KDOQI US Commentary on the KDIGO 2026 Clinical Practice Guideline for the Management of Anemia in CKD.

KDOQI US Commentary on the 2012 KDIGO Clinical Practice Guideline for Anemia in CKD

Evolution of Treatment for Anemia in Chronic Kidney Disease

Canadian Society of Nephrology Commentary on the 2009 KDIGO Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of CKD–Mineral and Bone Disorder (CKD-MBD)

The KDOQI US Commentary on KDIGO Anemia Guideline and Quality of Life

Hypoxia-Inducible Factor–Prolyl Hydroxylase Inhibitors for the Treatment of Anemia in CKD: Additional Pieces of the Jigsaw Puzzle

A Decade After the KDOQI CKD Guidelines: Impact on CKD Guidelines

Background and Aims Anaemia is a common complication of chronic kidney disease (CKD), affecting up to 53.4% of patients with Stage 5 CKD compared to 8.4% of patients with Stage 1 CKD [1]. Anaemia of CKD is associated with increased risk of cardiovascular events and death, increased healthcare resource utilisation (HRU), and reduced health-related quality of life (HRQoL) [2]. Established treatments for anaemia of CKD include erythropoiesis-stimulating agents (ESAs) [1,2]; however, hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs), targeting both erythropoietin production and iron metabolism (the two key mechanisms of anaemia of CKD), are an emerging class of agents in this indication [3]. The cost and HRQoL burden associated with anaemia of CKD treatment is not well characterised.1 Thus, we conducted a systematic literature review (SLR) to evaluate published economic models (including the cost inputs, time horizon, subgroups, and clinical assumptions used) and HRU data in patients with anaemia of CKD. Findings of the SLR will help guide future economic model development and inform economic evaluation strategies as part of health technology assessment submissions to support daprodustat, an HIF-PHI under development for use in both dialysis-dependent and non-dialysis-dependent patients. Method Relevant publications were identified using structured searching of MEDLINE, Embase, MEDLINE In-Process, Cochrane Controlled Trials Register, and the Cochrane Database of Systematic Reviews from database inception to 10 April 2022 using disease- (e.g. CKD, chronic kidney failure, anaemia) and economic-associated (e.g. economics, economic evaluation, quality-adjusted life-years, model structure) search terms. Additional supplemental searches (conference proceedings [2016–2021], grey literature, and bibliographies) were conducted. Studies were assessed for inclusion or exclusion by two independent reviewers, with any discrepancies resolved by a third reviewer. Objectives were to determine the structure of any published economic models and the availability of health utility data in patients with anaemia and additional complications of CKD, and to examine what cost inputs, time horizons, subgroups, and clinical assumptions are used to inform economic modelling. Results From 1397 citations identified in the searches, 40 primary studies were included in the final analysis. Review of the data revealed an established approach for modelling the ESA cost-effectiveness (i.e. a Markov model with health states defined according to CKD treatment received or anaemia status): most studies were conducted from a North American or European perspective, time horizons varied, and reporting of cycle length was poor. Only one economic evaluation included an HIF-PHI model: given the different mechanisms of action of ESAs and newer treatments, a modelling strategy focused mainly on a Markov approach may not be the most optimal way of assessing cost-effectiveness in anaemia of CKD where HIF-PHIs are used. Considerations of modelling factors that could influence cost-effectiveness of HIF-PHIs are shown in Fig. 1. While existing models typically only stratified patient populations according to age (<65 vs >65 years), for appropriate modelling of treatment effectiveness, the impact of prior treatments (including response to prior ESAs) was also considered. As in every model, comorbidities may also have a role in effect modification and this impact will need to be considered in economic models of anaemia of CKD treatment. Due to the natural history of anaemia in CKD, innovative modelling techniques that retain the Markov approach and which account for respective haemoglobin levels, CKD stage, and potential kidney transplantation should be incorporated into the economic evaluation (Fig. 2). Conclusion Adjustment of existing models using the approaches described may provide more reliable estimates of treatment efficacy in a highly heterogenous population of patients with anaemia of CKD.

Background and Aims While the percentage of women entering nephrology has increased over the years, women representation and sex disparities in the authorship of major nephrology Clinical practice guidelines (CPG) has not been examined. Our study evaluates current sex disparities and women representation, and the nationalities of women authors in nephrology CPGs developed by the Kidney Disease: Improving Global Outcomes (KDIGO), Kidney Disease Outcomes Quality Initiative (KDOQI), and the European Renal Best Practice (ERBP), the official guideline body of the ERA-EDTA. Method We examined the number of female versus male guideline workgroup members (panelists) for all available CPGs in each of the three organizations as of Dec. 2020, which are available on their respective websites. We discerned the sex of the panelists based on google search and their affiliated institutional websites. We obtained the nationalities of the workgroup members from the authorship information of the respective CPG. Results Of the total 488 panelists in all three organizations, 115 (23.6%) were females and 373 (76.4%) males. KDIGO had 184 panelists, of which 46 (25%) were females. The CPGs with the highest and the least women representation are ‘Diabetes in Chronic Kidney Disease (CKD)’ (41.2%) and ‘Anemia in CKD’ (11.8%), respectively. The countries with the highest number of women representations are the USA (20), followed by Canada (6), and China (4). In KDOQI, 39 (31%) of 127 panelists were female. While CPGs related to ‘Evaluation and management of CKD’ and ‘Nutrition in children with CKD’ each had 50% female panelists, ‘Blood pressure management in CKD’ CPG had 10% female panelists. 28 (72%) of the total 39 women were from the USA. The ERBP had 30 (17%) females of the total 177 panelists. ‘CKD in older patients’ CPG comprised 42.1% female panelists. CPGs for ‘Glycemic control in diabetes’ and ‘Glucose lowering drugs in diabetes’ had no female panelists. Belgium and UK each had six women representatives, while France and The Netherlands 4 women representatives each. Conclusion The guidelines developed by the most prominent organizations – KDIGO, KDOQI, and ERA-EDTA have less than 25% women representation. While it is encouraging to note that there is more women representation in some of the CPGs developed by KDIGO in 2020, evaluating the barriers contributing to the under-representation of women in major nephrology organizations is warranted. Also notable is a lack of women representation from developing countries.

Peginesatide: First once-monthly ESA

Definition and Classification of CKD: The Debate Should Be About Patient Prognosis—A Position Statement From KDOQI and KDIGO

Epoetinalfa, the first erythropoiesis-stimulating agent (ESA), was approved in 1989 for the treatment of anemia in patients with chronic kidney disease (CKD). By 1991, in dialysis, there were no longer patients requiring regular transfusions for severe anemia (eg, hemoglobin concentration, <7g/dL [toconvert togramsper liter,multiplyby 10]), anddialysis center–based transfusions haddecreased bymore than 65%.1 For many reasons, including the establishment of financial incentives that rewarded overuse, aggressive treatment of anemia in dialysis-requiring patients with increasingly higher doses of ESA became the norm, and mean hemoglobin concentrations in patients receivingdialysis increased from10.5 g/dL in 1995 to 12.0 g/dL in 2005.1,2 Anemia during CKD stages 4 and 5ND (not receiving dialysis) is less frequent and less severe than in patients receiving dialysis. In 1 observational study, mean hemoglobin concentrationwas 12.0 g/dL in stage 4 and 10.9 g/dL in stage 5ND. Consequently, patients with CKD do not require transfusions except during acutemedical illness, atwhichpoint their prior degree of anemia is relatively unimportant. In this issueof JAMA InternalMedicine,Winkelmayer and colleagues3 examineddata onMedicare recipients 67 years or older who started dialysis to capture information on anemia management practices in the 2 years prior to initiation of dialysis. In 2010, nondialysis ESA administration in physician’s offices accounted for $701 million in Medicare Part B spending. Erythropoiesis-stimulating agents increase hemoglobin levels andmay reduce the need for transfusions, but trials in patients with CKD who either were or were not receiving dialysis show that ESAs increase the risk of death, thrombovascularandcardiovascularevents, cancer recurrence,andcancerrelated death and have not been proven to improve quality of life or fatigue.4-7 Howdid these drugs becomeblockbusters? I place the observational data of Winkelmayer et al in the context of contemporaneous trial results and guidelines addressing anemia management in CKD. Paralleling growth observed in patients receiving dialysis, Winkelmayer et al found marked growth in ESA use between 1995and2007, from3.2%to40.8% inpatientswithCKD who were not receiving dialysis.3 In adjusted analyses, patients in 2007 were 11.5 times more likely to receive an ESA, and treatment started 7months earlier relative to dialysis initiation than in 1995.3 Growth in ESA use was slower between 1995and2000butaccelerated in2001,correspondingwithpublication of the first Kidney Disease Outcomes Quality Initiative (KDOQI)guidelinesaddressinganemia in thenon–dialysisrequiring CKD population. Amgen, the maker of ESAs, is the “foundingandprincipal sponsorof theKDOQIguidelines.”8(pA6) Both the 1997 KDOQI guidelines, which focused on dialysis, and the 2001 guidelines recommended targeting hemoglobin to 11 to 12 g/dL, higher than the then-approvedUSFood and Drug Administration (FDA) target of 10 to 12 g/dL. The guidelines outlined 6 strands of largely associational evidence linking hemoglobin concentrations below 10 g/dLwith worse outcomes. The message from guidelines, ESA manufacturers,dialysis chains, andanemiaexperts to the renal communitywas that anemiawasharmful and thatmaintaininghemoglobin concentrations above 11 g/dL was beneficial.2 The KDOQI anemia guidelineswere fundedby themakers ofESAs, and many anemia experts, including me, were paid by ESA makers to expound on the value of treating anemia in CKD. By 2001, the only completed large outcome trial of ESAs was the Normal Hematocrit Trial. Terminated in 1996 by the data safetymonitoring committeebecause “...the resultswere nearing the statistical boundary of a higher mortality rate in the normal hematocrit group”4(p589) and published in 1998, it had randomized dialysis-requiring patients to an ESA-driven hemoglobin target of 9 to 11 g/dL or a normal range of 13 to 15 g/dL.4 In the published report, the group with the higher hemoglobin target had a statistically insignificant higher risk of the primary end point (death or nonfatal myocardial infarction [MI], 202 events [183 deaths, 19 MIs] vs 164 events [150 deaths, 14 MIs]; risk ratio [RR], 1.3 [95% CI, 0.9-1.9]) but had reduced transfusions and improved physical functioning as measured on the SF-36 quality-of-life instrument.4 The framers of the 2001 guidelines believed that these dangers conflicted with data from observational and small intervention trials and noted that the higher risk of death or nonfatal MI “was not statistically significant at the time the study was terminated.”9(pS191)However, thetrial reportwas less thanforthcoming as it had adjusted theCIs for repeated reviews anddid not report theunadjustedCIs.4,5 In2007, theFDAreported that the high-target arm had significantly higher unadjusted risk for death (RR, 1.27 [95%CI, 1.04-1.54]) and death plusMI (RR, 1.28 [95% CI, 1.06-1.56]).4,5 In 2012, it was also revealed that, contrary to the 1998 report, targetingnormalhemoglobin concentrations had led to no improvement in any component of quality of life.5 Knowledge of the serious risk of ESAswith no benefits in 1998maywellhavealtered the trajectoryof thedata of Winkelmayer et al. Although Amgen and the authors believed that the trialwas flawedanddidnot showdefinitiveevidence of harm,withholding the unadjusted statistics and the real quality-of-life results prevented physicians and guideline groups from reaching their own conclusions. Winkelmayer et al showthatmeanhemoglobinconcentrationpeaked in2006,useofESAsreachedaplateau in2007, then bothgraduallydeclined through2010.3 In2006, theKDOQIhad publishednewanemiaguidelines, stating that all patientswith Related article page 699 Research Original Investigation Trends in Predialysis Anemia Care

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors are a new class of agents for the treatment of anemia in chronic kidney disease (CKD). Unlike traditional treatments such as erythropoiesis-stimulating agents (ESAs), HIF-PH inhibitors are orally administered drugs and may increase endogenous erythropoietin and improve iron homeostasis. However, a significant concern is their possible side effect on blood pressure. The current mini-review summarizes the data of 26 randomized controlled (placebo or ESAs) trials on six different HIF-PH inhibitors with regard to their potential influence on blood pressure and hypertension in the management of anemia in CKD. Overall, the use of HIF-PH inhibitors was associated with a higher risk of hypertension than placebo (pooled risk ratio 1.36, 95% confidence interval [CI] 1.16-1.59), but a lower risk of hypertension than ESA treatment (pooled risk ratio 0.92, 95% CI 0.86-0.98), especially in CKD patients not undergoing dialysis (pooled risk ratio 0.85, 95% CI 0.73-0.98). This review highlights the importance of blood pressure monitoring during the treatment of HIF-PH inhibitors, especially out-of-office blood pressure measurement.

Background Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors were introduced for the treatment of anaemia in chronic kidney disease (CKD) in Japan in 2020; however, data on their use in clinical practice remain limited. Methods This retrospective cohort study used data from the Medical Data Vision database to assess treatment patterns and hemoglobin trends in non-dialysis-dependent (NDD)-CKD anaemia. Cohort 1 included patients starting HIF-PH inhibitors or erythropoiesis-stimulating agents (ESAs) between 2021 and 2024, while Cohort 2 included patients who had received ESAs in 2020. Sub-cohort 1, patients with iron repletion status in Cohort 1, were also examined. Results Cohort 1 included 9,253 patients. The patients starting HIF-PH inhibitors increased annually from 15.1% in 2021 to 54.8% in the first quarter of 2024. In Sub-cohort 1, prescriptions of HIF-PH inhibitors also annually increased. In these cohorts, initiation with HIF-PH inhibitors showed trends to maintain higher hemoglobin levels than ESAs. In patients with functional iron deficiency, the reduction in proportion with Hb <10 g/dL was more pronounced in HIF-PH inhibitors than ESAs. Cohort 2 (n = 1,998) had a low annual switch rate from ESAs to HIF-PH inhibitors (2.4%–3.9%), and improvement of anaemia was observed in the switched patients in whom ESAs do not sufficiently correct anaemia. Conclusions Real-world database analysis shows that initiation of HIF-PH inhibitors for renal anaemia in NDD-CKD increased to match that of ESAs by 2024, although switching from ESAs remained low. HIF-PH inhibitors showed a trend towards improvement in anaemia compared to ESAs, suggesting clinical benefit.

Nomenclature for kidney function and disease: Executive summary and glossary from a Kidney Disease: Improving Global Outcomes (KDIGO) consensus conference

The 2026 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Anemia in Chronic Kidney Disease represents a substantial update, more than a decade since the previous KDIGO guideline on the topic. This time lapse was necessary for accumulating new scientific evidence meaningful for an updated guideline. The new guideline now includes updated recommendations and practice points for anaemia management, incorporating recent evidence on intravenous iron therapies and hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs). This European Renal Best Practice commentary critically evaluates and comments on relevant and newer recommendations and practice points, focusing on key aspects from a European perspective. The new guideline emphasises the need for a comprehensive evaluation of the patient at the time of diagnosis, to identify additional causes of anaemia other than erythropoietin insufficiency. Coherently, the timing and the type of treatment should be individualised. Moreover, it introduces more proactive thresholds for intravenous iron supplementation, especially for haemodialysis patients. Erythropoiesis-stimulating agents (ESAs) are recommended as the preferred first-line therapy due to persisting concerns regarding cardiovascular safety and methodological limitations of available HIF-PHI trials. The commentary includes considerations on special aspects not considered by the new KDIGO guideline, such as pregnancy, gender-specific considerations, and interactions with SGLT2 inhibitors or inflammation. The commentary also highlights regional regulatory differences between European and US drug approvals for HIF-PHIs. While supporting most recommendations, European nephrologists should consider local contexts, regulatory approvals, and emerging evidence when implementing these guidelines in clinical practice.