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Background: Patients with kidney failure often lack robust evidence because they are excluded from randomized trials. Trial emulation provides an alternative approach to derive treatment effect estimates when randomized trials cannot be conducted. Critical questions about the comparative efficacy and safety of interventions in kidney failure are now being answered using this approach or parts of it. However, variations and inconsistencies in reporting cast doubt on the reliability and validity of effect estimates not derived from randomized trials. The aim of this methodological systematic review is to understand the extent to which the target study approach is used in kidney failure and the appropriateness of this approach. By identifying and evaluating studies that qualify as emulating a target trial, compared with studies that did not apply the principles. We aim to provide more specific methodological guidance to increase the clarity and reliability of reporting treatment effect estimates when running a trial in kidney failure is not feasible., Methods: This protocol is developed in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocols (PRISMA-P) statement. MEDLINE, Embase, and reference lists (backwards citation chasing) will be searched up until 1st July 2023 and the search updated prior to publication to identify all studies evaluating patient outcomes in late-stage kidney disease and failure that use target trial emulation as the primary approach for analysis. Two authors (A. A., P. K.) will select articles based on title and abstract and then full text, with a third reviewer settling disagreements (J. P.). The prespecified variables will be extracted, and the risk of bias will be assessed by at least two authors (A. A., P. K., A. N.) using prespecified data forms. This will enable the determination of the robustness of the methodological quality of observational studies in using the whole or elements of the target trial approach. We will thereby assess their ability to reliably report treatment effect estimates., Discussion: We will provide specific methodological recommendations on how to design target trials and model assumptions for emulation to get reliable treatment effect estimates for therapeutic interventions in kidney failure., Methodological Systematic Review Registration: Open Science Framework: Identifier https://doi.org/10.17605/OSF.IO/Z4Y29 ., Competing Interests: Declarations Ethics approval and consent to participate The protocol plan does not contain active involvement of participants which would require ethical consent. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

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 m 2 ) 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 m 2 . 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; I 2 = 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., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

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 m 2 , 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., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

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., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: The slow transformation of new research findings into clinical guidelines is a barrier to providing evidence-based care. The Caring for Australians and New Zealanders with Kidney Impairment (CARI) guidelines are developing models to improve guideline production, one methodology involves more functional concordance between trial groups, such as the Australian Kidney Trials Network (AKTN) and CARI. The objective of this project was to rapidly produce an evidence-based guideline on urate-lowering therapy in patients with chronic kidney disease (CKD), in response to new clinical trial publications on the topic by the AKTN., Methods: To produce a guideline as rapidly as possible, an existing systematic review was utilized as the evidence base, and then updated with the inclusion of clinical trials that had been published subsequently. A Work Group was convened to review the evidence and compose an appropriate guideline using CARI/GRADE methodology. The group met 3 times over 45 days to formulate the guideline., Results: The result was a strong recommendation against the use urate-lowering therapies in individuals with CKD (not receiving dialysis) and asymptomatic hyperuricemia. The process of identifying an appropriate existing systematic review, updating the literature search, and synthesizing the evidence, was done by 2 individuals over 15 days. The Work Group was formulated and composed the guideline over 45 days. In all, a new guideline incorporating the most up-to-date evidence was formulated in 60 days., Conclusion: This method of guideline development represents a potentially new way of releasing guidelines that encapsulates all available evidence in a time-efficient manner., (© 2022 Published by Elsevier Inc. on behalf of the International Society of Nephrology.)

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., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

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., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

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

Objectives: To describe the experiences, priorities, and needs of patients with rheumatic disease and their parents during transition from paediatric to adult healthcare., Setting: Face-to-face and telephone semistructured interviews were conducted from December 2018 to September 2019 recruited from five hospital centres in Australia., Participants: Fourteen young people and 16 parents were interviewed. Young people were included if they were English speaking, aged 14-25 years, diagnosed with an inflammatory rheumatic disease (eg, juvenile idiopathic arthritis, juvenile dermatomyositis, systemic lupus erythematosus, panniculitis, familial Mediterranean fever) before 18 years of age. Young people were not included if they were diagnosed in the adult setting., Results: We identified four themes with respective subthemes: avoid repeat of past disruption (maintain disease stability, preserve adjusted personal goals, protect social inclusion); encounter a daunting adult environment (serious and sombre mood, discredited and isolated identity, fear of a rigid system); establish therapeutic alliances with adult rheumatology providers (relinquish a trusting relationship, seek person-focused care, redefine personal-professional boundaries, reassurance of alternative medical supports, transferred trust to adult doctor) and negotiate patient autonomy (confidence in formerly gained independence, alleviate burden on patients, mediate parental anxiety)., Conclusions: During transition, patients want to maintain disease stability, develop a relationship with their adult provider centralised on personal goals and access support networks. Strategies to comprehensively communicate information between providers, support self-management, and negotiate individualised goals for independence during transition planning may improve satisfaction, and health and treatment outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (Copyright © 2020 KDIGO. Published by Elsevier Inc. All rights reserved.)

Objective: Patients with chronic kidney disease (CKD) requiring kidney replacement therapy (KRT) in rural communities encounter many barriers in accessing equitable care and have worse outcomes compared with patients in urban areas. This study aims to describe the perspectives of patients and caregivers on access to KRT in rural communities to inform strategies to maximise access to quality care, and thereby reduce disadvantage, inequity and improve health outcomes., Setting: 18 studies (n=593 participants) conducted across eight countries (Australia, Canada, the UK, New Zealand, Ghana, the USA, Tanzania and India)., Results: We identified five themes: uncertainty in navigating healthcare services (with subthemes of struggling to absorb information, without familiarity and exposure to options, grieving former roles and yearning for cultural safety); fearing separation from family and home (anguish of homesickness, unable to fulfil family roles and preserving sense of belonging in community); intense burden of travel and cost (poverty of time, exposure to risks and hazards, and taking a financial toll); making life-changing sacrifices; guilt and worry in receiving care (shame in taking resources from others, harbouring concerns for living donor, and coping and managing in isolation)., Conclusion: Patients with CKD in rural areas face profound and inequitable challenges of displacement, financial burden and separation from family in accessing KRT, which can have severe consequences on their well-being and outcomes. Strategies are needed to improve access and reduce the burden of obtaining appropriate KRT in rural communities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To describe the range and depth of perspectives and experiences of patients with psoriasis and psoriatic arthritis to inform gaps in patient-centered care., Methods: We searched MEDLINE, Embase, PsycINFO, and CINAHL to April 2018. Thematic synthesis was used to analyze the findings., Results: We included 56 studies involving 1,484 adult patients with psoriasis (n = 1,147) and psoriatic arthritis (n = 337). Six themes (and subthemes) were identified: suffering uncontrollable and ongoing upheaval (dictating life choices and course, disrupting family and social roles, limited by debilitating symptoms, unstoppable and far-reaching fatigue), weighed down by mental load (anxiety provoked by the volatility of symptoms, dreading deterioration, struggling with unrecognized distress, helpless and nihilistic), harboring shame and judgement (marked as unhygienic and contagious, rejected and isolated, hiding away and resenting own appearance, pain and embarrassment in intimacy), demoralized by inadequacies and burden of therapy (disappointed by unmet expectations of treatment benefit, daily drudgery, deterred by unpalatable or inconvenient treatments, disempowered by lack of personalized care), gaining control (making sense of the condition, accepting a new health status, regaining independence and normality, attuning to the body), and making confident treatment decisions (trading off perceptible benefits against safety and convenience, relying on family input, seeking empowering and reassuring relationships)., Conclusion: Patients with psoriasis and psoriatic arthritis contend with disruption in their functioning, roles, and life course and have unmet expectations about treatment. Enhanced therapeutic relationships, addressing treatment expectations and supporting psychosocial needs may improve satisfaction and outcomes., (© 2019, American College of Rheumatology.)

Objective: Systemic lupus erythematosus (SLE) is a complex autoimmune disease that can affect multiple organ systems, with specialists from many disciplines often involved, which may lead to inconsistent care. We aimed to describe the attitudes and perspectives of specialists from different medical disciplines on the management of people with SLE., Methods: Face-to-face semistructured interviews were conducted with rheumatologists (n = 16), nephrologists (n = 16), and immunologists (n = 11) providing care to adults with SLE from 19 centers across Australia in 2015. All interviews were transcribed and analyzed thematically., Results: Five themes were identified: uncertainties in judgments (hampered by unknown and unclear etiology, inapplicable evidence, comprehending information dispersion), reflexive responses (anchoring to specialty training, anticipating outcomes, avoiding disaster, empathy for the vulnerable), overarching duty to patients (achieving patient priorities, maximizing adherence, controlling the disease, providing legitimate information, having adequate and relevant expertise), safeguarding professional opportunities (diversifying clinical skills, protecting colleagues' interests), and optimizing access to treatment (capitalizing on multidisciplinary care, acquiring breakthrough therapies)., Conclusion: Specialists strive to deliver evidence-informed patient-centered care, but recognize that they are anchored by their training. To overcome uncertainties in clinical management due to lack of high-quality evidence and specialty silo structures, specialists translated evidence from other disease settings and collaborated with other specialists in routine care. Developing robust evidence, tools to support evidence-informed decisions, and multidisciplinary shared-care pathways may improve the management of people with this complex disease., (© 2017, American College of Rheumatology.)

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

Objective: Nonadherence to disease-modifying antirheumatic drugs (DMARDS) in rheumatoid arthritis (RA) and spondyloarthritis (SpA) results in increased disease activity and symptoms and poorer quality of life. We aimed to describe patients' attitudes and experiences of DMARDs in RA and SpA to inform strategies to improve medication adherence., Methods: Databases (MEDLINE, Embase, PsycINFO, and CINAHL) were searched to January 2016. Thematic synthesis was used to analyze the findings., Results: From 56 studies involving 1,383 adult patients (RA [n = 1,149], SpA [n = 191], not specified [n = 43]), we identified 6 themes (with subthemes): intensifying disease identity (severity of sudden pharmacotherapy, signifying deteriorating health, daunting lifelong therapy), distressing uncertainties and consequences (poisoning the body, doubting efficacy, conflicting and confusing advice, prognostic uncertainty with changing treatment regimens), powerful social influences (swayed by others' experiences, partnering with physicians, maintaining roles, confidence in comprehensive and ongoing care, valuing peer support), privilege and right of access to biologic agents (expensive medications must be better, right to receive a biologic agent, fearing dispossession), maintaining control (complete ownership of decision, taking extreme risks, minimizing lifestyle intrusion), and negotiating treatment expectations (miraculous recovery, mediocre benefit, reaching the end of the line)., Conclusion: Patients perceive DMARDs as strong medications with alarming side effects that intensify their disease identity. Trust and confidence in medical care, positive experiences with DMARDS among other patients, and an expectation that medications will help maintain participation in life can motivate patients to use DMARDs. Creating a supportive environment for patients to voice their concerns may improve treatment satisfaction, adherence, and health outcomes., (© 2017, The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Objective: Disease activity, organ damage, and treatment burden are often substantial in children and adolescents with systemic lupus erythematous (SLE), and the complex interplay among the developing child, parents, and peers makes effective management difficult. We aimed to describe the experiences and perspectives of adolescents and young adults diagnosed with juvenile-onset SLE to inform strategies for improving treatment and health outcomes., Methods: Focus groups and face-to-face semistructured interviews were conducted with 26 patients ages 14-26 years, from 5 Australian hospitals in 2013-2014. Focus groups and interview transcripts were thematically analyzed., Results: Five themes were identified: marring identity (misrepresented self, heightened self-consciousness, sense of isolation), restricting major life decisions (narrowed career options, threat to parenthood), multifaceted confusion and uncertainty (frustration at delayed diagnosis or misdiagnosis, needing age and culturally appropriate information, ambiguity about cause of symptoms, prognostic uncertainty, confronting transition to adult care), resentment of long-term treatment (restricting ambition, animosity toward medication use), and gaining resilience and coping capacities (desire for independence, developing self-reliance, recalibrating perceived disease severity, depending on family and friends, trusting physicians)., Conclusion: Young patients with SLE perceive they have substantially limited physical and social capacities and restricted personal and career goals. Psychosocial and educational interventions targeted at improving confidence, self-efficacy, disease-related knowledge, and social support, and at resolving insecurities regarding patients' capacity for self-management may alleviate psychosocial distress and improve adherence, and thus optimize health outcomes of adolescents and young adults with SLE., (© 2016, American College of Rheumatology.)

Objective: Management of systemic lupus erythematosus (SLE) is complex and variability in practices exists. Guidelines have been developed to help improve the management of SLE patients, but there has been no formal evaluation of these guidelines. This study aims to compare the scope, quality, and consistency of clinical practice guidelines on the diagnosis, monitoring, and treatment of patients with SLE., Methods: Electronic databases were searched up to April 2014. The Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument and textual synthesis was used to appraise and compare recommendations., Results: Nine clinical practice guidelines and 5 consensus statements were identified, which covered 7 topics: diagnosis, monitoring, treatment, neuropsychiatric SLE, lupus nephritis, antiphospholipid syndrome, and other manifestations of lupus. The methodological quality of the guidelines was variable, with the overall mean AGREE II scores ranging from 31% to 75%, out of a maximum 100%. Scores were consistently low for applicability, with only 1 guideline scoring above 50%. There was substantial variability in the treatments recommended for class II and V lupus nephritis, the recommended duration of maintenance therapy for class III/IV lupus nephritis (from 1 to 4 years), and timing of ophthalmologic examination for patients taking corticosteroids., Conclusion: Published guidelines on SLE cover a complex area of clinical care, but the methodological quality, scope, and recommendations varied substantially. Collaborative and multidisciplinary efforts to develop comprehensive, high-quality evidence-based guidelines are needed to promote best treatment and health outcomes for patients with SLE., (© 2015, American College of Rheumatology.)

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening genetic disorder and has multiple complications including, infection, pain, intracranial aneurysm and kidney failure leading to significantly impaired quality of life and reduced survival. These outcomes are well described, but patient perspectives and experiences of living with ADPKD are under-recognized., Methods: MEDLINE, Embase, PsycINFO and CINAHL were searched to August 2014. Studies were analyzed using thematic synthesis., Results: From 21 studies (n = 247), we derived five themes: unvalidated pain (medical trivialization, inadequacy of pain management); persisting uncertainties and ambiguities (lacking diagnostic clarity, disempowerment in self-care, unpredictable daily disruptions, inability to plan ahead, financial discrimination); genetic guilt and resentment (blaming parents, self-blame, constant burden of guilt); precariousness in pursuing parenthood (prognostic uncertainty, owning the decision, needing directive counselling); and defining parental responsibility for genetic testing and disclosure (preserving normality, doubting necessity of genetic testing, respecting the child's autonomy and hope in future technologies, facilitating preparedness)., Conclusions: The erratic onset of pain contributes to the substantial unpredictability of daily living and prevents patients from establishing long-term life goals. Decisions about family planning, genetic testing of children and disclosure involves making profoundly difficult judgments about ethical parental responsibility. Patient engagement in pain management, strategies for self-care, counselling to reduce the burden of 'genetic guilt' and specific family planning decision support tools may be priorities for care to improve patient-centred outcomes in ADPKD., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)