Antihypertensive agents for preventing diabetic nephropathy and retarding its progression: a systematic review of randomized controlled trials [RCTs]

Giovanni FM Strippoli¹ Jonathan C Craig ¹ Maria Craig ² Francesco P Schena ³
1. Cochrane Renal Group
2.Centre for Kidney Research, Children’s Hospital at Westmead, Australia
3. DETO, Unviersity of Bari, Italy.

Antihypertensive agents are widely used to prevent diabetic nephropathy (DN) and retard its progression. We conducted a systematic review to evaluate the use of antihypertensive agents in the prevention of DN in comparison with placebo, other agents or no therapy, and to assess variability across studies. The Cochrane Controlled Trials Register, Medline (1966-2002), Embase (1988-2002) and article reference lists were searched for RCTs. Two reviewers independently assessed studies for inclusion criteria and quality and extracted data. Data were analyzed by Cochrane RevMan and Metaview software (version 4.1) using a random effects model. From 3910 abstracts retrieved, 185 full text articles were analyzed for eligibility. To date 22 have been included of which 18 relied on surrogate outcomes (e.g. albuminuria) and 8 were pooled in meta-analyses. End stage renal disease was lower in the Angiotensin II receptor antagonists group compared to placebo (2 RCTs, 2661 patients, relative risk=0.85, 95% CIs 0.75 to 0.95, p=0.006), as was doubling of serum creatinine (2 RCT, 2661 patients, relative risk=0.82, 95% CIs 0.72 to 0.93, p=0.001). Angiotensin converting enzyme inhibitors decreased the progression from micro- to macroalbuminuria (2 RCTs, 553 patients, relative risk=0.06, 95% CIs 0.02 to 0.19, p<0.00001) and did not affect the glomerular filtration rate (4 RCTs, 104 patients, weighted mean difference=2.76, 95% CIs 1.10 to 6.62, p=0.16). Further analysis of quality, variability across studies and effects on other outcomes (serum creatinine, mortality) is in progress. In particular, “head to head” comparisons of the use of single agents versus other “groups” of agents will be obtained by direct or indirect methods according to the available data in RCTs or data provided by individual authors.

Presented at the Australian and New Zealand Society of Nephrology, Annual Meeting, Sydney Convention Centre, 2 - 4 Sept 2002 Sydney NSW.

Correspondence
Giovanni Strippoli
Cochrane Renal Group
Centre for Kidney Research
The Children’s Hospital at Westmead
Locked Bag 4001
Westmead NSW 2145 Sydney Australia
Tel: +61 2 9845 1306
Fax: +6 12 9845 3038
Email1:Giovanni Strippoli
Email2:Giovanni Strippoli