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Background. Cardiac and vascular mortality are common in end-stage renal disease (ERSD) and are often attributed to accelerated atherosclerosis. [ABSTRACT FROM PUBLISHER]

This article present a letter to the editor regarding chronic kidney disease and the reporting of glomerular filtration rates (eGFR).

Background: Impaired quality of life is common in patients with end-stage kidney disease. We report the baseline quality of life measures in participants from the PIVOTAL randomized controlled trial and the potential relationship with the primary outcome (all-cause mortality, myocardial infarction, stroke, and heart failure hospitalisation), and associations with key baseline characteristics., Methods: This was a post hoc analysis of 2141 patients enrolled in the PIVOTAL trial. Quality of life was measured using EQ5D index, Visual Analogue Scale, and the KD-QoL [Physical Component Score and Mental Component Score]., Results: Mean baseline EQ5D index and visual analogue scale scores were 0.68 and 60.7 and 33.7 (Physical Component Score) and 46.0 (Mental Component Score), respectively. Female sex, higher Body Mass Index, diabetes mellitus, history of myocardial infarction, stroke or heart failure were associated with significantly worse EQ5D index and visual analogue scale. Higher C-reactive protein levels and lower transferrin saturation were associated with worse quality of life. Haemoglobin was not an independent predictor of quality of life. A lower transferrin saturation was an independent predictor of worse physical component score. A higher C-reactive protein level was associated with most aspects of worse quality of life. Impaired functional status was associated with mortality., Conclusion: Quality of life was impaired in patients starting haemodialysis. A higher C-reactive protein level level was a consistent independent predictor of the majority of worse quality of life. Transferrin saturation ≤ 20% was associated with worse physical component score of quality of life. Baseline quality of life was predictive of all-cause mortality and the primary outcome measure., Eudract Registration Number: 2013-002267-25., (© 2023. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Aims: To investigate the effect of high-dose iron vs. low-dose intravenous (IV) iron on myocardial infarction (MI) in patients on maintenance haemodialysis., Methods and Results: This was a pre-specified analysis of secondary endpoints of the Proactive IV Iron Therapy in Hemodialysis Patients trial (PIVOTAL) randomized, controlled clinical trial. Adults who had started haemodialysis within the previous year, who had a ferritin concentration <400 μg per litre and a transferrin saturation <30% were randomized to high-dose or low-dose IV iron. The main outcome measure for this analysis was fatal or non-fatal MI. Over a median of 2.1 years of follow-up, 8.4% experienced a MI. Rates of type 1 MIs (3.2/100 patient-years) were 2.5 times higher than type 2 MIs (1.3/100 patient-years). Non-ST-elevation MIs (3.3/100 patient-years) were 6 times more common than ST-elevation MIs (0.5/100 patient-years). Mortality was high after non-fatal MI (1- and 2-year mortality of 40% and 60%, respectively). In time-to-first event analyses, proactive high-dose IV iron reduced the composite endpoint of non-fatal and fatal MI [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.52-0.93, P = 0.01] and non-fatal MI (HR 0.69, 95% CI 0.51-0.93; P = 0.01) when compared with reactive low-dose IV iron. There was less effect of high-dose IV iron on recurrent MI events than on the time-to-first event analysis., Conclusion: In total, 8.4% of patients on maintenance haemodialysis had an MI over 2 years. High-dose compared to low-dose IV iron reduced MI in patients receiving haemodialysis., Eudract Registration Number: 2013-002267-25., Competing Interests: Conflict of interest: M.C.P. reported receiving lecture fees from AstraZeneca, Novartis, and Eli Lilly, grant support, advisory board fees, and fees for serving on an endpoint committee from Boehringer Ingelheim, advisory board fees, lecture fees, and fees for serving on an endpoint committee from Novo Nordisk, advisory board fees from Napp Pharmaceuticals, and fees for serving on an endpoint committee from Takeda Pharmaceutical and Bayer. P.S.J. receiving consulting fees, advisory board fees, and lecture fees from Novartis, advisory board fees from Cytokinetics, and grant support from Boehringer Ingelheim. S.D.A. reported receiving fees for serving on a steering committee for Vifor, Bayer, Boehringer Ingelheim, Novartis, Servier, and grant support from Abbott Vascular. S.B. reported receiving lecture fees from Vifor Pharma and Pharmacosmos. P.A.K. reported receiving grants, personal fees and non-financial support from Vifor Fresenius, personal fees and non-financial support from Pharmacosmos. D.C.W. reported receiving personal fees from AstraZeneca, Akebia, Boehringer Ingelheim, Jannsen, Napp, Vifor Fresenius, and Amgen. C.R.V.T. has nothing to disclose. I.F. reported receiving grant support from Kidney Research UK, Vifor Pharma, and Pharmacosmos. J.J.V.Mc.M. reports receiving fees (all fees listed paid to Glasgow University) for serving on a steering committee from Bayer, fees for serving on a steering committee, fees for serving on an endpoint committee, and travel support from Cardiorentis, fees for serving on a steering committee and travel support from Amgen, fees for serving on a steering committee and travel support from Oxford University–Bayer, fees for serving as principal investigator of a trial and travel support from Theracos, fees for serving on a steering committee and travel support from AbbVie, fees for serving on a steering committee from DalCor Pharmaceuticals, fees for serving on a data and safety monitoring committee from Pfizer, fees for serving on a data and safety monitoring committee from Merck, fees for serving on an executive committee, fees for serving as co-principal investigator of a trial, fees for serving on a steering committee, fees for serving on an executive committee, travel support, and advisory board fees from Novartis, fees for serving as co-principal investigator for a trial, fees for serving on a steering committee, and travel support from GlaxoSmithKline, fees for serving on a steering committee from Bristol-Myers Squibb, and fees for serving on a steering committee, fees for serving on an endpoint adjudication committee, and travel support from Vifor Pharma–Fresenius. I.C.M. reported receiving grants from Kidney Research UK, Akebia, Bayer, and Astellas, personal fees from AMAG, FibroGen, Pharmacosmos and Vifor Pharma and grants and personal fees from GlaxoSmithKline., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: People with kidney failure treated with hemodialysis (HD) are at increased risk of stroke compared with similarly aged people with normal kidney function. One concern is that treatment of renal anemia might increase stroke risk. We studied risk factors for stroke in a prespecified secondary analysis of a randomized, controlled trial of intravenous iron treatment strategies in HD., Methods: We analyzed data from the Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial, focusing on variables associated with risk of stroke. The trial randomized 2141 adults who had started HD <12 months earlier and who were receiving an erythropoiesis-stimulating agent (ESA) to high-dose IV iron administered proactively or low-dose IV iron administered reactively in a 1:1 ratio. Possible stroke events were independently adjudicated. We performed analyses to identify variables associated with stroke during follow-up and assessed survival following stroke., Results: During a median 2.1 years of follow-up, 69 (3.2%) patients experienced a first postrandomization stroke. Fifty-seven (82.6%) were ischemic strokes, and 12 (17.4%) were hemorrhagic strokes. There were 34 postrandomization strokes in the proactive arm and 35 postrandomization strokes in the reactive arm (hazard ratio, 0.90; 95% confidence interval, 0.56 to 1.44; P =0.66). In multivariable models, women, diabetes, history of prior stroke at baseline, higher baseline systolic BP, lower serum albumin, and higher C-reactive protein were independently associated with stroke events during follow-up. Hemoglobin, total iron, and ESA dose were not associated with risk of stroke. Fifty-eight percent of patients with a stroke event died during follow-up compared with 23% without a stroke., Conclusions: In patients on HD, stroke risk is broadly associated with risk factors previously described to increase cardiovascular risk in this population. Proactive intravenous iron does not increase stroke risk. Clinical Trial registry name and registration number: Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL), 2013-002267-25., Competing Interests: S.D. Anker reports grants and personal fees from Abbott Vascular, grants and personal fees from Vifor Int, personal fees from Bayer, personal fees from Boehringer Ingelheim, personal fees from Impulse Dynamics, personal fees from Novartis, personal fees from Servier, and personal fees from SJM outside the submitted work. P.S. Jhund reports advisory board fees and grants from Boehringer Ingelheim, speakers and advisory board fees from AstraZeneca, and speakers and advisory board fees from Novartis. P.A. Kalra reports grants from BergenBio, grants and personal fees from Astellas, grants and personal fees from Vifor, personal fees from AstraZeneca, personal fees from Bayer, personal fees from Boehringer Ingelheim, personal fees from MundiPharma, personal fees from Napp, personal fees from Novonordisk, and personal fees from Pharmacosmos outside the submitted work. P.B. Mark reports grants from Boehringer Ingelheim; personal fees from Astellas, AstraZeneca, Janssen, and Novartis; and personal fees and nonfinancial support from Napp, Pharmacosmos, and Vifor outside the submitted work. I.C. Macdougall reports personal fees from GlaxoSmithKline and Vifor Pharma. The employer of J.J.V. McMurray, the University of Glasgow, has been remunerated by Abbvie, Amgen, AstraZeneca, Bayer, Bristol Myers and Squibb, Cardiorentis, DalCor, GlaxoSmithKline, Kidney Research UK, Merck, Novartis, Oxford University/Bayer, Pfizer, Theracos, and Vifor-Fresenius. M.C. Petrie reported receiving lecture fees from AstraZeneca and Eli Lilly during the conduct of the study and personal fees from AstraZeneca, NAPP Pharmaceuticals, Novo Nordisk, and Takeda. A. Power reports personal fees from Bayer GmBH and personal fees from Vifor Fresenius Renal Pharma outside the submitted work. D.C. Wheeler has an ongoing consultancy contract with AstraZeneca and has received honoraria from Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Janssen, Merck Sharp and Dohme, Mundipharma, Napp, Tricida, and Vifor Fresenius. C.G. Winearls is an employee of Pfizer. All remaining authors have nothing to disclose., (Copyright © 2021 by the American Society of Nephrology.)

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 clinical practice guideline for the management of blood pressure (BP) in patients with chronic kidney disease (CKD) not receiving dialysis is an update of the KDIGO 2012 guideline on the same topic and reflects new evidence on the risks and benefits of BP-lowering therapy among patients with CKD. It is intended to support shared decision making by health care professionals working with patients with CKD worldwide. This article is a synopsis of the full guideline., Methods: The KDIGO leadership commissioned 2 co-chairs to convene an international Work Group of researchers and clinicians. After a Controversies Conference in September 2017, the Work Group defined the scope of the evidence review, which was undertaken by an evidence review team between October 2017 and April 2020. Evidence reviews were done according to the Cochrane Handbook. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to guide the development of the recommendations and rate the strength and quality of the evidence. Practice points were included to provide guidance when evidence was insufficient to make a graded recommendation. The guideline was revised after public consultation between January and March 2020., Recommendations: The updated guideline comprises 11 recommendations and 20 practice points. This synopsis summarizes key recommendations pertinent to the diagnosis and management of high BP in adults with CKD, excluding those receiving kidney replacement therapy. In particular, the synopsis focuses on recommendations for standardized BP measurement and a target systolic BP of less than 120 mm Hg, because these recommendations differ from some other guidelines.

Purpose of Review: To summarize and explain the new guideline on blood pressure (BP) management in chronic kidney disease (CKD) published by Kidney Disease: Improving Global Outcomes (KDIGO), an independent global nonprofit organization which develops and implements evidence-based clinical practice guidelines in kidney disease. KDIGO issued its first clinical practice guideline for the Management of Blood Pressure (BP) in Chronic Kidney Disease (CKD) for patients not receiving dialysis in 2012 and now updated the guideline in 2021., Recent Findings: Recommendations in this update were developed based on systematic literature reviews and appraisal of the quality of the evidence and strength of recommendation following the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. The updated guideline includes five chapters covering BP measurement techniques, lifestyle interventions for lowering BP, and management of BP in three target populations, namely adults (with and without diabetes), kidney transplant recipients, and children. A dedicated chapter on BP measurement emphasizing standardized preparation and measurement protocols for office BP measurement is a new addition, following protocols used in large randomized trials of BP targets with pivotal clinical outcomes. Based on the available evidence, and in particular in the CKD subgroup of the SPRINT trial, the 2021 guideline suggests a systolic BP target of <120 mm Hg, based on standardized measurements, for most individuals with CKD not receiving dialysis, with the exception of kidney transplant recipients and children. This recommendation is strictly contingent on the measurement of BP using standardized office readings and not routine office readings., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This study sought to examine the effect of intravenous iron on heart failure events in hemodialysis patients., Background: Heart failure is a common and deadly complication in patients receiving hemodialysis and is difficult to diagnose and treat., Methods: The study analyzed heart failure events in the PIVOTAL (Proactive IV Iron Therapy in Hemodialysis Patients) trial, which compared intravenous iron administered proactively in a high-dose regimen with a low-dose regimen administered reactively. Heart failure hospitalization was an adjudicated outcome, a component of the primary composite outcome, and a prespecified secondary endpoint in the trial., Results: Overall, 2,141 participants were followed for a median of 2.1 years. A first fatal or nonfatal heart failure event occurred in 51 (4.7%) of 1,093 patients in the high-dose iron group and in 70 (6.7%) of 1,048 patients in the low-dose group (HR: 0.66; 95% CI: 0.46-0.94; P = 0.023). There was a total of 63 heart failure events (including first and recurrent events) in the high-dose iron group and 98 in the low-dose group, giving a rate ratio of 0.59 (95% CI: 0.40-0.87; P = 0.0084). Most patients presented with pulmonary edema and were mainly treated by mechanical removal of fluid. History of heart failure and diabetes were independent predictors of a heart failure event., Conclusions: Compared with a lower-dose regimen, high-dose intravenous iron decreased the occurrence of first and recurrent heart failure events in patients undergoing hemodialysis, with large relative and absolute risk reductions. (UK Multicentre Open-label Randomised Controlled Trial Of IV Iron Therapy In Incident Haemodialysis Patients; 2013-002267-25)., Competing Interests: Funding Support and Author Disclosures This work was supported by Kidney Research UK, which was supported by an unrestricted grant from Vifor Fresenius Medical Care Renal Pharma. Drs. Petrie and McMurray are supported by British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217. The supporter/ funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Dr Jhund has received consulting fees from Novartis; advisory board fees from Novartis and Cytokinetics; lecture fees from Novartis; and grant support from Boehringer Ingelheim. Dr Petrie has received lecture fees from AstraZeneca, Novartis, Eli Lilly, and Novo Nordisk; grant support from Boehringer Ingelheim; advisory board fees from Boehringer Ingelheim, Novo Nordisk, and Napp Pharmaceuticals; and fees for serving on an endpoint committee from Boehringer Ingelheim, Novo Nordisk, Takeda Pharmaceutical, and Bayer. Dr Anker has received receiving fees for serving on steering committees for Vifor, Bayer, Boehringer Ingelheim, Novartis, and Servier; and grant support from Abbott Vascular. Dr Bhandari has received lecture fees from Vifor Pharma and Pharmacosmos. Dr Kalra has received grants from Vifor Fresenius; and personal fees and nonfinancial support from Vifor Fresenius and Pharmacosmos. Dr Wheeler has received personal fees from AstraZeneca, Akebia, Boehringer Ingelheim, Janssen, Napp, Vifor Fresenius, and Amgen. Dr Ford has received grant support from Kidney Research UK, Vifor Pharma and Pharmacosmos. Dr McMurray has received fees (all fees listed paid to Glasgow University) for serving on a steering committee from Bayer, Cardiorentis, Amgen, Oxford University–Bayer, AbbVie, DalCor Pharmaceuticals, Novartis, Bristol Myers Squibb, Vifor Pharma–Fresenius; fees for serving on an endpoint committee from Cardiorentis; travel support from Cardiorentis, Amgen, Oxford University–Bayer, Theracos, AbbVie, Novartis, GlaxoSmithKline, Vifor Pharma–Fresenius; fees for serving as principal investigator of a trial from Theracos; fees for serving on a data and safety monitoring committee from Pfizer and Merck; fees for serving on an executive committee from Novartis; fees for serving as co-principal investigator of a trial from Novartis and GlaxoSmithKline; advisory board fees from Novartis; and fees for serving on an endpoint adjudication committee from Vifor Pharma–Fresenius. Dr Macdougall has received grants from Kidney Research UK, Akebia, Bayer, and Astellas; personal fees from AMAG, FibroGen, Pharmacosmos, and Vifor Pharma; and grants and personal fees from GlaxoSmithKline. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease for patients not receiving dialysis represents an update to the KDIGO 2012 guideline on this topic. Development of this guideline update followed a rigorous process of evidence review and appraisal. Guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence. The strength of recommendations is based on the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. The scope includes topics covered in the original guideline, such as optimal blood pressure targets, lifestyle interventions, antihypertensive medications, and specific management in kidney transplant recipients and children. Some aspects of general and cardiovascular health, such as lipid and smoking management, are excluded. This guideline also introduces a chapter dedicated to proper blood pressure measurement since all large randomized trials targeting blood pressure with pivotal outcomes used standardized preparation and measurement protocols adhered to by patients and clinicians. Based on previous and new evidence, in particular the Systolic Blood Pressure Intervention Trial (SPRINT) results, we propose a systolic blood pressure target of less than 120 mm Hg using standardized office reading for most people with chronic kidney disease (CKD) not receiving dialysis, the exception being children and kidney transplant recipients. The goal of this guideline is to provide clinicians and patients a useful resource with actionable recommendations supplemented with practice points. The burden of the recommendations on patients and resources, public policy implications, and limitations of the evidence are taken into consideration. Lastly, knowledge gaps and recommendations for future research are provided., (Copyright © 2021 KDIGO. Published by Elsevier Inc. All rights reserved.)

There is ethnic inequity in access to living-donor kidney transplants in the UK. This study asked kidney patients from Black, Asian and minority ethnic groups why members of their family were not able to be living kidney donors. Responses were compared with responses from White individuals. This questionnaire-based mixed-methods study included adults transplanted between 1/4/13-31/3/17 at 14 UK hospitals. Participants were asked to indicate why relatives could not donate, selecting all options applicable from: Age; Health; Weight; Location; Financial/Cost; Job; Blood group; No-one to care for them after donation. A box entitled 'Other-please give details' was provided for free-text entries. Multivariable logistic regression was used to analyse the association between the likelihood of selecting each reason for non-donation and the participant's self-reported ethnicity. Qualitative responses were analysed using inductive thematic analysis. In total, 1240 questionnaires were returned (40% response). There was strong evidence that Black, Asian and minority ethnic group individuals were more likely than White people to indicate that family members lived too far away to donate (adjusted odds ratio (aOR) = 3.25, 95% Confidence Interval (CI) 2.30-4.58), were prevented from donating by financial concerns (aOR = 2.95, 95% CI 2.02-4.29), were unable to take time off work (aOR = 1.88, 95% CI 1.18-3.02), were "not the right blood group" (aOR = 1.65, 95% CI 1.35-2.01), or had no-one to care for them post-donation (aOR = 3.73, 95% CI 2.60-5.35). Four qualitative themes were identified from responses from Black, Asian and minority ethnic group participants: 'Burden of disease within the family'; 'Differing religious interpretations'; 'Geographical concerns'; and 'A culture of silence'. Patients perceive barriers to living kidney donation in the UK Black, Asian and minority ethnic population. If confirmed, these could be targeted by interventions to redress the observed ethnic inequity.

We examined quality of life (QoL) and other patient-reported outcome measures (PROMs) in 95 simultaneous pancreas and kidney transplant (SPKT) recipients and 41 patients wait-listed for SPKT recruited to the UK Access to Transplantation and Transplant Outcome Measures (ATTOM) programme. Wait-listed patients transplanted within 12 months of recruitment (n = 22) were followed 12 months post-transplant and compared with those still wait-listed (n = 19) to examine pre- to post-transplant changes. Qualitative interviews with ten SPKT recipients 12 months post-transplant were analysed thematically. Cross-sectional analyses showed several better 12-month outcomes for SPKT recipients compared with those still wait-listed, a trend to better health utilities but no difference in diabetes-specific QoL or diabetes treatment satisfaction. Pre- to post-transplant, SPKT recipients showed improved treatment satisfaction, well-being, self-reported health, generic QoL and less negative impact on renal-specific QoL (ps < 0.05). Health utility values were better overall in transplant recipients and neither these nor diabetes-specific QoL changed significantly in either group. Pre-emptive transplant advantages seen in 12-month cross-sectional analyses disappeared when controlling for baseline values. Qualitative findings indicated diabetes complications, self-imposed blood glucose monitoring and dietary restrictions continued to impact QoL negatively post-transplant. Unrealistic expectations of SPKT caused some disappointment. Measuring condition-specific PROMs over time will help in demonstrating the benefits and limitations of SPKT., (© 2020 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.)

Background and Objectives: The Effect of a Reduction in GFR after Nephrectomy on Arterial Stiffness and Central Hemodynamics (EARNEST) study was a multicenter, prospective, controlled study designed to investigate the associations of an isolated reduction in kidney function on BP and arterial hemodynamics., Design, Setting, Participants, & Measurements: Prospective living kidney donors and healthy controls who fulfilled criteria for donation were recruited from centers with expertise in vascular research. Participants underwent office and ambulatory BP measurement, assessment of arterial stiffness, and biochemical tests at baseline and 12 months., Results: A total of 469 participants were recruited, and 306 (168 donors and 138 controls) were followed up at 12 months. In the donor group, mean eGFR was 27 ml/min per 1.73 m 2 lower than baseline at 12 months. Compared with baseline, at 12 months the mean within-group difference in ambulatory day systolic BP in donors was 0.1 mm Hg (95% confidence interval, -1.7 to 1.9) and 0.6 mm Hg (95% confidence interval, -0.7 to 2.0) in controls. The between-group difference was -0.5 mm Hg (95% confidence interval, -2.8 to 1.7; P =0.62). The mean within-group difference in pulse wave velocity in donors was 0.3 m/s (95% confidence interval, 0.1 to 0.4) and 0.2 m/s (95% confidence interval, -0.0 to 0.4) in controls. The between-group difference was 0.1 m/s (95% confidence interval, -0.2 to 0.3; P =0.49)., Conclusions: Changes in ambulatory peripheral BP and pulse wave velocity in kidney donors at 12 months after nephrectomy were small and not different from controls., Clinical Trial Registry Name and Registration Number: NCT01769924 (https://clinicaltrials.gov/ct2/show/NCT01769924)., (Copyright © 2020 by the American Society of Nephrology.)

Background: Comorbidity is increasingly common in kidney transplant recipients, yet the implications for transplant outcomes are not fully understood. We analyzed the relationship between recipient comorbidity and survival outcomes in a UK-wide prospective cohort study-Access to Transplantation and Transplant Outcome Measures (ATTOM)., Methods: A total of 2100 adult kidney transplant recipients were recruited from all 23 UK transplant centers between 2011 and 2013. Data on 15 comorbidities were collected at the time of transplantation. Multivariable Cox regression models were used to analyze the relationship between comorbidity and 2-year graft survival, patient survival, and transplant survival (earliest of graft failure or patient death) for deceased-donor kidney transplant (DDKT) recipients (n = 1288) and living-donor kidney transplant (LDKT) recipients (n = 812)., Results: For DDKT recipients, peripheral vascular disease (hazard ratio [HR] 3.04, 95% confidence interval [CI]: 1.37-6.74; P = 0.006) and obesity (HR 2.27, 95% CI: 1.27-4.06; P = 0.006) were independent risk factors for graft loss, while heart failure (HR 3.77, 95% CI: 1.79-7.95; P = 0.0005), cerebrovascular disease (HR 3.45, 95% CI: 1.72-6.92; P = 0.0005), and chronic liver disease (HR 4.36, 95% CI: 1.29-14.71; P = 0.018) were associated with an increased risk of mortality. For LDKT recipients, heart failure (HR 3.83, 95% CI: 1.15-12.81; P = 0.029) and diabetes (HR 2.23, 95% CI: 1.03-4.81; P = 0.042) were associated with poorer transplant survival., Conclusions: The key comorbidities that predict poorer 2-year survival outcomes after kidney transplantation have been identified in this large prospective cohort study. The findings will facilitate assessment of individual patient risks and evidence-based decision making.

Background: Experimental and observational studies have raised concerns that giving intravenous (IV) iron to patients, such as individuals receiving maintenance hemodialysis, might increase the risk of infections. The Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial randomized 2141 patients undergoing maintenance hemodialysis for ESKD to a high-dose or a low-dose IV iron regimen, with a primary composite outcome of all-cause death, heart attack, stroke, or hospitalization for heart failure. Comparison of infection rates between the two groups was a prespecified secondary analysis., Methods: Secondary end points included any infection, hospitalization for infection, and death from infection; we calculated cumulative event rates for these end points. We also interrogated the interaction between iron dose and vascular access (fistula versus catheter)., Results: We found no significant difference between the high-dose IV iron group compared with the lose-dose group in event rates for all infections (46.5% versus 45.5%, respectively, which represented incidences of 63.3 versus 69.4 per 100 patient years, respectively); rates of hospitalization for infection (29.6% versus 29.3%, respectively) also did not differ. We did find a significant association between risk of a first cardiovascular event and any infection in the previous 30 days. Compared with patients undergoing dialysis with an arteriovenous fistula, those doing so via a catheter had a higher incidence of having any infection, hospitalization for infection, or fatal infection, but IV iron dosing had no effect on these outcomes., Conclusions: The high-dose and low-dose IV iron groups exhibited identical infection rates. Risk of a first cardiovascular event strongly associated with a recent infection., (Copyright © 2020 by the American Society of Nephrology.)

There is evidence of socioeconomic inequity in access to living-donor kidney transplantation, but limited evidence as to why. We investigated possible mediators of the inequity., Methods: This questionnaire-based case-control study included 14 UK hospitals. Participants were adults transplanted between April 1, 2013 and March 31, 2017. Living-donor kidney transplant (LDKT) recipients (cases) were compared with deceased-donor kidney transplant recipients (controls). We collected data on mediators identified in earlier qualitative work: perceived social support (Interpersonal Support Evaluation List shortened version-12), patient activation (Patient Activation Measure 13), and LDKT knowledge (Rotterdam Renal Replacement Knowledge Test). We performed mediation analyses to investigate what proportion of the effect of socioeconomic position (education and income) on case-control status was mediated by these variables., Results: One thousand two-hundred and forty questionnaires were returned (40% response). Receipt of an LDKT over a deceased-donor kidney transplant was associated with higher socioeconomic position [adjusted odds ratio (aOR) university degree versus no degree aOR = 1.48 (95% confidence interval [CI], 1.18-1.84), P = 0.001 and aOR per +£1000 increase in monthly household income after tax 1.14 (95% CI, 1.11-1.17), P < 0.001] higher perceived social support (aOR per +1-point Interpersonal Support Evaluation List shortened version-12 score = 1.05 (95% CI, 1.03-1.08), P < 0.001), higher levels of patient activation (aOR per +1 patient activation measure level = 1.35 (95% CI, 1.24-1.48), P < 0.001), and greater LDKT knowledge (aOR per + 1-point Rotterdam Renal Replacement Knowledge Test score = 1.59 (95% CI, 1.49-1.69), P < 0.001). Mediation analyses revealed that perceived social support, patient activation, and LDKT knowledge together mediate 48.5% (95% CI, 12.7-84.3, P = 0.008) of the association between university education and LDKT status, and 46.0% (95% CI, 28.7-63.4, P < 0.001) of the association between income and LDKT status., Conclusions: LDKT knowledge, perceived social support, and patient activation are associated with the socioeconomic position of people with kidney disease, and mediate approximately 50% of the association between the socioeconomic position and receipt of an LDKT. Interventions that target these factors may redress observed socioeconomic inequity., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

In September 2017, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference titled Blood Pressure in Chronic Kidney Disease (CKD). The purpose of the meeting was to consider which recommendations from the 2012 KDIGO Clinical Practice Guideline for the Management of Blood Pressure in CKD should be reevaluated based on new evidence from clinical trials. Participants included a multidisciplinary panel of clinical and scientific experts. Discussions focused on the optimal means for measuring blood pressure (BP) as well as managing BP in CKD patients. Consistent with the 2012 Guideline, the conference did not address BP management in patients on maintenance dialysis., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Intravenous iron is a standard treatment for patients undergoing hemodialysis, but comparative data regarding clinically effective regimens are limited., Methods: In a multicenter, open-label trial with blinded end-point evaluation, we randomly assigned adults undergoing maintenance hemodialysis to receive either high-dose iron sucrose, administered intravenously in a proactive fashion (400 mg monthly, unless the ferritin concentration was >700 μg per liter or the transferrin saturation was ≥40%), or low-dose iron sucrose, administered intravenously in a reactive fashion (0 to 400 mg monthly, with a ferritin concentration of <200 μg per liter or a transferrin saturation of <20% being a trigger for iron administration). The primary end point was the composite of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or death, assessed in a time-to-first-event analysis. These end points were also analyzed as recurrent events. Other secondary end points included death, infection rate, and dose of an erythropoiesis-stimulating agent. Noninferiority of the high-dose group to the low-dose group would be established if the upper boundary of the 95% confidence interval for the hazard ratio for the primary end point did not cross 1.25., Results: A total of 2141 patients underwent randomization (1093 patients to the high-dose group and 1048 to the low-dose group). The median follow-up was 2.1 years. Patients in the high-dose group received a median monthly iron dose of 264 mg (interquartile range [25th to 75th percentile], 200 to 336), as compared with 145 mg (interquartile range, 100 to 190) in the low-dose group. The median monthly dose of an erythropoiesis-stimulating agent was 29,757 IU in the high-dose group and 38,805 IU in the low-dose group (median difference, -7539 IU; 95% confidence interval [CI], -9485 to -5582). A total of 320 patients (29.3%) in the high-dose group had a primary end-point event, as compared with 338 (32.3%) in the low-dose group (hazard ratio, 0.85; 95% CI, 0.73 to 1.00; P<0.001 for noninferiority; P=0.04 for superiority). In an analysis that used a recurrent-events approach, there were 429 events in the high-dose group and 507 in the low-dose group (rate ratio, 0.77; 95% CI, 0.66 to 0.92). The infection rate was the same in the two groups., Conclusions: Among patients undergoing hemodialysis, a high-dose intravenous iron regimen administered proactively was superior to a low-dose regimen administered reactively and resulted in lower doses of erythropoiesis-stimulating agent being administered. (Funded by Kidney Research UK; PIVOTAL EudraCT number, 2013-002267-25 .).

Background: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown., Methods: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin < 400 µg/L and transferrin saturation (TSAT) levels < 30% receiving erythropoiesis-stimulating agents (ESA) were eligible. Enrolled patients were randomized to a proactive, high-dose IV iron arm (iron sucrose 400 mg/month unless ferritin > 700 µg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 µg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2-4 years., Results: Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry., Conclusions: PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice., Trial Registration: EudraCT number: 2013-002267-25., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

This multicenter prospective potential living kidney donor cohort study investigated which sociodemographic and other factors predict progression to living kidney donation or donor withdrawal as little is known on this topic. Therefore, we examined data on individuals undergoing living donor assessment at seven hospitals in the United Kingdom. Multivariable logistic regression was used to explore the relationships between donor and recipient characteristics and likelihood of kidney donation. A total of 805 individuals presented for directed donation to 498 intended recipients, of which 112 received a transplant from a living donor. Potential donors were less likely to donate if their intended recipient was female rather than male with an odds ratio of 0.60, a friend rather than relative 0.18, or had renal failure due to a systemic disease rather than another cause 0.41. The most socioeconomically deprived quintile was less likely to donate than the least 0.49, but the trend with deprivation was consistent with chance. Higher body mass index was associated with a lower likelihood of donation (odds ratio per each kg/m 2 increase, 0.92). Younger potential donors (odds ratio per each year increase 0.97), those of nonwhite ethnicity 2.98, and friend donors 2.43 were more likely to withdraw from work-up. This is the first study in the United Kingdom of potential living kidney donors to describe predictors of non-donation. Qualitative work with individuals who withdraw might identify possible ways of supporting those who wish to donate but experience difficulties doing so., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The self-management and decision-making skills required to manage CKD successfully may be diminished in those with low health literacy. A 2012 review identified five papers reporting the prevalence of limited health literacy in CKD, largely from United States dialysis populations. The literature has expanded considerably since., Design, Setting, Participants, & Measurements: We used systematic review, pooled prevalence analysis, metaregression, and exploration of heterogeneity in studies of patients with CKD (all stages)., Results: From 433 studies, 15 new studies met the inclusion criteria and were analyzed together with five studies from the 2012 review. These included 13 cross-sectional surveys, five cohort studies (using baseline data), and two using baseline clinical trial data. Most (19 of 20) were from the United States. In total, 12,324 patients were studied (3529 nondialysis CKD, 5289 dialysis, 2560 transplant, and 946 with unspecified CKD; median =198.5; IQR, 128.5-260 per study). Median prevalence of limited health literacy within studies was 23% (IQR, 16%-33%), and pooled prevalence was 25% (95% confidence interval, 20% to 30%) with significant between-study heterogeneity ( I 2 =97%). Pooled prevalence of limited health literacy was 25% (95% confidence interval, 16% to 33%; I 2 =97%) among patients with CKD not on dialysis, 27% (95% confidence interval, 19% to 35%; I 2 =96%) among patients on dialysis, and 14% (95% confidence interval, 7% to 21%; I 2 =97%) among patients with transplants. A higher proportion of nonwhite participants was associated with increased limited health literacy prevalence ( P =0.04), but participant age was not ( P =0.40). Within studies, nonwhite ethnicity and low socioeconomic status were consistently and independently associated with limited health literacy. Studies were of low or moderate quality. Within-study participant selection criteria had potential to introduce bias., Conclusions: Limited health literacy is common in CKD, especially among individuals with low socioeconomic status and nonwhite ethnicity. This has implications for the design of self-management and decision-making initiatives to promote equity of care and improve quality. Lower prevalence among patients with transplants may reflect selection of patients with higher health literacy for transplantation either because of less comorbidity in this group or as a direct effect of health literacy on access to transplantation., (Copyright © 2017 by the American Society of Nephrology.)

Background: Living donor kidney transplantation (LDKT) provides more timely access to transplantation and better clinical outcomes than deceased donor kidney transplantation (DDKT). This study investigated disparities in the utilization of LDKT in the UK., Methods: A total of 2055 adults undergoing kidney transplantation between November 2011 and March 2013 were prospectively recruited from all 23 UK transplant centres as part of the Access to Transplantation and Transplant Outcome Measures (ATTOM) study. Recipient variables independently associated with receipt of LDKT versus DDKT were identified., Results: Of the 2055 patients, 807 (39.3%) received LDKT and 1248 (60.7%) received DDKT. Multivariable modelling demonstrated a significant reduction in the likelihood of LDKT for older age {odds ratio [OR] 0.11 [95% confidence interval (CI) 0.08-0.17], P < 0.0001 for 65-75 years versus 18-34 years}; Asian ethnicity [OR 0.55 (95% CI 0.39-0.77), P = 0.0006 versus White]; Black ethnicity [OR 0.64 (95% CI 0.42-0.99), P = 0.047 versus White]; divorced, separated or widowed [OR 0.63 (95% CI 0.46-0.88), P = 0.030 versus married]; no qualifications [OR 0.55 (95% CI 0.42-0.74), P < 0.0001 versus higher education qualifications]; no car ownership [OR 0.51 (95% CI 0.37-0.72), P = 0.0001] and no home ownership [OR 0.65 (95% CI 0.85-0.79), P = 0.002]. The odds of LDKT varied significantly between countries in the UK., Conclusions: Among patients undergoing kidney transplantation in the UK, there are significant age, ethnic, socio-economic and geographic disparities in the utilization of LDKT. Further work is needed to explore the potential for targeted interventions to improve equity in living donor transplantation., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA.)