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Background Chronic hemodialysis (HD) patients exhibit severe morpho-functional cardiac alterations, putting them at a high risk of death and adverse cardiovascular (CV) outcomes. Despite the fact that an unbalanced expression of various microRNAs (miRNAs) has been related to pathological cardiac remodeling and worse CV outcomes, scarce evidence exists on their role in this setting. Methods We evaluated circulating levels of a selected miRNAs panel (30a-5p, 23a-3p, 451a and let7d-5p) in 74 chronic HD patients together with a thorough clinical and echocardiography assessment. Individuals were then prospectively followed (median 22 months). The primary endpoint was a composite of all-cause and CV mortality and non-fatal CV events. Results Circulating levels of all miRNAs were lower in HD patients as compared with healthy controls and independently correlated to the severity of cardiac dysfunction. miRNA 30a-5p, 23a-3p and 451a expression was even lower in 30 subjects (40.5%) reaching the composite endpoint (P  < .001), while no differences were reported for let7d-5p. The predictive value of these miRNAs was supported by univariate followed by multivariate Cox regression analyses [hazard ratio (HR) ranging from 0.943 to 0.995; P  = .05 to.02] while Kaplan–Meier analyses confirmed a faster progression to the endpoint in individuals displaying miRNA levels below an optimal receiver operating characteristic–derived cut-off value (P ranging from.001 to <.0001; crude HRs 7.95 to 8.61). Conclusions Lower circulating levels of miRNA 30-5p, 23a-3p and 451a in HD patients may reflect cardiac abnormalities and predict a higher risk of worse clinical outcomes in the short mid-term. Future studies on larger HD populations are needed to generalize these findings. [ABSTRACT FROM AUTHOR]

Background We conducted a systematic review and meta-analysis to compare benefits and harms of different antihypertensive drug classes in kidney transplant recipients, as post-transplant hypertension (HTN) associates with increased cardiovascular (CV) morbidity and mortality. Methods The Ovid-MEDLINE, PubMed and CENTRAL databases were searched for randomized controlled trials (RCTs) comparing all main antihypertensive agents versus placebo/no treatment, routine treatment. Results The search identified 71 RCTs. Calcium channel blockers (CCBs) (26 trials) reduced the risk for graft loss {risk ratio [RR] 0.58 [95% confidence interval (CI) 0.38–0.89]}, increased glomerular filtration rate (GFR) [mean difference (MD) 3.08 mL/min (95% CI 0.38–5.78)] and reduced blood pressure (BP). Angiotensin-converting enzyme inhibitors (ACEIs) (13 trials) reduced the risk for graft loss [RR 0.62 (95% CI 0.40–0.96)] but decreased renal function and increased the risk for hyperkalaemia. Angiotensin receptor blockers (ARBs) (10 trials) did not modify the risk of death, graft loss and non-fatal CV events and increased the risk for hyperkalaemia. When pooling ACEI and ARB data, the risk for graft failure was lower in renin–angiotensin system (RAS) blockade as compared with control treatments. In direct comparison with ACEIs or ARBs (11 trials), CCBs increased GFR [MD 11.07 mL/min (95% CI 6.04–16.09)] and reduced potassium levels but were not more effective in reducing BP. There are few available data on mortality, graft loss and rejection. Very few studies performed comparisons with other active drugs. Conclusions CCBs could be the preferred first-step antihypertensive agents in kidney transplant patients, as they improve graft function and reduce graft loss. No definite patient or graft survival benefits were associated with RAS inhibitor use over conventional treatment. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is diagnosed when glomerular filtration rate (GFR) falls below 60 ml/min/1.73 m2 or urinary albumin:creatinine ratio (UACR) reaches ≥30 mg/g, as these two thresholds indicate a higher risk of adverse health outcomes, including cardiovascular mortality. CKD is classified as mild, moderate or severe, based on GFR and UACR values, and the latter two classifications convey a high or very high cardiovascular risk, respectively. Additionally, CKD can be diagnosed based on abnormalities detected by histology or imaging. Lupus nephritis (LN) is a cause of CKD. Despite the high cardiovascular mortality of patients with LN, neither albuminuria nor CKD are discussed in the 2019 European League Against Rheumatism (EULAR)/European Renal Association–European Dialysis and Transplant Association recommendations for the management of LN or the more recent 2022 EULAR recommendations for cardiovascular risk management in rheumatic and musculoskeletal diseases. Indeed, the proteinuria target values discussed in the recommendations may be present in patients with severe CKD and a very high cardiovascular risk who may benefit from guidance detailed in the 2021 European Society of Cardiology guidelines on cardiovascular disease prevention in clinical practice. We propose that the recommendations should move from a conceptual framework of LN as an entity separate from CKD to a framework in which LN is considered a cause of CKD and evidence generated from large CKD trials applies unless demonstrated otherwise. [ABSTRACT FROM AUTHOR]

Background Several studies have examined the frequency of sleep apnoea (SA) in patients with chronic kidney disease (CKD), reporting different prevalence rates. Our systematic review and meta-analysis aimed to define the clinical penetrance of SA in CKD and end-stage kidney disease (ESKD) patients. Methods Ovid-MEDLINE and PubMed databases were explored up to 5 June 2023 to identify studies providing SA prevalence in CKD and ESKD patients assessed by different diagnostic methods, either sleep questionnaires or respiration monitoring equipment [such as polysomnography (PSG), type III portable monitors or other diagnostic tools]. Single-study data were pooled using the random-effects model. The Chi2 and Cochrane-I2 tests were used to assess the presence of heterogeneity, which was explored performing sensitivity and/or subgroup analyses. Results A cumulative analysis from 32 single-study data revealed a prevalence of SA of 57% [95% confidence interval (CI) 42%–71%] in the CKD population, whereas a prevalence of 49% (95% CI 47%–52%) was found pooling data from 91 studies in ESKD individuals. The prevalence of SA using instrumental sleep monitoring devices, including classical PSG and type III portable sleep monitors, was 62% (95% CI 52%–72%) and 56% (95% CI 42%–69%) in CKD and ESKD populations, respectively. Sleep questionnaires revealed a prevalence of 33% (95% CI 16%–49%) and 39% (95% CI 30%–49%). Conclusions SA is commonly seen in both non-dialysis CKD and ESKD patients. Sleep-related questionnaires underestimated the presence of SA in this population. This emphasizes the need to use objective diagnostic tools to identify such a syndrome in kidney disease. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is common and is associated with increased mortality, morbidity and cost. However, insufficient high-quality trial data are available to answer many relevant clinical questions in this field. In addition, a wide range of variable outcomes are used in studies, and often they are incompletely reported. Furthermore, there is a lack of patient-relevant outcomes, such as mortality, morbidity, quality of life, pain, need for dialysis or costs. Common problems with outcome reporting are as follows: choosing the wrong domains to measure; within domains, choosing the wrong measures (invalid surrogates, composite, non-patient relevant); within measures, choosing the wrong/variablemetrics; and within metrics, choosing variable presentation methods. With this article, we aim to underline why standardized outcome reporting is key to achieving evidence-based guidance and improving clinical care for patients; highlight the frameworks available for achieving core outcome sets; and starting from these frameworks, we propose steps needed to develop a core outcome set in the field of CKD. We hope that standardized core outcome sets for nephrology will lead to the most important outcome of guideline production, improving outcomes for our patients. [ABSTRACT FROM AUTHOR]

Proteinuria is a distinguishing feature in primary and secondary forms of chronic glomerulonephritis, which contribute to no more than the 20% of the end-stage kidney disease (ESKD) population. The contribution of non-proteinuric nephropathies to the global ESKD burden is still poorly focused and scarce research efforts are dedicated to the elucidation of risk factors and mechanistic pathways triggering ESKD in these diseases. We abstracted information on proteinuria in the main renal diseases other than glomerulonephritides that may evolve into ESKD. In type 2 diabetes, non-proteinuric diabetic kidney disease (DKD) is more frequent than proteinuric DKD, and risk factors for non-proteinuric forms of DKD now receive increasing attention. Similarly, proteinuria is most often inconspicuous or absent in the most frequent cause of ESKD, i.e. hypertension-related chronic kidney disease (CKD), as well as in progressive cystic diseases like autosomal dominant polycystic kidney disease and in pyelonephritis/tubulo-interstitial diseases. Maintaining a high degree of attention in the care of CKD patients with proteinuria is fundamental to effectively retard progression toward kidney failure. However, substantial research efforts are still needed to develop treatment strategies that may help the vast majority of CKD patients who eventually develop ESKD via mechanistic pathways other than proteinuria. [ABSTRACT FROM AUTHOR]

Background. The utility of renal biopsy in patients with diabetes is highly debated. Diabetics with rapidly worsening renal disease are often 'clinically' labelled as having diabetic nephropathy (DN), whereas, inmany cases, they are rather developing a nondiabetic renal disease (NDRD) or mixed forms (DN+ NDRD). Methods. We performed a systematic search for studies on patients with diabetes with data on the frequency of DN, NDRD and mixed forms, and assessed the positive predictive values (PPVs) and odds ratios (ORs) for such diagnoses by metaanalysing single-study prevalence. Possible factors explaining heterogeneity among the different diagnoses were explored by meta-regression. Results. In the 48 included studies (n = 4876), the prevalence of DN, NDRD and mixed forms ranged from 6.5 to 94%, 3 to 82.9% and 4 to 45.5% of the overall diagnoses, respectively. IgA nephropathy was the most common NDRD (3-59%). PPVs for DN, NDRD and mixed forms were 50.1% [95% confidence interval (CI): 44.7-55.2], 36.9% (95% CI: 32.3-41.8) and 19.7% (95% CI: 16.3-23.6), respectively. The PPV when combining NDRD and mixed forms was 49.2% (95% CI: 43.8-54.5). Metaregression identified systolic pressure, HbA1c, diabetes duration and retinopathy as factors explaining heterogeneity for NDRD, creatinine and glomerular filtration rate for mixed forms and only serum creatinine for DN. ORs of DN versus NDRD and mixed forms were 1.71 (95% CI: 1.54-1.91) and 4.1 (95% CI: 3.43-4.80), respectively. Conclusions. NDRD are highly prevalent in patients with diabetes. Clinical judgment alone can lead to wrong diagnoses and delay the establishment of adequate therapies. Risk stratification according to individual factors is needed for selecting patients whomight benefit from biopsy. [ABSTRACT FROM AUTHOR]

Background. Diabetes mellitus is a frequent cause of the need for renal replacement therapy (RRT). Historically, RRT was started earlier in patients with diabetes, in an attempt to prevent complications of uraemia and diabetes. We did a systematic review to find support for this earlier start of dialysis in patients with versus without diabetes. Methods. The MEDLINE, EMBASE and CENTRAL databases were searched for articles about the timing of dialysis initiation in (subgroups of ) patients with diabetes and CKD Stage 5. Results. A total of 340 papers were screened and 11 papers were selected to be reviewed. Only three studies showed data of at least one subgroup of patients with diabetes. Two observational studies concluded that start of dialysis with a higher estimated glomerular filtration rate (eGFR) is beneficial with regard to survival, one did not find a difference and six observational studies concluded that start of dialysis with a lower eGFR is associated with better survival in patients with diabetes. The effect of timing of initiation of dialysis did not differ between patients with versus without diabetes. Lastly, one randomized controlled trial (two papers) reported that there was no difference in survival between start at higher versus lower eGFR overall and a P-value for the interaction with diabetes of P = 0.63, indicating no difference between patients with versus without diabetes with regard to the timing of start of dialysis and subsequent mortality on dialysis. Conclusions. There is no difference between early (eGFR) and late (lower eGFR) start of RRT with regard to mortality in patients with versus without diabetes. RRT should thus be initiated based on the same criteria in all patients, irrespective of the presence or absence of diabetes. [ABSTRACT FROM AUTHOR]

…Couchoud et al. have been able to analyse data from more than one million patients with diabetes and ESKD, gathered from 25 studies selected from several hundred references…Background Diabetes is the leading cause of end-stage kidney disease (ESKD). Because of conflicting results in observational studies, it is still subject to debate whether in diabetic patients the dialysis modality selected as first treatment (haemodialysis or peritoneal dialysis) may have a major impact on outcomes. We therefore aimed at performing a systematic review of the available evidence. Methods MEDLINE, EMBASE and CENTRAL databases were searched until February 2014 for English-language articles without time or methodology restrictions by highly sensitive search strategies focused on diabetes, end-stage kidney disease and dialysis modality. Selection of relevant studies, data extraction and analysis were performed by two independent reviewers. Results Twenty-five observational studies (23 on incident and 2 on prevalent cohorts) were included in this review. Mortality was the only main outcome addressed in large cohorts. When considering patient survival, results were inconsistent and varied across study designs, follow-up period and subgroups. We therefore found no evidence-based arguments in favour or against a particular dialysis modality as first choice treatment in patients with diabetes and ESKD. However, peritoneal dialysis (PD) as first choice seems to convey a higher risk of death in elderly and frail patients. Conclusions The available evidence derived from observational studies is inconsistent. Therefore evidence-based arguments indicating that HD or PD as first treatment may improve patient-centred outcomes in diabetics with ESKD are lacking. In the absence of such evidence, modality selection should be governed by patient preference, after unbiased patient information. [ABSTRACT FROM AUTHOR]

Among renal diseases, over 100 conditions meet the epidemiological criteria to be defined as rare, including disorders in development, transport and metabolism. Clinical management of rare diseases is likely to be less investigated than that of common disorders and for this reason the scientific evidence to support clinical practice is limited. Furthermore, no specific and validated methods for designing, carrying out or analyzing clinical trials in small populations exist with important consequences for evidence-based medicine. In this paper we aim at discussing the inherent difficulty in finding evidence in rare renal diseases, providing some suggestions on how the quality of evidence and the guidance in these diseases can be improved. [ABSTRACT FROM AUTHOR]

The achievement of a good glycaemic control is one of the cornerstones for preventing and delaying progression of microvascular and macrovascular complications in patients with both diabetes and chronic kidney disease (CKD). As for other drugs, the presence of an impaired renal function may significantly affect pharmacokinetics of the majority of glucose-lowering agents, thus exposing diabetic CKD patients to a higher risk of side effects, mainly hypoglycaemic episodes. As a consequence, a reduction in dosing and/or frequency of administration is necessary to keep a satisfactory efficacy/safety profile. In this review, we aim to summarize the pharmacology of the most widely used glucose-lowering agents, discuss whether and how it is altered by a reduced renal function, and the recommendations that can be made for their use in patients with different degrees of CKD. [ABSTRACT FROM AUTHOR]

Background. An iron deficiency is often present in haemodialysis (HD) patients; however, although transferrin saturation (TSAT) of <20% and/or serum ferritin of <200 ng/mL should express iron scarcity, in HD patients high ferritin levels could be related to inflammation rather than reflecting optimal iron stores. [ABSTRACT FROM PUBLISHER]

The clinical practice guideline Management of Obesity in Kidney Transplant Candidates and Recipients was developed to guide decision-making in caring for people with end-stage kidney disease (ESKD) living with obesity. The document considers the challenges in defining obesity, weighs interventions for treating obesity in kidney transplant candidates as well as recipients and reflects on the impact of obesity on the likelihood of wait-listing as well as its effect on transplant outcomes. It was designed to inform management decisions related to this topic and provide the backdrop for shared decision-making. This guideline was developed by the European Renal Association's Developing Education Science and Care for Renal Transplantation in European States working group. The group was supplemented with selected methodologists to supervise the project and provide methodological expertise in guideline development throughout the process. The guideline targets any healthcare professional treating or caring for people with ESKD being considered for kidney transplantation or having received a donor kidney. This includes nephrologists, transplant physicians, transplant surgeons, general practitioners, dialysis and transplant nurses. Development of this guideline followed an explicit process of evidence review. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendations Assessment, Development and Evaluation approach. Limitations of the evidence are discussed and areas of future research are presented. [ABSTRACT FROM AUTHOR]

KDIGO is a good example of a global guidelines body derived from a country initiative (KDOQI) which could give local standards of care. This body should then also spend efforts in the integration and harmonization of guidelines for related or common co-existing diseases in such a way that practice recommendations in different guidelines are complementary rather than contradictory. This approach would most likely: efficient use of expertise, time, and money; one standardized methodology; no duplication; better discussion on the common themes and on the exceptions; learning from each other; central repository for skills, training, techniques and data as well as the issued guidelines…The prime mission of European Renal Best Practice (ERBP) is to improve the outcome of patients with kidney disease in a sustainable way through enhancing the availability of the knowledge on the management of these patients in a format that stimulates its use in clinical practice in Europe. A key activity is to produce clinical practice guidelines to help clinicians make the healthcare decisions they face. To further improve the quality and validity of its clinical practice guidelines, ERBP has revised its guideline development process. The present document outlines the principles of ERBP's 10-step approach. Important features include standard procedures for selecting topics, for assembling the guideline development group, for choosing and formulating questions, for finding, appraising and summarizing the evidence, for generating recommendations, for preparing reports and organizing peer review. ERBP has adopted the Grading of Recommendations Assessment, Development and Evaluation system for rating the quality of the evidence and strength of recommendations and has addressed implementation in the development process by integrating the GuideLine Implementability Appraisal tool. Ultimately, it is anticipated that these changes will not only further improve the quality of the guideline development process, but also enhance the quality of care and improve outcomes of patients with kidney disease across Europe. [ABSTRACT FROM AUTHOR]

Background Hypertension (HTN) is common following renal transplantation and it is associated with adverse effects on cardiovascular (CV) and graft health. Ambulatory blood pressure monitoring (ABPM) is the preferred method to characterize blood pressure (BP) status, since HTN misclassification by office BP (OBP) is quite common in this population. We performed a systematic review and meta-analysis aimed at determining the clinical utility of 24-h ABPM and its potential implications for the management of HTN in this population. Methods Ovid-MEDLINE and PubMed databases were searched for interventional or observational studies enrolling adult kidney transplant recipients (KTRs) undergoing 24-h ABP readings compared with OBP or home BP. The main outcome was the proportion of KTRs diagnosed with HTN by ABPM, home or OBP recordings. Additionally, day–night BP variability and dipper/non-dipper status were assessed. Results Forty-two eligible studies (4115 participants) were reviewed. A cumulative analysis including 27 studies (3481 participants) revealed a prevalence of uncontrolled HTN detected by ABPM of 56% [95% confidence interval (CI) 46–65%]. The pooled prevalence of uncontrolled HTN according to OBP was 47% (95% CI 36–58%) in 25 studies (3261 participants). Very few studies reported on home BP recordings. The average concordance rate between OBP and ABPM measurements in classifying patients as controlled or uncontrolled hypertensive was 66% (95% CI 59–73%). ABPM revealed HTN phenotypes among KTRs. Two pooled analyses of 11 and 10 studies, respectively, revealed an average prevalence of 26% (95% CI 19–33%) for masked HTN (MHT) and 10% (95% CI 6–17%) for white-coat HTN (WCH). The proportion of non-dippers was variable across the 28 studies that analysed dipping status, with an average prevalence of 54% (95% CI 45–63%). Conclusions In our systematic review, comparison of OBP versus ABP measurements disclosed a high proportion of MHT, uncontrolled HTN and, to a lesser extent, WCH in KTRs. These results suggest that HTN is not adequately diagnosed and controlled by OBP recordings in this population. Furthermore, the high prevalence of non-dippers confirmed that circadian rhythm is commonly disturbed in KTRs. [ABSTRACT FROM AUTHOR]

Background Few studies show that ambulatory blood pressure (BP) monitoring (ABPM) is superior to office BP (oBP) measurements to predict target organ damage and cardiovascular (CV) events in kidney transplant recipients (KTRs). We performed a systematic review aimed at determining the potential associations between BP recordings by different methods and renal and CV outcomes in this population. Methods Major medical databases were searched for studies enrolling adult KTRs undergoing 24-h ABPM compared with office or home BP measurements. The main outcomes were associations between different BP recordings and renal and CV outcomes. Additionally, any association between the circadian BP pattern (dipping/non-dipping status) and outcomes was assessed. Results Twenty-two studies (2078 participants) were reviewed. Among 12 studies collecting data on renal endpoints, 10 studies found that BP assessed by ABPM was a stronger predictor of renal function decline, assessed by serum creatinine and/or creatinine clearance or estimated glomerular filtration rate, than traditional office measurements. Twelve studies analysed the relation between different BP recordings and CV target organ damage and reported robust correlations between echocardiographic abnormalities (i.e. left ventricular mass index) and 24-h ABPM, but not with office BPs. Furthermore, 24-h ABPM correlated better than oBP with markers of vascular damage, such as carotid intima-media thickness, diffuse thickening and endothelial dysfunction. Additionally, an abnormal circadian BP pattern (non-dippers and reverse dippers) identified a group of kidney recipients at risk for kidney function loss and CV abnormalities. Conclusions In our systematic review, ABPM reflected target organ damage more closely than oBP in KTRs. Furthermore, an altered circadian BP profile associated with renal and CV target organ damage. [ABSTRACT FROM AUTHOR]

The presumed superiority of renin-angiotensin-aldosterone system (RAAS)-blocking agents over other antihypertensive agents in patients with diabetes to delay development of endstage kidney disease (ESKD) has recently been challenged. In addition, there is ongoing uncertainty whether RAAS-blocking agents reduce mortality and/or delay ESKD in patients with diabetes and chronic kidney disease (CKD) stages 3-5. In this subgroup, there might be an expedited need for renal replacement therapy (RRT) when RAAS-blocking agents are used. We conducted a meta-analysis of randomized controlled trials (RCTs) of at least 6-months duration in adult patients with diabetes who also have non-dialysis CKD stages 3-5. RCTs comparing single RAAS-blocking agents to placebo or alternative antihypertensive agents were included. Outcomes of interest were allcause mortality, cardiovascular morbidity, progression of renal function, ESKD and adverse events. A total of nine trials (n=9797 participants with CKD stages 3-5) fit our inclusion criteria. There was no difference between the RAAS group and control group regarding all-cause mortality {relative risk [RR]=0.97 [95% confidence interval (CI) 0.85-1.10]}, cardiovascular mortality [RR=1.03 (95% CI 0.75-1.41)] and adverse events [RR=1.05 (95% CI 0.89-1.25)]. There was a trend for a favourable effect for non-fatal cardiovascular events [RR=0.90 (95% CI 0.81-1.00)] and a lower risk of the composite endpoint need for RRT/doubling of serum creatinine [RR=0.81 (95% CI 0.70-0.92)] in the RAAS-blocking agents group versus the control group. We found evidence that in patients with diabetes mellitus and CKD stages 3-5, treatment with RAAS-blocking agents did not result in a clear survival advantage. The effect on renal outcomes did depend on the selected outcome measure. However, we did not find evidence that the use of RAASblocking agents expedited the need for RRT in patients with CKD stages 3-5. [ABSTRACT FROM AUTHOR]

Background: Catheter-based renal denervation (RDN) is a possible treatment to lower blood pressure. The invasive nature of RDN and the use of contrast agents raise concerns about potential consequent kidney damage. Our objective was to determine the change in renal function after RDN by performing a systematic review on hypertensive patients treated with RDN. Methods: A systematic search was performed in the Embase and MEDLINE databases to identify studies reporting on the effects of catheter-based RDN on renal outcome. Studies published between January 2009 and May 2016, irrespective of study design, device used or indication for treatment were included. We performed random effects meta-analyses on the change in estimated glomerular filtration rate (eGFR), serum creatinine, serum cystatin C and albumin:creatinine ratio after RDN. We only extracted and meta-analysed data from patients treated with RDN. Results: From 1034 citations, 52 studies (38 cohort studies, 4 non-randomized comparative studies and 10 randomized controlled trials) reporting on 56 RDN cohorts were included in meta-analyses and another 14 studies in a qualitative review. Of these 56 cohorts, 48 were specifically eligible for determining the change in eGFR after RDN, totaling 2381 patients. There was no statistically significant change in eGFR after a mean follow-up time of 9.1±7.0months [0.64mL/min/1.73 m2 (95% confidence interval --0.47 to 1.76), P=0.26]. The pooled mean change in serum creatinine and the results of the qualitative review further supported these findings. Conclusions: Based on meta-analyses of 52 studies and a qualitative review of an additional 14 studies, reporting on 2898 patients in total, we conclude that renal function does not significantly change up to at least 9months after RDN. [ABSTRACT FROM AUTHOR]

Background. It is the object of debate whether a low or high dialysate sodium concentration (DNa+) should be advocated in chronic haemodialysis patients. In this paper, we aimed at evaluating benefits and harms of different DNa+ prescriptions through a systematic review of the available literature. Methods. MEDLINE and CENTRAL databases were searched for studies comparing low or high DNa+ prescriptions. Outcomes of interest were mortality, blood pressure (BP), interdialytic weight gain (IDWG), plasma sodium, hospitalizations, use of anti-hypertensive agents and intradialytic complications. Results. Twenty-three studies (76 635 subjects) were reviewed. There was high heterogeneity in the number of patients analysed, overall study quality, duration of follow-up, DNa+ and even in the definition of 'high' or 'low' DNa+. The only three studies looking at mortality were observational. The risk of death was related to the plasma-DNa+ gradient, but was also shown to be confounded by indication from the dialysate sodium prescription itself. BP was not markedly affected by high or low DNa+. Patients treated with higher DNa+ had overall higher IDWG when compared with those with lower DNa+. Three studies reported a significant increase in intra-dialytic hypotensive episodes in patients receiving low DNa+. Data on hospitalizations and use of anti-hypertensive agents were sparse and inconclusive. Conclusions. There is currently no definite evidence proving the superiority of a low or high uniform DNa+ on hard or surrogate endpoints in maintenance haemodialysis patients. Future trials adequately powered to evaluate the impact of different DNa+ on mortality or other patient-centred outcomes are needed. [ABSTRACT FROM AUTHOR]