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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

      Submit here before July 31, 2024

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      To Treat or Not to Treat? Cost-Effectiveness of Ace Inhibitors in Non-Diabetic Advanced Renal Disease - a Dutch Perspective

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          Abstract

          Background: Treating non-diabetic proteinuric patients with advanced renal disease with an angiotensin-converting enzyme (ACE) inhibitor is still subject to discussion. This study aims to determine the cost-effectiveness of ACE inhibitor therapy in this patient population in the Netherlands. Methods: We compared two strategies: first, treating patients with advanced renal disease with an ACE inhibitor and no-treatment. A lifetime Markov decision model was developed simulating the progression of renal disease and using published data on costs and health outcomes. A health care perspective was adopted. Results: In the base-case analysis, treatment with ACE inhibitors leads to higher benefits and lower costs and dominates the no-treatment strategy. Sensitivity analysis shows that the probability of savings is 83%. Conclusion: ACE inhibitor treatment for non-diabetic patients with advanced renal disease in the Netherlands is highly cost-effective and should therefore be considered.

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          Relation between kidney function, proteinuria, and adverse outcomes.

          Brenda R. Hemmelgarn, Braden J. Manns, Anita Lloyd … (2010)
          The current staging system for chronic kidney disease is based primarily on estimated glomerular filtration rate (eGFR) with lower eGFR associated with higher risk of adverse outcomes. Although proteinuria is also associated with adverse outcomes, it is not used to refine risk estimates of adverse events in this current system. To determine the association between reduced GFR, proteinuria, and adverse clinical outcomes. Community-based cohort study with participants identified from a province-wide laboratory registry that includes eGFR and proteinuria measurements from Alberta, Canada, between 2002 and 2007. There were 920 985 adults who had at least 1 outpatient serum creatinine measurement and who did not require renal replacement treatment at baseline. Proteinuria was assessed by urine dipstick or albumin-creatinine ratio (ACR). All-cause mortality, myocardial infarction, and progression to kidney failure. The majority of individuals (89.1%) had an eGFR of 60 mL/min/1.73 m(2) or greater. Over median follow-up of 35 months (range, 0-59 months), 27 959 participants (3.0%) died. The fully adjusted rate of all-cause mortality was higher in study participants with lower eGFRs or heavier proteinuria. Adjusted mortality rates were more than 2-fold higher among individuals with heavy proteinuria measured by urine dipstick and eGFR of 60 mL/min/1.73 m(2) or greater, as compared with those with eGFR of 45 to 59.9 mL/min/1.73 m(2) and normal protein excretion (rate, 7.2 [95% CI, 6.6-7.8] vs 2.9 [95% CI, 2.7-3.0] per 1000 person-years, respectively; rate ratio, 2.5 [95% CI, 2.3-2.7]). Similar results were observed when proteinuria was measured by ACR (15.9 [95% CI, 14.0-18.1] and 7.0 [95% CI, 6.4-7.6] per 1000 person-years for heavy and absent proteinuria, respectively; rate ratio, 2.3 [95% CI, 2.0-2.6]) and for the outcomes of hospitalization with acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine level. The risks of mortality, myocardial infarction, and progression to kidney failure associated with a given level of eGFR are independently increased in patients with higher levels of proteinuria.
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            Angiotensin-converting enzyme inhibitors.

            N J Brown, D E Vaughan (1998)
            ACE inhibitors have achieved widespread usage in the treatment of cardiovascular and renal disease. ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and hypertrophic properties of angiotensin II (Ang II) and the vasodilatory and natriuretic properties of bradykinin and alter the metabolism of a number of other vasoactive substances. ACE inhibitors differ in the chemical structure of their active moieties, in potency, in bioavailability, in plasma half-life, in route of elimination, in their distribution and affinity for tissue-bound ACE, and in whether they are administered as prodrugs. Thus, the side effects of ACE inhibitors can be divided into those that are class specific and those that relate to specific agents. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have proved effective in the treatment of hypertension, they decrease mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction, and they delay the progression of diabetic nephropathy. Ongoing studies will elucidate the effect of ACE inhibitors on cardiovascular mortality in essential hypertension, the role of ACE inhibitors in patients without ventricular dysfunction after myocardial infarction, and the role of ACE inhibitors compared with newly available angiotensin AT1 receptor antagonists.
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              Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial.

              Naoyuki Nakao, Ashio Yoshimura, Hiroyuki Morita … (2003)
              Present angiotensin-converting-enzyme inhibitor treatment fails to prevent progression of non-diabetic renal disease. We aimed to assess the efficacy and safety of combined treatment of angiotensin-converting-enzyme inhibitor and angiotensin-II receptor blocker, and monotherapy of each drug at its maximum dose, in patients with non-diabetic renal disease. 336 patients with non-diabetic renal disease were enrolled from one renal outpatient department in Japan. After screening and an 18-week run-in period, 263 patients were randomly assigned angiotensin-II receptor blocker (losartan, 100 mg daily), angiotensin-converting-enzyme inhibitor (trandolapril, 3 mg daily), or a combination of both drugs at equivalent doses. Survival analysis was done to compare the effects of each regimen on the combined primary endpoint of time to doubling of serum creatinine concentration or end-stage renal disease. Analysis was by intention to treat. Seven patients discontinued or were otherwise lost to follow-up. Ten (11%) of 85 patients on combination treatment reached the combined primary endpoint compared with 20 (23%) of 85 on trandolapril alone (hazard ratio 0.38, 95% CI 0.18-0.63, p=0.018) and 20 (23%) of 86 on losartan alone (0.40, 0.17-0.69, p=0.016). Covariates affecting renal survival were combination treatment (hazard ratio 0.38, 95% CI 0.18-0.63, p=0.011), age (1.30, 1.03-2.29, p=0.009), baseline renal function (1.80, 1.02-2.99, p=0.021), change in daily urinary protein excretion rate (0.58, 0.24-0.88, p=0.022), use of diuretics (0.80, 0.30-0.94, p=0.043), and antiproteinuric response to trandolapril (0.81, 0.21-0.91, p=0.039). Frequency of side-effects with combination treatment was the same as with trandolapril alone. Combination treatment safely retards progression of non-diabetic renal disease compared with monotherapy. However, since some patients reached the combined primary endpoint on combined treatment, further strategies for complete management of progressive non-diabetic renal disease need to be researched.
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                Author and article information

                Journal
                Journal ID (publisher-id): KBR
                Journal ID (nlm-ta): Kidney Blood Press Res
                Journal ID (doi): 10.1159/issn.1420-4096
                Title: Kidney and Blood Pressure Research
                Publisher: S. Karger AG
                ISSN (Print): 1420-4096
                ISSN (Electronic): 1423-0143
                Publication date Subscription-year: 2013
                Publication date (Print): May 2013
                Publication date (Electronic): 06 May 2013
                Volume: 37
                Issue: 2-3
                Pages: 168-180
                Affiliations
                aCAPHRI School for Public Health and Primary Care, Department of Health Services Research, Maastricht University, Maastricht, The Netherlands; bDepartment of General Practice/Family Medicine, Philipps University Marburg, Marburg, Germany; cFrankfurt School of Finance and Management, Frankfurt, Germany; dDepartment of Medicine III, RWTH-University Hospital Aachen, Aachen, Germany
                Author notes
                *Dr. Charles Christian Adarkwah, Department of Health Services Research, CAPHRI School for Public Health and, Primary Care, Maastricht University, Duboisdomein 30, 6229 GT Maastricht, (The Netherlands) E-Mail c.adarkwah@maastrichtuniversity.nl
                Article
                Publisher ID: 350142 Other ID: Kidney Blood Press Res 2013;37:168-180
                DOI: 10.1159/000350142
                PubMed ID: 23689440
                SO-VID: 7a866304-b6eb-4f21-80a7-ee147c5e0154
                Copyright © © 2013 S. Karger AG, Basel
                License:

                Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) ( http://www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date accepted : 12 April 2013
                Page count
                Pages: 13
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Angiotensin-converting enzyme inhibitors,Markov model,Advanced renal disease,Cost-effectiveness,Decision modeling
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Angiotensin-converting enzyme inhibitors, Markov model, Advanced renal disease, Cost-effectiveness, Decision modeling

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