Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated Vasculitis.

In 2021, the Kidney Disease: Improving Global Outcomes (KDIGO) Guideline for the Management of Glomerular Diseases was published. KDIGO is committed to providing the nephrology community with periodic updates, based on new developments for each disease. For patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), avacopan received regulatory approval in late 2021, leading to this KDIGO guideline update. In addition, the evidence supporting a lower-dose glucocorticoid induction regimen or even complete replacement of glucocorticoids has become stronger. Herein, an executive summary of the most important guideline changes from the AAV chapter is provided as a quick reference.

Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus Nephritis.

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Glomerular Diseases was published in 2021. Since then, the pace of drug development for glomerular diseases has accelerated, due in large part to rapidly accumulating insights into disease pathogenesis from genetic and molecular studies of afflicted patients. To keep the Glomerular Diseases Guideline as current as possible, KDIGO made a commitment to the nephrology community to provide periodic updates, based on new developments for each disease. After the 2021 guideline was published, two novel drugs received regulatory approval for the management of lupus nephritis, leading to the first KDIGO guideline update. Herein, an executive summary of the most important guideline changes from the Lupus Nephritis chapter is provided as a quick reference.

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.

Trends in nephrology referral patterns for patients with chronic kidney disease: Retrospective cohort study.

INTRODUCTION: Information on early, guideline discordant referrals in nephrology is limited. Our objective was to investigate trends in referral patterns to nephrology for patients with chronic kidney disease (CKD). METHODS: Retrospective cohort study of adults with ≥1 visits to a nephrologist from primary care with ≥1 serum creatinine and/or urine protein measurement <180 days before index nephrology visit, from 2006 and 2019 in Alberta, Canada. Guideline discordant referrals were those that did not meet ≥1 of: Estimated glomerular filtration rate (eGFR) ˂ 30 mL/min/1.73m2, persistent albuminuria (ACR ≥ 300 mg/g, PCR ≥ 500 mg/g, or Udip ≥ 2+), or progressive and persistent decline in eGFR until index nephrology visit (≥ 5 mL/min/1.73m2). RESULTS: Of 69,372 patients with CKD, 28,518 (41%) were referred in a guideline concordant manner. The overall rate of first outpatient visits to nephrology increased from 2006 to 2019, although guideline discordant referrals showed a greater increase (trend 21.9 per million population/year, 95% confidence interval 4.3, 39.4) versus guideline concordant referrals (trend 12.4 per million population/year, 95% confidence interval 5.7, 19.0). The guideline concordant cohort were more likely to be on renin-angiotensin system blockers or beta blockers (hazard ratio 1.14, 95% confidence interval 1.12, 1.16), and had a higher risk of CKD progression (hazard ratio 1.09, 95% confidence interval 1.06, 1.13), kidney failure (hazard ratio 7.65, 95% confidence interval 6.83, 8.56), cardiovascular event (hazard ratio 1.40, 95% confidence interval 1.35,1.45) and mortality (hazard ratio 1.58, 95% confidence interval 1.52, 1.63). CONCLUSIONS: A significant proportion nephrology referrals from primary care were not consistent with current guideline-recommended criteria for referral. Further work is needed to identify quality improvement initiatives aimed at enhancing referral patterns of patients with CKD.

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.

Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4+): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences.

Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder: Synopsis of the Kidney Disease: Improving Global Outcomes 2017 Clinical Practice Guideline Update.

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a selective update of the prior CKD-MBD guideline published in 2009. The guideline update and the original publication are intended to assist practitioners caring for adults with CKD and those receiving long-term dialysis. Methods: Development of the guideline update followed an explicit process of evidence review and appraisal. The approach adopted by the Work Group and the evidence review team was based on systematic reviews of relevant trials, appraisal of the quality of the evidence, and rating of the strength of recommendations according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Searches of the English-language literature were conducted through September 2015 and were supplemented with targeted searches through February 2017. Final modification of the guidelines was informed by a public review process involving numerous stakeholders, including patients, subject matter experts, and industry and national organizations. Recommendations: The update process resulted in the revision of 15 recommendations. This synopsis focuses primarily on recommendations for diagnosis of and testing for CKD-MBD and treatment of CKD-MBD that emphasizes decreasing phosphate levels, maintaining calcium levels, and addressing elevated parathyroid hormone levels in adults with CKD stage G3a to G5 and those receiving dialysis. Key elements include basing treatment on trends in laboratory values rather than a single abnormal result and being cautious to avoid hypercalcemia when treating secondary hyperparathyroidism.

Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what's changed and why it matters.

The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD represents a selective update of the prior CKD-MBD Guideline published in 2009. This update, along with the 2009 publication, is intended to assist the practitioner caring for adults and children with chronic kidney disease (CKD), those on chronic dialysis therapy, or individuals with a kidney transplant. This review highlights key aspects of the 2017 CKD-MBD Guideline Update, with an emphasis on the rationale for the changes made to the original guideline document. Topic areas encompassing updated recommendations include diagnosis of bone abnormalities in CKD-mineral and bone disorder (MBD), treatment of CKD-MBD by targeting phosphate lowering and calcium maintenance, treatment of abnormalities in parathyroid hormone in CKD-MBD, treatment of bone abnormalities by antiresorptives and other osteoporosis therapies, and evaluation and treatment of kidney transplant bone disease.

Revisiting KDIGO clinical practice guideline on chronic kidney disease-mineral and bone disorder: a commentary from a Kidney Disease: Improving Global Outcomes controversies conference.

A new definition and classification of chronic kidney disease-mineral and bone disorder (CKD-MBD) was proposed in 2005 and it was later followed by a guideline publication on this topic from Kidney Disease: Improving Global Outcomes (KDIGO) in 2009. This work recognized that CKD-MBD is a syndrome of bone abnormalities, laboratory abnormalities, and vascular calcification linked to fractures, cardiovascular disease, and mortality. Because of limited data at the time of the original guideline systematic review, many of the recommendations were cautiously vague. KDIGO convened a Controversies Conference in October 2013 to review the CKD-MBD literature published since the 2009 guideline. Specifically, the objective of this conference was to determine whether sufficient new data had emerged to support a reassessment of the CKD-MBD guideline and if so to determine the scope of these potential revisions. This report summarizes the results of these proceedings, highlighting important new studies conducted in the interval since the original KDIGO CKD-MBD guideline.

A population-based study on care and clinical outcomes in remote dwellers with heavy proteinuria.

Patients with proteinuria are at high risk of cardiovascular and renal complications. Since this risk can be reduced by appropriate interventions, we hypothesized that remote dwellers, who are known to have lower access to health care, might have a higher risk of complications. Using a database of all adults with at least one measure of urine protein between May 2002 and March 2009, we examined the frequency of heavy proteinuria, quality of care delivery, and rates of adverse clinical outcomes across travel distance categories to the nearest nephrologist. Heavy proteinuria was defined by an albumin:creatinine ratio ⩾60 mg/mmol, protein:creatinine ratio ⩾100 mg/mmol, or protein ⩾2+ on dipstick urinalysis. Of 1,359,330 subjects in the study, 262,209 were remote dwellers. The overall prevalence of proteinuria was 2.3%, 2.9%, and 2.5% in those who live >200, 100.1-200, and 50.1-100 km, respectively, as compared to 1.5% in those who live within 50 km of the nearest nephrologist (P<0.001). Similarly, the prevalence of heavy proteinuria was increased among remote dwellers compared to urban dwellers (P=0.001 for trend). There were no differences in markers of good-quality care or the rate of adverse outcomes (all-cause mortality, heart failure, and renal outcomes) across distance categories. However, the rates of hospitalizations and stroke were significantly higher with increased distance from the nearest nephrologist (P<0.001and 0.02, respectively). In conclusion, heavy proteinuria was common in Alberta residents, especially in remote dwellers. Care seemed similar across distance categories of travel, but with higher risk of hospitalizations and stroke among remote dwellers. Further work is needed to understand the basis for the increased risk of hospitalizations and stroke.

Incidence and causes of end-stage renal disease among Aboriginal children and young adults.

BACKGROUND: Although Aboriginal adults have a higher risk of end-stage renal disease than non-Aboriginal adults, the incidence and causes of end-stage renal disease among Aboriginal children and young adults are not well described. METHODS: We calculated age- and sex-specific incidences of end-stage renal disease among Aboriginal people less than 22 years of age using data from a national organ failure registry. Incidence rate ratios were used to compare rates between Aboriginal and white Canadians. To contrast causes of end-stage renal disease by ethnicity and age, we calculated the odds of congenital diseases, glomerulonephritis and diabetes for Aboriginal people and compared them with those for white people in the following age strata: 0 to less than 22 years, 22 to less than 40 years, 40 to less than 60 years and older than 60 years. RESULTS: Incidence rate ratios of end-stage renal disease for Aboriginal children and young adults (age < 22 yr, v. white people) were 1.82 (95% confidence interval [CI] 1.40-2.38) for boys and 3.24 (95% CI 2.60-4.05) for girls. Compared with white people, congenital diseases were less common among Aboriginal people aged less than 22 years (odds ratio [OR] 0.56, 95% CI 0.36-0.86), and glomerulonephritis was more common (OR 2.18, 95% CI 1.55-3.07). An excess of glomerulonephritis, but not diabetes, was seen among Aboriginal people aged 22 to less than 40 years. The converse was true (higher risk of diabetes, lower risk of glomerulonephritis) among Aboriginal people aged 40 years and older. INTERPRETATION: The incidence of end-stage renal disease is higher among Aboriginal children and young adults than among white children and young adults. This higher incidence may be driven by an increased risk of glomerulonephritis in this population.

Survival and transplantation outcomes of children less than 2 years of age with end-stage renal disease.

BACKGROUND: Young children with end-stage renal disease (ESRD) requiring renal replacement therapy (RRT) have traditionally experienced high rates of morbidity and mortality; however, detailed long-term follow-up data is limited. METHODS: Using a population-based retrospective cohort with data from a national organ failure registry and administrative data from Canada's universal health care system, we analysed the outcomes of 87 children starting RRT (before age 2 years) and followed them until death or date of last contact [median follow-up 4.7 years, interquartile range (IQR) 1.4-9.8). We assessed secular trends in survival and the influence of: (1) age at start of RRT and (2) etiology of ESRD with survival and time to transplantation. RESULTS: Patients were mostly male (69.0 %) with ESRD predominantly due to renal malformations (54.0 %). Peritoneal dialysis was the most common initial RRT (83.9 %). Fifty-seven (65.5 %) children received a renal transplant (median age at first transplant: 2.7 years, IQR 2.0-3.3). During 490 patient-years of follow-up, there were 23 (26.4 %) deaths, of which 22 occurred in patients who had not received a transplant. Mortality was greater for patients commencing dialysis between 1992 and 1999 and among the youngest children starting RRT (0-3 months). Children with ESRD secondary to renal malformations had better survival than those with ESRD due to other causes. Among the transplanted patients, all but one survived to the end of the observation period. CONCLUSION: Children who start RRT before 3 months of age have a high risk of mortality. Among our paediatric patient cohort, mortality rates were much lower among children who had received a renal transplant.

Dialysis and transplantation among Aboriginal children with kidney failure.

BACKGROUND: Relatively little is known about the management and outcomes of Aboriginal children with renal failure in Canada. We evaluated differences in dialysis modality, time spent on dialysis, rates of kidney transplantation, and patient and allograft survival between Aboriginal children and non-Aboriginal children. METHODS: For this population-based cohort study, we used data from a national pediatric end-stage renal disease database. Patients less than 18 years old who started renal replacement treatment (dialysis or kidney transplantation) in nine Canadian provinces (Quebec data were not available) and all three territories between 1992 and 2007 were followed until death, loss to follow-up or end of the study period. We compared initial modality of dialysis and time to first kidney transplant between Aboriginal children, white children and children of other ethnicity. We examined the association between ethnicity and likelihood of kidney transplantation using adjusted Cox proportional hazard models for Aboriginal and white children (data for the children of other ethnicity did not meet the assumptions of proportional hazards). RESULTS: Among 843 pediatric patients included in the study, 104 (12.3%) were Aboriginal, 521 (61.8%) were white, and 218 (25.9%) were from other ethnic minorities. Hemodialysis was the initial modality of dialysis for 48.0% of the Aboriginal patients, 42.7% of the white patients and 62.6% of those of other ethnicity (p < 0.001). The time from start of dialysis to first kidney transplant was longer among the Aboriginal children (median 1.75 years, interquartile range 0.69-2.81) than among the children in the other two groups (p < 0.001). After adjustment for confounders, Aboriginal children were less likely than white children to receive a transplant from a living donor (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.21-0.61) or a transplant from any donor (HR 0.54, 95% CI 0.40-0.74) during the study period. INTERPRETATION: The time from start of dialysis to first kidney transplant was longer among Aboriginal children than among white children. Further evaluation is needed to determine barriers to transplantation among Aboriginal children.

Graft failure and adaptation period to adult healthcare centers in pediatric renal transplant patients.

BACKGROUND: Transfer from pediatric to adult care may require a period of adaptation to the new healthcare environment. We sought to determine whether this adaptation period was associated with an increased risk of graft failure. METHODS: Children (age, 0-18 years) recorded in the Canadian Organ Replacement Register who received a first kidney transplant in a pediatric health center between 1992 and 2007, and who had more than or equal to 3 months of graft function, were followed up until death, loss to follow-up, or December 31, 2007. Cox proportional hazards models were used to estimate the excess risk associated with a period of adaptation to adult-oriented care, defined as the interval 0.5 years before to 2.5 years after the first recorded adult care visit. Models were adjusted for age, gender, donor source, and ethnicity. RESULTS: Of the 413 patients evaluated, 149 were transferred to adult care during study period. In total, 78 (18.9%) patients experienced graft failure-23 during the adaptation period. Compared with the period before adaptation, the adjusted hazard ratio for graft loss within the adaptation period was 2.24 (95% confidence interval [CI]: 1.19-4.20). The adjusted graft failure rate was 2.26 (1.04-4.93) times higher after 18 years of age than between 0 and 13 years. Aboriginal ethnicity and deceased donor source were also associated with a significantly higher risk of graft failure. CONCLUSIONS: The period of adaptation to adult-oriented care is associated with a high risk of graft failure in pediatric renal transplant patients.

Survival in pediatric dialysis and transplant patients.

BACKGROUND AND OBJECTIVES: Long-term follow-up data are few in children with ESRD. We sought to describe long-term survival, assess risk factors for death, and compare survival between two time periods in pediatric ESRD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used a population-based retrospective cohort utilizing data from a national organ failure registry and from Canada's universal healthcare system. We included 843 children (ages, 0 to 18) initiating renal replacement therapy from 1992 to 2007 and followed them until death or date of last contact (median follow-up, 6.8 years; interquartile range, 3.0 to 10.6). We assessed risk factors for death and examined cause-specific mortality. RESULTS: During 5991 patient-years of follow-up, 107 (12.7%) patients died. Unadjusted cumulative survival for the cohort was: 91.7% (95% CI, 89.8 to 93.7%) at 5 years and 85.8% (95% CI, 82.8 to 88.8%) at 10 years. Among patients commencing dialysis, overall adjusted survival was poorest among those who started dialysis at age <1 year. No secular trends in survival were noted for either dialysis or transplant patients. The proportion of incident patients receiving pre-emptive transplantation increased over time. Pre-emptively transplanted patients did not demonstrate superior adjusted survival compared with those who spent >2 years on dialysis before transplant (hazard ratio, 1.53; 95% CI, 0.63 to 3.67). CONCLUSIONS: No significant improvements in survival were observed among ESRD patients over the study period. Time with transplant function had the strongest association with survival. Pre-emptive transplantation was not associated with improved survival in adjusted models.

Overview of the Canadian pediatric end-stage renal disease database.

BACKGROUND: Performing clinical research among pediatric end-stage renal disease patients is challenging. Barriers to successful initiation and completion of clinical research projects include small sample sizes and resultant limited statistical power and lack of longitudinal follow-up for hard clinical end-points in most single center studies. DESCRIPTION: Existing longitudinal organ failure disease registry and administrative health datasets available within a universal access health care system can be used to study outcomes of end-stage renal disease among pediatric patients in Canada. To construct the Canadian Pediatric End-Stage Renal Disease database, registry data were linked to administrative health data through deterministic linkage techniques creating a research database which consists of socio-demographic variables, clinical variables, all-cause hospitalizations, and relevant outcomes (death and renal allograft loss) for this patient population. The research database also allows study of major cardiovascular events using previously validated administrative data definitions. CONCLUSION: Organ failure registry linked to health administrative data can be a powerful tool to perform longitudinal studies in pediatric end-stage renal disease patients. The rich clinical and demographic information found in this database will facilitate study of important medical and non-medical risk factors for death, graft loss and cardiovascular disease among pediatric end-stage renal disease patients.

Cost-effectiveness of hemofiltration to prevent contrast nephropathy in patients with chronic kidney disease.

OBJECTIVE: Prophylactic hemofiltration has been reported, in one study, to reduce renal complications and death but necessitates additional up-front health care resource deployment in a critical care setting. We sought to explore the potential scope and cost-effectiveness of this strategy. DESIGN: Economic evaluation using decision analysis. SETTING: Tertiary or quaternary care hospital. PATIENTS: Subjects undergoing angiography at risk for developing contrast nephropathy. INTERVENTION: Prophylactic hemofiltration was compared with intravenous saline. Secondary models incorporated sodium bicarbonate and N-acetylcysteine as comparators. MEASUREMENT AND MAIN RESULTS: The cost per quality-adjusted life year (QALY) gained with hemofiltration compared with intravenous saline in high-risk subjects (mean serum creatinine, 265 micromol/L) was 3,900 US dollars. This finding was sensitive to variations in several important variables. For instance, the cost-effectiveness ratio became less attractive (i.e., >50,000 US dollars/QALY) when hemofiltration was used in lower-risk subjects (serum creatinine, <265 micromol/L). The cost-effectiveness remained <50,000 US dollars/QALY provided that the relative risk of hemofiltration compared with saline alone was below 0.65 (reported relative risk, 0.10). Although based on indirect comparison of clinical efficacy, when N-acetylcysteine or sodium bicarbonate was used as the comparator, the cost per QALY gained for hemofiltration became markedly less attractive (50,100 US dollars and >1,000,000 US dollars), although the relative effectiveness of these three strategies strongly influenced the results. CONCLUSIONS: Use of prophylactic hemofiltration in patients at high risk for contrast nephropathy may be potentially cost-effective only if certain conditions are satisfied, and its attractiveness is materially diminished when compared to other strategies. As this invasive therapy would entail certain immediate resource outlay, before considering its implementation it is crucial to confirm the clinical effectiveness and health care resource consequences of hemofiltration relative to current standards of care in future studies.