International consensus on post-transplantation diabetes mellitus.

Post-transplantation diabetes mellitus (PTDM) remains a leading complication after solid organ transplantation. Previous international PTDM consensus meetings in 2003 and 2013 provided standardized frameworks to reduce heterogeneity in diagnosis, risk stratification and management. However, the last decade has seen significant advancements in our PTDM knowledge complemented by rapidly changing treatment algorithms for management of diabetes in the general population. In view of these developments, and to ensure reduced variation in clinical practice, a 3rd international PTDM Consensus Meeting was planned and held from 6-8 May 2022 in Vienna, Austria involving global delegates with PTDM expertise to update the previous reports. This update includes opinion statements concerning optimal diagnostic tools, recognition of prediabetes (impaired fasting glucose and/or impaired glucose tolerance), new mechanistic insights, immunosuppression modification, evidence-based strategies to prevent PTDM, treatment hierarchy for incorporating novel glucose-lowering agents and suggestions for the future direction of PTDM research to address unmet needs. Due to the paucity of good quality evidence, consensus meeting participants agreed that making GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) recommendations would be flawed. Although kidney-allograft centric, we suggest that these opinion statements can be appraised by the transplantation community for implementation across different solid organ transplant cohorts. Acknowledging the paucity of published literature, this report reflects consensus expert opinion. Attaining evidence is desirable to ensure establishment of optimized care for any solid organ transplant recipient at risk of, or who develops, PTDM as we strive to improve long-term outcomes.

Sex differences in the survival benefit of kidney transplantation: a retrospective cohort study using target trial emulation.

BACKGROUND: Kidney transplantation is the preferred treatment for eligible patients with kidney failure who need renal replacement therapy. However, it remains unclear whether the anticipated survival benefit from kidney transplantation is different for women and men. METHODS: We included all dialysis patients recorded in the Austrian Dialysis and Transplant Registry who were waitlisted for their first kidney transplant between 2000 and 2018. In order to estimate the causal effect of kidney transplantation on 10-year restricted mean survival time, we mimicked a series of controlled clinical trials and applied inverse probability of treatment and censoring weighted sequential Cox models. RESULTS: This study included 4408 patients (33% female) with a mean age of 52 years. Glomerulonephritis was the most common primary renal disease both in women (27%) and men (28%). Kidney transplantation led to a gain of 2.22 years (95% CI 1.88 to 2.49) compared with dialysis over a 10-year follow-up. The effect was smaller in women (1.95 years, 95% CI 1.38 to 2.41) than in men (2.35 years, 95% CI 1.92 to 2.70) due to a better survival on dialysis. Across ages the survival benefit of transplantation over a follow-up of 10 years was smaller in younger women and men and increased with age, showing a peak for both women and men aged about 60 years. CONCLUSIONS: There were few differences in survival benefit by transplantation between females and males. Females had better survival than males on the waitlist receiving dialysis and similar survival to males after transplantation.

Effect of the phosphate binder sucroferric oxyhydroxide in dialysis patients on endogenous calciprotein particles, inflammation, and vascular cells.

BACKGROUND: Calciprotein particles (CPPs), colloidal mineral-protein nanoparticles, have emerged as potential mediators of phosphate toxicity in dialysis patients, with putative links to vascular calcification, endothelial dysfunction and inflammation. We hypothesized that phosphate binder therapy with sucroferric oxyhydroxide (SO) would reduce endogenous CPP levels and attenuate pro-calcific and pro-inflammatory effects of patient serum towards human vascular cells in vitro. METHODS: This secondary analysis of a randomised controlled crossover study compared the effect of 2-week phosphate binder washout with high-dose (2000 mg/day) and low-dose (250 mg/day) SO therapy in 28 haemodialysis patients on serum CPP levels, inflammatory cytokine/chemokine arrays and human aortic smooth muscle cell (HASMC) and coronary artery endothelial cell (HCAEC) bioassays. RESULTS: In our cohort (75% male, 62 ± 12 years) high-dose SO reduced primary (amorphous) and secondary (crystalline) CPP levels {-62% [95% confidence interval (CI) -76 to -44], P < .0001 and -38% [-62 to -0.14], P < .001, respectively} compared with washout. Nine of 14 plasma cytokines/chemokines significantly decreased with high-dose SO, with consistent reductions in interleukin-6 (IL-6) and IL-8. Exposure of HASMC and HCAEC cultures to serum of SO-treated patients reduced calcification and markers of activation (IL-6, IL-8 and vascular cell adhesion protein 1) compared with washout. Serum-induced HASMC calcification and HCAEC activation was ameliorated by removal of the CPP-containing fraction from patient sera. Effects of CPP removal were confirmed in an independent cohort of chronic kidney disease patients. CONCLUSIONS: High-dose SO reduced endogenous CPP formation in dialysis patients and yielded serum with attenuated pro-calcific and inflammatory effects in vitro.

Modeling pulse wave velocity trajectories-challenges, opportunities, and pitfalls.

In this commentary, we discuss the analysis of trajectories of pulse wave velocity in a longitudinal cohort study of children with chronic kidney disease (the Cardiovascular Comorbidity in Children with Chronic Kidney Disease - Transplantation study). We revisit the analysis made by the study authors and unravel some additional limitations. We also reevaluate the implicit assumptions that were made in the chosen analysis and suggest extensions of the basic linear mixed model to obtain more differentiated answers to research questions in nephrology.

European Renal Best Practice endorsement of guidelines for diagnosis and therapy of thrombotic thrombocytopaenic purpura published by the International Society on Thrombosis and Haemostasis.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease that is caused by severe ADAMTS-13 deficiency. Immune-mediated TTP develops due to autoantibodies against ADAMTS-13, whereas congenital TTP is caused by mutations in the ADAMTS13 gene. Diagnostic possibilities and treatment options in TTP have emerged in recent years, which prompted the International Society on Thrombosis and Haemostasis (ISTH) to publish clinical practice guidelines for the diagnosis and treatment of TTP in 2020. In this article, the European Renal Best Practice Working Group endorsed the ISTH guidelines and emphasizes a number of considerations, including the importance of rapid ADAMTS-13 activity testing, the use of rituximab and anti-von Willebrand factor therapies such as caplacizumab, that enhance the clinical applicability of the guidelines in Europe.

Predicting donor, recipient and graft survival in living donor kidney transplantation to inform pretransplant counselling: the donor and recipient linked iPREDICTLIVING tool - a retrospective study.

Although separate prediction models for donors and recipients were previously published, we identified a need to predict outcomes of donor/recipient simultaneously, as they are clearly not independent of each other. We used characteristics from transplantations performed at the Oslo University Hospital from 1854 live donors and from 837 recipients of a live donor kidney transplant to derive Cox models for predicting donor mortality up to 20 years, and recipient death, and graft loss up to 10 years. The models were developed using the multivariable fractional polynomials algorithm optimizing Akaike's information criterion, and optimism-corrected performance was assessed. Age, year of donation, smoking status, cholesterol and creatinine were selected to predict donor mortality (C-statistic of 0.81). Linear predictors for donor mortality served as summary of donor prognosis in recipient models. Age, sex, year of transplantation, dialysis vintage, primary renal disease, cerebrovascular disease, peripheral vascular disease and HLA mismatch were selected to predict recipient mortality (C-statistic of 0.77). Age, dialysis vintage, linear predictor of donor mortality, HLA mismatch, peripheral vascular disease and heart disease were selected to predict graft loss (C-statistic of 0.66). Our prediction models inform decision-making at the time of transplant counselling and are implemented as online calculators.

Markers of potassium homeostasis in salt losing tubulopathies- associations with hyperaldosteronism and hypomagnesemia.

BACKGROUND: Renal loss of potassium (K+) and magnesium (Mg2+) in salt losing tubulopathies (SLT) leads to significantly reduced Quality of Life (QoL) and higher risks of cardiac arrhythmia. The normalization of K+ is currently the most widely accepted treatment target, however in even excellently designed RCTs the increase of K+ was only mild and rarely normalized. These findings question the role of K+ as the ideal marker of potassium homeostasis in SLT. Aim of this hypothesis-generating study was to define surrogate endpoints for future treatment trials in SLT in terms of their usefulness to determine QoL and important clinical outcomes. METHODS: Within this prospective cross-sectional study including 11 patients with SLTs we assessed the biochemical, clinical and cardiological parameters and their relationship with QoL (RAND SF-36). The primary hypothesis was that QoL would be more dependent of higher aldosterone concentration, assessed by the transtubular-potassium-gradient (TTKG). Correlations were evaluated using Pearson's correlation coefficient. RESULTS: Included patients were mainly female (82%, mean age 34 ± 12 years). Serum K+ and Mg2+ was 3.3 ± 0.6 mmol/l and 0.7 ± 0.1 mmol/l (mean ± SD). TTKG was 9.5/3.4-20.2 (median/range). While dimensions of mental health mostly correlated with serum Mg2+ (r = 0.68, p = 0.04) and K+ (r = 0.55, p = 0.08), better physical health was associated with lower aldosterone levels (r = -0.61, p = 0.06). TTKG was neither associated with aldosterone levels nor with QoL parameters. No relevant abnormalities were observed in neither 24 h-ECG nor echocardiography. CONCLUSIONS: Hyperaldosteronism, K+ and Mg2+ were the most important parameters of QoL. TTKG was no suitable marker for hyperaldosteronism or QoL. Future confirmatory studies in SLT should assess QoL as well as aldosterone, K+ and Mg2+.

Dialysis vintage and outcomes in renal transplantation.

Pre-emptive kidney transplantation is the recommended strategy for patients with end-stage renal failure in all guidelines [Kidney Disease: Improving Global Outcomes (KDIGO), The Australian and New Zealand Dialysis and Transplantation Registry (ANZDATA), European Renal Best Practice Guideline (ERBP), British Transplant Society (BTS)]. This recommendation is intuitive and based on few older studies with considerable limitations. In addition, there is conflicting evidence as to whether the duration of dialysis vintage impacts on graft and patient survival after transplantation. The objective of this structured review was to critically review the published evidence on dialysis vintage and outcomes by including the most recent papers on that topic. We searched Medline using keywords for kidney transplantation, pre-emptive, dialysis vintage and relevant outcomes, and found 14 eligible cohort studies. The best evidence was found for pre-emptive transplantation, which was found to be associated with a lower risk of actual graft loss (including death as event) compared with non-pre-emptive transplantation. When only patients were considered that have been registered pre-emptively but then received or did not receive a pre-emptive transplant, the association with functional graft survival (excluding death as event) was only marginal. Dialysis vintage had a graded association with patient survival in most of the studies, but an unclear estimate with functional graft survival. Older studies also found an association of dialysis vintage with death-censored graft survival, but this association is likely confounded by selection and the competing risk of death and was no longer observed in recent eras, i.e. in transplants performed in the last decade. In summary, the recommendation for pre-emptive kidney transplantation for optimal patient and graft survival remains valid even in recent periods but the association of dialysis vintage after dialysis initiation with death-censored graft survival is less clear. The association of dialysis vintage with mortality after transplantation depends on the median duration of dialysis of the wait-listed population as well as acceptance rates for transplantation, and may thus be country specific. Nevertheless, it is reasonable to advocate pre-emptive kidney transplantation in all age groups. What remains unsolved is the selection issues since the reasons for longer waiting time on dialysis are difficult to capture in retrospective observational studies, and lead time as well as immortal time bias may have confounded the mortality data.

Interventions for chronic non-hypovolaemic hypotonic hyponatraemia.

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.

Steroid withdrawal after renal transplantation: a retrospective cohort study.

BACKGROUND: Immunosuppressive regimens in renal transplantation frequently contain corticosteroids, but many centers withdraw steroids as a consequence of unwanted side effects of steroids. The optimal timing to withdraw steroids after transplantation, however, remains unclear. The aim of this study was to determine an optimal time point following kidney transplantation that is associated with reduced mortality without jeopardizing the allograft to allow safe discontinuation of steroids. METHODS: We conducted a retrospective cohort study and computed a concatenated landmark-stratified Cox supermodel to estimate hazard ratios and 95% confidence intervals for mortality and graft loss using dynamic propensity score matching to adjust for confounding by indication. RESULTS: A total of 6070 first kidney transplant recipients in the Austrian Dialysis and Transplant Registry who were transplanted between 1990 and 2012 were evaluated and classified according to steroid treatment status throughout follow-up after kidney transplantation; 2142 patients were withdrawn from steroids during the study period. Overall, 1131 patients lost their graft and 821 patients in the study cohort died. Steroid withdrawal within 18 months after transplantation was associated with an increased rate of graft loss compared to steroid maintenance during that time (6 months after transplantation: HR = 1.8; 95% CI, 1.3 to 2.6; 18 months after transplantation: HR = 1.3; 95% CI, 1.1 to 1.6; 24 months after transplantation: HR = 1.2; 95% CI, 0.9 to 1.5), while mortality was not different between groups. CONCLUSIONS: Our findings suggest that steroid withdrawal after anti-IL-2 induction in the first 18 months after transplantation is associated with an increased risk of allograft loss.

Risk prediction models for graft failure in kidney transplantation: a systematic review.

Risk prediction models are useful for identifying kidney recipients at high risk of graft failure, thus optimizing clinical care. Our objective was to systematically review the models that have been recently developed and validated to predict graft failure in kidney transplantation recipients. We used PubMed and Scopus to search for English, German and French language articles published in 2005-15. We selected studies that developed and validated a new risk prediction model for graft failure after kidney transplantation, or validated an existing model with or without updating the model. Data on recipient characteristics and predictors, as well as modelling and validation methods were extracted. In total, 39 articles met the inclusion criteria. Of these, 34 developed and validated a new risk prediction model and 5 validated an existing one with or without updating the model. The most frequently predicted outcome was graft failure, defined as dialysis, re-transplantation or death with functioning graft. Most studies used the Cox model. There was substantial variability in predictors used. In total, 25 studies used predictors measured at transplantation only, and 14 studies used predictors also measured after transplantation. Discrimination performance was reported in 87% of studies, while calibration was reported in 56%. Performance indicators were estimated using both internal and external validation in 13 studies, and using external validation only in 6 studies. Several prediction models for kidney graft failure in adults have been published. Our study highlights the need to better account for competing risks when applicable in such studies, and to adequately account for post-transplant measures of predictors in studies aiming at improving monitoring of kidney transplant recipients.

Prognostic value of bone- and vascular-derived molecular biomarkers in hemodialysis and renal transplant patients: a systematic review and meta-analysis.

BACKGROUND: Patients undergoing hemodialysis and kidney graft recipients are high-risk populations for cardiovascular and all-cause mortality. Fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), RANK ligand, osteopontin (OPN), Klotho protein and bone morphogenetic protein-7 (BMP-7) are bone- and vascular-derived molecular biomarkers that have been shown to be associated with cardiovascular surrogate end points; however, currently available data on the prognostic value of these biomarkers is inconsistent. The aim of the present study was to conduct a systematic review and meta-analysis in order to summarize the available evidence on the association of molecular biomarkers with mortality in individuals undergoing hemodialysis and renal transplant patients. METHODS: Two databases (MEDLINE and Embase) were systematically searched. Studies were eligible if the association of biomarker and mortality was reported as time-to-event data [hazard Ratio (HR)] or as effect size with a fixed time of follow-up [odds Ratio (OR)]. Abstracted HRs were converted onto a standard scale of effect and combined using a random effects model. RESULTS: From a total of 1170 studies identified in initial searches, 21 met the inclusion criteria. In hemodialysis patients, comparing the lower third with the upper third of baseline FGF23 distribution, pooled HRs (95% confidence intervals) were 1.94 (1.47, 2.56) for all-cause mortality and 2.4 (1.64, 3.51) for cardiovascular mortality. For the same comparison of baseline OPG distribution, pooled HRs were 1.8 (0.95, 3.39) for all-cause mortality and 2.53 (1.29, 4.94) for cardiovascular mortality. Reported risk estimates of RANK ligand, OPN, Klotho protein and BMP-7 were not suitable for pooling; however, only Klotho protein was significantly related to mortality. For kidney graft recipients, four studies that investigated the relationship of FGF23 and OPG with mortality were identified, all of which reported a significant association. CONCLUSIONS: In hemodialysis patients, FGF23 is a predictor of all-cause and cardiovascular mortality, whereas the predictive value of OPG is restricted to cardiovascular mortality. Further studies are needed in order to gain insight into the prognostic value of these biomarkers in renal transplant recipients.

Why creating standardized core outcome sets for chronic kidney disease will improve clinical practice.

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/variable metrics; 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.

Does pre-emptive transplantation versus post start of dialysis transplantation with a kidney from a living donor improve outcomes after transplantation? A systematic literature review and position statement by the Descartes Working Group and ERBP.

This position statement brings up guidance on pre-emptive kidney transplantation from living donors. The provided guidance is based on a systematic review of the literature.

Steroid avoidance or withdrawal for kidney transplant recipients.

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.

A survey on the methodological processes and policies of renal guideline groups as a first step to harmonize renal guidelines.

BACKGROUND: 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. METHODS: 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). RESULTS: 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 <5 (N = 1) to 13-20 persons (N = 3). Three explicitly seek patient perspectives, for example, by involving patients in the scoping process, and four incorporate health economic considerations. All provide training in methodology for guideline development groups and six make their methods public. All try to avoid overlapping topics already planned or published by others. There is no common conflict of interest policy. CONCLUSIONS: Overall, there is considerable commonality in methods and approaches in renal guideline development by the different organizations, although some procedural differences remain. As the financial and human resource costs of guideline production are high, a collaborative approach is required to maximize impact and develop a sustainable work plan. Coming to consensus on methods and procedures is the first step and appears feasible.

Health economics and European Renal Best Practice--is it time to bring health economics into evidence-based guideline production in Europe?

Medical management of patients with kidney disease is complex and resource intensive. In times of limited health care budgets, economic evaluations have become more important over the past few years in identifying interventions with a beneficial cost-effectiveness to maximize the benefits served from the available resources. However, integrating evidence from health-economic evaluations into clinical practice guidelines remains a challenge. European Renal Best Practice (ERBP), the official guideline body of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) herewith presents some lines of thought that need consideration in the discussion on incorporating health-economic considerations into clinical guideline development.

European Renal Best Practice (ERBP) Guideline development methodology: towards the best possible 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.