Medline ® Abstracts for References 6,52-57

of 'Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults'

6
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Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis.
AU
Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, de Jong PE, de Zeeuw D, Shahinfar S, Toto R, Levey AS, AIPRD Study Group
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Ann Intern Med. 2003;139(4):244.
 
BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure and urine protein excretion and slow the progression of chronic kidney disease.
PURPOSE: To determine the levels of blood pressure and urine protein excretion associated with the lowest risk for progression of chronic kidney disease during antihypertensive therapy with and without ACE inhibitors.
DATA SOURCES: 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens with or without ACE inhibitors for patients with predominantly nondiabetic kidney disease.
STUDY SELECTION: MEDLINE database search for English-language studies published between 1977 and 1999.
DATA EXTRACTION: Data on 1860 nondiabetic patients were pooled in a patient-level meta-analysis. Progression of kidney disease was defined as a doubling of baseline serum creatinine level or onset of kidney failure. Multivariable regression analysis was performed to assess the association of systolic and diastolic blood pressure and urine protein excretion with kidney disease progression at 22 610 patient visits.
DATA SYNTHESIS: Mean duration of follow-up was 2.2 years. Kidney disease progression was documented in 311 patients. Systolic blood pressure of 110 to 129 mm Hg and urine protein excretion less than 2.0 g/d were associated with the lowest risk for kidney disease progression. Angiotensin-converting enzyme inhibitors remained beneficial after adjustment for blood pressure and urine protein excretion (relative risk, 0.67 [95% CI, 0.53 to 0.84]). The increased risk for kidney progression at higher systolic blood pressure levels was greater in patients with urine protein excretion greater than 1.0 g/d (P<0.006).
CONCLUSION: Although reverse causation cannot be excluded with certainty, a systolic blood pressure goal between 110 and 129 mm Hg may be beneficial in patients with urine protein excretion greater than 1.0 g/d. Systolic blood pressure less than 110 mm Hg may be associated with a higher risk for kidney disease progression.
AD
Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.
PMID
52
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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.
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Fink HA, Ishani A, Taylor BC, Greer NL, MacDonald R, Rossini D, Sadiq S, Lankireddy S, Kane RL, Wilt TJ
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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.
AD
Geriatric Research, Education, and Clinical Center, Minneapolis, Minnesota, USA. howard.fink@va.gov
PMID
53
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Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data.
AU
Jafar TH, Schmid CH, Landa M, Giatras I, Toto R, Remuzzi G, Maschio G, Brenner BM, Kamper A, Zucchelli P, Becker G, Himmelmann A, Bannister K, Landais P, Shahinfar S, de Jong PE, de Zeeuw D, Lau J, Levey AS
SO
Ann Intern Med. 2001;135(2):73.
 
PURPOSE: To examine the efficacy of ACE inhibitors for treatment of nondiabetic renal disease.
DATA SOURCES: 11 randomized, controlled trials comparing the efficacy of antihypertensive regimens including ACE inhibitors to the efficacy of regimens without ACE inhibitors in predominantly nondiabetic renal disease.
STUDY SELECTION: Studies were identified by searching the MEDLINE database for English-language studies evaluating the effects of ACE inhibitors on renal disease in humans between May 1977 (when ACE inhibitors were approved for trials in humans) and September 1997.
DATA EXTRACTION: Data on 1860 nondiabetic patients were analyzed.
DATA SYNTHESIS: Mean duration of follow-up was 2.2 years. Patients in the ACE inhibitor group had a greater mean decrease in systolic and diastolic blood pressure (4.5 mm Hg [95% CI, 3.0 to 6.1 mm Hg]) and 2.3 mm Hg [CI, 1.4 to 3.2 mm Hg], respectively) and urinary protein excretion (0.46 g/d [CI, 0.33 to 0.59 g/d]). After adjustment for patient and study characteristics at baseline and changes in systolic blood pressure and urinary protein excretion during follow-up, relative risks in the ACE inhibitor group were 0.69 (CI, 0.51 to 0.94) for end-stage renal disease and 0.70 (CI, 0.55 to 0.88) for the combined outcome of doubling of the baseline serum creatinine concentration or end-stage renal disease. Patients with greater urinary protein excretion at baseline benefited more from ACE inhibitor therapy (P = 0.03 and P = 0.001, respectively), but the data were inconclusive as to whether the benefit extended to patients with baseline urinary protein excretion less than 0.5 g/d.
CONCLUSION: Antihypertensive regimens that include ACE inhibitors are more effective than regimens without ACE inhibitors in slowing the progression of nondiabetic renal disease. The beneficial effect of ACE inhibitors is mediated by factors in addition to decreasing blood pressure and urinary protein excretion and is greater in patients with proteinuria. Angiotensin-converting inhibitors are indicated for treatment of nondiabetic patients with chronic renal disease and proteinuria and, possibly, those without proteinuria.
AD
Department of Medicine, The Aga Khan University, Stadium Road, PO Box 3500, Karachi, Pakistan.
PMID
54
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Effect of angiotensin-converting enzyme inhibitors on the progression of nondiabetic renal disease: a meta-analysis of randomized trials. Angiotensin-Converting-Enzyme Inhibition and Progressive Renal Disease Study Group.
AU
Giatras I, Lau J, Levey AS
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Ann Intern Med. 1997;127(5):337.
 
BACKGROUND: The effect of angiotensin-converting enzyme (ACE) inhibitors in slowing the decline in renal function in nondiabetic renal disease varies among studies.
PURPOSE: To use meta-analysis to assess the effect of ACE inhibitors on the development of end-stage renal disease caused by factors other than diabetes.
DATA SOURCES: The English-language medical literature, identified by a MEDLINE search and unpublished studies.
STUDY SELECTION: All randomized studies that compared ACE inhibitors with other antihypertensive agents and had at least 1 year of planned follow-up were selected. Studies of diabetic renal disease and renal transplants were excluded. A total of 1594 patients in 10 studies was included.
DATA EXTRACTION: Data on end-stage renal disease, death, drop out, and blood pressure wereextracted. Study investigators confirmed results and provided additional data.
DATA SYNTHESIS: Among 806 patients receiving ACE inhibitors, 52 (6.4%) developed end-stage renal disease and 17 (2.1%) died; in the 788 controls, the respective values were 72 (9.1%) and 12 (1.5%). The pooled relative risks were 0.70 (95% CI, 0.51 to 0.97) for end-stage renal disease and 1.24 (CI, 0.55 to 2.83) for death; the studies were not significantly heterogeneous. The decreases in weighted mean systolic and diastolic blood pressures during follow-up were 4.9 and 1.2 mm Hg greater, respectively, in the patients who received ACE inhibitors.
CONCLUSIONS: Angiotensin-converting enzyme inhibitors are more effective than other antihypertensive agents in reducing the development of end-stage nondiabetic renal disease, and they do not increase mortality. It could not be determined whether this beneficial effect is due to the greater decline in blood pressure or to other effects of ACE inhibition.
AD
New England Medical Center, Boston, Massachusetts, USA.
PMID
55
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Progression risk, urinary protein excretion, and treatment effects of angiotensin-converting enzyme inhibitors in nondiabetic kidney disease.
AU
Kent DM, Jafar TH, Hayward RA, Tighiouart H, Landa M, de Jong P, de Zeeuw D, Remuzzi G, Kamper AL, Levey AS
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J Am Soc Nephrol. 2007;18(6):1959.
 
It is unclear whether patients with nondiabetic kidney disease benefit from angiotensin-converting enzyme inhibitor (ACEI) therapy when they are at low risk for disease progression or when they have low urinary protein excretion. With the use of a combined database from 11 randomized, clinical trials (n = 1860), a Cox proportional hazards model, based on known predictors of risk and the composite outcome kidney failure or creatinine doubling, was developed and used to stratify patients into equal-sized quartiles of risk. Outcome risk and treatment effect were examined across various risk strata. Use of this risk model for targeting ACEI therapy was also compared with a strategy based on urinary protein excretion alone. Control patients in the highest quartile of predicted risk had an annualized outcome rate of 28.7%, whereas control patients in the lowest quartile of predicted risk had an annualized outcome rate of 0.4%. Despite the extreme variation in risk, there was no variation in the degree of benefit of ACEI therapy (P = 0.93 for the treatment x risk interaction). Significant interaction was detected between baseline urine protein and ACEI therapy (P = 0.003). When patients were stratified according to their baselineurinary protein excretion, among the subgroup of patients with proteinuria>or =500 mg/d, significant treatment effect was seen across all patients with a measurable outcome risk, including those at relatively low risk (1.7% annualized risk for progression). However, there was no benefit of ACEI therapy among patients with proteinuria<500 mg/d, even among higher risk patients (control outcome rate 19.7%). Patients with nondiabetic kidney disease vary considerably in their risk for disease progression, but the treatment effect of ACEI does not vary across risk strata. Patients with proteinuria<500 mg/d do not seem to benefit, even when at relatively high risk for progression.
AD
Institute for Clinical Research and Health Policy Studies, Tufts-New England Medical Center, 750 Washington Street #63, Boston, MA 02111, USA. dkent1@tufts-nemc.org
PMID
56
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Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis.
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Casas JP, Chua W, Loukogeorgakis S, Vallance P, Smeeth L, Hingorani AD, MacAllister RJ
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Lancet. 2005;366(9502):2026.
 
BACKGROUND: A consensus has emerged that angiotensin-converting-enzyme (ACE) inhibitors and angiotensin-II receptor blockers (ARBs) have specific renoprotective effects. Guidelines specify that these are the drugs of choice for the treatment of hypertension in patients with renal disease. We sought to determine to what extent this consensus is supported by the available evidence.
METHODS: Electronic databases were searched up to January, 2005, for randomised trials assessing antihypertensive drugs and progression of renal disease. Effects on primary discrete endpoints (doubling of creatinine and end-stage renal disease) and secondary continuous markers of renal outcomes (creatinine, albuminuria, and glomerular filtration rate) were calculated with random-effect models. The effects of ACE inhibitors or ARBs in placebo-controlled trials were compared with the effects seen in trials that used an active comparator drug.
FINDINGS: Comparisons of ACE inhibitors or ARBs with other antihypertensive drugs yielded a relative risk of 0.71 (95% CI 0.49-1.04) for doubling of creatinine and a small benefit on end-stage renal disease (relative risk 0.87, 0.75-0.99). Analyses of the results by study size showed a smaller benefit in large studies. In patients with diabetic nephropathy, no benefit was seen in comparative trials of ACE inhibitors or ARBs on the doubling of creatinine (1.09, 0.55-2.15), end-stage renal disease (0.89, 0.74-1.07), glomerular filtration rate, or creatinine amounts. Placebo-controlled trials of ACE inhibitors or ARBs showed greater benefits than comparative trials on all renal outcomes, but were accompanied by substantial reductions in blood pressure in favour of ACE inhibitors or ARBs.
INTERPRETATION: The benefits of ACE inhibitors or ARBs on renal outcomes in placebo-controlled trials probably result from a blood-pressure-lowering effect. In patients with diabetes, additional renoprotective actions of these substances beyond lowering blood pressure remain unproven, and there is uncertainty about the greater renoprotection seen in non-diabetic renal disease.
AD
Centre for Clinical Pharmacology, Department of Medicine, BHF laboratories at University College London, London, UK. juan.pablo-casas@lshtm.ac.uk
PMID
57
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Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease.
AU
Sharma P, Blackburn RC, Parke CL, McCullough K, Marks A, Black C
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Cochrane Database Syst Rev. 2011;
 
BACKGROUND: Chronic kidney disease (CKD) is a long term condition that occurs as a result of damage to the kidneys. Early recognition of CKD is becoming increasingly common due to widespread laboratory estimated glomerular filtration rate (eGFR) reporting, raised clinical awareness, and international adoption of Kidney Disease Outcomes Quality Initiative (K/DOQI) classification. Early recognition and management of CKD affords the opportunity not only to prepare for progressive kidney impairment and impending renal replacement therapy, but also for intervening to reduce the risk of progression and cardiovascular disease. Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) are two classes of antihypertensive drugs that act on the renin-angiotensin-aldosterone system. Beneficial effects of ACEi and ARB on renal outcomes and survival in people with a wide range of severity of renal impairment have been reported; however, their effectiveness in the subgroup of people with early CKD (stage 1 to 3) is less certain.
OBJECTIVES: This review aimed to evaluate the benefits and harms of ACEi and ARB or both in the management of people with early (stage 1 to 3) CKD whodo not have diabetes mellitus.
SEARCH STRATEGY: In March 2010 we searched The Cochrane Library, including The Cochrane Renal Group's specialised register and The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. Reference lists of review articles and relevant studies were also checked. The search was conducted using the optimally sensitive strategy developed by the Cochrane Collaboration for the identification of randomised controlled trials (RCTs) with input from an expert in trial search strategy.
SELECTION CRITERIA: All RCTs reporting the effect of ACEi or ARB in people with early (stage 1 to 3) CKD who did not have diabetes mellitus were selected for inclusion. Only studies of at least four weeks duration were selected. Authors, working in teams of two, independently assessed the retrieved titles and abstracts, and whenever necessary the full text of these studies were screened to determine which studies satisfied the inclusion criteria.
DATA COLLECTION AND ANALYSIS: Data extraction was carried out by two authors, independently, using a standard data extraction form and cross checked by two other authors. Methodological quality of included studies was assessed using the Cochrane risk of bias tool. Data entry was carried out by one author and cross checked by another author. When more than one study reported similar outcomes, data were pooled using the random-effects model, but a fixed-effect model was also analysed to ensure the robustness of the model chosen and to check susceptibility to outliers. Heterogeneity was analysed using a Chi²test on N-1 degrees of freedom, with an alpha of 0.05 used for statistical significance and with the I²test. Where data permitted, subgroup analysis was used to explore possible sources of heterogeneity. The quality of the evidence was analysed.
MAIN RESULTS: Four RCTs enrolling 2177 participants met our inclusion criteria. Of these, three compared ACEi with placebo and one compared ACEi with ARB. Two studies had an overall low risk of bias, and the other two were considered to be at moderate to high risk of bias. Low to moderate quality of evidence (from two studies representing 1906 patients) suggested that ACEi had no impact on all-cause mortality (RR 1.80, 95% CI 0.17 to 19.27, P = 0.63) or cardiovascular events (RR 0.87, 95% CI 0.66 to 1.14, P = 0.31) in people with stage 3 CKD. For all-cause mortality, there was substantial heterogeneity in the results. One study (quality assessment: low risk of bias) reported no difference in the risk of end-stage kidney disease in those with an eGFR> 45 mL/min/1.74 m²treated with ACEi versus placebo (RR 1.00, 95% CI 0.09 to 1.11, P = 0.99). The (high risk of bias) study that compared ACEi with ARB reported little difference in effect between the treatments when urinary protein, blood pressure or creatinine clearance were compared. No published studies comparing ARB with placebo or ACEi and ARB with placebo were identified.
AUTHORS' CONCLUSIONS: Our review demonstrated that there is currently insufficient evidence to determine the effectiveness of ACEi or ARB in patients with stage 1 to 3 CKD who do not have diabetes mellitus. We have identified an area of significant uncertainty for a group of patients who account for most of those labelled as having CKD.
AD
Health Services Research Unit, University of Aberdeen, Foresterhill, Aberdeen, Grampian, UK, AB25 2ZD.
PMID