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.

Kidney Failure from Kidney Stones: An ANZDATA Registry Study.

INTRODUCTION: Kidney stones is common with an increasing trend over time and has been well studied in the general population. However, incidence and outcomes of kidney stones leading to kidney failure (KF) and receiving kidney replacement therapy (KRT) is poorly examined. We examined the incidence of KF due to kidney stones and compared outcomes to KRT patients due to other causes. METHODS: Adult patients who started KRT (January 1981-December 2020) and based in the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry. Exposure was KRT patients due to kidney stones comparing them to those with other causes. We examined incidence, prevalence, patient survival (KRT and transplant) and graft survival (transplant). Cox regression models were fit to compare patient survival between kidney stones and non-kidney stones groups, overall KRT, dialysis and patient and graft survival after kidney transplant. RESULTS: A total of 834 (1.1%) patients commenced KRT due to kidney stones. Incidence was 1.17 per million population per year and remained stable during the study period (annual percentage change -0.3% [95%CI -1.5% to 0.9%]. Survival was higher in kidney stone patients receiving dialysis compared to the non-kidney stone group (hazard ratio [HR], 0.89, 95%CI 0.82- 0.96) with similar estimates in a matched cohort. In kidney transplant patients, time to transplant was longer for patients with kidney stone compared to non-kidney stone patients (2.5 vs 1.7 years, P=0.001). There was no mortality difference (HR 1.02, 95%CI 0.82- 1.28) or graft loss (HR 1.07, 95%CI 0.79- 1.45) between kidney stones vs non-kidney stones in the kidney transplant group. CONCLUSION: KF due to kidney stones incidence is unchanged over the study period. Survival of patients with kidney stones who require KRT was better compared to patients from other causes. For the kidney transplant group, survival and risk of graft failure were similar.

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.

Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes.

BACKGROUND: Diabetes is associated with high risks of premature chronic kidney disease (CKD), cardiovascular diseases, cardiovascular death and impaired quality of life. People with diabetes are more likely to develop kidney impairment, and approximately one in three adults with diabetes have CKD. People with CKD and diabetes experience a substantially higher risk of cardiovascular outcomes. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors have shown potential effects in preventing kidney and cardiovascular outcomes in people with CKD and diabetes. However, new trials are emerging rapidly, and evidence synthesis is essential to summarising cumulative evidence. OBJECTIVES: This review aimed to assess the benefits and harms of SGLT2 inhibitors for people with CKD and diabetes. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 17 November 2023 using a search strategy designed by an Information Specialist. Studies in the Register are continually identified through regular searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled studies were eligible if they evaluated SGLT2 inhibitors versus placebo, standard care or other glucose-lowering agents in people with CKD and diabetes. CKD includes all stages (from 1 to 5), including dialysis patients. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the study risk of bias. Treatment estimates were summarised using random effects meta-analysis and expressed as a risk ratio (RR) or mean difference (MD), with a corresponding 95% confidence interval (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The primary review outcomes were all-cause death, 3-point and 4-point major adverse cardiovascular events (MACE), fatal or nonfatal myocardial infarction (MI), fatal or nonfatal stroke, and kidney failure. MAIN RESULTS: Fifty-three studies randomising 65,241 people with CKD and diabetes were included. SGLT2 inhibitors with or without other background treatments were compared to placebo, standard care, sulfonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitors, or insulin. In the majority of domains, the risks of bias in the included studies were low or unclear. No studies evaluated the treatment in children or in people treated with dialysis. No studies compared SGLT2 inhibitors with glucagon-like peptide-1 receptor agonists or tirzepatide. Compared to placebo, SGLT2 inhibitors decreased the risk of all-cause death (20 studies, 44,397 participants: RR 0.85, 95% CI 0.78 to 0.94; I2 = 0%; high certainty) and cardiovascular death (16 studies, 43,792 participants: RR 0.83, 95% CI 0.74 to 0.93; I2 = 29%; high certainty). Compared to placebo, SGLT2 inhibitors probably make little or no difference to the risk of fatal or nonfatal MI (2 studies, 13,726 participants: RR 0.95, 95% CI 0.80 to 1.14; I2 = 24%; moderate certainty), and fatal or nonfatal stroke (2 studies, 13,726 participants: RR 1.07, 95% CI 0.88 to 1.30; I2 = 0%; moderate certainty). Compared to placebo, SGLT2 inhibitors probably decrease 3-point MACE (7 studies, 38,320 participants: RR 0.89, 95% CI 0.81 to 0.98; I2 = 46%; moderate certainty), and 4-point MACE (4 studies, 23,539 participants: RR 0.82, 95% CI 0.70 to 0.96; I2 = 77%; moderate certainty), and decrease hospital admission due to heart failure (6 studies, 28,339 participants: RR 0.70, 95% CI 0.62 to 0.79; I2 = 17%; high certainty). Compared to placebo, SGLT2 inhibitors may decrease creatinine clearance (1 study, 132 participants: MD -2.63 mL/min, 95% CI -5.19 to -0.07; low certainty) and probably decrease the doubling of serum creatinine (2 studies, 12,647 participants: RR 0.70, 95% CI 0.56 to 0.89; I2 = 53%; moderate certainty). SGLT2 inhibitors decrease the risk of kidney failure (6 studies, 11,232 participants: RR 0.70, 95% CI 0.62 to 0.79; I2 = 0%; high certainty), and kidney composite outcomes (generally reported as kidney failure, kidney death with or without ≥ 40% decrease in estimated glomerular filtration rate (eGFR)) (7 studies, 36,380 participants: RR 0.68, 95% CI 0.59 to 0.78; I2 = 25%; high certainty) compared to placebo. Compared to placebo, SGLT2 inhibitors incur less hypoglycaemia (16 studies, 28,322 participants: RR 0.93, 95% CI 0.89 to 0.98; I2 = 0%; high certainty), and hypoglycaemia requiring third-party assistance (14 studies, 26,478 participants: RR 0.75, 95% CI 0.65 to 0.88; I2 = 0%; high certainty), and probably decrease the withdrawal from treatment due to adverse events (15 studies, 16,622 participants: RR 0.94, 95% CI 0.82 to 1.08; I2 = 16%; moderate certainty). The effects of SGLT2 inhibitors on eGFR, amputation and fracture were uncertain. No studies evaluated the effects of treatment on fatigue, life participation, or lactic acidosis. The effects of SGLT2 inhibitors compared to standard care alone, sulfonylurea, DPP-4 inhibitors, or insulin were uncertain. AUTHORS' CONCLUSIONS: SGLT2 inhibitors alone or added to standard care decrease all-cause death, cardiovascular death, and kidney failure and probably decrease major cardiovascular events while incurring less hypoglycaemia compared to placebo in people with CKD and diabetes.

Australian and New Zealand Living Guideline cholesterol-lowering therapy for people with chronic kidney disease (CARI Guidelines): Reducing the evidence-practice gap.

AIM: People with chronic kidney disease experience high rates of cardiovascular disease. Cholesterol-lowering therapy is a mainstay in the management but there is uncertainty in the treatment effects on patient-important outcomes, such as fatigue and rhabdomyolysis. Here, we summarise the updated CARI Australian and New Zealand Living Guidelines on cholesterol-lowering therapy in chronic kidney disease. METHODS: We updated a Cochrane review and monitored newly published studies weekly to inform guideline development according to international standards. The Working Group included expertise from nephrology, cardiology, Indigenous Health, guideline development and people with lived experience of chronic kidney disease. RESULTS: The guideline recommends people with chronic kidney disease (eGFR ≥15 mL/min/1.73 m2) and an absolute cardiovascular risk of 10% or higher should receive statin therapy (with or without ezetimibe) to reduce the risk of cardiovascular events and death (strong recommendation, moderate certainty evidence). The guidelines also recommends a lower absolute cardiovascular risk threshold (≥5%) for Aboriginal and Torres Strait Islander Peoples and Maori with chronic kidney disease to receive statin therapy (with or without ezetimibe) (strong recommendation, low certainty evidence). The evidence was actively surveyed from 2020-2023 and updated as required. No changes to guideline recommendations were made, with no new data on the balance and benefits of harms. CONCLUSIONS: The development of living guidelines was feasible and provided the opportunity to update recommendations to improve clinical decision-making in real-time. Living guidelines provide the opportunity to transform chronic kidney disease guidelines.

Diabetes Management in Chronic Kidney Disease: Synopsis of the KDIGO 2022 Clinical Practice Guideline Update.

DESCRIPTION: The KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease is an update of the 2020 guideline from Kidney Disease: Improving Global Outcomes (KDIGO). METHODS: The KDIGO Work Group updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the Work Group used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and expert judgment to develop consensus practice points. New evidence led to updating of recommendations in the chapters Comprehensive Care in Patients With Diabetes and CKD (Chapter 1) and Glucose-Lowering Therapies in Patients With T2D and CKD (Chapter 4). New evidence did not change recommendations in the chapters Glycemic Monitoring and Targets in Patients With Diabetes and CKD (Chapter 2), Lifestyle Interventions in Patients With Diabetes and CKD (Chapter 3), and Approaches to Management of Patients With Diabetes and CKD (Chapter 5). RECOMMENDATIONS: The updated guideline includes 13 recommendations and 52 practice points for clinicians caring for patients with diabetes and chronic kidney disease (CKD). A focus on preserving kidney function and maintaining well-being is recommended using a layered approach to care, starting with a foundation of lifestyle interventions, self-management, and first-line pharmacotherapy (such as sodium-glucose cotransporter-2 inhibitors) demonstrated to improve clinical outcomes. To this are added additional drugs with heart and kidney protection, such as glucagon-like peptide-1 receptor agonists and nonsteroidal mineralocorticoid receptor antagonists, and interventions to control risk factors for CKD progression and cardiovascular events, such as blood pressure, glycemia, and lipids.

Recommendations for culturally safe clinical kidney care for First Nations Australians: a guideline summary.

INTRODUCTION: First Nations Australians display remarkable strength and resilience despite the intergenerational impacts of ongoing colonisation. The continuing disadvantage is evident in the higher incidence, prevalence, morbidity and mortality of chronic kidney disease (CKD) among First Nations Australians. Nationwide community consultation (Kidney Health Australia, Yarning Kidneys, and Lowitja Institute, Catching Some Air) identified priority issues for guideline development. These guidelines uniquely prioritised the knowledge of the community, alongside relevant evidence using an adapted GRADE Evidence to Decision framework to develop specific recommendations for the management of CKD among First Nations Australians. MAIN RECOMMENDATIONS: These guidelines explicitly state that health systems have to measure, monitor and evaluate institutional racism and link it to cultural safety training, as well as increase community and family involvement in clinical care and equitable transport and accommodation. The guidelines recommend earlier CKD screening criteria (age ≥ 18 years) and referral to specialists services with earlier criteria of kidney function (eg, estimated glomerular filtration rate [eGFR], ≤ 45 mL/min/1.73 m2 , and a sustained decrease in eGFR, > 10 mL/min/1.73 m2 per year) compared with the general population. CHANGES IN MANAGEMENT AS RESULT OF THE GUIDELINES: Our recommendations prioritise health care service delivery changes to address institutional racism and ensure meaningful cultural safety training. Earlier detection of CKD and referral to nephrologists for First Nations Australians has been recommended to ensure timely implementation to preserve kidney function given the excess burden of disease. Finally, the importance of community with the recognition of involvement in all aspects and stages of treatment together with increased access to care on Country, particularly in rural and remote locations, including dialysis services.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a long-term condition that occurs as a result of damage to the kidneys. Early recognition of CKD is becoming increasingly common due to widespread laboratory estimated glomerular filtration rate (eGFR) reporting, raised clinical awareness, and international adoption of the Kidney Disease Improving Global Outcomes (KDIGO) classifications. Early recognition and management of CKD affords the opportunity to prepare for progressive kidney impairment and impending kidney replacement therapy and for intervention to reduce the risk of progression and cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are two classes of antihypertensive drugs that act on the renin-angiotensin-aldosterone system. Beneficial effects of ACEi and ARB on kidney outcomes and survival in people with a wide range of severity of kidney impairment have been reported; however, their effectiveness in the subgroup of people with early CKD (stage 1 to 3) is less certain. This is an update of a review that was last published in 2011. OBJECTIVES: To evaluate the benefits and harms of ACEi and ARB or both in the management of people with early (stage 1 to 3) CKD who do not have diabetes mellitus (DM). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 6 July 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, and Embase, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) reporting the effect of ACEi or ARB in people with early (stage 1 to 3) CKD who did not have DM were selected for inclusion. Only studies of at least four weeks duration were selected. Authors independently assessed the retrieved titles and abstracts and, where necessary, the full text to determine which satisfied the inclusion criteria. DATA COLLECTION AND ANALYSIS: Data extraction was carried out by two authors independently, using a standard data extraction form. The methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross-checked by another. When more than one study reported similar outcomes, data were pooled using the random-effects model. Heterogeneity was analysed using a Chi² test and the I² test. 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: Six studies randomising 9379 participants with CKD stages 1 to 3 (without DM) met our inclusion criteria. Participants were adults with hypertension; 79% were male from China, Europe, Japan, and the USA. Treatment periods ranged from 12 weeks to three years. Overall, studies were judged to be at unclear or high risk of bias across all domains, and the quality of the evidence was poor, with GRADE rated as low or very low certainty. In low certainty evidence, ACEi (benazepril 10 mg or trandolapril 2 mg) compared to placebo may make little or no difference to death (any cause) (2 studies, 8873 participants): RR 2.00, 95% CI 0.26 to 15.37; I² = 76%), total cardiovascular events (2 studies, 8873 participants): RR 0.97, 95% CI 0.90 to 1.05; I² = 0%), cardiovascular-related death (2 studies, 8873 participants): RR 1.73, 95% CI 0.26 to 11.66; I² = 54%), stroke (2 studies, 8873 participants): RR 0.76, 95% CI 0.56 to 1.03; I² = 0%), myocardial infarction (2 studies, 8873 participants): RR 1.00, 95% CI 0.84 to 1.20; I² = 0%), and adverse events (2 studies, 8873 participants): RR 1.33, 95% CI 1.26 to 1.41; I² = 0%). It is uncertain whether ACEi (benazepril 10 mg or trandolapril 2 mg) compared to placebo reduces congestive heart failure (1 study, 8290 participants): RR 0.75, 95% CI 0.59 to 0.95) or transient ischaemic attack (1 study, 583 participants): RR 0.94, 95% CI 0.06 to 15.01; I² = 0%) because the certainty of the evidence is very low. It is uncertain whether ARB (losartan 50 mg) compared to placebo (1 study, 226 participants) reduces: death (any-cause) (no events), adverse events (RR 19.34, 95% CI 1.14 to 328.30), eGFR rate of decline (MD 5.00 mL/min/1.73 m2, 95% CI 3.03 to 6.97), presence of proteinuria (MD -0.65 g/24 hours, 95% CI -0.78 to -0.52), systolic blood pressure (MD -0.80 mm Hg, 95% CI -3.89 to 2.29), or diastolic blood pressure (MD -1.10 mm Hg, 95% CI -3.29 to 1.09) because the certainty of the evidence is very low. It is uncertain whether ACEi (enalapril 20 mg, perindopril 2 mg or trandolapril 1 mg) compared to ARB (olmesartan 20 mg, losartan 25 mg or candesartan 4 mg) (1 study, 26 participants) reduces: proteinuria (MD -0.40, 95% CI -0.60 to -0.20), systolic blood pressure (MD -3.00 mm Hg, 95% CI -6.08 to 0.08) or diastolic blood pressure (MD -1.00 mm Hg, 95% CI -3.31 to 1.31) because the certainty of the evidence is very low. AUTHORS' CONCLUSIONS: There is currently insufficient evidence to determine the effectiveness of ACEi or ARB in patients with stage 1 to 3 CKD who do not have DM. The available evidence is overall of very low certainty and high risk of bias. We have identified an area of large uncertainty for a group of patients who account for most of those diagnosed as having CKD.

HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis.

BACKGROUND: Cardiovascular disease is the most frequent cause of death in people with early stages of chronic kidney disease (CKD), and the absolute risk of cardiovascular events is similar to people with coronary artery disease. This is an update of a review first published in 2009 and updated in 2014, which included 50 studies (45,285 participants). OBJECTIVES: To evaluate the benefits and harms of statins compared with placebo, no treatment, standard care or another statin in adults with CKD not requiring dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 4 October 2023. 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. An updated search will be undertaken every three months. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care, or other statins, on death, cardiovascular events, kidney function, toxicity, and lipid levels in adults with CKD (estimated glomerular filtration rate (eGFR) 90 to 15 mL/min/1.73 m2) were included. DATA COLLECTION AND ANALYSIS: Two or more authors independently extracted data and assessed the study risk of bias. Treatment effects were expressed as mean difference (MD) for continuous outcomes and risk ratios (RR) for dichotomous benefits and harms with 95% confidence intervals (CI). The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We included 63 studies (50,725 randomised participants); of these, 53 studies (42,752 participants) compared statins with placebo or no treatment. The median duration of follow-up was 12 months (range 2 to 64.8 months), the median dosage of statin was equivalent to 20 mg/day of simvastatin, and participants had a median eGFR of 55 mL/min/1.73 m2. Ten studies (7973 participants) compared two different statin regimens. We were able to meta-analyse 43 studies (41,273 participants). Most studies had limited reporting and hence exhibited unclear risk of bias in most domains. Compared with placebo or standard of care, statins prevent major cardiovascular events (14 studies, 36,156 participants: RR 0.72, 95% CI 0.66 to 0.79; I2 = 39%; high certainty evidence), death (13 studies, 34,978 participants: RR 0.83, 95% CI 0.73 to 0.96; I² = 53%; high certainty evidence), cardiovascular death (8 studies, 19,112 participants: RR 0.77, 95% CI 0.69 to 0.87; I² = 0%; high certainty evidence) and myocardial infarction (10 studies, 9475 participants: RR 0.55, 95% CI 0.42 to 0.73; I² = 0%; moderate certainty evidence). There were too few events to determine if statins made a difference in hospitalisation due to heart failure. Statins probably make little or no difference to stroke (7 studies, 9115 participants: RR 0.64, 95% CI 0.37 to 1.08; I² = 39%; moderate certainty evidence) and kidney failure (3 studies, 6704 participants: RR 0.98, 95% CI 0.91 to 1.05; I² = 0%; moderate certainty evidence) in people with CKD not requiring dialysis. Potential harms from statins were limited by a lack of systematic reporting. Statins compared to placebo may have little or no effect on elevated liver enzymes (7 studies, 7991 participants: RR 0.76, 95% CI 0.39 to 1.50; I² = 0%; low certainty evidence), withdrawal due to adverse events (13 studies, 4219 participants: RR 1.16, 95% CI 0.84 to 1.60; I² = 37%; low certainty evidence), and cancer (2 studies, 5581 participants: RR 1.03, 95% CI 0.82 to 1.30; I² = 0%; low certainty evidence). However, few studies reported rhabdomyolysis or elevated creatinine kinase; hence, we are unable to determine the effect due to very low certainty evidence. Statins reduce the risk of death, major cardiovascular events, and myocardial infarction in people with CKD who did not have cardiovascular disease at baseline (primary prevention). There was insufficient data to determine the benefits and harms of the type of statin therapy. AUTHORS' CONCLUSIONS: Statins reduce death and major cardiovascular events by about 20% and probably make no difference to stroke or kidney failure in people with CKD not requiring dialysis. However, due to limited reporting, the effect of statins on elevated creatinine kinase or rhabdomyolysis is unclear. Statins have an important role in the primary prevention of cardiovascular events and death in people who have CKD and do not require dialysis. Editorial note: This is a living systematic review. We will search for new evidence every three months and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Executive summary of the KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease: an update based on rapidly emerging new evidence.

The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (CKD) represents a focused update of the KDIGO 2020 guideline on the topic. The guideline targets a broad audience of clinicians treating people with diabetes and CKD. Topic areas for which recommendations are updated based on new evidence include Chapter 1: Comprehensive care in patients with diabetes and CKD and Chapter 4: Glucose-lowering therapies in patients with type 2 diabetes (T2D) and CKD. The content of previous chapters on Glycemic monitoring and targets in patients with diabetes and CKD (Chapter 2), Lifestyle interventions in patients with diabetes and CKD (Chapter 3), and Approaches to management of patients with diabetes and CKD (Chapter 5) has been deemed current and was not changed. This guideline update was developed according to an explicit process of evidence review and appraisal. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence, and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, and areas for which additional research is needed are presented.

Management of Blood Pressure in Patients With Chronic Kidney Disease Not Receiving Dialysis: Synopsis of the 2021 KDIGO Clinical Practice Guideline.

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

Diabetes Management in Chronic Kidney Disease: Synopsis of the 2020 KDIGO Clinical Practice Guideline.

DESCRIPTION: The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed a clinical practice guideline in 2020 for the management of patients with diabetes and chronic kidney disease (CKD). METHODS: The KDIGO Work Group (WG) was tasked with developing the guideline for diabetes management in CKD. It defined the scope of the guideline, gathered evidence, determined systematic review topics, and graded evidence that had been summarized by an evidence review team. The English-language literature searches, which were initially done through October 2018, were updated in February 2020. The WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of the recommendations. Expert judgment was used to develop consensus practice points supplementary to the evidence-based graded recommendations. The guideline document underwent open public review. Comments from various stakeholders, subject matter experts, and industry and national organizations were considered before the document was finalized. RECOMMENDATIONS: The guideline includes 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and CKD. This synopsis focuses on the key recommendations pertinent to the following issues: comprehensive care needs, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and educational and integrated care approaches.

Executive summary of the KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease.

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

Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases is an update to the KDIGO 2012 guideline. The aim is to assist clinicians caring for individuals with glomerulonephritis (GN), both adults and children. The scope includes various glomerular diseases, including IgA nephropathy and IgA vasculitis, membranous nephropathy, nephrotic syndrome, minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), infection-related GN, antineutrophil cytoplasmic antibody (ANCA) vasculitis, lupus nephritis, and anti-glomerular basement membrane antibody GN. In addition, this guideline will be the first to address the subtype of complement-mediated diseases. Each chapter follows the same format providing guidance related to diagnosis, prognosis, treatment, and special situations. The goal of the guideline is to generate a useful resource for clinicians and patients by providing actionable recommendations based on evidence syntheses, with useful infographics incorporating views from experts in the field. Another aim is to propose research recommendations for areas where there are gaps in knowledge. The guideline targets a broad global audience of clinicians treating GN while being mindful of implications for policy and cost. Development of this guideline update followed an explicit process whereby treatment approaches and guideline recommendations are based on systematic reviews of relevant studies, and appraisal of the quality of the evidence and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, with areas of future research also presented.

Immunosuppressive treatment for primary membranous nephropathy in adults with nephrotic syndrome.

BACKGROUND: Primary membranous nephropathy (PMN) is a common cause of nephrotic syndrome in adults. Without treatment, approximately 30% of patients will experience spontaneous remission and one third will have persistent proteinuria. Approximately one-third of patients progress toward end-stage kidney disease (ESKD) within 10 years. Immunosuppressive treatment aims to protect kidney function and is recommended for patients who do not show improvement of proteinuria by supportive therapy, and for patients with severe nephrotic syndrome at presentation due to the high risk of developing ESKD. The efficacy and safety of different immunosuppressive regimens are unclear. This is an update of a Cochrane review, first published in 2004 and updated in 2013. OBJECTIVES: The aim was to evaluate the safety and efficacy of different immunosuppressive treatments for adult patients with PMN and nephrotic syndrome. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 1 April 2021 with support from the Cochrane Kidney and Transplant Information Specialist 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 Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) investigating effects of immunosuppression in adults with PMN and nephrotic syndrome were included. DATA COLLECTION AND ANALYSIS: Study selection, data extraction, quality assessment, and data synthesis were performed using Cochrane-recommended methods. 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: Sixty-five studies (3807 patients) were included. Most studies exhibited a high risk of bias for the domains, blinding of study personnel, participants and outcome assessors, and most studies were judged unclear for randomisation sequence generation and allocation concealment. Immunosuppressive treatment versus placebo/no treatment/non-immunosuppressive treatment In moderate certainty evidence, immunosuppressive treatment probably makes little or no difference to death, probably reduces the overall risk of ESKD (16 studies, 944 participants: RR 0.59, 95% CI 0.35 to 0.99; I² = 22%), probably increases total remission (complete and partial) (6 studies, 879 participants: RR 1.44, 95% CI 1.05 to 1.97; I² = 73%) and complete remission (16 studies, 879 participants: RR 1.70, 95% CI 1.05 to 2.75; I² = 43%), and probably decreases the number with doubling of serum creatinine (SCr) (9 studies, 447 participants: RR 0.46, 95% CI 0.26 to 0.80; I² = 21%). However, immunosuppressive treatment may increase the number of patients relapsing after complete or partial remission (3 studies, 148 participants): RR 1.73, 95% CI 1.05 to 2.86; I² = 0%) and may lead to a greater number experiencing temporary or permanent discontinuation/hospitalisation due to adverse events (18 studies, 927 participants: RR 5.33, 95% CI 2.19 to 12.98; I² = 0%). Immunosuppressive treatment has uncertain effects on infection and malignancy. Oral alkylating agents with or without steroids versus placebo/no treatment/steroids Oral alkylating agents with or without steroids had uncertain effects on death but may reduce the overall risk of ESKD (9 studies, 537 participants: RR 0.42, 95% CI 0.24 to 0.74; I² = 0%; low certainty evidence). Total (9 studies, 468 participants: RR 1.37, 95% CI 1.04 to 1.82; I² = 70%) and complete remission (8 studies, 432 participants: RR 2.12, 95% CI 1.33 to 3.38; I² = 37%) may increase, but had uncertain effects on the number of patients relapsing, and decreasing the number with doubling of SCr. Alkylating agents may be associated with a higher rate of adverse events leading to discontinuation or hospitalisation (8 studies 439 participants: RR 6.82, 95% CI 2.24 to 20.71; I² = 0%). Oral alkylating agents with or without steroids had uncertain effects on infection and malignancy. Calcineurin inhibitors (CNI) with or without steroids versus placebo/no treatment/supportive therapy/steroids We are uncertain whether CNI with or without steroids increased or decreased the risk of death or ESKD, increased or decreased total or complete remission, or reduced relapse after complete or partial remission (low to very low certainty evidence). CNI also had uncertain effects on decreasing the number with a doubling of SCr, temporary or permanent discontinuation or hospitalisation due to adverse events, infection, or malignancy. Calcineurin inhibitors (CNI) with or without steroids versus alkylating agents with or without steroids We are uncertain whether CNI with or without steroids increases or decreases the risk of death or ESKD. CNI with or without steroids may make little or no difference to total remission (10 studies, 538 participants: RR 1.01, 95% CI 0.89 to 1.15; I² = 53%; moderate certainty evidence) or complete remission (10 studies, 538 participants: RR 1.15, 95% CI 0.84 to 1.56; I² = 56%; low certainty evidence). CNI with or without steroids may increase relapse after complete or partial remission. CNI with or without steroids had uncertain effects on SCr increase, adverse events, infection, and malignancy. Other immunosuppressive treatments Other interventions included azathioprine, mizoribine, adrenocorticotropic hormone, traditional Chinese medicines, and monoclonal antibodies such as rituximab. There were insufficient data to draw conclusions on these treatments. AUTHORS' CONCLUSIONS: This updated review strengthened the evidence that immunosuppressive therapy is probably superior to non-immunosuppressive therapy in inducing remission and reducing the number of patients that progress to ESKD. However, these benefits need to be balanced against the side effects of immunosuppressive drugs. The number of included studies with high-quality design was relatively small and most studies did not have adequate follow-up. Clinicians should inform their patients of the lack of high-quality evidence. An alkylating agent (cyclophosphamide or chlorambucil) combined with a corticosteroid regimen had short- and long-term benefits, but this was associated with a higher rate of adverse events. CNI (tacrolimus and cyclosporin) showed equivalency with alkylating agents however, the certainty of this evidence remains low. Novel immunosuppressive treatments with the biologic rituximab or use of adrenocorticotropic hormone require further investigation and validation in large and high-quality RCTs.

Commentary on the KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in CKD.

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

Executive summary of the 2020 KDIGO Diabetes Management in CKD Guideline: evidence-based advances in monitoring and treatment.

THE KIDNEY DISEASE: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease represents the first KDIGO guideline on this subject. The guideline comes at a time when advances in diabetes technology and therapeutics offer new options to manage the large population of patients with diabetes and chronic kidney disease (CKD) at high risk of poor health outcomes. An enlarging base of high-quality evidence from randomized clinical trials is available to evaluate important new treatments offering organ protection, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. The goal of the new guideline is to provide evidence-based recommendations to optimize the clinical care of people with diabetes and CKD by integrating new options with existing management strategies. In addition, the guideline contains practice points to facilitate implementation when insufficient data are available to make well-justified recommendations or when additional guidance may be useful for clinical application. The guideline covers comprehensive care of patients with diabetes and CKD, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and self-management and health systems approaches to management of patients with diabetes and CKD.

Patients' attitudes and experiences of transition from paediatric to adult healthcare in rheumatology: a qualitative systematic review.

OBJECTIVES: We aimed to describe patients' attitudes and experiences of transition from paediatric to adult healthcare in rheumatology to inform patient-centred transitional care programmes. METHODS: We searched MEDLINE, EMBASE, PsycINFO and CINAHL to August 2019 and used thematic synthesis to analyse the findings. RESULTS: From 26 studies involving 451 people with juvenile-onset rheumatic conditions we identified six themes: a sense of belonging (comfort in familiarity, connectedness in shared experiences, reassurance in being with others of a similar age, desire for normality and acceptance); preparedness for sudden changes (confidence through guided introductions to the adult environment, rapport from continuity of care, security in a reliable point of contact, minimizing lifestyle disruptions); abandonment and fear of the unknown (abrupt and forced independence, ill-equipped to hand over medical information, shocked by meeting adults with visible damage and disability, vulnerability in the loss of privacy); anonymous and dismissed in adult care (deprived of human focus, sterile and uninviting environment, disregard of debilitating pain and fatigue); quest for autonomy (controlled and patronized in the paediatric environment, liberated from the authority of others, freedom to communicate openly); and tensions in parental involvement (overshadowed by parental presence, guilt of excluding parents, reluctant withdrawal of parental support). CONCLUSION: Young people feel dismissed, abandoned, ill-prepared and out of control during transition. However, successful transition can be supported by preparing for changes, creating a sense of belonging and negotiating parental involvement and autonomy. Incorporating patient-identified priorities into transitional services may improve satisfaction and outcomes in young people with juvenile-onset rheumatic conditions.

Kidney Health Australia - Caring for Australasians with Renal Impairment guideline recommendations for infection control for haemodialysis units.

AIM: There is no national consensus on infection control in haemodialysis units in Australia and New Zealand. The primary aim of this guideline was to provide recommendations on screening for blood-borne viruses and multi-resistant organisms for dialysis units based on the available evidence. METHODS: The Kidney Health Australia Caring for Australasians with Renal Impairment guidelines, overall approach to guideline development follows the GRADE framework. A facilitated workshop was conducted to ensure that patient and caregiver concerns were considered. The evidence from relevant medical databases on the impact of screening on detection and transmission rates, hospitalization, mortality and psychosocial care, was reviewed and critically appraised. The guideline group made recommendations from the evidence available. RESULTS: The main guideline recommendations are: Dialysis units adopt a comprehensive approach that encompasses standard infection control precautions. Conduct routine surveillance for key blood-borne viruses and methicillin-resistant Staphylococcus aureus. Conduct routine surveillance of individual levels of protection against hepatitis B for patients on haemodialysis. Use dedicated dialysis machines for HBV-infected patients. The evidence in totality was not found to support routine surveillance of vancomycin-resistant Enterococci . Enhanced surveillance in light of the local risk of transmittable infectious agents should be considered by dialysis units. Very few studies have reported on the potential adverse effects of screening and associated practices. CONCLUSIONS: Future research should focus on the potential benefits and adverse effects of screening and associated practices on clinical outcomes including infections prevented and health service delivery, and psychosocial domains for patients. Given the results of trials in the critical setting, the effectiveness of methicillin-resistant Staphylococcus aureus decolonization in people receiving dialysis therapy warrants further research.