères de financement et les agents IS qui figurent sur leur formulaire public. Dans le cas des agents IS nécessitant une autorisation au préalable ou un examen au cas par cas, les délais varient d'une province à l'autre; les décisions pouvant prendre de quelques jours à quelques semaines. La Colombie-Britannique, qui dispose d'un formulaire de médicaments pour traiter spécifiquement la GN, présente le système le plus intégré et le plus efficace pour les patients et les prescripteurs. Limites: Cette analyse s'est principalement appuyée sur des renseignements accessibles au public en ce qui concerne les critères de couverture des médicaments et l'expérience des cliniciens en matière d'accès dans leur province. Les critères de couverture des médicaments publics et les processus de demande pourraient avoir changé depuis que cette analyse a été effectuée. Conclusion: Bien que les patients de la plupart des provinces aient des besoins similaires et que les néphrologues aient des habitudes de prescription similaires, des lacunes subsistent en ce qui concerne le financement public des médicaments pour traiter la GN. Les différences interprovinciales entre les médicaments financés, les critères de financement et le processus de demande peuvent avoir une incidence sur l'accès opportun et équitable aux médicaments pour traiter la GN à travers le Canada. Étant donné la rareté de cette maladie, une approche de financement pancanadienne pourrait être justifiée afin d'améliorer l'état actuel.

Kidney Biopsy Findings Among Allogenic Hematopoietic Stem Cell Transplant Recipients With Kidney Injury: A Case Series.

Rationale and Objective: The incidence of kidney disease is high in patients after allogeneic hematopoietic cell transplantation (aHCT). Although rarely performed, kidney biopsy may be useful to make a precise diagnosis because several mechanisms and risk factors can be involved, and to adjust the treatment accordingly. This case series aimed to report the spectrum of biopsy findings from patients with kidney injury after aHCT. Study Design: Single-center retrospective case series. Setting and Participants: All individuals who underwent a native kidney biopsy, among all adult patients who received aHCT in a tertiary hospital in Montreal (Canada) from January 1, 2010, to December 31, 2020, were identified, and the clinical data were extracted from their medical records. Results: A total of 17 patients were included. Indications for biopsy included acute kidney injury (n=6), chronic kidney disease (n=5), nephrotic syndrome (n=4), and subnephrotic proteinuria (n=2). Pathologic findings from the kidney biopsy were heterogenous: 10 patients showed evidence of thrombotic microangiopathy (TMA), 5 of acute tubular injury, and 4 of membranous nephropathy. Cases of acute interstitial nephritis, BK virus nephropathy, immune complex nephropathy, focal and segmental glomerulosclerosis, minimal change disease, and karyomegalic-like interstitial nephritis were also described. Limitations: There was no systematic kidney biopsy performed for all patients with kidney injury after aHCT. Only a small proportion of patients with kidney damage underwent biopsy, making the results less generalizable. Conclusions: Kidney biopsy is useful in patients with kidney disease after aHCT to make a precise diagnosis and tailor therapy accordingly. This series is one of the few published studies describing pathologic findings of biopsies performed after aHCT in the context of acute kidney injury and chronic kidney disease. TMA was widely present on biopsy even when there was no clinical suspicion of such a diagnosis, suggesting that the current clinical criteria for a diagnosis of TMA are not sensitive enough for kidney-limited TMA.

SMOC2 promotes an epithelial-mesenchymal transition and a pro-metastatic phenotype in epithelial cells of renal cell carcinoma origin.

Renal Cell Carcinoma (RCC) is the most common form of all renal cancer cases, and well-known for its highly aggressive metastatic behavior. SMOC2 is a recently described non-structural component of the extracellular matrix (ECM) that is highly expressed during tissue remodeling processes with emerging roles in cancers, yet its role in RCC remains elusive. Using gene expression profiles from patient samples, we identified SMOC2 as being significantly expressed in RCC tissue compared to normal renal tissue, which correlated with shorter RCC patient survival. Specifically, de novo protein synthesis of SMOC2 was shown to be much higher in the tubular epithelial cells of patients with biopsy-proven RCC. More importantly, we provide evidence of SMOC2 triggering kidney epithelial cells into an epithelial-to-mesenchymal transition (EMT), a phenotype known to promote metastasis. We found that SMOC2 induced mesenchymal-like morphology and activities in both RCC and non-RCC kidney epithelial cell lines. Mechanistically, treatment of RCC cell lines ACHN and 786-O with SMOC2 (recombinant and enforced expression) caused a significant increase in EMT-markers, -matrix production, -proliferation, and -migration, which were inhibited by targeting SMOC2 by siRNA. We further characterized SMOC2 activation of EMT to occur through the integrin ß3, FAK and paxillin pathway. The proliferation and metastatic potential of SMOC2 overexpressing ACHN and 786-O cell lines were validated in vivo by their significantly higher tumor growth in kidneys and systemic dissemination into other organs when compared to their respective controls. In principle, understanding the impact that SMOC2 has on EMT may lead to more evidence-based treatments and biomarkers for RCC metastasis.

Assisted Peritoneal Dialysis Implementation: A Pilot Program From a Large Dialysis Unit in Quebec.

Background: Kidney failure prevalence is increasing in older patients for whom dialysis initiation can be challenging. Assisted peritoneal dialysis (PD), where PD is performed with the help of a healthcare worker, can facilitate PD for frailer patients who may not be candidate otherwise. Objectives: This study aimed to assess the feasibility of implementing the first pilot assisted PD program in Quebec (Canada) and to evaluate the characteristics and outcomes of the PD cohort before and after assisted PD availability. Design: Observational retrospective cohort study. Setting and Population: All adult patients initiating PD between 2015 and 2020 in a single-center dialysis unit were included. Measurements: Incidence, characteristics, and outcomes of patients with PD were compared between (1) the "pre" (2015-2017) and the "post" assisted PD era (2018-2020) and (2) patients with assisted PD and independent PD in the more recent period. Methods: The primary outcome was peritonitis rate over the first year. Secondary outcomes included hospitalization, transfers to in-center hemodialysis (HD) and mortality. Results: Overall, 124 patients initiated PD with an annual incidence of 17 ± 3 patients during the "pre" and 24 ± 8 patients during the "post" assisted PD era (P = .18). First-year peritonitis rate was similar over the 2 eras. Years of PD initiation and use of assisted PD were not associated with risk peritonitis (over total follow-up) after adjustment. Adjusted hazard of transfer to HD or death was higher during the "post" era (hazard ratio [HR]: 2.77; 95% confidence interval [CI]: 1.42-5.58). Seventeen patients received assisted PD including 13 (18%) of the 72 patients initiated between 2018 and 2020. Patients with assisted PD were older than those with independent PD (72 [64-84] vs. 59 [47-67], P = .006) and received assistance for 0.8 (0.4-1.5) years. When comparing assisted and independent cohorts, there were no differences in crude rates of peritonitis or hospitalization. Limitations: Single-center study with small sample size. Conclusion: This study shows the feasibility of implementing an assisted PD program, with favorable overall outcomes including similar rates of peritonitis during the first year after PD initiation.

Contexte: La prévalence de l'insuffisance rénale augmente chez les patients plus âgés chez qui l'initiation de la dialyse peut être difficile. La dialyse péritonéale (DP) assistée, soit avec l'aide d'un professionnel de la santé, peut faciliter cette modalité chez les patients fragiles qui, autrement, ne seraient pas candidats. Objectifs de l'étude: Cette étude visait deux objectifs: 1) évaluer la faisabilité de la mise en œuvre du premier program pilote de DP assistée au Québec (Canada) et, 2) évaluer les caractéristiques et les résultats de la cohorte avant et après l'accès à la DP assistée. Conception: Étude de cohorte observationnelle rétrospective. Cadre et participants: Ont été inclus tous les patients adultes ayant initié une DP entre 2015 et 2020 dans l'unité de dialyse d'un center hospitalier. Mesures: L'incidence de la DP, ainsi que les caractéristiques et les résultats des patients sous DP ont été comparés entre [1] les patients « pré ¼ (2015-2017) et « post ¼ DP assistée (2018-2020) et entre [2] les patients sous DP assistée et sous DP autonome au cours de la période la plus récente. Méthodologie: Le principal critère d'évaluation était le taux de péritonite dans la première année. Les résultats secondaires comprenaient hospitalisation, les transferts à l'hémodialyse (HD) en centre et le taux de mortalité. Résultats: En tout, 124 patients ont amorcé un traitement de DP avec une incidence annuelle de 17 ± 3 patients au cours de la période « pré ¼ et de 24 ± 8 patients au cours de la période « post ¼ (p = 0,18). Le taux de péritonite dans la première année était semblable pour les deux périodes. Après ajustement, les années d'initiation et l'utilisation de la DP assistée n'étaient pas associées à un risque de péritonite accru (pour la période totale de suivi). Le risque ajusté de transfert à l'HD ou de décès était plus élevé durant la période « post ¼ (RR 2,77; IC 95 %: 1,42-5,58). Dix-sept patients ont reçu la DP assistée, dont 13 (18 %) des 72 patients initiés entre 2018 et 2020. Les patients sous DP assistée étaient plus âgés que ceux sous DP autonome (72 [64-84] ans c. 59 [47-67] ans; p = 0,006) et ont reçu de l'aide pendant 0,8 (0,4-1,5) an. Aucune différence n'a été observée dans les taux bruts de péritonite ou d'hospitalization lors de la comparaison des cohortes assistée et autonome. Limites: Étude menée dans un seul center, sur un faible échantillon de patients. Conclusion: Cette étude montre que la mise en œuvre d'un program de DP assistée est faisable et qu'elle donne de bons résultats, notamment des taux similaires de péritonite dans l'année suivant l'initiation de la DP.

Qualitative and Quantitative Dosage of the Anti M-Type Phospholipase A2 Receptor Autoantibody: One-Year Experience in Quebec's Reference Center.

BACKGROUND: Quantification of the M-type phospholipase A2 receptor antibodies (anti-PLA2R) is now an essential tool for diagnosis and management of primary membranous nephropathy (MN). Since October 2018, Hôpital Maisonneuve-Rosemont (HMR) has been designated as Quebec's reference center for serum anti-PLA2R antibody testing by the Institut National d'Excellence en Santé et Services Sociaux (INESSS), the regulatory body on drugs and tests usage in Quebec. OBJECTIVES: To describe the 2-step method of serum qualitative and quantitative anti-PLA2R antibody testing during its first year of use in Quebec and analyze its diagnostic value in the province's population. DESIGN: Retrospective cohort study. SETTING: Single-center academic teaching hospital in Quebec, Canada. PATIENTS: All patients who had a serum anti-PLA2R antibody test analyzed at HMR from October 1, 2018, to October 1, 2019, were included in the study. MEASUREMENTS: Serum anti-PLA2R antibodies were screened by indirect immunofluorescence tests. If results were positive or undetermined, it was followed by a quantitative enzyme-linked immunosorbent assay (ELISA) test. Both tests were based on a commercial kit developed by the same company. METHODS: We calculated sensitivity, specificity, predictive value, and likelihood ratio for both tests, using kidney biopsy findings performed at HMR as the gold standard. RESULTS: In Quebec, a total of 1690 tests were performed among 1025 patients during the study year. A small proportion of these patients (8%) were followed at HMR. Patients tested at HMR and in the rest of Quebec had similar characteristics. Test validity was only characterized for patients tested at HMR. Sensitivity and specificity were, respectively, 58% and 100% for the qualitative test, and 71% and 100% for the quantitative test. The combined net sensitivity was 42% and the net specificity 100%. The net positive and negative predictive value were 100% and 84% respectively, whereas the net negative likelihood ratio was 0.58. LIMITATIONS: As the detailed analysis was only possible in the small proportion of patients clinically followed at HMR, there is a possible selection bias. Another potential selection bias was the focus on patients who were selected to have a kidney biopsy, probably because of more severe disease, higher probability of glomerulonephritis, or lesser number of comorbidities. Given the retrospective nature of this study, there was no systematic kidney biopsy or serum PLA2R antibody testing performed. Finally, we were unable to provide detailed information on the timing between immunosuppressive therapy and anti-PLA2R results. CONCLUSIONS: Serum anti-PLA2R antibody testing was widely used in Quebec during its first year of availability. A 2-step approach, using a qualitative test first, followed by a quantitative test if the results are positive or undetermined, appears efficient to avoid useless quantitative testing in negative patients and to better characterize undetermined results on immunofluorescence. TRIAL REGISTRATION: Due to the retrospective nature of this study, no trial registration was performed.

CONTEXTE: La quantification des anticorps des récepteurs de la phospholipase A2 de type M (anti-PLA2R) est désormais un outil essentiel pour le diagnostic et la prise en charge de la glomérulonéphrite extra-membraneuse primaire (GEMp). Depuis octobre 2018, l'Hôpital Maisonneuve-Rosemont (HMR) a été désigné par l'Institut National d'Excellence en Santé et Services Sociaux (INESSS)­l'organisme règlementant l'usage des médicaments et des tests au Québec­comme le centre hospitalier de référence dans la province pour le dépistage des anticorps sériques anti-PLA2R. OBJECTIFS: Décrire la méthode en deux étapes du test qualitatif et quantitatif des anticorps anti-PLA2R sériques au cours de sa première année d'utilisation au Québec et évaluer sa valeur diagnostique dans la population de la province. TYPE D'ÉTUDE: Étude de cohorte rétrospective. CADRE: Un centre hospitalier universitaire du Québec (Canada). SUJETS: Ont été inclus tous les patients dont le test des anticorps sériques anti-PLA2R a été analysé à HMR entre le 1er octobre 2018 et le 1er octobre 2019. MESURES: Les anticorps sériques anti-PLA2R ont été détectés par immunofluorescence indirecte. Les résultats positifs ou indéterminés ont été suivis d'un test ELISA quantitatif. Les deux tests ont été réalisés à l'aide de trousses commerciales développées par la même entreprise. MÉTHODOLOGIE: Nous avons analysé la sensibilité, la spécificité, la valeur prédictive et le rapport de vraisemblance des deux tests avec comme référence des résultats de biopsie rénale obtenus à HMR. RÉSULTATS: Au Québec, au cours de l'année de l'étude, 1 690 tests ont été effectués sur 1 025 patients; une faible proportion de ces patients (8 %) étaient suivis à HMR. Les patients, qu'ils aient été testés à HMR et ailleurs au Québec, présentaient des caractéristiques semblables. La validité du test n'a été caractérisée que pour les patients testés à HMR. La sensibilité et la spécificité s'établissaient respectivement à 58 % et à 100 % pour le test qualitatif, et à 71 % et 100 % pour le test quantitatif. La sensibilité nette combinée était de 42 % et la spécificité nette, de 100 %. Les valeurs prédictives nettes, positive et négative, étaient respectivement de 100 % et de 84 %, alors que le ratio net de probabilité négative était de 0,58. LIMITES: L'étude présente un possible biais de sélection puisque l'analyse détaillée n'était possible que pour la faible proportion de patients suivis à HMR. L'accent mis sur les patients sélectionnés pour une biopsie rénale, probablement en raison d'une maladie plus grave, d'une probabilité plus élevée de glomérulonéphrite ou d'un moins grand nombre de comorbidités, constitue un autre possible biais de sélection. Aucune biopsie rénale ou test d'anticorps de PLA2R sérique systématique n'a été effectué puisque l'étude est rétrospective. Enfin, il n'a pas été possible de fournir des informations détaillées sur le temps écoulé entre le traitement immunosuppresseur et les résultats du test d'anticorps anti-PLA2R. CONCLUSION: Le test d'anticorps sériques anti-PLA2R a été largement utilisé au Québec au cours de sa première année de disponibilité. Une approche en deux étapes, constituée d'un test qualitatif suivi d'un test quantitatif si le résultat est positif ou indéterminé, semble efficace pour éviter de procéder inutilement à des tests quantitatifs chez les patients négatifs et pour caractériser plus précisément les résultats indéterminés par immunofluorescence. ENREGISTREMENT DE L'ESSAI: L'essai n'a pas été enregistré puisqu'il s'agit d'une étude rétrospective.

Minimal Change Disease With Severe Acute Kidney Injury Following the Oxford-AstraZeneca COVID-19 Vaccine: A Case Report.

We report a case of minimal change disease (MCD) with severe acute kidney injury (AKI) following the first injection of the ChAdOx1 nCoV-19 (AZD1222) vaccine from Oxford-AstraZeneca against coronavirus disease 2019 (COVID-19). A 71-year-old man with a history of dyslipidemia and a baseline serum creatinine of 0.7mg/dL presented with nephrotic syndrome, AKI, and severe hypertension 13 days after receiving the Oxford-AstraZeneca vaccine. Refractory hyperkalemia and hypervolemia with oligoanuria prompted initiation of hemodialysis. His serum albumin was 2.6g/dL and his urinary protein-creatinine ratio was 2,321mg/mmol. Given a high suspicion for rapidly progressive glomerulonephritis, empirical glucocorticoid treatment was initiated (3 methylprednisolone pulses followed by high-dose prednisone). A kidney biopsy showed MCD and acute tubular injury. Kidney function and proteinuria subsequently improved, and hemodialysis was discontinued 38 days after the start of therapy. This case describes de novo MCD after the Oxford-AstraZeneca vaccine. It adds to the few published case reports of MCD after the Pfizer-BioNTech COVID-19 vaccine. Further reports and studies will be needed to elucidate whether MCD is truly associated with COVID-19 vaccination.

Risk of hospitalization, technique failure, and death with increased training duration in 3-days-a-week home hemodialysis.

INTRODUCTION: Quality training is a core component of successful home hemodialysis (HHD) and training duration varies significantly between dialysis centers as well as at the patient level. This study aimed to assess the adverse outcomes associated with HHD training duration. METHODS: All HHD patients successfully trained in a single dialysis center between January 2005 and July 2017 were included. A multivariable multiple-events (Andersen-Gill) survival model was built to evaluate the association between training time and main adverse events, including hospitalizations, technique failure, and death on HHD. Potential confounding factors were defined a priori (age, diabetes, coronary artery disease, and year of training start). Adjusted risk of vascular interventions (arteriovenous fistula angioplasties and central venous catheter replacements) was assessed as the secondary outcome in a negative binomial regression. FINDINGS: Forty-eight patients were included in the study. Median HHD training duration was 86 (67-108) days, using a thrice weekly training schedule. Over a follow-up median time of 2.0 (0.7-3.3) years, three patients died while on HHD, 10 had a definitive transfer to HD, and 18 experienced a least 1 hospitalization (38 hospitalizations in total). Training duration was associated with a higher risk of hospitalization, technique failure, and death in unadjusted (hazard ratio [HR] 1.16 per month, 95% confidence interval [CI] 1.08-1.24) and adjusted multiple events model (HR 1.21, 95% CI 1.04-1.43). Risk of vascular access intervention was also significantly higher with increased training time (adjusted incidence rate ratio 1.31, 95% CI 1.03-1.64, per training month). DISCUSSION: In this single-center observational study, HHD training duration was associated with a higher risk of adverse events including, death, technique failure, hospitalizations, and vascular access intervention. Enhanced clinical follow-up and home support should be offered to these more vulnerable patients to mitigate this heightened risk.

Improving data quality in observational research studies: Report of the Cure Glomerulonephropathy (CureGN) network.

BACKGROUND: High data quality is of crucial importance to the integrity of research projects. In the conduct of multi-center observational cohort studies with increasing types and quantities of data, maintaining data quality is challenging, with few published guidelines. METHODS: The Cure Glomerulonephropathy (CureGN) Network has established numerous quality control procedures to manage the 70 participating sites in the United States, Canada, and Europe. This effort is supported and guided by the activities of several committees, including Data Quality, Recruitment and Retention, and Central Review, that work in tandem with the Data Coordinating Center to monitor the study. We have implemented coordinator training and feedback channels, data queries of questionable or missing data, and developed performance metrics for recruitment, retention, visit completion, data entry, recording of patient-reported outcomes, collection, shipping and accessing of biological samples and pathology materials, and processing, cataloging and accessing genetic data and materials. RESULTS: We describe the development of data queries and site Report Cards, and their use in monitoring and encouraging excellence in site performance. We demonstrate improvements in data quality and completeness over 4 years after implementing these activities. We describe quality initiatives addressing specific challenges in collecting and cataloging whole slide images and other kidney pathology data, and novel methods of data quality assessment. CONCLUSIONS: This paper reports the CureGN experience in optimizing data quality and underscores the importance of general and study-specific data quality initiatives to maintain excellence in the research measures of a multi-center observational study.

Arteriovenous Fistula Creation and Estimated Glomerular Filtration Rate Decline in Advanced CKD: A Matched Cohort Study.

Background: Kidney failure is associated with a high burden of morbidity and mortality. Previous studies have raised the possibility that arteriovenous fistula (AVF) creation may attenuate eGFR decline. This study aimed to compare eGFR decline in predialysis patients with an AVF, matched to patients oriented toward peritoneal dialysis (PD). Methods: Predialysis patients with an AVF and those oriented toward PD were retrospectively matched using a propensity score. Time zero was defined as the "AVF creation date" for the AVF group and the "date when eGFR was closest to the matched patient's eGFR at AVF creation" for the PD group. Crude and predicted eGFR decline in AVF and PD groups were compared before and after time zero using mixed-effect linear regressions. Results: In total, 61 pairs were matched. Crude annual eGFR decline before AVF creation/time zero was -4.1 ml/min per m2 per year in the AVF group versus -5.3 ml/min per m2 per year in the PD group (P=0.75) and after time zero, -2.5 ml/min per m2 per year in the AVF group versus -4.5 ml/min per m2 per year in the PD group (P=0.02). The predicted annual decline decreased from -5.1 ml/min per m2 per year in the AVF group before AVF creation to -2.8 ml/min per m2 per year after (P<0.01), whereas there was no difference in the PD group (-5.5 versus -5.1 ml/min per m2 per year respectively, P=0.41). Conclusions: In this matched study, AVF creation was associated with a deceleration of kidney function decline compared with a control PD-oriented group. Prospective studies are needed to assess the potential mechanisms between vascular access creation and eGFR slope attenuation.

Use of Desmopressin Prior to Kidney Biopsy in Patients With High Bleeding Risk.

INTRODUCTION: To prevent bleeding after native kidney biopsy (NKB), nephrologists often prescribe desmopressin, especially for patients with reduced estimated glomerular filtration rate (eGFR) at risk of uremia-related platelet dysfunction. However, only 1 randomized study has suggested a beneficial effect for desmopressin in patients with eGFR ≥60 ml/min per 1.73 m2. This retrospective cohort study aimed to evaluate desmopressin effect on postbiopsy bleeding in all patients, regardless of eGFR and other comorbidities. METHODS: In this retrospective cohort study, all adult patients who underwent an NKB from April 1, 2013, to April 30, 2018, in a tertiary hospital were identified. The association between desmopressin use and bleeding complications, including hemoglobin fall, transfusion, hematoma, symptomatic hematoma, urgent radiologic study, and hypotension, was analyzed using multivariable logistic regression models. RESULTS: A total of 413 native kidney biopsies were studied, 79% of which were performed after receiving desmopressin. Patients receiving desmopressin had worse chronic kidney disease (eGFR 28 vs. 45 ml/min per 1.73 m2; P < 0.001) and were more often hospitalized (48% vs. 32%; P = 0.009). Despite higher bleeding risk, patients using desmopressin had a similar likelihood of symptomatic hematomas (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.13-1.14) and a lower need for urgent radiologic studies (OR, 0.33; 95% CI, 0.11-0.98). CONCLUSION: Patients at higher risk of bleeding using desmopressin before kidney biopsy had bleeding complications similar to those not using desmopressin. These results highlight potential important clinical and financial benefits of desmopressin use before kidney biopsy.

Alk1 haploinsufficiency causes glomerular dysfunction and microalbuminuria in diabetic mice.

Endothelial dysfunction has been shown to play an important role in the pathogenesis of glomerular damage during diabetic kidney disease (DKD). As such, a better understanding of the molecular mechanisms involved in glomerular endothelial dysfunctions could provide novel therapeutic strategies for the prevention of DKD. We have previously shown that Alk1/BMP9 signaling plays an important function to maintain vascular integrity in diabetic animals. As such, we evaluated the effects of Alk1 suppression on glomerular endothelial function in diabetic mice. In the present study, we used mice with conditional heterozygote deletion of Alk1 in the endothelium (Alk1ΔEC) to evaluate the role of Alk1 on kidney function during STZ-induced diabetes. DKD was investigated in diabetic control and Alk1ΔEC mice euthanized eight weeks after the onset of diabetes. We showed that Alk1 expression is reduced in the glomeruli of human DKD patients. While renal function was not altered in Alk1ΔEC non-diabetic mice, we showed that Alk1 haploinsufficiency in the glomerular endothelium leads to microalbuminuria, thickening of the glomerular basement membrane, glomerular apoptosis and podocyte loss in diabetic mice. These data suggest that Alk1 is important for the proper function of glomerular endothelial cells and that decreased Alk1 combined with chronic hyperglycemia can impair renal function.

Persistent Disease Activity in Patients With Long-Standing Glomerular Disease.

INTRODUCTION: Glomerular diseases are characterized by variable disease activity over many years. We aimed to analyze the relationship between clinical disease activity and duration of glomerular disease. METHODS: Disease activity in adults with chronic minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and IgA nephropathy (IgAN; first diagnostic biopsy >5 years before enrollment; Of Longstanding Disease [OLD] cohort, n = 256) followed at Columbia University Medical Center (CUMC), was compared with disease activity of an internal and external cohort of patients with first diagnostic biopsy <5 years before enrollment drawn from the Cure Glomerulonephropathy Network (CureGN cohort, n = 1182; CUMC-CureGN cohort, n = 362). Disease activity was defined by (i) Kidney Disease: Improving Global Outcomes-recommended threshold criteria for initiation of immunosuppression in primary glomerulonephropathy (GN) and (ii) CureGN's Disease Activity Working Group definitions for activity. RESULTS: No significant differences were detected among the 3 cohorts in terms of age, sex, serum creatinine, and urinary protein-to-creatinine ratio. For each GN subtype, disease activity in the OLD cohort was comparable with disease activity in the entire CureGN and the CUMC-CureGN cohort. When limiting our comparisons to disease activity in incident CUMC-CureGN patients (first diagnostic biopsy within 6 months of enrollment), OLD patients demonstrated similar activity rates as incident patients. CONCLUSION: Disease activity did not differ among patients with shorter versus longer duration of disease. Such survivor patients, with long-term but persistent disease, are potentially highly informative for understanding the clinical course and pathogenesis of GN and may help identify factors mediating more chronic subtypes of disease.

Treatment Patterns Among Adults and Children With Membranous Nephropathy in the Cure Glomerulonephropathy Network (CureGN).

INTRODUCTION: The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for Glomerulonephritis recommend that patients with membranous nephropathy (MN) at risk for progression receive immunosuppressive therapy (IST), usually after 6 months of observation. A cyclophosphamide (CYC) or calcineurin inhibitor (CNI)-based regimen is recommended as first-line IST. However, the extent to which KDIGO recommendations are adopted in practice remains largely unknown. METHODS: We evaluated prescribing practice among patients with primary MN (diagnosed 2010-2018) enrolled in the Cure Glomerulonephropathy Network (CureGN) cohort study. We also evaluated the availability of testing for phospholipase A2 receptor (PLA2R) in the contemporary era. RESULTS: Among 361 patients (324 adults and 37 children) with MN who were IST-naïve at biopsy and had at least 6 months of follow-up, 55% of adults and 58% of children initiated IST <6 months after biopsy. Of these, 1 in 5 had no indication for (i.e., urine protein-to-creatinine ratio [uPCR] <4 g/g) or an apparent contraindication to (i.e., an estimated glomerular filtration rate [eGFR] <30 ml/min per 1.73 m2) IST. As first-line IST, half of treated patients received either CYC (16% of adults; 0% of children) or a CNI (40% and 46%, respectively), whereas 1 in 5 received corticosteroid monotherapy (20% and 27%, respectively) and 1 in 6 rituximab (15% and 15%, respectively). More than 80% of surveyed centers had access to PLA2R testing. CONCLUSION: These findings suggest that providers are not aware of, or lack confidence in, current KDIGO guidelines for MN. Treatment patterns observed in this cohort might critically inform the drafting of planned updates to KDIGO guidelines.

Impact of Arteriovenous fistula creation on estimated glomerular filtration rate decline in Predialysis patients.

BACKGROUND: Arteriovenous fistula (AVF) is the vascular access of choice for patients on hemodialysis. Recent evidence suggests that AVF creation may slow estimated glomerular filtration rate (eGFR) decline. The study objective was to assess the impact of the AVF creation on eGFR decline, after controlling for key confounding factors. METHODS: This retrospective cohort study included adult patients followed in a single-center predialysis clinic between 1999 and 2016. Patients with a patent AVF were followed up to 2 years pre- and post-AVF creation. Estimated GFR trajectory was reported using linear mixed models adjusted for demographic characteristics, comorbidities and use of renin-angiotensin-aldosterone blockade. RESULTS: A total of 146 patients were studied with a median age 68.7 (60.5-75.4) years and a median eGFR at time of AVF creation of 12.8 (11.3-13.9) mL/min/1.73m2. The crude annual eGFR decline rates were - 3.60 ± 4.00 mL/min/1.73 m2 pre- and - 2.28 ± 3.56 mL/min/1.73 m2 post-AVF, resulting in a mean difference of 1.28 mL/min/1.73 m2 (95% CI 0.49, 2.07). In a mixed effect linear regression model, monthly eGFR decline was - 0.63 (95% CI -0.81, - 0.46; p <  0.001) mL/min/1.73m2/month. The period after AVF creation was associated with a relatively higher eGFR (ß 0.94, 95% CI 0.61-1.26, p <  0.001). There was a significant association between follow-up time and the period pre/post AVF (ß 0.19, 95% CI 0.16, 0.22; p <  0.001) such that eGFR decline was more attenuated each month after AVF creation. CONCLUSIONS: In this cohort, AVF creation was associated with a significant reduction of eGFR decline. Further prospective studies are needed to confirm this association.

Pharmacodynamics of 250 mg and 500 mg oral furosemide in peritoneal dialysis
.

Residual renal function and diuresis preservation are associated with improved volume control and lower mortality in peritoneal dialysis (PD). Loop diuretics are used to maintain diuresis, although their optimal dosage remains unclear. This study aimed to compare the pharmacodynamics of a 250-mg and a 500-mg dose of oral furosemide in PD patients. 12 patients with a diuresis > 100 mL per day were randomized in a crossover pattern to successively receive an oral dose of 250 mg and 500 mg of furosemide. Twelve-hour natriuresis and diuresis were measured before and after each furosemide dose. Fractional excretion of sodium (FENa) and absolute sodium excretion increased after each dose, although these rises were not statistically significantly different (5.8% (250 mg) vs. 6.9% (500 mg), p = 0.57 for FENa and 42.6 mmol/12h (250 mg) vs. 70.8 mmol/12h (500 mg), p = 0.07 for absolute sodium excretion). Urinary volume was significantly increased after the 500-mg dose, whilst the difference did not reach statistical significance after the 250-mg dose. Furthermore, the higher dose was associated with a greater increase in diuresis than the lower dose (226 mL (250 mg) vs. 522 mL (500 mg), p = 0.04). Furosemide could be used at oral single doses reaching 500 mg in PD patients requiring greater volume control.