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.

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.

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.

The effect of renin-angiotensin-aldosterone system inhibitors on continuous and binary kidney outcomes in subgroups of patients with diabetes: a meta-analysis of randomized clinical trials.

INTRODUCTION: Diabetic nephropathy is the leading cause of kidney failure. Clinical practice guidelines recommend prescribing renin-angiotensin aldosterone system inhibitors (RAASi) to prevent diabetic nephropathy at any stage. We conducted this systematic review and meta-analysis to compare the effects of RAASi with placebo and other antihypertensive agents in adults with diabetes on continuous and binary kidney outcomes to provide a comprehensive review of the class effect of RAASi on several subgroups. METHODS: A systematic electronic search to identify randomized clinical trials of a duration of ≥ 12 months that recruited ≥ 50 adult participants with type 1 or 2 diabetes with any stage of chronic kidney disease and proteinuria was conducted in MEDLINE, CINAHL, EMBASE, and Cochrane library with no language restriction. Studies were screened against the inclusion and exclusion criteria by two reviewers independently. RESULTS: In this meta-analysis, evidence was drawn from 26,551 patients with diabetes from 46 studies. Our analysis shows that RAASi were better than placebo in reducing SrCr (the raw mean difference [RMD] = -13.4 µmol/L; 95%CI: -16.78; -10.01) and albuminuria levels (standardized mean difference [SMD] = -1; 95%CI: -1.57, -0.44, I2 = 96%). When compared to other active treatments, RAASi did not reduce SrCr (RMD = 0.03 µmol/L; 95%CI: -6.4, 6.10, I2 = 76%), caused a non-significant reduction of GFR levels (RMD = -1.21 mL/min; 95%CI: -4.52, 2.09, I2 = 86%), and resulted in modest reduction of albuminuria levels (SMD = -0.55; 95%CI: -0.95, -0.16, I2 = 90%). RAASi were superior to placebo in reducing the risks of kidney failure (OR = 0.74; 95%CI: 0.56, 0.97) and doubling of serum creatinine levels (SrCr; OR = 0.71; 95%CI: 0.55, 0.91), but not in promoting the regression of albuminuria (OR = 3.00; 95%CI: 0.96, 9.37). RAASi, however, were not superior to other antihypertensives in reducing the risks of these outcomes. Patients with type 2 diabetes, macroalbuminuria and longer duration of diabetes had less risk of developing kidney failure in placebo-controlled trials, while longer duration of diabetes, normal kidney function, and hypertension increased the probability of achieving regression of albuminuria in active-controlled trials. CONCLUSION: While our findings revealed the non-superiority of RAASi over other antihypertensives and portrayed a class effect on several subgroups of study participants, it raised a challenging question on whether RAASi deserve their place as first-line therapy in managing diabetic nephropathy.

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.

Successful surgical weight loss with laparoscopic sleeve gastrectomy for morbid obesity prior to kidney transplantation.

Morbid obesity in kidney transplant (KT) candidates is associated with increased complications and graft failure. Multiple series have demonstrated rapid and significant weight loss after laparoscopic sleeve gastrectomy (LSG) in this population. Long-term and post-transplant weight evolutions are still largely unknown. A retrospective review was performed in eighty patients with end-stage kidney disease (ESKD) who underwent LSG in preparation for KT. From a median initial BMI of 43.7 kg/m2 , the median change at 1-year was -10.0 kg/m2 . Successful surgical weight loss (achieving a BMI < 35 kg/m2 or an excess body weight loss >50%) was attained in 76.3% and was associated with male gender, predialysis status, lower obesity class and lack of coronary artery disease. Thirty-one patients subsequently received a KT with a median delay of 16.7 months. Weight regain (increase in BMI of 5 kg/m2 postnadir) and recurrent obesity (weight regain + BMI > 35) remain a concern, occurring post-KT in 35.7% and 17.9%, respectively. Early LSG should be considered for morbidly obese patients with ESKD for improved weight loss outcomes. Early KT after LSG does not appear to affect short-term surgical weight loss. Candidates with a BMI of up to 45 kg/m2 can have a reasonable expectation to achieve the limit within 1 year.

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.

Estimating glomerular filtration rate in patients with acute kidney injury: a prospective multicenter study of diagnostic accuracy.

BACKGROUND: Estimating glomerular filtration rate (GFR) in acute kidney injury (AKI) is challenging, with limited data comparing estimated and gold standard methods to assess GFR. The objective of our study was to assess the performance of the kinetic estimated GFR (KeGFR) and Jelliffe equations to estimate GFR in AKI, using a radioisotopic method (technetium-diethylenetriaminepentaacetic acid) as a reference measure. METHODS: We conducted a prospective multicenter observational study in hospitalized patients with AKI. We computed the Jelliffe and KeGFR equations to estimate GFR and compared these estimations to measured GFR (mGFR) by a radioisotopic method. The performances were assessed by correlation, Bland-Altman plots and smoothed and linear regressions. We conducted stratified analyses by age and chronic kidney disease (CKD). RESULTS: The study included 119 patients with AKI, mostly from the intensive care unit (63%) and with Stage 1 AKI (71%). The eGFR obtained from the Jelliffe and KeGFR equations showed a good correlation with mGFR (r = 0.73 and 0.68, respectively). The median eGFR by the Jelliffe and KeGFR equations was less than the median mGFR, indicating that these equations underestimated the mGFR. On Bland-Altman plots, the Jelliffe and KeGFR equations displayed a considerable lack of agreement with mGFR, with limits of agreement >40 mL/min/1.73 m2. Both equations performed better in CKD and the KeGFR performed better in older patients. Results were similar across AKI stages. CONCLUSIONS: In our study, the Jelliffe and KeGFR equations had good correlations with mGFR; however, they had wide limits of agreement. Further studies are needed to optimize the prediction of mGFR with estimatation equations.

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.

Osteoporotic fracture rates in chronic hemodialysis and effect of heparin exposure: a retrospective cohort study.

BACKGROUND: Patients receiving chronic hemodialysis treatments are at a higher risk of fracture compared to the general population. While the use of heparin during dialysis is crucial to avoid thrombosis of the extracorporeal circuit, the association of unfractionated heparin (UFH) and the risk of osteoporotic fracture has been shown for many years. However, this association was not as clear for low-molecular-weight heparin (LMWH) and the few collected data originated from studies among pregnant women. Our aim was to measure osteoporotic fracture rate among hemodialysis patients and to evaluate the association of LMWH compared to UFH in hemodialysis. METHODS: A retrospective cohort study was conducted on data extracted from the RAMQ and Med-Echo databases from January 2007 to March 2013 with patients chronically hemodialyzed in 21 participating centers. Incidence rates for each fracture sites were measured per 1000 patient-year (p-y) and their 95% confidence intervals (CI). Osteoporotic fracture risk for a first event with LMWH compared to UFH was estimated using a cox proportional hazard model using demographics, comorbidities and drug use as covariates. RESULTS: 4796 patients undergoing chronic hemodialysis were identified. The incidence rate for all fracture sites was 22.7 /1000 p-y (95% CI: 19.6-26.1) and 12.8 /1000 p-y (95% CI: 10.5-15.4) for hip and femur fractures. We found a similar risk of osteoporotic fracture for LMWH compared to UFH (adjusted HR = 1.01; 95%CI: 0.72-1.42). Age and malignancy increased the risk of fracture while cerebrovascular disease decreased the risk of fracture. CONCLUSIONS: Compared to UFH, LMWH did not change the risk of osteoporotic fracture when used for the extracorporeal circuit anticoagulation in chronic hemodialysis.

Prospective study of the changes in pharmacokinetics of immunosuppressive medications after laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy induces weight loss via the creation of a restrictive gastric tube for early satiety and is associated with an accelerated gastric transit time. A prospective, single-dose pharmacokinetic study was performed, prior to and after laparoscopic sleeve gastrectomy, for tacrolimus, extended-release tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium. The study included 12 morbidly obese patients in chronic renal failure. The median decrease in body mass index was 8.8 kg/m2 with an excess body weight loss of 54.9%. The AUC24 of all drugs were increased after laparoscopic sleeve gastrectomy by 46%, 55%, 77%, and 74%, respectively. The maximum concentrations were increased for tacrolimus, extended-release tacrolimus, and mycophenolate mofetil by 43%, 46%, and 65%. The apparent total clearances were decreased for tacrolimus, mycophenolate mofetil, and enteric-coated mycophenolate sodium by 36%, 57%, and 38%. Laparoscopic sleeve gastrectomy can be associated with significant changes in pharmacokinetics of the drugs evaluated. The mechanism is likely decreased apparent drug clearance due to an increased drug exposure (from a more distal site of intestinal absorption with decreased intestinal metabolism), or decreased clearance (liver metabolism). Adapting the monitoring of immunosuppression will be important to avoid overdosing and potential side effects.

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.

Association Between Low-Molecular-Weight Heparin and Risk of Bleeding Among Hemodialysis Patients: A Retrospective Cohort Study.

BACKGROUND: Low-molecular-weight heparins (LMWH) replaced unfractionated heparin (UFH) in multiple indications. Although LMWH efficacy in hemodialysis was demonstrated through multiple studies, their safety remains controversial. The potential bioaccumulation in patients undergoing chronic hemodialysis raised the question of bleeding risk among this population. OBJECTIVE: The aim of this study was to evaluate bleeding risk among patients with chronic hemodialysis receiving LMWH or UFH for the extracorporeal circuit anticoagulation. DESIGN: We conducted a retrospective cohort study on data extracted from the Régie de l'assurance maladie du Québec (RAMQ) and Med-Echo databases from January 2007 to March 2013. SETTING: Twenty-one hemodialysis centers in the province of Québec, Canada. PATIENTS: Chronic hemodialysis patients. MEASUREMENTS: Bleeding risk evaluated by proportional Cox model for time-dependent exposure using demographics, comorbidities, and drug use as covariates. METHODS: Minor, major, and total bleeding events identified using International Classification of Diseases, Ninth Revision (ICD-9)/International Classification of Diseases, Tenth Revision (ICD-10) codes in the RAMQ and Med-Echo databases. Exposure status to LMWH or UFH was collected through surveys at the facility level. RESULTS: We identified 5322 prevalent and incident patients with chronic hemodialysis. The incidence rate for minor, major, and total bleeding was 9.45 events/1000 patient-year (95% confidence interval [CI]: 7.61-11.03), 24.18 events/1000 patient-year (95% CI: 21.52-27.08), and 32.88 events/1000 patient-year (95% CI: 29.75-36.26), respectively. We found similar risks of minor adjusted hazard ratio (HR: 1.04; 95% CI: 0.68-1.61), major (HR: 0.83; 95% CI: 0.63-1.10), and total bleeding (HR: 0.90; 95% CI: 0.72-1.14) when comparing LMWH with UFH. LIMITATIONS: Potential misclassification of patients' exposure status and possible underestimation of minor bleeding risk. CONCLUSION: LMWH was not associated with a higher minor, major, or total bleeding risk. LMWH did not increase the risk of bleeding compared with UFH for the extracorporeal circuit anticoagulation in hemodialysis. The convenience of use and predictable effect made LMWH a suitable alternative to UFH in hemodialysis.

CONTEXTE: Les héparines de faible poids moléculaire (HFPM) ont remplacé les héparines non fractionnées (HNF) dans de multiples indications. Quoique l'efficacité des HFPM en hémodialyse ait été démontrée par un grand nombre d'études, leur innocuité demeure controversée; la possible bioaccumulation des HFPM chez les patients en hémodialyse chronique soulève le risque d'hémorragie au sein de cette population. OBJECTIF DE L'ÉTUDE: Cette étude visait à évaluer le risque d'hémorragie dans une cohorte de patients en hémodialyse chronique et traités par HFPM ou HNF comme anticoagulant pour le circuit extracorporel. TYPE D'ÉTUDE: Nous avons mené une étude de cohorte rétrospective sur les données de janvier 2007 à mars 2013, extraites des bases de données de la RAMQ et de Med-Echo. CADRE: Les données proviennent de 21 centres d'hémodialyse de la province de Québec (Canada). SUJETS: Patients en hémodialyse chronique. MESURES: Le risque d'hémorragie a été évalué par un modèle proportionnel de Cox pour l'exposition en fonction du temps et avec les covariables suivantes : données démographiques, comorbidités existantes et usage de médicaments. MÉTHODOLOGIE: Les épisodes d'hémorragie mineure, majeure et totale ont été colligés à l'aide des codes de la CIM-9 et de la CIM-10 dans les bases de données de la RAMQ et de Med-Echo. Des sondages menés dans les établissements ont permis de déterminer l'exposition aux HFPM ou aux HNF. RÉSULTATS: Nous avons retenu un total de 5 322 cas incidents et prévalents de patients en hémodialyse chronique pour l'étude. Les taux d'incidence pour les hémorragies mineures, majeures et totales étaient de 9,45 événements par 1 000 années-patients (IC 95 % : 7,61-11,03), de 24,18 événements par 1 000 années-patients (IC 95 % : 21,52-27,08) et de 32,88 événements par 1 000 années-patients (IC 95 % : 29,75-36,26) respectivement. Nous avons observé un risque comparable d'hémorragie mineure (rapport de risque corrigé : 1,04; IC 95 % : 0,68-1,61), majeure (rapport de risque corrigé : 0,83; IC 95 % : 0,63-1,10) et totale (rapport de risque corrigé : 0,90; IC 95 % : 0,72-1,14) lorsque nous avons comparé les HFPM aux HNF. LIMITES: Nos résultats sont limités par les probables erreurs dans le classement de l'exposition des patients aux héparines, de même que par une possible sous-évaluation des risques d'hémorragies mineures. CONCLUSION: Les HFPM n'ont pas été associées à un risque accru d'hémorragies mineures, majeures ou totales. De plus, lorsqu'elles ont été utilisées comme anticoagulant du circuit extracorporel en hémodialyse, les HFPM n'ont pas augmenté le risque d'hémorragie par rapport aux HNF. Ainsi, la commodité d'utilisation et l'effet prévisible des HFPM en font une solution de remplacement adéquate aux HNF en hémodialyse.

Safety of low-molecular-weight heparin compared to unfractionated heparin in hemodialysis: a systematic review and meta-analysis.

BACKGROUND: Low molecular weight heparins (LMWH) have been extensively studied and became the treatment of choice for several indications including pulmonary embolism. While their efficacy in hemodialysis is considered similar to unfractionated heparin (UFH), their safety remains controversial mainly due to a risk of bioaccumulation in patients with renal impairment. The aim of this systematic review was to evaluate the safety of LMWH when compared to UFH for extracorporeal circuit (ECC) anticoagulation. METHODS: We used Pubmed, Embase, Cochrane central register of controlled trials, Trip database and NICE to retrieve relevant studies with no language restriction. We looked for controlled experimental trials comparing LMWH to UFH for ECC anticoagulation among end-stage renal disease patients undergoing chronic hemodialysis. Studies were kept if they reported at least one of the following outcomes: bleeding, lipid profile, cardiovascular events, osteoporosis or heparin-induced thrombocytopenia. Two independent reviewers conducted studies selection, quality assessment and data extraction with discrepancies solved by a third reviewer. Relative risk and 95% CI was calculated for dichotomous outcomes and mean weighted difference (MWD) with 95% CI was used to pool continuous variables. RESULTS: Seventeen studies were selected as part of the systematic. The relative risk for total bleeding was 0.76 (95% CI 0.26-2.22). The WMD calculated for total cholesterol was -28.70 mg/dl (95% CI -51.43 to -5.98), a WMD for triglycerides of -55.57 mg/dl (95% CI -94.49 to -16.66) was estimated, and finally LDL-cholesterol had a WMD of -14.88 mg/dl (95% CI -36.27 to 6.51). CONCLUSIONS: LMWH showed to be at least as safe as UFH for ECC anticoagulation in chronic hemodialysis. The limited number of studies reporting on osteoporosis and HIT does not allow any conclusion for these outcomes. Larger studies are needed to evaluate properly the safety of LMWH in chronic hemodialysis.

Association of erythropoiesis-stimulating agents and the incidence risk of cancer diagnosis among chronic dialysis patients: a nested case-control study.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are the cornerstone of the treatment for anemia in end-stage renal disease (ESRD) patients. Although a correlation has been established between ESAs and increased tumor growth among patients with cancer-related anemia, an association with a higher incidence of cancer among chronic dialysis patients remains relatively unclear. METHODS: We completed a nested case-control study in a cohort of 4574 patients who began chronic dialysis treatment between 1 January 2001 and 31 December 2007 in Quebec, Canada, utilizing dialysis registry and administrative databases exclusively to extract our data. We excluded patients with a prior diagnosis of cancer. Eligible cases were identified by the time of initial cancer diagnosis obtained from either the hospital's discharge or physician billing form. We then randomly selected up to 10 controls for each case. ESA exposure was evaluated between 6 and 9 months prior to the initial cancer diagnosis. The mean weekly exposure was used to categorize ESA usage as either a low dose (<30 µg/week), moderate dose (30-70 µg/week) or high dose (>70 µg/week). We estimated the association between ESAs and the risk of developing cancer using a multivariable conditional logistic regression. RESULTS: We identified 419 cases of cancer and 3895 matched controls during the study period. The use of ESAs was associated with a higher risk of cancer {odds ratio [OR] 1.04 [95% confidence interval (CI) 1.02-1.07]}. Specifically, patients in the high exposure group (>70 µg/week) had an increased risk of developing cancer [OR 1.77 (95% CI 1.18-2.66)] compared with patients in the unexposed group. CONCLUSION: High-dose ESA was associated with an increased incidence risk of new cancer diagnosis among chronic dialysis patients.

Association between acetylsalicylic acid and the risk of dialysis-related infections or septicemia among incident hemodialysis patients: a nested case-control study.

BACKGROUND: Vascular access-related infections and septicemia are the main causes of infections among hemodialysis patients, the majority of them caused by Staphylococcus species. Acetylsalicylic acid (ASA) has recently been reported with a probable antistaphylococcal activity. This study aimed to evaluate the effect of ASA on the risk of dialysis-related infection and septicemia among incident chronic hemodialysis patients. METHODS: In a nested case-control study, we identified 449 cases of vascular access-related infections and septicemia, and 4156 controls between 2001 and 2007 from our incident chronic hemodialysis patients' cohort. Cases were defined as patients hospitalized with a main diagnosis of vascular access-related infection or septicemia on the discharge sheet (ICD-9 codes). Up to ten controls per case were selected by incidence density sampling and matched to cases on age, sex and follow-up time. ASA exposure was measured at the admission and categorized as: no use, low dose (80-324 mg/d), high dose (≥325 mg/d). Odds ratios (OR) for infections were estimated using multivariable conditional logistic regression analysis, adjusting for potential confounders. RESULTS: Compared to no use, neither dose of ASA was associated with a decreased risk of infection: low dose (OR 1.03, 95 % CI 0.82-1.28) and high dose (OR 1.30, 95 % CI 0.96-1.75). However, diabetes (OR = 1.32, 95 % CI = 1.07-1.62) and anticoagulant use (OR = 1.62, 95 % CI = 1.30-2.02) were associated with a higher risk. CONCLUSION: Among hemodialysis patients, ASA use was not associated with a reduced risk of hospitalizations for dialysis-related infections or septicemia. However, ASA may remain beneficial for its cardiovascular indications.

Outcomes of Infection-Related Hospitalization according to Dialysis Modality.

BACKGROUND AND OBJECTIVES: Peritoneal dialysis (PD) is associated with an increased risk of infection-related hospitalization (IRH) compared with hemodialysis. The objective of this study was to compare mortality and overall readmission after an IRH between PD and hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This propensity score-matched retrospective cohort study assessed patients undergoing long-term dialysis patients, derived from the Canadian Organ Replacement Register and Régie de l'assurance maladie du Québec, who had at least one IRH between January 2001 and December 2007. Patients were followed until death, kidney transplantation, or end of the study period. To estimate the probability of receiving PD versus hemodialysis, propensity scores were obtained using multivariable logistic regression. Mortality and overall readmission risks after the initial IRH were compared using a Cox survival model. RESULTS: A total of 354 pairs of patients who had at least one IRH were matched for propensity score. During follow-up (median, 1.25 years), 138 hemodialysis patients (24.7/100 patient-years; 95% confidence interval [95% CI], 20.7 to 29.1) and 130 PD patients (21.2/100 patient-years; 95% CI, 17.7 to 25.1) died; 265 hemodialysis patients (144.6/100 patient-years; 95% CI, 127.7 to 163.1) and 299 PD patients (173.2/100 patient-years; 95% CI, 154.1 to 194.0) were readmitted for any cause; and 121 hemodialysis patients (29.7/100 patient-years; 95% CI, 24.7 to 35.5) and 168 PD patients (44.7/100 patient-years; 95% CI, 38.2 to 52.0) were readmitted for an infection. Compared with hemodialysis, PD was not associated with a different mortality risk after an IRH (hazard ratio [HR], 0.87; 95% CI, 0.69 to 1.11). PD was associated with a higher risk of infection-related overall readmission compared with hemodialysis (HR, 1.44; 95% CI, 1.14 to 1.81), but not with the risk of all-cause overall readmission (HR, 1.15; 95% CI, 0.98 to 1.36). CONCLUSIONS: PD was not associated with higher mortality or all-cause overall readmission following an IRH compared with hemodialysis, but PD patients were at higher risk of infection-related overall readmission after IRH. IRHs are associated with significant mortality and overall readmissions. Evaluation of strategies to reduce infections in both hemodialysis and PD recipients are needed to improve patient care and outcomes.

Trends in infection-related hospital admissions and impact of length of time on dialysis among patients on long-term dialysis: a retrospective cohort study.

BACKGROUND: After cardiovascular disease, infection is the second leading reason for admission to hospital among patients receiving long-term dialysis. We examined whether duration of dialysis treatment influences the rate of infection-related admission to hospital. METHODS: Using provincial administrative databases for Quebec, we built a retrospective cohort of all adults receiving long-term dialysis (hemodialysis or peritoneal dialysis) between 2001 and 2007. We evaluated rates of infection-related admission to hospital according to length of time on dialysis. RESULTS: A cohort of 9822 patients (mean age 66.3 [standard deviation ± 14.7] yr; 39.7% female) were followed for a median of 2.1 (range 1.0-3.9) years. Between 2001 and 2007, infection-related hospital admissions remained stable (from 0.20 to 0.19 per person-year; p = 0.7). All-cause hospital admission rates decreased by 22.9% (from 1.53 to 1.18 per person-year; p < 0.001), and cardiovascular-related admission rates decreased by 46.7% (from 0.45 to 0.24 per person-year; p < 0.001). The rate of infection-related admission remained stable with increasing time on dialysis (p = 0.1); however, both all-cause and cardiovascular-related admission rates decreased with length of time on dialysis (p < 0.001). Standardization of hospital admission rates by age, sex or length of time on dialysis did not change trends. INTERPRETATION: We found a stable rate of infection-related hospital admission between 2001 and 2007 among patients on long-term dialysis, independent of age, sex and length of time on dialysis. A decrease in all-cause and cardiovascular-related admission rates during the same period meant that the proportion of admissions related to infection increased. Because admissions to hospital are potentially preventable, understanding the epidemiology of infection-related admissions may inform future studies on prevention of this serious outcome.

Association between vitamin D receptor activator and the risk of infection-related hospitalizations among incident hemodialysis patients: a nested case-control study.

BACKGROUND: Patients suffering from chronic kidney disease are at greater risk of developing infection than the normal population, and infections are the second cause of mortality after cardiovascular complications in this population. Some reports suggest that the intake of active vitamin D might be beneficial to prevent infections. Therefore, we aimed to determine if the oral intake of vitamin D receptor activator (VDRA) is associated with a lower risk of infection-related hospitalization (IRH) among incident chronic hemodialysis patients. METHODS: We conducted a nested case-control study in a cohort of 4933 patients initiating chronic hemodialysis between 1 January 2001 and 31 December 2007 in Quebec, Canada, using administrative databases. We identified cases of hospital admission indicating an infection as main diagnosis on the hospital's discharge sheet. Up to 10 controls were randomly selected for each case. Association between oral VDRA use and risk of IRH was estimated using conditional logistic regression. RESULTS: We identified 1136 cases of IRH and 10396 controls during the study period. The intake of VDRA was not associated with the risk of being hospitalized due to an infection (odds ratio [OR], 1.07; 95% confidence interval [CI], 0.95-1.20). Using the prior 6-month cumulative dose of VDRA, we also found that a cumulative VDRA dose of less than 45 mcg (OR, 1.05; 95%CI, 0.92-1.19) or greater than 45 mcg (OR, 1.15; 95%CI, 0.96-1.36) was not associated with the IRH risk. CONCLUSIONS: The oral intake of VDRA was not associated with the risk of IRH in incident hemodialysis patients.