Medline ® Abstracts for References 6,55,61,65,98

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
SO
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
55
TI
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
SO
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
61
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Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group.
AU
Maschio G, Alberti D, Janin G, Locatelli F, Mann JF, Motolese M, Ponticelli C, Ritz E, Zucchelli P
SO
N Engl J Med. 1996;334(15):939.
 
BACKGROUND: Drugs that inhibit angiotensin-converting enzyme slow the progression of renal insufficiency in patients with diabetic neuropathy. Whether these drugs have a similar action in patients with other renal diseases is not known. We conducted a study to determine the effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of renal insufficiency in patients with various underlying renal diseases.
METHODS: In a three-year trial involving 583 patients with renal insufficiency caused by various disorders, 300 patients received benazepril and 283 received placebo. The underlying diseases included glomerulopathies (in 192 patients), interstitial nephritis (in 105), nephrosclerosis (in 97), polycystic kidney disease (in 64), diabetic nephropathy (in 21), and miscellaneous or unknown disorders (in 104). The severity of renal insufficiency was classified according to the base-line creatinine clearance: 227 patients had mild insufficiency (creatinine clearance, 46 TO 60 ml per minute), and 356 had moderate insufficiency (creatinine clearance, 30 to 45 ml per minute). The primary end point was a doubling of the base-lineserum creatine concentration or the need for dialysis.
RESULTS: At three years. 31 patients in the benazepril group and 57 in the placebo group had reached the primary end point (P<0.001). In the benazepril group, the reduction in the risk of reaching the end point was 53 percent overall (95 percent confidence interval, 27 to 70 percent), 71 percent (95 percent confidence interval, 21 to 90 percent) among the patients with mild renal insufficiency, and 46 percent (95 percent confidence interval, 12 to 67 percent) among those with moderate renal insufficiency. The reduction in risk was greatest among the male patients; those with glomerular diseases, diabetic nephropathy, or miscellaneous or unknown causes of renal disease; and those with base-line urinary protein excretion above 1 g per 24 hours. Benazepril was not effective in patients with polycystic disease. Diastolic pressure decreased by 3.5 to 5.0 mm Hg in the benazepril group and increased by 0.2 to 1.5 mm Hg in the placebo group.
CONCLUSIONS: Benazepril provides protection against the progression of renal insufficiency in patients with various renal diseases.
AD
Divisione di Nefrologia, Ospedale Civile, Verona, Italy.
PMID
65
TI
Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria.
AU
Ruggenenti P, Perna A, Gherardi G, Garini G, Zoccali C, Salvadori M, Scolari F, Schena FP, Remuzzi G
SO
Lancet. 1999;354(9176):359.
 
BACKGROUND: Stratum 2 of the Ramipril Efficacy in Nephropathy (REIN) study has already shown that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, angiotensin-converting enzyme (ACE) inhibition reduced the rate of decline in glomerular filtration and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF) found in controls on placebo plus conventional antihypertensives. In REIN stratum 1, reported here, 24 h proteinuria was 1 g or more but less than 3 g per 24 h.
METHODS: In stratum 1 of this double-blind trial 186 patients were randomised to a ramipril or a control (placebo plus conventional antihypertensive therapy) group targeted at achieving a diastolic blood pressure of less than 90 mm Hg. The primary endpoints were change in glomerular filtration rate (GFR) and time to ESRF or overt proteinuria (>or =53 g/24 h). Median follow-up was 31 months.
FINDINGS: The decline in GFR per month was not significantly different (ramipril 0.26 [SE 0.05]mL per min per 1.73m2, control 0.29 [0.06]). Progression to ESRF was significantly less common in the ramipril group (9/99 vs 18/87) for a relative risk (RR) of 2.72 (95% CI 1.22-6.08); so was progression to overt proteinuria (15/99 vs 27/87, RR 2.40 [1.27-4.52]). Patients with a baseline GFR of 45 mL/min/1.73 m2 or less and proteinuria of 1.5 g/24 h or more had more rapid progression and gained the most from ramipril treatment. Proteinuria decreased by 13% in the ramipril group and increased by 15% in the controls. Cardiovascular events were similar. As expected, the rate of decline in GFR and the frequency of ESRF were much lower in stratum 1 than they had been in stratum 2.
INTERPRETATION: In non-diabetic nephropathies, ACE inhibition confers renoprotection even to patients with non-nephrotic proteinuria.
AD
Mario Negri Institute for Pharmacological Research, Clinical Research Centre for Rare Diseases, Aldo e Cele Dacco Villa Camozzi, Ranica, Bergamo, Italy.
PMID
98
TI
Systematic review: blood pressure target in chronic kidney disease and proteinuria as an effect modifier.
AU
Upadhyay A, Earley A, Haynes SM, Uhlig K
SO
Ann Intern Med. 2011;154(8):541.
 
BACKGROUND: The optimal blood pressure target in patients with chronic kidney disease (CKD) is unclear.
PURPOSE: To summarize trials comparing lower versus higher blood pressure targets in adult patients with CKD and focus on proteinuria as an effect modifier.
DATA SOURCES: MEDLINE and the Cochrane Central Register of Controlled Trials (July 2001 through January 2011) were searched for reports from randomized, controlled trials with no language restriction.
STUDY SELECTION: Authors screened abstracts to identify reports from trials comparing blood pressure targets in adults with CKD that had more than 50 participants per group; at least 1-year follow-up; and outcomes of death, kidney failure, cardiovascular events, change in kidney function, number of antihypertensive agents, and adverse events.
DATA EXTRACTION: Reviewers extracted data on study design, methods, sample characteristics, interventions, comparators, outcomes, number of medications, and adverse events and rated study quality and quality of analyses for proteinuria subgroups.
DATA SYNTHESIS: Three trials with a total of 2272 participants were included. Overall, trials did not show that a blood pressure target of less than 125/75 to 130/80 mm Hg is more beneficial than a target of less than 140/90 mm Hg. Lower-quality evidence suggests that a low target may be beneficial in subgroups with proteinuria greater than 300 to 1000 mg/d. Participants in the low target groups needed more antihypertensive medications and had a slightly higher rate of adverse events.
LIMITATIONS: No study included patients with diabetes. Trial duration may have been too short to detect differences in clinically important outcomes, such as death and kidney failure. Ascertainment and reporting of adverse events was not uniform.
CONCLUSION: Available evidence is inconclusive but does not prove that a blood pressure target of less than 130/80 mm Hg improves clinical outcomes more than a target of less than 140/90 mm Hg in adults with CKD. Whether a lower target benefits patients with proteinuria greater than 300 to 1000 mg/d requires further study.
AD
Tufts University School of Medicine, Boston, MA, USA.
PMID