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.
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.
Lowest systolic blood pressure is associated with stroke in stages 3 to 4 chronic kidney disease.
Weiner DE, Tighiouart H, Levey AS, Elsayed E, Griffith JL, Salem DN, Sarnak MJ
J Am Soc Nephrol. 2007;18(3):960.
Hypertension is a risk factor for stroke in the general population, whereas in hemodialysis patients, higher systolic BP (SBP) may be protective. Therefore, this study evaluated the relationship between SBP and stroke in individuals with and without chronic kidney disease (CKD) to assess whether this altered relationship exists in earlier stages of CKD. A secondary evaluation of two community-based, longitudinal, limited-access data sets was performed: Atherosclerosis Risk in Communities and Cardiovascular Health Study. CKD was defined as estimated GFR<60 ml/min per 1.73 m(2). The primary study outcome was definite or probable incident stroke. We used Cox proportional hazards models to assess the relationship between CKD and stroke, focusing on the role of SBP. Among 20,358 individuals studied, 1549 (7.6%) had CKD. During a median duration of 111 mo, 1029 (5.1%) individuals had a stroke. CKD and elevated SBP both independently predicted incident stroke (hazard ratio [HR]1.22 [95% confidence interval [CI]1.02 to 1.44]and HR 1.18 [95% CI 1.14 to 1.21]per 10-mmHg rise, respectively). Individuals with CKD had a J-shaped relationship with stroke outcomes such that those with SBP<120 mmHg were at significantly increased risk compared with individuals with CKD and SBP 120 to 129 mmHg (HR 2.51; 95% CI 1.30 to 4.87); risk increased for BP>130 mmHg in CKD. This J shape was not seen in individuals without CKD. CKD and elevated SBP are independent risk factors for incident stroke. In CKD, individuals with the lowest BP are at increased risk for stroke. This pattern is not seen in the general population.
Division of Nephrology, Box 391, Tufts-New England Medical Center, Boston, MA 02111, USA. firstname.lastname@example.org
Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy.
Ruggenenti P, Perna A, Gherardi G, Gaspari F, Benini R, Remuzzi G
BACKGROUND: The Ramipril Efficacy In Nephropathy (REIN) study found that in patients with chronic nephropathies and proteinuria of 3 g or more per 24 h, ramipril safely reduced the rate of decline of the glomerular filtration rate (GFR) and halved the combined risk of doubling of serum creatinine or end-stage renal failure (ESRF), as compared with placebo plus conventional antihypertensive drugs at the same level of blood pressure control. At the end of the core study patients continued on or shifted to ramipril and were formally enrolled into the REIN follow-up study.
METHODS: 97 patients entered the follow-up study. Patients originally randomised to ramipril continued with the same daily dose (n=51), whereas those originally on placebo plus conventional antihypertensive drugs switched to ramipril after the first visit of the follow-up study (n=46). Ramipril (1.25 to 5.00 mg/day) and conventional antihypertensive therapy were targeted at achieving diastolic blood pressure under 90 mm Hg. The main efficacy variables were GFR decline and ESRF (need for dialysis). Analysis was by intention to treat.
FINDINGS: During the follow-up study the mean rate of GFR decline per month decreased from 0.44 (SD 0.54) mL/min per 1.73 m2 in the core study to 0.10 (0.50) mL/min per 1.73 m2 in patients originally randomised to ramipril (p=0.017), and from 0.81 (1.12) to 0.14 (0.87) mL/min per 1.73 m2 in those originally randomised to placebo plus conventional antihypertensive therapy (p=0.017). At the final visit, mean absolute GFR values were 12 mL/min per 1.73 m2 higher (33% better) in patients randomised to ramipril than in those assigned placebo (n=26 and 17, respectively: 35.5 [19.0]vs 23.8 [9.4]mL/min per 1.73 m2, p=0.01). 19 of the patients originally on ramipril versus 35 switched from placebo to ramipril progressed to ESRF (p=0.027) during the whole observation period; of these, six (8%) versus 14 (16%) reached that endpoint during the follow-up study; and the risk ratios were 1.86 (95% CI 1.07-3.26) over the whole observation period and 2.95 (1.13-7.68) during follow-up. Beyond follow-up at month 36, the incidence of ESRF was zero in patients originally randomised to ramipril but 30% in patients on placebo plus conventional antihypertensive therapy.
INTERPRETATION: In patients with chronic nephropathy and high risk of rapid progression to ESRF, ramipril reversed the tendency of GFR to decline with time. Moreover, a treatment period of sufficient duration (>or =36 months) eliminated the need for dialysis. Even patients previously treated with antihypertensive drugs other than angiotensin-converting-enzyme inhibitors benefited from shifting to ramipril.
Mario Negri Institute for Pharmacological Research, Clinical Research Centre for Rare Diseases Aldo e Cele Daccò, Ranica, Italy.
The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group.
Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, Striker G
N Engl J Med. 1994;330(13):877.
BACKGROUND: Restricting protein intake and controlling hypertension delay the progression of renal disease in animals. We tested these interventions in 840 patients with various chronic renal diseases.
METHODS: In study 1, 585 patients with glomerular filtration rates of 25 to 55 ml per minute per 1.73 m2 of body-surface area were randomly assigned to a usual-protein diet or a low-protein diet (1.3 or 0.58 g of protein per kilogram of body weight per day) and to a usual- or a low-blood-pressure group (mean arterial pressure, 107 or 92 mm Hg). In study 2, 255 patients with glomerular filtration rates of 13 to 24 ml per minute per 1.73 m2 were randomly assigned to the low-protein diet (0.58 g per kilogram per day) or a very-low-protein diet (0.28 g per kilogram per day) with a keto acid-amino acid supplement, and a usual- or a low-blood-pressure group (same values as those in study 1). An 18-to-45-month follow-up was planned, with monthly evaluations of the patients.
RESULTS: The mean follow-up was 2.2 years. In study 1, the projected mean decline in the glomerular filtration rate at three years did not differ significantly between the diet groups or between the blood-pressure groups. As compared with the usual-protein group and the usual-blood-pressure group, the low-protein group and the low-blood-pressure group had a more rapid decline in the glomerular filtration rate during the first four months after randomization and a slower decline thereafter. In study 2, the very-low-protein group had a marginally slower decline in the glomerular filtration rate than did the low-protein group (P = 0.07). There was no delay in the time to the occurrence of end-stage renal disease or death. In both studies, patients in the low-blood-pressure group who had more pronounced proteinuria at base line had a significantly slower rate of decline in the glomerular filtration rate.
CONCLUSIONS: Among patients with moderate renal insufficiency, the slower decline in renal function that started four months after the introduction of a low-protein diet suggests a small benefit of this dietary intervention. Among patients with more severe renal insufficiency, a very-low-protein diet, as compared with a low-protein diet, did not significantly slow the progression of renal disease.
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Md.