Medline ® Abstracts for References 6,52-57
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.
The blunting of the antiproteinuric efficacy of ACE inhibition by high sodium intake can be restored by hydrochlorothiazide.
Buter H, Hemmelder MH, Navis G, de Jong PE, de Zeeuw D
Nephrol Dial Transplant. 1998;13(7):1682.
BACKGROUND: Dietary sodium restriction enhances the antiproteinuric and blood pressure lowering effect of ACE inhibition. In clinical practice, however, long-term compliance to a low-sodium diet may be difficult to obtain. We therefore investigated whether the blunting of the antiproteinuric and blood pressure lowering efficacy of ACE inhibition by high sodium intake can be restored by the addition of a diuretic.
PATIENTS AND METHODS: Seven proteinuric patients with non-diabetic renal disease on chronic ACE inhibition were studied during three consecutive 4-week periods: low sodium (50 mmol/day), high sodium (200 mmol/day) and high sodium plus hydrochlorothiazide (50 mg o.i.d.).
RESULTS: During low sodium intake proteinuria was 3.1 (0.7-5.2) g/day, during high sodium intake proteinuria increased to 4.5 (1.6-9.2) g/day (P<0.05). Interestingly, addition of hydrochlorothiazide again reduced proteinuria to 2.8 (0.6-5.8) g/day (P<0.05). Mean arterial blood pressure was 89 (84-96), 98 (91-104) and 89 (83-94) mmHg (P<0.05) during the three periods, respectively.
CONCLUSION: Addition of hydrochlorothiazide can overcome the blunting of the therapeutic efficacy of ACE inhibition on proteinuria and blood pressure by a high sodium intake.
Groningen Institute for Drug Studies, Division of Nephrology, State University Hospital, The Netherlands.
Diuretic and enhanced sodium restriction results in improved antiproteinuric response to RAS blocking agents.
Esnault VL, Ekhlas A, Delcroix C, Moutel MG, Nguyen JM
J Am Soc Nephrol. 2005;16(2):474.
Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and diuretics may exert synergistic antiproteinuric effects. Eighteen patients with a proteinuria>1 g/24 h after 6 mo of treatment with ramipril at 5 mg/d were assigned to receive in random order ramipril at 10 mg/d, valsartan at 160 mg/d, or combined ramipril at 5 mg/d and valsartan at 80 mg/d in addition to their antihypertensive treatment. The treatment periods lasted 4 wk and were separated by a 4-wk washout with ramipril at 5 mg/d. At the end of this crossover sequence, patients received combined ramipril at 5 mg/d, valsartan at 80 mg/d, and an increased furosemide dosage for an additional 4-wk period. The primary end point was the urinary protein/creatinine ratio for two 24-h urine collections at the end of each treatment period. No significant differences were noted between the study end points of the ramipril 10, valsartan 160, and combined ramipril 5 and valsartan 80 treatment groups. However, the urinary protein/creatinine ratio was lower with combined ramipril 5 and valsartan 80-increased furosemide dosage than with valsartan 160 and combined ramipril 5 and valsartan 80, with a similar tendency compared with ramipril 10. Combined ramipril 5 and valsartan 80-increased furosemide dosage decreased systolic home BP and increased serum creatinine but did not significantly increase the number of symptomatic hypotension cases compared with the other three treatments. Thus, in patients with severe proteinuria and hypertension, a cautious increase in diuretic dosage in addition to combined angiotensin-converting enzyme inhibitors and angiotensin receptor blockers decreases proteinuria and BP but may expose the patient to prerenal failure.
Service de Néphrologie et Immunologie Clinique, CHU de Nantes, 30 Boulevard Jean Monnet, 44093 Nantes, France. email@example.com
Effects of dietary sodium and hydrochlorothiazide on the antiproteinuric efficacy of losartan.
Vogt L, Waanders F, Boomsma F, de Zeeuw D, Navis G
J Am Soc Nephrol. 2008;19(5):999.
There is large interindividual variability in the antiproteinuric response to blockade of the renin-angiotensin-aldosterone system (RAAS). A low-sodium diet or addition of diuretics enhances the effects of RAAS blockade on proteinuria and BP, but the efficacy of the combination of these interventions is unknown. Therefore, this randomized, double-blind, placebo-controlled trial to determine the separate and combined effects of a low-sodium diet and hydrochlorothiazide (HCT) on proteinuria and BP was performed. In 34 proteinuric patients without diabetes, mean baseline proteinuria was 3.8 g/d, and this was reduced by 22% by a low-sodium diet alone. Losartan monotherapy reduced proteinuria by 30%, and the addition of a low-sodium diet led to a total reduction by 55% and the addition of HCT to 56%. The combined addition of HCT and a low-sodium diet reduced proteinuria by 70% from baseline (all P<0.05). Reductions in mean arterial pressure showed a similar pattern (all P<0.05). In addition, individuals who did not demonstrate an antiproteinuric response to losartan monotherapy did respond when a low-sodium diet or a diuretic was added. In conclusion, a low-sodium diet and HCT are equally efficacious in reducing proteinuria and BP when added to a regimen containing losartan and especially seem to benefit individuals who are resistant to RAAS blockade. Combining these interventions in sodium status is an effective method to maximize the antiproteinuric efficacy of RAAS blockade.
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
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. firstname.lastname@example.org
Angiotensin-converting enzyme inhibitors and progression of nondiabetic renal disease. A meta-analysis of patient-level data.
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
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.
Department of Medicine, The Aga Khan University, Stadium Road, PO Box 3500, Karachi, Pakistan.
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.
Giatras I, Lau J, Levey AS
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.
New England Medical Center, Boston, Massachusetts, USA.