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Barriers to ACEI/ARB Use in Proteinuric Chronic Kidney Disease: An Observational Study



      To assess present angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) use among patients with proteinuric chronic kidney disease (CKD) and examine barriers limiting this guideline-concordant care.

      Patients and Methods

      Using a nationwide database containing patient-level claims and integrated clinical information, we examined current ACEI/ARB prescriptions on the index date (April 15, 2017) and prior ACEI/ARB use in 41,743 insured adults with proteinuric CKD. Using multivariable logistic regression, we estimated adjusted associations between current ACEI/ARB use and putative barriers including past acute kidney injury (AKI), hyperkalemia, advanced CKD, and lack of nephrology care.


      Only 49% (n=20,641) of patients had an active ACEI/ARB prescription on the index date, but 87% (n=36,199) had been previously prescribed an ACEI/ARB. Use was lower in patients with past AKI, hyperkalemia, CKD stages 4 or 5, and a lack of nephrology care (adjusted odds ratios were 0.61 [95% CI, 0.58 to 0.64], 0.76 [95% CI, 0.72 to 0.80], 0.48 [95% CI, 0.45 to 0.51], and 0.85 [95% CI, 0.81 to 0.89], respectively).


      Discontinuing, rather than never initiating, ACEI/ARB treatment limits guideline-concordant care in proteinuric CKD. Past AKI, hyperkalemia, advanced CKD, and lack of nephrology care were associated with lower use of ACEIs/ARBs, but these putative barriers may in many instances be inappropriate (AKI and advanced CKD) or modifiable (hyperkalemia and lack of nephrology care).

      Abbreviations and Acronyms:

      ACEI (angiotensin-converting enzyme inhibitor), AKI (acute kidney injury), ARB (angiotensin receptor blocker), CKD (chronic kidney disease), eGFR (estimated glomerular filtration rate), ICD-9/10 (International Classification of Diseases, Ninth/Tenth Revision), MRA (mineralocorticoid receptor antagonist), NSAID (nonsteroidal anti-inflammatory drug), RAAS (renin-angiotensin-aldosterone system), UACR (urinary albumin-creatinine ratio), UPCR (urinary protein-creatinine ratio)
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        • Brenner B.
        • Cooper M.
        • de Zeeuw D.
        • et al.
        • RENAAL Study Investigators
        Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.
        N Engl J Med. 2001; 345: 861-869
        • Lewis E.
        • Hunsicker L.
        • Clarke W.
        • et al.
        • Collaborative Study Group
        Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.
        N Engl J Med. 2001; 345: 851-860
        • Li P.K.T.
        • Leung C.B.
        • Chow K.M.
        • et al.
        • HKVIN Study Group
        Hong Kong Study Using Valsartan in IgA Nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study.
        Am J Kidney Dis. 2006; 47: 751-760
        • Jafar T.H.
        • Schmid C.H.
        • Landa M.
        • et al.
        Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data.
        Ann Intern Med. 2001; 135: 73-87
        • Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group
        KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease.
        Kidney Int Suppl. 2012; 2: 337-414
        • National Quality Forum
        NQF-endorsed measures for renal conditions 2015-2017. Published February 2017.
        (Accessed April 1, 2020.)
        • National Kidney Foundation
        K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Published 2004.
        • Mendu M.L.
        • Tummalapalli S.L.
        • Lentine K.L.
        • et al.
        Measuring quality in kidney care: an evaluation of existing quality metrics and approach to facilitating improvements in care delivery.
        J Am Soc Nephrol. 2020; 31: 602-614
      1. Measure #120. In: 2008 Physician Quality Reporting Initiative Specifications Document. The Centers for Medicare and Medicaid Services. Published 2008.
        (Accessed April 1, 2020.)
        • Tummalapalli S.L.
        • Powe N.R.
        • Keyhani S.
        Trends in quality of care for patients with CKD in the United States.
        Clin J Am Soc Nephrol. 2019; 14: 1142-1150
        • Murphy D.P.
        • Drawz P.E.
        • Foley R.N.
        Trends in angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker use among those with impaired kidney function in the United States.
        J Am Soc Nephrol. 2019; 30: 1314-1321
        • Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group
        KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.
        Kidney Int Suppl. 2013; 3: 1-150
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • et al.
        • CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612
      2. National Collaborating Centre for Chronic Conditions (UK). Chronic Kidney Disease: National Clinical Guideline for Early Identification and Management in Adults in Primary and Secondary Care. London: Royal College of Physicians (UK). 2018.

        • Qiao Y.
        • Shin J.I.
        • Sang Y.
        • et al.
        Discontinuation of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in chronic kidney disease.
        Mayo Clin Proc. 2019; 94: 2220-2229
        • Ohkuma T.
        • Jun M.
        • Rodgers A.
        • et al.
        • ADVANCE Collaborative Group
        Acute increases in serum creatinine after starting angiotensin-converting enzyme inhibitor-based therapy and effects of its continuation on major clinical outcomes in type 2 diabetes mellitus.
        Hypertension. 2019; 73: 84-91
        • Bakris G.L.
        • Weir M.R.
        Angiotensin-converting enzyme inhibitor–associated elevations in serum creatinine; is this a cause for concern?.
        Arch Intern Med. 2000; 160: 685-693
      3. National Institute for Health and Care Excellence Chronic kidney disease in adults: assessment and management: Clinical guideline [CG182]. NICE, 2014. Accessed April 1, 2020.

        • Whelton P.K.
        • Carey R.M.
        • Aronow W.S.
        • et al.
        2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults a report of the American College of Cardiology/American Heart Association Task Force on Clinical Prctice Guidelines.
        Hypertension. 2018; 71: E13-E115
        • Clark A.L.
        • Kalra P.R.
        • Petrie M.C.
        • Mark P.B.
        • Tomlinson L.A.
        • Tomson C.R.
        Change in renal function associated with drug treatment in heart failure: national guidance.
        Heart. 2019; 105: 904-910
        • Tomson C.
        • Tomlinson L.A.
        Stopping RAS inhibitors to minimize AKI more harm than good?.
        Clin J Am Soc Nephrol. 2019; 14: 617-619
        • Testani J.M.
        • Kimmel S.E.
        • Dries D.L.
        • Coca S.G.
        Prognostic importance of early worsening renal function after initiation of angiotensin-converting enzyme inhibitor therapy in patients with cardiac dysfunction.
        Circ Heart Fail. 2011; 4: 685-691
        • Chiu M.H.
        • Miller R.J.H.
        • Barry R.
        • et al.
        Kidney function, ACE-inhibitor/angiotensin receptor blocker use, and survival following hospitalization for heart failure: a cohort study.
        Can J Kidney Health Dis. 2018; 5 (2054358118804838)
        • Holtkamp F.A.
        • De Zeeuw D.
        • Thomas M.C.
        • et al.
        An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function.
        Kidney Int. 2011; 80: 282-287
        • McCoy I.E.
        • Chertow G.M.
        AKI—a relevant safety end point?.
        Am J Kidney Dis. 2020; 75: 508-512
        • Yildirim T.
        • Arici M.
        • Piskinpasa S.
        • et al.
        Major barriers against renin angiotensin aldosterone system blocker use in chronic kidney disease stages 3-5 in clinical practice: a safety concern?.
        Ren Fail. 2012; 34: 1095-1099
        • Raebel M.A.
        Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.
        Cardiovasc Ther. 2012; 30: 156-166
        • Bakris G.L.
        • Siomos M.
        • Richardson D.
        • et al.
        ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure.
        Kidney Int. 2000; 58: 2084-2092
        • Agarwal R.
        • Rossignol P.
        • Romero A.
        • et al.
        Patiromer versus placebo to enable spironolactone use in patients with resistant hypertension and chronic kidney disease (AMBER): a phase 2, randomised, double-blind, placebo-controlled trial.
        Lancet. 2019; 394: 1540-1550
        • Baron J.
        Tradeoffs among reasons for action.
        J Theory Soc Behav. 1986; 16: 173-195
        • Kahneman D.
        • Tversky A.
        The psychology of preferences.
        Sci Am. 1982; 246: 160-173
        • Murray E.
        • Reaven N.L.
        • Funk S.E.
        • McGaughey K.J.
        • Oestreicher N.
        • Knispel J.
        Evaluation of the treatment gap between clinical guidelines and the utilization of renin-angiotensin-aldosterone system inhibitors.
        Am J Manag Care. 2015; 21: S212-S220
        • Linde C.
        • Bakhai A.
        • Furuland H.
        • et al.
        Real-world associations of renin–angiotensin–aldosterone system inhibitor dose, hyperkalemia, and adverse clinical outcomes in a cohort of patients with new-onset chronic kidney disease or heart failure in the United Kingdom.
        J Am Heart Assoc. 2019; 8: e012655
        • Plantinga L.
        • Grubbs V.
        • Sarkar U.
        • et al.
        • CDC CKD Surveillance Team
        Nonsteroidal anti-inflammatory drug use among persons with chronic kidney disease in the United States.
        Ann Fam Med. 2011; 9: 423-430
        • Amsterdam E.A.
        • Wenger N.K.
        • Brindis R.G.
        • et al.
        2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
        J Am Coll Cardiol. 2014; 64: e139-e228
        • Yancy C.W.
        • Jessup M.
        • Bozkurt B.
        • et al.
        2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.
        Circulation. 2017; 136: e137-e161