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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.

BACKGROUND: The negative role of HLA class II donor-specific antibody on graft outcome is well recognized. However, the potentially negative cardiovascular effects of preformed HLA class II antibodies and donor HLA in kidney transplant recipients (KTRs) remain unestablished. METHODS: We conducted a single-center, retrospective cohort study including 1115 KTRs (2003-2016) with up to 4449 person-years of follow-up after transplantation and a median follow-up time of 5.1 years (interquartile range, 2.7-7.6). We evaluated the unadjusted and multivariable-adjusted association between pretransplant HLA class I and II antibodies, as well as HLA-DR1 donor/recipient genotype and the primary (major adverse cardiac and cerebrovascular event [MACCE] or all-cause mortality) and secondary (MACCE or cardiovascular mortality) outcome. RESULTS: In a multivariate Cox proportional hazard model, HLA class II antibodies before transplantation were associated with increased adjusted hazard ratio (aHR) for MACCE or all-cause mortality (aHR, 1.71 [1.13-2.60]; P = 0.012) even after adjustment for time-varying covariate graft loss (aHR, 1.68 [1.08-2.62]; P = 0.022) and biopsy-proven acute rejection (aHR, 1.71 [1.13-2.60]; P = 0.012). HLA class II antibodies were also associated with increased aHR for the secondary outcome, MACCE, or cardiovascular mortality (aHR, 1.92 [1.12-3.30]; P = 0.018). We investigated the effect of donor and recipient HLA-DR1 on these outcome parameters and demonstrated that KTRs with HLA-DR1 positive donors had an increased aHR for MACCE with all-cause (aHR, 1.45 [1.09-1.94]; P = 0.012) and cardiovascular mortality (aHR, 1.49 [1.00-2.22]; P = 0.05). CONCLUSIONS: Prior sensitization against HLA class II antigens is associated with unfavorable long-term cardiovascular outcome in KTRs independent of graft loss or rejection. Recipients of an HLA-DR1 donor also have an impaired cardiovascular outcome. ispartof: TRANSPLANTATION vol:104 issue:4 pages:823-834 ispartof: location:United States status: published

BACKGROUND Hypomagnesemia is associated with a disturbed glucose metabolism. Insulin hypo-secretion predicts diabetes in the general population and in transplant recipients. We aimed to assess whether magnesium improves insulin secretion and glycemic control after transplantation in prevalent hypomagnesemic kidney transplant recipients. MATERIAL AND METHODS We conducted an open-label, randomized, parallel-group study. Eligible participants were adults more than 4 months after kidney transplantation on tacrolimus with persisting serum magnesium concentrations

Background: Polycystic kidney disease (PKD) is characterized by urinary tract infections and extrarenal abnormalities such as an increased risk of cancer. As mutations in polycystin-1 and -2 are associated with decreased proliferation of immortalized lymphoblastoid cells in PKD, we investigated whether lymphopenia could be an unrecognized trait of PKD. Methods: We studied 700 kidney transplant recipients with ( n = 126) or without PKD at the time of kidney transplantation between 1 January 2003 and 31 December 2014 at Ghent University Hospital. We also studied 204 patients with chronic kidney disease (CKD) with PKD and 204 matched CKD patients without PKD across comparable CKD strata with assessment between 1 January 1999 and 1 February 2016 at three renal outpatient clinics. We compared lymphocyte counts with multiple linear regression analysis to adjust for potential confounders. We analysed flow cytometric immunophenotyping data and other haematological parameters. Results: Lymphocyte counts were 264/µL [95% confidence interval (CI) 144-384] and 345/µL (95% CI 245-445) (both P

Smoking is associated with unfavourable outcome in solid-organ transplant recipients. Nicotine may predispose to kidney injury by increasing oxidative stress. We hypothesized that former smoking negatively affects graft outcome in kidney transplant recipients and especially those with delayed graft function (DGF). We included adult recipients of a kidney transplant between 1 January 2003 and 1 October 2015 at Ghent University Hospital and recorded outcomes until 31 October 2015. We used Kaplan-Meier and multivariable Cox proportional hazard analysis to examine the relationship between former smoking at the time of transplantation and the incidence of 10-year graft loss with and without censoring for death in 1013 participants. We evaluated mean differences in eGFR over time by a random intercept and slope model, considering a linear time effect. After adjusting for potential confounders, a history of smoking was associated with an increased hazard of graft loss (adjusted hazard ratio (aHR) 1.60; 95% CI: 1.17-2.17; P = 0.003) and death-censored graft loss (aHR 2.29; 95% CI: 1.41-3.72; P = 0.001). The linear time trend of eGFR was different between former and never smokers (P = 0.001). To conclude, former smoking exerts long-lasting negative effects on graft outcome and this independent of DGF.

The strengths and the limitations of research activities currently present in Europe are explored in order to outline how to proceed in the near future. Epidemiological and clinical research and public policy in Europe are generally considered to be comprehensive and successful, and the European Renal Association – European Dialysis and Transplant Association (ERA-EDTA) is playing a key role in the field of nephrology research. The Nephrology and Public Policy Committee (NPPC) aims to improve the current situation and translation into public policy by planning eight research topics to be supported in the coming 5 years by ERA-EDTA.

Magnesium is a co-factor in natural killer and T cell reactivity and may modify the course of infections. We examined the association between baseline serum magnesium concentration and infections requiring admission the first year after kidney transplantation.Inclusion of adults transplant recipients between January 2003 and 31 December 2013. Cox piecewise linear regression model estimating the hazard ratio for first admission for infection. Outcomes until one year post-transplantation or up to May 1, 2014.Overall, 371 of 873 persons were admitted at least once the first year after transplantation (65 events per 100 person-years). The infection-specific cumulative incidence increased with lower serum magnesium concentration (P = 0.008). After adjustment for confounders, a low serum magnesium was associated with an increased hazard of infection (P 0.0001 in type 3 test). With 2 mg/dL as the reference value, every 0.1 mg/dL reduction in serum magnesium at baseline below 2 mg/dL (N = 165) increased the hazard ratio by 15% (HR 1.15, 95%CI 1.05-1.27; P = 0.002) while every increase of 0.1 mg/dL in those with a serum magnesium between 2 and 3 mg/dL (N = 661) decreased the hazard ratio by 4% (HR 0.96, 95%CI 0.93-1.00; P = 0.08).A lower baseline serum magnesium concentration is associated with an increased risk of infection after kidney transplantation.

In this publication, we review the definitions, symptoms, causes, differential diagnoses and therapies of hypokalemia and hyperkalemia.Comprehensive tables and diagnostic algorithms are provided when appropriate.Although both hypokalemia and hyperkalemia may be life-threatening, this is essentially the case with severe changes (serum potassium 2.5 or 6.5 mmol/L), the presence of symptoms or electrocardiographic deviations, the association with aggravating factors (e.g. digitalis intake) and/or rapid acute changes. Only these truly need an emergency therapeutic approach. In all other cases, a careful consideration of the causes and their correction should prevail over additional approaches to modify serum potassium concentration. Although most therapeutic approaches to both hypokalemia and hyperkalemia have been well established since many years, recently two new intestinal potassium binders have been introduced on the market. It remains to be elucidated whether these drugs truly have an additional role on top of the existing treatments.

Background : Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer hospital stays. Many treatments, such as fluid restriction or vasopressin receptor antagonists can be used to improve the hyponatraemia, but whether that translates into improved patient-important outcomes is less certain. Objectives : This review aimed to 1) look at the benefits and harms of interventions for chronic non-hypovolaemic hypotonic hyponatraemia when compared with placebo, no treatment or head-to-head; and 2) determine if benefits and harms vary in absolute or relative terms dependent on the specific compound within a drug class, on the dosage used, or the underlying disorder causing the hyponatraemia. Search methods : We searched the Cochrane Kidney and Transplant Register of Studies up to 1 December 2017 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. We also screened the reference lists of potentially relevant studies, contacted authors, and screened the websites of regulatory agencies. Selection criteria : We included randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of any intervention with placebo, no treatment, standard care, or any other intervention in patients with chronic non-hypovolaemic hypotonic hyponatraemia. We also included subgroups with hyponatraemia from studies with broader inclusion criteria (e.g. people with chronic heart failure or people with cirrhosis with or without hyponatraemia), provided we could obtain outcomes for participants with hyponatraemia from the report or the study authors. Data collection and analysis : Two authors independently extracted data and assessed risk of bias. We expressed treatment effects as mean difference (MD) for continuous outcomes (health-related quality of life, length of hospital stay, change from baseline in serum sodium concentration, cognitive function), and risk ratio (RR) for dichotomous outcomes (death, response and rapid increase in serum sodium concentration, hypernatraemia, polyuria, hypotension, acute kidney injury, liver function abnormalities) together with 95% confidence intervals (CI). Main results : We identified 35 studies, enrolling 3429 participants. Twenty-eight studies (3189 participants) compared a vasopressin receptor antagonist versus placebo, usual care, no treatment, or fluid restriction. In adults with chronic, non-hypovolaemic hypotonic hyponatraemia, vasopressin receptor antagonists have uncertain effects on death at six months (15 studies, 2330 participants: RR 1.11, 95% CI 0.92 to 1.33) due to risk of selective reporting and serious imprecision; and on health-related quality of life because results are at serious risk of performance, selective reporting and attrition bias, and suffer from indirectness related to the validity of the Short Form Health Survey (SF -12) in the setting of hyponatraemia. Vasopressin receptor antagonists may reduce hospital stay (low certainty evidence due to risk of performance bias and imprecision) (3 studies, 610 participants: MD-1.63 days, 95% CI -2.96 to -0.30), and may make little or no difference to cognitive function (low certainty evidence due to indirectness and imprecision). Vasopressin receptor antagonists probably increase the intermediate outcome of serum sodium concentration (21 studies, 2641 participants: MD 4.17 mmol/L, 95% CI 3.18 to 5.16), corresponding to two and a half as many people having a 5 to 6 mmol/L increase in sodium concentration compared with placebo at 4 to 180 days (moderate certainty evidence due to risk of attrition bias) (18 studies, 2014 participants: RR 2.49, 95% CI 1.95 to 3.18). But they probably also increase the risk of rapid serum sodium correction - most commonly defined as > 12 mmol/L/d (moderate certainty evidence due to indirectness) (14 studies, 2058 participants: RR 1.67, 95% CI 1.16 to 2.40) and commonly cause side-effects such as thirst (13 studies, 1666 participants: OR 2.77, 95% CI 1.80 to 4.27) and polyuria (6 studies, 1272 participants): RR 4.69, 95% CI 1.59 to 13.85) (high certainty evidence). The potential for liver toxicity remains uncertain due to large imprecision. Effects were generally consistent across the different agents, suggesting class effect. Data for other interventions such as fluid restriction, urea, mannitol, loop diuretics, corticosteroids, demeclocycline, lithium and phenytoin were largely absent. Authors' conclusions : In people with chronic hyponatraemia, vasopressin receptor antagonists modestly raise serum sodium concentration at the cost of a 3% increased risk of it being rapid. To date there is very low certainty evidence for patient-important outcomes; the effects on mortality and health-related quality of life are unclear and do not rule out appreciable benefit or harm; there does not appear to be an important effect on cognitive function, but hospital stay may be slightly shorter, although available data are limited. Treatment decisions must weigh the value of an increase in serum sodium concentration against its short-term risks and unknown effects on patient-important outcomes. Evidence for other treatments is largely absent. Further studies assessing standard treatments such as fluid restriction or urea against placebo and one-another would inform practice and are warranted. Given the limited available evidence for patient-important outcomes, any study should include these outcomes in a standardised manner.

Worldwide, several bodies produce renal guidelines, potentially leading to duplication of effort while other topics may remain uncovered. A collaborative work plan could improve efficiency and impact, but requires a common approved methodology. The aim of this study was to identify organizational and methodological similarities and differences among seven major renal guideline bodies to identify methodological barriers to a collaborative effort. An electronic 62-item survey with questions based on the Institute of Medicine standards for guidelines was completed by representatives of seven major organizations producing renal guidelines: the Canadian Society of Nephrology (CSN), European Renal Best Practice (ERBP), Kidney Disease Improving Global Outcome (KDIGO), Kidney Health Australia-Caring for Australians with Renal Insufficiency (KHA-CARI), Kidney Disease Outcome Quality Initiative (KDOQI), Sociedad Latino-Americano de Nefrologia e Hipertension (SLANH) and United Kingdom Renal Association (UK-RA). Five of the seven groups conduct systematic searches for evidence, two include detailed critical appraisal and all use the GRADE framework. Five have public review of the guideline draft. Guidelines are updated as new evidence comes up in all, and/or after a specified time frame has passed (N = 3). Commentaries or position statements on guidelines published by other groups are produced by five, with the ADAPTE framework (N = 1) and the AGREEII (N = 2) used by some. Funding is from their parent organizations (N = 5) or directly from industry (N = 2). None allow funders to influence topic selection or guideline content. The budgets to develop a full guideline vary from $2000 to $500 000. Guideline development groups vary in size from

The European Best Practice Guideline group (EBPG) issued guidelines on the evaluation and selection of kidney donor and kidney transplant candidates, as well as post-transplant recipient care, in the year 2000 and 2002. The new European Renal Best Practice board decided in 2009 that these guidelines needed updating. In order to avoid duplication of efforts with kidney disease improving global outcomes, which published in 2009 clinical practice guidelines on the post-transplant care of kidney transplant recipients, we did not address these issues in the present guidelines.The guideline was developed following a rigorous methodological approach: (i) identification of clinical questions, (ii) prioritization of questions, (iii) systematic literature review and critical appraisal of available evidence and (iv) formulation of recommendations and grading according to Grades of Recommendation Assessment, Development, and Evaluation (GRADE). The strength of each recommendation is rated 1 or 2, with 1 being a 'We recommend' statement, and 2 being a 'We suggest' statement. In addition, each statement is assigned an overall grade for the quality of evidence: A (high), B (moderate), C (low) or D (very low). The guideline makes recommendations for the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and perioperative recipient care.All together, the work group issued 112 statements. There were 51 (45%) recommendations graded '1', 18 (16%) were graded '2' and 43 (38%) statements were not graded. There were 0 (0%) recommendations graded '1A', 15 (13%) were '1B', 19 (17%) '1C' and 17 (15%) '1D'. None (0%) were graded '2A', 1 (0.9%) was '2B', 8 (7%) were '2C' and 9 (8%) '2D'. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research.We present here the complete recommendations about the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and the perioperative recipient care. We hope that this document will help caregivers to improve the quality of care they deliver to patients. The full version with methods, rationale and references is published in Nephrol Dial Transplant (2013) 28: i1-i71; doi: 10.1093/ndt/gft218 and can be downloaded freely from http://www.oxfordjournals.org/our_journals/ndt/era_edta.html.

Background Steroid-sparing strategies have been attempted in recent decades to avoid morbidity from long-term steroid intake among kidney transplant recipients. Previous systematic reviews of steroid withdrawal after kidney transplantation have shown a significant increase in acute rejection. There are various protocols to withdraw steroids after kidney transplantation and their possible benefits or harms are subject to systematic review. This is an update of a review first published in 2009. Objectives To evaluate the benefits and harms of steroid withdrawal or avoidance for kidney transplant recipients. Search methods We searched the Cochrane Kidney and Transplant Specialised Register to 15 February 2016 through contact with the Information Specialist using search terms relevant to this review. Selection criteria All randomised and quasi-randomised controlled trials (RCTs) in which steroids were avoided or withdrawn at any time point after kidney transplantation were included. Data collection and analysis Assessment of risk of bias and data extraction was performed by two authors independently and disagreement resolved by discussion. Statistical analyses were performed using the random-effects model and dichotomous outcomes were reported as relative risk (RR) and continuous outcomes as mean difference (MD) with 95% confidence intervals. Main results We included 48 studies (224 reports) that involved 7803 randomised participants. Of these, three studies were conducted in children (346 participants). The 2009 review included 30 studies (94 reports, 5949 participants). Risk of bias was assessed as low for sequence generation in 19 studies and allocation concealment in 14 studies. Incomplete outcome data were adequately addressed in 22 studies and 37 were free of selective reporting. The 48 included studies evaluated three different comparisons: steroid avoidance or withdrawal compared with steroid maintenance, and steroid avoidance compared with steroid withdrawal. For the adult studies there was no significant difference in patient mortality either in studies comparing steroid withdrawal versus steroid maintenance (10 studies, 1913 participants, death at one year post transplantation: RR 0.68, 95% CI 0.36 to 1.30) or in studies comparing steroid avoidance versus steroid maintenance (10 studies, 1462 participants, death at one year after transplantation: RR 0.96, 95% CI 0.52 to 1.80). Similarly no significant difference in graft loss was found comparing steroid withdrawal versus steroid maintenance (8 studies, 1817 participants, graft loss excluding death with functioning graft at one year after transplantation: RR 1.17, 95% CI 0.72 to 1.92) and comparing steroid avoidance versus steroid maintenance (7 studies, 1211 participants, graft loss excluding death with functioning graft at one year after transplantation: RR 1.09, 95% CI 0.64 to 1.86). The risk of acute rejection significantly increased in patients treated with steroids for less than 14 days after transplantation (7 studies, 835 participants: RR 1.58, 95% CI 1.08 to 2.30) and in patients who were withdrawn from steroids at a later time point after transplantation (10 studies, 1913 participants, RR 1.77, 95% CI 1.20 to 2.61). There was no evidence to suggest a difference in harmful events, such as infection and malignancy, in adult kidney transplant recipients. The effect of steroid withdrawal in children is unclear. Authors' conclusions This updated review increases the evidence that steroid avoidance and withdrawal after kidney transplantation significantly increase the risk of acute rejection. There was no evidence to suggest a difference in patient mortality or graft loss up to five year after transplantation, but long-term consequences of steroid avoidance and withdrawal remain unclear until today, because prospective long-term studies have not been conducted.

An estimated 60% of kidney transplant recipients have mineral bone disease and about 0.5% break their hip within the first year after transplantation. We conducted a systematic review of benefits and harms of bisphosphonates in kidney transplant recipients. We searched CENTRAL (Issue 5, 2015) for randomized controlled trials in all languages and screened the reference list of an earlier Cochrane review. One reviewer identified the trials, extracted all data, and assessed risk of bias. Meta-analysis used a random effects model, with results expressed as risk ratios (RR) or mean differences (MD) with 95% confidence intervals (CI). Bisphosphonates have uncertain effects on death (RR 0.45, CI 0.04-4.69) and vertebral fractures (RR 0.58, CI 0.24-1.43, I(2) 0%). Bisphosphonates moderately to importantly reduce the loss of vertebral bone mineral density (MD 5.98%, CI 3.77-8.18% change from baseline in g calcium/cm² at 12 months, I(2) 91%) and femoral bone mineral density (MD 5.57%, 3.12-8.01% change from baseline in g calcium/cm² at 12 months, I(2) 69%). At this stage, insufficient evidence exists to support routine use of bisphosphonates to reduce fracture risk after kidney transplantation. Data on important health outcomes are lacking, surrogate outcomes poorly reflect bone quality in kidney transplant recipients, and serious adverse events are not studied and reported systematically.

Elevated vasopressin may increase systemic vascular resistance and pulmonary capillary wedge pressure, subsequently decrease stroke volume and cardiac output. Vasopressin receptor antagonists may counteract these effects and improve outcomes in heart failure. We aimed to assess benefits and harms of vasopressin receptor antagonists (VRAs) versus placebo in addition to standard care in adults with heart failure (HF).We conducted a systematic review of randomized controlled trials with searches of CENTRAL and MEDLINE to January 2014 and reference lists without language restriction. Meta-analysis using a random-effects model was done for all-cause and cardiovascular mortality, hospitalization for heart failure, changes in clinical assessment of HF, serum sodium concentration (Na), kidney function and treatment-specific side effects.We identified 13 trials and 5,525 participants. In 10 trials, participants received standard therapy for HF. In low-quality evidence, VRAs in patients with HF had no effect on all-cause mortality risk ratios (RR 0.98; CI 0.88-1.08), cardiovascular mortality (RR 1.03; CI 0.91-1.16) or change in creatinine mean difference (MD -0.01; CI -0.10 to 0.09 mg/dL), but reduced body weight by 0.8 kg from baseline (MD -0.83; CI -1.10 to -0.55 kg) and increased Na (MD 2.61; 95 % CI 1.88-3.35 mmol/L). Compared with placebo, VRAs increased the risk of adverse events by 14 % (RR 1.14; CI 1.04-1.26). Studies were generally limited to short-term follow-up with limited data available on patient important outcomes.Vasopressin receptors antagonists may reduce body weight and increase Na but do not improve all-cause mortality, cardiovascular mortality or kidney function. In addition, acceptability of long-term treatment side effects and hospitalization appears problematic.

A growing number of publications supports a biologic effect of the protein-bound uremic retention solutes indoxyl sulfate and p-cresyl sulfate. However, the use of unrealistically high free concentrations of these compounds and/or inappropriately low albumin concentrations may blur the interpretation of these results. Here, we performed a systematic review, selecting only studies in which, depending on the albumin concentration, real or extrapolated free concentrations of indoxyl sulfate and p-cresyl sulfate remained in the uremic range. The 27 studies retrieved comprised in vitro and animal studies. A quality score was developed, giving 1 point for each of the following criteria: six or more experiments, confirmation by more than one experimental approach, neutralization of the biologic effect by counteractive reagents or antibodies, use of a real-life model, and use of dose-response analyses in vitro and/or animal studies. The overall average score was 3 of 5 points, with five studies scoring 5 of 5 points and six studies scoring 4 of 5 points, highlighting the superior quality of a substantial number of the retrieved studies. In the 11 highest scoring studies, most functional deteriorations were related to uremic cardiovascular disease and kidney damage. We conclude that our systematic approach allowed the retrieval of methodologically correct studies unbiased by erroneous conditions related to albumin binding. Our data seem to confirm the toxicity of indoxyl sulfate and p-cresyl sulfate and support their roles in vascular and renal disease progression.

Background : Asymptomatic bacteriuria, defined as bacteriuria without signs or symptoms of urinary tract infection (UTI), occurs in 17% to 51% of kidney transplant recipients and is thought to increase the risk for a subsequent UTI. No consensus exists on the role of antibiotics for asymptomatic bacteriuria in kidney transplantation. Objectives : To assess the benefits and harms of treating asymptomatic bacteriuria in kidney transplant recipients with antimicrobial agents to prevent symptomatic UTI, all-cause mortality and the indirect effects of UTI (acute rejection, graft loss, worsening of graft function). Search methods : We searched the Cochrane Kidney and Transplant Register of Studies up to 1 September 2017 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 : All randomised controlled trials (RCTs) and quasi-RCTs in any language assessing treatment of asymptomatic bacteriuria in kidney transplant recipients at any time-point after transplantation. Data collection and analysis : Two authors independently determined study eligibility, assessed quality and extracted data. Primary outcomes were incidence of symptomatic UTI and incidence of antimicrobial resistance. Other outcomes included incidences of all-cause mortality, graft loss, graft rejection, graft function, hospitalisation for UTI, adverse reactions to antimicrobial agents and relapse or persistence of asymptomatic bacteriuria. We expressed dichotomous outcomes as absolute risk difference (RD) or risk ratio (RR) with 95% confidence intervals (CI) and continuous data as mean differences (MD) with 95% CI. Data were pooled using the random effects model. Main results : We included two studies (212 participants) comparing antibiotics versus no treatment, and identified three on-going studies. Overall, incidence of symptomatic UTI varied between 19% and 31% in the groups not treated for asymptomatic bacteriuria. Antibiotic treatment had uncertain effects on preventing symptomatic UTI (2 studies, 200 participants: RR 0.86, 95% CI 0.51 to 1.45). Risk for selecting multidrug-resistant organisms was uncertain with antibiotic treatment (1 study, 112 participants: RR 1.21, 95% CI 0.60 to 2.41). Persistence of asymptomatic bacteriuria was high regardless of treatment. Antibiotics also have uncertain effects on other important patient and graft outcomes, for instance on all-cause mortality (1 study, 112 participants: RR 2.23, 95% CI 0.21 to 23.86), graft loss (1 study, 112 participants: RR 1.11, 95% CI 0.07 to 17.36), acute rejection (1 study, 112 participants: RR 0.93, 95% CI 0.44 to 1.97), hospitalisation for UTI (1 study, 112 participants: RR 0.74, 95% CI 0.13 to 4.27), graft function (2 studies, 200 participants, MD in serum creatinine concentration -0.06 mg/dL, 95% CI -0.19 to 0.08) and adverse reactions (1 study, 112 participants: no severe adverse event attributable to the antibiotic treatment). Evidence quality was low for all outcomes. Authors' conclusions : Currently, there is insufficient evidence to support routinely treating kidney transplant recipientswith antibiotics in case of asymptomatic bacteriuria after transplantation, but data are scarce. Further studies assessing routine antibiotic treatment would inform practice and we await the results of three ongoing randomised studies, which may help resolve existing uncertainties.

Post-transplantation hypomagnesemia is common and predicts diabetes. Magnesium improves glycemic control in diabetics and insulin sensitivity in insulin resistant subjects. We aimed to assess the effectiveness of oral magnesium for improving glycemic control and insulin sensitivity at 3 months post-transplantation. We conducted a single-center, open-label, randomized parallel group study. We included adults with serum magnesium

Hypomagnesemia predicts cardiovascular morbidity and mortality in the general population and accelerated loss of kidney function in renal transplant recipients and diabetics. It is associated with risk factors for cardiovascular and renal injury such as hyperaldosteronism, endothelial dysfunction, oxidative stress, insulin resistance, and hypertension. We aimed to establish the prognostic significance of hypomagnesemia for all-cause mortality and decline in estimated glomerular filtration rate (eGFR) in chronic kidney disease.Baseline parameters and serial follow-up measurements of serum creatinine were obtained in 1650 patients with chronic kidney disease and follow-up in a tertiary hospital between January 2002 and June 2011. We used Cox proportional hazards regression to assess the predictive value of magnesium for all-cause mortality and a random-effects mixed linear model for longitudinal analysis of the effect of serum magnesium on eGFR decline.After a median follow-up of 5.1 years, 284 deaths occurred. Higher magnesium was associated with reduced mortality (adjusted hazard ratio 0.930 per 0.1 mg/dL increase; 95% confidence interval [CI], 0.887-0.974; P = .002) after adjustment for potential confounders including age, sex, diabetes, kidney function, and hypertension. Patients with low (1.8 mg/dL) versus high (2.2 mg/dL) serum magnesium had a 61% increased mortality risk (adjusted hazard ratio 1.613; 95% CI, 1.113-2.338; P = .012). On average, eGFR changed by 0.934 per year (95% CI, 0.927-0.941; P.0001) or an annual decrease of 6.6%. After adjustment for age, sex, diabetes, and hypertension, this change was modified by a factor of 1.033 (95% CI, 1.003-1.065; P = .032) per 1-mg/dL increase in baseline magnesium, corresponding to an annual eGFR decrease of 3.5%. The effect of magnesium lost significance after adjustment for additional covariates, including diuretics.Hypomagnesemia predicts mortality and kidney function decline in chronic kidney disease patients. Confounding factors and treatment effects may affect these associations. Its potential as a modifiable risk factor remains to be established.

Background. The prevalence of major depression in stage 5 chronic kidney disease (CKD) varies between 14 and 30%. Patients with CKD who are depressed have a worse quality of life, are hospitalized more often and die sooner than those who are not depressed. Antidepressant drugs are effective in the general population, but whether they improve outcomes in CKD is uncertain. Drug pharmacokinetics are altered in CKD, which may necessitate dose adjustment. We aimed to systematically review available evidence of the pharmacokinetics, efficacy and safety of antidepressant drugs when used in patients with CKD3 to CKD5 (CKD3-5). Methods. This is a systematic review of randomized clinical trials and observational studies examining antidepressants in patients with CKD3-5, regardless of whether or not patients are on dialysis. Through comprehensive searches of seven databases, we identified all studies examining pharmacokinetic properties or clinical outcomes in patients with CKD3-5. One author assessed studies for eligibility and quality and extracted all data. Antidepressant drugs were the studied intervention. The main outcomes were pharmacokinetic parameters, clinical outcomes such as response to treatment, reduction in depression severity and adverse events. Results. We identi fied 28 studies evaluating pharmacokinetic parameters in CKD for 24 antidepressants. Sparse and heterogeneous data precluded informative meta-analysis. Drug clearance in CKD3-5 was markedly reduced for selegiline, amitriptylinoxide, venlafaxine, desvenlafaxine, milnacipran, bupropion, reboxetine and tianeptine. We identified one randomized controlled trial (RCT) in 14 patients on haemodialysis for fluoxetine versus placebo which showed no difference for efficacy and safety measures. One other RCT of escitalopram versus placebo in 62 patients on haemodialysis provided no efficacy data. There were nine non-randomized trials, all suggesting benefit for the antidepressant under investigation. Side-effects were common, but mild in most patients. The limitations of this review include the scarcity of randomized trial data, the small size of the observational studies and possibility of publication bias. In addition, study selection and data extraction were done by one reviewer only, increasing the risk for errors made in handling of the data. Conclusions. Dose reduction in CKD3-5 is necessary for selegiline, amitriptylinoxide, venlafaxine, desvenlafaxine, milnacipran, bupropion, reboxetine and tianeptine. The evidence on effectiveness of antidepressants versus placebo in patients with CKD3-5, and with the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)-defined depression is insufficient, and in view of the high prevalence, a well-designed RCT is greatly needed.

Introduction The Model for End-Stage Liver Disease (MELD) has been found to accurately predict pre-transplant mortality and is a valuable system for ranking patients in need of liver transplantation. Its association with post-transplant outcome, however, remains unclear. Materials and methods We retrospectively studied 121 adult patients who were transplanted for non-fulminant liver failure between January 1991 and December 2001. MELD scores were calculated taking variables as close as possible prior to liver transplantation. Patients were stratified into two or three groups using different cut-off values of the MELD score. Results Indications for liver transplantation were mainly alcoholic liver disease (47.1%) or hepatitis C virus (19.0%). Gender distribution was male 62% vs female 38%. Mean age was 54 years 10 years. Mean MELD score was 16 +/- 6. Follow-up time was 5.4 years (range, 1.6-12.3 years). The use of different MELD cut-off levels yielded no difference in survival at different time points. Conclusion Higher MELD scores did not have a negative impact on patient and graft survival following OLT. Since MELD is good at identifying those urgently in need of liver transplantation and high MELD scores do not appear to have an influence on long-term outcome, use of MELD in liver allocation seems warranted.