Antihypertensive treatment for kidney transplant recipients.

BACKGROUND: The comparative effects of specific blood pressure (BP) lowering treatments on patient-important outcomes following kidney transplantation are uncertain. Our 2009 Cochrane review found that calcium channel blockers (CCBs) improved graft function and prevented graft loss, while the evidence for other BP-lowering treatments was limited. This is an update of the 2009 Cochrane review. OBJECTIVES: To compare the benefits and harms of different classes and combinations of antihypertensive drugs in kidney transplant recipients. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 3 July 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating any BP-lowering agent in recipients of a functioning kidney transplant for at least two weeks were eligible. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risks of bias and extracted data. Treatment estimates were summarised using the random-effects model and expressed as relative risk (RR) or mean difference (MD) with 95% confidence intervals (CI). Evidence certainty was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) processes. The primary outcomes included all-cause death, graft loss, and kidney function. MAIN RESULTS: Ninety-seven studies (8706 participants) were included. One study evaluated treatment in children. The overall risk of bias was unclear to high across all domains. Compared to placebo or standard care alone, CCBs probably reduce all-cause death (23 studies, 3327 participants: RR 0.83, 95% CI 0.72 to 0.95; I2 = 0%; moderate certainty evidence) and graft loss (24 studies, 3577 participants: RR 0.84, 95% CI 0.75 to 0.95; I2 = 0%; moderate certainty evidence). CCBs may make little or no difference to estimated glomerular filtration rate (eGFR) (11 studies, 2250 participants: MD 1.89 mL/min/1.73 m2, 95% CI -0.70 to 4.48; I2 = 48%; low certainty evidence) and acute rejection (13 studies, 906 participants: RR 10.8, 95% CI 0.85 to 1.35; I2 = 0%; moderate certainty evidence). CCBs may reduce systolic BP (SBP) (3 studies, 329 participants: MD -5.83 mm Hg, 95% CI -10.24 to -1.42; I2 = 13%; low certainty evidence) and diastolic BP (DBP) (3 studies, 329 participants: MD -3.98 mm Hg, 95% CI -5.98 to -1.99; I2 = 0%; low certainty evidence). CCBs have uncertain effects on proteinuria. Compared to placebo or standard care alone, angiotensin-converting-enzyme inhibitors (ACEi) may make little or no difference to all-cause death (7 studies, 702 participants: RR 1.13, 95% CI 0.58 to 2.21; I2 = 0%; low certainty evidence), graft loss (6 studies, 718 participants: RR 0.75, 95% CI 0.49 to 1.13; I2 = 0%; low certainty evidence), eGFR (4 studies, 509 participants: MD -2.46 mL/min/1.73 m2, 95% CI -7.66 to 2.73; I2 = 64%; low certainty evidence) and acute rejection (4 studies, 388 participants: RR 1.75, 95% CI 0.76 to 4.04; I2 = 0%; low certainty evidence). ACEi may reduce proteinuria (5 studies, 441 participants: MD -0.33 g/24 hours, 95% CI -0.64 to -0.01; I2 = 67%; low certainty evidence) but had uncertain effects on SBP and DBP. Compared to placebo or standard care alone, angiotensin receptor blockers (ARB) may make little or no difference to all-cause death (6 studies, 1041 participants: RR 0.69, 95% CI 0.36 to 1.31; I2 = 0%; low certainty evidence), eGRF (5 studies, 300 participants: MD -1.91 mL/min/1.73 m2, 95% CI -6.20 to 2.38; I2 = 57%; low certainty evidence), and acute rejection (4 studies, 323 participants: RR 1.00, 95% CI 0.44 to 2.29; I2 = 0%; low certainty evidence). ARBs may reduce graft loss (6 studies, 892 participants: RR 0.35, 95% CI 0.15 to 0.84; I2 = 0%; low certainty evidence), SBP (10 studies, 1239 participants: MD -3.73 mm Hg, 95% CI -7.02 to -0.44; I2 = 63%; moderate certainty evidence) and DBP (9 studies, 1086 participants: MD -2.75 mm Hg, 95% CI -4.32 to -1.18; I2 = 47%; moderate certainty evidence), but has uncertain effects on proteinuria. The effects of CCBs, ACEi or ARB compared to placebo or standard care alone on cardiovascular outcomes (including fatal or nonfatal myocardial infarction, fatal or nonfatal stroke) or other adverse events were uncertain. The comparative effects of ACEi plus ARB dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone were rarely evaluated. Head-to-head comparisons of ACEi, ARB or thiazide versus CCB, ACEi versus ARB, CCB or ACEi versus alpha- or beta-blockers, or ACEi plus CCB dual therapy versus ACEi or CCB monotherapy were scarce. No studies reported outcome data for cancer or life participation. AUTHORS' CONCLUSIONS: For kidney transplant recipients, the use of CCB therapy to reduce BP probably reduces death and graft loss compared to placebo or standard care alone, while ARB may reduce graft loss. The effects of ACEi and ARB compared to placebo or standard care on other patient-centred outcomes were uncertain. The effects of dual therapy, alpha-blockers, and mineralocorticoid receptor antagonists compared to placebo or standard care alone and the comparative effects of different treatments were uncertain.

Assessing clinician competence in the delivery of cognitive-behavioural therapy for eating disorders: development of the Cognitive-Behavioural Therapy Scale for Eating Disorders (CBTS-ED).

Evidence-based cognitive-behaviour therapy for eating disorders (CBT-ED) differs from other forms of CBT for psychological disorders, making existing generic CBT measures of therapist competence inadequate for evaluating CBT-ED. This study developed and piloted the reliability of a novel measure of therapist competence in this domain-the Cognitive Behaviour Therapy Scale for Eating Disorders (CBTS-ED). Initially, a team of CBT-ED experts developed a 26-item measure, with general (i.e. present in every session) and specific (context- or case-dependent) items. To determine statistical properties of the measure, nine CBT-ED experts and eight non-experts independently observed six role-played mock CBT-ED therapy sessions, rating the therapists' performance using the CBTS-ED. The inter-item consistency (Cronbach's alpha and McDonald's omega) and inter-rater reliability (ICC) were assessed, as appropriate to the clustering of the items. The CBTS-ED demonstrated good internal consistency and moderate/good inter-rater reliability for the general items, at least comparable to existing generic CBT scales in other domains. An updated version is proposed, where five of the 16 "specific" items are reallocated to the general group. These preliminary results suggest that the CBTS-ED can be used effectively across both expert and non-expert raters, though less experienced raters might benefit from additional training in its use.

Functions of disordered eating behaviors: a qualitative analysis of the lived experience and clinician perspectives.

BACKGROUND: One method to improve treatment outcomes for individuals with eating disorders (EDs) may be understanding and targeting individuals' motives for engaging in DE behaviors-or the functions of DE behaviors. The goal of this study was to investigate and categorize the various functions of DE behaviors from the perspectives of adults who engage in DE behaviors and clinicians who treat EDs. METHODS: Individuals who engage in DE behaviors (n = 16) and clinicians who treat EDs (n = 14) were interviewed, and a thematic analysis was conducted to determine key functions of DE behaviors. RESULTS: Four main functions of DE behaviors were identified by the authors: (1) alleviating shape, weight, and eating concerns; (2) regulating emotions; (3) regulating one's self-concept; and (4) regulating interpersonal relationships/communicating with others. CONCLUSIONS: Differences in participant responses, particularly regarding the relevance of alleviating shape and weight concerns as an DE behavior function, highlight the importance of individualized conceptualizations of DE behavior functions for any given client.

There are many reasons why individuals engage in disordered eating (DE) behaviors, and gathering information on these functions of one's DE behaviors might help clinicians decide which treatments to administer to individual clients. This study identified and organized numerous functions of DE behaviors based on perspectives of both adults who engage in DE behaviors and clinicians who treat EDs. These functions can be largely grouped into four categories: (1) reducing concerns about one's shape, weight, and/or eating habits; (2) managing one's emotions; (3) managing one's beliefs about themselves as a person; and (4) managing relationships with others or communicating with others. Using treatments that address these reasons for one's DE behaviors may be beneficial for clients.

Le trouble de l'accès hyperphagique: Aperçu actualisé à l'intention des professionnels des soins primaires.

OBJECTIF: Fournir aux professionnels des soins primaires un aperçu actualisé du trouble de l'accès hyperphagique (TAH), qui comporte des recommandations pertinentes. QUALITÉ DES DONNÉES: Une recension a été effectuée dans PubMed, PsycInfo et Google Scholar, sans restrictions temporelles, à l'aide des expressions clés en anglais binge eating disorder, treatment, review, guidelines, psychotherapy, primary care et pharmacotherapy. Le niveau des données probantes pour toutes les recommandations varie de I à III. MESSAGE PRINCIPAL: Le trouble de l'accès hyperphagique est associé à une grande détresse et à une incapacité considérable chez le patient, ainsi qu'à des comorbidités médicales et psychiatriques; il a été ajouté dans la 5e édition du Manuel diagnostique et statistique des troubles mentaux, en 2013. Les médecins de soins primaires sont bien placés pour le dépistage, le diagnostic et l'amorce du traitement du TAH. Une approche par étapes du traitement commence par un développement personnel guidé, suivi par l'ajout ou le changement de la pharmacothérapie, ou par une psychothérapie individuelle, au besoin. Les psychothérapies dont l'efficacité est le plus corroborée par la recherche sont la thérapie cognitivo-comportementale, la thérapie interpersonnelle et la thérapie comportementale dialectique. CONCLUSION: Cet aperçu présente des conseils sur le dépistage, le diagnostic et les approches thérapeutiques fondés sur les données probantes actuellement disponibles, de même les avis d'un groupe diversifié d'experts, pour aider à orienter les cliniciens lorsque les données probantes sont limitées.

How Different Are Threshold and Other Specified Feeding and Eating Disorders? Comparing Severity and Treatment Outcome.

Background: Other Specified Feeding and Eating Disorders (OSFED) are characterized by less frequent symptoms or symptoms that do not meet full criteria for another eating disorder. Despite its high prevalence, limited research has examined differences in severity and treatment outcome among patients with OSFED compared to threshold EDs [Anorexia Nervosa (AN), Bulimia Nervosa (BN), and Binge Eating Disorder (BED)]. The purpose of the current study was to examine differences in clinical presentation and treatment outcome between a heterogenous group of patients with OSFED or threshold EDs. Method: Patients with threshold EDs (AN = 42, BN = 50, BED = 14) or OSFED (n = 66) presenting for eating disorder treatment completed self-report questionnaires at intake and discharge to assess eating disorder symptoms, depression symptoms, impairment, and self-esteem. Results: At intake, OSFED patients showed lower eating concerns compared to patients with BN, but similar levels compared to AN and BED. The OSFED group showed higher restraint symptoms compared to BED, and similar restraint to AN and BN. Global symptoms as well as shape and weight concerns were similar between OSFED and threshold ED groups. There were no differences between diagnostic groups in self-esteem, depression scores, or symptom change from intake to discharge. Discussion: Our findings suggest that individuals with OSFED showed largely similar ED psychopathology and similar decreases in symptoms across treatment as individuals diagnosed with threshold EDs. Taken together, findings challenge the idea that OSFED is less severe and more resistant to treatment than threshold EDs.

Epidemiology of cardiovascular death in kidney failure: An Australian and New Zealand cohort study using data linkage.

AIM: Cardiovascular mortality risk evolves over the lifespan of kidney failure (KF), as patients develop comorbid disease and transition between treatment modalities. Absolute cardiovascular death rates would help inform clinical practice and health-care provision, but are not well understood across a continuum of dialysis and transplant states. We aimed to characterize cardiovascular death across the natural history of KF using a lifespan approach. METHODS: We performed a population-based cohort study of incident patients commencing kidney replacement therapy in Australia and New Zealand. Cardiovascular deaths were identified using data linkage to national death registers. We estimated the probability of death and kidney transplant using multi-state models, and calculated rates of graft failure and cardiovascular death across demographic factors and comorbidities. RESULTS: Among 60 823 incident patients followed over 381 874 person-years, 25% (8492) of deaths were from cardiovascular disease. At 15 years from treatment initiation, patients had a 15.2% probability of cardiovascular death without being transplanted, but only 2.3% probability of cardiovascular death post-transplant. Females had a 3% lower probability of cardiovascular death at 15 years (15.3% vs. 18.6%) but 4% higher probability of non-cardiovascular death (54.5% vs. 50.8%). Within the first year of dialysis, cardiovascular mortality peaked in the second month and showed little improvement across treatment era. CONCLUSION: Despite improvements over time, cardiovascular death remains common in KF, particularly among the dialysis population and in the first few months of treatment. Multi-state models can provide absolute measures of cardiovascular mortality across both dialysis and transplant states.

Sex differences in mortality among binational cohort of people with chronic kidney disease: population based data linkage study.

OBJECTIVE: To evaluate sex differences in mortality among people with kidney failure compared with the general population. DESIGN: Population based cohort study using data linkage. SETTING: The Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), which includes all patients receiving kidney replacement therapy in Australia (1980-2019) and New Zealand (1988-2019). Data were linked to national death registers to determine deaths and their causes, with additional details obtained from ANZDATA. PARTICIPANTS: Of 82 844 people with kidney failure, 33 329 were female (40%) and 49 555 were male (60%); 49 376 deaths (20 099 in female patients; 29 277 in male patients) were recorded over a total of 536 602 person years of follow-up. MAIN OUTCOME MEASURES: Relative measures of survival, including standardised mortality ratios, relative survival, and years of life lost, using general population data to account for background mortality (adjusting for country, age, sex, and year). Estimates were stratified by dialysis modality (haemodialysis or peritoneal dialysis) and for the subpopulation of kidney transplant recipients. RESULTS: Few differences in outcomes were found between male and female patients with kidney failure. However, compared with the general population, female patients with kidney failure had greater excess all cause deaths than male patients (female patients: standardised mortality ratio 11.3, 95% confidence interval 11.2 to 11.5, expected deaths 1781, observed deaths 20 099; male patients: 6.9, 6.8 to 6.9, expected deaths 4272, observed deaths 29 277). The greatest difference was observed among younger patients and those who died from cardiovascular disease. Relative survival was also consistently lower in female patients, with adjusted excess mortality 11% higher (95% confidence interval 8% to 13%). Average years of life lost was 3.6 years (95% confidence interval 3.6 to 3.7) greater in female patients with kidney failure compared with male patients across all ages. No major differences were found in mortality by sex for haemodialysis or peritoneal dialysis. Kidney transplantation reduced but did not entirely remove the sex difference in excess mortality, with similar relative survival (P=0.83) and years of life lost difference reduced to 2.3 years (95% confidence interval 2.2 to 2.3) between female and male patients. CONCLUSIONS: Compared with the general population, female patients had greater excess deaths, worse relative survival, and more years of life lost than male patients, however kidney transplantation reduced these differences. Future research should investigate whether systematic differences exist in access to care and possible strategies to mitigate excess mortality among female patients.

Frailty score before admission as risk factor for mortality of renal patients during the first wave of the COVID pandemic in London.

Background: Frailty is a known predictor of mortality and poor outcomes during hospital admission. In this large renal retrospective cohort study, we investigated whether frailer COVID-19 positive renal patients had worse outcomes. Design: All SARS-Cov-2 positive renal patients aged ≥18 years who presented to the emergency department at the Royal Free Hospital or at the satellite dialysis centres from 10th of March until the 10th of May 2020, with recent data on frailty, were included. The follow up was until 26th of May 2020. Age, gender, ethnicity, body mass index, chronic kidney disease stage, modality of renal replacement therapy, co-morbidities, Rockwood clinical frailty score (CFS), C reactive protein and the neutrophil-to-lymphocyte count were collected at presentation. The primary outcome was the overall mortality rate following COVID-19 diagnosis. Secondary outcomes included the need for hospital admission. Results: A total of 200 renal patients were SARS-Cov-2 positive. In the 174 patients who had a CFS recorded, the age was 65.4 years ± 15.8 (mean ± SD) and 57,5% were male. At the end of follow up, 26% had died. Frail patients (CFS 5-7) were more than three times more likely to die compared to less frail patients (CFS of 1-4) (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.0-10.6). 118 patients (68%) required admission, but there was no difference in hospital admission rates for frail vs non-frail patients (OR 0.6, CI 0.3-1.7). Conclusions: Frailty is a better predictor of mortality than age and co-morbidities in COVID-19 positive renal patients.

Interventions for atypical haemolytic uraemic syndrome.

BACKGROUND: Atypical haemolytic uraemic syndrome (aHUS) is a rare disorder characterised by thrombocytopenia, microangiopathic haemolytic anaemia, and acute kidney injury. The condition is primarily caused by inherited or acquired dysregulation of complement regulatory proteins with ~40% of those affected aged < 18 years. Historically, kidney failure and death were common outcomes, however, improved understanding of the condition has led to discovery of novel therapies. OBJECTIVES: To evaluate the benefits and harms of interventions for aHUS. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies for randomised controlled studies (RCTs) up to 3 September 2020 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. MEDLINE(OVID) 1946 to 27 July 2020 and EMBASE (OVID) 1974 to 27 July 2020 were searched for non-RCTs. SELECTION CRITERIA: All randomised and non-randomised clinical trials comparing an intervention with placebo, an intervention with supportive therapy, or two or more interventions for aHUS were included. Given the rare nature of the condition in question, prospective single-arm studies of any intervention for aHUS were also included. DATA COLLECTION AND ANALYSIS: Two authors independently extracted pre-specified data from eligible studies and evaluated risk of bias using a newly developed tool based on existing Cochrane criteria. As statistical meta-analysis was not appropriate, qualitative analysis of data was then performed. MAIN RESULTS: We included five single-arm studies, all of which evaluated terminal complement inhibition for the treatment of aHUS. Four studies evaluated the short-acting C5 inhibitor eculizumab and one study evaluated the longer-acting C5 inhibitor ravulizumab. All included studies within the review were of non-randomised, single-arm design. Thus, risk of bias is high, and it is challenging to draw firm conclusions from this low-quality evidence. One hundred patients were included within three primary studies evaluating eculizumab, with further data reported from 37 patients in a secondary study. Fifty-eight patients were included in the ravulizumab study. After 26 weeks of eculizumab therapy there were no deaths and a 70% reduction in the number of patients requiring dialysis. Complete thrombotic microangiopathic (TMA) response was observed in 60% of patients at 26 weeks and 65% at two years. After 26 weeks of ravulizumab therapy four patients had died (7%) and complete TMA response was observed in 54% of patients. Substantial improvements were seen in estimated glomerular filtration rate and health-related quality of life in both eculizumab and ravulizumab studies. Serious adverse events occurred in 42% of patients, and meningococcal infection occurred in two patients, both treated with eculizumab. AUTHORS' CONCLUSIONS: When compared with historical data, terminal complement inhibition appears to offer favourable outcomes in patients with aHUS, based upon very low-quality evidence drawn from five single-arm studies. It is unlikely that an RCT will be conducted in aHUS and therefore careful consideration of future single-arm data as well as longer term follow-up data will be required to better understand treatment duration, adverse outcomes and risk of disease recurrence associated with terminal complement inhibition.

Cardiac Mortality in Kidney Transplant Patients: A Population-based Cohort Study 1988-2013 in Australia and New Zealand.

BACKGROUND: Transplant recipients experience excess cardiac mortality. We compared circulatory death rates in Australian and New Zealand kidney transplant recipients to the general population and identified risk factors for circulatory death in kidney transplant recipients. METHODS: The primary cause of death for kidney transplant recipients aged ≥18 was established through ICD-10-AM codes using data linkage between the Australia and New Zealand dialysis and transplant registry and national death registers. We estimated standardized mortality ratios (SMRs) and developed a Fine-Gray competing risks model to determine risk factors for cardiac mortality. RESULTS: Of 5089 deaths in 16 329 kidney transplant recipients (158 325 person-years), 918 (18%) were cardiac. An increased risk of circulatory death was associated with older age (P < 0.001), male sex (P < 0.001), longer dialysis duration (P = 0.004), earlier era of transplantation (P < 0.001), ever graft failure (P < 0.001), known coronary artery disease (P = 0.002), and kidney failure from diabetes or hypertension (P < 0.001). The cardiac SMR was 5.4 [95% confidence interval (CI): 5.0-5.8], falling from 8.0 (95% CI: 4.9-13.1) in 1988 to 5.3 (95% CI: 4.0-7.0) in 2013 (P < 0.001). Females, particularly young ones, had significantly higher relative cardiac mortality than men. In recipients aged 40 years, the cardiac SMR was 26.5 (95% CI: 15.0-46.6) in females and 7.5 (95% CI: 5.0-11.1) for males. CONCLUSIONS: Cardiac risks remain elevated in kidney transplant recipients and may be under-recognized, and prevention and treatment interventions less accessed, less effective or even harmful in female recipients.

Incidence of Ischaemic Heart Disease in Men and Women With End-Stage Kidney Disease: A Cohort Study.

BACKGROUND: The incidence of ischaemic heart disease (IHD) has fallen consistently in the general population; attributed to effective primary prevention strategies. Differences in incidence have been demonstrated by sex. Whether this fall in incidence and sex differences is mirrored in people with end-stage kidney disease (ESKD) is unclear. We aimed to establish the relative risk of IHD events in the ESKD population. METHODS: We performed a retrospective cohort study from 2000 to 2010 in people with ESKD in New South Wales. We performed data linkage of the Australia and New Zealand Dialysis and Transplant Registry and state wide hospital admission and death registry data and compared this to general population data. The primary outcome was the incidence rate, incidence rate ratio (IRR), and time-trend for any IHD event. We calculated these using indirect standardisation by IHD event. RESULTS: 10,766 participants, contributed 44,149 years of observation time. Incidence rates were substantially higher than the general population for all IHD events (any IHD event: IRR 1.8, 95% confidence interval [CI] 1.7-1.9 for men, IRR 3.4, 95% CI 3.1-3.6 for women). Excess risk was higher in younger people (age 30-49 IRR 4.8, 95% CI 4.2-5.4), and in women with a three-fold increase risk overall and nearly a 10-fold increase in risk in young women (female age 30-49 years: IRR 9.8 95% CI 7.7-12.3), results were similar for angina and acute myocardial infarction. Ischaemic heart disease rates showed some decline for men over time, (ratio of IRR 0.93, 95% CI 0.90-0.95) but were stable for women (ratio of IRR 0.97, 95% CI 0.94-1.01). CONCLUSIONS: People with ESKD have substantially higher rates of IHD than the general population, especially women, in whom no improvement appears evident over the past 10 years.

Excess Stroke Deaths in Kidney Transplant Recipients: A Retrospective Population-based Cohort Study Using Data Linkage.

BACKGROUND: Kidney transplant recipients are thought to experience a high risk of stroke; however, little data exist. We aimed to compare the stroke deaths in kidney transplant recipients with the general population and identify risk factors for stroke death in kidney transplant recipients. METHODS: Cause of death was established using data linkage between the Australian and New Zealand Dialysis and Transplant Registry and national death registers: Australia, 1980-2013, and New Zealand, 1988-2012. We estimated standardized mortality ratios (SMR) and used competing risks models to identify risk factors. Subanalysis explored those with polycystic kidney disease. RESULTS: Among 17 628 kidney transplant recipients, there were 158 stroke deaths and 5126 nonstroke deaths in 175 084 person-years. Those aged 30-49 years experienced more stroke deaths than expected, especially women (SMR in females: 19.7 [95% confidence interval, 12.9-30.3] and males: 9.1 [95% confidence interval, 5.6-14.6]). Higher risk of stroke death was associated with older age at transplant, ever graft failure, earlier era of transplant, preexisting cerebrovascular disease, and no previous malignancy. Polycystic kidney disease did not result in different SMR. CONCLUSIONS: Kidney transplant recipients had excess stroke deaths, particularly at younger ages and women. Preexisting cerebrovascular disease was a potentially modifiable risk factor for stroke death, suggesting further studies of secondary stroke prevention for kidney transplant recipients.

Absolute risk and risk factors for stroke mortality in patients with end-stage kidney disease (ESKD): population-based cohort study using data linkage.

INTRODUCTION: People with end-stage kidney disease (ESKD) have up to 30-fold higher risk of stroke than the general population. OBJECTIVE: To determine risk factors associated with stroke death in the ESKD population. METHODS: We identified all patients with incident ESKD in Australia (1980-2013) and New Zealand (1988-2012) from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) registry. We ascertained underlying cause of death from data linkage with national death registries and risk factors from ANZDATA. Using a competing risks multivariable regression model, we estimated cumulative incidence of stroke and non-stroke deaths, and risk factors for stroke deaths (adjusted sub-HR, SHR). RESULTS: We included 60 823 people with ESKD. There were 941 stroke deaths and 33 377 non-stroke deaths during 381 874 person-years of follow-up. Overall, the cumulative incidence of stroke death was 0.9% and non-stroke death was 36.8% 5 years after starting ESKD treatment. The risk of stroke death was higher at older ages (SHR 1.92, 95% CI 1.45 to 2.55), in females (SHR 1.41, 95% CI 1.21 to 1.64), in people with cerebrovascular disease (SHR 2.39, 95% CI 1.99 to 2.87), with ESKD caused by hypertensive/renovascular disease (SHR 1.39, 95% CI 1.09 to 1.78) or polycystic kidney disease (SHR 1.38, 95% CI 1.00 to 1.90), with earlier year of ESKD treatment initiation (SHR 1.93, 95% CI 1.56 to 2.39) and receiving dialysis (transplant vs haemodialysis SHR 0.27, 95% CI 0.09 to 0.84). CONCLUSION: Patients with ESKD with higher risk of stroke death are older, women, with cerebrovascular disease, with hypertensive/renovascular or polycystic kidney disease cause of ESKD, with earlier year of ESKD treatment and receiving dialysis. These groups may benefit from targeted stroke prevention interventions.

Death From Stroke in End-Stage Kidney Disease.

Background and Purpose- People with end-stage kidney disease (ESKD) are at greater risk of stroke. We aimed to compare stroke mortality between the ESKD population and the general population. Methods- We included all patients with incident ESKD in Australia, 1980 to 2013, and New Zealand, 1988 to 2012. The primary cause of death was ascertained using data linkage with national death registers. We produced standardized mortality ratios for stroke deaths, by age, sex, and calendar year. Results- We included 60 823 patients with ESKD, where 941 stroke deaths occurred during 381 874 person-years. Patients with ESKD had >3× the stroke deaths compared with the general population (standardized mortality ratio, 3.4; 95% CI, 3.2-3.6), markedly higher in younger people and women. The greatest excess was in intracerebral hemorrhages (standardized mortality ratio, 5.2; 95% CI, 4.5-5.9). Excess stroke deaths in patients with ESKD decreased over time, although were still double in 2013 (2013 standardized mortality ratio, 2.1; 95% CI, 1.5-2.9). Conclusions- People with ESKD experience much greater stroke mortality with the greatest difference for women and younger people. However, mortality has improved over time.

Immunosuppressive treatment for proliferative lupus nephritis.

BACKGROUND: Cyclophosphamide, in combination with corticosteroids, has been first-line treatment for inducing disease remission for proliferative lupus nephritis, reducing death at five years from over 50% in the 1950s and 1960s to less than 10% in recent years. Several treatment strategies designed to improve remission rates and minimise toxicity have become available. Treatments, including mycophenolate mofetil (MMF) and calcineurin inhibitors, alone and in combination, may have equivalent or improved rates of remission, lower toxicity (less alopecia and ovarian failure) and uncertain effects on death, end-stage kidney disease (ESKD) and infection. This is an update of a Cochrane review first published in 2004 and updated in 2012. OBJECTIVES: Our objective was to assess the evidence and evaluate the benefits and harms of different immunosuppressive treatments in people with biopsy-proven lupus nephritis. The following questions relating to management of proliferative lupus nephritis were addressed: 1) Are new immunosuppressive agents superior to or as effective as cyclophosphamide plus corticosteroids? 2) Which agents, dosages, routes of administration and duration of therapy should be used? 3) Which toxicities occur with the different treatment regimens? SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register up to 2 March 2018 with support from the Cochrane Information Specialist using search terms relevant to this review. Studies in the Specialised 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: Randomised controlled trials (RCTs) and quasi-RCTs comparing any immunosuppressive treatment for biopsy-proven class III, IV, V+III and V+VI lupus nephritis in adult or paediatric patients were included. DATA COLLECTION AND ANALYSIS: Data were abstracted and the risks of bias were assessed independently by two authors. Dichotomous outcomes were calculated as risk ratio (RR) and measures on continuous scales calculated as mean differences (MD) with 95% confidence intervals (CI). The primary outcomes were death (all causes) and complete disease remission for induction therapy and disease relapse for maintenance therapy. Evidence certainty was determined using GRADE. MAIN RESULTS: In this review update, 26 new studies were identified, to include 74 studies involving 5175 participants overall. Twenty-nine studies included children under the age of 18 years with lupus nephritis, however only two studies exclusively examined the treatment of lupus nephritis in patients less than 18 years of age.Induction therapy Sixty-seven studies (4791 participants; median 12 months duration (range 2.5 to 48 months)) reported induction therapy. The effects of all treatment strategies on death (all causes) and ESKD were uncertain (very low certainty evidence) as this outcome occurred very infrequently. Compared with intravenous (IV) cyclophosphamide, MMF may have increased complete disease remission (RR 1.17, 95% CI 0.97 to 1.42; low certainty evidence), although the range of effects includes the possibility of little or no difference.Compared to IV cyclophosphamide, MMF is probably associated with decreased alopecia (RR 0.29, 95% CI 0.19 to 0.46; 170 less (129 less to 194 less) per 1000 people) (moderate certainty evidence), increased diarrhoea (RR 2.42, 95% CI 1.64 to 3.58; 142 more (64 more to 257 more) per 1000 people) (moderate certainty evidence) and may have made little or no difference to major infection (RR 1.02, 95% CI 0.67 to 1.54; 2 less (38 less to 62 more) per 1000 people) (low certainty evidence). It is uncertain if MMF decreased ovarian failure compared to IV cyclophosphamide because the certainty of the evidence was very low (RR 0.36, 95% CI 0.06 to 2.18; 26 less (39 less to 49 more) per 1000 people). Studies were not generally designed to measure ESKD.MMF combined with tacrolimus may have increased complete disease remission (RR 2.38, 95% CI 1.07 to 5.30; 336 more (17 to 1048 more) per 1000 people (low certainty evidence) compared with IV cyclophosphamide, however the effects on alopecia, diarrhoea, ovarian failure, and major infection remain uncertain. Compared to standard of care, the effects of biologics on most outcomes were uncertain because of low to very low certainty of evidence.Maintenance therapyNine studies (767 participants; median 30 months duration (range 6 to 63 months)) reported maintenance therapy. In maintenance therapy, disease relapse is probably increased with azathioprine compared with MMF (RR 1.75, 95% CI 1.20 to 2.55; 114 more (30 to 236 more) per 1000 people (moderate certainty evidence). Multiple other interventions were compared as maintenance therapy, but patient-outcome data were sparse leading to imprecise estimates. AUTHORS' CONCLUSIONS: In this review update, studies assessing treatment for proliferative lupus nephritis were not designed to assess death (all causes) or ESKD. MMF may lead to increased complete disease remission compared with IV cyclophosphamide, with an acceptable adverse event profile, although evidence certainty was low and included the possibility of no difference. Calcineurin combined with lower dose MMF may improve induction of disease remission compared with IV cyclophosphamide, but the comparative safety profile of these therapies is uncertain. Azathioprine may increase disease relapse as maintenance therapy compared with MMF.

Developing Consensus-Based Priority Outcome Domains for Trials in Kidney Transplantation: A Multinational Delphi Survey With Patients, Caregivers, and Health Professionals.

BACKGROUND: Inconsistencies in outcome reporting and frequent omission of patient-centered outcomes can diminish the value of trials in treatment decision making. We identified critically important outcome domains in kidney transplantation based on the shared priorities of patients/caregivers and health professionals. METHODS: In a 3-round Delphi survey, patients/caregivers and health professionals rated the importance of outcome domains for trials in kidney transplantation on a 9-point Likert scale and provided comments. During rounds 2 and 3, participants rerated the outcomes after reviewing their own score, the distribution of the respondents' scores, and comments. We calculated the median, mean, and proportion rating 7 to 9 (critically important), and analyzed comments thematically. RESULTS: One thousand eighteen participants (461 [45%] patients/caregivers and 557 [55%] health professionals) from 79 countries completed round 1, and 779 (77%) completed round 3. The top 8 outcomes that met the consensus criteria in round 3 (mean, ≥7.5; median, ≥8; proportion, >85%) in both groups were graft loss, graft function, chronic rejection, acute rejection, mortality, infection, cancer (excluding skin), and cardiovascular disease. Compared with health professionals, patients/caregivers gave higher priority to 6 outcomes (mean difference of 0.5 or more): skin cancer, surgical complications, cognition, blood pressure, depression, and ability to work. We identified 5 themes: capacity to control and inevitability, personal relevance, debilitating repercussions, gaining awareness of risks, and addressing knowledge gaps. CONCLUSIONS: Graft complications and severe comorbidities were critically important for both stakeholder groups. These stakeholder-prioritized outcomes will inform the core outcome set to improve the consistency and relevance of trials in kidney transplantation.

Chronic Kidney Disease.

The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m2, or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests (urinary dipstick or blood tests), or when symptoms become severe. The best available indicator of overall kidney function is GFR, which is measured either via exogenous markers (eg, DTPA, iohexol), or estimated using equations. Presence of proteinuria is associated with increased risk of progression of CKD and death. Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemia due to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease. This increased risk of death rises exponentially as kidney function worsens and is largely attributable to death from cardiovascular disease, although cancer incidence and mortality are also increased. Health-related quality of life is substantially lower for people with CKD than for the general population, and falls as GFR declines. Interventions targeting specific symptoms, or aimed at supporting educational or lifestyle considerations, make a positive difference to people living with CKD. Inequity in access to services for this disease disproportionally affects disadvantaged populations, and health service provision to incentivise early intervention over provision of care only for advanced CKD is still evolving in many countries.