The current consensus, based on several clinical trials, is that RAS inhibition provides no benefit for primary prevention in normoalbuminuric, normotensive patients with diabetes and may actually lead to harm (18). HHS Arnold AC, Okamoto LE, Gamboa A, Shibao C, Raj SR, Robertson D, Biaggioni I. designed the clinical trial. HRs for the various outcomes in each baseline albuminuria stratum and for the combined strata are shown in Table 2. Cumulative HRs and 95% CIs for the primary GFR outcome at trial closeout and each year of the posttrial follow-up (bottom panel). The Collaborative Study Group, Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy, Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes, Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group, The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes, The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group, Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency, An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function, initial angiotensin receptor blockade-induced decrease in albuminuria is associated with long-term renal outcome in type 2 diabetic patients with microalbuminuria: a post hoc analysis of the IRMA-2 trial, KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update, The Randomized Olmesartan and Diabetes Microalbuminuria Prevention (ROADMAP) observational follow-up study: benefits of RAS blockade with olmesartan treatment are sustained after study discontinuation, Adjusting for treatment effects in studies of quantitative traits: antihypertensive therapy and systolic blood pressure, Long-term effects of ramipril on cardiovascular events and on diabetes: results of the HOPE study extension, Long-term hemodynamic and molecular effects persist after discontinued renin-angiotensin system blockade in patients with type 1 diabetes mellitus, Changing patterns of type 2 diabetes incidence among Pima Indians, Effect of youth-onset type 2 diabetes mellitus on incidence of end-stage renal disease and mortality in young and middle-aged Pima Indians, Predominant effect of kidney disease on mortality in Pima Indians with or without type 2 diabetes, Regression to the Mean Contributes to the Apparent Improvement in Glycemia 3.8 Years After Screening: The ELSA-Brasil Study, Postintervention Effects of Varying Treatment Arms on Glycemic Failure and β-Cell Function in the TODAY Trial, Worldwide Epidemiology of Diabetes-Related End-Stage Renal Disease, 2000–2015, Institutional Subscriptions and Site Licenses, Special Podcast Series: Therapeutic Inertia, Special Podcast Series: Influenza Podcasts, http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc16-0795/-/DC1, http://www.diabetesjournals.org/content/license. contributed to the data collection and critical revision of the manuscript for intellectual content. GFR was measured annually, and the primary end point that was specified in the protocol prior to completion of the clinical trial was a decline in GFR to ≤60 mL/min or to half of the baseline value in participants with a baseline GFR <120 mL/min. Twenty-six participants progressed to ESRD during follow-up (11 were randomized to placebo and 15 to losartan). Characteristics at the last clinical trial visit for the 149 participants who remained posttrial were similar between treatment groups (Table 1). Although the cumulative HR increased initially following completion of the clinical trial, it then began to decline again, but remained not statistically significant during the follow-up period. Data on other antihypertensive drugs received during and after the trial were ascertained by self-report. CONCLUSIONS Long-term risk of GFR decline was not significantly different between persons randomized to early treatment with losartan and those randomized to placebo. R.G.N. Dashed line, placebo; solid line, losartan. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Angiotensin II, independent of plasma renin activity, contributes to the hypertension of autonomic failure. Losartan is an angiotensin II receptor blocker (ARB). The Different Therapeutic Choices with ARBs. performed the statistical analysis. G.D.F. In participants who progressed to ESRD without a GFR measurement indicating that they had reached the GFR outcome, a GFR of zero was assigned as of the date of onset of renal replacement therapy. Because the acute and chronic effects are different, accounting for them is difficult, particularly when change in GFR is the outcome. In this study, we report results from analyses that include the posttrial period. In conclusion, we found that early treatment with losartan in American Indians with type 2 diabetes did not lead to a statistically significant reduction in the risk of renal function loss relative to placebo during extended follow-up that included a median of ∼8 years of observation following 6 years of randomized treatment. To study the losartan influence on renal function and uric acid (UA), CRP and baseline immunoreactive insulin (IRI) plasma concentration in essential hypertensive (EH) patients (pts) with hypertensive Chronic Kidney Disease (CKD). This site needs JavaScript to work properly. Progression to macroalbuminuria (ACR ≥300 mg/g) was examined as a secondary outcome. The 2-year follow-up interval was selected because it represented the median time interval between the last GFR measurement and the onset of ESRD in the study cohort. Besides, because the medicine contains potassium, which will be harmful for kidney disease patients who have high potassiu… In the microalbuminuria group, the HR for developing macroalbuminuria was 0.68 (95% CI 0.40–1.18). The dosage of losartan was 50 mg/day. NCT00340678, clinicaltrials.gov. Smith MC, Barrows S, Meibohm A, Shahinfar S, Simpson RL, Weigel K, Dunn MJ. Our study highlights the need for larger studies and long-term follow-up to evaluate the renoprotective efficacy of RAS inhibitors in persons with early diabetic kidney disease or with no clinically apparent kidney disease if currently accepted outcomes are used. The Epidemiology of Diabetes Interventions and Complications (EDIC) study showed significant sustained reduction in risk of impaired glomerular filtration rate (GFR) (1) and nephropathy during the posttrial period in participants with type 1 diabetes who received intensive glucose control for 6.5 years (2). Losartan is used to treat high blood pressure (hypertension) and to help protect the kidneys from damage due to diabetes. Consistent with previous findings in antihypertensive drug trials in type 2 diabetes (12–14,19), risk of all-cause mortality in our study did not differ between those randomized to losartan or placebo. Losartan potassium is a prescription medication commonly used to lower blood pressure in people with hypertension (high blood pressure). One trial reported that treatment with losartan slowed the rate of estimated GFR decline in patients with macroalbuminuria (16), whereas another found that a reduction in the development of elevated albuminuria in irbesartan-treated patients with microalbuminuria was independently associated with reduced estimated GFR decline (17), but neither study demonstrated reduction in clinical outcomes such as ESRD. 11. The advantages of angiotensin II antagonism. Although the number of ESRD events was insufficient for informative analyses, the HR for death in those receiving losartan versus placebo was 0.79 (95% CI 0.47–1.32) and for either ESRD or death was 0.88 (95% CI 0.56–1.40). Kidney damage is one of several reported risks and side effects for statins. Calcium oxalate (CaOx) is the most common type of urinary stone. There was a significant difference in MAP by treatment group throughout the study period (P = 0.04), but not for HbA1c. Subjects who did not participate in the posttrial follow-up did not differ from those who did in terms of age, sex, diabetes duration, BMI, blood pressure, HbA1c, GFR, and ACR at baseline. © 2016 by the American Diabetes Association. Kidney stones is found among people who take Losartan potassium, especially for people who are male, 60+ old, have been taking the drug for 1 - 6 months. The main strengths of this study include the use of measured GFR and the long follow-up period. At baseline, 92 participants had normoalbuminuria (albumin/creatinine ratio [ACR] <30 mg/g) and 78 had microalbuminuria (ACR 30 to <300 mg/g). Intervals between research examinations sometimes increased as kidney disease progressed, which could lead to differential misclassification of the study-based outcomes (GFR and albuminuria), requiring an imputation method to compute these outcomes. In this single-blind study, renal hemodynamic parameters were determined twice (patients were their own controls) first after a 15-day single-blind placebo run-in period and again after a 1-month losartan period. It prevents the blood vessels in your body from narrowing, thus lowering your blood pressure and improving the blood circulation. Blocking angiotensin II widens (dilates) blood vessels which lowers blood pressure. Losartan belongs to the angiotensin II receptor antagonists group of drugs. This eMedTV page provides other warnings and precautions with losartan, including information on who should not take this drug. Losartan is also used to slow long-term kidney damage in people with type 2 diabetes who also have high blood pressure. The same approach was used to compute follow-up time and event status for the albuminuria outcome, assuming that development of ESRD also reflected progression to macroalbuminuria. Closing date for the clinical trial was determined either by date of last examination during the randomized treatment study or by date of biopsy for those who agreed to a kidney biopsy. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. In addition, a decision was made midway through the clinical trial to suggest that those who managed these patients consider using other RAS inhibitors in their treatment regimens. E.J.W. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. The proportionality assumption was met by each covariate. It is also used to lower the risk of strokes in patients with high blood pressure and an enlarged heart. To avoid extrapolations over too long an interval, the imputation was truncated at 2 years after the last measured GFR, so that follow-up continued for each participant for 2 years after the last measured GFR or until the primary GFR outcome, death, or 31 December 2015, whichever came first. Among the 51 participants with microalbuminuria who had a kidney biopsy at the end of the clinical trial, those who received losartan during the 6-year trial had lower mesangial fractional volume and higher filtration surface area than those who received a placebo. Am J Hypertens. We examined the renal hemodynamic modifications induced by a selective angiotensin II (AII) AT1 receptor antagonist, losartan, in 10 patients with essential hypertension. Participants in the current study had previously completed a 6-year randomized clinical trial of losartan versus placebo in which few participants reached the primary GFR outcome, and the risk of progression between treatment groups was not statistically significant. At enrollment, GFR averaged 165 mL/min (interquartile range 49–313 mL/min). Characteristics of the study population at the beginning of posttrial follow-up were compared between treatment groups using an independent samples t test for normally distributed variables and the Kruskal-Wallis test for nonnormally distributed variables. R.G.N. 2. Ischemia/reperfusion (I/R) is a major cause of acute kidney injury. Times to outcomes were compared by treatment group using Kaplan-Meier survival curves and the log-rank test. The effect of treatment on death or the combined end point of end-stage renal disease (ESRD) or death was also examined. Given the apparent structural preservation associated with early losartan treatment, we hypothesized that early treatment would provide an extended benefit in reducing the risk of GFR decline in diabetic kidney disease, similar to that observed for early intensive glycemic control. Nakamura M, Sasai N, Hisatome I, Ichida K. Clin Pharmacol. After 1-month losartan treatment, systolic and diastolic BP (SBP, DBP) decreased significantly throughout the 210-min recording whereas heart rate (HR) was unchanged. An extended benefit of early intensive glycemic control on microvascular complications even after subsequent return to conventional glycemic control is well described. This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Losartan works by blocking the effect of angiotensin II, a hormone that causes blood vessels to narrow (constrict) increasing blood pressure. As no significant interaction was found between treatment assignment and albuminuria group (P = 0.20), the overall treatment effect was estimated. Chida R, Hisauchi I, Toyoda S, Kikuchi M, Komatsu T, Hori Y, Nakahara S, Sakai Y, Inoue T, Taguchi I. Hypertens Res. 1); 16 were randomized to placebo and 18 to losartan in the normoalbuminuria group (P = 0.14) and 28 to placebo and 24 to losartan in the microalbuminuria group (P = 0.26). To estimate the date of onset of the primary GFR outcome, a linear GFR slope was computed in each participant based on the last two GFR values, with the last GFR value defined as follows: In participants who did not reach the primary GFR outcome, the GFR measured at their last examination; In participants who reached the primary GFR outcome at an examination, the GFR value measured at that examination; and. Losartan may also be used for purposes not listed in this medication guide. Doctors prescribe it to treat hypertension and nephropathy, which is damage … We examined the renal hemodynamic modifications induced by a selective angiotensin II (AII) AT1 receptor antagonist, losartan, in 10 patients with essential hypertension. The estimated date of onset of the primary GFR outcome was then imputed for all participants from the GFR slope. RESEARCH DESIGN AND METHODS We conducted a 6-year clinical trial in 169 American Indians with type 2 diabetes and urine albumin/creatinine ratio <300 mg/g; 84 participants were randomly assigned to receive losartan and 85 to placebo. 1995 Dec;8(12 Pt 1):1177-83. doi: 10.1016/0895-7061(95)00361-4. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. During a median of 13.5 years following randomization, 29 participants originally assigned to losartan and 35 to placebo reached the primary GFR outcome with an HR of 0.72 (95% CI 0.44–1.18). Clipboard, Search History, and several other advanced features are temporarily unavailable. This medication has the ability to lower the possible risk of a stroke in people suffering from any heart condition. Clin Sci (Lond). During the trial, nine persons reached the primary outcome with a hazard ratio (HR; losartan vs. placebo) of 0.50 (95% CI 0.12–1.99). Acute kidney failure is found among people who take Losartan potassium, especially for people who are female, 60+ old, have been taking the drug for 5 - 10 years. Combining Blood Pressure Drugs May Increase Kidney Damage Risk November 19, 2013 Written by: Martha Garcia 1 Comment; New research suggests that …  |  This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc16-0795/-/DC1. 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