Application of the updated International IgA Nephropathy Prediction Tool in children one or two years post-biopsy.

The pediatric International IgA Nephropathy (IgAN) Prediction Tool comprises two models with and without ethnicity and is the first method to predict the risk of a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure in children at the time of biopsy using clinical risk factors and Oxford MEST histology scores. However, it is unknown if the Prediction Tool can be applied after a period of observation post-biopsy. Using an international multi-ethnic cohort of 947 children with IgAN, 38% of whom were followed into adulthood, the Prediction Tool was updated for use one year after biopsy. Compared to the original pediatric Prediction Tool, the updated post-biopsy Prediction Tool had a better model fit with higher R2D (51%/50% vs 20%), significant increase in 4-year C-statistics (0.83 vs 0.73/0.69, ΔC 0.09 [95% confidence interval 0.07-0.10] and ΔC 0.14 [0.12-0.15]) and better 4-year calibration with lower integrated calibration indices (0.74/0.54 vs 2.45/1.01). Results were similar after internal validation and when the models were applied two years after biopsy. Trajectories of eGFR after a baseline one year post-biopsy were non-linear and those at higher predicted risk started with a lower eGFR and experienced a more rapid decline over time. In children, eGFR had a variable rate of increase until 15-18 years old and then decreased linearly with a more rapid decline in higher risk groups that was similar to young adults of comparable risk. Thus, the original pediatric Prediction Tool should be used in children at the time of biopsy, and the updated pediatric Prediction Tool should be used to re-evaluate risk one or two years after biopsy.

A Population-Based Analysis of the Risk of Glomerular Disease Relapse after COVID-19 Vaccination.

BACKGROUND: Although case reports have described relapses of glomerular disease after COVID-19 vaccination, evidence of a true association is lacking. In this population-level analysis, we sought to determine relative and absolute risks of glomerular disease relapse after COVID-19 vaccination. METHODS: In this retrospective population-level cohort study, we used a centralized clinical and pathology registry (2000-2020) to identify 1105 adult patients in British Columbia, Canada, with biopsy-proven glomerular disease that was stable on December 14, 2020 (when COVID-19 vaccines first became available). The primary outcome was disease relapse, on the basis of changes in kidney function, proteinuria, or both. Vaccination was modeled as a 30-day time-varying exposure in extended Cox regression models, stratified on disease type. RESULTS: During 281 days of follow-up, 134 (12.1%) patients experienced a relapse. Although a first vaccine dose was not associated with relapse risk (hazard ratio [HR]=0.67; 95% confidence interval [95% CI], 0.33 to 1.36), exposure to a second or third dose was associated with a two-fold risk of relapse (HR=2.23; 95% CI, 1.06 to 4.71). The pattern of relative risk was similar across glomerular diseases. The absolute increase in 30-day relapse risk associated with a second or third vaccine dose varied from 1%-2% in ANCA-related glomerulonephritis, minimal change disease, membranous nephropathy, or FSGS to 3%-5% in IgA nephropathy or lupus nephritis. Among 24 patients experiencing a vaccine-associated relapse, 4 (17%) had a change in immunosuppression, and none required a biopsy. CONCLUSIONS: In a population-level cohort of patients with glomerular disease, a second or third dose of COVID-19 vaccine was associated with higher relative risk but low absolute increased risk of relapse.

Application of the International IgA Nephropathy Prediction Tool one or two years post-biopsy.

The International IgA Nephropathy (IgAN) Prediction Tool is the preferred method in the 2021 KDIGO guidelines to predict, at the time of kidney biopsy, the risk of a 50% drop in estimated glomerular filtration rate or kidney failure. However, it is not known if the Prediction Tool can be accurately applied after a period of observation post-biopsy. Using an international multi-ethnic derivation cohort of 2,507 adults with IgAN, we updated the Prediction Tool for use one year after biopsy, and externally validated this in a cohort of 722 adults. The original Prediction Tool applied at one-year without modification had a coefficient of variation (R2) of 55% and 54% and four-year concordance (C statistic) of 0.82 but poor calibration with under-prediction of risk (integrated calibration index (ICI) 1.54 and 2.11, with and without race, respectively). Our updated Prediction Tool had a better model fit with higher R2 (61% and 60%), significant increase in four-year C-statistic (0.87 and 0.86) and better four-year calibration with lower ICI (0.75 and 0.35). On external validation, the updated Prediction Tool had similar R2 (60% and 58%) and four-year C-statistics (both 0.85) compared to the derivation analysis, with excellent four-year calibration (ICI 0.62 and 0.56). This updated Prediction Tool had similar prediction performance when used two years after biopsy. Thus, the original Prediction Tool should be used only at the time of biopsy whereas our updated Prediction Tool can be used for risk stratification one or two years post-biopsy.

Differential expression of microRNA miR-150-5p in IgA nephropathy as a potential mediator and marker of disease progression.

Understanding why certain patients with IgA nephropathy progress to kidney failure while others maintain normal kidney function remains a major unanswered question. To help answer this, we performed miRNome profiling by next generation sequencing of kidney biopsies in order to identify microRNAs specifically associated with the risk of IgA nephropathy progression. Following sequencing and validation in independent cohorts, four microRNAs (-150-5p, -155-5p, -146b-5p, -135a-5p) were found to be differentially expressed in IgA nephropathy progressors compared to non-progressors, and patients with thin membrane nephropathy, lupus nephritis and membranous nephropathy, and correlated with estimated glomerular filtration rate, proteinuria, and the Oxford MEST-C scores (five histological features that are independent predictors of clinical outcome). Each individual microRNA increased the discrimination score of the International IgAN Prediction Tool, although due to the small number of samples the results did not reach statistical significance. miR-150-5p exhibited the largest amplitude of expression between cohorts and displayed the best discrimination between IgA nephropathy progressors and non-progressors by receiver operating curve analysis (AUC: 0.8). However, expression was similarly upregulated in kidneys with established fibrosis and low estimated glomerular filtration rates at the time of biopsy. Consistent with a more generic role in kidney fibrosis, in situ hybridization revealed that miR-150-5p was found in lymphoid infiltrates, and areas of proliferation and fibrosis consistent with the known drivers of progression. Thus, miR-150-5p may be a potential functional mediator of kidney fibrosis that may add value in predicting risk of progression in IgA nephropathy and other kidney diseases.

Updating the International IgA Nephropathy Prediction Tool for use in children.

Although IgA nephropathy (IgAN) is a common cause of glomerulonephritis in children, the absence of a method to predict disease progression limits personalized risk-based treatment decisions. The adult International IgAN Prediction Tool comprises two validated Cox survival models that predict a 50% decline in estimated glomerular filtration rate (eGFR) or end stage kidney disease (ESKD) using clinical risk factors and Oxford MEST histology scores. Here, we updated the Prediction Tool for use in children using a multiethnic international cohort of 1,060 children with IgAN followed into adulthood. The updated pediatric Prediction Tool had better model fit than the original adult tool with lower Akaike Information Criterion, higher R2D and similar C-statistics. However, calibration showed very poor agreement between predicted and observed risks likely due to the observed disease trajectory in children. Therefore, the Tool was updated using a secondary outcome of a 30% reduction in eGFR or ESKD, resulting in better R2D (30.3%/22.2%) and similar C-statistics (0.74/0.68) compared to the adult tool but with good calibration. The trajectory of eGFR over time in children differed from adults being highly non-linear with an increase until 18 years old followed by a linear decline similar to that of adults. A higher predicted risk was associated with a smaller increase in eGFR followed by a more rapid decline, suggesting that children at risk of a 30% decrease in eGFR will eventually experience a larger 50% decrease in eGFR when followed into adulthood. As such, these two outcomes are analogous between pediatric and adult Prediction Tools. Thus, our pediatric Prediction Tool can accurately predict the risk of a 30% decline in eGFR or ESKD in children with IgAN.

Validity of different dose reduction criteria for apixaban.

Reduced-dose apixaban is recommended in patients fulfilling 2 of 3 criteria: age ≥80 years, body weight ≤60 kg, and serum creatinine ≥1.5 mg/dL. However, patient weight is often not available in electronic health data. We examined the validity of alternative definitions based on age and renal function alone using an observational dataset of patients with atrial fibrillation and chronic kidney disease which included weight measurements.

Improving treatment decisions using personalized risk assessment from the International IgA Nephropathy Prediction Tool.

Immunosuppression in IgA nephropathy (IgAN) should be reserved for patients at high-risk of disease progression, which KDIGO guidelines determine based solely on proteinuria 1g or more/day. To investigate if treatment decisions can be more accurately accomplished using individualized risk from the International IgAN Prediction Tool, we simulated allocation of a hypothetical immunosuppression therapy in an international cohort of adults with IgAN. Two decision rules for treatment were applied based on proteinuria of 1g or more/day or predicted risk from the Prediction Tool above a threshold probability. An appropriate decision was defined as immunosuppression allocated to patients experiencing the primary outcome (50% decline in eGFR or ESKD) and withheld otherwise. The net benefit and net reduction in treatment are the proportion of patients appropriately allocated to receive or withhold immunosuppression, adjusted for the harm from inappropriate decisions, calculated for all threshold probabilities from 0-100%. Of 3299 patients followed for 5.1 years, 522 (15.8%) experienced the primary outcome. Treatment allocation based solely on proteinuria of 1g or more/day had a negative net benefit (was harmful) because immunosuppression was increasingly allocated to patients without progressive disease. Compared to using proteinuria, treatment allocation using the Prediction Tool had a larger net benefit up to 23.4% (95% confidence interval 21.5-25.2%) and a larger net reduction in treatment up to 35.1% (32.3-37.8%). Thus, allocation of immunosuppression to high-risk patients with IgAN can be substantially improved using the Prediction Tool compared to using proteinuria.

External validation and clinical utility of a prediction model for 6-month mortality in patients undergoing hemodialysis for end-stage kidney disease.

BACKGROUND: End-stage kidney disease is associated with poor prognosis. Health care professionals must be prepared to address end-of-life issues and identify those at high risk for dying. A 6-month mortality prediction model for patients on dialysis derived in the United States is used but has not been externally validated. AIM: We aimed to assess the external validity and clinical utility in an independent cohort in Canada. DESIGN: We examined the performance of the published 6-month mortality prediction model, using discrimination, calibration, and decision curve analyses. SETTING/PARTICIPANTS: Data were derived from a cohort of 374 prevalent dialysis patients in two regions of British Columbia, Canada, which included serum albumin, age, peripheral vascular disease, dementia, and answers to the "the surprise question" ("Would I be surprised if this patient died within the next year?"). RESULTS: The observed mortality in the validation cohort was 11.5% at 6 months. The prediction model had reasonable discrimination (c-stat = 0.70) but poor calibration (calibration-in-the-large = -0.53 (95% confidence interval: -0.88, -0.18); calibration slope = 0.57 (95% confidence interval: 0.31, 0.83)) in our data. Decision curve analysis showed the model only has added value in guiding clinical decision in a small range of threshold probabilities: 8%-20%. CONCLUSION: Despite reasonable discrimination, the prediction model has poor calibration in this external study cohort; thus, it may have limited clinical utility in settings outside of where it was derived. Decision curve analysis clarifies limitations in clinical utility not apparent by receiver operating characteristic curve analysis. This study highlights the importance of external validation of prediction models prior to routine use in clinical practice.

Oral Nutritional Supplement Prescription and Patient-Reported Symptom Burden Among Patients With Late-Stage Non-Dialysis Chronic Kidney Disease.

Background: Malnutrition and protein-energy wasting (PEW) are nutritional complications of advanced chronic kidney disease (CKD) that contribute to morbidity, mortality, and decreased quality of life. No previous studies have assessed the effect of oral nutritional supplements (ONSs) on patient-reported symptom burden among patients with non-dialysis CKD (CKD-ND) who have or are at risk of malnutrition/PEW. Objective: The objective of this study was (1) to quantify the associations between baseline nutritional parameters and patient-reported symptom scores for wellbeing, tiredness, nausea, and appetite and (2) to compare the change in symptom scores among patients prescribed ONS with patients who did not receive ONS in a propensity-score-matched analysis. Design: This study conducted observational cohort analysis using provincial registry data. Setting: This study was done in multidisciplinary CKD clinics in British Columbia. Patients: Adult patients >18 years of age with CKD-ND entering multidisciplinary CKD clinics between January 1, 2010-July 31, 2019 who had at least 2 Edmonton Symptom Assessment System Revised: Renal (ESASr:Renal) assessments. Measurements: The measurements include nutrition-related parameters such as body mass index (BMI), serum albumin, serum phosphate, serum bicarbonate, neutrophil-to-lymphocyte ratio (NLR), and ESASr:Renal scores (overall and subscores for wellbeing, tiredness, nausea, and appetite). Methods: Multivariable linear regression was applied to assess associations between nutritional parameters and ESASr:Renal scores. Propensity-score matching using the greedy method was used to match patients prescribed ONS with those not prescribed ONS using multiple demographic, comorbidity, health care utilization, and temporal factors. Linear regression was used to assess the association between first ONS prescription and change in ESASr:Renal overall score and subscores for wellbeing, tiredness, nausea, and appetite. Results: Of total, 2076 patients were included. Higher baseline serum albumin was associated with lower overall ESASr:Renal score (-0.20, 95% confidence interval [CI] = -0.40 to -0.01 per 1 g/L increase in albumin), lower subscores for tiredness (-0.04, 95% CI = -0.07 to -0.01), nausea (-0.03, 95% CI = -0.04 to -0.01), and appetite (-0.03, 95% CI = -0.06 to -0.01). Higher BMI was associated with higher overall ESASr:Renal score (0.32, 95% CI = 0.16 to 0.48 per 1 kg/m2 increase in BMI), higher symptom subscores for wellbeing (0.02, 95% CI = 0.00 to 0.04) and tiredness (0.05, 95% CI = 0.02 to 0.07). Higher baseline NLR was associated with higher overall score (0.21, 95% CI = 0.03 to 0.39 per 1 unit increase in NLR), higher symptom subscores for wellbeing (0.03, 95% CI = 0.01 to 0.05) and nausea (0.03, 95% CI = 0.02 to 0.05). In the propensity-score-matched analysis, there were no statistically significant associations between ONS prescription and change in overall ESASr:Renal (beta coefficient for change in ESASr:Renal = 0.17, 95% CI = -2.64 to 2.99) or for subscores for appetite, tiredness, nausea, and wellbeing. Limitations: Possible residual confounding. The ESASr:Renal assessments were obtained routinely only in patients with G5 CKD-ND and/or experiencing significant CKD-related symptoms. Conclusions: This exploratory observational analysis of patients with advanced non-dialysis CKD demonstrated BMI, serum albumin, and NLR were modestly associated with patient-reported symptoms, but we did not observe an association between ONS use and change in ESASr:Renal scores.

Contexte: La malnutrition et la dénutrition protéino-énergétique (DPÉ) sont des complications nutritionnelles de l'insuffisance rénale chronique (IRC) de stade avancé qui contribuent à la morbidité, à la mortalité et à la diminution de la qualité de vie associées à la maladie. Aucune étude n'a évalué l'effet des suppléments nutritionnels administrés par voie orale (SNO) sur le fardeau des symptômes autodéclarés par les patients non dialysés atteints d'IRC (IRC-ND) et souffrant de malnutrition/DPÉ ou risquant d'en souffrir. Objectifs: (1) Quantifier les associations entre les paramètres nutritionnels initiaux et les scores des symptômes autodéclarés en lien avec le bien-être, la fatigue, les nausées et l'appétit. (2) Comparer, dans une analyse des scores de propension appariés, la variation des scores associés aux symptômes des patients ayant reçu une ordonnance de SNO par rapport aux patients n'en ayant pas reçu. Conception: Analyse de cohorte observationnelle à partir des données du registre provincial. Cadre: Cliniques multidisciplinaires d'IRC en Colombie-Britannique. Sujets: Des patients adultes atteints d'IRC-ND admis entre le 1er janvier 2010 et le 31 juillet 2019 dans des cliniques multidisciplinaires d'IRC avec au moins deux évaluations selon l'Échelle d'évaluation Edmonton pour l'insuffisance rénale (ESASr:renal­Edmonton Symptom Assessment System Revised: Renal). Mesures: Les paramètres liés à la nutrition: indice de masse corporelle (IMC), albumine sérique, phosphate sérique, bicarbonate sérique, rapport neutrophiles/lymphocytes (RNL), ainsi que les scores ESASr:renal (scores globaux et scores secondaires pour le bien-être, la fatigue, les nausées et l'appétit). Méthodologie: La régression linéaire multivariable a servi à évaluer les associations entre les paramètres nutritionnels et les scores ESASr:renal. Une correspondance des scores de propension par la méthode Greedy a été utilisée pour apparier des patients ayant reçu ordonnance de SNO avec des patients n'en ayant pas reçu selon plusieurs facteurs démographiques, les comorbidités, l'utilisation des soins de santé et des facteurs temporels. La régression linéaire a servi à évaluer l'association entre la première ordonnance de SNO et la variation des scores globaux et des scores secondaires de l'ESASr:renal pour le bien-être, la fatigue, les nausées et l'appétit. Résultats: Au total, 2 076 patients ont été inclus à l'étude. Un taux d'albumine sérique plus élevé à l'inclusion était associé à un score ESASr:rénal global plus faible (-0,20 [IC 95 %: -0,40 à -0,01 pour 1 g/L d'augmentation de l'albumine]) et à des scores secondaires plus faibles pour la fatigue (-0,04 [IC 95 %: -0,07 à -0,01]), les nausées (-0,03 [IC 95 %: -0,04 à 0,01]) et l'appétit (0,03 [IC 95 %: -0,06 à -0,01]). Un IMC plus élevé était associé à un score ESASr:renal global plus élevé (0,32 [IC 95 %: 0,16 à 0,48 par augmentation de 1 kg/m2 de l'IMC]), des scores secondaires de symptômes plus élevés pour le bien-être (0,02 [IC 95 %: 0,00 à 0,04]) et la fatigue (0,05 [IC 95 %: 0,02 à 0,07]). Un RNL initial plus élevé était associé à un score ESASr:renal global plus élevé (0,21 [IC 95 %: 0,03 à 0,39 par unité d'augmentation du RNL]), des scores secondaires de symptômes plus élevés pour le bien-être (0,03 [IC 95 %: 0,01 à 0,05]) et les nausées (0,03 [IC 95 %: 0,02 à 0,05]). Dans l'analyse des scores de propension appariés, aucune association statistiquement significative n'a été observée entre une ordonnance de SNO et une variation significative dans les scores globaux de l'ESASr:renal (coefficient bêta de variation de l'ESASr:rénal: 0,17 [IC 95 %: -2,64 ­ à 2,99]) ou les scores secondaires pour l'appétit, la fatigue, les nausées et le bien-être. Limites: Possibilité de facteurs de confusion résiduels. Les évaluations ESASr:renal ont été effectuées de routine uniquement pour les patients atteints d'IRC-ND G5 et/ou présentant des symptômes importants liés à l'IRC. Conclusion: Cette analyse observationnelle exploratoire portant sur des patients atteints d'IRC avancée non dialysés a démontré que l'IMC, l'albumine sérique et le RNL étaient associés de façon modeste aux symptômes autodéclarés. Toutefois, aucune association n'a été observée entre une ordonnance de SNO et une variation des scores ESASr:renal.

Kidney Failure Risk Equation in vascular access planning: a population-based study supporting value in decision making.

Background: The Kidney Failure Risk Equation (KFRE) can play a better role in vascular access (VA) planning in patients with chronic kidney disease (CKD) requiring hemodialysis (HD). We described the VA creation and utilization pattern under existing estimated glomerular filtration rate (eGFR)-based referral, and investigated the utility of KFRE score as an adjunct variable in VA planning. Methods: Patients with CKD aged ≥18 years with eGFR <20 mL/min/1.73 m2 who chose HD as dialysis modality from January 2010 to August 2020 were included from a population-based database in British Columbia, Canada. Modality selection date was the index date. Exposures were categorized as (i) current eGFR-based referral, (ii) eGFR-based referral plus KRFE 2-year risk score on index date (KFRE-2) >40% and (iii) eGFR-based referral plus KFRE-2 ≤40%. We estimated the proportion of patients who started HD on arteriovenous fistula/graft (AVF/G) within 2 years, indicating timely pre-emptive creation, and the proportion of patients in whom AVF/G was created but did not start HD within 2 years, indicating too-early creation. Results: Study included 2581 patients, median age 71 years, 60% male. Overall, 1562(61%) started HD and 276 (11%) experienced death before HD initiation within 2 years. Compared with current referral, the proportion of patients who started HD on AVF/G was significantly higher when KFRE-2 was considered in addition to current referral (49% vs 58%, P-value <.001). Adjunct KFRE-2 significantly reduced too-early creation (31% vs 18%, P-value <.001). Conclusions: KFRE in addition to existing eGFR-based referral for VA creation has the potential to improve VA resource utilization by ensuring more patients start HD on AVF/G and may minimize too-early/unnecessary creation. Prospective research is necessary to validate these findings.

Implications of Implementing the 2021 CKD-EPI Equation Without Race on Managing Patients With Kidney Disease in British Columbia, Canada.

Introduction: We investigated the implications of implementing race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation among real-world patients with chronic kidney disease (CKD) from British Columbia (BC), Canada. Methods: This study included nondialysis-dependent patients with CKD aged ≥19 years who were registered in the Patient Records and Outcome Management Information System (PROMIS) as of March 31, 2016 (index date) with ≥1 serum creatinine measurement within 1 year before the index date. Patients with a history of kidney transplantation before the index date were excluded. CKD-EPI 2021 versus 2009 equation was the exposure variable. Difference in mean estimated glomerular filtration rate (eGFR) and number (%) of patients reclassified to a different eGFR category were estimated. We used Fine and Gray subdistribution hazard model to investigate the association between change in eGFR category and progression to kidney failure (incident maintenance dialysis or kidney transplantation) within 2 years. Results: A total of 11,604 patients (median age 73 years, 52% male) were included. Compared to the 2009 equation, eGFR from 2021 equation was on average 2.7 ml/min per 1.73 m2 higher. Variation was higher among males. Overall, ∼17% of the study sample were reclassified to a category with higher eGFR by 2021 equation (switchers). The highest proportion (28%) of patients were reclassified from G5 to G4. The risk of progressing to kidney failure was 22% less among switchers compared to nonswitchers; adjusted subdistribution hazard ratio (HR) (95% confidence interval [CI]) is 0.78 (0.65, 0.94). Conclusion: CKD-EPI 2021 equation appeared to provide higher eGFR compared to 2009 equation. This higher eGFR values appeared to be concordant with subsequent real-world CKD progression outcomes. Higher eGFR from the 2021 equation may have substantial clinical implications in both diagnosis as well as long-term care of patients with CKD.

Humoral Response Following 3 Doses of mRNA COVID-19 Vaccines in Patients With Non-Dialysis-Dependent CKD: An Observational Study.

Background: Chronic kidney disease (CKD) is associated with a lower serologic response to vaccination compared to the general population. There is limited information regarding the serologic response to coronavirus disease 2019 (COVID-19) vaccination in the non-dialysis-dependent CKD (NDD-CKD) population, particularly after the third dose and whether this response varies by estimated glomerular filtration rate (eGFR). Methods: The NDD-CKD (G1-G5) patients who received 3 doses of mRNA COVID-19 vaccines were recruited from renal clinics within British Columbia and Ontario, Canada. Between August 27, 2021, and November 30, 2022, blood samples were collected serially for serological testing every 3 months within a 9-month follow-up period. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike, anti-receptor binding domain (RBD), and anti-nucleocapsid protein (NP) levels were determined by enzyme-linked immunosorbent assay (ELISA). Results: Among 285 NDD-CKD patients, the median age was 67 (interquartile range [IQR], 52-77) years, 58% were men, 48% received BNT162b2 as their third dose, 22% were on immunosuppressive treatment, and COVID-19 infection by anti-NP seropositivity was observed in 37 of 285 (13%) patients. Following the third dose, anti-spike and anti-RBD levels peaked at 2 months, with geometric mean levels at 1131 and 1672 binding antibody units per milliliter (BAU/mL), respectively, and seropositivity rates above 93% and 85%, respectively, over the 9-month follow-up period. There was no association between eGFR or urine albumin-creatinine ratio (ACR) with mounting a robust antibody response or in antibody levels over time. The NDD-CKD patients on immunosuppressive treatment were less likely to mount a robust anti-spike response in univariable (odds ratio [OR] 0.43, 95% confidence interval [CI]: 0.20, 0.93) and multivariable (OR 0.52, 95% CI: 0.25, 1.10) analyses. An interaction between age, immunoglobulin G (IgG) antibody levels, and time was observed in both unadjusted (anti-spike: P = .005; anti-RBD: P = .03) and adjusted (anti-spike: P = .004; anti-RBD: P = .03) models, with older individuals having a more pronounced decline in antibody levels over time. Conclusion: Most NDD-CKD patients were seropositive for anti-spike and anti-RBD after 3 doses of mRNA COVID-19 vaccines and we did not observe any differences in the antibody response by eGFR.

Histologic and Clinical Factors Associated with Kidney Outcomes in IgA Vasculitis Nephritis.

BACKGROUND: Nephritis is a common manifestation of IgA vasculitis and is morphologically indistinguishable from IgA nephropathy. While MEST-C scores are predictive of kidney outcomes in IgA nephropathy, their value in IgA vasculitis nephritis has not been investigated in large multiethnic cohorts. METHODS: Biopsies from 262 children and 99 adults with IgA vasculitis nephritis ( N =361) from 23 centers in North America, Europe, and Asia were independently scored by three pathologists. MEST-C scores were assessed for correlation with eGFR/proteinuria at biopsy. Because most patients ( N =309, 86%) received immunosuppression, risk factors for outcomes were evaluated in this group using latent class mixed models to identify classes of eGFR trajectories over a median follow-up of 2.7 years (interquartile range, 1.2-5.1). Clinical and histologic parameters associated with each class were determined using logistic regression. RESULTS: M, E, T, and C scores were correlated with either eGFR or proteinuria at biopsy. Two classes were identified by latent class mixed model, one with initial improvement in eGFR followed by a late decline (class 1, N =91) and another with stable eGFR (class 2, N =218). Class 1 was associated with a higher risk of an established kidney outcome (time to ≥30% decline in eGFR or kidney failure; hazard ratio, 5.84; 95% confidence interval, 2.37 to 14.4). Among MEST-C scores, only E1 was associated with class 1 by multivariable analysis. Other factors associated with class 1 were age 18 years and younger, male sex, lower eGFR at biopsy, and extrarenal noncutaneous disease. Fibrous crescents without active changes were associated with class 2. CONCLUSIONS: Kidney outcome in patients with biopsied IgA vasculitis nephritis treated with immunosuppression was determined by clinical risk factors and endocapillary hypercellularity (E1) and fibrous crescents, which are features that are not part of the International Study of Diseases of Children classification.

Responsiveness of FGF-23 and mineral metabolism to altered dietary phosphate intake in chronic kidney disease (CKD): results of a randomized trial.

BACKGROUND: High fibroblast growth factor-23 (FGF-23) levels are associated with adverse outcomes. We studied the responsiveness of FGF-23 and mineral metabolism to altered dietary phosphate intake in chronic kidney disease (CKD) and healthy control patients. METHODS: Thirty patients were enrolled: 18 normophosphatemic CKD subjects and 12 healthy controls. The study duration was 21 days with three 7-day dietary interventions; a high phosphate (HP, 2000 mg/day), low phosphate (750 mg/day) and low phosphate plus phosphate binder (aluminum hydroxide, 500 mg thrice daily with meals), with comparable macronutrient content, administered in random sequence. Baseline and weekly fasting morning measurements of FGF-23, serum phosphate (sPO(4)), 1,25-hydroxyvitamin D (1,25 D) and 24-h urinary calcium (uCa) and phosphate (uPO(4)) were collected. RESULTS: FGF-23 levels were higher in subjects versus controls (72 pg/mL versus 30 pg/mL) at baseline, while sPO(4) remained in the normal range throughout the study. The absolute changes of uPO(4) and uCa for CKD and controls vary according to diet. The absolute changes of FGF-23 and sPO(4) suggest that the effect of the diets might also depend on the CKD status (P-values interaction effect = 0.08 and 0.07, respectively); nonetheless, these changes are evident as a function of dietary interventions, irrespective of CKD status (P-values diet effect = 0.006 and <0.001, respectively). CONCLUSIONS: FGF-23 levels appear to be responsive to changes in diet in both CKD patients and controls. Further studies are required to determine whether lowering dietary phosphate and thus FGF-23 levels are of long-term benefit in CKD patients, irrespective of sPO(4) levels.

Evaluation and outcomes of a 5-year assisted peritoneal dialysis program.

BACKGROUND: In 2016, Peritoneal Dialysis Assist (PDA) was implemented in British Columbia, Canada, as a pilot program to allow patients with physical, cognitive and social impairments to access an independent dialysis modality. This is a presentation of the usage and 5-year clinical outcomes of our provincial assisted peritoneal dialysis (PD) program. METHODS: Patients who utilised long-term or respite PDA services in British Columbia, Canada, from 2016 to 2021 were included in this program evaluation. Incident and prevalent patient numbers were characterised annually as well as indications for PDA and patient demographics both annually and over time. Outcomes of interest included death, transfer to haemodialysis, transplantation and cessation of the PDA program but retention on PD. RESULTS: Three hundred twenty-two total patients received services through the PDA program. The percentage of PD patients supported by long-term PDA service has grown to 11.2% in the most recent year. Patients spend a median of 13.6 (95% CI: 11.0, 16.1) months on long-term PDA, prolonging overall patient duration on PD by a little over a year. Of the patients who exited the long-term PDA program, 73 (37.4%) were able to utilise the service until they died. CONCLUSION: PDA is an accessible, patient-centric service with clear and standardised referral criteria. Through the implementation of a local PDA program, patients have accessed PD and may have extended their PD life span, through avoidance of in-centre haemodialysis, by over 13 months during this 5-year study period. A significant proportion of patients on long-term PDA were able to use their preferred kidney replacement modality at home until they reached end of life.

COVID-19 Vaccine Effectiveness Among Patients With Maintenance Dialysis; Observations From Population Level Cohort Studies in 2 Large Canadian Provinces.

Background: It was unknown if the effectiveness of COVID-19 vaccines could vary between regions. Objective: To explore key differences in COVID-19 pandemics in British Columbia (BC) and Ontario (ON) and to investigate if the vaccine effectiveness (VE) among maintenance dialysis population could vary between these 2 provinces. Study Design: Retrospective cohort. Setting and Patients: This retrospective cohort study included patients from population-level registry in BC who were on maintenance dialysis from December 14, 2020, to December 31, 2021. The COVID-19 VE among BC patients were compared to the previously published VE among similar patient population in ON. Two-sample t-test for unpaired data were used to investigate if the VE estimates from BC and ON were statistically significantly different. Exposure: Exposure to COVID-19 vaccines (BNT162b2, ChAdOx1nCoV-19, mRNA-1273) was modeled in a time-dependent fashion. Outcome: Reverse transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 infection and related severe outcome defined by hospitalization or death. Analytical Approach: Time-dependent Cox regression analysis. Results: This study using BC data included 4284 patients. Median age was 70 years and 61% was male. Median follow-up time was 382 days. 164 patients developed COVID-19 infection. The ON study by Oliver et al included 13 759 patients with a mean age of 68 years. 61% of the study sample was male. Median follow-up time for patients in the ON study was 102 days. A total of 663 patients developed COVID-19 infection. During the overlapped study periods, BC had 1 pandemic wave compared to 2 in Ontario with substantially higher infection rates. Vaccination timing and roll out among the study population were substantially different. Median time between first and second dose was 77 days (interquartile range [IQR] 66-91) in BC compared to 39 days (IQR = 28-56) in Ontario. Distribution of COVID-19 variants during the study period appeared to be similar. In BC, compared to pre-vaccination person-time, risk of developing COVID-19 infection was 64% (aHR [95% CI] 0.36 [0.21, 0.63]), 80% (0.20 [0.12, 0.35]) and 87% (0.13 [0.06, 0.29]) less when exposed to 1 dose, 2 doses, and 3 doses, respectively. In contrast, risk reduction among Ontario patients was 41% (0.59 [0.46, 0.76]) and 69% (0.31 [0.22, 0.42]) for 1 dose and 2 doses, respectively (patients did not receive the third dose by study end date of June 30, 2021). VE against COVID-19 infection in BC and ON was not statistically significantly different, the P values for exposure to 1 dose and 2 doses comparisons were 0.103 and 0.163, respectively. Similarly, in BC, risk of developing COVID-19-related hospitalization or death were 54% (0.46 [0.24, 0.90]), 75% (0.25 [0.13, 0.48]) and 86% (0.14 [0.06, 0.34]) less for 1 dose, 2 doses, and 3 doses, respectively. Interestingly, exposure to second dose appeared to provide better protection against severe outcomes in Ontario versus BC, risk reduction was 83% (aHR = 0.17, 95% CI [0.10, 0.30]) and 75% (aHR = 0.25, 95% CI [0.13, 0.48]), respectively. However, the adjusted hazard ratios were not statistically significantly different between BC and ON, the P values were 0.676 and 0.369 for exposure to 1 dose and 2 doses, respectively. Limitations: Infection rate, variant distribution, and vaccination strategies were compared using publicly available data. VE estimates were compared from 2 independent cohort studies from 2 provinces without patient-level data sharing. Conclusions: Health Canada approved COVID-19 vaccines were highly effective among patients with maintenance dialysis from BC and ON. Although there appeared to be between province differences in pandemic waves and vaccination strategies, the VE against COVID-19 infection as well as related severe outcome appeared to be not statistically significantly different. A nationally representative VE could be estimated using pooled data from multiple regions.

Contexte: On ignore si l'efficacité des vaccins contre la COVID-19 varie d'une région à l'autre. Objectif: Examiner les principales différences entre les infections à la COVID-19 en Colombie-Britannique (C.-B.) et en Ontario et déterminer si l'efficacité des vaccins (EV) varie entre ces deux provinces dans la population des personnes sous dialyze d'entretien. Type d'étude: Étude de cohorte rétrospective. Sujets et cadre de l'étude: Cette étude de cohorte rétrospective porte sur des patients issus du registre de la population de Britanno-Colombiens sous dialyze d'entretien entre le 14 décembre 2020 et le 31 décembre 2021. L'EV contre la COVID-19 chez les patients de la C.-B. a été comparée à l'EV précédemment publiée pour une population de patients similaires en Ontario. Un test t à deux échantillons de données non appariées a été utilisé pour déterminer si les estimations de l'EV en C.-B. et en Ontario étaient statistiquement différentes. Exposition: L'exposition aux vaccins contre la COVID-19 (BNT162b2, ChAdOx1nCoV-19, mRNA-1273) a été modélisée en fonction du temps. Résultats: La RT-PCR a confirmé l'infection à la COVID-19 et les résultats graves liés à la maladie ont été définis par une hospitalization ou le décès. Approche analytique: Analyze par régression Cox dépendante du temps. Résultats: L'étude en cours utilisant les données de la C.-B. incluait 4 284 patients. L'âge médian était de 70 ans et 61 % étaient des hommes. Le temps médian de suivi était de 382 jours. De ces patients, 164 avaient contracté la COVID-19. L'étude de l'Ontario (Oliver et coll.) porte sur 13 759 patients (61 % d'hommes) dont la moyenne d'âge était de 68 ans. Le temps médian de suivi pour les patients de l'étude ontarienne était de 102 jours. Un total de 663 patients avait contracté la COVID-19. Au cours des périodes d'étude qui se sont chevauchées, la Colombie-Britannique a connu une vague pandémique, contre deux en Ontario, avec des taux d'infection beaucoup plus élevés. Le calendrier et le déploiement de la vaccination parmi la population étudiée étaient sensiblement différents. Le temps médian entre la première et la deuxième dose de vaccin était de 77 jours en C.-B. (ÉIQ: 66-91) et de 39 jours en Ontario (ÉIQ: 28-56). La répartition des différents variants du virus de la COVID-19 au cours de la période d'étude semble similaire. En C.-B., comparativement au temps-personne avant la vaccination, le risque de contracter la COVID-19 était réduit de 64 % (risque relatif corrigé [IC 95 %]: 0,36 [0,21-0,63]) après une dose, de 80 % (RRc: 0,20 (0,12-0,35)) après deux doses et de 87 % (RRc: 0,13 (0,06-0,29)) après 3 doses. En Ontario, la réduction de ce même risque était de 41 % (RRc: 0,59 (0,46-0,76)) après une dose et de 69 % (RRc: 0,31 (0,22-0,42)) après deux doses (les patients n'avaient pas reçu de troisième dose le 30 juin 2021, la date de fin de l'étude). L'EV contre une infection à la COVID-19 n'était pas statistiquement différente entre les deux provinces, avec des valeurs p pour les comparaisons d'exposition respectivement de 0,103 et de 0,163 pour la 1re et 2e dose. De même, en Colombie-Britannique, le risque d'être hospitalisé ou de décéder en raison d'une infection à la COVID-19 était réduit de 54 % (RRc: 0,46 (0,24-0,90)) après une dose, de 75 % (RRc: 0,25 (0,13-0,48)) après deux doses et de 86 % (RRc: 0,14 [0,06-0,34] après trois doses. Il est intéressant de noter que la deuxième dose semblait offrir une meilleure protection contre les complications graves aux patients de l'Ontario par rapport à ceux de la C.-B., avec une réduction du risque de 83 % [RRc: 0,17 (0,10-0,30)] et de 75 % [RRc: 0,25 (0,13-0,48)], respectivement. Les valeurs du risque relatif corrigé n'étaient cependant pas statistiquement différentes, leurs valeurs p s'établissant à 0,676 après la 1re dose et à 0,369 après la 2e. Limites: Le taux d'infection, la distribution des variants et les stratégies de vaccination ont été comparés à partir des données disponibles au public. Les estimations de l'EV ont été comparées à partir de deux études de cohortes indépendantes dans deux provinces, sans partage de données au niveau des patients. Conclusion: Les vaccins contre la COVID-19 approuvés par Santé Canada ont été très efficaces chez les patients sous dialyze d'entretien en Colombie-Britannique et en Ontario. Bien qu'il y ait des différences entre les provinces en ce qui concerne les vagues de pandémie et les stratégies de vaccination, l'efficacité des vaccins contre une infection à la COVID-19 et ses complications graves ne semble pas significativement différente. Une estimation représentative à l'échelle nationale de l'efficacité des vaccins pourrait être calculée à partir de données regroupées provenant de plusieurs régions.

Regional Variation in Hemoglobin Distribution Among Individuals With CKD: the ISN International Network of CKD Cohorts.

Introduction: Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin. Methods: In this cross-sectional study, hemoglobin distribution was evaluated in each cohort overall and stratified by sex and estimated glomerular filtration rate (eGFR). Relationships between candidate predictors and hemoglobin were assessed from linear regression models in each cohort. Estimates were subsequently pooled in a random effects model. Results: A total of 58,613 participants from 21 adult cohorts (median eGFR range of 17-49 ml/min) and 3 pediatric cohorts (median eGFR range of 26-45 ml/min) were included with broad geographic representation. Hemoglobin values varied substantially among the cohorts, overall and within eGFR categories, with particularly low mean hemoglobin observed in women from Asian and African cohorts. Across the eGFR range, women had a lower hemoglobin compared to men, even at an eGFR of 15 ml/min (mean difference 5.3 g/l, 95% confidence interval [CI] 3.7-6.9). Lower eGFR, female sex, older age, lower body mass index, and diabetic kidney disease were all independent predictors of a lower hemoglobin value; however, this only explained a minority of variance (R2 7%-44% across cohorts). Conclusion: There are substantial regional differences in hemoglobin distribution among individuals with CKD, and the majority of variance is unexplained by demographics, eGFR, or comorbidities. These findings call for a renewed interest in improving our understanding of hemoglobin determinants in specific CKD populations.

Towards rational approaches of health care utilization in complex patients: an exploratory randomized trial comparing a novel combined clinic to multiple specialty clinics in patients with renal disease-cardiovascular disease-diabetes.

BACKGROUND: Optimal utilization of health care resources for patients with chronic conditions is an increasing focus of health care policy researchers and clinicians. Kidney disease, diabetes (DM) and cardiovascular disease (CVD) often coexist within one individual, but current systems are designed to manage individual conditions. We sought to examine if streamlining medical care of complex patients (two or more conditions) is associated with similar, worse or improved outcomes using a randomized controlled study design. METHODS: Patients attending a kidney care clinic (KCC) and at least one other specialty clinic of interest (DM, CVD) were randomly assigned to either the 'combined clinic (CC)' arm, where resources from all three were integrated into one clinic, or to the 'standard care' arm with continued attendance at multiple specialty clinics (MC), including the KCC. The primary outcome was hospitalization rate and sample size was calculated based on non-inferiority. RESULTS: Of 150 subjects enrolled, 11 subjects exited before study commencement: 139 remained for final analysis. Other than older age in the MC group (P = 0.009), the demographics were comparable. Hospitalization rates were not different (95% CI for the difference: 0.013-0.207; P = 0.03). Similar proportions in each group achieved clinical and laboratory targets. Mortality (13%) and dialysis (32%) rates were the same between groups. Differences in the cost of clinic visits alone were $86,400 per year in favor of the CC. CONCLUSIONS: Medical care of complex patients may be delivered in a single combined specialty clinic as compared to multiple disease specific clinics without compromising patient care or important health outcomes, with demonstrable outpatient costs savings.

The effect of a multidisciplinary care clinic on the outcomes in pediatric chronic kidney disease.

BACKGROUND: Current best evidence-based practice for children with chronic kidney disease (CKD) attempts to achieve good clinical outcomes through careful management of comorbidities and is likely best achieved with a multidisciplinary care (MDC) CKD clinic. METHODS: In this retrospective study of children with CKD in British Columbia, Canada, we analyzed clinical outcomes in a cohort of 73 CKD patients from 2003 under a standard care model and a second cohort of 125 CKD patients from 2009 under a MDC clinic model. RESULTS: Patient demographics were similar, but there was a decrease in the percentage of patients with CKD stage 3-5 in 2009 (59 vs. 75 %; p = 0.002), although the absolute number increased. After adjustment for severity of CKD, hemoglobin was significantly higher (13.0 g/dl vs. 12.2 g/dl, p < 0.03), calcium was significantly higher (9.6 mg/dl vs. 9.1 mg/dl, p < 0.001), and albumin was significantly higher (4.4 g/dl vs. 3.8 g/dl, p < 0.001) in the 2009 MDC cohort. The rate of disease progression, assessed by annualized estimated glomerular filtration rate (eGFR) slope, improved from -4.0 ml/min/1.73 m(2) in the 2003 cohort to 0.5 ml/min/1.73 m(2) in the 2009 cohort (p < 0.01). Blood pressure control was better in 2009 although not statistically significant. CONCLUSIONS: Multidisciplinary care improved the outcomes of children with CKD especially in anemia management, bone mineral metabolism, nutrition, and renal disease progression.