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Purpose An increasing body of evidence suggests that excreting a generous volume of diluted urine is associated with short- and long-term beneficial health effects, especially for kidney and metabolic function. However, water intake and hydration remain under-investigated and optimal hydration is poorly and inconsistently defined. This review tests the hypothesis that optimal chronic water intake positively impacts various aspects of health and proposes an evidence-based definition of optimal hydration. Methods Search strategy included PubMed and Google Scholar using relevant keywords for each health outcome, complemented by manual search of article reference lists and the expertise of relevant practitioners for each area studied. Results The available literature suggest the effects of increased water intake on health may be direct, due to increased urine flow or urine dilution, or indirect, mediated by a reduction in osmotically -stimulated vasopressin (AVP). Urine flow affects the formation of kidney stones and recurrence of urinary tract infection, while increased circulating AVP is implicated in metabolic disease, chronic kidney disease, and autosomal dominant polycystic kidney disease. Conclusion In order to ensure optimal hydration, it is proposed that optimal total water intake should approach 2.5 to 3.5 L day−1 to allow for the daily excretion of 2 to 3 L of dilute (−1) urine. Simple urinary markers of hydration such as urine color or void frequency may be used to monitor and adjust intake.

Our aim was to investigate the validity of osmolality from 24-h urine collection in examining the risk for calcium-oxalate (CaOx) kidney stone formation in patients with recurrent urolithiasis. Three hundred and twelve subjects (males/females: 184/128) from France with a history of recurrent kidney stones from confirmed or putative CaOx origin were retrospectively included in the study (46 ± 14 years, BMI: 25.3 ± 5.0 kg·m−2). Tiselius’ crystallization risk index (CRI) was calculated based on urinary calcium, oxalate, citrate, magnesium, and volume from 24-h samples. The diagnostic ability of 24-h urine osmolality to classify patients as high risk for kidney stone crystallization was examined through the receivers operating characteristics analysis. High risk for CaOx crystallization was defined as CRI > 1.61 and > 1.18, for males and females, respectively. The accuracy of urine osmolality to diagnose risk of CaOx stone formation (AUC, area under the curve) for females was 84.6%, with cut-off point of 501 mmol·kg−1 (sensitivity: 83.3%, specificity: 76.0%). Males had AUC of 85.8% with threshold of 577 mmo·kg−1 (sensitivity: 85.5%, specificity: 77.6%). A negative association was found between 24-h urine volume and osmolality (r = − 0.63, P 501 and > 577 mmol·kg−1, in female and in male, respectively, was associated with a risk for CaOx kidney stone formation in patients with a history of recurrent urolithiasis. Thus, when CaOx origin is confirmed or suspected, 24-h urine osmolality provides a simple way to define individualized target of urine dilution to prevent urine crystallization and stone formation.

Purpose Inter-individual variation in median plasma copeptin is associated with incident type 2 diabetes mellitus, progression of chronic kidney disease, and cardiovascular events. In this study, we examined whether 24-h urine osmolality was associated with plasma copeptin and whether increasing daily water intake could impact circulating plasma copeptin. Methods This trial was a prospective study conducted at a single investigating center. Eighty-two healthy adults (age 23.6 ± 2.9 years, BMI 22.2 ± 1.5 kg/m2, 50% female) were stratified based upon habitual daily fluid intake volumes: arm A (50–80% of EFSA dietary reference values), arm B (81–120%), and arm C (121–200%). Following a baseline visit, arms A and B increased their water intake to match arm C for a period of 6 consecutive weeks. Results At baseline, plasma copeptin was positively and significantly associated with 24-h urine osmolality (p = 0.002) and 24-h urine specific gravity (p = 0.003) but not with plasma osmolality (p = 0.18), 24-h urine creatinine (p = 0.09), and total fluid intake (p = 0.52). Over the 6-week follow-up, copeptin decreased significantly from 5.18 (3.3;7.4) to 3.90 (2.7;5.7) pmol/L (p = 0.012), while urine osmolality and urine specific gravity decreased from 591 ± 206 to 364 ± 117 mOsm/kg (p

Chronic vasopressin secretion induced by recurrent mild heat stress exposure is significantly enhanced by limited rehydration with a fructose-containing beverage both in rodents and in humans. Moreover, this effect has been associated with upregulation of the polyol&ndash, fructokinase pathway and increased renal oxidative stress. Previously, we have shown that pharmacological inhibition of both V1a and V2 vasopressin receptors with conivaptan improved such renal alterations. The aim of this study was to evaluate the independent contributions of V1a and V2 receptors to the renal damage caused by mild heat stress and limited rehydration with a fructose-containing beverage. Osmotic minipumps were used to deliver either relcovaptan (0.64 mg/day) or tolvaptan (0.25 mg/day) in male Wistar rats for two weeks. Corresponding dilution vehicles were used as controls. To induce dehydration, rats were exposed to mild heat stress (37 &deg, C for 1 h, Monday to Friday). All groups received a 10% fructose solution as a rehydration fluid for 2 h after mild heat stress. For the remainder of the day and on weekends, rats received tap water. The independent blockade of either the V1a or the V2 receptor prevented renal damage, reduced oxidative stress, and decreased plasma cortisol and systemic inflammation. However, the beneficial effects were regulated by different mechanisms. Tolvaptan inhibited polyol&ndash, fructokinase pathway overactivation, while relcovaptan prevented upregulation of the renin&ndash, angiotensin system and SGK1 expression. These data suggest that both V1a and V2 receptors participate in renal damage caused by heat stress-induced dehydration when fructose-containing beverages are used as rehydration fluids.

Recently repeated heat stress and dehydration have been reported to cause oxidative stress and kidney damage that is enhanced by rehydrating with fructose solutions. We hypothesized that antioxidants might provide a novel way to prevent kidney damage. To test this hypothesis, mild heat stress was induced by exposing rats to 37 °C during 1 h in a closed chamber. The supplementation with water-soluble antioxidants (Antiox), ascorbic acid 1% plus N-acetyl cysteine 600 mg/L was done either in the 10% fructose 2 h rehydration fluid immediately after heat stress (Fructose 10% + Antiox), and/or in the tap water (Water + Antiox) for the remainder of the day, or in both fluids. After 4 weeks, control rats exposed to heat with fructose rehydration developed impaired renal function, tubular injury, intrarenal oxidative stress, a reduction in Nrf2-Keap1 antioxidant pathway, stimulation of vasopressin and the intrarenal polyol-fructokinase pathway. In contrast, dosing the antioxidants in the tap water (i.e., before the heat exposure and rehydration with fructose) preserved renal function, prevented renal tubule dysfunction and avoided the increase in systemic blood pressure. These effects were likely due to the amplification of the antioxidant defenses through increased Nrf2 nuclear translocation stimulated by the antioxidants and by the prevention of polyol fructokinase pathway overactivation. More studies to understand the mechanisms implicated in this pathology are warranted as there is recent evidence that they may be operating in humans as well.

Growing evidence suggests a distinction between water intake necessary for maintaining a euhydrated state, and water intake considered to be adequate from a perspective of long-term health. Previously, we have proposed that maintaining a 24-h urine osmolality (UOsm) of ⩽500 mOsm/kg is a desirable target for urine concentration to ensure sufficient urinary output to reduce renal health risk and circulating vasopressin. In clinical practice and field monitoring, the measurement of UOsm is not practical. In this analysis, we calculate criterion values for urine-specific gravity (USG) and urine color (UCol), two measures which have broad applicability in clinical and field settings. A receiver operating characteristic curve analysis performed on 817 urine samples demonstrates that a USG ⩾1.013 detects UOsm>500 mOsm/kg with very high accuracy (AUC 0.984), whereas a subject-assessed UCol⩾4 offers high sensitivity and moderate specificity (AUC 0.831) for detecting UOsm >500 m Osm/kg.

BACKGROUND: Phosphate binders are used to reduce positive phosphate balance and to lower serum phosphate levels for people with chronic kidney disease (CKD) with the aim to prevent progression of chronic kidney disease‐mineral and bone disorder (CKD‐MBD). This is an update of a review first published in 2011. OBJECTIVES: The aim of this review was to assess the benefits and harms of phosphate binders for people with CKD with particular reference to relevant biochemical end‐points, musculoskeletal and cardiovascular morbidity, hospitalisation, and death. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 July 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or quasi‐RCTs of adults with CKD of any GFR category comparing a phosphate binder to another phosphate binder, placebo or usual care to lower serum phosphate. Outcomes included all‐cause and cardiovascular death, myocardial infarction, stroke, adverse events, vascular calcification and bone fracture, and surrogates for such outcomes including serum phosphate, parathyroid hormone (PTH), and FGF23. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion and extracted study data. We applied the Cochrane 'Risk of Bias' tool and used the GRADE process to assess evidence certainty. We estimated treatment effects using random‐effects meta‐analysis. Results were expressed as risk ratios (RR) for dichotomous outcomes together with 95% confidence intervals (CI) or mean differences (MD) or standardised MD (SMD) for continuous outcomes. MAIN RESULTS: We included 104 studies involving 13,744 adults. Sixty‐nine new studies were added to this 2018 update. Most placebo or usual care controlled studies were among participants with CKD G2 to G5 not requiring dialysis (15/25 studies involving 1467 participants) while most head to head studies involved participants with CKD G5D treated with dialysis (74/81 studies involving 10,364 participants). Overall, seven studies compared sevelamer with placebo or usual care (667 participants), seven compared lanthanum to placebo or usual care (515 participants), three compared iron to placebo or usual care (422 participants), and four compared calcium to placebo or usual care (278 participants). Thirty studies compared sevelamer to calcium (5424 participants), and fourteen studies compared lanthanum to calcium (1690 participants). No study compared iron‐based binders to calcium. The remaining studies evaluated comparisons between sevelamer (hydrochloride or carbonate), sevelamer plus calcium, lanthanum, iron (ferric citrate, sucroferric oxyhydroxide, stabilised polynuclear iron(III)‐oxyhydroxide), calcium (acetate, ketoglutarate, carbonate), bixalomer, colestilan, magnesium (carbonate), magnesium plus calcium, aluminium hydroxide, sucralfate, the inhibitor of phosphate absorption nicotinamide, placebo, or usual care without binder. In 82 studies, treatment was evaluated among adults with CKD G5D treated with haemodialysis or peritoneal dialysis, while in 22 studies, treatment was evaluated among participants with CKD G2 to G5. The duration of study follow‐up ranged from 8 weeks to 36 months (median 3.7 months). The sample size ranged from 8 to 2103 participants (median 69). The mean age ranged between 42.6 and 68.9 years. Random sequence generation and allocation concealment were low risk in 25 and 15 studies, respectively. Twenty‐seven studies reported low risk methods for blinding of participants, investigators, and outcome assessors. Thirty‐one studies were at low risk of attrition bias and 69 studies were at low risk of selective reporting bias. In CKD G2 to G5, compared with placebo or usual care, sevelamer, lanthanum, iron and calcium‐based phosphate binders had uncertain or inestimable effects on death (all causes), cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. Sevelamer may lead to constipation (RR 6.92, CI 2.24 to 21.4; low certainty) and lanthanum (RR 2.98, CI 1.21 to 7.30, moderate certainty) and iron‐based binders (RR 2.66, CI 1.15 to 6.12, moderate certainty) probably increased constipation compared with placebo or usual care. Lanthanum may result in vomiting (RR 3.72, CI 1.36 to 10.18, low certainty). Iron‐based binders probably result in diarrhoea (RR 2.81, CI 1.18 to 6.68, high certainty), while the risks of other adverse events for all binders were uncertain. In CKD G5D sevelamer may lead to lower death (all causes) (RR 0.53, CI 0.30 to 0.91, low certainty) and induce less hypercalcaemia (RR 0.30, CI 0.20 to 0.43, low certainty) when compared with calcium‐based binders, and has uncertain or inestimable effects on cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification. The finding of lower death with sevelamer compared with calcium was present when the analysis was restricted to studies at low risk of bias (RR 0.50, CI 0.32 to 0.77). In absolute terms, sevelamer may lower risk of death (all causes) from 210 per 1000 to 105 per 1000 over a follow‐up of up to 36 months, compared to calcium‐based binders. Compared with calcium‐based binders, lanthanum had uncertain effects with respect to all‐cause or cardiovascular death, myocardial infarction, stroke, fracture, or coronary artery calcification and probably had reduced risks of treatment‐related hypercalcaemia (RR 0.16, CI 0.06 to 0.43, low certainty). There were no head‐to‐head studies of iron‐based binders compared with calcium. The paucity of placebo‐controlled studies in CKD G5D has led to uncertainty about the effects of phosphate binders on patient‐important outcomes compared with placebo. It is uncertain whether the effects of binders on clinically‐relevant outcomes were different for patients who were and were not treated with dialysis in subgroup analyses. AUTHORS' CONCLUSIONS: In studies of adults with CKD G5D treated with dialysis, sevelamer may lower death (all causes) compared to calcium‐based binders and incur less treatment‐related hypercalcaemia, while we found no clinically important benefits of any phosphate binder on cardiovascular death, myocardial infarction, stroke, fracture or coronary artery calcification. The effects of binders on patient‐important outcomes compared to placebo are uncertain. In patients with CKD G2 to G5, the effects of sevelamer, lanthanum, and iron‐based phosphate binders on cardiovascular, vascular calcification, and bone outcomes compared to placebo or usual care, are also uncertain and they may incur constipation, while iron‐based binders may lead to diarrhoea.

While associations exist between water, hydration, and disease risk, research quantifying the dose-response effect of water on health is limited. Thus, the water intake necessary to maintain optimal hydration from a physiological and health standpoint remains unclear. The aim of this analysis was to derive a 24 h urine osmolality (UOsm) threshold that would provide an index of “optimal hydration,” sufficient to compensate water losses and also be biologically significant relative to the risk of disease. Ninety-five adults (31.5 ± 4.3 years, 23.2 ± 2.7 kg·m−2) collected 24 h urine, provided morning blood samples, and completed food and fluid intake diaries over 3 consecutive weekdays. A UOsmthreshold was derived using 3 approaches, taking into account European dietary reference values for water; total fluid intake, and urine volumes associated with reduced risk for lithiasis and chronic kidney disease and plasma vasopressin concentration. The aggregate of these approaches suggest that a 24 h urine osmolality ≤500 mOsm·kg−1may be a simple indicator of optimal hydration, representing a total daily fluid intake adequate to compensate for daily losses, ensure urinary output sufficient to reduce the risk of urolithiasis and renal function decline, and avoid elevated plasma vasopressin concentrations mediating the increased antidiuretic effort.

Background Diabetes is the leading cause of end-stage kidney disease (ESKD) around the world. Blood pressure lowering and glucose control are used to reduce diabetes-associated disability including kidney failure. However there is a lack of an overall evidence summary of the optimal target range for blood glucose control to prevent kidney failure. Objectives To evaluate the benefits and harms of intensive (HbA1c < 7% or fasting glucose levels < 120 mg/dL versus standard glycaemic control (HbA1c ≥ 7% or fasting glucose levels ≥ 120 mg/dL for preventing the onset and progression of kidney disease among adults with diabetes. Search methods We searched the Cochrane Kidney and Transplant Specialised Register up to 31 March 2017 through contact with the Information Specialist 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; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria Randomised controlled trials evaluating glucose-lowering interventions in which people (aged 14 year or older) with type 1 or 2 diabetes with and without kidney disease were randomly allocated to tight glucose control or less stringent blood glucose targets. Data collection and analysis Two authors independently assessed studies for eligibility and risks of bias, extracted data and checked the processes for accuracy. Outcomes were mortality, cardiovascular complications, doubling of serum creatinine (SCr), ESKD and proteinuria. Confidence in the evidence was assessing using GRADE. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Main results Fourteen studies involving 29,319 people with diabetes were included and 11 studies involving 29,141 people were included in our meta-analyses. Treatment duration was 56.7 months on average (range 6 months to 10 years). Studies included people with a range of kidney function. Incomplete reporting of key methodological details resulted in uncertain risks of bias in many studies. Using GRADE assessment, we had moderate confidence in the effects of glucose lowering strategies on ESKD, all-cause mortality, myocardial infarction, and progressive protein leakage by kidney disease and low or very low confidence in effects of treatment on death related to cardiovascular complications and doubling of serum creatinine (SCr). For the primary outcomes, tight glycaemic control may make little or no difference to doubling of SCr compared with standard control (4 studies, 26,874 participants: RR 0.84, 95% CI 0.64 to 1.11; I2= 73%, low certainty evidence), development of ESKD (4 studies, 23,332 participants: RR 0.62, 95% CI 0.34 to 1.12; I2= 52%; low certainty evidence), all-cause mortality (9 studies, 29,094 participants: RR 0.99, 95% CI 0.86 to 1.13; I2= 50%; moderate certainty evidence), cardiovascular mortality (6 studies, 23,673 participants: RR 1.19, 95% CI 0.73 to 1.92; I2= 85%; low certainty evidence), or sudden death (4 studies, 5913 participants: RR 0.82, 95% CI 0.26 to 2.57; I2= 85%; very low certainty evidence). People who received treatment to achieve tighter glycaemic control probably experienced lower risks of non-fatal myocardial infarction (5 studies, 25,596 participants: RR 0.82, 95% CI 0.67 to 0.99; I2= 46%, moderate certainty evidence), onset of microalbuminuria (4 studies, 19,846 participants: RR 0.82, 95% CI 0.71 to 0.93; I2= 61%, moderate certainty evidence), and progression of microalbuminuria (5 studies, 13,266 participants: RR 0.59, 95% CI 0.38 to 0.93; I2= 75%, moderate certainty evidence). In absolute terms, tight versus standard glucose control treatment in 1,000 adults would lead to between zero and two people avoiding non-fatal myocardial infarction, while seven adults would avoid experiencing new-onset albuminuria and two would avoid worsening albuminuria. Authors' conclusions This review suggests that people who receive intensive glycaemic control for treatment of diabetes had comparable risks of kidney failure, death and major cardiovascular events as people who received less stringent blood glucose control, while experiencing small clinical benefits on the onset and progression of microalbuminuria and myocardial infarction. The adverse effects of glycaemic management are uncertain. Based on absolute treatment effects, the clinical impact of targeting an HbA1c < 7% or blood glucose < 6.6 mmol/L is unclear and the potential harms of this treatment approach are largely unmeasured.

People with chronic kidney disease (CKD) have a high symptom burden and experience poorer quality of life than the general population. People with CKD frequently report fatigue, anorexia, pain, sleep disturbance, itching and restless legs. Depression and sexual dysfunction may also be common in CKD, although questions about optimal diagnosis and treatment remain unanswered. People with kidney disease identify lifestyle and the impact of CKD on family and psychosocial supports as key priorities and rate symptoms such as sexual dysfunction and psychological distress as severe. Here, we outline the current state of research underlying depression and sexual dysfunction in this population focusing on prevalence, diagnosis, screening, outcomes and interventions and suggest areas requiring additional specific research.

Increased hydration is often recommended as a preventive measure for women with recurrent cystitis, but supportive data are sparse.To assess the efficacy of increased daily water intake on the frequency of recurrent cystitis in premenopausal women.Randomized, open-label, controlled, 12-month trial at a clinical research center (years 2013-2016). Among 163 healthy women with recurrent cystitis (≥3 episodes in past year) drinking less than 1.5 L of fluid daily assessed for eligibility, 23 were excluded and 140 assigned to water or control group. Assessments of daily fluid intake, urinary hydration, and cystitis symptoms were performed at baseline, 6- and 12-month visits, and monthly telephone calls.Participants were randomly assigned to drink, in addition to their usual fluid intake, 1.5 L of water daily (water group) or no additional fluids (control group) for 12 months.Primary outcome measure was frequency of recurrent cystitis over 12 months. Secondary outcomes were number of antimicrobial regimens used, mean time interval between cystitis episodes, and 24-hour urinary hydration measurements.The mean (SD) age of the 140 participants was 35.7 (8.4) years, and the mean (SD) number of cystitis episodes in the previous year was 3.3 (0.6). During the 12-month study period, the mean (SD) number of cystitis episodes was 1.7 (95% CI, 1.5-1.8) in the water group compared with 3.2 (95% CI, 3.0-3.4) in the control group, with a difference in means of 1.5 (95% CI, 1.2-1.8; P .001). Overall, there were 327 cystitis episodes, 111 in the water group and 216 in the control group. The mean number of antimicrobial regimens used to treat cystitis episodes was 1.9 (95% CI, 1.7-2.2) and 3.6 (95% CI, 3.3-4.0), respectively, with a difference in means of 1.7 (95% CI, 1.3-2.1; P .001). The mean time interval between cystitis episodes was 142.8 (95% CI, 127.4-160.1) and 84.4 (95% CI, 75.4-94.5) days, respectively, with a difference in means of 58.4 (95% CI, 39.4-77.4; P .001). Between baseline and 12 months, participants in the water group, compared with those in the control group, had increased mean (SD) urine volume (1.4 [0.04] vs 0.1 [0.04] L; P .001) and voids (2.4 [0.2] vs -0.1 [0.2]; P .001) and decreased urine osmolality (-402.8 [19.6] vs -24.0 [19.5] mOsm/kg; P .001).Increased water intake is an effective antimicrobial-sparing strategy to prevent recurrent cystitis in premenopausal women at high risk for recurrence who drink low volumes of fluid daily.ClinicalTrials.gov identifier: NCT02444975.

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

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 Chi2 test and explored the amount of variation in treatment estimates beyond that expected by chance using the I2 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; I2 = 34%), but significantly reduced cardiovascular mortality (6 studies, 2889 participants: RR 0.75, 95% CI 0.61 to 0.92; I2 = 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; I2 = 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; I2 = 94%) and increased dialysis dose (Kt/V urea) (14 studies, 2022 participants: MD 0.07, 95% CI -0.00 to 0.14; I2 = 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 Increased hydration is commonly recommended as a preventive measure for women with recurrent acute uncomplicated cystitis (rAUC), but supportive data are sparse. The aim of this study was to assess the efficacy of increased daily water intake on the frequency of rAUC in premenopausal women. Methods 140 healthy premenopausal asymptomatic women drinking less than 1.5 L of total fluid daily (24 hours) and suffering from rAUC (33 episodes in the past year) were randomized to receive, in addition to their usual daily fluid intake, either 1.5 L water daily (water group) or no additional fluids (control group), for 12 months. Assessments of daily water and total fluid intake, urine volume and osmolality, number of urine voids, and occurrence of AUC symptoms and a reminder to notify investigators of any such symptoms were performed at baseline, 6- and 12-month clinic visits in addition to monthly telephone calls. The primary outcome was frequency of rAUC episodes (31 AUC symptom and 3103 CFU/mL of a uropathogen in voided urine) over 12 months. Results Between baseline and 12 month’s follow-up, the water group, compared with the control group, had statistically significant increases in mean daily water intake (1.15 vs. −0.01 L), total fluid intake (1.65 vs. 0.03 L), urine volume (1.40 vs. 0.04 L), and number of urine voids (2.2 vs. −0.2), and a decrease in urine osmolality (−408 vs. −35 mOsm/Kg). The mean number of rAUC episodes in the water group was significantly less than in the control group (1.6 vs. 3.1; odds ratio 0.52, 95% CI 0.46–0.60, P < 0.0001) (figure shows cumulative sum of AUC episodes over 12 months in both study groups). The mean number of antimicrobial regimens used to treat AUC events was 1.8 in the water group vs. 3.5 in the control group (P < 0.0001). In addition, the mean number of days to first rAUC and the mean number of days between rAUC episodes was longer in the water group compared with the control group (148 vs. 93, P = 0.0005 and 143 vs. 85, P < 0.0001, respectively). Conclusions Our results provide strong evidence that increased water intake is an effective antimicrobial-sparing preventive strategy for women with rAUC. Increasing daily water intake by approximately 1.5 L reduced rAUC episodes by 48% and antimicrobial regimens by 47% over 12 months. Disclosures M. Vecchio, Danone Research: Employee, Salary. A. Iroz, Dzanone Research: Employee, Salary. I. Tack, Danone Research: Consultant, Consulting fee and Speaker honorarium. Q. Dornic, Danone research: Employee, Salary. I. Seksek, Danone Research: Employee, Salary.

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 β 2 -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 β 2 -microglobulin (mean difference, −5.77 [95% CI, −10.97 to −0.56]mg/dL) and increased dialysis dose (Kt/V urea 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.

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 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.

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 methods 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.