Background Hemodialysis vascular access failure occurs often and increases morbidity for people on hemodialysis therapy. Antiplatelet agents may prevent hemodialysis vascular access failure, but ...potentially may be hazardous in people with end-stage kidney disease who have impaired hemostasis. Study Design Systematic review and meta-analysis of randomized controlled trials. Setting & Population Adults on long-term hemodialysis therapy. Selection Criteria Trials evaluating hemodialysis vascular access outcomes identified by searches in Cochrane CENTRAL and Renal Group Trial Registers and Embase, without language restriction. Intervention Antiplatelet therapy. Outcomes Hemodialysis vascular access failure (thrombosis or loss of patency), failure to attain vascular access suitable for dialysis, need for intervention to attain patency or assist maturation, major bleeding, minor bleeding, and antiplatelet treatment withdrawal. Treatment effects were summarized as RRs with 95% CIs using random-effects meta-analysis. Results 21 eligible trials (4,826 participants) comparing antiplatelet treatment with placebo or no treatment were included. 12 trials (3,118 participants) started antiplatelet therapy around the time of dialysis vascular access surgery and continued treatment for approximately 6 months. Antiplatelet treatment reduced fistula failure (thrombosis or loss of patency) by one-half (6 trials, 1,222 participants; RR, 0.49; 95% CI, 0.30-0.81) but had uncertain effects on graft patency and attaining fistula or graft function suitable for dialysis. Overall, antiplatelet treatment had uncertain effects on major bleeding. Limitations Unclear or high risk of bias in most trials and few trial data, particularly for antiplatelet effects on graft function and vascular access suitability for dialysis. Conclusions Antiplatelet treatment protects fistula from thrombosis or loss of patency, but has little or no effect on graft patency and uncertain effects on vascular access maturation for dialysis and major bleeding. Interventions that demonstrably improve vascular access suitability for dialysis are needed.
Background Phosphate binders are widely used to control serum phosphorus levels in patients with chronic kidney disease (CKD). We analyzed the effects of phosphate binders on biochemical and ...patient-level end points in patients with CKD. Study Design Systematic review and meta-analysis by searching MEDLINE (1966 to April 2009), EMBASE (1980 to April 2009), and the Cochrane Renal Group Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL). Setting & Population Patients with CKD. Selection Criteria for Studies Randomized controlled trials. Intervention Phosphate binders. Outcomes Serum phosphorus, calcium, and parathyroid hormone levels; incidence of hypercalcemia; all-cause mortality; adverse effects. Results 40 trials (6,406 patients) were included. There was no significant decrease in all-cause mortality (10 randomized controlled trials; 3,079 patients; relative risk RR, 0.73; 95% confidence interval CI, 0.46 to 1.16), hospitalization, or end-of-treatment serum calcium-phosphorus product levels with sevelamer compared with calcium-based agents. There was a significant decrease in end-of-treatment phosphorus and parathyroid hormone levels with calcium salts compared with sevelamer and a significant decrease in risk of hypercalcemia (RR, 0.47; 95% CI, 0.36 to 0.62) with sevelamer compared with calcium-based agents. There was a significant increase in risk of gastrointestinal adverse events with sevelamer in comparison to calcium salts (RR, 1.39; 95% CI, 1.04 to 1.87). Compared with calcium-based agents, lanthanum significantly decreased end-of-treatment serum calcium and calcium-phosphorus product levels, but with similar end-of-treatment phosphorus levels. Effects of calcium acetate on biochemical end points were similar to those of calcium carbonate. Existing data are insufficient to conclude for a differential impact of any phosphate binder on cardiovascular mortality or other patient-level outcome. Limitations Few long-term studies of the efficacy of phosphate binders on mortality and musculoskeletal morbidity, significant heterogeneity for many surrogate outcomes, and suboptimal reporting of study methods to determine trial quality. Conclusion Currently, there are insufficient data to establish the comparative superiority of non–calcium-binding agents over calcium-containing phosphate binders for such important patient-level outcomes as all-cause mortality and cardiovascular end points. Additional trials are still required to examine the differential effects of phosphate-binding agents on these end points and the mineral homeostasis pathway.
Background Convective dialysis therapies (hemofiltration or hemodiafiltration) are associated with lower mortality compared to hemodialysis in observational studies. A previous meta-analysis of ...randomized trials comparing convective modalities with hemodialysis in 2006 was inconclusive due to insufficient data. Additional randomized trials recently have reported conflicting results. Study Design Systematic review and meta-analysis of randomized trials to February 27, 2013. Setting & Population Patients with chronic kidney failure treated by hemodialysis, hemodiafiltration, hemofiltration, or biofiltration. Selection Criteria for Studies Randomized controlled trials. Intervention Convective therapies (hemodiafiltration, hemofiltration, and acetate-free biofiltration) compared with hemodialysis. Outcomes All-cause and cardiovascular mortality, nonfatal cardiovascular events, hospitalization, change in dialysis modality, health-related quality of life, adverse events, blood pressure, and clearances of urea and β2 -microglobulin. Results 35 trials (4,039 participants) were included. In low-quality evidence, convective dialysis had little or no effect on all-cause mortality (relative risk RR, 0.87; 95% CI, 0.70-1.07) and may reduce cardiovascular mortality (RR, 0.75; 95% CI, 0.58-0.97) and hypotension (RR, 0.72; 95% CI, 0.66-0.80) during dialysis, but had uncertain effects on nonfatal cardiovascular events (RR, 1.14; 95% CI, 0.85-1.52) and hospitalization (RR, 1.21; 95% CI, 0.12-12.05). Adverse events were not reported systematically and health-related quality-of-life outcomes were sparse. Convective therapies reduced predialysis levels of β2 -microglobulin (mean difference, −5.77 95% CI, −10.97 to −0.56 mg/dL) and increased dialysis dose (Kt/Vurea mean difference, 0.10; 95% CI, 0.02-0.19), but these effects were very heterogeneous. Sensitivity analyses limited to trials comparing hemodiafiltration with hemodialysis showed similar results. Limitations Studies had important risks of bias leading to low confidence in the summary estimates and generally were limited to patients who had adequate dialysis vascular access. Conclusions Treatment effects of convective dialysis are unreliable due to limitations in trial methods and reporting. Convective dialysis may reduce cardiovascular but not all-cause mortality, and effects on nonfatal cardiovascular events and hospitalization are inconclusive.
Background Depression occurs relatively commonly in people with chronic kidney disease (CKD), but it is uncertain whether depression is a risk factor for premature death in this population. ...Interventions to reduce mortality in CKD consistently have been ineffective and new strategies are needed. Study Design Systematic review and meta-analysis of cohort studies. Setting & Population Adults with CKD. Selection Criteria for Studies Cohort studies identified in Ovid MEDLINE through week 3 December 2012 without language restriction. Predictor Depression status as determined by physician diagnosis, clinical coding, or self-reported scales. Selection Criteria for Studies All-cause and cardiovascular mortality. Outcomes were summarized as relative risks (RRs) with 95% CIs using random-effects meta-analysis. Results 22 studies (83,381 participants) comprising 12,063 cases of depression (mean prevalence, 27.4%; 95% CI, 20.0%-36.3%) with a follow-up of 3 months to 6.5 years were included. Methodological quality generally was good or fair. Depression consistently increased the risk of death from any cause (RR, 1.59; 95% CI, 1.35-1.87), but had less certain effects on cardiovascular mortality (RR, 1.88; 95% CI, 0.84-4.19). Associations for mortality were similar regardless of the diagnostic method used for depression, but were weaker in analyses controlled for preexisting cardiovascular disease (RR, 1.36; 95% CI, 1.23-1.50). Limitations Meta-analyses adjusting for antidepressant medication use were not possible, and data for kidney transplant recipients and individuals with earlier stages of CKD not treated with dialysis were limited. Conclusions Depression is associated with a substantially increased risk of death in people with CKD. Effective treatment for depression in people with CKD may reduce mortality.
Background Sexual dysfunction is an under-recognized problem in men and women with chronic kidney disease (CKD). The prevalence, correlates, and predictors of this condition in patients with CKD have ...not been evaluated comprehensively. Study Design Systematic review and meta-analysis. Setting & Population Patients treated using dialysis (dialysis patients), patients treated using transplant (transplant recipients), and patients with CKD not treated using dialysis or transplant (nondialysis nontransplant patients with CKD). Selection Criteria for Studies Observational studies conducted in patients with CKD only or including a control group without CKD. Predictor Type of study population. Outcomes Sexual dysfunction in men and women with CKD using validated tools, such as the International Index of Erectile Function, the Female Sexual Function Index (FSFI), or other measures as reported by study investigators. Results 50 studies (8,343 patients) of variable size (range, 16-1,023 patients) were included in this review. Almost all studies explored sexual dysfunction in men and specifically erectile dysfunction. The summary estimate of erectile dysfunction in men with CKD was 70% (95% CI, 62%-77%; 21 studies, 4,389 patients). Differences in reported prevalence rates of erectile dysfunction between different studies were attributable primarily to age, study populations, and type of study tool used to assess the presence of erectile dysfunction. In women, the reported prevalence of sexual dysfunction was assessed in only 306 patients from 2 studies and ranged from 30%-80%. Compared with the general population, women with CKD had a significantly lower overall FSFI score (8 studies or subgroups, 407 patients; mean difference, −9.28; 95% CI, −12.92 to −5.64). Increasing age, diabetes mellitus, and depression consistently were found to correlate with sexual dysfunction in 20 individual studies of patients with CKD using different methods. Limitations Suboptimal and lack of uniform assessment of outcome measures. Conclusions Sexual dysfunction is highly prevalent in both men and women with CKD, especially among those on dialysis. Larger studies enrolling different ethnic groups, using validated study tools, and analyzing the influence of various factors on the development of sexual dysfunction are needed.
Background Peritonitis frequently complicates peritoneal dialysis. Appropriate treatment is essential to reduce adverse outcomes. Available trial evidence about peritoneal dialysis peritonitis ...treatment was evaluated. Selection Criteria for Studies The Cochrane CENTRAL Registry (2005 issue), MEDLINE (1966 to February 2006), EMBASE (1985 to February 2006), and reference lists were searched to identify randomized trials of treatments for patients with peritoneal dialysis peritonitis. Interventions Trials of antibiotics (comparisons of routes, agents, and dosing regimens), fibrinolytic agents, peritoneal lavage, and intraperitoneal immunoglobulin. Outcomes Treatment failure, relapse, catheter removal, microbiological eradication, hospitalization, all-cause mortality, and adverse reactions. Results 36 eligible trials were identified: 30 trials (1,800 patients) of antibiotics; 4 trials (229 patients) of urokinase; 1 trial of peritoneal lavage (36 patients); and 1 trial of intraperitoneal immunoglobulin (24 patients). No superior antimicrobial class was identified. In particular, glycopeptides and first-generation cephalosporins were equivalent (3 trials, 387 patients; relative risk RR, 1.84; 95% confidence interval CI, 0.95 to 3.58). Simultaneous catheter removal/replacement was superior to urokinase at decreasing treatment failures (1 trial, 37 patients; RR, 2.35; 95% CI, 1.13 to 4.91). Continuous and intermittent intraperitoneal antibiotic dosing were equivalent regarding treatment failure (4 trials, 338 patients; RR, 0.69; 95% CI, 0.37 to 1.30) and relapse (4 trials, 324 patients; RR, 0.93; 95% CI, 0.63 to 1.39). One trial showed superiority of intraperitoneal antibiotics over intravenous therapy. Limitations The method quality of trials generally was suboptimal and outcome definitions were inconsistent. Small patient numbers led to inadequate power to show an effect. Interventions, such as optimal duration of antibiotic therapy, were not evaluated. Conclusions Trials did not identify superior antibiotic regimens. Intermittent and continuous antibiotic dosing are equivalent treatment strategies.
