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Objective: Hypertension affects 50-90% of kidney transplant recipients and is associated with cardiovascular disease and graft loss. We aimed to evaluate the comparative benefits and harms of blood pressure lowering agents in people with a functioning kidney transplant., Methods: We conducted a systematic review with network meta-analysis of randomized controlled trials (RCTs). We searched MEDLINE, Embase, and CENTRAL through to October 2023. RCTs evaluating blood pressure lowering agents administered for at least 2 weeks in people with a functioning kidney transplant with and without preexisting hypertension were eligible. Two reviewers independently extracted data. The primary outcome was graft loss. Treatment effects were estimated using random effects network meta-analysis, with treatment effects expressed as an odds ratio (OR) for binary outcomes and mean difference (MD) for continuous outcomes together with their 95% confidence interval (CI). Confidence in the evidence was assessed using GRADE for network meta-analysis., Results: Ninety-four studies (7547 adults) were included. Two studies were conducted in children. No blood pressure-lowering agent reduced the risk of graft loss, withdrawal because of adverse events, death, cardiovascular or kidney outcomes compared with placebo/other drug class. Angiotensin-converting enzyme inhibitors and angiotensin receptor blocker therapy may incur greater odds of hyperkalemia compared with calcium channel blockers [odds ratio (OR) 5.48, 95% confidence interval (CI) 2.47-12.16; and OR 8.67, 95% CI 2.65-28.36; low certainty evidence, respectively)., Conclusion: The evidentiary basis for the comparative benefits and safety of blood pressure lowering agents in people with a functioning kidney transplant is limited to guide treatment decision-making., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Dietary phosphorus restrictions are usually recommended for people on haemodialysis, although its impact on patient-relevant outcomes is uncertain. We aimed to evaluate the association between total phosphorus intake and its sources with mortality in haemodialysis. Phosphorus intake was ascertained within the DIET-HD study in 8110 adults on haemodialysis. Adjusted Cox regression analyses were conducted to evaluate the association between the total and source-specific phosphorus (plant-, animal-, or processed and other sources) with mortality. During a median 3.8 years of follow-up, there were 2953 deaths, 1160 cardiovascular-related. The median phosphorus intake was 1388 mg/day. Every standard deviation (SD) (896 mg/day) increase in total phosphorus was associated with higher all-cause mortality [hazard ratio (HR), 1.16; 95% confidence intervals (CI), 1.06-1.26] and cardiovascular mortality (HR, 1.18; 95% CI, 1.03-1.36). Every SD (17%) increase in the proportion of phosphorus from plant sources was associated with lower all-cause mortality (HR, 0.95; 95% CI, 0.90-0.99). Every SD (9%) increase in the proportion of phosphorus from the processed and other sources was associated with higher all-cause mortality (HR, 1.06; 95% CI, 1.02-1.10). A higher total phosphorus intake was associated with increased all-cause and cardiovascular death. This association is driven largely by the phosphorus intake from processed food. Plant based phosphorus was associated with lower all-cause mortality.

Rationale & Objective: A healthy lifestyle promotes cardiovascular health and reduces cardiac-related mortality in the general population, but its benefits for people receiving maintenance hemodialysis are uncertain., Study Design: Prospective cohort study., Setting & Participants: 5,483 of 9,757 consecutive adults receiving maintenance hemodialysis (January 2014 to June 2017, median dialysis vintage: 3.6 years) in a multinational private dialysis network and with complete lifestyle data., Exposure: Based on the American Heart Association's recommendations for cardiovascular prevention, a modified healthy lifestyle score was the sum of 4 components addressing use of smoking tobacco, physical activity, diet, and control of systolic blood pressure., Outcome: Cardiovascular and all-cause mortality., Analytical Approach: Adjusted proportional hazards regression analyses with country as a random effect to estimate the associations between lifestyle score (low [0-2 points] as the referent, medium [3-5], and high [6-8]) and mortality. Associations were expressed as adjusted hazard ratio (AHR) with 95% CI., Results: During a median of 3.8 years (17,451 person-years in total), there were 2,163 deaths, of which 826 were related to cardiovascular disease. Compared with patients who had a low lifestyle score, the AHRs for all-cause mortality among those with medium and high lifestyle scores were 0.75 (95% CI, 0.65-0.85) and 0.64 (95% CI, 0.54-0.76), respectively. Compared with patients who had a low lifestyle score, the AHRs for cardiovascular mortality among those with medium and high lifestyle scores were 0.73 (95% CI, 0.59-0.91) and 0.65 (95% CI, 0.49-0.85), respectively., Limitations: Self-reported lifestyle, data-driven approach., Conclusions: A healthier lifestyle is associated with lower all-cause and cardiovascular mortality among patients receiving maintenance hemodialysis., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Dietary potassium restriction in people receiving maintenance hemodialysis is standard practice and is recommended in guidelines, despite a lack of evidence. We aimed to assess the association between dietary potassium intake and mortality and whether hyperkalemia mediates this association., Design, Setting, Participants, & Measurements: A total of 8043 adults undergoing maintenance hemodialysis in Europe and South America were included in the DIETary intake, death and hospitalization in adults with end-stage kidney disease treated with HemoDialysis (DIET-HD) study. We measured baseline potassium intake from the Global Allergy and Asthma European Network food frequency questionnaire and performed time-to-event and mediation analyses., Results: The median potassium intake at baseline was 3.5 (interquartile range, 2.5-5.0) g/d. During a median follow-up of 4.0 years (25,890 person-years), we observed 2921 (36%) deaths. After adjusting for baseline characteristics, including cardiac disease and food groups, dietary potassium intake was not associated with all-cause mortality (per 1 g/d higher dietary potassium intake: hazard ratio, 1.00; 95% confidence interval [95% CI], 0.95 to 1.05). A mediation analysis showed no association of potassium intake with mortality, either through or independent of serum potassium (hazard ratio, 1.00; 95% CI, 1.00 to 1.00 and hazard ratio, 1.01; 95% CI, 0.96 to 1.06, respectively). Potassium intake was not significantly associated with serum levels (0.03; 95% CI, -0.01 to 0.07 mEq/L per 1 g/d higher dietary potassium intake) or the prevalence of hyperkalemia (≥6.0 mEq/L) at baseline (odds ratio, 1.11; 95% CI, 0.89 to 1.37 per 1 g/d higher dietary potassium intake). Hyperkalemia was associated with cardiovascular death (hazard ratio, 1.23; 95% CI, 1.03 to 1.48)., Conclusions: Higher dietary intake of potassium is not associated with hyperkalemia or death in patients treated with hemodialysis., (Copyright © 2021 by the American Society of Nephrology.)

Introduction: Regular physical activity is associated with longevity in adults receiving hemodialysis, but it is uncertain whether this association varies by causal pathways (cardiovascular and noncardiovascular)., Methods: DIET-HD was a prospective, multinational study of adults undergoing hemodialysis across Europe and Argentina. We classified participants as physically inactive, occasionally active (irregularly to once a week), or frequently active (twice a week or more), using a self-reported questionnaire. Potential confounders were balanced across exposure groups using propensity scores. Weighted Cox proportional hazards models with double robust estimators evaluated the association between physical activity and all-cause, cardiovascular, and noncardiovascular mortality., Results: Of 8043 participants in DIET-HD, 6147 (76%) had information on physical activity. A total of 2940 (48%) were physically inactive, 1981 (32%) occasionally active, and 1226 (20%) frequently active. In a median follow-up of 3.8 years (19,677 person-years), 2337 (38%) deaths occurred, including 1050 (45%) from cardiovascular causes. After propensity score weighting, occasional physical activity was associated with lower all-cause (adjusted hazard ratio [aHR] = 0.80, 95% CI = 0.72-0.89), cardiovascular (aHR = 0.82, 95% CI = 0.70-0.96), and noncardiovascular (aHR = 0.81, 95% CI = 0.69-0.94) mortality compared with inactivity. Frequent physical activity was associated with lower all-cause (aHR = 0.82, 95% CI = 0.71-0.95) and cardiovascular (aHR = 0.77, 95% CI = 0.62-0.94) mortality, but not noncardiovascular mortality (aHR = 0.88, 95% CI = 0.72-1.08). A dose-dependent association of physical activity with cardiovascular death was observed ( P trend = 0.01)., Conclusion: Compared with self-reported physical inactivity, occasional and frequent physical activities were associated, dose dependently, with lower cardiovascular mortality in adults receiving hemodialysis., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Objective: To describe patient perspectives on recruitment and retention in clinical trials., Study Design and Setting: Systematic review of qualitative studies that reported the perspective of adult patients with any health condition who accepted or declined to participate in clinical trials., Results: Sixty-three articles involving 1681 adult patients were included. Six themes were identified. Four themes reflected barriers: ambiguity of context and benefit - patients were unaware of the research question and felt pressured in making decisions; lacking awareness of opportunities - some believed health professionals obscured trials opportunities, or felt confused because of language barriers; wary of added burden - patients were without capacity because of sickness or competing priorities; and skepticism, fear and mistrust - patients feared loss of privacy, were suspicious of doctor's motivation, afraid of being a guinea pig, and disengaged from not knowing outcomes. Two themes captured facilitators: building confidence - patients hoped for better treatment, were supported from family members and trusted medical staff; and social gains and belonging to the community - altruism, a sense of belonging and peer encouragement motivated participation in trials., Conclusion: Improving the visibility and transparency of trials, supporting informed decision making, minimizing burden, and ensuring confidence and trust may improve patient participation in trials., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To compare functional and anatomical results of combined phacoemulsification and dexamethasone intravitreal implant (Ozurdex; DEX-I) with standard phacoemulsification in diabetic patients with cataract., Methods: Retrospective, comparative, cohort study. Patients with nonproliferative diabetic retinopathy, macular edema, and cataract, treated routinely at the Eye Clinic, Azienda Ospedaliero Universitaria Policlinico, Bari, Italy with phacoemulsification associated with DEX-I (n = 23; Phaco-Dex) or standard phacoemulsification (n = 23; Phaco-alone). Best-correct visual acuity, central subfield thickness, and intraocular pressure were assessed at baseline and monthly for 3 months after surgery, and t-test was used to assess change from baseline. A multilevel regression model with an unstructured correlation-type matrix to account for repeated data measures was used for statistical analysis in and between groups., Results: With Phaco-Dex, best-correct visual acuity increased significantly from the first month (P = 0.0005 vs. baseline) and remained stable at the following visits; central subfield thickness decreased significantly from Month 2 (P = 0.049 and P = 0.04 vs. baseline, respectively); at each timepoint, central subfield thickness was significantly lower in the Phaco-Dex group versus Phaco-alone. Intraocular pressure increased significantly during follow-up (P = 0.001 at Month 3 vs. baseline) but remained within the normal range. In the Phaco-alone group, best-correct visual acuity, and intraocular pressure did not show any significant changes after surgery, whereas central subfield thickness increased from Month 2 (P = 0.05 vs. baseline)., Conclusion: In diabetic patients with macular edema and visually significant cataract, combined treatment with phacoemulsification and DEX-I seemed to be effective, safe, and superior to standard phacoemulsification considering both functional and tomographic parameters., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Health data are often plagued with missing values that can greatly reduce the sample size if only complete cases are considered for analysis. Furthermore, analyses that ignore missing data have the potential to introduce bias in the parameter estimates. Multiple imputation techniques have been developed to recover the information that would otherwise be lost when excluding observations with missing data and to help minimize bias. However, the validity of analyses using imputed data relies on the imputation model having been correctly specified. The aim of this guide is to aid the reader in the decision-making process when conducting an analysis with multiply imputed data in the context of nephrology research. We discuss (i) missing mechanism assumption, (ii) imputation method, (iii) imputation model, (iv) derived variables, (v) the number of imputed data sets, (vi) diagnostic checks, (vii) analysis and pooling of results, and (viii) reporting the results. This process is demonstrated using data from the National Health and Nutrition Examination Survey to explore the association between hypertension and kidney disease in adults from the general population. Example code is provided for SAS software and the mice package in R., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objectives: There are over 4,000 trials conducted in people with coronavirus disease 2019. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for coronavirus disease 2019 trials., Design: In an online survey conducted in English, Chinese, Italian, Portuguese, and Spanish languages, adults with coronavirus disease 2019, their family members, health professionals, and the general public rated the importance of outcomes using a 9-point Likert scale (7-9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analyzed thematically., Setting: International., Subjects: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public, and health professionals (including clinicians, policy makers, regulators, funders, and researchers)., Interventions: None., Measurements: None., Main Results: In total, 9,289 participants from 111 countries (776 people with coronavirus disease 2019 or family members, 4,882 health professionals, and 3,631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia, and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean > 7.5, median ≥ 8, and > 70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems, and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating, and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes., Conclusions: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals.

Objectives: Solid organ transplant recipients are at increased risk of skin cancer, affecting more than 50% of recipients. We aimed to determine the effectiveness of interventions for behavioural change for sun protection or skin cancer prevention in solid organ transplant recipients., Design: Systematic review., Data Sources: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL) and CINAHL from inception to November 2019., Eligibility Criteria: We included randomised controlled trials that evaluated the effect of behavioural or pharmaceutical interventions on behavioural change or skin cancer prevention in solid organ transplant recipients., Data Extraction and Synthesis: Risks of bias and evidence certainty were assessed using Cochrane and the Grading of Recommendations Assessment Development and Evaluation framework., Results: Twenty trials (n=2295 participants) were included. It is uncertain whether behavioural interventions improve sun protection behaviour (n=3, n=414, standardised mean difference (SMD) 0.89, 95% CI -0.84 to 2.62, I 2 =98%) and knowledge (n=4, n=489, SMD 0.50, 95% CI 0.12 to 0.87, I 2= 76%) as the quality of evidence is very low. We are uncertain of the effects of mammalian target of rapamaycin inhibitors on the incidence of non-melanocytic skin cancer (n=5, n=1080, relative risk 0.46, 95% CI 0.28 to 0.75, I 2 = 72%) as the quality of evidence is very low., Conclusions: Behavioural and pharmaceutical preventive interventions may improve sun protective behaviour and knowledge, and reduce the incidence of non-melanocytic skin cancer, but the overall quality of the evidence is very low and insufficient to guide decision-making and clinical practice., Prospero Registration Number: CRD42017063962., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Modifying lifestyle can prevent the progression of chronic kidney disease (CKD) but the specific elements which lead to favourable behaviour change are not well understood. We aimed to identify and evaluate behaviour change techniques and functions in lifestyle interventions for preventing the progression of CKD., Design: Systematic review., Data Sources: MEDLINE, EMBASE, CINAHL and PsycINFO., Eligibility Criteria: Trials of lifestyle behaviour change interventions (including diet, physical activity, smoking and/or alcohol) published to September 2018 in adults with CKD stages 1-5., Data Extraction and Synthesis: Trial characteristics including population, sample size, study setting, intervention, comparator, outcomes and study duration, were extracted. Study quality was independently assessed by two reviewers using the Cochrane risk of bias tool. The Behaviour Change Technique Taxonomy v1 was used to identify behaviour change techniques (eg, goal setting) and the Health Behaviour Change Wheel was used to identify intervention functions (eg, education). Both were independently assessed by three reviewers., Results: In total, 26 studies involving 4263 participants were included. Risk of bias was high or unclear in most studies. Interventions involved diet (11), physical activity (8) or general lifestyle (7). Education was the most frequently used function (21 interventions), followed by enablement (18), training (12), persuasion (4), environmental restructuring (4), modelling (2) and incentivisation (2). The most common behaviour change techniques were behavioural instruction (23 interventions), social support (16), behavioural demonstration (13), feedback on behaviour (12) and behavioural practice/rehearsal (12). Eighteen studies (69%) showed a significant improvement in at least one primary outcome, all of which included education, persuasion, modelling and incentivisation., Conclusion: Lifestyle behaviour change interventions for CKD patients frequently used education, goal setting, feedback, monitoring and social support. The most promising interventions included education and used a variety of intervention functions (persuasion, modelling and incentivisation)., Prospero Registration Number: CRD42019106053., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale & Objective: In the general population, cognitive impairment is associated with increased mortality, and higher levels of education are associated with lower risks for cognitive impairment and mortality. These associations are not well studied in patients receiving long-term hemodialysis and were the focus of the current investigation., Study Design: Prospective cohort study., Setting & Participants: Adult hemodialysis patients treated in 20 Italian dialysis clinics., Exposures: Patients' cognitive function across 5 domains (memory, attention, executive function, language, and perceptual-motor function), measured using a neuropsychological assessment comprising 10 tests; and patients' self-reported years of education., Outcome: All-cause mortality., Analytical Approach: Nested multivariable Cox regression models were used to examine associations of cognition (any domain impaired, number of domains impaired, and global function score from principal components analysis of unadjusted test scores) and education with mortality and whether there were interactions between them., Results: 676 (70.6%) patients participated, with a median age of 70.9 years and including 38.8% women. Cognitive impairment was present in 79.4% (527/664; 95% CI, 76.3%-82.5%). During a median follow-up of 3.3 years (1,874 person-years), 206 deaths occurred. Compared to no cognitive impairment, adjusted HRs for mortality were 1.77 (95% CI, 1.07-2.93) for any impairment, 1.48 (95% CI, 0.82-2.68) for 1 domain impaired, 1.88 (95% CI, 1.01-3.53) for 2 domains, and 2.01 (95% CI, 1.14-3.55) for 3 to 5 domains. The adjusted HR was 0.68 (95% CI, 0.51-0.92) per standard deviation increase in global cognitive function score. Compared with primary or lower education, adjusted HRs were 0.79 (95% CI, 0.53-1.20) for lower secondary and 1.13 (95% CI, 0.80-1.59) for upper secondary or higher. The cognition-by-education interaction was not significant (P=0.7)., Limitations: Potential selection bias from nonparticipation and missing data; no data for cognitive decline; associations with education were not adjusted for other socioeconomic factors., Conclusions: Cognitive impairment is associated with premature mortality in hemodialysis patients. Education does not appear to be associated with mortality., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Chronic kidney disease is a risk factor for oral diseases, which may be associated with premature death. We evaluated the risk of all-cause and cardiovascular mortality associated with oral mucosal lesions in adults with kidney failure treated with long-term haemodialysis., Methods: Oral mucosal lesions (herpes, ulceration, neoformation, white lesion, red lesion, oral candidiasis, geographical tongue, petechial lesions, and fissured tongue) were evaluated within the Oral Diseases in Haemodialysis (ORAL-D) study, a multinational cohort study of 4726 haemodialysis adults. We conducted cox regression analyses adjusted for demographic and clinical variables to evaluate the association with all-cause and cardiovascular mortality., Results: Overall, 4205 adults (mean age 61.6 ± 15.6 years) underwent oral mucosal examination with 40% affected by at least one lesion. The prevalence of oral lesions was (in order of frequency): oral herpes 0.5%, mucosal ulceration 1.7%, neoformation 2.0%, white lesion 3.5%, red lesion 4.0%, oral candidiasis 4.6%, geographical tongue 4.9%, petechial lesions 7.9%, and fissured tongue 10.7%. During median follow-up of 3.5 years, 2114 patients died (1013 due to cardiovascular disease). No association was observed between any individual oral lesion and all-cause or cardiovascular mortality when adjusted for comorbidities, except for oral candidiasis, which was associated with all-cause mortality (adjusted hazard ratio 1.37, 95% CI 1.00 to 1.86) and cardiovascular mortality (adjusted hazard ratio 1.64, 95% CI 1.09 to 2.46)., Conclusion: Oral mucosal lesions are prevalent in haemodialysis patients. Oral candidiasis appears to be a risk factor for death due to cardiovascular diseases., Competing Interests: MR, PN, VS, EC, RG, MRL, MT, PS, AB-S, JD, LF, JNF, DC, SS, AGB, JH, CW, LG are employees of Diaverum. GS holds a consultancy with Diaverum Renal Services. JH and GS received unrestricted funding from Diaverum Renal Services, a provider of renal services and LCO (Le Cliniche Odontoiatriche, Italy). Funding was used to assist with the cost of oral examination visits in countries where these required specific funding. Funding was also applied to cover overhead costs for study coordinators in each contributing country, material printing and distribution and procurement of standardized examination kits for all patient assessments. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: The comparative effectiveness of treatment with angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), or their combination in people with albuminuria and cardiovascular risk factors is unclear., Methods: In a multicenter, randomized, open label, blinded end point trial, we evaluated the effectiveness on cardiovascular events of ACE or ARB monotherapy or combination therapy, targeting BP<130/80 in patients with moderate or severe albuminuria and diabetes or other cardiovascular risk factors. End points included a primary composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, and hospitalization for cardiovascular causes and a revised end point of all-cause mortality. Additional end points included ESRD, doubling of serum creatinine, albuminuria, eGFR, BP, and adverse events., Results: Because of slow enrollment, the trial was modified and stopped 41% short of targeted enrollment of 2100 participants, corresponding to 35% power to detect a 25% reduced risk in the primary outcome. Our analysis included 1243 adults, with median follow-up of 2.7 years. Efficacy outcomes were similar between groups (ACE inhibitor versus ARB, ACE inhibitor versus combination, ARB versus combination) as were rates of serious adverse events. The rate of permanent discontinuation for ARB monotherapy (6.3%) was significantly lower than for ACE inhibitor monotherapy (15.7%) or combined therapy (18.3%)., Conclusions: Patients may tolerate ARB monotherapy better than ACE inhibitor monotherapy. However, data from this trial and similar trials, although as yet inconclusive, show no trend suggesting differences in mortality and renal outcomes with ACE inhibitors or ARBs as dual or monotherapy in patients with albuminuria and diabetes or other cardiovascular risk factors., (Copyright © 2018 by the American Society of Nephrology.)

Objectives: To examine the effect of age on associations between household income and overall health from birth to adolescence, and whether age patterns vary by country. It is uncertain whether income-related health inequalities remain stable, widen, or narrow as children age, which impacts optimal timing of equity-focused interventions., Study Design: Systematic review (CRD42016038583) of MEDLINE, Embase, PsycINFO, CINAHL, SocINDEX (full-text), and EconLit (full-text) to April 2017. We included observational studies and trials in children and adolescents (0-18 years of age), examining age differences in associations between income and overall health (self-rated, clinician-rated, proxy-rated). One reviewer extracted data; 2 evaluated risk of bias., Results: Thirty-eight articles containing 43 studies (30 cross-sectional, 13 cohort) were identified, from high-income (n = 39) and middle-income (n = 4) countries. In the US (n = 21), positive income-health associations emerged in early childhood, and these inequalities typically widened progressively into adolescence. Relative to 0- to 3-year-olds, ratios of income-health coefficients ranged from 1.10-3.71 for 4-8 years of age, 1.26-3.86 for 9-12 years of age, 1.36-6.71 for 13-17 years. In the United Kingdom and Ireland (n = 8), inequalities emerged in early-to-mid childhood, but age patterns were less consistent. In other high-income countries (Australia, Canada, France, Germany, Japan, Republic of Korea), inequalities mostly persisted or widened with age. In middle-income countries, inequalities appeared to narrow (Indonesia n = 2) or persist (Brazil n = 2) with age. Limitations are unclear/high risk of bias and dataset overlap for some studies., Conclusions: In many countries, income-related health status inequalities persist or widen as children age. Interventions that improve health equity early in the life-course are needed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Mounting evidence indicates an increased risk of cognitive impairment in adults with end-stage kidney disease on dialysis, but the extent and pattern of deficits across the spectrum of cognitive domains are uncertain., Methods: We conducted a cross-sectional study of 676 adult hemodialysis patients from 20 centers in Italy, aiming to evaluate the prevalence and patterns of cognitive impairment across five domains of learning and memory, complex attention, executive function, language and perceptual-motor function. We assessed cognitive function using a neuropsychological battery of 10 tests and calculated test and domain z-scores using population norms (age or age/education). We defined cognitive impairment as a z-score  ≤ -1.5., Results: Participants' median age was 70.9 years (range 21.6-94.1) and 262 (38.8%) were women. Proportions of impairment on each domain were as follows: perceptual-motor function 31.5% (150/476), language 41.2% (273/662), executive function 41.7% (281/674), learning and memory 42.2% (269/638), complex attention 48.8% (329/674). Among 474 participants with data for all domains, only 28.9% (n  =  137) were not impaired on any domain, with 25.9% impaired on a single domain (n  =  123), 17.3% on two (n  =  82), 13.9% on three (n  =  66), 9.1% on four (n  =  43) and 4.9% (n  =  23) on all five. Across patients, patterns of impairment combinations were diverse., Conclusions: In conclusion, cognitive impairment is extremely common in hemodialysis patients, across numerous domains, and patients often experience multiple deficits simultaneously. Clinical care should be tailored to meet the needs of patients with different types of cognitive impairment and future research should focus on identifying risk factors for cognitive decline.

Sexual dysfunction may affect 80% of women in hemodialysis. However the specific patterns and clinical correlates of sexual functioning remain poorly described. The aim of this study was to assess prevalence and correlates of the individual domains of sexual functioning in women treated with hemodialysis. We recruited, into this multinational cross-sectional study, women treated with long-term hemodialysis (Collaborative Working Group on Depression and Sexual dysfunction in Hemodialysis study). Self-reported domains of sexual functioning were assessed by the Female Sexual Function Index, which is routinely administered within the network of dialysis patients followed by the working group. Lower scores represented lower sexual functioning. Socio-demographic and clinical correlates of each domain of sexual functioning were identified by stepwise multivariable linear regression. Sensitivity analyses were restricted to women who reported being sexually active. We found that of 1309 enrolled women, 659 (50.3%) provided complete responses to FSFI survey questions and 232 (35%) reported being sexually active. Overall, most respondents reported either no sexual activity or low sexual functioning in all measured domains (orgasm 75.1%; arousal 64.0%; lubrication 63.3%; pain 60.7%; satisfaction 60.1%; sexual desire 58.0%). Respondents who were waitlisted for a kidney transplant reported scores with higher sexual functioning, while older respondents reported scores with lower functioning. The presence of depression was associated with worse lubrication and pain scores [mean difference for depressed versus non-depressed women (95% CI) -0.42 (-0.73 to -0.11), -0.53 (-0.89 to -0.16), respectively] while women who had experienced a previous cardiovascular event reported higher pain scores [-0.77 (-1.40- to -0.13)]. In conclusion, women in hemodialysis reported scores consistent with marked low sexual functioning across a range of domains; the low functioning appeared to be associated with comorbidity.

Background: Periodontitis is associated with cardiovascular mortality in the general population and adults with chronic diseases. However, it is unclear whether periodontitis predicts survival in the setting of kidney failure., Methods: ORAL-D was a propensity matched analysis in 3338 dentate adults with end-stage kidney disease treated in a hemodialysis network in Europe and South America designed to examine the association between periodontitis and all-cause and cardiovascular-related mortality in people on long-term hemodialysis. Participants were matched 1:1 on their propensity score for moderate to severe periodontitis assessed using the World Health Organization Community Periodontal Index. A random-effects Cox proportional hazards model was fitted with shared frailty to account for clustering of mortality risk within countries., Results: Among the 3338 dentate participants, 1355 (40.6%) had moderate to severe periodontitis at baseline. After using propensity score methods to generate a matched cohort of participants with periodontitis similar to those with none or mild periodontal disease, moderate to severe periodontitis was associated with a lower risk of all-cause (9.1 versus 13.0 per 100 person years, hazard ratio 0.74, 95% confidence interval 0.61 to 0.90) and cardiovascular (4.3 versus 6.9 per 100 person years, hazard ratio 0.67, 0.51 to 0.88) mortality. These associations were not changed substantially when participants were limited to those with 12 or more natural teeth and when accounting for competing causes of cardiovascular death., Conclusion: In contrast to the general population, periodontitis does not appear to be associated with an increased risk of early death in adults treated with hemodialysis.

The increased risks of death and adverse events with erythropoiesis-stimulating agent (ESA) therapy targeting a higher hemoglobin level are established. It is uncertain whether the adverse effects of ESA therapy are related to dose and are mitigated when a fixed low ESA dose is used. We conducted a multicenter, prospective randomized open-label, blinded-endpoint (PROBE) trial to evaluate fixed low versus high dose ESA therapy on patient outcomes. We intended to recruit 2104 hemodialysis patients >18 years with anemia or receiving ESA treated at dialysis clinics in Italy. The intervention was fixed low (4000 IU epoetin alfa equivalent weekly) or high (18,000 IU epoetin alfa equivalent weekly) dose ESA for 12 months. Primary outcomes were serum transferrin, ferritin, albumin, C-reactive protein and ESA dose. Secondary outcomes were the composite of death or cardiovascular event, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, cardiovascular hospitalization, and quality of life. Study recruitment was terminated after inclusion of 656 participants with convergence of ESA dose between groups during follow up. Fixed low dose ESA had uncertain effects on serum ferritin (delta of delta (DD) 3.9 ng/ml, 95% CI -85.0 to 92.8), transferrin (9.2 mg/dl, -6.3 to 24.8), transferrin saturation (3.7%, -5.0 to 12.3), serum albumin (-0.03 g/dl, -0.2 to 0.1), or C-reactive protein (-0.6 mg/l, -3.3 to 2.1). In addition, fixed dose therapy had inconclusive effects on the composite endpoint of mortality and cardiovascular events (hazard ratio [HR] 0.95, 95% CI 0.66 to 1.37), death (0.98, 0.64 to 1.52), nonfatal myocardial infarction (0.52, 0.18 to 1.52), nonfatal stroke (no events), hospital admission for cardiovascular causes (0.93, 0.50 to 1.72) or health-related quality of life. A fixed low ESA dose in hemodialysis patients has uncertain effects on serum parameters, mortality, cardiovascular events, and quality of life. Hemoglobin targets may be so entrenched in nephrology practice that a trial of ESA dose is no longer possible.

Background: Depression and early death are both common in adults with Stage 5 chronic kidney disease. Studies have shown an association between depression and total mortality, but the association between depression and cardiovascular death is less certain., Methods: We conducted a prospective multinational cohort study involving adults who were treated with long-term haemodialysis within a single dialysis network between April and November 2010. Depression was considered present when patients reported a Beck Depression Inventory (BDI) II score ≥14 at baseline. Sensitivity analyses considered a BDI II score ≥20 to identify moderate depression. Multivariable Cox proportional hazards regression was used to assess adjusted hazards for all-cause and cardiovascular mortality at 12 months., Results: Three thousand and eighty-six participants in the network received the BDI II questionnaire, and 2278 (73%) provided complete responses to the survey questions. Among these, 1047 (46%) reported depression. During a mean follow-up of 11 (standard deviation: 2.5) months (2096 person-years), we recorded 175 deaths, of which 66 were attributable to cardiovascular causes. Depression (BDI score ≥14) was not associated with all-cause mortality [adjusted hazard ratio: 1.26 (95% confidence interval: 0.93–1.71)] or cardiovascular mortality [0.82 (0.50–1.34)]. When a higher BDI score (BDI score ≥20) was used to identify moderate depression, depression was associated with total mortality [1.40 (1.02–1.93)] but not cardiovascular mortality [1.05 (0.63–1.77)]., Conclusions: The association between depression and cardiovascular mortality in adults with kidney failure treated with haemodialysis is uncertain. Depression is a heterogeneous disorder and may only be a risk factor for premature death when at least of moderate severity.

Background: Oral disease is a potentially treatable determinant of mortality and quality of life. No comprehensive multinational study to quantify oral disease burden and to identify candidate preventative strategies has been performed in the dialysis setting., Methods: The ORAL disease in hemoDialysis (ORALD) study was a prospective study in adults treated with hemodialysis in Europe (France, Hungary, Italy, Poland, Portugal and Spain) and Argentina. Oral disease was assessed using standardized WHO methods. Participants self-reported oral health practices and symptoms. Sociodemographic and clinical factors associated with oral diseases were determined and assessed within nation states., Results: Of 4726 eligible adults, 4205 (88.9%) participated. Overall, 20.6% were edentulous [95% confidence interval (CI), 19.4-21.8]. Participants had on average 22 (95% CI 21.7-22.2) decayed, missing or filled teeth, while moderate to severe periodontitis affected 40.6% (95% CI 38.9-42.3). Oral disease patterns varied markedly across countries, independent of participant demographics, comorbidity and health practices. Participants in Spain, Poland, Italy and Hungary had the highest mean adjusted odds of edentulousness (2.31, 1.90, 1.90 and 1.54, respectively), while those in Poland, Hungary, Spain and Argentina had the highest odds of ≥14 decayed, missing or filled teeth (23.2, 12.5, 8.14 and 5.23, respectively). Compared with Argentina, adjusted odds ratios for periodontitis were 58.8, 58.3, 27.7, 12.1 and 6.30 for Portugal, Italy, Hungary, France and Poland, respectively. National levels of tobacco consumption, diabetes and child poverty were associated with edentulousness within countries., Conclusions: Oral disease in adults on hemodialysis is very common, frequently severe and highly variable among countries, with much of the variability unexplained by participant characteristics or healthcare. Given the national variation and high burden of disease, strategies to improve oral health in hemodialysis patients will require implementation at a country level rather than at the level of individuals., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Importance: Numerous glucose-lowering drugs are used to treat type 2 diabetes., Objective: To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin., Data Sources: Cochrane Library Central Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016., Study Selection: Randomized clinical trials of 24 weeks' or longer duration., Data Extraction and Synthesis: Random-effects network meta-analysis., Main Outcomes and Measures: The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight., Results: A total of 301 clinical trials (1,417,367 patient-months) were included; 177 trials (56,598 patients) of drugs given as monotherapy; 109 trials (53,030 patients) of drugs added to metformin (dual therapy); and 29 trials (10,598 patients) of drugs added to metformin and sulfonylurea (triple therapy). There were no significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality. Compared with metformin, sulfonylurea (standardized mean difference [SMD], 0.18 [95% CI, 0.01 to 0.34]), thiazolidinedione (SMD, 0.16 [95% CI, 0.00 to 0.31]), DPP-4 inhibitor (SMD, 0.33 [95% CI, 0.13 to 0.52]), and α-glucosidase inhibitor (SMD, 0.35 [95% CI, 0.12 to 0.58]) monotherapy were associated with higher HbA1C levels. Sulfonylurea (odds ratio [OR], 3.13 [95% CI, 2.39 to 4.12]; risk difference [RD], 10% [95% CI, 7% to 13%]) and basal insulin (OR, 17.9 [95% CI, 1.97 to 162]; RD, 10% [95% CI, 0.08% to 20%]) were associated with greatest odds of hypoglycemia. When added to metformin, drugs were associated with similar HbA1C levels, while SGLT-2 inhibitors offered the lowest odds of hypoglycemia (OR, 0.12 [95% CI, 0.08 to 0.18]; RD, -22% [-27% to -18%]). When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60 [95% CI, 0.39 to 0.94]; RD, -10% [95% CI, -18% to -2%])., Conclusions and Relevance: Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality. Metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug classes. All drugs were estimated to be effective when added to metformin. These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations.

Introduction: The prevalence of cognitive impairment may be increased in adults with end-stage kidney disease compared with the general population. However, the specific patterns of cognitive impairment and association of cognitive dysfunction with activities of daily living and clinical outcomes (including withdrawal from treatment) among haemodialysis patients remain incompletely understood. The COGNITIVE impairment in adults with end-stage kidney disease treated with HemoDialysis (COGNITIVE-HD) study aims to characterise the age-adjusted and education-adjusted patterns of cognitive impairment (using comprehensive testing for executive function, perceptual-motor function, language, learning and memory, and complex attention) in patients on haemodialysis and association with clinical outcomes., Methods and Analysis: A prospective, longitudinal, cohort study of 750 adults with end-stage kidney disease treated with long-term haemodialysis has been recruited within haemodialysis centres in Italy (July 2013 to April 2014). Testing for neurocognitive function was carried out by a trained psychologist at baseline to assess cognitive functioning. The primary study factor is cognitive impairment and secondary study factors will be specific domains of cognitive function. The primary outcome will be total mortality. Secondary outcomes will be cause-specific mortality, major cardiovascular events, fatal and non-fatal myocardial infarction and stroke, institutionalisation, and withdrawal from treatment at 12 months., Ethics and Dissemination: This protocol was approved before study conduct by the following responsible ethics committees: Catania (approval reference 186/BE; 26/09/2013), Agrigento (protocol numbers 61-62; 28/6/2013), USL Roma C (CE 39217; 24/6/2013), USL Roma F (protocol number 0041708; 23/7/2013), USL Latina (protocol number 20090/A001/2011; 12/7/2013), Trapani (protocol number 3413; 16/7/2013) and Brindisi (protocol number 40259; 6/6/2013). All participants have provided written and informed consent and can withdraw from the study at any time. The findings of the study will be disseminated through peer-reviewed journals and national and international conference presentations and to the participants through communication within the dialysis network in which this study is conducted., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Serum parathyroid hormone (PTH), phosphorus, and calcium levels are surrogate outcomes that are central to the evaluation of drug treatments in chronic kidney disease (CKD). This systematic review evaluates the evidence for the correlation between drug effects on biochemical (PTH, phosphorus, and calcium) and all-cause and cardiovascular mortality end points in adults with CKD., Study Design: Systematic review and meta-analysis., Setting & Population: Adults with CKD., Selection Criteria for Studies: Randomized trials reporting drug effects on biochemical and mortality end points., Intervention: Drug interventions with effects on serum PTH, phosphorus, and calcium levels, including vitamin D compounds, phosphate binders, cinacalcet, bisphosphonates, and calcitonin., Outcomes: Correlation between drug effects on biochemical and all-cause and cardiovascular mortality., Results: 28 studies (6,999 participants) reported both biochemical and mortality outcomes and were eligible for analysis. Associations between drug effects on surrogate biochemical end points and corresponding effects on mortality were weak and imprecise. All correlation coefficients were less than 0.70, and 95% credible intervals were generally wide and overlapped with zero, consistent with the possibility of no association. The exception was an inverse correlation between drug effects on serum PTH levels and all-cause mortality, which was nominally significant (-0.64; 95% credible interval, -0.85 to -0.15), but the strength of this association was very imprecise. Risk of bias within available trials was generally high, further reducing confidence in the summary correlations. Findings were robust to adjustment for age, baseline serum PTH level, allocation concealment, CKD stage, and drug class., Limitations: Low power in analyses and combining evidence from many different drug comparisons with incomplete data across studies., Conclusions: Drug effects on serum PTH, phosphorus, and calcium levels are weakly and imprecisely correlated with all-cause and cardiovascular death in the setting of CKD. Risks of mortality (patient-level outcome) cannot be inferred from treatment-induced changes in biochemical outcomes in people with CKD. Similarly, existing data do not exclude a mortality benefit with treatment. Trials need to address patient-centered outcomes to evaluate drug effectiveness in this setting., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Dental disease is more extensive in adults with chronic kidney disease, but whether dental health and behaviors are associated with survival in the setting of hemodialysis is unknown., Study Design: Prospective multinational cohort., Setting & Participants: 4,205 adults treated with long-term hemodialysis, 2010 to 2012 (Oral Diseases in Hemodialysis [ORAL-D] Study)., Predictors: Dental health as assessed by a standardized dental examination using World Health Organization guidelines and personal oral care, including edentulousness; decayed, missing, and filled teeth index; teeth brushing and flossing; and dental health consultation., Outcomes: All-cause and cardiovascular mortality at 12 months after dental assessment., Measurements: Multivariable-adjusted Cox proportional hazards regression models fitted with shared frailty to account for clustering of mortality risk within countries., Results: During a mean follow-up of 22.1 months, 942 deaths occurred, including 477 cardiovascular deaths. Edentulousness (adjusted HR, 1.29; 95% CI, 1.10-1.51) and decayed, missing, or filled teeth score ≥ 14 (adjusted HR, 1.70; 95% CI, 1.33-2.17) were associated with early all-cause mortality, while dental flossing, using mouthwash, brushing teeth daily, spending at least 2 minutes on oral hygiene daily, changing a toothbrush at least every 3 months, and visiting a dentist within the past 6 months (adjusted HRs of 0.52 [95% CI, 0.32-0.85], 0.79 [95% CI, 0.64-0.97], 0.76 [95% CI, 0.58-0.99], 0.84 [95% CI, 0.71-0.99], 0.79 [95% CI, 0.65-0.95], and 0.79 [95% CI, 0.65-0.96], respectively) were associated with better survival. Results for cardiovascular mortality were similar., Limitations: Convenience sample of clinics., Conclusions: In adults treated with hemodialysis, poorer dental health was associated with early death, whereas preventive dental health practices were associated with longer survival., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Convective dialysis modalities (haemofiltration (HF), haemodiafiltration (HDF), and acetate-free biofiltration (AFB)) removed excess body fluid across the dialysis membrane with positive pressure and accumulated middle- and larger-size accumulated solutes more efficiently than haemodialysis (HD). This increased larger solute removal combined with use of ultra-pure dialysis fluid in convective dialysis is hypothesised to reduce the frequency and severity of symptoms during dialysis as well as improve clinical outcomes. Convective dialysis therapies (HDF and HF) are associated with lower mortality compared to diffusive therapy (HD) in observational studies. This is an update of a review first published in 2006., Objectives: To compare convective (HF, HDF, or AFB) with diffusive (HD) dialysis modalities on clinical outcomes (mortality, major cardiovascular events, hospitalisation and treatment-related adverse events) in men and women with end-stage kidney disease (ESKD)., Search Methods: We searched the Cochrane Renal Group's Specialised Register (to 18 February 2015) through contact with a Trials' Search Co-ordinator using search terms relevant to this review., Selection Criteria: We included randomised controlled trials comparing convective therapy (HF, HDF, AFB) with another convective therapy or diffusive therapy (HD) for treatment of ESKD., Data Collection and Analysis: Two independent authors identified studies, extracted data and assessed study risk of bias. We summarised treatment effects using the random effects model. We reported results as a risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous data together with 95% confidence intervals (CI). We assessed for heterogeneity using the Chi(2) test and explored the amount of variation in treatment estimates beyond that expected by chance using the I(2) statistic., Main Results: Twenty studies comprising 667 participants were included in the 2006 review. In that review, there was insufficient evidence of treatment effects on major clinical outcomes to draw clinically meaningful conclusions. Searching to February 2015 identified 40 eligible studies comprising 3483 participants overall. In total, 35 studies (4039 participants) compared HF, HDF or AFB with HD, three studies (54 participants) compared AFB with HDF, and three studies (129 participants) compared HDF with HF.Risks of bias in all studies were generally high resulting in low confidence in estimated treatment effects. Convective dialysis had no significant effect on all-cause mortality (11 studies, 3396 participants: RR 0.87, 95% CI 0.72 to 1.05; I(2) = 34%), but significantly reduced cardiovascular mortality (6 studies, 2889 participants: RR 0.75, 95% CI 0.61 to 0.92; I(2) = 0%). One study reported no significant effect on rates of nonfatal cardiovascular events (714 participants: RR 1.14, 95% CI 0.86 to 1.50) and two studies showed no significant difference in hospitalisation (2 studies, 1688 participants: RR 1.23, 95% CI 0.93 to 1.63; I(2) = 0%). One study reported rates of hypotension during dialysis were significantly reduced with convective therapy (906 participants: RR 0.72, 95% CI 0.66 to 0.80). Adverse events were not systematically evaluated in most studies and data for health-related quality of life were sparse. Convective therapies significantly reduced predialysis levels of B2 microglobulin (12 studies, 1813 participants: MD -5.55 mg/dL, 95% CI -9.11 to -1.98; I(2) = 94%) and increased dialysis dose (Kt/V urea) (14 studies, 2022 participants: MD 0.07, 95% CI -0.00 to 0.14; I(2) = 90%) compared to diffusive therapy, but results across studies were very heterogeneous. Sensitivity analyses limited to studies comparing HDF with HD showed very similar results. Directly comparative data for differing types of convective dialysis were insufficient to draw conclusions.Studies had important risks of bias leading to low confidence in the summary estimates and were generally limited to patients who had adequate dialysis vascular access., Authors' Conclusions: Convective dialysis may reduce cardiovascular but not all-cause mortality and effects on nonfatal cardiovascular events and hospitalisation are inconclusive. However, any treatment benefits of convective dialysis on all patient outcomes including cardiovascular death are unreliable due to limitations in study methods and reporting. Future studies which assess treatment effects of convection dose on patient outcomes including mortality and cardiovascular events would be informative.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening genetic disorder and has multiple complications including, infection, pain, intracranial aneurysm and kidney failure leading to significantly impaired quality of life and reduced survival. These outcomes are well described, but patient perspectives and experiences of living with ADPKD are under-recognized., Methods: MEDLINE, Embase, PsycINFO and CINAHL were searched to August 2014. Studies were analyzed using thematic synthesis., Results: From 21 studies (n = 247), we derived five themes: unvalidated pain (medical trivialization, inadequacy of pain management); persisting uncertainties and ambiguities (lacking diagnostic clarity, disempowerment in self-care, unpredictable daily disruptions, inability to plan ahead, financial discrimination); genetic guilt and resentment (blaming parents, self-blame, constant burden of guilt); precariousness in pursuing parenthood (prognostic uncertainty, owning the decision, needing directive counselling); and defining parental responsibility for genetic testing and disclosure (preserving normality, doubting necessity of genetic testing, respecting the child's autonomy and hope in future technologies, facilitating preparedness)., Conclusions: The erratic onset of pain contributes to the substantial unpredictability of daily living and prevents patients from establishing long-term life goals. Decisions about family planning, genetic testing of children and disclosure involves making profoundly difficult judgments about ethical parental responsibility. Patient engagement in pain management, strategies for self-care, counselling to reduce the burden of 'genetic guilt' and specific family planning decision support tools may be priorities for care to improve patient-centred outcomes in ADPKD., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Introduction: Adults with end-stage kidney disease (ESKD) treated with haemodialysis experience mortality of between 15% and 20% each year. Effective interventions that improve health outcomes for long-term dialysis patients remain unproven. Novel and testable determinants of health in dialysis are needed. Nutrition and dietary patterns are potential factors influencing health in other health settings that warrant exploration in multinational studies in men and women treated with dialysis. We report the protocol of the "DIETary intake, death and hospitalisation in adults with end-stage kidney disease treated with HaemoDialysis (DIET-HD) study," a multinational prospective cohort study. DIET-HD will describe associations of nutrition and dietary patterns with major health outcomes for adults treated with dialysis in several countries., Methods and Analysis: DIET-HD will recruit approximately 10,000 adults who have ESKD treated by clinics administered by a single dialysis provider in Argentina, France, Germany, Hungary, Italy, Poland, Portugal, Romania, Spain, Sweden and Turkey. Recruitment will take place between March 2014 and June 2015. The study has currently recruited 8000 participants who have completed baseline data. Nutritional intake and dietary patterns will be measured using the Global Allergy and Asthma European Network (GA(2)LEN) food frequency questionnaire. The primary dietary exposures will be n-3 and n-6 polyunsaturated fatty acid consumption. The primary outcome will be cardiovascular mortality and secondary outcomes will be all-cause mortality, infection-related mortality and hospitalisation., Ethics and Dissemination: The study is approved by the relevant Ethics Committees in participating countries. All participants will provide written informed consent and be free to withdraw their data at any time. The findings of the study will be disseminated through peer-reviewed journals, conference presentations and to participants via regular newsletters. We expect that the DIET-HD study will inform large pragmatic trials of nutrition or dietary interventions in the setting of advanced kidney disease., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: Several erythropoiesis-stimulating agents (ESAs) are available for treating anaemia in people with chronic kidney disease (CKD). Their relative efficacy (preventing blood transfusions and reducing fatigue and breathlessness) and safety (mortality and cardiovascular events) are unclear due to the limited power of head-to-head studies., Objectives: To compare the efficacy and safety of ESAs (epoetin alfa, epoetin beta, darbepoetin alfa, or methoxy polyethylene glycol-epoetin beta, and biosimilar ESAs, against each other, placebo, or no treatment) to treat anaemia in adults with CKD., Search Methods: We searched the Cochrane Renal Group's Specialised Register to 11 February 2014 through contact with the Trials' Search Co-ordinator using search terms relevant to this review., Selection Criteria: Randomised controlled trials (RCTs) that included a comparison of an ESA (epoetin alfa, epoetin beta, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, or biosimilar ESA) with another ESA, placebo or no treatment in adults with CKD and that reported prespecified patient-relevant outcomes were considered for inclusion., Data Collection and Analysis: Two independent authors screened the search results and extracted data. Data synthesis was performed by random-effects pairwise meta-analysis and network meta-analysis. We assessed for heterogeneity and inconsistency within meta-analyses using standard techniques and planned subgroup and meta-regression to explore for sources of heterogeneity or inconsistency. We assessed our confidence in treatment estimates for the primary outcomes within network meta-analysis (preventing blood transfusions and all-cause mortality) according to adapted GRADE methodology as very low, low, moderate, or high., Main Results: We identified 56 eligible studies involving 15,596 adults with CKD. Risks of bias in the included studies was generally high or unclear for more than half of studies in all of the risk of bias domains we assessed; no study was low risk for allocation concealment, blinding of outcome assessment and attrition from follow-up. In network analyses, there was moderate to low confidence that epoetin alfa (OR 0.18, 95% CI 0.05 to 0.59), epoetin beta (OR 0.09, 95% CI 0.02 to 0.38), darbepoetin alfa (OR 0.17, 95% CI 0.05 to 0.57), and methoxy polyethylene glycol-epoetin beta (OR 0.15, 95% CI 0.03 to 0.70) prevented blood transfusions compared to placebo. In very low quality evidence, biosimilar ESA therapy was possibly no better than placebo for preventing blood transfusions (OR 0.27, 95% CI 0.05 to 1.47) with considerable imprecision in estimated effects. We could not discern whether all ESAs were similar or different in their effects on preventing blood transfusions and our confidence in the comparative effectiveness of different ESAs was generally very low. Similarly, the comparative effects of ESAs compared with another ESA, placebo or no treatment on all-cause mortality were imprecise.All proprietary ESAs increased the odds of hypertension compared to placebo (epoetin alfa OR 2.31, 95% CI 1.27 to 4.23; epoetin beta OR 2.57, 95% CI 1.23 to 5.39; darbepoetin alfa OR 1.83, 95% CI 1.05 to 3.21; methoxy polyethylene glycol-epoetin beta OR 1.96, 95% CI 0.98 to 3.92), while the effect of biosimilar ESAs on developing hypertension was less certain (OR 1.18, 95% CI 0.47 to 2.99). Our confidence in the comparative effects of ESAs on hypertension was low due to considerable imprecision in treatment estimates. The comparative effects of all ESAs on cardiovascular mortality, myocardial infarction (MI), stroke, and vascular access thrombosis were uncertain and network analyses for major cardiovascular events, end-stage kidney disease (ESKD), fatigue and breathlessness were not possible. Effects of ESAs on fatigue were described heterogeneously in the available studies in ways that were not useable for analyses., Authors' Conclusions: In the CKD setting, there is currently insufficient evidence to suggest the superiority of any ESA formulation based on available safety and efficacy data. Directly comparative data for the effectiveness of different ESA formulations based on patient-centred outcomes (such as quality of life, fatigue, and functional status) are sparse and poorly reported and current research studies are unable to inform care. All proprietary ESAs (epoetin alfa, epoetin beta, darbepoetin alfa, and methoxy polyethylene glycol-epoetin beta) prevent blood transfusions but information for biosimilar ESAs is less conclusive. Comparative treatment effects of different ESA formulations on other patient-important outcomes such as survival, MI, stroke, breathlessness and fatigue are very uncertain.For consumers, clinicians and funders, considerations such as drug cost and availability and preferences for dosing frequency might be considered as the basis for individualising anaemia care due to lack of data for comparative differences in clinical benefits and harms.

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., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Erythropoiesis-stimulating agents are used to treat anaemia in people with chronic kidney disease (CKD). Several agents are available including epoetin alfa or beta as well as agents with a longer duration of action, darbepoetin alfa and methoxy polyethylene glycol-epoetin beta., Objectives: To assess the benefits and harms of darbepoetin alfa to treat anaemia in adults and children with CKD (stages 3 to 5, 5D, and kidney transplant recipients)., Search Methods: We searched the Cochrane Renal Group's Specialised Register (to 13 January 2014) through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE., Selection Criteria: We included randomised controlled trials of any darbepoetin alfa treatment of at least three months duration in adults or children with CKD (any stage)., Data Collection and Analysis: Data were extracted by two independent investigators. Patient-centred outcomes (need for blood transfusion, iron therapy, progression of kidney disease, total and cardiovascular mortality, cardiovascular events, cancer, hypertension, seizures, and health-related quality of life) and other outcomes (haemoglobin levels) were assessed using random effects meta-analysis. We calculated risk ratios for dichotomous outcomes and mean differences for continuous outcomes, both with 95% confidence intervals., Main Results: We identified 32 studies comprising 9414 participants; 21 studies in 8328 participants could be included in our meta-analyses. One study (4038 participants) compared darbepoetin alfa to placebo, 16 studies (2955 participants) compared darbepoetin alfa to epoetin alfa or beta, four studies (1198 participants) compared darbepoetin alfa to methoxy polyethylene glycol-epoetin beta, three studies (420 participants) compared more frequent with less frequent darbepoetin alfa administration and four studies (303 participants) compared intravenous with subcutaneous darbepoetin alfa administration.In a single large study, darbepoetin alfa reduced the need for blood transfusion and iron therapy compared with placebo in adults with CKD stage 3 to 5, but had little or no effect on survival, increased risks of hypertension, and had uncertain effects on quality of life. Data comparing darbepoetin alfa with epoetin alfa or beta or methoxy polyethylene glycol-epoetin beta were sparse and inconclusive. Comparisons of differing dosing schedules and routes of administration were compared in small numbers of participants and studies. Evidence for treatment effects of darbepoetin alfa were particularly limited for children with CKD, adults with CKD stage 5D, and recipients of a kidney transplant.Studies included in this review were generally at high or unclear risk of bias for all items (random sequence generation, allocation concealment, incomplete outcome data, blinding of participants and personnel, blinding of outcome assessment, selective outcome reporting, intention to treat analysis and other sources of bias). One large study comparing darbepoetin alfa with placebo was at low risk of bias for most items assessed., Authors' Conclusions: Data suggest that darbepoetin alfa effectively reduces need for blood transfusions in adults with CKD stage 3 to 5, but has little or no effect on mortality or quality of life. The effects of darbepoetin alfa in adults with CKD stage 5D and kidney transplant recipients and children with CKD remain uncertain as do the relative benefits and harms of darbepoetin alfa compared with other ESAs (epoetin alfa or beta and methoxy polyethylene glycol-epoetin beta).

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., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Prevalence estimates of depression in chronic kidney disease (CKD) vary widely in existing studies. We conducted a systematic review and meta-analysis of observational studies to summarize the point prevalence of depressive symptoms in adults with CKD. We searched MEDLINE and Embase (through January 2012). Random-effects meta-analysis was used to estimate the prevalence of depressive symptoms. We also limited the analyses to studies using clinical interview and prespecified criteria for diagnosis. We included 249 populations (55,982 participants). Estimated prevalence of depression varied by stage of CKD and the tools used for diagnosis. Prevalence of interview-based depression in CKD stage 5D was 22.8% (confidence interval (CI), 18.6-27.6), but estimates were somewhat less precise for CKD stages 1-5 (21.4% (CI, 11.1-37.2)) and for kidney transplant recipients (25.7% (12.8-44.9)). Using self- or clinician-administered rating scales, the prevalence of depressive symptoms for CKD stage 5D was higher (39.3% (CI, 36.8-42.0)) relative to CKD stages 1-5 (26.5% (CI, 18.5-36.5)) and transplant recipients (26.6% (CI, 20.9-33.1)) and suggested that self-report scales may overestimate the presence of depression, particularly in the dialysis setting. Thus, interview-defined depression affects approximately one-quarter of adults with CKD. Given the potential prevalence of depression in the setting of CKD, randomized trials to evaluate effects of interventions for depression on patient-centered outcomes are needed.

Background: People with end-stage kidney disease treated with dialysis experience high rates of premature death that are at least 30-fold that of the general population, and have markedly impaired quality of life. Despite this, interventions that lower risk factors for mortality (including antiplatelet agents, epoetins, lipid lowering, vitamin D compounds, or dialysis dose) have not been shown to improve clinical outcomes for this population. Although mortality outcomes may be improving overall, additional modifiable determinants of health in people treated with dialysis need to be identified and evaluated. Oral disease is highly prevalent in the general population and represents a potential and preventable cause of poor health in dialysis patients. Oral disease may be increased in patients treated with dialysis due to their lower uptake of public dental services, as well as increased malnutrition and inflammation, although available exploratory data are limited by small sample sizes and few studies evaluating links between oral health and clinical outcomes for this group, including mortality and cardiovascular disease. Recent data suggest periodontitis may be associated with mortality in dialysis patients and well-designed, larger studies are now required., Methods/design: The ORAL Diseases in hemodialysis (ORAL-D) study is a multinational, prospective (minimum follow-up 12 months) study. Participants comprise consecutive adults treated with long-term in-center hemodialysis. Between July 2010 and February 2012, we recruited 4500 dialysis patients from randomly selected outpatient dialysis clinics in Europe within a collaborative network of dialysis clinics administered by a dialysis provider, Diaverum, in Europe (France, Hungary, Italy, Poland, Portugal, and Spain) and South America (Argentina). At baseline, dental surgeons with training in periodontology systematically assessed the prevalence and characteristics of oral disease (dental, periodontal, mucosal, and salivary) in all participants. Oral hygiene habits and thirst were evaluated using self-administered questionnaires. Data for hospitalizations and mortality (total and cause-specific) according to baseline oral health status will be collected once a year until 2022., Discussion: This large study will estimate the prevalence, characteristics and correlations of oral disease and clinical outcomes (mortality and hospitalization) in adults treated with dialysis. We will further evaluate any association between periodontitis and risk of premature death in dialysis patients that has been suggested by existing research. The results from this study should provide powerful new data to guide strategies for future interventional studies for preventative and curative oral disease strategies in adults who have end-stage kidney disease.

Background: Anaemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with chronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are the most used treatment option. In observational studies, higher haemoglobin (Hb) levels (around 11-13 g/dL) are associated with improved survival and quality of life compared to Hb levels around 9-10 g/dL. Randomized studies found that targeting higher Hb levels with ESA causes an increased risk of death, mainly due to adverse cardiovascular outcomes. It is possible that this is mediated by ESA dose rather than haemoglobin concentration, although this hypothesis has never been formally tested., Methods: We present the protocol of the Clinical Evaluation of the Dose of Erythropoietins (C.E. DOSE) trial, which will assess the benefits and harms of a high versus a low ESA dose therapeutic strategy for the management of anaemia of end stage kidney disease (ESKD). This is a randomized, prospective open label blinded end-point (PROBE) design trial due to enroll 900 haemodialysis patients. Patients will be randomized 1:1 to 4000 UI/week i. v. versus 18000 UI/week i. v. of epoetin alfa, beta or any other epoetin in equivalent doses. The primary outcome of the trial is a composite of cardiovascular events. In addition, quality of life and costs of these two strategies will be assessed. The study has been approved and funded by the Italian Agency of Drugs (Agenzia Italiana del Farmaco (AIFA)) within the 2006 funding plan for independent research on drugs (registered at www.clinicaltrials.gov (NCT00827021)).

Background and Objectives: The few existing studies of sexual dysfunction in women on hemodialysis are limited by small sample size. This large, cross-sectional study evaluated the prevalence and correlates of female sexual dysfunction in advanced kidney disease. DESIGN, SETTING, PARTICIPANTS, METHODS: A total of 1472 women with ESRD undergoing hemodialysis were recruited to a multinational, cross-sectional study conducted within a collaborative dialysis network in Europe and South America. Sexual dysfunction was identified by the Female Sexual Function Index. Correlates of self-reported sexual dysfunction were identified by regression analyses., Results: Of the 1472 women, 659 completed questionnaires (45%). More than half (362 of 659 [55%]) lived with a partner, and 232 of 659 (35%) reported being sexually active. Of these 659 respondents, 555 (84%) reported sexual dysfunction. Women with a partner (282 of 362 [78%]) were less likely to report sexual dysfunction than those without a partner (273 of 297 [92%]) (P<0.001). Sexual dysfunction was independently associated with age, depressive symptoms, less education, menopause, diabetes, and diuretic therapy. Nearly all women who were not wait-listed for a kidney transplant and were living without a partner (249 of 260 [96%]) reported sexual dysfunction. More than half (128 of 232 [55%]) of sexually active women reported sexual dysfunction, associated with age, depressive symptoms, menopause, low serum albumin, and diuretic therapy., Conclusions: This descriptive study suggests most women on hemodialysis experience sexual problems. Additional research on the relevance of sexual dysfunction to symptom burden and quality of life in these women is needed.

Background: Factors associated with erectile dysfunction in men on haemodialysis are incompletely identified due to suboptimal existing studies. We determined the prevalence and correlates of erectile dysfunction and identified combinations of clinical characteristics associated with a higher risk of erectile dysfunction using recursive partitioning and amalgamation (REPCAM) analysis., Methods: We conducted a multinational cross-sectional study in men on haemodialysis within a collaborative network. Erectile dysfunction and depressive symptoms were evaluated using the erectile function domain of the International Index of Erectile Function questionnaire and the Center for Epidemiological Studies-Depression Scale, respectively., Results: Nine hundred and forty-six (59%) of 1611 eligible men provided complete data for erectile dysfunction. Eighty-three per cent reported erectile dysfunction and 47% reported severe erectile dysfunction. Four per cent of those with erectile dysfunction were receiving pharmacological treatment. Depressive symptoms were the strongest correlate of erectile dysfunction [adjusted odds ratio 2.41 (95% confidence interval (CI) 1.57-3.71)]. Erectile dysfunction was also associated with age (1.06, 1.05-1.08), being unemployed (1.80, 1.17-2.79) or receiving a pension (2.05, 1.14-3.69) and interdialytic weight gain (1.9-2.87 kg, 1.92 [CI 1.19-3.09]; >2.87 kg, 1.57 [CI 1.00-2.45]). Married men had a lower risk of erectile dysfunction (0.49, 0.31-0.76). The prevalence of erectile dysfunction was highest (94%) in unmarried and unemployed or retired men who have depressive symptoms., Conclusions: Most men on haemodialysis experience erectile dysfunction and are untreated. Given the prevalence of this condition and the relative lack of efficacy data for pharmacological agents, we suggest that large trials of pharmacological and non-pharmacological interventions for erectile dysfunction and depression are needed.

Background: Sexual dysfunction is very common in patients with chronic kidney disease (CKD), but it is still significantly understudied. Treatment options exist but concerns have been raised relating to their efficacy and safety in CKD., Objectives: We assessed the benefits and harms of existing interventions for treatment of sexual dysfunction in patients with CKD., Search Strategy: In October 2010 we searched the Cochrane Renal Group's specialised register, CENTRAL (The Cochrane Library, issue 10), MEDLINE (from 1966) and EMBASE (from 1980)., Selection Criteria: Randomised controlled trials (RCTs) and quasi-RCTs of any pharmacological and non-pharmacological interventions used to treat sexual dysfunction in male and female CKD patients (predialysis, dialysis and kidney transplant) were included., Data Collection and Analysis: Two authors independently selected eligible studies, extracted data and assessed study quality. Disagreements were resolved in consultation with an arbitrator. Treatment effects were summarised as risk ratios (RR), mean differences (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) using a random-effects model., Main Results: Fifteen studies (8 parallel, 7 crossover; 352 patients) were included. Only one study enrolled women. Studies evaluated the effects of phosphodiesterase-5 inhibitors (PDE5i), zinc, vitamin E, vitamin D or bromocriptine compared to placebo. PDE5i significantly increased the overall International Index of Erectile Function-5 (IIEF-5) score (2 studies, 101 patients, MD 10.65, 95% CI 5.34 to 15.96), all its individual domains and the complete 15-item IIEF tool (1 study, 41 patients, MD 2.64, 95% CI 1.32 to 3.96). End of treatment testosterone levels were not significantly increased by addition of zinc to dialysate (2 studies, 22 patients, MD 0.21 ng/mL, 95% CI -2.14 to 2.55) but oral zinc improved end of treatment testosterone levels (1 study, 20 patients, SMD 1.62, 95% CI 0.58 to 2.66). There was no difference in plasma luteinizing and follicle-stimulating hormone levels at the end of the study period with zinc therapy. Only sparse data were available for vitamin E, bromocriptine and dihydroxycholecalciferol in CKD patients and there were no studies of intracavernous injections, transurethral injections, mechanical devices or psychosexual therapies in people with CKD., Authors' Conclusions: PDE5i and zinc are promising interventions for treating sexual dysfunction in men with CKD. Evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for both male and female sexual dysfunction in CKD, considering the significant disease burden.

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., (Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Sexual dysfunction is very common in patients with chronic kidney disease (CKD), but treatment options are limited. The benefits and harms of existing interventions for treatment of sexual dysfunction were assessed in patients with CKD., Design, Setting, Participants, & Measurements: MEDLINE (1966 to December 2008), EMBASE (1980 to December 2008), and the Cochrane Trial Registry (Issue 4 2008) were searched for parallel and crossover randomized and quasi-randomized trials. Treatment effects were summarized as mean differences (MD) or standardized mean difference (SMD) with 95% confidence intervals (CI) using a random effects model., Results: Fourteen trials (328 patients) were included. Phosphodiesterase-5 inhibitors (PDE5i) compared with placebo significantly increased the overall International Index of Erectile Function-5 (IIEF-5) score (three trials, 101 patients, MD 1.81, 95% CI 1.51 to 2.10), all of its individual domains, and the complete 15-item IIEF-5 (two trials, 80 patients, MD 10.64, 95% CI 5.32 to 15.96). End-of-treatment testosterone levels were not significantly increased by addition of zinc to dialysate (two trials, 22 patients, SMD 0.19 ng/dl, 95% CI -2.12 to 2.50), but oral zinc improved end-of-treatment testosterone levels. There was no difference in plasma luteinizing and follicle-stimulating hormone level at the end of the study period with zinc therapy., Conclusions: PDE5i and zinc are promising interventions for treating sexual dysfunction in CKD. Evidence supporting their routine use in CKD patients is limited. There is an unmet need for studying interventions for male and female sexual dysfunction in CKD considering the significant disease burden.