Background A predictive histologic classification recently was proposed to determine the prognostic value of kidney biopsy in patients with antineutrophil cytoplasmic antibody–associated renal ...vasculitis (AAV). Study Design A dual-purpose retrospective observational cohort study to assess the reproducibility of the new classification and clinical variables that predict outcomes. Setting & Participants 169 consecutive patients with AAV were identified; 145 were included in the reproducibility study, and 120, in the outcomes study. Predictor Kidney biopsy specimens were classified according to the predominant glomerular lesion: focal, mixed, crescentic, and sclerotic. An assessment of tubular atrophy also was performed. Outcomes The primary outcome was time to end-stage kidney disease or all-cause mortality, modeled using Cox regression analysis. Measurements Estimated glomerular filtration rate, requirement for renal replacement therapy. Results For the reproducibility study, the overall inter-rater reliability of the classification demonstrated variability among 3 histopathologists (intraclass correlation coefficient, 0.48; 95% CI, 0.38-0.57; κ statistic = 0.46). Although agreement was high in the sclerotic group (κ = 0.70), it was less consistent in other groups (κ = 0.51, κ = 0.47, and κ = 0.23 for crescentic, focal, and mixed, respectively). For the clinical outcomes study, patients with sclerotic patterns of glomerular injury displayed the worst outcomes. Patients with focal (HR, 0.26; 95% CI, 0.12-0.58; P = 0.001), crescentic (HR, 0.33; 95% CI, 0.16-0.69; P = 0.003), and mixed (HR, 0.39; 95% CI, 0.18-0.81; P = 0.01) patterns of injury had lower risk of the primary outcome. Tubular atrophy correlated with outcome, and advanced injury was associated with worse outcomes (HR, 5.9; 95% CI, 2.25-15.47; P < 0.001). Level of kidney function at presentation strongly predicted outcome (HR per 10-mL/min/1.73 m2 increase in estimated glomerular filtration rate, 0.63; 95% CI, 0.46-0.81; P < 0.001). Limitations Data availability, given the retrospective nature of the study. Conclusions Reproducibility of the classification was seen only in patients with sclerotic patterns of glomerular injury. Sclerotic pattern of glomerular injury, advanced chronic interstitial injury, and decreased kidney function all predicted poor outcomes.
Background There is a resurgence of interest in home hemodialysis (HD), especially frequent or extended forms involving unconventionally frequent (>3 times/wk) and/or long (>6 hours) treatments. This ...resurgence is driven by cost containment and experience suggesting lower mortality risk compared with facility HD and peritoneal dialysis (PD). Study Design We performed an observational cohort study using the Australia and New Zealand Dialysis and Transplant Registry, using marginal structural modeling to adjust for time-varying medical comorbidity as both a source of selection bias and an intermediary variable on the causal pathway to death. Setting & Participants All adult patients starting renal replacement therapy in Australia and New Zealand since March 31, 1996, followed up to December 31, 2007. Predictor The main predictor was dialysis modality (conventional facility HD, conventional home HD, frequent/extended facility HD, frequent/extended home HD, and PD). We adjusted for the confounding effects of patient demographics and comorbid conditions. Outcome Patient mortality. Results We analyzed 26,016 patients with 856,007 patient-months of follow-up. Relative to conventional facility HD, adjusted mortality HRs were 0.51 (95% CI, 0.44-0.59) for conventional home HD, 1.16 (95% CI, 0.94-1.44) for frequent/extended facility HD, 0.53 (95% CI, 0.41-0.68) for frequent/extended home HD, and 1.10 (95% CI, 1.06-1.16) for PD. The apparent benefit of home HD on mortality risk was less for patients who were nonwhite, non-Asian, and older. Limitations Potential for residual confounding from the limited collection of comorbid conditions (no collection of cognitive or motor impairment, depression, left ventricular volume or structure, or blood pressure/fluid volume status) and lack of socioeconomic, medication, and biochemical data in analyses. Conclusions Our study supports a survival advantage of home HD without a difference between conventional and frequent/extended modalities. Suitably designed clinical trials of frequent/extended HD are needed to determine the presence and extent of mortality benefit with this modality.
The evidence supporting an initial mycophenolate mofetil (MMF) dose of 2 g daily in tacrolimus-treated renal transplant recipients is limited. In a non-contemporaneous single-centre cohort study we ...compared the incidence of leukopaenia, rejection and graft dysfunction in patients initiated on MMF 1.5 g and 2 g daily. Baseline characteristics and tacrolimus trough levels were similar by MMF group. MMF doses became equivalent between groups by 12-months post-transplant, driven by dose reductions in the 2 g group. Leukopaenia occurred in 42.4% of patients by 12-months post-transplant. MMF 2 g was associated with a 1.80-fold increased risk of leukopaenia compared to 1.5 g. Rejection occurred in 44.8% of patients by 12-months post-transplantation. MMF 2 g was associated with half the risk of rejection relative to MMF 1.5 g. Over the first 7-years post-transplantation there was no difference in renal function between groups. Additionally, the development of leukopaenia or rejection did not result in reduced renal function at 7-years post-transplant. Leukopaenia was not associated with an increased incidence of serious infections or rejection. This study demonstrates the initial MMF dose has implications for the incidence of leukopaenia and rejection. Since neither dose produced superior long-term graft function, clinical equipoise remains regarding the optimal initial mycophenolate dose in tacrolimus-treated renal transplant recipients.
Mortality is an important outcome for all dialysis stakeholders. We examined associations between dialysis modality and mortality in the modern era.
Observational study comparing dialysis inception ...cohorts 1998-2002, 2003-2007, 2008-2012, and 2013-2017.
Australia and New Zealand (ANZ) dialysis population.
The primary exposure was dialysis modality: facility hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), automated PD (APD), or home HD.
The main outcome was death.
Cause-specific proportional hazards models with shared frailty and subdistribution proportional hazards (Fine and Gray) models, adjusting for available confounding covariates.
In 52,097 patients, the overall death rate improved from ~15 deaths per 100 patient-years in 1998-2002 to ~11 in 2013-2017, with the largest cause-specific contribution from decreased infectious death. Relative to facility HD, mortality with CAPD and APD has improved over the years, with adjusted hazard ratios in 2013-2017 of 0.88 (95% CI, 0.78-0.99) and 0.91 (95% CI, 0.82-1.00), respectively. Increasingly, patients with lower clinical risk have been adopting APD, and to a lesser extent CAPD. Relative to facility HD, mortality with home HD was lower throughout the entire period of observation, despite increasing adoption by older patients and those with more comorbidities. All effects were generally insensitive to the modeling approach (initial vs time-varying modality, cause-specific versus subdistribution regression), different follow-up time intervals (5 year vs 7 year vs 10 year). There was no effect modification by diabetes, comorbidity, or sex.
Potential for residual confounding, limited generalizability.
The survival of patients on PD in 2013-2017 appears greater than the survival for patients on facility HD in ANZ. Additional research is needed to assess whether changing clinical risk profiles over time, varied dialysis prescription, and morbidity from dialysis access contribute to these findings.
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Background The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) is more accurate than the Modification of Diet in Renal Disease (MDRD) Study equation. We applied both equations in a cohort ...representative of the Australian adult population. Study Design Population-based cohort study. Setting & Participants 11,247 randomly selected noninstitutionalized Australians aged ≥ 25 years who attended a physical examination during the baseline AusDiab (Australian Diabetes, Obesity and Lifestyle) Study survey. Predictors & Outcomes Glomerular filtration rate (GFR) was estimated using the MDRD Study and CKD-EPI equations. Kidney damage was defined as urine albumin-creatinine ratio ≥ 2.5 mg/mmol in men and ≥ 3.5 mg/mmol in women or urine protein-creatinine ratio ≥ 0.20 mg/mg. Chronic kidney disease (CKD) was defined as estimated GFR (eGFR) ≥ 60 mL/min/1.73 m2 or kidney damage. Participants were classified into 3 mutually exclusive subgroups: CKD according to both equations; CKD according to the MDRD Study equation, but no CKD according to the CKD-EPI equation; and no CKD according to both equations. All-cause mortality was examined in subgroups with and without CKD. Measurements Serum creatinine and urinary albumin, protein, and creatinine measured on a random spot morning urine sample. Results 266 participants identified as having CKD according to the MDRD Study equation were reclassified to no CKD according to the CKD-EPI equation (estimated prevalence, 1.9%; 95% CI, 1.4-2.6). All had an eGFR ≥ 45 mL/min/1.73 m2 using the MDRD Study equation. Reclassified individuals were predominantly women with a favorable cardiovascular risk profile. The proportion of reclassified individuals with a Framingham-predicted 10-year cardiovascular risk ≥ 30% was 7.2% compared with 7.9% of the group with no CKD according to both equations and 45.3% of individuals retained in stage 3a using both equations. There was no evidence of increased all-cause mortality in the reclassified group (age- and sex-adjusted hazard ratio vs no CKD, 1.01; 95% CI, 0.62-1.97). Using the MDRD Study equation, the prevalence of CKD in the Australian population aged ≥ 25 years was 13.4% (95% CI, 11.1-16.1). Using the CKD-EPI equation, the prevalence was 11.5% (95% CI, 9.42-14.1). Limitations Single measurements of serum creatinine and urinary markers. Conclusions The lower estimated prevalence of CKD using the CKD-EPI equation is caused by reclassification of low-risk individuals.
Research aims to improve health outcomes for patients. However, the setting of research priorities is usually performed by clinicians, academics, and funders, with little involvement of patients or ...caregivers and using processes that lack transparency. A national workshop was convened in Australia to generate and prioritize research questions in chronic kidney disease (CKD) among diverse stakeholder groups. Patients with CKD (n = 23), nephrologists/surgeons (n = 16), nurses (n = 8), caregivers (n = 7), and allied health professionals and researchers (n = 4) generated and voted on intervention questions across 4 treatment categories: CKD stages 1 to 5 (non–dialysis dependent), peritoneal dialysis, hemodialysis, and kidney transplantation. The 5 highest ranking questions (in descending order) were as follows: How effective are lifestyle programs for preventing deteriorating kidney function in early CKD? What strategies will improve family consent for deceased donor kidney donation, taking different cultural groups into account? What interventions can improve long-term post-transplant outcomes? What are effective interventions for post hemodialysis fatigue? How can we improve and individualize drug therapy to control post-transplant side effects? Priority questions were focused on prevention, lifestyle, quality of life, and long-term impact. These prioritized research questions can inform funding agencies, patient/consumer organizations, policy makers, and researchers in developing a CKD research agenda that is relevant to key stakeholders.
Hyperphosphatemia is associated with increased fibroblast growth factor 23 (FGF23), arterial calcification, and cardiovascular mortality. Effects of phosphate-lowering medication on vascular ...calcification and arterial stiffness in CKD remain uncertain.
To assess the effects of non-calcium-based phosphate binders on intermediate cardiovascular markers, we conducted a multicenter, double-blind trial, randomizing 278 participants with stage 3b or 4 CKD and serum phosphate >1.00 mmol/L (3.10 mg/dl) to 500 mg lanthanum carbonate or matched placebo thrice daily for 96 weeks. We analyzed the primary outcome, carotid-femoral pulse wave velocity, using a linear mixed effects model for repeated measures. Secondary outcomes included abdominal aortic calcification and serum and urine markers of mineral metabolism.
A total of 138 participants received lanthanum and 140 received placebo (mean age 63.1 years; 69% male, 64% White). Mean eGFR was 26.6 ml/min per 1.73 m
; 45% of participants had diabetes and 32% had cardiovascular disease. Mean serum phosphate was 1.25 mmol/L (3.87 mg/dl), mean pulse wave velocity was 10.8 m/s, and 81.3% had abdominal aortic calcification at baseline. At 96 weeks, pulse wave velocity did not differ significantly between groups, nor did abdominal aortic calcification, serum phosphate, parathyroid hormone, FGF23, and 24-hour urinary phosphate. Serious adverse events occurred in 63 (46%) participants prescribed lanthanum and 66 (47%) prescribed placebo. Although recruitment to target was not achieved, additional analysis suggested this was unlikely to have significantly affected the principle findings.
In patients with stage 3b/4 CKD, treatment with lanthanum over 96 weeks did not affect arterial stiffness or aortic calcification compared with placebo. These findings do not support the role of intestinal phosphate binders to reduce cardiovascular risk in patients with CKD who have normophosphatemia.
Australian Clinical Trials Registry, ACTRN12610000650099.
Objective
To identify barriers and enablers to COVID‐19 vaccination in renal transplant recipients who are undecided about vaccination.
Methods
An online survey was distributed to 876 adult kidney ...transplant recipients at a tertiary referral service, who had not been vaccinated against COVID‐19. The survey assessed willingness to be vaccinated, attitudes toward COVID‐19 vaccines, and barriers and enablers to proceeding with vaccination.
Results
The survey response rate was 54% (473/876). Three hundred and forty‐six (73.1%) participants planned to receive vaccination (yes group), 105 (22.2%) were undecided, and 22 (4.7%) refused vaccination. The undecided group were younger but were not different in other demographic characteristics to the yes group. The undecided group were less positive toward (34.29% vs. 91.3%, p < .001) and more concerned about (93.3% vs. 25.1%, p < .001) vaccination than the yes group. Their concerns related to vaccine safety (including harm to their transplant), poor efficacy, and a lack of rigorous testing in transplant recipients. Undecided recipients had received less vaccine‐specific information from medical specialists than the yes group. Most undecided participants (95.1%) were willing to proceed with vaccination with appropriate supports. The most desired supports were information and a recommendation to proceed with vaccination from their treating transplant specialist and team.
Conclusion(s)
Concerns about vaccine safety (including harm to transplant), poor vaccine efficacy, and lack of rigorous testing were barriers to vaccine uptake. Most undecided recipients would proceed with vaccination with specific recommendations and vaccine information provided by their transplant specialist/team. These simple interventions can be readily implemented to optimize vaccine uptake.
22.2% of transplant recipients were undecided about having the COVID‐19 vaccine. This group were less positive and more concerned about the vaccine. Concerns about vaccine safety, insufficient vaccine information and concerns about vaccine efficacy were barriers to vaccine uptake whereas information and recommendation to have the vaccine by their transplant specialist/team and transplant clinic consultation were enablers of vaccine uptake. The majority (95.1%) would proceed with vaccination with the right supports.
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