Peritoneal dialysis versus haemodialysis for people commencing dialysis.

BACKGROUND: Peritoneal dialysis (PD) and haemodialysis (HD) are two possible modalities for people with kidney failure commencing dialysis. Only a few randomised controlled trials (RCTs) have evaluated PD versus HD. The benefits and harms of the two modalities remain uncertain. This review includes both RCTs and non-randomised studies of interventions (NRSIs). OBJECTIVES: To evaluate the benefits and harms of PD, compared to HD, in people with kidney failure initiating dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies from 2000 to June 2024 using search terms relevant to this review. Studies in the Register were identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. MEDLINE and EMBASE were searched for NRSIs from 2000 until 28 March 2023. SELECTION CRITERIA: RCTs and NRSIs evaluating PD compared to HD in people initiating dialysis were eligible. DATA COLLECTION AND ANALYSIS: Two investigators independently assessed if the studies were eligible and then extracted data. Risk of bias was assessed using standard Cochrane methods, and relevant outcomes were extracted for each report. The primary outcome was residual kidney function (RKF). Secondary outcomes included all-cause, cardiovascular and infection-related death, infection, cardiovascular disease, hospitalisation, technique survival, life participation and fatigue. MAIN RESULTS: A total of 153 reports of 84 studies (2 RCTs, 82 NRSIs) were included. Studies varied widely in design (small single-centre studies to international registry analyses) and in the included populations (broad inclusion criteria versus restricted to more specific participants). Additionally, treatment delivery (e.g. automated versus continuous ambulatory PD, HD with catheter versus arteriovenous fistula or graft, in-centre versus home HD) and duration of follow-up varied widely. The two included RCTs were deemed to be at high risk of bias in terms of blinding participants and personnel and blinding outcome assessment for outcomes pertaining to quality of life. However, most other criteria were assessed as low risk of bias for both studies. Although the risk of bias (Newcastle-Ottawa Scale) was generally low for most NRSIs, studies were at risk of selection bias and residual confounding due to the constraints of the observational study design. In children, there may be little or no difference between HD and PD on all-cause death (6 studies, 5752 participants: RR 0.81, 95% CI 0.62 to 1.07; I2 = 28%; low certainty) and cardiovascular death (3 studies, 7073 participants: RR 1.23, 95% CI 0.58 to 2.59; I2 = 29%; low certainty), and was unclear for infection-related death (4 studies, 7451 participants: RR 0.98, 95% CI 0.39 to 2.46; I2 = 56%; very low certainty). In adults, compared with HD, PD had an uncertain effect on RKF (mL/min/1.73 m2) at six months (2 studies, 146 participants: MD 0.90, 95% CI 0.23 to 3.60; I2 = 82%; very low certainty), 12 months (3 studies, 606 participants: MD 1.21, 95% CI -0.01 to 2.43; I2 = 81%; very low certainty) and 24 months (3 studies, 334 participants: MD 0.71, 95% CI -0.02 to 1.48; I2 = 72%; very low certainty). PD had uncertain effects on residual urine volume at 12 months (3 studies, 253 participants: MD 344.10 mL/day, 95% CI 168.70 to 519.49; I2 = 69%; very low certainty). PD may reduce the risk of RKF loss (3 studies, 2834 participants: RR 0.55, 95% CI 0.44 to 0.68; I2 = 17%; low certainty). Compared with HD, PD had uncertain effects on all-cause death (42 studies, 700,093 participants: RR 0.87, 95% CI 0.77 to 0.98; I2 = 99%; very low certainty). In an analysis restricted to RCTs, PD may reduce the risk of all-cause death (2 studies, 1120 participants: RR 0.53, 95% CI 0.32 to 0.86; I2 = 0%; moderate certainty). PD had uncertain effects on both cardiovascular (21 studies, 68,492 participants: RR 0.96, 95% CI 0.78 to 1.19; I2 = 92%) and infection-related death (17 studies, 116,333 participants: RR 0.90, 95% CI 0.57 to 1.42; I2 = 98%) (both very low certainty). Compared with HD, PD had uncertain effects on the number of patients experiencing bacteraemia/bloodstream infection (2 studies, 2582 participants: RR 0.34, 95% CI 0.10 to 1.18; I2 = 68%) and the number of patients experiencing infection episodes (3 studies, 277 participants: RR 1.23, 95% CI 0.93 to 1.62; I2 = 20%) (both very low certainty). PD may reduce the number of bacteraemia/bloodstream infection episodes (2 studies, 2637 participants: RR 0.44, 95% CI 0.27 to 0.71; I2 = 24%; low certainty). Compared with HD; It is uncertain whether PD reduces the risk of acute myocardial infarction (4 studies, 110,850 participants: RR 0.90, 95% CI 0.74 to 1.10; I2 = 55%), coronary artery disease (3 studies, 5826 participants: RR 0.95, 95% CI 0.46 to 1.97; I2 = 62%); ischaemic heart disease (2 studies, 58,374 participants: RR 0.86, 95% CI 0.57 to 1.28; I2 = 95%), congestive heart failure (3 studies, 49,511 participants: RR 1.10, 95% CI 0.54 to 2.21; I2 = 89%) and stroke (4 studies, 102,542 participants: RR 0.94, 95% CI 0.90 to 0.99; I2 = 0%) because of low to very low certainty evidence. Compared with HD, PD had uncertain effects on the number of patients experiencing hospitalisation (4 studies, 3282 participants: RR 0.90, 95% CI 0.62 to 1.30; I2 = 97%) and all-cause hospitalisation events (4 studies, 42,582 participants: RR 1.02, 95% CI 0.81 to 1.29; I2 = 91%) (very low certainty). None of the included studies reported specifically on life participation or fatigue. However, two studies evaluated employment. Compared with HD, PD had uncertain effects on employment at one year (2 studies, 593 participants: RR 0.83, 95% CI 0.20 to 3.43; I2 = 97%; very low certainty). AUTHORS' CONCLUSIONS: The comparative effectiveness of PD and HD on the preservation of RKF, all-cause and cause-specific death risk, the incidence of bacteraemia, other vascular complications (e.g. stroke, cardiovascular events) and patient-reported outcomes (e.g. life participation and fatigue) are uncertain, based on data obtained mostly from NRSIs, as only two RCTs were included.

Metformin for preventing the progression of chronic kidney disease.

BACKGROUND: Metformin has been used in the management of diabetes for decades. It is an effective, low-cost intervention with a well-established safety profile. Emerging evidence suggests that metformin targets a number of pathways that lead to chronic kidney damage, and long-term use may, therefore, slow the rate of kidney function decline and chronic kidney disease (CKD) progression. OBJECTIVES: To evaluate the effect of metformin therapy on kidney function decline in patients with CKD with or without diabetes mellitus and assess the safety and dose tolerability in this population. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 19 July 2023 with assistance from an 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 Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that reported kidney-related outcomes with a minimum duration of 12 months delivery of the metformin intervention and whose eligibility criteria included adult participants with either i) a diagnosis of CKD of any aetiology and/or ii) those with a diagnosis of diabetes mellitus. Comparisons included placebo, no intervention, non-pharmacological interventions, other antidiabetic medications or any other active control. Studies that included patients on any modality of kidney replacement therapy were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently carried out data extraction using a standard data extraction form. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: This review included 11 studies reporting on 8449 randomised participants. Studies were conducted in patient populations with Autosomal Dominant Polycystic Kidney Disease (ADPKD) (four studies) or diabetes mellitus (seven studies). Six studies compared metformin with no active control, four studies compared metformin with active controls (rosiglitazone, glyburide, pioglitazone, or glipizide), and one study included treatment arms that randomised to either metformin, diet and lifestyle modifications, or other antidiabetic therapies. The risk of bias in included studies varied; two studies were abstract-only publications and were judged to have a high risk of bias in most domains. Other included publications were judged to have a low risk of bias in most domains. Across comparisons, GRADE evaluations for most outcomes were judged as low or very low certainty, except for those relating to side effects, tolerance, and withdrawals, which were judged as moderate certainty. The evidence suggests that compared to placebo, metformin may result in i) a slightly smaller decline in kidney function (3 studies, 505 participants: MD 1.92 mL/min, 95% CI 0.33 to 3.51; I2 = 0%; low certainty), ii) very uncertain effects on the incidence of kidney failure (1 study, 753 participants: RR 1.20, 95% CI 0.17 to 8.49), iii) little or no effect on death (3 studies, 865 participants: RR 1.00, 95% CI 0.76 to 1.32; I2 = 0%; moderate certainty), iv) little or no effect on the incidence of serious adverse events (3 studies, 576 participants: RR 1.15, 95% CI 0.76 to 1.72; I2 = 0%; moderate certainty), and v) likely higher incidence of intolerance leading to study withdrawal than placebo (4 studies, 646 participants: RR 2.19, 95% CI 1.46 to 3.27; I2 = 0%; moderate certainty). The certainty of the evidence for proteinuria was very uncertain. Compared to other active controls (rosiglitazone, glyburide, pioglitazone, or glipizide), metformin i) demonstrated very uncertain effects on kidney function decline, ii) may result in little or no difference in death (3 studies, 5608 participants: RR 0.95 95% CI 0.63 to 1.43; I2 = 0%; low certainty), iii) probably results in little or no difference in intolerance leading to study withdrawal (3 studies, 5593 participants: RR 0.92, 95% CI, 0.79 to 1.08; I2 = 0%; moderate certainty), iv) probably results in little or no difference in the incidence of serious adverse events (2 studies, 5545 participants: RR 1.16, 95% CI 0.79 to 1.71; I2 = 0%; moderate certainty), and v) may increase the urinary albumin-creatinine ratio (2 studies, 3836 participants: MD 14.61, 95% CI 8.17 to 21.05; I2 = 0%; low certainty). No studies reported the incidence of kidney failure. AUTHORS' CONCLUSIONS: This review highlights the lack of RCTs reporting on the effects of metformin on kidney function, particularly in patients with CKD. Future research in this field requires adequately powered RCTs comparing metformin to placebo or standard care in those with CKD. Seven ongoing studies were identified in this review, and future updates, including their findings, may further inform the results of this review.

Nanopores map the acid-base properties of a single site in a single DNA molecule.

Nanopores are increasingly powerful tools for single molecule sensing, in particular, for sequencing DNA, RNA and peptides. This success has spurred efforts to sequence non-canonical nucleic acid bases and amino acids. While canonical DNA and RNA bases have pKas far from neutral, certain non-canonical bases, natural RNA modifications, and amino acids are known to have pKas near neutral pHs at which nanopore sequencing is typically performed. Previous reports have suggested that the nanopore signal may be sensitive to the protonation state of an individual moiety. We sequenced ion currents with the MspA nanopore using a single stranded DNA containing a single non-canonical DNA base (Z) at various pH conditions. The Z-base has a near-neutral pKa ∼ 7.8. We find that the measured ion current is remarkably sensitive to the protonation state of the Z-base. We demonstrate how nanopores can be used to localize and determine the pKa of individual moieties along a polymer. More broadly, these experiments provide a path to mapping different protonation sites along polymers and give insight in how to optimize sequencing of polymers that contain moieties with near-neutral pKas.

On the efficacy of facial masks to suppress the spreading of pathogen-carrying saliva particles during human respiratory events: Insights gained via high-fidelity numerical modeling.

Respiratory fluid dynamics is integral to comprehending the transmission of infectious diseases and the effectiveness of interventions such as face masks and social distancing. In this research, we present our recent studies that investigate respiratory particle transport via high-fidelity large eddy simulation coupled with the Lagrangian particle tracking method. Based on our numerical simulation results for human respiratory events with and without face masks, we demonstrate that facial masks could significantly suppress particle spreading. The studied respiratory events include coughing and normal breathing through mouth and nose. Using the Lagrangian particle tracking simulation results, we elucidated the transport pathways of saliva particles during inhalation and exhalation of breathing cycles, contributing to our understanding of respiratory physiology and potential disease transmission routes. Our findings underscore the importance of respiratory fluid dynamics research in informing public health strategies to reduce the spread of respiratory infections. Combining advanced mathematical modeling techniques with experimental data will help future research on airborne disease transmission dynamics and the effectiveness of preventive measures such as face masks.

Hypertension and Cardiovascular Risk Among Children with Chronic Kidney Disease.

PURPOSE OF REVIEW: Cardiovascular disease is the most common cause of mortality across the lifespan of children with chronic kidney disease (CKD). Hypertension is a common and important contributor, but other factors such as obesity, dyslipidemia and mineral bone disease play a role. This narrative review focusses on studies published in the past five years that have investigated hypertension and cardiovascular risk among children with CKD. RECENT FINDINGS: Cohort studies such as Chronic Kidney Disease in Children (CKiD) and Cardiovascular Comorbidity in Children with CKD (4C) have continued to develop our understanding of blood pressure (BP) phenotypes, and of progressive changes in the structure and function of the heart and blood vessels occurring in children with CKD. Metabolic risk factors, such as dyslipidemia, may represent an under-recognized component of care. Trial data are less common than observational evidence, but support lifestyle interventions currently used, mainly the low sodium dietary approaches to stop hypertension (DASH) diet. The findings of the recently reported Hypertension Optimal Treatment in Children with Chronic Kidney Disease trial (HOT-KID) are described in relation to the use of office BP treatment targets. Cardiovascular health is critical to the long-term outcomes of children with CKD. Recognizing and treating hypertension remains a critical component to improving outcomes, along with measures to improve concurrent cardiovascular risk factors. Some cardiovascular changes may not be reversible with transplantation and further research is needed for children at all stages of CKD.

Socioeconomic Position and Health Among Children and Adolescents With CKD Across the Life-Course.

Children and adolescents in families of lower socioeconomic position (SEP) experience an inequitable burden of reduced access to healthcare and poorer health. For children living with chronic kidney disease (CKD), disadvantaged SEP may exacerbate their considerable disease burden. Across the life-course, CKD may also compromise the SEP of families and young people, leading to accumulating health and socioeconomic disadvantage. This narrative review summarizes the current evidence on relationships of SEP with kidney care and health among children and adolescents with CKD from a life-course approach, including impacts of family SEP on kidney care and health, and bidirectional impacts of CKD on SEP. It highlights relevant conceptual models from social epidemiology, current evidence, clinical and policy implications, and provides directions for future research. Reflecting the balance of available evidence, we focus primarily on high-income countries (HICs), with an overview of key issues in low- and middle-income countries (LMICs). Overall, a growing body of evidence indicates sobering socioeconomic inequities in health and kidney care among children and adolescents with CKD, and adverse socioeconomic impacts of CKD. Dedicated efforts to tackle inequities are critical to ensuring that all young people with CKD have the opportunity to live long and flourishing lives. To prevent accumulating disadvantage, the global nephrology community must advocate for local government action on upstream social determinants of health; and adopt a life-course approach to kidney care that proactively identifies and addresses unmet social needs, targets intervening factors between SEP and health, and minimizes adverse socioeconomic outcomes across financial, educational and vocational domains.

Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients.

BACKGROUND: The risk of cytomegalovirus (CMV) infection in solid organ transplant recipients has resulted in the frequent use of prophylaxis to prevent the clinical syndrome associated with CMV infection. This is an update of a review first published in 2005 and updated in 2008 and 2013. OBJECTIVES: To determine the benefits and harms of antiviral medications to prevent CMV disease and all-cause death in solid organ transplant recipients. SEARCH METHODS: We contacted the information specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 5 February 2024 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 Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing antiviral medications with placebo or no treatment, comparing different antiviral medications or different regimens of the same antiviral medications for CMV prophylaxis in recipients of any solid organ transplant. Studies examining pre-emptive therapy for CMV infection are studied in a separate review and were excluded from this review. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study eligibility, risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: This 2024 update found four new studies, bringing the total number of included studies to 41 (5054 participants). The risk of bias was high or unclear across most studies, with a low risk of bias for sequence generation (12), allocation concealment (12), blinding (11) and selective outcome reporting (9) in fewer studies. There is high-certainty evidence that prophylaxis with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment is more effective in preventing CMV disease (19 studies: RR 0.42, 95% CI 0.34 to 0.52), all-cause death (17 studies: RR 0.63, 95% CI 0.43 to 0.92), and CMV infection (17 studies: RR 0.61, 95% CI 0.48 to 0.77). There is moderate-certainty evidence that prophylaxis probably reduces death from CMV disease (7 studies: RR 0.26, 95% CI 0.08 to 0.78). Prophylaxis reduces the risk of herpes simplex and herpes zoster disease, bacterial and protozoal infections but probably makes little to no difference to fungal infection, acute rejection or graft loss. No apparent differences in adverse events with aciclovir, ganciclovir or valaciclovir compared with placebo or no treatment were found. There is high certainty evidence that ganciclovir, when compared with aciclovir, is more effective in preventing CMV disease (7 studies: RR 0.37, 95% CI 0.23 to 0.60). There may be little to no difference in any outcome between valganciclovir and IV ganciclovir compared with oral ganciclovir (low certainty evidence). The efficacy and adverse effects of valganciclovir or ganciclovir were probably no different to valaciclovir in three studies (moderate certainty evidence). There is moderate certainty evidence that extended duration prophylaxis probably reduces the risk of CMV disease compared with three months of therapy (2 studies: RR 0.20, 95% CI 0.12 to 0.35), with probably little to no difference in rates of adverse events. Low certainty evidence suggests that 450 mg/day valganciclovir compared with 900 mg/day valganciclovir results in little to no difference in all-cause death, CMV infection, acute rejection, and graft loss (no information on adverse events). Maribavir may increase CMV infection compared with ganciclovir (1 study: RR 1.34, 95% CI: 1.10 to 1.65; moderate certainty evidence); however, little to no difference between the two treatments were found for CMV disease, all-cause death, acute rejection, and adverse events at six months (low certainty evidence). AUTHORS' CONCLUSIONS: Prophylaxis with antiviral medications reduces CMV disease and CMV-associated death, compared with placebo or no treatment, in solid organ transplant recipients. These data support the continued routine use of antiviral prophylaxis in CMV-positive recipients and CMV-negative recipients of CMV-positive organ transplants.

Improving Diverse and Equitable Involvement of Patients and Caregivers in Research in CKD: Report of a Better Evidence and Translation - Chronic Kidney Disease (BEAT-CKD) Workshop.

Patient and caregiver involvement can enhance the uptake and impact of research, however, the involvement of patients and caregivers who are underserved and marginalized is often limited. A better understanding of how to make involvement in research more broadly accessible, supportive, and inclusive for patients with CKD and caregivers is needed. We conducted a national workshop involving patients, caregivers, clinicians and researchers across Australia to identify strategies to increase the diversity of patients and caregivers involved in CKD research. Six themes were identified. Building trust and a sense of safety was considered pivotal to establishing meaningful relationships to support knowledge exchange. Establishing community and connectedness was expected to generate a sense of belonging to motivate involvement. Balancing stakeholder goals, expectations and responsibilities involved demonstrating commitment and transparency by researchers. Providing adequate resources andsupport included strategies to minimize the burden of involvement for patients and caregivers. Making research accessible and relatable was about nurturing patient and caregiver interest by appealing to intrinsic motivators. Adapting to patient and caregiver needs and preferences required tailoring the approach for individuals and the target community. Strategies and actions to support these themes may support more diverse and equitable involvement of patients and caregivers in research in CKD.

The Ottawa Statement implementation guidance document for cluster randomized trials in the hemodialysis setting.

Research teams are increasingly interested in using cluster randomized trial (CRT) designs to generate practice-guiding evidence for in-center maintenance hemodialysis. However, CRTs raise complex ethical issues. The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials, published in 2012, provides 15 recommendations to address ethical issues arising within 7 domains: justifying the CRT design, research ethics committee review, identifying research participants, obtaining informed consent, gatekeepers, assessing benefits and harms, and protecting vulnerable participants. But applying the Ottawa Statement recommendations to CRTs in the hemodialysis setting is complicated by the unique features of the setting and population. Here, with the help of content experts and patient partners, we co-developed this implementation guidance document to provide research teams, research ethics committees, and other stakeholders with detailed guidance on how to apply the Ottawa Statement recommendations to CRTs in the hemodialysis setting, the result of a 4-year research project. Thus, our work demonstrates how the voices of patients, caregivers, and all stakeholders may be included in the development of research ethics guidance.

An Economic Evaluation of a Web-Based Management Support System for Children With Urinary Incontinence: The eADVICE Trial.

PURPOSE: Children who require specialist outpatient care typically wait substantial periods during which their condition may progress, making treatment more difficult and costly. Timely and effective therapy during this period may reduce the need for lengthy specialist care. This study evaluated the cost-effectiveness of an individualized, evidence-informed, web-based program for children with urinary incontinence awaiting a specialist appointment (Electronic Advice and Diagnosis Via the Internet following Computerized Evaluation [eADVICE]) compared to usual care. eADVICE was supervised by a primary physician and delivered by an embodied conversational agent. MATERIALS AND METHODS: A trial-based cost-effectiveness analysis was performed from the perspective of the health care funder as a substudy of eADVICE, a multicenter, waitlist-controlled, randomized trial. Outcomes measures were incremental cost per incremental change in continence status and quality of life on an intention-to-treat basis. Uncertainty was examined using cost-effectiveness planes, scenarios, and 1-way sensitivity analyses. Costs were valued in 2021 Australian dollars. RESULTS: The use of eADVICE was found to be cost saving and beneficial (dominant) over usual care, with a higher proportion of children dry over 14 days at 6 months (risk difference 0.13; 95%CI 0.02-0.23, P = .03) and mean health care costs reduced by $188 (95%CI $61-$315) per participant. CONCLUSIONS: An individualized, evidence-informed, web-based program delivered by an embodied conversational agent is likely cost saving for children with urinary incontinence awaiting a specialist appointment. The potential economic impact of such a program is favorable and substantial, and may be transferable to outpatient clinic settings for other chronic health conditions.

Home versus in-centre haemodialysis for people with kidney failure.

BACKGROUND: Home haemodialysis (HHD) may be associated with important clinical, social or economic benefits. However, few randomised controlled trials (RCTs) have evaluated HHD versus in-centre HD (ICHD). The relative benefits and harms of these two HD modalities are uncertain. This is an update of a review first published in 2014. This update includes non-randomised studies of interventions (NRSIs). OBJECTIVES: To evaluate the benefits and harms of HHD versus ICHD in adults with kidney failure. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 9 October 2022 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 Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. We searched MEDLINE (OVID) and EMBASE (OVID) for NRSIs. SELECTION CRITERIA: RCTs and NRSIs evaluating HHD (including community houses and self-care) compared to ICHD in adults with kidney failure were eligible. The outcomes of interest were cardiovascular death, all-cause death, non-fatal myocardial infarction, non-fatal stroke, all-cause hospitalisation, vascular access interventions, central venous catheter insertion/exchange, vascular access infection, parathyroidectomy, wait-listing for a kidney transplant, receipt of a kidney transplant, quality of life (QoL), symptoms related to dialysis therapy, fatigue, recovery time, cost-effectiveness, blood pressure, and left ventricular mass. DATA COLLECTION AND ANALYSIS: Two authors independently assessed if the studies were eligible and then extracted data. The risk of bias was assessed, and relevant outcomes were extracted. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Meta-analysis was performed on outcomes where there was sufficient data. MAIN RESULTS: From the 1305 records identified, a single cross-over RCT and 39 NRSIs proved eligible for inclusion. These studies were of varying design (prospective cohort, retrospective cohort, cross-sectional) and involved a widely variable number of participants (small single-centre studies to international registry analyses). Studies also varied in the treatment prescription and delivery (e.g. treatment duration, frequency, dialysis machine parameters) and participant characteristics (e.g. time on dialysis). Studies often did not describe these parameters in detail. Although the risk of bias, as assessed by the Newcastle-Ottawa Scale, was generally low for most studies, within the constraints of observational study design, studies were at risk of selection bias and residual confounding. Many study outcomes were reported in ways that did not allow direct comparison or meta-analysis. It is uncertain whether HHD, compared to ICHD, may be associated with a decrease in cardiovascular death (RR 0.92, 95% CI 0.80 to 1.07; 2 NRSIs, 30,900 participants; very low certainty evidence) or all-cause death (RR 0.80, 95% CI 0.67 to 0.95; 9 NRSIs, 58,984 patients; very low certainty evidence). It is also uncertain whether HHD may be associated with a decrease in hospitalisation rate (MD -0.50 admissions per patient-year, 95% CI -0.98 to -0.02; 2 NRSIs, 834 participants; very low certainty evidence), compared with ICHD. Compared with ICHD, it is uncertain whether HHD may be associated with receipt of kidney transplantation (RR 1.28, 95% CI 1.01 to 1.63; 6 NRSIs, 10,910 participants; very low certainty evidence) and a shorter recovery time post-dialysis (MD -2.0 hours, 95% CI -2.73 to -1.28; 2 NRSIs, 348 participants; very low certainty evidence). It remains uncertain if HHD may be associated with decreased systolic blood pressure (SBP) (MD -11.71 mm Hg, 95% CI -21.11 to -2.46; 4 NRSIs, 491 participants; very low certainty evidence) and decreased left ventricular mass index (LVMI) (MD -17.74 g/m2, 95% CI -29.60 to -5.89; 2 NRSIs, 130 participants; low certainty evidence). There was insufficient data to evaluate the relative association of HHD and ICHD with fatigue or vascular access outcomes. Patient-reported outcome measures were reported using 18 different measures across 11 studies (QoL: 6 measures; mental health: 3 measures; symptoms: 1 measure; impact and view of health: 6 measures; functional ability: 2 measures). Few studies reported the same measures, which limited the ability to perform meta-analysis or compare outcomes. It is uncertain whether HHD is more cost-effective than ICHD, both in the first (SMD -1.25, 95% CI -2.13 to -0.37; 4 NRSIs, 13,809 participants; very low certainty evidence) and second year of dialysis (SMD -1.47, 95% CI -2.72 to -0.21; 4 NRSIs, 13,809 participants; very low certainty evidence). AUTHORS' CONCLUSIONS: Based on low to very low certainty evidence, HHD, compared with ICHD, has uncertain associations or may be associated with decreased cardiovascular and all-cause death, hospitalisation rate, slower post-dialysis recovery time, and decreased SBP and LVMI. HHD has uncertain cost-effectiveness compared with ICHD in the first and second years of treatment. The majority of studies included in this review were observational and subject to potential selection bias and confounding, especially as patients treated with HHD tended to be younger with fewer comorbidities. Variation from study to study in the choice of outcomes and the way in which they were reported limited the ability to perform meta-analyses. Future research should align outcome measures and metrics with other research in the field in order to allow comparison between studies, establish outcome effects with greater certainty, and avoid research waste.

Angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers for preventing the progression of diabetic kidney disease.

BACKGROUND: Guidelines suggest that adults with diabetes and kidney disease receive treatment with angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). This is an update of a Cochrane review published in 2006. OBJECTIVES: We compared the efficacy and safety of ACEi and ARB therapy (either as monotherapy or in combination) on cardiovascular and kidney outcomes in adults with diabetes and kidney disease. SEARCH METHODS: We searched the Cochrane Kidney and Transplants Register of Studies to 17 March 2024 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 Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: We included studies evaluating ACEi or ARB alone or in combination, compared to each other, placebo or no treatment in people with diabetes and kidney disease. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias and extracted data. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) and 95% CI for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: One hundred and nine studies (28,341 randomised participants) were eligible for inclusion. Overall, the risk of bias was high. Compared to placebo or no treatment, ACEi may make little or no difference to all-cause death (24 studies, 7413 participants: RR 0.91, 95% CI 0.73 to 1.15; I2 = 23%; low certainty) and with similar withdrawals from treatment (7 studies, 5306 participants: RR 1.03, 95% CI 0.90 to 1.19; I2 = 0%; low certainty). ACEi may prevent kidney failure (8 studies, 6643 participants: RR 0.61, 95% CI 0.39 to 0.94; I2 = 0%; low certainty). Compared to placebo or no treatment, ARB may make little or no difference to all-cause death (11 studies, 4260 participants: RR 0.99, 95% CI 0.85 to 1.16; I2 = 0%; low certainty). ARB have uncertain effects on withdrawal from treatment (3 studies, 721 participants: RR 0.85, 95% CI 0.58 to 1.26; I2 = 2%; low certainty) and cardiovascular death (6 studies, 878 participants: RR 3.36, 95% CI 0.93 to 12.07; low certainty). ARB may prevent kidney failure (3 studies, 3227 participants: RR 0.82, 95% CI 0.72 to 0.94; I2 = 0%; low certainty), doubling of serum creatinine (SCr) (4 studies, 3280 participants: RR 0.84, 95% CI 0.72 to 0.97; I2 = 32%; low certainty), and the progression from microalbuminuria to macroalbuminuria (5 studies, 815 participants: RR 0.44, 95% CI 0.23 to 0.85; I2 = 74%; low certainty). Compared to ACEi, ARB had uncertain effects on all-cause death (15 studies, 1739 participants: RR 1.13, 95% CI 0.68 to 1.88; I2 = 0%; low certainty), withdrawal from treatment (6 studies, 612 participants: RR 0.91, 95% CI 0.65 to 1.28; I2 = 0%; low certainty), cardiovascular death (13 studies, 1606 participants: RR 1.15, 95% CI 0.45 to 2.98; I2 = 0%; low certainty), kidney failure (3 studies, 837 participants: RR 0.56, 95% CI 0.29 to 1.07; I2 = 0%; low certainty), and doubling of SCr (2 studies, 767 participants: RR 0.88, 95% CI 0.52 to 1.48; I2 = 0%; low certainty). Compared to ACEi plus ARB, ACEi alone has uncertain effects on all-cause death (6 studies, 1166 participants: RR 1.08, 95% CI 0.49 to 2.40; I2 = 20%; low certainty), withdrawal from treatment (2 studies, 172 participants: RR 0.78, 95% CI 0.33 to 1.86; I2 = 0%; low certainty), cardiovascular death (4 studies, 994 participants: RR 3.02, 95% CI 0.61 to 14.85; low certainty), kidney failure (3 studies, 880 participants: RR 1.36, 95% CI 0.79 to 2.32; I2 = 0%; low certainty), and doubling of SCr (2 studies, 813 participants: RR 1.14, 95% CI 0.70 to 1.85; I2 = 0%; low certainty). Compared to ACEi plus ARB, ARB alone has uncertain effects on all-cause death (7 studies, 2607 participants: RR 1.02, 95% CI 0.76 to 1.37; I2 = 0%; low certainty), withdrawn from treatment (3 studies, 1615 participants: RR 0.81, 95% CI 0.53 to 1.24; I2 = 0%; low certainty), cardiovascular death (4 studies, 992 participants: RR 3.03, 95% CI 0.62 to 14.93; low certainty), kidney failure (4 studies, 2321 participants: RR 1.15, 95% CI 0.67 to 1.95; I2 = 29%; low certainty), and doubling of SCr (3 studies, 2252 participants: RR 1.18, 95% CI 0.85 to 1.64; I2 = 0%; low certainty). Comparative effects of different ACEi or ARB and low-dose versus high-dose ARB were rarely evaluated. No study compared different doses of ACEi. Adverse events of ACEi and ARB were rarely reported. AUTHORS' CONCLUSIONS: ACEi or ARB may make little or no difference to all-cause and cardiovascular death compared to placebo or no treatment in people with diabetes and kidney disease but may prevent kidney failure. ARB may prevent the doubling of SCr and the progression from microalbuminuria to macroalbuminuria compared with a placebo or no treatment. Despite the international guidelines suggesting not combining ACEi and ARB treatment, the effects of ACEi or ARB monotherapy compared to dual therapy have not been adequately assessed. The limited data availability and the low quality of the included studies prevented the assessment of the benefits and harms of ACEi or ARB in people with diabetes and kidney disease. Low and very low certainty evidence indicates that it is possible that further studies might provide different results.

Antecedent Cardiac Arrest Status of Donation After Circulatory Determination of Death (DCDD) Kidney Donors and the Risk of Delayed Graft Function After Kidney Transplantation: A Cohort Study.

BACKGROUND: The number of donors from donation after circulatory determination of death (DCDD) has increased by at least 4-fold over the past decade. This study evaluated the association between the antecedent cardiac arrest status of controlled DCDD donors and the risk of delayed graft function (DGF). METHODS: Using data from the Australia and New Zealand Dialysis and Transplant, the associations between antecedent cardiac arrest status of DCDD donors before withdrawal of cardiorespiratory support, DGF, posttransplant estimated glomerular filtration rate (eGFR), and allograft loss were examined using adjusted logistic, linear mixed modeling, and cox regression, respectively. Among donors who experienced cardiac arrest, we evaluated the association between duration and unwitnessed status of arrest and DGF. RESULTS: A total of 1173 kidney transplant recipients received DCDD kidneys from 646 donors in Australia between 2014 and 2019. Of these, 335 DCDD had antecedent cardiac arrest. Compared with recipients of kidneys from donors without antecedent cardiac arrest, the adjusted odds ratio (95% confidence interval) for DGF was 0.85 (0.65-1.11) among those with kidneys from donors with cardiac arrest. There was no association between antecedent cardiac arrest and posttransplant eGFR or allograft loss. The duration of cardiac arrest and unwitnessed status were not associated with DGF. CONCLUSIONS: This focused analysis in an Australian population showed that the allograft outcomes were similar whether DCDD donors had experienced a prior cardiac arrest, with no associations between duration or unwitnessed status of arrest and risk of DGF. This study thus provides important reassurance to transplant programs and the patients they counsel, to accept kidneys from donors through the DCDD pathway irrespective of a prior cardiac arrest.

Consumer involvement in the development and dissemination of chronic kidney disease guidelines: a summary of a meaningful and sustainable approach developed by Caring for Australians and New ZealandeRs with kidney Impairment guidelines.

OBJECTIVES: The involvement of consumers (people with lived experience of disease) in guidelines is widely advocated to improve their relevance and uptake. However, the approaches to consumer involvement in guidelines vary and are not well documented. We describe the consumer involvement framework of Caring for Australians and New ZealandeRs with kidney Impairment Guidelines. STUDY DESIGN AND SETTING: We used a descriptive document analysis to collate all relevant policies, documents, e-mails, and presentations on consumer involvement in our organizations. We performed a narrative synthesis of collated data to summarize our evolving consumer involvement approach in guidelines. RESULTS: We involve consumers at all levels of Caring for Australians and New ZealandeRs with kidney Impairment guideline development and dissemination according to their capacity, from conducting consumer workshops to inform the scope of guidelines, to including consumers as members of the guideline Working Groups and overseeing operations and governance as members of the Steering Committee and staff. Our approach has resulted in tangible outcomes including high-priority topics on patient education, psychosocial care, and clinical care pathways, and focusing the literature reviews to assess patient-important outcomes. The ongoing partnership with consumers led to the generation of consumer version guidelines to improve guideline dissemination and translation to support shared decision-making. CONCLUSION: Meaningful consumer involvement can be achieved through a comprehensive approach across the entire lifecycle of guidelines. However, it must be individualized by ensuring that the involvement of consumers is timely and flexible. Future work is needed to assess the impact of consumer involvement in guideline development.

Nephrologists' perspectives on communication and decision-making regarding technique survival in peritoneal dialysis: an international qualitative interview study.

OBJECTIVES: Peritoneal dialysis (PD) allows patients increased autonomy and flexibility; however, both infectious and non-infectious complications may lead to technique failure, which shortens treatment longevity. Maintaining patients on PD remains a major challenge for nephrologists. This study aims to describe nephrologists' perspectives on technique survival in PD. DESIGN: Qualitative semistructured interview study. Transcripts were thematically analysed. SETTING AND PARTICIPANTS: 30 nephrologists across 11 countries including Australia, the USA, the UK, Hong Kong, Canada, Singapore, Japan, New Zealand, Thailand, Colombia and Uruguay were interviewed from April 2017 to November 2019. RESULTS: We identified four themes: defining patient suitability (confidence in capacity for self-management, ensuring clinical stability and expected resilience), building endurance (facilitating access to practical support, improving mental well-being, optimising quality of care and training to reduce risk of complications), establishing rapport through effective communications (managing expectations to enhance trust, individualising care and harnessing a multidisciplinary approach) and confronting fear and acknowledging barriers to haemodialysis (preventing crash landing to haemodialysis, facing concerns of losing independence and positive framing of haemodialysis). CONCLUSION: Nephrologists reported that technique survival in PD is influenced by patients' medical circumstances, psychological motivation and positively influenced by the education and support provided by treating clinicians and families. Strategies to enhance patients' knowledge on PD and communication with patients about technique survival in PD are needed to build trust, set patient expectations of treatment and improve the process of transition off PD.

It matters who you are and where you live: Commonwealth, state and territory policies for access to care for Australians with chronic kidney disease and their caregivers.

OBJECTIVE: To describe how Commonwealth, state and territory policies address access to care for Australians living with chronic kidney disease (CKD) with an emphasis on Aboriginal and Torres Strait Islanders and people residing in rural and remote areas. METHODS: We searched government health department websites for current policies up to March 2022 that addressed access to care for people with CKD. RESULTS: We included 98 policies: 28 were Commonwealth, and 70 were state or territory-based. There was wide variation in the policies for people with CKD in number and type across the jurisdictions. Of CKD specific policies, only three policies were specific for people living with CKD in rural and remote areas and no policies were specific for Aboriginal and Torres Strait Islander people. CONCLUSION: There is a lack of CKD-specific policies addressing access to care for Aboriginal and Torres Strait Islander people and people living in rural and remote communities. IMPLICATIONS FOR PUBLIC HEALTH: Despite the known disparities in the burden of CKD there are few policies addressing CKD disparities for Aboriginal and Torres Strait Islander people and Australians living in rural and remote areas. Policies that specifically address the barriers to accessing care are required to reduce inequities.

Non-immunosuppressive treatment for IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerular disease, with approximately 20% to 40% of patients progressing to kidney failure within 25 years. Non-immunosuppressive treatment has become a mainstay in the management of IgAN by improving blood pressure (BP) management, decreasing proteinuria, and avoiding the risks of long-term immunosuppressive management. Due to the slowly progressive nature of the disease, clinical trials are often underpowered, and conflicting information about management with non-immunosuppressive treatment is common. This is an update of a Cochrane review, first published in 2011. OBJECTIVES: To assess the benefits and harms of non-immunosuppressive treatment for treating IgAN in adults and children. We aimed to examine all non-immunosuppressive therapies (e.g. anticoagulants, antihypertensives, dietary restriction and supplementation, tonsillectomy, and herbal medicines) in the management of IgAN. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to December 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are 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 of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed search results, extracted data and assessed study quality. Results were expressed as mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using random-effects meta-analysis. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: This review includes 80 studies (4856 participants), of which 24 new studies (2018 participants) were included in this review update. The risk of bias within the included studies was mostly high or unclear for many of the assessed methodological domains, with poor reporting of important key clinical trial methods in most studies. Antihypertensive therapies were the most examined non-immunosuppressive therapy (37 studies, 1799 participants). Compared to placebo or no treatment, renin-angiotensin system (RAS) inhibition probably decreases proteinuria (3 studies, 199 participants: MD - 0.71 g/24 h, 95% CI -1.04 to -0.39; moderate certainty evidence) but may result in little or no difference to kidney failure or doubling of serum creatinine (SCr), or complete remission of proteinuria (low certainty evidence). Death, remission of haematuria, relapse of proteinuria or > 50% increase in SCr were not reported. Compared to symptomatic treatment, RAS inhibition (3 studies, 168 participants) probably decreases proteinuria (MD -1.16 g/24 h, 95% CI -1.52 to -0.81) and SCr (MD -9.37 µmol/L, 95% CI -71.95 to -6.80) and probably increases creatinine clearance (2 studies, 127 participants: MD 23.26 mL/min, 95% CI 10.40 to 36.12) (all moderate certainty evidence); however, the risk of kidney failure is uncertain (1 study, 34 participants: RR 0.20, 95% CI 0.01 to 3.88; very low certainty evidence). Death, remission of proteinuria or haematuria, or relapse of proteinuria were not reported. The risk of adverse events may be no different with RAS inhibition compared to either placebo or symptomatic treatment (low certainty evidence). In low certainty evidence, tonsillectomy in people with IgAN in addition to standard care may increase remission of proteinuria compared to standard care alone (2 studies, 143 participants: RR 1.90, 95% CI 1.45 to 2.47) and remission of microscopic haematuria (2 studies, 143 participants: RR 1.93, 95% CI 1.47 to 2.53) and may decrease relapse of proteinuria (1 study, 73 participants: RR 0.70, 95% CI 0.57 to 0.85) and relapse of haematuria (1 study, 72 participants: RR 0.70, 95% CI 0.51 to 0.98). Death, kidney failure and a > 50% increase in SCr were not reported. These trials have only been conducted in Japanese people with IgAN, and the findings' generalisability is unclear. Anticoagulant therapy, fish oil, and traditional Chinese medicines exhibited small benefits to kidney function in patients with IgAN when compared to placebo or no treatment. However, compared to standard care, the kidney function benefits are no longer evident. Antimalarial therapy compared to placebo in one study reported an increase in a > 50% reduction of proteinuria (53 participants: RR 3.13 g/24 h, 95% CI 1.17 to 8.36; low certainty evidence). Although, there was uncertainty regarding adverse events from this study due to very few events. AUTHORS' CONCLUSIONS: Available RCTs focused on a diverse range of interventions. They were few, small, and of insufficient duration to determine potential long-term benefits on important kidney and cardiovascular outcomes and harms of treatment. Antihypertensive agents appear to be the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined were predominantly angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The benefits of RAS inhibition appear to outweigh the harms in patients with IgAN. The certainty of the evidence of RCTs demonstrating a benefit of tonsillectomy to patients with Japanese patients with IgAN was low. In addition, these findings are inconsistent across observational studies in people with IgAN of other ethnicities; hence, tonsillectomy is not widely recommended, given the potential harm of therapy. The RCT evidence is insufficiently robust to demonstrate efficacy for the other non-immunosuppressive treatments evaluated here.