Medline ® Abstracts for References 6,55,61,65,98
of 'Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults'
Time-updated systolic blood pressure and the progression of chronic kidney disease: a cohort study.
Anderson AH, Yang W, Townsend RR, Pan Q, Chertow GM, Kusek JW, Charleston J, He J, Kallem R, Lash JP, Miller ER 3rd, Rahman M, Steigerwalt S, Weir M, Wright JT Jr, Feldman HI, Chronic Renal Insufficiency Cohort Study Investigators
Ann Intern Med. 2015 Feb;162(4):258-65.
BACKGROUND: Previous reports of the longitudinal association between achieved blood pressure (BP) and end-stage renal disease (ESRD) among patients with chronic kidney disease (CKD) have not incorporated time-updated BP with appropriate covariate adjustment.
OBJECTIVE: To assess the association between baseline and time-updated systolic blood pressure (SBP) with CKD progression.
DESIGN: Observational, prospective cohort study. (ClinicalTrials.gov: NCT00304148).
SETTING: 7 U.S. clinical centers.
PATIENTS: Patients in the Chronic Renal Insufficiency Cohort Study (n = 3708) followed for a median of 5.7 years (25th to 75th percentile, 4.6 to 6.7 years).
MEASUREMENTS: The mean of 3 seated SBP measurements made up the visit-specific SBP. Time-updated SBP was the mean of that and all previous visits. Outcomes were ESRD and the composite end point of ESRD or halving of the estimated glomerular filtration rate. Analyses investigating baseline and time-updated SBP used Cox proportional hazards models and marginal structural models, respectively.
RESULTS: Systolic blood pressure was 130 mm Hg or greater at all visits in 19.2% of patients. The hazard ratio for ESRD among patients with SBP of 130 to 139 mm Hg, compared with SBP less than 120 mm Hg, was 1.46 (95% CI, 1.13 to 1.88) using only baseline data and 2.37 (CI, 1.48 to 3.80) using time-updated data. Among patients with SBP of 140 mm Hg or greater, corresponding hazard ratios were 1.46 (CI, 1.18 to 1.88) and 3.37 (CI, 2.26 to 5.03) for models using only baseline data and those using time-updated data, respectively.
LIMITATION: Blood pressure was measured once annually, and the cohort was not a random sample.
CONCLUSION: Time-updated SBP greater than 130 mm Hg was more strongly associated with CKD progression than analyses based on baseline SBP.
PRIMARY FUNDING SOURCE: National Institute of Diabetes and Digestive and Kidney Diseases.
Screening for, monitoring, and treatment of chronic kidney disease stages 1 to 3: a systematic review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline.
Fink HA, Ishani A, Taylor BC, Greer NL, MacDonald R, Rossini D, Sadiq S, Lankireddy S, Kane RL, Wilt TJ
Ann Intern Med. 2012;156(8):570.
BACKGROUND: Screening and monitoring for chronic kidney disease (CKD) could lead to earlier interventions that improve clinical outcomes.
PURPOSE: To summarize evidence about the benefits and harms of screening for and monitoring and treatment of CKD stages 1 to 3 in adults.
DATA SOURCES: MEDLINE (1985 through November 2011), reference lists, and expert suggestions.
STUDY SELECTION: English-language, randomized, controlled trials that evaluated screening for or monitoring or treatment of CKD and that reported clinical outcomes.
DATA EXTRACTION: Two reviewers assessed study characteristics and rated quality and strength of evidence.
DATA SYNTHESIS: No trials evaluated screening or monitoring, and 110 evaluated treatments. Angiotensin-converting enzyme inhibitors (relative risk, 0.65 [95% CI, 0.49 to 0.88]) and angiotensin II-receptor blockers (relative risk, 0.77 [CI, 0.66 to 0.90]) reduced end-stage renal disease versus placebo, primarily in patients with diabetes who have macroalbuminuria. Angiotensin-converting enzyme inhibitors reduced mortality versus placebo (relative risk, 0.79 [CI, 0.66 to 0.96]) in patients with microalbuminuria and cardiovascular disease or high-risk diabetes. Statins andβ-blockers reduced mortality and cardiovascular events versus placebo or control in patients with impaired estimated glomerular filtration rate and either hyperlipidemia or congestive heart failure, respectively. Risks for mortality, end-stage renal disease, or other clinical outcomes did not significantly differ between strict and usual blood pressure control. The strength of evidence was rated high for angiotensin II-receptor blockers and statins, moderate for angiotensin-converting enzyme inhibitors andβ-blockers, and low for strict blood pressure control.
LIMITATIONS: Evidence about outcomes was sometimes scant and derived from post hoc analyses of subgroups of patients enrolled in trials. Few trials reported or systematically collected information about adverse events. Selective reporting and publication bias were possible.
CONCLUSION: The role of CKD screening or monitoring in improving clinical outcomes is uncertain. Evidence for CKD treatment benefit is strongest for angiotensin-converting enzyme inhibitors and angiotensin II-receptor blockers, and in patients with albuminuria combined with diabetes or cardiovascular disease.
PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.
Geriatric Research, Education, and Clinical Center, Minneapolis, Minnesota, USA. email@example.com
Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and combined therapy in patients with micro- and macroalbuminuria and other cardiovascular risk factors: a systematic review of randomized controlled trials.
Maione A, Navaneethan SD, Graziano G, Mitchell R, Johnson D, Mann JF, Gao P, Craig JC, Tognoni G, Perkovic V, Nicolucci A, De Cosmo S, Sasso A, Lamacchia O, Cignarelli M, Manfreda VM, Gentile G, Strippoli GF
Nephrol Dial Transplant. 2011 Sep;26(9):2827-47. Epub 2011 Mar 3.
BACKGROUND: A recent clinical trial showed harmful renal effects with the combined use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) in people with diabetes or vascular disease. We examined the benefits and risks of these agents in people with albuminuria and one or more cardiovascular risk factors.
METHODS: MEDLINE, EMBASE and Renal Health Library were searched for trials comparing ACEI, ARB or their combination with placebo or with one another in people with albuminuria and one or more cardiovascular risk factor.
RESULTS: Eighty-five trials (21,708 patients) were included. There was no significant reduction in the risk of all-cause mortality or fatal cardiac-cerebrovascular outcomes with ACEI versus placebo, ARB versus placebo, ACEI versus ARBor with combined therapy with ACEI + ARB versus monotherapy. There was a significant reduction in the risk of nonfatal cardiovascular events with ACEI versus placebo but not with ARB versus placebo, ACEI versus ARB or with combined therapy with ACEI + ARB versus monotherapy. Development of end-stage kidney disease and progression of microalbuminuria to macroalbuminuria were reduced significantly with ACEI versus placebo and ARB versus placebo but not with combined therapy with ACEI + ARB versus monotherapy.
CONCLUSIONS: ACEI and ARB exert independent renal and nonfatal cardiovascular benefits while their effects on mortality and fatal cardiovascular disease are uncertain. There is a lack of evidence to support the use of combination therapy. A comparative clinical trial with ACE, ARB and its combination in people with albuminuria and a cardiovascular risk factor is warranted.
Department of Pharmacology and Clinical Epidemiology, Mario Negri Sud Consortium, S. Maria Imbaro (Ch), Italy.
Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia)
BACKGROUND: In diabetic nephropathy, angiotensin-converting-enzyme (ACE) inhibitors have a greater effect than other antihypertensive drugs on proteinuria and the progressive decline in glomerular filtration rate (GFR). Whether this difference applies to progression of nondiabetic proteinuric nephropathies is not clear. The Ramipril Efficacy in Nephropathy study of chronic nondiabetic nephropathies aimed to address whether glomerular protein traffic influences renal-disease progression, and whether an ACE inhibitor was superior to conventional treatment, with the same blood-pressure control, in reducing proteinuria, limiting GFR decline, and preventing endstage renal disease.
METHODS: In this prospective double-blind trial, 352 patients were classified according to baseline proteinuria (stratum 1: 1-3 g/24 h; stratum 2:>or = 3 g/24 h), and randomly assigned ramipril or placebo plus conventional antihypertensive therapy targeted at achieving diastolic blood pressure under 90 mm Hg. The primary endpoint was the rate of GFR decline. Analysis was by intention to treat.
FINDINGS: At the second planned interim analysis, the difference in declinein GFR between the ramipril and placebo groups in stratum 2 was highly significant (p = 0.001). The Independent Adjudicating Panel therefore decided to open the randomisation code and do the final analysis in this stratum (stratum 1 continued in the trial). Data (at least three GFR measurements including baseline) were available for 56 ramipril-assigned patients and 61 placebo-assigned patients. The decline in GFR per month was significantly lower in the ramipril group than the placebo group (0.53 [0.08]vs 0.88 [0.13]mL/min, p = 0.03). Among the ramipril-assigned patients, percentage reduction in proteinuria was inversely correlated with decline in GFR (p = 0.035) and predicted the reduction in risk of doubling of baseline creatinine or endstage renal failure (18 ramipril vs 40 placebo, p = 0.04). The risk of progression was still significantly reduced after adjustment for changes in systolic (p = 0.04) and diastolic (p = 0.04) blood pressure, but not after adjustment for changes in proteinuria. Blood-pressure control and the overall number of cardiovascular events were similar in the two treatment groups.
INTERPRETATION: In chronic nephropathies with proteinuria of 3 g or more per 24 h, ramipril safely reduces proteinuria and the rate of GFR decline to an extent that seems to exceed the reduction expected for the degree of blood-pressure lowering.
Cardiovascular and renal outcomes with telmisartan, ramipril, or both in people at high renal risk: results from the ONTARGET and TRANSCEND studies.
Tobe SW, Clase CM, Gao P, McQueen M, Grosshennig A, Wang X, Teo KK, Yusuf S, Mann JF, ONTARGET and TRANSCEND Investigators
BACKGROUND: In the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), dual therapy did not reduce cardiovascular or renal outcomes compared with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers alone. Previous controlled trials with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have demonstrated greater cardiovascular and renal benefit in people with renal risk. We hypothesized that dual therapy would be more effective than monotherapy in patients with low glomerular filtration rate and elevated albuminuria.
METHODS AND RESULTS: Post hoc analysis was performed of renal subgroups of dual therapy versus monotherapy for the ONTARGET study and angiotensin receptor blocker versus placebo for the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND). The studies featured hazard ratios by subgroups and Cox regression models with factors for treatment, subgroup, and interactions. The main cardiovascular outcome was the composite of cardiovasculardeath, myocardial infarction, stroke, or hospitalization for heart failure, and the main renal outcome was the composite of chronic dialysis or doubling of creatinine. In ONTARGET, there was no cardiovascular or renal benefit from dual over monotherapy in any subgroup, even with low glomerular filtration rate and/or elevated albuminuria. In TRANSCEND, in the comparison of angiotensin receptor blocker with placebo, there was a significant interaction for the main renal outcome (P = 0.01) in the direction of harm for patients with normoalbuminuria (0.37 versus 0.16 events per 100 patient-years; hazard ratio, 2.35; confidence interval, 1.33 to 4.15) but a trend to benefit with microalbuminuria (0.52 versus 0.89 events per 100 patient-years; hazard ratio, 0.60; confidence interval, 0.25 to 1.46) and macroalbuminuria (1.57 versus 2.60 events per 100 patient-years; hazard ratio, 0.71; confidence interval, 0.21 to 2.44).
CONCLUSIONS: This post hoc analysis does not support dual therapy over monotherapy in high-vascular risk patients with low glomerular filtration rate or albuminuria. This observation is a post hoc comparison and should be interpreted appropriately.
CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov Identifier: NCT00153101.
Division of Nephrology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada. firstname.lastname@example.org