Toward Guideline-Directed Medical Therapy in Nephrology DOI Open Access
Evan Zeitler, Amy K. Mottl

Clinical Journal of the American Society of Nephrology, Journal Year: 2022, Volume and Issue: 17(12), P. 1710 - 1712

Published: Nov. 22, 2022

Nephrology has seen a revolution over the last decade with discovery of multiple therapies to slow progression CKD and reduce cardiovascular disease burden. In addition angiotensin-converting enzyme inhibitors (ACEis) angiotensin receptor blockers (ARBs), there is trial-level evidence for nonsteroidal mineralocorticoid antagonists, endothelin glucagon-like peptide 1 agonists, and, at head pack, sodium-glucose cotransporter-2 (SGLT2is). This watershed provides tremendous opportunities turn from an inevitably progressive lethal into one that can be managed proactively, but lack implementation kept this possibility becoming reality. The barriers are myriad. First, screening rates very low, receipt albuminuria testing in only 35% people diabetes 4% hypertension (1). recommendation urine albumin-creatinine ratio well established; however, despite consensus such indicated other high-risk populations (2), dearth guidelines support it. Even after diagnosed, prescribing ACEis/ARBs SGLT2is remain unacceptably 30%–50% patients eligible 3%–8% prescribed treatment (3,4). Rates prescription historically marginalized communities even lower than those general population, contributing existing inequities kidney care (5). patients, low may related perceived side effects, cost, access medicine clinical inertia. Limited recognition clear impactful benefits nephroprotective treatments among prescribers impedes their uptake. problem particularly relevant nondiabetic CKD, whom few effective options have been available. issue CJASN, Vart et al. (6) attempt address barrier by providing robust estimates real-world (in terms eventfree life years gained) when appropriately treated combination medications plus versus no therapy. authors took advantage individual-level trial data three large randomized studies enrolled albuminuric, CKD: Ramipril Efficacy Nephropathy (7), Guangzhou (8), Dapagliflozin Chronic Kidney Disease (9). primary composite end point consisted sustained doubling serum creatinine, failure, or all-cause mortality, secondary creatinine failure. Assuming independent hazard ratios were estimated therapy using indirect comparison methods. To account effect age on size, survival was basis initiation, ranging 50–75 years. effects were, perhaps not surprisingly, remarkable. Over 3 years, resulted absolute risk reductions 17%–29% 15%–22% point. Corresponding numbers needed treat four six five seven, respectively. sizeable reduction translated additional 7.4 free between ages 50 75 ACEi SGLT2i combination. Treatment declined, still significant, started later 50, improvements 5.6, 3.6, 2.8 initiated 55, 60, 65 sensitivity analysis observational Renal Insufficiency Cohort, participants who ACEi/ARB showed similar results, expected provide benefit 7.7 survival. explored variations size depending less fully additive models, adherence, loss efficacy time. all variables projected as suboptimal, gained remained meaningful 3.7 work thus first clear, evidence-derived assessments tangible disease. These entryway nephrology implement goal-directed medical (Figure 1). Such information will prove invaluable providers, both how they balance risks joint decision making. Ideally, translate improved personalized assessments, Failure Risk Equation (10), if it include without treatments, assisting providers advance also commended integrating calculated therapy, note competing greater advancing age, resulting diminished size. notion rising elderly highly prevalent often burdens, altering profile.Figure 1.: Proposed flow chart establishing guideline-directed dashed arrow represents theoretical direct connection whereas solid arrows represent necessary steps implementation. figure focused specific guideline puts context.The impressive findings tool advocacy efforts improve coverage medicines, especially SGLT2is, which currently cost prohibitive many, most need. Although become generic next drug pipeline consists recently approved more appear way. ability convey importance slowing policy makers payors critical maximizing broad availability these medications. Study methods allowing comparisons, used study, increasingly important available, we tailor combinations better suited populations. Lastly, major made prevention platform launch high CKD. 2012, US Preventive Services Task Force (USPSTF) decided against review update recommendations screening. Much changed since including increase appreciation factors apart hypertension, disease, obesity, genetic factors, APOL1-associated African ancestry. "coronary equivalent" role eGFR play future events death come forefront. evidenced article (6), now clearly least now, presence indicator use. USPTF again asked consider risk, regardless diabetes, hopefully, results study considered. cusp era evidence-based morbidity mortality associated development new reaching point, equally essential order afforded benefit. Cardiology led way opportunity follow suit. A shared understanding crucial step. Disclosures A.K. Mottl reports consulting fees Bayer Chinook; research funding Alexion, Aurinia, Bayer, Calliditas, Duke Clinical Research Institute, Pfizer, University Pennsylvania; honoraria UpToDate; advisory leadership roles Chinook. E.M. Zeitler's spouse Dexcom, Novo Nordisk, Rhythm Pharmaceuticals, VTV Therapeutics. Funding None.

Language: Английский

Unlocking the potential: boosting SGLT2 inhibitor uptake to prevent the cardiorenal consequences of chronic kidney disease DOI Creative Commons
Julio A. Lamprea‐Montealegre

The Lancet Regional Health - Western Pacific, Journal Year: 2024, Volume and Issue: 43, P. 101004 - 101004

Published: Jan. 15, 2024

Chronic kidney disease (CKD) is projected to become the fifth leading cause of death worldwide by 2030.1Foreman K.J. Marquez N. Dolgert A. et al.Forecasting life expectancy, years lost, and all-cause cause-specific mortality for 250 causes death: reference alternative scenarios 2016-40 195 countries territories.Lancet. 2018; 392: 2052-2090Summary Full Text PDF PubMed Scopus (1102) Google Scholar Considering its severe health consequences, including renal cardiovascular complications, it imperative adopt measures that mitigate these risks from both clinical public perspectives. The advent SGLT2 inhibitors marks a significant advancement in therapeutic options prevent cardiorenal consequences CKD. With robust evidence supporting their efficacy, time now intensify implementation efforts ensure life-saving drugs reach patients who need them most. As class, have consistently demonstrated protective effects. Meta-analyses randomized trials involving with CKD shown reductions progression, end-stage disease, acute injury, heart failure hospitalizations, mortality.2Nuffield Department Population Health Renal Studies GroupSGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists' ConsortiumImpact diabetes on effects sodium glucose co-transporter-2 outcomes: collaborative meta-analysis large placebo-controlled trials.Lancet. 2022; 400: 1788-1801Summary (182) These been observed across spectrum are evident irrespective presence diabetes. However, despite compelling protection, data potential impact medications broader population still relatively scarce. In Lancet Regional Health—Western Pacific,3Neuen B.L. Jun M. Wick J. al.Estimating population-level impacts improved uptake chronic disease: cross-sectional observational study using routinely collected Australian primary care data.Lancet Reg Western Pac. 2024; 43100988https://doi.org/10.1016/j.lanwpc.2023.100988Summary Neuen colleagues report comprehensive analysis conducted MedicineInsight, nationally representative individual-level dataset encompassing 392 practices Australia. aimed quantify absolute number cardio-renal events potentially preventable through optimal usage– defined as 75% among adult population. authors utilized MedicineInsight identify an eGFR < 60 ml/min/1.73 m2 and/or urinary albumin creatinine ratio >3.4 mg/mmol. individuals were then matched inclusion criteria three pivotal CKD: CREDENCE, DAPA-CKD, EMPA-KIDNEY. Subsequently, they extrapolated age- sex-stratified prevalence (using different UACR definitions) national census data. This allowed estimate Australia, drawing effectiveness trials. Overall, during 2020–2021, 147,119 (12.1%) adults found > 3.5 Nearly half (44%) met EMPA-KIDNEY, 17% 7% CREDENCE.4Perkovic V. Jardine M.J. Neal B. al.Canagliflozin outcomes type 2 nephropathy.N Engl J Med. 2019; 380: 2295-2306Crossref (3459) Scholar, 5Heerspink H.J.L. Stefánsson B.V. Correa-Rotter R. al.Dapagliflozin disease.N 2020; 383: 1436-1446Crossref (2191) 6Herrington W.G. Staplin Wanner C. al.The EMPA-KIDNEY Collaborative Group. Empagliflozin 2023; 388: 117-127Crossref (0) Compared trials, was older, had higher eGFR, less likely established disease. Notably, renin angiotensin system (RAS) blockade usage substantially lower compared where virtually all participants background RAS inhibition. Baseline use very low ranging 4.1% eligible 14.4% CREDENCE patients. Using strict (eGFR 3.4 mgl/L at least occasions, 90 days apart), yielded numbers needed treat (NNT) one event 14 25, 15 27 avert over years. estimates translated into more than 3500 1000 could be prevented annually this therapy. findings remained various definitions, thresholds "optimal use," or absence provides valuable glimpse tangible real-world setting. It underscores key points: portion benefit inhibitors; current disappointingly low, only 15% high-risk (eligible CREDENCE) treatment; and, implementations yield benefits, far outweighing adverse study's limitation reliance rather directly inhibitors, trial Discrepancies often exist between demographic characteristics Additionally, medication adherence real world may not levels reducing expected benefits. Therefore, future studies should measure adherence, side effects, discontinuation rates accurately assess general Despite benefits society, remains strikingly low. Structural barriers care, such inadequate testing albuminuria treatment paradox those albuminuria—and consequently risk—are receive preventive treatments,7Chu C.D. Xia F. Du Y. al.Estimated US risk disease.JAMA Netw Open. 6e2326230Crossref (1) Scholar,8Lamprea-Montealegre J.A. Madden E. Tummalapalli S.L. al.Prescription patterns cardiovascular- kidney-protective therapies disease.Diabetes Care. 45: 2900-2906Crossref exacerbated SGLT2-specific challenges. include high costs, racial ethnic disparities prescriptions, lack knowledge about indications, effects.9Tummalapalli Montealegre J.L. Warnock Green Ibrahim S.A. Estrella M.M. Coverage, formulary restrictions, affordability sodium-glucose cotransporter insurance plan types.JAMA Forum. 2021; 2e214205Crossref (9) Scholar,10Lamprea-Montealegre al.Association race ethnicity prescription GLP1 receptor agonists veterans administration system.JAMA. 328: 861-871Crossref (20) To address barriers, coordinate multi-disciplinary critically needed. substantial advantages can realized proper warrant immediate concerted action. JALM supported funding National Heart, Lung, Blood Institute (1K99HL157721-01A1) related topic. Estimating dataImproved Australia has experiencing progression dying due Identifying strategies increase critical realising drug class. Full-Text Open Access

Language: Английский

Citations

1
Beyond clinical practice guidelines: The risk-treatment paradox in frail older adults DOI
Liang‐Kung Chen

Archives of Gerontology and Geriatrics, Journal Year: 2024, Volume and Issue: 119, P. 105369 - 105369

Published: Feb. 13, 2024

Language: Английский

Citations

1
Estimating the population-level kidney benefits of improved uptake of SGLT2 inhibitors in patients with chronic kidney disease in Australian primary care DOI Open Access
Brendon L. Neuen, Min Jun, James Wick

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 28, 2023

Abstract Background Although sodium glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of kidney failure and death in patients with chronic disease (CKD), they are underused routine clinical practice. We evaluated number CKD Australia that would be eligible for treatment an SGLT2 inhibitor estimated cardiorenal events could averted improved uptake inhibitors. Methods Using nationally-representative Australian primary care data (MedicineInsight), we identified have met inclusion criteria CREDENCE, DAPA-CKD, EMPA-KIDNEY trials between 1 January 2020 31 December 2021. applied these to age sex-stratified estimates prevalence from broader population (using national census data) generate population-level for: (1) (2) annual potentially preventable (CKD progression, failure, or due cardiovascular failure), based on trial event rates. Results In MedicineInsight, 44.2% adults eligibility inhibitor; baseline use was 4.1%. Applying population, 230,246 been any inhibitor. Optimal implementation (75% patients) annually by 3,644 (95% CI 3,526-3,764) 1,312 1,242-1,385), respectively. Conclusions Improved has potential prevent large numbers experiencing progression dying disease. Identifying strategies increase is critical realising benefits this drug class.

Language: Английский

Citations

2
Long-term lessons from EMPA-KIDNEY DOI
Lauren Heath, Carol A. Pollock

Nature Reviews Nephrology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

Language: Английский

Citations

0
Toward Guideline-Directed Medical Therapy in Nephrology DOI Open Access
Evan Zeitler, Amy K. Mottl

Clinical Journal of the American Society of Nephrology, Journal Year: 2022, Volume and Issue: 17(12), P. 1710 - 1712

Published: Nov. 22, 2022

Nephrology has seen a revolution over the last decade with discovery of multiple therapies to slow progression CKD and reduce cardiovascular disease burden. In addition angiotensin-converting enzyme inhibitors (ACEis) angiotensin receptor blockers (ARBs), there is trial-level evidence for nonsteroidal mineralocorticoid antagonists, endothelin glucagon-like peptide 1 agonists, and, at head pack, sodium-glucose cotransporter-2 (SGLT2is). This watershed provides tremendous opportunities turn from an inevitably progressive lethal into one that can be managed proactively, but lack implementation kept this possibility becoming reality. The barriers are myriad. First, screening rates very low, receipt albuminuria testing in only 35% people diabetes 4% hypertension (1). recommendation urine albumin-creatinine ratio well established; however, despite consensus such indicated other high-risk populations (2), dearth guidelines support it. Even after diagnosed, prescribing ACEis/ARBs SGLT2is remain unacceptably 30%–50% patients eligible 3%–8% prescribed treatment (3,4). Rates prescription historically marginalized communities even lower than those general population, contributing existing inequities kidney care (5). patients, low may related perceived side effects, cost, access medicine clinical inertia. Limited recognition clear impactful benefits nephroprotective treatments among prescribers impedes their uptake. problem particularly relevant nondiabetic CKD, whom few effective options have been available. issue CJASN, Vart et al. (6) attempt address barrier by providing robust estimates real-world (in terms eventfree life years gained) when appropriately treated combination medications plus versus no therapy. authors took advantage individual-level trial data three large randomized studies enrolled albuminuric, CKD: Ramipril Efficacy Nephropathy (7), Guangzhou (8), Dapagliflozin Chronic Kidney Disease (9). primary composite end point consisted sustained doubling serum creatinine, failure, or all-cause mortality, secondary creatinine failure. Assuming independent hazard ratios were estimated therapy using indirect comparison methods. To account effect age on size, survival was basis initiation, ranging 50–75 years. effects were, perhaps not surprisingly, remarkable. Over 3 years, resulted absolute risk reductions 17%–29% 15%–22% point. Corresponding numbers needed treat four six five seven, respectively. sizeable reduction translated additional 7.4 free between ages 50 75 ACEi SGLT2i combination. Treatment declined, still significant, started later 50, improvements 5.6, 3.6, 2.8 initiated 55, 60, 65 sensitivity analysis observational Renal Insufficiency Cohort, participants who ACEi/ARB showed similar results, expected provide benefit 7.7 survival. explored variations size depending less fully additive models, adherence, loss efficacy time. all variables projected as suboptimal, gained remained meaningful 3.7 work thus first clear, evidence-derived assessments tangible disease. These entryway nephrology implement goal-directed medical (Figure 1). Such information will prove invaluable providers, both how they balance risks joint decision making. Ideally, translate improved personalized assessments, Failure Risk Equation (10), if it include without treatments, assisting providers advance also commended integrating calculated therapy, note competing greater advancing age, resulting diminished size. notion rising elderly highly prevalent often burdens, altering profile.Figure 1.: Proposed flow chart establishing guideline-directed dashed arrow represents theoretical direct connection whereas solid arrows represent necessary steps implementation. figure focused specific guideline puts context.The impressive findings tool advocacy efforts improve coverage medicines, especially SGLT2is, which currently cost prohibitive many, most need. Although become generic next drug pipeline consists recently approved more appear way. ability convey importance slowing policy makers payors critical maximizing broad availability these medications. Study methods allowing comparisons, used study, increasingly important available, we tailor combinations better suited populations. Lastly, major made prevention platform launch high CKD. 2012, US Preventive Services Task Force (USPSTF) decided against review update recommendations screening. Much changed since including increase appreciation factors apart hypertension, disease, obesity, genetic factors, APOL1-associated African ancestry. "coronary equivalent" role eGFR play future events death come forefront. evidenced article (6), now clearly least now, presence indicator use. USPTF again asked consider risk, regardless diabetes, hopefully, results study considered. cusp era evidence-based morbidity mortality associated development new reaching point, equally essential order afforded benefit. Cardiology led way opportunity follow suit. A shared understanding crucial step. Disclosures A.K. Mottl reports consulting fees Bayer Chinook; research funding Alexion, Aurinia, Bayer, Calliditas, Duke Clinical Research Institute, Pfizer, University Pennsylvania; honoraria UpToDate; advisory leadership roles Chinook. E.M. Zeitler's spouse Dexcom, Novo Nordisk, Rhythm Pharmaceuticals, VTV Therapeutics. Funding None.

Language: Английский

Citations

1