Summary Since the first living-donor kidney transplantation in 1954, more than half a million living kidney donations have occurred and research has advanced knowledge about long-term donor outcomes. ...Donors in developed countries have a similar life expectancy and quality of life as healthy non-donors. Living kidney donation is associated with an increased risk of end-stage renal disease, although this outcome is uncommon (<0·5% increase in incidence at 15 years). Kidney donation seems to elevate the risks of gestational hypertension and pre-eclampsia. Many donors incur financial expenses due to factors such as lost wages, need for sick days, and travel expenses. Yet, most donors have no regrets about donation. Living kidney donation is practised ethically when informed consent incorporates information about risks, uncertainty about outcomes is acknowledged when it exists, and a donor's risks are proportional to benefits for the donor and recipient. Future research should determine whether outcomes are similar for donors from developing countries and donors with pre-existing conditions such as obesity.
Peritoneal dialysis (PD)-related peritonitis carries high morbidity for PD patients. Understanding the characteristics and risk factors for peritonitis can guide regional development of prevention ...strategies. We describe peritonitis rates and the associations of selected facility practices with peritonitis risk among countries participating in the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS).
Observational prospective cohort study.
7,051 adult PD patients in 209 facilities across 7 countries (Australia, New Zealand, Canada, Japan, Thailand, United Kingdom, United States).
Facility characteristics (census count, facility age, nurse to patient ratio) and selected facility practices (use of automated PD, use of icodextrin or biocompatible PD solutions, antibiotic prophylaxis strategies, duration of PD training).
Peritonitis rate (by country, overall and variation across facilities), microbiology patterns.
Poisson rate estimation, proportional rate models adjusted for selected patient case-mix variables.
2,272 peritonitis episodes were identified in 7,051 patients (crude rate, 0.28 episodes/patient-year). Facility peritonitis rates were variable within each country and exceeded 0.50/patient-year in 10% of facilities. Overall peritonitis rates, in episodes per patient-year, were 0.40 (95% CI, 0.36-0.46) in Thailand, 0.38 (95% CI, 0.32-0.46) in the United Kingdom, 0.35 (95% CI, 0.30-0.40) in Australia/New Zealand, 0.29 (95% CI, 0.26-0.32) in Canada, 0.27 (95% CI, 0.25-0.30) in Japan, and 0.26 (95% CI, 0.24-0.27) in the United States. The microbiology of peritonitis was similar across countries, except in Thailand, where Gram-negative infections and culture-negative peritonitis were more common. Facility size was positively associated with risk for peritonitis in Japan (rate ratio RR per 10 patients, 1.07; 95% CI, 1.04-1.09). Lower peritonitis risk was observed in facilities that had higher automated PD use (RR per 10 percentage points greater, 0.95; 95% CI, 0.91-1.00), facilities that used antibiotics at catheter insertion (RR, 0.83; 95% CI, 0.69-0.99), and facilities with PD training duration of 6 or more (vs <6) days (RR, 0.81; 95% CI, 0.68-0.96). Lower peritonitis risk was seen in facilities that used topical exit-site mupirocin or aminoglycoside ointment, but this association did not achieve conventional levels of statistical significance (RR, 0.79; 95% CI, 0.62-1.01).
Sampling variation, selection bias (rate estimates), and residual confounding (associations).
Important international differences exist in the risk for peritonitis that may result from varied and potentially modifiable treatment practices. These findings may inform future guidelines in potentially setting lower maximally acceptable peritonitis rates.
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Timely, effective, and individualised dietary interventions are essential for patients undergoing dialysis. However, delivery of dietary advice is challenging due to limited access to renal ...dietitians, as well as logistic and scheduling difficulties for patients receiving dialysis. The objectives of this study were to explore consumer perspectives regarding dietary advice utilising telehealth technology. Twenty-two participants (seventeen patients receiving dialysis, five caregivers) were purposively recruited from a local dialysis centre and participated in one of three focus groups. Each focus group was recorded, transcribed, and analysed using inductive thematic analysis. One overarching theme: "a desire to learn" was apparent. The four themes that facilitated this process are herein described: Meaningful
-a need for improved and individualised communication about diet using positively framed messages with consistency among clinicians. Conducive
-a preference for tailored, current, and clear dietary information (plain language was preferred, with practical advice on making dietary changes).
-health advice at the right time (consumers felt overwhelmed, not supported enough with timely advice, and experienced difficulty attending appointments in addition to dialysis treatments).
-delivering information using different technologies (consumers preferred a combination of delivery methods for dietetic advice including text/SMS/App messages as an adjunct to face-to-face care). The results showed that consumers believe that telehealth options are an acceptable adjunct to receive dietary advice in a timely manner, and feedback from patients and caregivers has informed the design of a clinical trial to incorporate the use of telehealth to improve the management of serum phosphate.
Non-randomized studies suggest an association between serum uric acid levels and progression of chronic kidney disease (CKD). The aim of this systematic review is to summarize evidence from ...randomized controlled trials (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal outcomes.
Medline, Excerpta Medical Database and Cochrane Central Register of Controlled Trials were searched with English language restriction for RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment on renal outcomes. Treatment effects were summarized using random-effects meta-analysis.
Eight trials (476 participants) evaluating allopurinol treatment were eligible for inclusion. There was substantial heterogeneity in baseline kidney function, cause of CKD and duration of follow-up across these studies. In five trials, there was no significant difference in change in glomerular filtration rate from baseline between the allopurinol and control arms mean difference (MD) 3.1 mL/min/1.73 m2, 95% confidence intervals (CI) -0.9, 7.1; heterogeneity χ2=1.9, I2=0%, P=0.75. In three trials, allopurinol treatment abrogated increases in serum creatinine from baseline (MD -0.4 mg/dL, 95% CI -0.8, -0.0 mg/dL; heterogeneity χ2=3, I2=34%, P=0.22). Allopurinol had no effect on proteinuria and blood pressure. Data for effects of allopurinol therapy on progression to end-stage kidney disease and death were scant. Allopurinol had uncertain effects on the risks of adverse events.
Uric acid-lowering therapy with allopurinol may retard the progression of CKD. However, adequately powered randomized trials are required to evaluate the benefits and risks of uric acid-lowering therapy in CKD.
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.
The clinical benefits of using "biocompatible" neutral pH solutions containing low levels of glucose degradation products for peritoneal dialysis compared with standard solutions are uncertain. In ...this multicenter, open-label, parallel-group, randomized controlled trial, we randomly assigned 185 incident adult peritoneal dialysis patients with residual renal function to use either biocompatible or conventional solution for 2 years. The primary outcome measure was slope of renal function decline. Secondary outcome measures comprised time to anuria, fluid volume status, peritonitis-free survival, technique survival, patient survival, and adverse events. We did not detect a statistically significant difference in the rate of decline of renal function between the two groups as measured by the slopes of GFR: -0.22 and -0.28 ml/min per 1.73 m(2) per month (P=0.17) in the first year in the biocompatible and conventional groups, respectively, and, -0.09 and -0.10 ml/min per 1.73 m(2) per month (P=0.9) in the second year. The biocompatible group exhibited significantly longer times to anuria (P=0.009) and to the first peritonitis episode (P=0.01). This group also had fewer patients develop peritonitis (30% versus 49%) and had lower rates of peritonitis (0.30 versus 0.49 episodes per year, P=0.01). In conclusion, this trial does not support a role for biocompatible fluid in slowing the rate of GFR decline, but it does suggest that biocompatible fluid may delay the onset of anuria and reduce the incidence of peritonitis compared with conventional fluid in peritoneal dialysis.
Nutritional guidelines recommended limiting dietary phosphorus as part of phosphorus management in patients with kidney failure. Currently, there is no validated phosphorus food frequency ...questionnaire (P-FFQ) to easily capture this nutrient intake. An FFQ of this type would facilitate efficient screening of dietary sources of phosphorus and assist in developing a patient-centered treatment plan. The objectives of this study were to develop and validate a P-FFQ by comparing it with the 24 hr multi-pass recall. Fifty participants (66% male, age 70 ± 13.3 years) with kidney failure undertaking dialysis were recruited from hospital nephrology outpatient departments. All participants completed the P-FFQ and 24 hr multi-pass recalls with assistance from a renal dietitian and then analysed using nutrient analysis software. Bland-Altman analyses were used to determine the agreement between P-FFQ and mean phosphorus intake from three 24 hr multi-pass recalls. Mean phosphorous intake was 1262 ± 400 mg as determined by the 24 hr multi pass recalls and 1220 ± 348 mg as determined by the P-FFQ. There was a moderate correlation between the P-FFQ and 24 hr multi pass recall (r = 0.62,
= 0.37) with a mean difference of 42 mg (95% limits of agreement: 685 mg; -601 mg,
= 0.373) between the two methods. The precision of the P-FFQ was 3.33%, indicating suitability as an alternative to the 24 hr multi pass recall technique. These findings indicate that the P-FFQ is a valid, accurate, and precise tool for assessing sources of dietary phosphorus in people with kidney failure undertaking dialysis and could be used as a tool to help identify potentially problematic areas of dietary intake in those who may have a high serum phosphate.
Patient outcomes in end-stage kidney disease (ESKD) secondary to lupus nephritis have not been well described. To help define this we compared dialysis and transplant outcomes of patients with ESKD ...due to lupus nephritis to all other causes. All patients diagnosed with ESKD who commenced renal replacement therapy in Australia and New Zealand (1963–2012) were included. Clinical outcomes were evaluated in both a contemporary cohort (1998–2012) and the entire 50-year cohort. Of 64,160 included patients, 744 had lupus nephritis as the primary renal disease. For the contemporary cohort of 425 patients with lupus nephritis, the 5-year dialysis patient survival rate was 69%. Of 176 contemporary patients with lupus nephritis who received their first renal allograft, the 5-year patient, overall renal allograft, and death-censored renal allograft survival rates were 95%, 88%, and 93%, respectively. Patients with lupus nephritis had worse dialysis patient survival (adjusted hazard ratio 1.33, 95% confidence interval 1.12–1.58) and renal transplant patient survival (adjusted hazard ratio 1.87, 95% confidence interval 1.18–2.98), but comparable overall renal allograft survival (adjusted hazard ratio 1.19, 95% confidence interval 0.84–1.68) and death-censored renal allograft survival (adjusted hazard ratio 1.05, 95% confidence interval 0.68–1.62) compared with ESKD controls. Similar results were found in the entire cohort and when using competing-risks analysis. Thus, the ESKD of lupus nephritis was associated with worse dialysis and transplant patient survival but comparable renal allograft survival compared with other causes of ESKD.
Background:
Peritoneal dialysis (PD)-associated peritonitis carries significant morbidity, mortality, and is a leading cause of PD technique failure. This study aimed to assess the scope and ...variability of PD-associated peritonitis reported in randomized trials and observational studies.
Methods:
Cochrane Controlled Register of Trials, MEDLINE, and Embase were searched from 2007 to June 2018 for randomized trials and observational studies in adult and pediatric patients on PD that reported PD-associated peritonitis as a primary outcome or as a part of composite primary outcome. We assessed the peritonitis definitions used, characteristics of peritonitis, and outcome reporting and analysis.
Results:
Seventy-seven studies were included, three were randomized trials. Thirty-eight (49%) of the included studies were registry-based observational studies. Twenty-nine percent (n = 22) of the studies did not specify how PD-associated peritonitis was defined. Among those providing a definition of peritonitis, three components were reported: effluent cell count (n = 42, 54%), clinical features consistent with peritonitis (e.g. abdominal pain and/or cloudy dialysis effluent) (n = 35, 45%), and positive effluent culture (n = 19, 25%). Of those components, 1 was required to make the diagnosis in 6 studies (8%), 2 out of 2 were required in 22 studies (29%), 2 out of 3 in 11 studies (14%), and 3 out of 3 in 4 studies (5%). Peritonitis characteristics and outcomes reported across studies included culture-negative peritonitis (n = 47, 61%), refractory peritonitis (n = 42, 55%), repeat peritonitis (n = 9, 12%), relapsing peritonitis (n = 5, 7%), concomitant exit site (n = 16, 21%), and tunnel infections (n = 8, 10%). Peritonitis-related hospitalization was reported in 38% of the studies (n = 29), and peritonitis-related mortality was variably defined and reported in 55% of the studies (n = 42). Peritonitis rate was most frequently reported as episodes per patient year (n = 40, 52%).
Conclusion:
Large variability exists in the definitions, methods of reporting, and analysis of PD-associated peritonitis across trials and observational studies. Standardizing definitions for reporting of peritonitis and associated outcomes will better enable assessment of the comparative effect of interventions on peritonitis. This will facilitate continuous quality improvement measures through reliable benchmarking of this patient-important outcome across centers and countries.
Background Left ventricular mass (LVM) is a widely used surrogate end point in randomized trials involving people with chronic kidney disease (CKD) because treatment-induced LVM reductions are ...assumed to lower cardiovascular risk. The aim of this study was to assess the validity of LVM as a surrogate end point for all-cause and cardiovascular mortality in CKD. Study Design Systematic review and meta-analysis. Setting & Population Participants with any stages of CKD. Selection Criteria for Studies Randomized controlled trials with 3 or more months’ follow-up that reported LVM data. Intervention Any pharmacologic or nonpharmacologic intervention. Outcomes The surrogate outcome of interest was LVM change from baseline to last measurement, and clinical outcomes of interest were all-cause and cardiovascular mortality. Standardized mean differences (SMDs) of LVM change and relative risk for mortality were estimated using pairwise random-effects meta-analysis. Correlations between surrogate and clinical outcomes were summarized across all interventions combined using bivariate random-effects Bayesian models, and 95% credible intervals were computed. Results 73 trials (6,732 participants) covering 25 intervention classes were included in the meta-analysis. Overall, risk of bias was uncertain or high. Only 3 interventions reduced LVM: erythropoiesis-stimulating agents (9 trials; SMD, −0.13; 95% CI, −0.23 to −0.03), renin-angiotensin-aldosterone system inhibitors (13 trials; SMD, −0.28; 95% CI, −0.45 to −0.12), and isosorbide mononitrate (2 trials; SMD, −0.43; 95% CI, −0.72 to −0.14). All interventions had uncertain effects on all-cause and cardiovascular mortality. There were weak and imprecise associations between the effects of interventions on LVM change and all-cause (32 trials; 5,044 participants; correlation coefficient, 0.28; 95% credible interval, −0.13 to 0.59) and cardiovascular mortality (13 trials; 2,327 participants; correlation coefficient, 0.30; 95% credible interval, −0.54 to 0.76). Limitations Limited long-term data, suboptimal quality of included studies. Conclusions There was no clear and consistent association between intervention-induced LVM change and mortality. Evidence for LVM as a valid surrogate end point in CKD is currently lacking.
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