KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease

S267 Table 42. Studies examining the timing of dialysis in people with CKD S268 Table 43. People with kidney failure who receive comprehensive conservative care S275 Table 44. Clinical questions and systematic review topics in PICOS format S280 Table 45. Classification for certainty of evidence S280 Table 46. GRADE system for grading the certainty of evidence S281 Table 47. KDIGO nomenclature and description for grading recommendations S281 Table 48. Determinants of the strength of recommendation FIGURES S136 Figure 1. Associations of chronic kidney disease (CKD) staging by estimated glomerular filtration rate by creatinine and cystatin C (eGFRcr-cys) and albumin-to-creatinine ratio (ACR) categories and risks for 10 common complications by age in multivariable-adjusted analyses S138 Figure 2. Age-standardized chronic kidney disease disability-adjusted life-year (DALY) rates for each location by sociodemographic index, both sexes combined, 2019 S139 Figure 3. Screening algorithm for diagnosis and staging of chronic kidney disease (CKD) in adults S141 Figure 4. Special considerations for chronic kidney disease (CKD) care across the lifespan S145 Figure 5. Associations of chronic kidney disease (CKD) staging by estimated glomerular filtration rate by creatinine (eGFRcr) and albumin-to-creatinine ratio (ACR) categories and risks for 10 common complications in multivariable-adjusted analyses S146 Figure 6. Associations of chronic kidney disease (CKD) staging by estimated glomerular filtration rate by creatinine and cystatin C (eGFRcr-cys) and albumin-to-creatinine ratio categories and risks for 10 common complications in multivariable-adjusted analyses S147 Figure 7. Hazard ratios for adverse outcomes using the continuous model of estimated glomerular filtration rate (eGFR), comparison of the shape of associations between creatinine-based eGFR (eGFRcr) and creatinine and cystatin C–based eGFR (eGFRcr-cys) in the population with cystatin C (eGFRcr-cys population) S173 Figure 8. Evaluation of cause of chronic kidney disease (CKD) S174 Figure 9. Actionable genes in kidney disease S175 Figure 10. Proposed organization for implementing genetics in nephrology S177 Figure 11. Approach to glomerular filtration rate (GFR) evaluation using initial and supportive tests S182 Figure 12. Sources and magnitude of error around measured glomerular filtration rate (mGFR) and estimated GFR (eGFR) S197 Figure 13. Frequency of monitoring glomerular filtration rate (GFR) and albuminuria in people with chronic kidney disease (CKD) S199 Figure 14. (a) Predicted risk of kidney failure and (b) ‡40% decline in estimated glomerular filtration rate (eGFR) by chronic kidney disease (CKD) eGFR (G1–G5) and albumin-to-creatinine ratio (ACR) (A1–A3) categories in Optum Labs Data Warehouse S201 Figure 15. Transition from an estimated glomerular filtration rate (eGFR)-based to a risk-based approach to chronic kidney disease care S202 Figure 16. Comparison of risk of chronic kidney disease (CKD) progression (5-year probability of estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m 2 ) versus kidney failure in adults with CKD G1– G2 calculated from the risk equation available at https://www.ckdpc.org/risk-models.html S205 Figure 17. Chronic kidney disease (CKD) treatment and risk modification S206 Figure 18. Holistic approach to chronic kidney disease (CKD) treatment and risk modification S208 Figure 19. Protein guideline for adults with chronic kidney disease not treated with dialysis c o n t e n t s www.kidney-international.org S120 Kidney International (2024) 105 (Suppl 4S), S117–S314 S209 Figure 20. Average protein content of foods in grams S214 Figure 21. Algorithm for monitoring of potassium and estimated glomerular filtration rate (eGFR) after the initiation of renin-angiotensin system inhibitors S215 Figure 22. Effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) with kidney disease outcomes by diabetes status S216 Figure 23. Effects of sodium-glucose cotransporter-2 (SGLT2) inhibition versus placebo on cardiovascular and mortality outcomes by diabetes status and trial population S217 Figure 24. Effects of sodium-glucose cotransporter-2 (SGLT2) inhibition versus placebo on kidney failure (chronic kidney disease [CKD] trials) S219 Figure 25. Effects of empagliflozin versus placebo on annual rate of change in estimated glomerular filtration rate (GFR) by key subgroups in the Study of Heart and Kidney Protection With Empagliflozin (EMPA- KIDNEY) S220 Figure 26. Serum potassium monitoring during treatment with a nonsteroidal mineralocorticoid receptor antagonist (MRA) (finerenone) S221 Figure 27. Effect of finerenone versus placebo on kidney and cardiovascular outcomes in pooled analyses from the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO- DKD) and Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD trials) S222 Figure 28. Association between estimated glomerular filtration rate (eGFR) with serum bicarbonate concentration in general population and high-risk cohorts from the Chronic Kidney Disease Prognosis Consortium, by level of albuminuria (A1–A3) S224 Figure 29. Distribution of blood potassium in general population and high-risk cohorts from the Chronic Kidney Disease Prognosis Consortium, by estimated glomerular filtration rate (eGFR) S224 Figure 30. Meta-analyzed adjusted prevalence of hyperkalemia (25th and 75th percentile cohort) in general population and high-risk cohorts from the Chronic Kidney Disease Prognosis Consortium, by diabetes status S225 Figure 31. Serum potassium concentration and confounder-adjusted risk of death by presence or absence of diabetes, heart failure (HF), or chronic kidney disease (CKD) S228 Figure 32. Actions to manage hyperkalemia (potassium >5.5 mmol/l) in chronic kidney disease S228 Figure 33. Potassium absorption rates of plant-based, animal-based, and processed foods S229 Figure 34. Association between estimated glomerular filtration rate (eGFR) and hemoglobin concentration from general population and high-risk cohorts from the Chronic Kidney Disease Prognosis Consortium, by diabetes status S230 Figure 35. Association between estimated glomerular filtration rate (eGFR) with serum concentrations of parathyroid hormone, phosphate, and serum calcium in general population and high-risk cohorts from the Chronic Kidney Disease Prognosis Consortium, by level of albuminuria (A1–A3) S233 Figure 36. Risk of all-cause and cardiovascular mortality by estimated glomerular filtration rate (eGFR) and level of albuminuria from general population cohorts contributing to the Chronic Kidney Disease Prognosis Consortium S235 Figure 37. Effect of lowering low-density lipoprotein (LDL) cholesterol per 1.0 mmol/l on risk of major vascular events by level of estimated glomerular filtration rate (eGFR) at recruitment S237 Figure 38. Predicted 5-year absolute benefits and harms of allocation to aspirin (A) versus control (C) using a secondary or primary prevention strategy, by different levels of risk (based on age and sex) S240 Figure 39. Meta-analyzed adjusted prevalence of atrial fibrillation from cohorts contributing to the Chronic Kidney Disease Prognosis Consortium, by diabetes status S241 Figure 40. Strategies for the diagnosis and management of atrial fibrillation S242 Figure 41. Pooled hazard ratio (HR) comparing non–vitamin K antagonist oral anticoagulants (NOACs) with warfarin among people with chronic kidney disease in terms of stroke S243 Figure 42. Pooled hazard ratio (HR) comparing non–vitamin K antagonist oral anticoagulants (NOACs) with warfarin among people with chronic kidney disease in terms of bleeding S244 Figure 43. Evidence from (a) randomized controlled trials (RCTs) regarding therapeutic anticoagulation dose by glomerular filtration rate (GFR) and (b) in areas where RCTs are lacking S245 Figure 44. Advice on when to discontinue non–vitamin K antagonist oral anticoagulants (NOACs) before procedures (low vs. high risk) www.kidney-international.org c o n t e n t s Kidney International (2024) 105 (Suppl 4S), S117–S314 S121 S248 Figure 45. Selected herbal remedies and dietary supplements with evidence of potential nephrotoxicity, grouped by the continent from where the reports first came S250 Figure 46. Suggested steps in the process of medication review and reconciliation S251 Figure 47. Essential steps for appropriate sick day rule implementation S255 Figure 48. Circumstances for referral to specialist kidney care services and goals of the referral S258 Figure 49. Common symptoms, prevalence, and severity in people with chronic kidney disease S261 Figure 50. Optimal care model by increasing severity of chronic kidney disease (CKD) S262 Figure 51. The chronic care model S262 Figure 52. Specific components of the chronic kidney disease model of care S263 Figure 53. Strategy for effective patient education programs for people with chronic kidney disease (CKD) S264 Figure 54. Telehealth technologies for people with chronic kidney disease (CKD) S265 Figure 55. The process of transition from pediatric to adult care in chronic kidney disease (CKD) S269 Figure 56. Relationship between supportive care, comprehensive conservative care, and end-of-life care S279 Figure 57. Search yield and study flow diagram SUPPLEMENTARY MATERIAL Supplementary File (PDF) Appendix A. Search strategies Table S1. Search strategies for systematic review topics Appendix B. Concurrence with Institute of Medicine (IOM) standards for guideline development Table S2. Guideline development checklist – IOM standards for development of trustworthy clinical practice guidelines Appendix C. Data supplement - Summary of findings (SoF) tables cited in the guideline text Chapter 1. Evaluation of CKD Table S3. Adults and children with or without CKD, estimated GFR (eGFR) based on measurements of cystatin C (eGFRcys); creatinine (eGFRcr); cystatin C and creatinine (eGFRcr-cys) versus measured GFR (mGFR; using urinary or plasma clearance of exogenous filtration marker) Table S4. Adults and children with suspected or diagnosed CKD, native kidney biopsy versus clinical or standard diagnosis or prognosis for studies evaluating diagnostic or prognostic benefit; no comparator for studies evaluating safety Table S5. Adults and children, machine-read quantitative or semiquantitative protein or albumin urine dipstick tests versus laboratory-based methods for measuring urinary protein or albumin (e.g., 24-hour urinary sample, spot urine protein-to-creatinine ratio [PCR], or albumin-to-creatinine ratio [ACR]) Chapter 2. Risk assessment in people with CKD Table S6. Adults, children, and young people with CKD G1–G5, C-statistics of kidney failure risk equations for predicting progression (e.g., Tangri equation [KFRE]) Table S7. Adults, children, and young people with CKD G1–G5, Brier scores of kidney failure risk equations for predicting progression (e.g., Tangri equation [KFRE]) Table S8. Adults, children, and young people with CKD G1–G5, R 2 statistics of kidney failure risk equations for predicting progression (e.g., Tangri equation [KFRE]) Table S9. Adults, children, and young people with CKD G1–G5, sensitivity and specificity to start kidney replacement therapy (KRT) for kidney failure risk equations for predicting progression (e.g., Tangri equation [KFRE]) Chapter 3. Delaying CKD progression and managing its complications Table S10. Adults and children with CKD, sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus placebo or usual care; active comparator (e.g., another glucose-lowering agent) Table S11. Adults and children with CKD and symptomatic hyperuricemia, uric acid–lowering therapy (ULT; allopurinol, benzbromarone, febuxostat, oxipurinol, pegloticase, probenecid, topiroxostat, rasburicase, sulfinpyrazone, lesinurad) versus active comparator, placebo, or usual care Table S12. Adults and children with CKD and asymptomatic hyperuricemia, uric acid–lowering therapy (ULT; allopurinol, benzbromarone, febuxostat, oxipurinol, pegloticase, probenecid, topiroxostat, rasburicase, sulfinpyrazone, lesinurad) versus active comparator, placebo, or usual care Table S13. Adults and children with CKD and ischemic heart disease, angiography or coronary revascularization versus medical treatment c o n t e n t s www.kidney-international.org S122 Kidney International (2024) 105 (Suppl 4S), S117–S314 Table S14. Adults and children with CKD and atrial fibrillation, non–vitamin K antagonist oral anticoagulant (NOAC) with warfarin or NOAC alone versus medical treatment—stroke outcomes Table S15. Adults and children with CKD and atrial fibrillation, non–vitamin K antagonist oral anticoagulant (NOAC) with warfarin or NOAC alone versus medical treatment—bleeding outcomes Appendix D – Data supplement - Summary of findings (SoF) tables not cited in the guideline text Chapter 3. Delaying CKD progression and managing its complications Table S16. Adults and children with CKD but not type 2 diabetes, steroidal mineralocorticoid receptor agonists (MRAs; canrenone, eplerenone, spironolactone) or non-steroidal MRAs (finerenone, esaxerenone) versus active comparator, placebo, or usual care Table S17. Adults and children with CKD at risk for cardiovascular disease (CVD), aspirin versus placebo Appendix E – PRISMA diagrams Chapter 1. Evaluation of CKD Figure S1. PRISMA diagram for the clinical question “What is the diagnostic and prognostic benefit and safety of kidney biopsy among people with CKD?” Figure S2. PRISMA diagram for the clinical question “What is the diagnostic accuracy of eGFR based on measurements of cystatin C, creatinine, or their combination compared to mGFR among people with and without CKD?” Figure S3. PRISMA diagram for the clinical question “In children and young adults with suspected or diagnosed CKD, what is the accuracy of ACR and PCR compared to 24-hour excretion of albumin or protein?” Figure S4. PRISMA diagram for the clinical question “What is the diagnostic accuracy and reproducibility of POC blood creatinine compared to laboratory-based tests among people with suspected or diagnosed CKD?” Figure S5. PRISMA diagram for the clinical question “What is the diagnostic accuracy of quantitative and semiquantitative protein or albumin urine dipstick tests compared to laboratory-based tests among people with suspected or diagnosed CKD?” Chapter 3. Delaying CKD progression and managing its complications Figure S6. PRISMA diagram for the clinical question “What is the effect of SGLT2i compared with placebo, usual care, or an active comparator among people with CKD in terms of mortality, progression of CKD, complications of CKD, and adverse events?” Figure S7. PRISMA diagram for the clinical question “What is the effect of MRAs compared with placebo, usual care, or an active comparator among people with CKD but not type 2 diabetes in terms of mortality, progression of CKD, complications of CKD, and adverse events?” Figure S8. PRISMA diagram for the clinical question “What is the effect of glucagon-like peptide-1 (GLP-1) receptor agonists compared with placebo, usual care, or an active comparator among people with CKD but not type 2 diabetes in terms of mortality, progression of CKD, complications of CKD, and adverse events?” Figure S9. PRISMA diagram for the clinical question “What is the effect of uric acid–lowering therapy compared with placebo, usual care, or an active comparator among people with CKD and hyperuricemia in terms of mortality, progression of CKD, complications of CKD, and adverse events?” Figure S10. PRISMA diagram for the clinical question “What is the effect of aspirin compared to placebo in terms of the primary prevention of cardiovascular disease (CVD) and safety among people with CKD?” Figure S11. PRISMA diagram for the clinical question “What are the effects of angiography or coronary revascularization compared to medical treatment among people with CKD and ischemic heart disease in terms of mortality, CVD events, kidney failure, and acute kidney injury (AKI)?” Figure S12. PRISMA diagram for the clinical question “What are the effects of NOACs with or without warfarin compared to placebo or warfarin alone among people with CKD and atrial fibrillation in terms of stroke and bleeding risks?” www.kidney-international.org c o n t e n t s Kidney International (2024) 105 (Suppl 4S), S117–S314 S123 KDIGO EXECUTIVE COMMITTEE Garabed Eknoyan, MD Norbert Lameire, MD, PhD Founding KDIGO Co-Chairs Wolfgang C. Winkelmayer, MD, MPH, ScD Immediate Past Co-Chair Michel Jadoul, MD KDIGO Co-Chair Morgan E. Grams, MD, PhD, MHS KDIGO Co-Chair Gloria E. Ashuntantang, MD Sunita Bavanandan, MBBS Irene de Lourdes Noronha, MD, PhD Michelle R. Denburg, MD, MSCE Joachim H. Ix, MD, MAS Vivekanand Jha, MD, DM, FRCP, FAMS Holly Kramer, MD, MPH Adrian Liew, MD, MBBS, MRCP, FAMS, FASN, FRCP, MClinEpid Reem A. Mustafa, MD, PhD, MPH Michelle M. O’Shaughnessy, MB, BCh, BAO, MS, MD Patrick Rossignol, MD, PhD Paul E. Stevens, MB, FRCP Rita S. Suri, MD, MSc Irma Tchokhonelidze, MD Marc G. Vervloet, MD, PhD, FERA Wolfgang C. Winkelmayer, MD, MPH, ScD Motoko Yanagita, MD, PhD KDIGO Staff John Davis, Chief Executive Officer Danielle Green, Executive Director Melissa Thompson, Chief Operating Officer Michael Cheung, Chief Scientific Officer Amy Earley, Guideline Development Director Jennifer King, Director of Medical Writing Tanya Green, Events Director Coral Cyzewski, Events Coordinator Kathleen Conn, Director of Communications K D I G O e x e c u t i v e c o m m i t t e e www.kidney-international.org S124 Kidney International (2024) 105 (Suppl 4S), S117–S314 Reference keys NOMENCLATURE AND DESCRIPTION FOR RATING GUIDELINE RECOMMENDATIONS Within each recommendation, the strength of recommendation is indicated as Level 1 or Level 2, and the certainty of the supporting evidence is shown as A, B, C, or D. Grade Implications Patients Clinicians Policy Level 1 “We recommend” Most people in your situation would want the recommended course of action, and only a small proportion would not. Most patients should receive the recommended course of action. The recommendation can be evaluated as a candidate for developing a policy or a performance measure. Level 2 “We suggest” The majority of people in your situation would want the recommended course of action, but many would not. Different choices will be appropriate for different patients. Each patient needs help to arrive at a management decision consistent with their values and preferences. The recommendation is likely to require substantial debate and involvement of stakeholders before policy can be determined. Grade Certainty of evidence Meaning A High We are confident that the true effect is close to the estimate of the effect. B Moderate The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. C Low The true effect may be substantially different from the estimate of the effect. D Very low The estimate of effect is very uncertain, and often, it will be far from the true effect. Practice points are consensus-based statements representing the expert judgment of the Work Group and are not graded. They are issued when a clinical question did not have a systematic review performed, to help readers implement the guidance from graded recommendation (e.g., frequency of monitoring, provision of standard care [such as regular clinic visits], referral to specialist care, etc.), or for issuing “good practice statements” when the alternative is considered to be absurd. Users should consider the practice point as expert guidance and use it as they see fit to inform the care of patients. Although these statements are developed based on a different methodology, they should not be seen as “less important” or a “downgrade” from graded recommendations. www.kidney-international.org r e f e r e n c e k e y s Kidney International (2024) 105 (Suppl 4S), S117–S314 S125 CURRENT CHRONIC KIDNEY DISEASE (CKD) NOMENCLATURE USED BY KDIGO CKD is defined as abnormalities of kidney structure or function, present for a minimum of 3 months, with implications for health. CKD is classified based on Cause, Glomerular filtration rate (GFR) category (G1–G5), and Albuminuria category (A1–A3), abbreviated as CGA. Persistent albuminuria categories Description and range GFR categories (ml/min/1.73 m 2 ) Description and range A1 G1 ≥90 G2 60–89 G3a 45–59 G3b 30–44 G4 15–29 G5 <15 Kidney failure Severely decreased Moderately to severely decreased Mildly to moderately decreased Mildly decreased Normal or high A2 A3 Normal to mildly increased Moderately increased Severely increased <30 mg/g <3 mg/mmol 30–300 mg/g 3–30 mg/mmol >300 mg/g >30 mg/mmol KDIGO: Prognosis of CKD by GFR and albuminuria categories Green: low risk (if no other markers of kidney disease, no CKD); Yellow: moderately increased risk; Orange: high risk; Red: very high risk. GFR, glomerular filtration rate. C K D n o m e n c l a t u r e www.kidney-international.org S126 Kidney International (2024) 105 (Suppl 4S), S117–S314 CONVERSION FACTORS OF CONVENTIONAL UNITS TO SI UNITS Conventional unit Conversion factor SI unit Albumin-to-creatinine ratio (ACR) mg/g 0.113 mg/mmol Calcium mg/dl 0.2495 mmol/l Creatinine mg/dl 88.4 mmol/l Protein-to-creatinine ratio (PCR) mg/g 0.113 mg/mmol Phosphate mg/dl 0.3229 mmol/l Urate mg/dl 59.48 mmol/l SI, International System of Units. Note: Conventional unit
conversion factor ¼ SI unit. EQUIVALENT ALBUMINURIA CATEGORIES IN CKD Category AER (mg/24 h) ACR (approximate equivalent) Terms (mg/mmol) (mg/g) A1 <30 <3 <30 Normal to mildly increased A2 30–300 3–30 30–300 Moderately increaseda A3 >300 >30 >300 Severely increased ACR, albumin-creatinine ratio; AER, albumin excretion rate; CKD, chronic kidney disease. a Relative to the young adult level. www.kidney-international.org c o n v e r s i o n f a c t o r s Kidney International (2024) 105 (Suppl 4S), S117–S314 S127 Abbreviations and acronyms ACEi angiotensin-converting enzyme inhibitor(s) ACR albumin-to-creatinine ratio ADA American Diabetes Association ADPKD autosomal dominant polycystic kidney disease AER albumin excretion rate AIDS acquired immune deficiency syndrome AKD acute kidney disease AKI acute kidney injury ARB angiotensin II receptor blocker ASCVD atherosclerotic cardiovascular disease BMI body mass index BP blood pressure BSA body surface area CI confidence interval CKD chronic kidney disease CKD-EPI Chronic Kidney Disease Epidemiology Collaboration CKiD Chronic Kidney Disease in Children CKD-MBD chronic kidney disease-mineral and bone disorder CKD-PC Chronic Kidney Disease Prognosis Consortium CrCl creatinine clearance CT computed tomography CVD cardiovascular disease DALY disability-adjusted life-year eGFR estimated glomerular filtration rate eGFRcr creatinine-based estimated glomerular filtration rate eGFRcr-cys creatinine and cystatin C–based estimated glomerular filtration rate eGFRcys cystatin C–based estimated glomerular filtration rate EKFC European Kidney Function Consortium EMA European Medicines Agency EMR electronic medical record ERT Evidence Review Team FDA Food and Drug Administration GBD Global Burden of Disease GFR glomerular filtration rate GLP-1 RA glucagon-like peptide-1 receptor agonist(s) GN glomerulonephritis HBV hepatitis B virus HCV hepatitis C virus HDL high-density lipoprotein HIV human immunodeficiency virus HR hazard ratio HRQoL health-related quality of life IgG immunoglobulin G IQR interquartile range i.v. intravenous KDIGO Kidney Disease: Improving Global Outcomes KDOQI Kidney Disease Outcomes Quality Initiative KFRE Kidney Failure Risk Equation KRT kidney replacement therapy LDL low-density lipoprotein LMIC low- and middle-income countries MACE major adverse cardiovascular events MDRD Modification of Diet in Renal Disease mGFR measured glomerular filtration rate MRA mineralocorticoid receptor antagonist(s) mTOR mammalian target of rapamycin NICE National Institute for Health and Care Excellence NIHR National Institute for Health and Care Research NOAC non–vitamin K antagonist oral anticoagulant NSAIDs nonsteroidal anti-inflammatory drugs OR odds ratio OTC over-the-counter PCR protein-to-creatinine ratio PCSK-9 proprotein convertase subtilisin/kexin type-9 PICOS population, intervention, comparator, outcomes, study design POCT point-of-care testing PROM patient-reported outcome measure QoL quality of life RAS(i) renin-angiotensin system (inhibitor) RAAS(i) renin-angiotensin-aldosterone system (inhibitor) RBC red blood cell RCT randomized controlled trial RR relative risk SCr serum creatinine SBP systolic blood pressure SES socioeconomic status SGLT2i sodium-glucose cotransporter-2 inhibitor(s) T1D Type 1 diabetes T2D Type 2 diabetes UK United Kingdom US United States USRDS United States Renal Data System WHO World Health Organization a b b r e v i a t i o n s a n d a c r o n y m s www.kidney-international.org S128 Kidney International (2024) 105 (Suppl 4S), S117–S314 Notice SECTION I: USE OF THE CLINICAL PRACTICE GUIDELINE This Clinical Practice Guideline document is based upon literature searches conducted from July 2022 through April 2023 and updated in July 2023. It is designed to assist decision-making. It is not intended to define a standard of care and should not be interpreted as prescribing an exclusive course of management. Variations in practice will inevitably and appropriately occur when clinicians consider the needs of individual patients, available resources, and limitations unique to an institution or type of practice. Healthcare providers using the statements in this document (both practice points and recommendations) should decide how to apply them to their own clinical practice. SECTION II: DISCLOSURE Kidney Disease: Improving Global Outcomes (KDIGO) makes every effort to avoid any actual or reasonably perceived conflicts of interest that may arise from an outside relationship or a personal, professional, or business interest of a member of the Work Group. All members of the Work Group are required to complete, sign, and submit a disclosure and attestation form showing all such relationships that might be perceived as or are actual conflicts of interest. This document is updated annually, and information is adjusted accordingly. All reported information is published in its entirety at the end of this document in the Work Group members’ Disclosure section and is kept on file at KDIGO. Copyright Ó 2023, Kidney Disease: Improving Global Outcomes (KDIGO). Published by Elsevier Inc. on behalf of the International Society of Nephrology. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/). Single copies may be made for personal use as allowed by national copyright laws. Special rates are available for educational institutions that wish to make photocopies for nonprofit educational use. No part of this publication may be reproduced, amended, or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without explicit permission in writing from KDIGO. Details on how to seek reprints, permission for reproduction or translation, and further information about KDIGO’s permissions policies can be obtained by contacting Melissa Thompson, Chief Operating Officer, at melissa.thompson@kdigo.org. Neither KDIGO, Kidney International, the Publisher, nor the authors, contributors, or editors shall have or assume any liability for any direct, indirect, incidental, special, exemplary, or consequential damages (including without limitation lost profits) or any injury and/or damage to persons or property, however caused and on any theory of liability, whether in contract, strict liability, or tort (including product liability, negligence or otherwise) arising in any way out of the use or operation of any methods, products, instructions, or ideas contained in the material herein. www.kidney-international.org n o t i c e Kidney International (2024) 105 (Suppl 4S), S117–S314 S129 Foreword Kidney International (2024) 105 (Suppl 4S), S117–S314; https://doi.org/10.1016/j.kint.2023.10.018 Copyright ª 2023, Kidney Disease: Improving Global Outcomes (KDIGO). Published by Elsevier Inc. on behalf of the International Society of Nephrology. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). The Kidney Disease: Improving Global Outcomes (KDIGO) organization was established in 2003 with the mission to improve the care and outcomes of people living with kidney disease worldwide. The development and implementation of global clinical practice guidelines is central to the many ac- tivities of KDIGO to fulfill its mission. Twenty years later, we are excited to present this update of the KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) to complement the existing 12 guidelines that address various other facets of kidney disease management. Our aspiration is that the KDIGO CKD Guideline serves as a comprehensive reference for evidence-based practices, of- fering clear and valuable guidance for the optimal diagnosis and treatment of CKD. The updated guideline is the result of a rigorous process, extensively detailed in the KDIGO Methods Manual. To promote objectivity and transparency, we screen Guideline Co-Chairs and Work Group members (which include clinicians, researchers, and patients) for con- flicts of interest. Over a span of 2–3 years, these individuals volunteer their time, starting with the creation of a Scope of Work that undergoes an open public review to engage all stakeholders. This document is then adapted into a Request for Proposal, which is used to enlist an independent Evidence Review Team. The Evidence Review Team conducts a systematic review of existing literature, extracting studies with appropriate design and outcomes deemed important by both people with CKD and clinicians. All work is meticulously graded on study quality and potential bias, forming the basis for quantifying the overall certainty of the evidence using the “Grading of Recommendations Assessment, Development, and Evalua- tion” (GRADE) approach. The penultimate version of the guideline also undergoes public review to capture additional perspectives. Thus, guidelines are the result of a rigorous and objective assessment of available evidence, enriched by the collective expertise of healthcare providers, researchers, and patients alike. Guideline statements (“We recommend” or “We suggest”) reflect clinical questions that were addressed by the evidence reviews from the Evidence Review Team. Practice points provide guidance on clinical questions that were not, and largely could not be, studied by the Evidence Review Team. We view the current guideline as a dynamic, evolving resource rather than a static document. We are delighted by the recent pace of clinical discovery that substantially increased the scientific basis of optimal CKD diagnosis and management, and we remain committed to updating recommendations and practice points as important evidence emerges. We hope that the guideline will serve as a useful tool for clinicians in their daily practice, providing clear insight into the evidence-based recommendations while highlighting areas requiring further research. Ultimately, our aim is to facilitate more effective and consistent care to patients with CKD worldwide, and the publication of the CKD Guideline will provide the foundation of many dissemination and implementation activities to in- crease the outreach and usefulness of this work. We extend our heartfelt gratitude for all those who have contributed to the CKD Guideline. First, to the members of the Methods Committee, particularly Dr. Marcello Tonelli, MD, SM, MSc, Chair of the Committee, and Amy Earley, BS, KDIGO Guideline Development Director, for setting the expectation of rigor, balance, and transparency throughout the process. Next, to the Evidence Review Team at Johns Hopkins University, for their meticulous work in reviewing the existing literature. Third, to the Work Group members, led by the indefatigable Drs. Adeera Levin, MD, and Paul Stevens, MB, for their diligence and innumerable hours vol- unteered to shepherd the guideline to publication. Fourth, to the many individuals who provided comments during the rounds of public review. Finally, to the whole KDIGO staff, for their steadfast, behind the scenes commitment to excel- lence in patient care. Sincerely, Morgan E. Grams, MD, PhD, MHS Michel Jadoul, MD KDIGO Co-Chairs f o r e w o r d www.kidney-international.org S130 Kidney International (2024) 105 (Suppl 4S), S117–S314 Work Group membership WORK GROUP CO-CHAIRS Paul E. Stevens, MB, FRCP, RCPathME East Kent Hospitals University NHS Foundation Trust Canterbury, United Kingdom Adeera Levin, MD, FRCPC University of British Columbia Vancouver, Canada WORK GROUP Sofia B. Ahmed, MD, MMSc, FRCPC University of Alberta Edmonton, Alberta, Canada Juan Jesus Carrero, Pharm, PhD Pharm, PhD Med, MBA, FNKF, FERA Karolinska Institutet Stockholm, Sweden Bethany Foster, MD, MSCE McGill University Montreal, Quebec, Canada Anna Francis, MBBS, FRACP, CF, MMed, PhD Queensland Children’s Hospital Brisbane, Australia Rasheeda K. Hall, MD, MBA, MHS Duke School of Medicine Durham, North Carolina, USA Will G. Herrington, MA, MBBS, MD, FRCP University of Oxford Oxford, United Kingdom Guy Hill Manchester, United Kingdom Lesley A. Inker, MD, MS, FRCP(C) Tufts Medical Center Boston, Massachusetts, USA Rümeyza Kazancıoglu, MD Bezmialem Vakif University Istanbul, Turkey Edmund Lamb, PhD, FRCPath East Kent Hospitals University NHS Foundation Trust Canterbury, United Kingdom Peter Lin, MD, CCFP Canadian Heart Research Center Toronto, Ontario, Canada Magdalena Madero, MD Instituto Nacional de Cardiología Ignacio Chavéz Mexico City, Mexico Natasha McIntyre, PhD Western University London Health Sciences Centre-Victoria Hospital London, Ontario, Canada Kelly Morrow, MS, RDN, CD, FAND Bastyr University, Osher Center for Integrative Medicine University of Washington Kenmore, Washington, USA Glenda Roberts UW Center for Dialysis Innovation & Kidney Research Institute Seattle, Washington, USA Dharshana Sabanayagam, MD, FRACP University of Sydney Sydney, Australia Elke Schaeffner, MD, MSc Charité Universitätsmedizin Berlin Berlin, Germany Michael Shlipak, MD, MPH University of California, San Francisco San Francisco, California, USA Rukshana Shroff, MD, FRCPCH, PhD UCL Great Ormond Street Hospital Institute of Child Health, London, United Kingdom Navdeep Tangri, MD, PhD, FRCP(C) University of Manitoba Winnipeg, Manitoba, Canada Teerawat Thanachayanont, MD, MSc Bhumirajanagarindra Kidney Institute Bangkok, Thailand Ifeoma Ulasi, MBBS, FWACP, PGD, MSc University of Nigeria, Ituku-Ozalla Campus Enugu, Nigeria www.kidney-international.org W o r k G r o u p m e m b e r s h i p Kidney International (2024) 105 (Suppl 4S), S117–S314 S131 Germaine Wong, MD, PhD University of Sydney Sydney, Australia Chih-Wei Yang, MD Chang Gung University Taoyuan, Taiwan Luxia Zhang, MD, MPH Peking University First Hospital Beijing, China METHODS COMMITTEE REPRESENTATIVE Bertram L. Kasiske, MD, FACP Hennepin County Medical Center University of Minnesota Minneapolis, MN, USA EVIDENCE REVIEW TEAM The Johns Hopkins University Evidence-based Practice Center Karen A. Robinson, PhD, Professor of Medicine Lisa Wilson, ScM, Research Associate Renee F. Wilson, MS, Research Associate Dipal M. Patel, MD, PhD, Assistant Professor of Medicine Troy Gharibani, BS, BA, Research Assistant Xuhao Yang, MSPH, Research Assistant Verna Lazar, MBBS, MPH, Research Assistant Jeongmin Hana Kim, PharmD, MSc, Research Assistant W o r k G r o u p m e m b e r s h i p www.kidney-international.org S132 Kidney International (2024) 105 (Suppl 4S), S117–S314 Abstract The Kidney Disease: Improving Global Outcomes (KDIGO) 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) is an update to the KDIGO 2012 guideline on the topic. The aim is to assist clinicians caring for people with CKD, both adults and children. People receiving dialysis and kidney transplant recipients are not the focus of this guideline. The scope includes chapters dedicated to the evaluation of CKD, risk assessment in people with CKD, management to delay CKD progression and manage its complications, medical management and drug stewardship in CKD, and optimal models of CKD care. In addition, this guideline includes a comprehensive introduction from the guideline Co-Chairs, a patient foreword, a discussion of special population considerations, a presentation of the relative and absolute risks associated with specific outcomes from the CKD Prognosis Consortium (CKD- PC), and an extensive section dedicated to research recommendations based on the current gaps in evidence. The goal of the guideline is to generate a useful resource for clinicians and patients by providing actionable recommendations based on a rigorous formal evidence review, practice points that serve to direct clinical care or activities for which a systematic review was not con- ducted, and useful infographics. The guideline targets a broad audience of healthcare providers involved in the care of people with CKD as well as people with CKD themselves while being mindful of implications for policy and payment. Development of this guideline update followed an explicit process of evidence review and appraisal. Treatment approaches and guideline rec- ommendations are based on systematic reviews of relevant studies, and appraisal of the certainty of the evidence and the strength of recommendations followed the “Grading of Recommenda- tions Assessment, Development, and Evaluation” (GRADE) approach. Limitations of the evi- dence are discussed, with areas of future research also presented. Keywords: chronic kidney disease; CKD; evaluation; guideline; KDIGO; management CITATION In citing this document, the following format should be used: Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S): S117–S314. www.kidney-international.org a b s t r a c t Kidney International (2024) 105 (Suppl 4S), S117–S314 S133 Patient foreword The identification of chronic kidney disease (CKD) begins a long journey for any patient that will have a direct impact on their lifestyle and future health outcomes. This guideline identifies the suitability of medical interventions that can improve or delay the seriousness of CKD and possible kidney failure. In a complicated world of health provision, having a set of evidential recommendations and practice points provides kidney service providers with the targets for a quality CKD service for people with kidney disease. However, if the starting point for many people is ignorance of what a kidney actually does, then without a holistic approach to patient care, much of the potential effectiveness of medical interventions can be diluted because of patient circumstances and psychological challenges. Acceptance of the seriousness of CKD can take a lot longer for a person to process, to the possible detriment of medical intervention, and may well lead to issues over adherence. A controlled, managed CKD decline is so beneficial to patients who have so many social issues to contend with, be it diet, tiredness, liquid control, pill overload, and a deep dive into the very mechanics of how we eat and drink to survive and excrete excesses. In an ever-increasingly busy world of medical care, as pa- tients, we believe that the best approach is for any physician to aim to achieve a partnership of knowledge with the patient regarding their CKD care. This will build patient confidence and self-awareness, with the aim that any patient who sadly arrives at possible dialysis is in the right state of mind, which is critical for a considered approach to the next stage of a patient’s journey. Guy Hill CKD Work Group Member p a t i e n t f o r e w o r d www.kidney-international.org S134 Kidney International (2024) 105 (Suppl 4S), S117–S314 Introduction, qualifying statements, and key concepts This 2024 update of the KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Dis- ease (CKD)1 is an evidence-based guideline that provides recommendations and practice points for clinical management activities. The past 10 years have provided new hope for improved treatment of CKD. A greater understanding of healthy lifestyle and lifestyle modifications together with new medications and technologies furnish improved options for treatment and monitoring of CKD. People with CKD, healthcare providers, and health systems are eager to implement these advances in the most effective and evidence-based manner. This requires integration of new therapies with lifestyle management and existing medications using approaches that engage patients and optimize application of health resources. The goal of this guideline document is to provide such guidance. The majority of statements from the 2012 guideline have been updated based on current knowledge and practice. Only 6 statements were retained in their original form in 2012. As Co-Chairs, we would like to recognize the outstanding efforts of the Work Group, the Evidence Review Team (ERT), and Kidney Disease: Improving Global Outcomes (KDIGO) staff. The Work Group was diverse, multinational, multidis- ciplinary, experienced, thoughtful, and dedicated. Notably, the Work Group included 2 members who have CKD who contributed actively as peers to keep the guideline relevant and patient-centered. We are indebted to each and every in- dividual who contributed to this process. We hope that the guidance provided here will help improve the care of people with CKD worldwide. The KDIGO 2012 CKD guideline was built on the United States (US)-based Kidney Disease Outcomes Quality Initiative (KDOQI) 2002 Guideline on Definition, Classification, and Evaluation of CKD,2 accepted by the international community in 2005. It reinforced the definition of CKD incorporating a persistent reduction in glomerular filtration rate (GFR) and markers of kidney damage and modified the staging and classification system to include elements that had begun to be appreciated by the clinical community. 3 Specifically, the 2012 guideline introduced the concept of a “CGA” classification of CKD based on cause (C), level of kidney function determined by GFR (G), and degree of albuminuria (A). The CGA classification laid a foundation upon which management, treatment, research, and risk assessment of CKD have since been based. The definition, staging, and classification of CKD pro- posed by the KDIGO 2012 CKD guideline have been widely accepted and implemented worldwide. Research has since highlighted that higher specific stages or categories of CKD, characterized by level of GFR and albuminuria independently, portend greater relative risk (RR) for adverse outcomes. 4–7 These include, but are not limited to, CKD progression, cardiovascular disease (CVD), mortality (all-cause and car- diovascular), kidney failure, and acute kidney injury (AKI). The development of risk-prediction tools has refined moni- toring and referral to specialist nephrology and has aided in the estimation of prognosis. 6,8–10 Although there remains ongoing discussion about application of the same thresholds to define disease in older adults, 11 it is still clear that even in older populations, risk of adverse outcomes increases with higher CKD stages (Figure 1). 12 In any field of medicine, although data from large population studies inform clinical practice guidelines and associated recommendations for care, it is critically important to consider the individual in front of you, their preferences, and their individual risks and benefits. We recognize that the threshold GFR <60 ml/min per 1.73 m 2 (GFR categories G3a–G5) for >3 months to indicate a diagnosis of CKD is well below the average in young adult men and women,13 but because a significant GFR reduction in younger people is also usually associated with other markers of kidney disease, the diagnosis of CKD would be captured. Similarly, we recognize that there is an average age- associated GFR decline observed in longitudinal and cross- sectional studies, 14 but with substantial variation among individuals within the population, 15 such that not all individuals will have a significant GFR decline with age. 12 This guideline is not intended to be a textbook, and thus statements regarding prevention and screening for CKD, although important topics, are not addressed in depth but are briefly discussed below in the context of the global burden of CKD and in Chapter 1. For a more detailed discussion of these issues, we refer readers to existing textbooks and reviews.16–18 Prevention and screening for CKD should be conducted mostly by healthcare providers in primary care and in other specialties, such as endocrinology, cardiology, and oncology, rather than restricted to nephrologists. We strongly support efforts aimed at the early detection and treatment of CKD among people at high risk for CKD, including those with hypertension, diabetes, and CVD. Screening efforts in these and other populations should include assessments of GFR (estimated or in certain situations measured [see Section 1.2] and albuminuria [or surrogate, see Section 1.3]). The intended starting point for this update of the KDIGO 2012 CKD guideline is an established diagnosis of CKD, though there are some practice points to clarify the evaluation of CKD and the ascertainment of chronicity. The care of people with CKD is multifaceted and complex. Several critical aspects of this comprehensive care, such as blood pressure (BP), diabetes, and lipid management, have been addressed in other KDIGO guidelines. These topics were not reviewed for the current guideline, but recommendations have been incorporated where relevant and we refer readers to those specific KDIGO guidelines and their updates. 19–23 www.kidney-international.org i n t r o d u c t i o n , q u a l i f y i n g s t a t e m e n t s , a n d k e y c o n c e p t s Kidney International (2024) 105 (Suppl 4S), S117–S314 S135 This clinical practice guideline includes 2 different types of statements: graded recommendations, which are supported by systematic reviews (i.e., de novo reviews conducted by the in- dependent ERT or existing high-quality reviews that have been systematically identified), and ungraded practice points, which serve to direct clinical care or activities for which a systematic review was not conducted for various reasons (e.g., lack of a sufficient evidence base or randomized controlled trials [RCTs] would be impractical/unethical). Both recommenda- tions and practice points are intended to help guide clinical practice and aid in decision-making; thus, they collectively are the guidance statements. They are clearly articulated and presented together so that all guideline statements can be implemented. The distinction between them is based on the process by which they are derived, that process is based on the framework methodology from the KDIGO Methods Com- mittee and aligns with other international guideline groups utilizing the “Grading of Recommendations Assessment, Development, and Evaluation” (GRADE) methodology. Several exciting developments have been introduced into clinical practice since the KDIGO 2012 CKD guideline was published. These include refinement of evaluation of GFR, population and individual risk prediction, and novel treat- ments which have all positively influenced the prognosis for people with CKD. The Work Group has aimed to generate a guideline that is both rigorously devoted to new and existing evidence, and clinically useful. Research recommendations are presented in a separate section at the end of this document and are intended to guide the next set of important research questions to inform and improve outcomes of people living with CKD. The research recommendations are not exhaustive but are intended to help focus the clinical and research communities on unanswered questions including improving diagnostic tools and evalua- tion of kidney function, development and testing of risk prediction equations in clinical and research settings, evalu- ation of different therapies to delay progression in various combinations, improved medication management, and optimal models of care. We specifically urge the community to be inclusive of people across the lifecycle and include sex and gender, and etiology of CKD, as important variables in all studies. Age <65 eGFRcr-cys <10 10–29 30–299 300+ <10 10–29 30–299 300+ 105+ 0.99 1.2 1.5 2.4 0.93 1.0 1.1 2.6 90–104 ref 1.3 1.5 2.5 ref 1.2 1.3 1.9 60–89 1.2 1.6 2.0 2.9 1.3 1.4 1.6 2.1 45–59 2.1 2.7 2.9 4.5 1.8 2.6 3.1 3.5 30–44 2.7 3.8 4.2 5.6 1.9 2.3 3.0 3.9 <30 5.2 4.0 7.1 8.6 4.1 3.6 4.7 5.8 105+ 0.95 1.4 1.7 4 0.96 1.2 1.6 2.7 90–104 ref 1.6 1.8 3.5 ref 1.2 1.5 2.2 60–89 1.3 1.7 2.3 3.9 1.2 1.4 1.7 2.6 45–59 2.5 4.0 4.6 6.0 1.9 2.0 2.5 3.8 30–44 3.1 6.6 5.3 7.1 2.6 3.7 3.5 3.5 <30 6.0 5.5 9.4 12 2.6 2.9 5.1 5.1 105+ 0.57 0.77 2.3 12 0.86 1.1 1.7 3.4 90–104 ref 1.4 3.9 11 ref 1.3 1.5 3.0 60–89 1.9 3.7 8.3 33 1.2 1.7 2.1 3.6 45–59 7.0 16 28 100 1.7 3.3 3.4 5.3 30–44 22 34 109 210 3.5 4.3 6.8 5.7 <30 335 267 419 625 7.5 6.3 9.7 8.9 105+ 0.75 1.0 1.4 3.4 0.93 1.0 1.3 1.9 90–104 ref 1.2 1.8 2.6 ref 1.2 1.4 2.3 60–89 1.6 2.7 2.9 5.8 1.1 1.3 1.5 1.8 45–59 4.2 6.0 5.6 7.6 1.5 2.0 2.1 2.6 30–44 5.7 9.4 9.8 9.4 1.8 2.4 3.0 2.8 <30 15 14 14 13 3.7 2.9 4.3 5.4 105+ 1.0 1.1 1.1 1.5 0.93 1.9 1.5 2.6 90–104 ref 1.1 1.2 1.3 ref 1.8 2.1 3.9 60–89 1.1 1.2 1.3 1.6 1.2 2.1 2.2 5.4 45–59 1.3 1.7 1.5 2.0 3.2 7.3 3.4 8.4 30–44 1.5 1.8 1.6 2.1 6.5 9.1 6.6 13 <30 2.1 2.4 2.4 3.5 1.4 7.6 18 16 esaesidyretralarehpireP noitazilatipsoH Kidney failure replacement therapy Heart failure ekortS ytilatro m ralucsavoidraC noitcrafnilaidracoy M ytilatro m esuac-llA +56egA g/g m ,RCA g/g m ,RCA eGFRcr-cys <10 10–29 30–299 300+ <10 10–29 30–299 105+ 1.2 1.4 1.9 3.5 0.97 1.4 2.0 90–104 ref 1.2 1.4 2.0 ref 1.2 1.1 60–89 1.2 1.5 1.8 2.3 1.1 1.4 1.5 45–59 1.6 2.0 2.4 2.9 1.6 1.9 2.3 30–44 2.0 2.4 3.2 4.1 2.1 2.6 3.1 <30 3.4 4.1 5.1 6.5 4.9 3.0 5.1 105+ 1.1 1.5 2.0 12 1.2 1.3 1.5 90–104 ref 1.4 1.4 3.4 ref 1.3 1.3 60–89 1.2 1.7 2.2 3.1 1.1 1.4 1.8 45–59 1.7 2.4 3.0 4.3 1.5 1.7 2.0 30–44 2.4 3.1 4.5 5.8 1.5 2.0 2.1 <30 5.7 5.2 5.1 7.8 1.7 2.0 2.4 105+ 2.0 1.0 2.1 0.99 1.5 1.7 90–104 ref 1.9 4.7 10 ref 1.3 1.5 60–89 1.4 2.6 6.2 19 1.2 1.5 2.0 45–59 3.7 7.9 16 42 1.6 2.0 2.9 30–44 14 14 46 137 2.3 2.9 3.5 <30 87 364 241 406 4.4 4.1 5.5 105+ 0.91 1.1 1.3 1.9 0.95 1.1 1.0 90–104 ref 1.3 1.4 3.9 ref 1.2 1.3 60–89 1.5 2.1 2.7 4.7 1.1 1.2 1.5 45–59 3.6 4.3 5.1 7.3 1.2 1.4 1.7 30–44 5.7 5.9 7.2 9.8 1.5 1.8 2.0 <30 10 11 11 22 1.8 1.8 2.2 105+ 1.0 1.1 1.2 2.2 1.1 2.3 2.9 90–104 ref 1.1 1.3 1.4 ref 1.3 2.0 60–89 1.1 1.2 1.3 1.5 1.3 1.6 2.0 45–59 1.2 1.2 1.4 1.6 2.0 2.8 3.1 30–44 1.5 1.4 1.6 2.0 3.5 2.8 3.8 <30 1.9 1.9 2.0 2.6 8.4 4.1 5.9 esaesidyretralarehpireP noitazilatipsoH Kidney failure replacement therapy Heart failure ekortS ytilatro m ralucsavoidraC noitcrafnilaidracoy M ytilatro m esuac-llA g/g m ,RCA g/g m ,RCA 300+ 19 1.9 1.9 3.4 3.8 5.0 3.3 2.8 2.5 2.3 2.3 4.8 7.0 2.2 3.2 4.1 6.1 7.2 3.7 2.4 2.0 1.9 2.2 3.2 4.9 4.8 3.2 3.1 5.9 10 Figure 1 | Associations of chronic kidney disease (CKD) staging by estimated glomerular filtration rate by creatinine and cystatin C (eGFRcr-cys) and albumin-to-creatinine ratio (ACR) categories and risks for 10 common complications by age in multivariable-adjusted analyses. Numbers reflect the adjusted hazard ratio compared with the reference cell. Adjustment variables included age, sex, smoking status (current, former, or never), systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, body mass index, use of antihypertensive medications, and a medical history of diabetes, coronary heart disease, stroke, heart failure, atrial fibrillation, peripheral artery disease, cancer, and chronic obstructive pulmonary disease, where relevant. The colors were determined for each outcome separately using the following rule: the percentile shaded the darkest green color corresponds to the proportion of cells in the grid without CKD (e.g., 6 of 24 cells), and the percentile shaded the darkest red color corresponds to proportion expected to be at highest risk (e.g., 5 of 24 cells). In this manner, the numbers of green and red cells are consistent across outcomes, but the patterns are allowed to differ. ref, reference cell. Reproduced with permission from JAMA, Writing Group for the CKD Prognosis Consortium; Grams ME, Coresh J, Matsushita K, et al. Estimated glomerular filtration rate, albuminuria, and adverse outcomes: an individual-participant data meta-analysis. JAMA. 2023;330(13):1266–1277. 12 Copyright ª 2023 American Medical Association. All rights reserved. i n t r o d u c t i o n , q u a l i f y i n g s t a t e m e n t s , a n d k e y c o n c e p t s www.kidney-international.org S136 Kidney International (2024) 105 (Suppl 4S), S117–S314 Definition and classification of CKD Defining CKD. CKD is defined as abnormalities of kidney structure or function, present for a minimum of 3 months, with implications for health (Table 1).1 Classifying CKD. CKD is classified based on Cause, GFR category (G1–G5), and Albuminuria category (A1–A3), abbreviated as CGA.1 These 3 components of the classification system are each critical in the assessment of people with CKD and help enable determination of severity and risk. Listed below are reference tables describing each component. Note that while the definition of CKD includes many different markers of kidney damage and is not confined to decreased GFR and albumin-to-creatinine ratio (ACR) >30 mg/g [>3 mg/mmol], the classification system is based on the 2 dimensions of GFR and degree of albuminuria (Tables 2 and 3). This nuance is often missed by healthcare providers and students. It is well established that patient advocates with CKD and healthcare providers prefer the more clinically useful and generally understood assessment of GFR resulting from the use of GFR estimating equations compared with serum creatinine (SCr) alone. Globally, although still not universally available in all countries, SCr is measured routinely and the approach to assessment of GFR is therefore to use SCr and an estimating equation for initial assessment of GFR. The approach to evaluation of GFR using initial and supportive tests is described in greater detail in Chapter 1. Etiology of CKD should be sought, and there are numerous systems for grouping various etiologies, some of which are evolving with new knowledge and diagnostic tools. There are congenital and genetic causes of CKD, some asso- ciated with systemic diseases, and others that are primary. It is beyond our remit to suggest a specific approach, but we highlight the importance of establishing a cause to individ- ualize management of CKD. The global burden of CKD The Global Burden of Disease, Injuries, and Risk Factors Study (GBD) pulls together data on premature death and disability from more than 350 diseases and injuries in 204 countries, by age and sex, from 1990 to the present. 24 Disease “burden” is the impact of a health problem as measured by financial cost, mortality, morbidity, or other indicators and can be measured by combining 2 indicators to describe the disability-adjusted life-years (DALYs): the number of years of life lost to disease and the number of years lived with disability due to disease. Globally, in 2017, a systematic analysis from the all-age GBD project found 697.5 million (95% uncertainty interval [UI]: 649.2–752.0) cases of all-stage CKD, for a global preva- lence of 9.1% (8.5%–9.8%).25 By 2021, a joint statement from the American Society of Nephrology, European Renal Association, and International Society of Nephrology indicated that more than 850 million people suffer from some form of kidney disease, roughly double the number of people who live with diabetes (422 million) and 20 times more than the prevalence of cancer worldwide (42 million) or people living with AIDS/HIV (36.7 million). These estimates derive from aggregation of studies worldwide, which have applied a variety of definitions of CKD; nevertheless, they furnish the best guide about global CKD prevalence. In 2017, CKD was estimated to account for 35.8 million (95% UI: 33.7e38.0) DALYs, and 1.2 million people died from CKD. Most of the burden of CKD was concentrated in the 3 lowest quintiles of sociodemographic index (SDI). In 2019, CKD was responsible for 41.5 million (95% UI: 38.3– 45.0) DALYs, and 1.43 million people died from CKD. 24 Age- standardized DALY rates (Figure 224 ) were highest in central and Andean Latin America, at 1348.1 (1203.6–1521.6) and 836.3 (704.2–981.6) per 100,000, respectively (global rate was 514.9 [474.9–558.9]). In 2017, CKD in diabetes represented a third of all DALYs, and there were 1.4 million Table 1 | Criteria for chronic kidney disease (either of the following present for a minimum of 3 months) Markers of kidney damage (1 or more) Albuminuria (ACR $30 mg/g [$3 mg/mmol]) Urine sediment abnormalities Persistent hematuria Electrolyte and other abnormalities due to tubular disorders Abnormalities detected by histology Structural abnormalities detected by imaging History of kidney transplantation Decreased GFR GFR <60 ml/min per 1.73 m 2 (GFR categories G3a–G5) ACR, albumin-to-creatinine ratio; GFR, glomerular filtration rate. Table 2 | GFR categories in CKD GFR category GFR (ml/min per 1.73 m 2 ) Terms G1 $90 Normal or high G2 60–89 Mildly decreaseda G3a 45–59 Mildly to moderately decreased G3b 30–44 Moderately to severely decreased G4 15–29 Severely decreased G5 <15 Kidney failure CKD, chronic kidney disease; GFR, glomerular filtration rate. a Relative to the young adult level. In the absence of evidence of kidney damage, neither G1 nor G2 fulfills the criteria for CKD. Table 3 | Albuminuria categories in chronic kidney disease Category AER (mg/24 h) ACR (approximately equivalent) Terms (mg/mmol) (mg/g) A1 <30 <3 <30 Normal to mildly increased A2 30–300 3–30 30–300 Moderately increaseda A3 >300 >30 >300 Severely increased ACR, albumin-to-creatinine ratio; AER, albumin excretion rate. a Relative to the young adult level. www.kidney-international.org i n t r o d u c t i o n , q u a l i f y i n g s t a t e m e n t s , a n d k e y c o n c e p t s Kidney International (2024) 105 (Suppl 4S), S117–S314 S137 (95% UI: 1.2–1.6) CVD-related deaths in people with CKD; 25.3 (22.2–28.9) million CVD DALYs were attributable to impaired kidney function. Overall, CKD and its effect on CVD resulted in 2.6 million (95% UI: 2.4–2.8) deaths in 2017 and CKD has risen from 19th to 11th in rank among leading causes of death between 1990 and 2019 due to aging and an increasing burden of risk factors for CKD (including diabetes and hypertension) that, together, contribute to more than half of the deaths from CKD. Screening and prevention Despite the increasing recognition of the true burden of CKD, there remains controversy and lack of consensus as to the utility of population screening for CKD 26 or targeted screening programs, 18 due to the complexity of the underlying sociopolitical and resource environment. Public health policy has a role to play in identifying and addressing risk factors to prevent CKD, to identify CKD early, and to delay its progression and associated adverse outcomes. Education of both health personnel and the populations at risk, implementation of early kidney disease detection programs, and incorporation of evidence-based treatment of CKD and its associated conditions, such as BP and diabetes, are all essential components of a strategy to address this burden. A systematic review suggested that screening for CKD is cost-effective in people with diabetes and hypertension, the 2 most common causes of CKD worldwide. 16 However, clinical trials have not been conducted to determine whether or not an intervention to detect, risk-stratify, and treat CKD would improve the health outcomes for the targeted population. Nevertheless, cost-effective analysis of population-wide screening for CKD incorporating evidence-based treatment with sodium- glucose cotransporter-2 inhibitors (SGLT2i) recently concluded that screening adults for albuminuria to identify CKD could be cost-effective in the United States. 27 This evidence aligns with the KDIGO Controversies Con- ference on Early Detection and Intervention in CKD, which concluded that early identification of CKD in people at risk, who are usually asymptomatic, would likely be beneficial in the community and primary care settings if the programs are interwoven with risk stratification and treatment.17 A community program must be able to provide treatment to the high-risk group of patients with newly detected CKD to justify systematic early detection strategies. An additional conclusion was that screening and treatment programs for CKD should be implemented based on risk stratification to prioritize people, particularly in settings with limited economic resources. Although globally people with hypertension, diabetes, or CVD are at high risk for CKD, other high-risk people may be identified through genetic risk factors or by varying exposure to environmental pollution, pesticides, water, and nephrotoxic medications including significant analgesic use and herbal medications, depending on geographical region. Frameworks in which to consider specific regional factors have been offered to facilitate discussion about the value and context of screening for CKD. 26 Currently, kidney disease awareness remains low, and worldwide only 6% of the general population and 10% of the high-risk population are aware of their CKD status. Impor- tant to note is that patient advocates with CKD strongly argue for earlier CKD screening and diagnosis. 17 They also advocate for CKD detection to be integrated with patient and family education and engagement to improve accessing appropriate healthcare and knowledge and adherence to recommended lifestyle modification and medications. 0 500 1000 1500 2000 2500 0 10 20 30 40 60 70 80 90 0 0 1 0 5 SDI DALY rate (per 100,000) Latin America and Caribbean Central Europe, eastern Europe, and central Asia Sub-Saharan Africa High income North Africa and Middle East South Asia Southeast Asia, east Asia, and Oceania GBD super-region Figure 2 | Age-standardized chronic kidney disease disability-adjusted life-year (DALY) rates for each location by sociodemographic index (SDI), both sexes combined, 2019. GBD, global burden of disease. Reproduced from Global Burden of Disease 2019: GBD cause and risk summaries chronic kidney disease. Lancet. 2020;396:S152–S153. 24 ª 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. i n t r o d u c t i o n , q u a l i f y i n g s t a t e m e n t s , a n d k e y c o n c e p t s www.kidney-international.org S138 Kidney International (2024) 105 (Suppl 4S), S117–S314 Use of a simple algorithm such as that shown above in settings such as primary care, cardiology, and endocrinology could significantly improve the early identification and treatment of CKD (Figure 3). 28 There are no current evidence-based recommendations regarding the frequency of screening in people at risk of CKD. In the setting of diabetes, a consensus report from the Amer- ican Diabetes Association (ADA) and KDIGO recommends annual screening of people with diabetes for CKD.29 CKD screening should start at diagnosis of type 2 diabetes (T2D) because evidence of CKD is often already apparent at this time. For type 1 diabetes (T1D), screening is recommended commencing 5 years after diagnosis. The overall costs of a screening program are largely driven by the frequency of repeat screening, so the timing of repeated testing should be guided by CKD risk. There are risk equations available to estimate the interval risk of developing CKD, and this risk stratification could guide repeat testing intervals.30 International considerations In low- and middle-income regions of the world and in the lower sociodemographic quintiles, there is a large gap between CKD burden and provision of adequate healthcare. There is limited access to kidney replacement therapy (KRT) combined with the rising prevalence of diabetes and hypertension and evidence of substantial sex and gender disparities in access to CKD treatment. These factors highlight the importance of early identification and treatment of risk factors in primary care. However, the majority of the world’s population with CKD is in low- and middle-income countries (LMIC) where there are disparities in access to laboratory diagnostic services, kidney biopsy, and imaging services, in availability of appropriately skilled healthcare providers and the availability and afford- ability of medications. The International Society of Nephrology survey assessing global kidney healthcare resources reported that fewer than 1 in 4 surveyed countries had facilities available for routine measurements of SCr or proteinuria.31 Identify adults at risk for CKD Test for GFR* and ACR ± other markers of kidney damage † Test for GFR or ACR if not performed and exclude AKI/AKD AKI/AKD present: follow AKI/AKD guidance GFR <60 ml/min per 1.73 m2 and/or ACR ≥30 mg/g [3 mg/mmol] after 3 months or earlier if evidence of chronicity Measure eGFRcr-cys if not performed and available CKD not present Timing of retesting based on individual characteristics such as risk of progression Stage according to GFR and ACR Establish underlying cause Estimate risk of progression Initiate treatment GFR ≥60 ml/min per 1.73 m 2 and ACR <30 mg/g [3 mg/mmol] and no other markers of kidney damage present GFR <60 ml/min per 1.73 m 2 or ACR ≥30 mg/g [3 mg/mmol] and/or other markers of kidney damage present Figure 3 | Screening algorithm for diagnosis and staging of chronic kidney disease (CKD) in adults. Risk factor conditions are listed in Table 5. *For recommended methods to estimate glomerular filtration rate (eGFR), see Section 1.2. †Markers of kidney damage other than albuminuria may also be used to diagnose CKD, but albumin-to-creatinine ratio (ACR) and GFR are still required to determine stage and estimate risk of progression. Acute kidney disease (AKD) is defined by the abnormalities of kidney function and/or structure with implications for health and with a duration of #3 months. 28 The orange boxes indicate actions in people at risk for CKD and in whom testing should be performed. The blue boxes indicate testing steps. The green boxes indicate the identification of CKD and its stages and the initiation of treatment. The purple box indicates the identification of AKD/acute kidney injury (AKI). Please also see the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Acute Kidney Injury. 97 www.kidney-international.org i n t r o d u c t i o n , q u a l i f y i n g s t a t e m e n t s , a n d k e y c o n c e p t s Kidney International (2024) 105 (Suppl 4S), S117–S314 S139 Importantly, slowing CKD progression at early stages should provide economic benefits and prevent the develop- ment of kidney failure and cardiovascular complications. A systematic review of care models in LMIC found that those supporting primary care providers or allied health workers achieved effectiveness in slowing GFR decline, as opposed to interventions centered on specialty care alone. 32 Where there are resource limitations, it is logical to deploy resources where they will be most cost-effective, for example, to higher-risk, preventable stages. Standardization/accuracy of testing tools including assays/equipment The KDIGO 2012 CKD guideline built on recommendations made to clinical laboratories in the earlier KDOQI 2002 guidance. Clinical laboratories were specifically charged with measuring SCr and serum cystatin C using assays with cali- bration traceable to the international standard reference materials recommending that, for SCr, there should be minimal bias compared with isotope-dilution mass spec- trometry. 1 Recommendations were also made with respect to measurement and reporting of albumin and protein in the urine. Although some of the recommendations have become part of routine practice, the effective use of clinical guidelines and therefore effective patient care, including accurate diagnosis and referral prioritization, clinical research, and public health prioritization, require comparability of laboratory results independent of time, place, and measurement procedure. Key to this is establishing precision and between-laboratory agreement with traceability to accepted reference standards wherever available. Therefore, this guidance document includes standards for laboratory tests. The International Consortium for Harmonization of Clinical Laboratory Results (ICHLR) was established to create a pathway for harmonization and aid implementation of clinical guidelines recommending the use of laboratory tests in the diagnosis and management of disease, 33 ensuring that both reference materials and test methodology are harmonized. The ICHLR aimed to prioritize measurands by medical importance and both coordinate and stimulate development of technical and regulatory processes to achieve harmonization of those measurands. 34 Although this has been achieved for SCr, the current status of other key measurands such as cystatin C and urinary albumin is not yet sufficiently clear. The foundations for this 2024 guideline have been devel- oped over the last 20 years, galvanizing the collaborative work of researchers, healthcare providers, laboratory physicians, patients, and carers. The current updated guideline document reinforces methods for accurate diagnosis of CKD and pre- diction, incorporates novel treatment strategies and ap- proaches to managing people living with CKD, and identifies further areas for research. Importantly, as the field is rapidly changing, we commit to updating relevant sections of this document as new evidence becomes available, to ensure more timely updates than have previously been possible. Adeera Levin, MD, FRCPC Paul E. Stevens, MB, FRCP CKD Guideline Co-Chairs i n t r o d u c t i o n , q u a l i f y i n g s t a t e m e n t s , a n d k e y c o n c e p t s www.kidney-international.org S140 Kidney International (2024) 105 (Suppl 4S), S117–S314 Special considerations The Work Group recognizes that kidney diseases affect people at different times and with different impacts across the whole lifespan. Thus, enabling a personalized approach, considering age, sex, and gender for diagnosis, risk assessment, and treatment is critical. At the extremes of age—the very young and the very old—diagnostic procedures, treatment aims, treatment modalities, and decision-making differ due to dif- ferences in prognosis, treatment options, and prioritization. In young and middle-aged adults, treatment approaches may differ due to specific circumstances, such as pregnancy or menopause. Sex (biological attributes) and gender (socio- cultural factors), as well as other important intersectional factors including but not limited to geographical location, socioeconomic status (SES), and race and ethnicity, play important roles in kidney health and disease. Here we introduce concepts as to why age, sex, and gender should be considered in the context of diagnosis, treatment, and care planning in people with CKD. In addition, the specific guideline chapters incorporate statements where special considerations regarding age, sex, and gender are relevant to clinical practice and understanding. Considerations in children and adolescents When the guideline refers to people with CKD, this includes children (people <10 years old) and adolescents (people 10–19 years old). When there are altered care recommenda- tions and practice points due to the unique needs of children or the lack of data to inform recommendations and practice points, these considerations are discussed within the Pediatric considerations sections of the guideline. The management of children and adolescents with CKD needs special consideration (Figure 4). Children and adults have different etiologies of CKD. Up to 40%–50% of childhood CKD is due to congenital anomalies of the kidneys and urinary tract (CAKUT); the younger the CKD population, the greater the proportion with CAKUT as the cause.35,36 CAKUT is characterized by slower progression to kidney failure and a higher likelihood of polyuria than the conditions causing CKD in adults. Pediatric CKD has several unique aspects: Delivery of care. Pediatric healthcare providers engage with not only the person with CKD but also their carers and sib- lings. Age-appropriate care and education, understood by both the child and their carers, is necessary. Holistic consid- eration of the needs and capabilities of the family unit is important in ensuring effective CKD care. Engagement with patients and families must change over the course of child- hood from being entirely carer-directed for infants, changing to include the whole family unit in childhood, and then leaning toward the young person to ensure successful tran- sition to adult-oriented care. Child/adolescent • Growth • Nutrition • Weight/BSA-based drug dosing • Neurocognitive development • Supporting education • Transition to adult care • Holistic approach to care for the whole family unit Pregnancy/lactation • Drug pharmacokinetics and pharmacodynamics • Drug teratogenicity • Risk of CKD progression • Increased risk of pregnancy complications, preterm birth and small for gestational age babies • Fertility Older adults • Multidimensionality of chronic conditions/ multimorbidity • Frailty (including sarcopenia) • Cognitive function • Polypharmacy • Prioritization • End-of-life care Gender • Gender identity • Gender roles • Gender relations • Institutionalized gender Sex • Menopause • Contraception of risk factors and complications Figure 4 | Special considerations for chronic kidney disease (CKD) care across the lifespan. BSA, body surface area. www.kidney-international.org s p e c i a l c o n s i d e r a t i o n s Kidney International (2024) 105 (Suppl 4S), S117–S314 S141 Growth, puberty, and young adulthood. Childhood and adolescence are characterized by physical growth and devel- opment. All CKD care aims to optimize these physiological processes, which are commonly disrupted by CKD. Puberty is a time of rapid somatic growth with an increase in muscle bulk and therefore constitutes a high-risk period for CKD progression as compromised kidneys may not hypertrophy to adapt to the larger body size. Adolescence and emerging adulthood bring individuation and exploration of sexuality and adult behaviors, and kidney disease care must recognize and adapt to these changes. Kidney development and long-term assessment of kidney risks. Although nephron formation is complete by 36 weeks of gestation, kidney function continues to develop throughout early childhood, with nephron growth and maturation pro- gressing particularly rapidly in the first year of life. An actual increase in GFR over the course of the first 1–2 years of life, and even up to 4 years of age, is expected. A trajectory of increasing GFR in infancy and very early childhood followed by a period of relative stability and a subsequent progression in CKD in adolescence or adulthood is common. Given the long life ex- pectancy of children, follow-up plans must take into account the risk of late CKD or kidney failure. Healthy children and adolescents should have excellent kidney function, so an esti- mated eGFR under 90 ml/min per 1.73 m 2 (CKD G2–G5) represents decreased kidney function in these age groups. Early assessment and intervention of children with CKD is crucial to maximize overall health across the lifespan. Neurodevelopment and education. A primary goal of pedi- atric CKD care is to optimize neurodevelopmental gains. CKD can affect development, cognition, school attendance, vocational outcomes, and future employment. Mitigating these deficits through effective, individualized care is essential to give children with CKD the best possible future. Considerations in older adults Older adults constitute a substantial and steadily growing proportion of people under nephrology and medical care globally, especially in Western industrialized countries. Longevity in many parts of the world is increasing, and thus the prevalence of CKD in those people is also increasing. The 2022 US Renal Data System (USRDS) annual data report highlights that the number of individuals initiating KRT is continuously ascending with increasing age. In Taiwan, for example, KRT incidence in those aged 75þ was 2858 per million population (pmp) compared with 1583 pmp among people aged 65–74 years, 530 pmp among people aged 45–64 years, and 97 pmp among people aged 20–44 years. The pattern is very similar across the globe with the majority of people initiating dialysis over the age of 75, which puts emphasis on a group of people who are not just old, but very old, and incorporates more and more people over the age of 80. Octo- and nonagenarians often demonstrate distinct patterns of disease complexity. These features include multi- morbidity often accompanied by polypharmacy, frailty, cognitive impairment, and gerontopsychiatric disorders among others. Often, several of these features coexist espe- cially in older adults with CKD. Implications for aging adults with CKD are important in both diagnosis and treatment. The interpretation of labora- tory results (specifically SCr) used in the staging system should factor in an older adult’s habitus given the frequency of sarcopenia. A creatinine-based eGFR (eGFRcr) will over- estimate GFR in the elderly (and others) with sarcopenia leading to drug overdosing. Urine ACR at the same time will be falsely high due to the falsely low creatinine in the de- nominator. Furthermore, the presence of frailty may alter treatment targets recommended for younger people with CKD, as they may not necessarily be transferable to older adults. Strict BP-lowering, for example, may come with the risk of dizziness, falls, and fractures in older adults, many of whom are on anticoagulants risking severe hemorrhage. The multidimensionality of comorbidities in old age poses challenges, as it demands a sophisticated integrated and complex multidisciplinary care and treatment approach, which may not be available in every healthcare system. Life expectancy in old age is naturally limited compared with younger people. Perspectives and treatment goals shift over the life course, and recognizing these in very old adults, as different from those in middle-aged or younger adults with CKD, is critical to the development of more personalized care plans and goals. Specifically, pure survival may become less of a priority for an older individual, whereas maintaining an acceptable, good quality of life (QoL) may be more impor- tant. The context of a person’s situation and own values and preferences may modify the prioritization for testing, treat- ment types, and treatment goals. For example, the decision- making between KRT and conservative care should be made on the basis of the person’s priorities, medical needs, and informed decision as to benefits and harms of various op- tions. These informed decisions require good communication between caregivers, people with CKD, and their relatives/ carers; they require time, “room,” adequate understandable language, patience, trust, and commitment. Repeated con- versations are critical, given the higher prevalence of cognitive deficits in older adults with CKD. These cognitive issues accompany both aging and CKD and frequently remain un- recognized, thus, impeding shared decision-making and advance care planning in this group. In summary, older adults constitute the largest group among all people with advanced CKD. Although every single person needs individual care, the multidimensional medical complexity inherent in very old age is challenging. Where specific recommendations or practice points require special consideration in the elderly, we make clear statements in the special considerations section and encourage clinicians to individualize therapies and goals of care in all patients, with special attention to those of advanced age. Considerations regarding sex and gender It is increasingly recognized that sex (biological attributes) and gender (sociocultural factors) factors across individuals s p e c i a l c o n s i d e r a t i o n s www.kidney-international.org S142 Kidney International (2024) 105 (Suppl 4S), S117–S314 contribute to differences in kidney health and disease. 37–39 Sex-based variation in genetics, physiology, immunology, and anatomy, as well as gender factors such as identity, roles, and relations in addition to institutionalized gender, influences kidney disease pathophysiology, presentation, response to therapy, complications, and outcomes, highlighting the need to take these factors into consideration in the care of the person living with kidney disease. Globally, the prevalence of CKD not being treated with dialysis defined by level of eGFR is greater in women than men. 40 Progression of CKD has been reported as more rapid in men, 41,42 in women,43 or no difference by sex or gender. 44 These incongruities are likely a reflection of differences in cause of kidney disease and definitions of outcomes (e.g., loss of eGFR or receipt of KRT). There is substantial literature demonstrating that both sex- and gender-related factors (e.g., puberty, menstrual patterns, hormonal contraception, pregnancy and pregnancy-related complications, menopause, menopausal hormone therapy, testosterone levels, and gender-affirming hormone therapy) play important roles in the risk, progression, complications, and treatment of kidney disease. 45 These factors will play prominent roles in progression of kidney disease across different stages of the life cycle. For example, the use of some recommended medications has not been studied in pregnant populations, highlighting the importance of contraceptive counseling in accordance with a person’s values and preferences. In other instances, precon- ception counseling, changing medications to nonteratogenic options and a multidisciplinary approach, is required to optimize the outcomes of a potential pregnancy in the setting of CKD. Sex-based differences in pharmacokinetics and pharmacodynamics that are accentuated with increasing age and changing hormonal status may alter the response to different therapies for the treatment of kidney disease. For example, women are more likely to report adverse reactions to angiotensin-converting enzyme inhibitors (ACEi), 46 which play a role in adherence and failure to reach guideline- recommended target doses. There are differences between women and men in the detection, recognition, monitoring, referrals, and manage- ment of CKD. 47,48 Although the reasons behind these disparities are unclear, access to kidney care may be limited by familial and other caregiving responsibilities, as well as financial challenges, occupational obligations, and time constraints, which are influenced by gender identity (how an individual self-identifies, behaves, expresses their gender, and is perceived by others, e.g., woman, man, girl, boy, and gender-diverse), roles (social expectations and norms typically associated with a given gender, e.g., primary household earner and caregiver), relations (interactions with and treatment by others based on an individual’s perceived and/or expressed gender identity), and institutionalized gender (e.g., distribution of power and resources in society). 37 A small but increasing proportion of the world’s popula- tion identifies as transgender, gender-diverse, or nonbinary where sex assigned at birth differs from gender identity, highlighting the urgent need to build transgender cultural safety within all aspects of kidney disease management and care.49 Taking sex and gender considerations into account is critical to optimize the care of the individual with kidney disease. Although there is increasing literature to inform sex- and gender-specific recommendations in nephrology, signif- icant knowledge gaps remain, underscoring the importance of a person-centered approach in kidney care. Considerations regarding fertility and pregnancy Neither fertility nor pregnancy in people with CKD was part of the scope of work for this guideline update, but there will be special consideration relating to fertility and pregnancy requiring specific reference in relevant sections of the guideline. Fertility. CKD is associated with decreased female and male fertility. 50,51 Progressively impaired function of the hypothalamic-pituitary-gonadal axis appears to play a key role in the pathophysiology, although multiple factors contribute to the reduction in fertility in this population. In conjunction with the decreased fertility associated in CKD and the uncertainty of the impact of assisted reproductive technologies on kidney function, ongoing discussion of family planning potential between the person with CKD and their healthcare provider is essential. Pregnancy. People with CKD are at risk for adverse preg- nancy-associated outcomes, including progression of their underlying CKD, a flare of their kidney disease, and adverse pregnancy complications including pre-eclampsia, preterm delivery, and small for gestational age infant. 52,53 The severity of CKD is associated with risk of adverse pregnancy outcomes. A multidisciplinary approach to preconception counseling and management of pregnancy is necessary to achieve optimal outcomes for both the person with CKD and the infant. 54 www.kidney-international.org s p e c i a l c o n s i d e r a t i o n s Kidney International (2024) 105 (Suppl 4S), S117–S314 S143 Summary of relative and absolute risks relevant to CKD from meta-analysis of large multinational population studies in the CKD Prognosis Consortium (CKD-PC) Outcomes relevant to CKD, and the prognostic importance of CKD categories The most highly evaluated endpoints in epidemiological studies have been all-cause mortality, cardiovascular events (myocardial infarction, stroke, and heart failure), and kidney- specific outcomes (progression to kidney failure and AKI), although additional outcomes such as all-cause hospitaliza- tion and incident atrial fibrillation have been studied more recently. In this section, we highlight newer data derived from the CKD Prognosis Consortium (CKD-PC). 12 We describe the associations of CKD categories with 10 of these important outcomes and demonstrate the importance of different methods of estimating GFR (i.e., using creatinine- or cystatin C–based equations) on these risk gradients. Healthcare providers, researchers, and policy makers should understand the association of CKD parameters (ACR and eGFR) in populations. The overall distributions of epidemiological risk across CKD categories on a population level are presented here. This is not to be confused with the information presented in Chapter 2, where individualized risk assessment tools are described, and those tools can be used to inform clinical and management decisions for individual people with CKD. Associations of all complications of CKD are incre- mentally increased with worsened categories of estimated glomerular filtration rate (eGFR) and albuminuria: updated data. The KDIGO 2012 Clinical Practice Guideline for the Evalu- ation and Management of Chronic Kidney Disease introduced the combined staging by eGFR and albuminuria categories, which were justified by their associations with CKD complica- tions.1 The combined associations of eGFR and ACR categories were presented as “heatmaps,” a color-coded depiction of the associations of increased risk with worsening CKD, for outcomes of all-cause mortality, kidney failure, AKI, and cardiovascular mortality on a population level. In this section, we provide an update to these CKD heatmaps, which have been provided by the CKD-PC.12 Several changes in the development of these updated heatmaps are important to highlight. (i) They now include several clinical databases that allow a much larger population base, comprising up to 27,503,140 people for the analyses of each adverse outcome. (ii) The eGFRcr has been changed to the 2021 CKD Epide- miology Collaboration (CKD-EPI) equation, as this newer version no longer includes race as a component. (iii) The number of outcomes has been increased to 10, including 6 that are cardiovascular related, 2 that are kidney specific (kidney failure and AKI), and 2 general outcomes (all-cause mortality and all-cause hospitalization). (iv) Additional analyses have been conducted using the 2021 CKD-EPI combined eGFR equation that incorporates both creatinine and cystatin C. Although the sample size for these subsequent analyses is much smaller (n ¼ 720,736), it does permit better differentiation of associ- ations of eGFR and risk and allows validation of CKD thresholds across populations. CKD staging by eGFRcr and ACR and association with adverse events Figure 512 presents the RRs for all eGFR/ACR combinations for the 10 identified outcomes. The RRs presented have all been adjusted for age, sex, smoking status (current, former, or never), systolic BP (SBP), total cholesterol, high-density lipoprotein (HDL) cholesterol, body mass index (BMI), use of antihypertensive medications, and a medical history of diabetes, coronary heart disease, stroke, heart failure, atrial fibrillation, peripheral artery dis- ease, cancer, and chronic obstructive pulmonary disease. Therefore, the RRs can be interpreted as the proportional elevation in risk for each outcome experienced by people in that stage of CKD (or non-CKD) compared with people in the healthiest group. Across all the heatmaps, a consistent color scheme is used. The figures reveal several common themes and highlight the necessity of having both eGFR and ACR parameters available in assessing risk. First, within the CKD popula- tion, the association of risk for all 10 outcomes increases with higher stages of both eGFR and albuminuria. The figures present only the RRs for each specific stage and not the absolute risk of experiencing that outcome for people in the risk cell. This distinction between relative and ab- solute risks demonstrates the importance of using indi- vidual risk prediction tools for persons with CKD, a subject of Chapter 2. Although nearly all CKD categories are at substantially elevated risk for most outcomes in Figure 5, a distinction must be made for people in the eGFRcr CKD G3a category and with the lowest ACR severity (<10 mg/g [<1 mg/mmol]). This group is portrayed in the lower-risk green color for 7 of the 10 outcomes presented, although they have 3-fold higher adjusted risk of AKI and 13-fold higher risk of kidney failure compared with the reference group. The inconsistent risk association for populations with CKD G3a, A1, particularly in older adults, has led to controversy over whether this group should be r e l a t i v e a n d a b s o l u t e r i s k s a s s o c i a t e d w i t h C K D www.kidney-international.org S144 Kidney International (2024) 105 (Suppl 4S), S117–S314 considered as having CKD.55 The CKD-PC investigators repeated all 10 heatmaps using creatinine- and cystatin C– based eGFR (eGFRcr-cys), in part to evaluate whether the weaker associations of CKD G3a, A1 with clinical outcomes were caused by the limitations of the specific creatinine-based equation eGFRcr, compared with eGFRcr-cys, which has been established as a better approximation of measured GFR (mGFR) than eGFRcr (Figure 612 ). Overall eGFRcr <10 10–29 30–299 300–999 1000+