2023+UKKA临床实践指南：钠-葡萄糖共转运蛋白2(+SGLT2)+抑制剂在成人肾脏病患者中的应用（更新版）.pdf

Roddicketal.BMC Nephrology (2023)24:310 https:/doi.org/10.1186/s12882-023-03339-3GUIDELINESOpen Access The Author(s)2023.Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the articles Creative Commons licence,unless indicated otherwise in a credit line to the material.If material is not included in the articles Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use,you will need to obtain permission directly from the copyright holder.To view a copy of this licence,visit http:/creat iveco mmons.org/licen ses/by/4.0/.The Creative Commons Public Domain Dedication waiver(http:/creat iveco mmons.org/publi cdoma in/zero/1.0/)applies to the data made available in this article,unless otherwise stated in a credit line to the data.BMC NephrologyUK Kidney Association Clinical Practice Guideline:Sodium-Glucose Co-transporter-2(SGLT-2)Inhibition inAdults withKidney Disease 2023 UPDATEAlistair J.Roddick1,2,Alexa Wonnacott3,David Webb4,Angela Watt5,Michael A.Watson5,Natalie Staplin1,Alex Riding6,Eirini Lioudaki7,Apexa Kuverji8,Mohsen El Kossi9,Patrick Holmes10,Matt Holloway11,Donald Fraser3,Chris Carvalho12,13,James O.Burton14,Sunil Bhandari15,William G.Herrington1,2 and Andrew H.Frankel16*Abstract Large placebo-controlled trials have demonstrated kidney and cardiovascular clinical benefits of SGLT-2 inhibitors.Data from the EMPA-KIDNEY and DELIVER trials and associated meta-analyses triggered an update to the UK Kidney Association Clinical Practice Guideline on Sodium-Glucose Co-transporter-2(SGLT-2)Inhibition in Adults with Kidney Disease.We provide a summary of the full guideline and highlight the rationale for recent updates.The use of SGLT-2 inhibitors in people with specific medical conditions,including type 1 diabetes,kidney transplants,and people admit-ted to hospital with heart failure is also considered,along with Recommendations for future research and Recom-mendations for implementation.A full“lay”summary of the guidelines is provided as an appendix to ensure that these guidelines are accessible and understandable to people who are not medical professionals.Keywords Guideline,Chronic kidney disease,Acute kidney injury,GliflozinWilliam G.Herrington and Andrew H.Frankel contributed equally to this work.*Correspondence:Andrew H.Frankela.frankelimperial.ac.uk1 The Medical Research Council Population Health Research Unit at the University of Oxford,Oxford,UK2 Oxford Kidney Unit,Oxford University Hospitals NHS Foundation Trust,Oxford,UK3 Wales Kidney Research Unit,Cardiff University,Cardiff,UK4 Diabetes Research Centre,College of Life Sciences,University of Leicester,Leicester,UK5 UKKA Patient Representative,Bristol,UK6 Royal Free London NHS Foundation Trust,London,UK7 Kings College Hospital NHS Trust,London,UK8 John Walls Renal Unit,Glenfield Hospital,Leicester,UK9 Doncaster Royal Infirmary,Doncaster,UK10 Primary Care Diabetes Society,Darlington,UK11 East Kent Hospitals University NHS Foundation Trust,Canterbury,UK12 North East London Integrated Care Board,London,UK13 Clinical Effectiveness Group,Queen Mary University of London,London,UK14 Department of Cardiovascular Sciences,University of Leicester,Leicester,UK15 Hull University Teaching Hospitals NHS Trust and Hull York Medical School,Hull,UK16 Imperial College Healthcare NHS Trust,London,UKPage 2 of 18Roddicketal.BMC Nephrology (2023)24:310 IntroductionSodium-glucose co-transporter-2(SGLT-2)inhibitors represent a major step in the management of chronic kid-ney disease(CKD),with evidence from several large ran-domised clinical trials and collaborative meta-analyses indicating that this medication class reduces progression of kidney disease and kidney failure in a broad range of people with CKD irrespective of diabetes(DM)status,level of kidney function,or primary kidney diagnosis 14.Furthermore,SGLT-2 inhibition has been shown to improve outcomes in people with diabetes with high car-diovascular risk,and in people with heart failure across the spectrum of left ventricular ejection fraction 46.In addition to well-established efficacy,SGLT-2 inhibi-tion has been shown to be safe,with few associated risks,which include mycotic infections,lower limb amputa-tions and ketoacidosis.Importantly,serious side effects are rare,particularly among people without diabetes 4.A recent meta-analysis assessing the balance of risk and benefit in CKD indicates that the absolute benefits of SGLT-2 inhibition in terms of kidney disease progression,cardiovascular death or hospitalisation for heart failure,and acute kidney injury substantially outweigh any asso-ciated risks in the studied populations(Fig.1)4.Given these findings,there is a need to provide prac-tical and pragmatic guidance for the use of this class of medication to facilitate rapid,effective and safe imple-mentation in clinical practice.In 2021,the UK Kid-ney Association(UKKA)Clinical Practice Guideline:SGLT-2 Inhibition in Adults with Kidney Disease Work-ing Group published a Clinical Practice Guideline on the use of SGLT-2 inhibitors in adults with kidney disease in order to facilitate this,with emphasis on relevant large-scale randomised evidence for the efficacy and safety of SGLT-2 inhibition.This 2023 guideline presents updated Recommendations in light of new evidence from the recent DELIVER and EMPA-KIDNEY trials 3,7.This guidelines aims were to:(i)provide guidance on use of SGLT-2 inhibitors in people with CKD,focusing on the potential to modify risk of kidney disease progression;and(ii)support safe implementation of SGLT-2 inhibi-tors into clinical practice in people with CKD.Guideline structureThis manuscript provides an overview of the Recommen-dations made within the guideline with associated ration-ale.More information regarding the evidence for the efficacy and safety of SGLT-2 inhibition can be found in the full guideline document,together with licencing infor-mation,sick day guidance,and a full lay summary of the guideline.The full guideline document is provided as a Sup-plementary appendix.The guideline Working Group pro-vided four types of Recommendations:(i)Use(who should be offered SGLT-2 inhibition);(ii)Implementation(how should SGLT-2 inhibition be used);(iii)Research(what are areas of ongoing clinical uncertainty);and(iv)Audit(how effective implementation can be demonstrated).The Recommendations for Use and Recommendations for Implementation presented in this guideline are graded according to the two-tier grading system recommended by the UKKA(Table 1).Throughout the guideline,we use the term“recommend”where Recommendations are based on Grade 1 evidence,and“suggest”for those based on Grade 2 evidence.Recommendations for research are not graded,and we offer Recommendations for audit only for those Recommendations with Grade 1 evidence.In this manuscript,we provide Recommendations for Use of SGLT-2 inhibition in people with and with-out diabetes separately,to acknowledge differences in the amount of available evidence(Table2).We also provide Recommendations for implementation of SGLT-2 inhibition in practice,with a focus on safety Fig.1 Absolute benefit and risks of SGLT-2 inhibition for people with CKD with and without diabetes,estimated from 13 large randomised clinical trials of SGLT-2 inhibition(adapted from 4).CKD chronic kidney disease.eGFR estimated glomerular filtration rate.SE standard error.SGLT-2i sodium-glucose co-transporter 2 inhibitor.Figure licensed under Creative Commons CC-BY licensePage 3 of 18Roddicketal.BMC Nephrology (2023)24:310 considerations(Table3).Finally,we discuss the use and implementation of SGLT-2 inhibition in populations of specific interest:people with type 1 diabetes,kidney transplant recipients,and people presenting with acute decompensated heart failure(Table 3).Research Rec-ommendations are detailed in Table4,and audit Rec-ommendations listed in Table 5.Further information on the use of SGLT-2 inhibition,including a summary of UK licencing and a full lay summary of the guideline,can be found in the full document.The Recommendations in this guideline were supported by a series of systematic literature searches for relevant SGLT-2 inhibitor randomised controlled trials,cover-ing the period from database inception to 5th Septem-ber 2022.Eligible studies were published parallel-group randomised controlled trials of SGLT-2 inhibitor versus placebo,active comparator or control,excluding phase 1 studies,studies in healthy volunteers,and non-English language reports.Trials were further subcategorised into large placebo-controlled trials and into subgroups of interest.Full details regarding search methodology can be found in the full guideline document(Supplementary appendix).The acknowledgements section and full guide-line text provide more information on methods used to arrive at a Recommendation.Recommendations foruse ofSGLT2 inhibitors inpeople withtype 2 diabetesDue to the benefits of SGLT-2 inhibitors on kidney out-comes(CKD and acute kidney injury(AKI)and cardio-vascular risk:1.We recommend initiating SGLT-2 inhibition in people with chronic kidney disease and type 2 diabetes,irre-Table 1 UK Kidney Associations grading system for Recommendations strength and evidence qualityLevel of evidenceEvidence quality Grade 1 Recommendation is a strong recommendation to do(or not do)something,where the benefits clearly outweigh the risks(or vice versa)for most,if not all patients(i.e.recommendations)Grade 2 Recommendation is a weaker recommendation,where the risks and benefits are more closely balanced or are more uncertain(i.e.sug-gestions)Grade A evidence means high-quality evidence that comes from con-sistent results from well-performed randomised controlled trials,or over-whelming evidence of some other sort Grade B evidence means moderate-quality evidence from randomised trials that suffer from serious flaws in conduct,inconsistency,indirectness,imprecise estimates,reporting bias,or some combination of these limita-tions,or from other study designs with special strength Grade C evidence means low-quality evidence from observational studies,or from controlled trials with several very serious limitations Grade D evidence is based only on case studies or expert opinionTable 2 Summary of Recommendations for Usea excludes people with polycystic kidney disease,type 1 diabetes,or a kidney transplantb urinary protein-to-creatinine ratio of 35mg/mmol can be considered equivalentRECOMMENDATIONS FOR USEPEOPLE WITH TYPE 2 DMGrade1We recommend initiating SGLT-2 inhibition in people with chronic kidney disease and type 2 diabetes,irrespective of primary kidney disease,a for any of the following 4 clinical scenarios:a)eGFR of 2045 mL/min/1.73m2b)eGFR of 45 mL/min/1.73m2 and a urinary albumin-to-creatinine ratio(uACR)of 25 mg/mmolbc)Symptomatic heart failure,irrespective of ejection fractiond)Established coronary disease1A2We suggest initiating SGLT-2 inhibition to modify cardiovascular risk and slow rate of kidney function decline in people with an eGFR 4560 mL/min/1.73m2 and a uACR of 25 mg/mmol,recognising effects on glycaemic control will be limited2B3We suggest clinicians consider initiating SGLT-2 inhibition in people with an eGFR below 20 mL/min/1.73m2 to slow progression of kidney disease2BPEOPLE WITHOUT DM1We recommend initiating SGLT-2 inhibition in people with chronic kidney disease,irrespective of primary kidney disease,a for any of the following clinical scenarios:(a)eGFR of 20 mL/min/1.73m2 and a urinary albumin-to-creatinine ratio(uACR)of 25 mg/mmolb(b)Symptomatic heart failure,irrespective of ejection fraction1A2We recommend initiating SGLT-2 inhibition to slow rate of kidney function decline in people with an eGFR of 2045 mL/min/1.73m2 and a uACR of 25 mg/mmolb1B3We suggest clinicians consider initiating SGLT-2 inhibition in people with an eGFR below 20 mL/min/1.73m2 to slow progression of kidney disease2BPage 4 of 18Roddicketal.BMC Nephrology (2023)24:310 Table 3 Summary of Recommendations for ImplementationRECOMMENDATIONS FOR IMPLEMENTATIONPEOPLE WITH OR WITHOUT DM(excluding TYPE 1)Grade1We recommend using SGLT-2 inhibitors with demonstrated efficacy for their given indications1A2We recommend using clinically appropriate single agent renin-angiotensin-system(RAS)blockade in combination with SGLT-2 inhibition,wherever RAS blockade is indicated and tolerated1A3We suggest following NICE guidelines on use of uACR for screening of albuminuria(NICE NG203).We recognise that more pragmatic approaches to identifying risk of kidney disease progression may be necessary whilst local access to uACR measurement is improved2C4We recommend that SGLT-2 inhibition can be continued until the need for dialysis or kidney transplantation arises1A5We suggest that co-prescription of SGLT-2 inhibition with mineralocorticoid receptor antagonists(MRA)can be considered,where each are individually indicated2B6We suggest the beneficial effects of SGLT-2 inhibition on kidney disease progression or risk of heart failure hospitalisation are likely to be a class effect2BDIABETIC KETOACIDOSIS1We recommend that people with type 1 DM should only have SGLT-2 inhibitors initiated under the strict direction of the diabetes team1C2We recommend that people with type 2 DM at greater risk of diabetic ketoacidosis(DKA;defined in Table 5a.1 of the supplementary appendix)should have SGLT-2 inhibitors initiated with caution after discussion with the diabetes team1C3We recommend SGLT-2 inhibitors are discontinued when an individual develops DKA1A4We suggest that after an episode of DKA and where a clear contributing factor has been identified,there should be discussion with the person and clinical team to establish whether the benefits of re-introducing an SGLT-2 inhibitor outweigh the risks2D5When initiating SGLT-2 inhibitors,we suggest that individuals should be advised on the signs and symptoms of DKA and be instructed to temporarily withhold SGLT-2 inhibitors and to seek immediate medical advice if symptoms develop1C6We recommend always offering advice on sick day guidance when initiating SGLT-2 inhibitors and reminding them of this at every medication review1C7We suggest that individuals taking SGLT-2 inhibitors should be advised against following a ketogenic diet2C8We suggest that for people who choose to intermittently fast(e.g.for Ramadan),and particularly for those who are elderly,on diuretics or have CKD,consider withholding SGLT-2 inhibitors for the duration of the fasting period and for those people with diabetes ketone testing should be undertaken if unwell2DHYPOGLYCAEMIA1We re