From Albuminuria Screening to Antihypertensive Therapy: Evidence-Based Approaches in Diabetes Care
Date Issued
2014
Date
2014
Author(s)
Wu, Hon-Yen
Abstract
Background: Due to the rising incidence of diabetes and the constrained health care resources in many countries, comparative effectiveness research are gaining importance for assisting decision making on controversial issues. Measurement of a random urine sample for albumin concentration (UAC) without simultaneously measuring urine creatinine is less expensive than measuring albumin to creatinine ratio (ACR), but whether their diagnostic performances for screening microalbuminuria are different has yet to be resolved. There is no consensus about the priority for treatments between angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), or the choice of antihypertensive drugs in combination with those renin-angiotensin system (RAS) blockers. The objective of this dissertation is to synthesize current evidence using advanced meta-analysis methods to resolve controversies regarding microalbuminuria screening and antihypertensive therapy in diabetic patients, and evaluate the effects of different antihypertensive treatments in a nationwide cohort study of diabetic patients
Methods: Three electronic databases (PubMed, MEDLINE, and Scopus) were systematically searched for studies assessing either UAC or ACR in detecting microalbuminuria among diabetic patients, and using urine albumin of 30-300 mg in 24-hour timed urine collection as the gold standard. Bivariate random-effects models were used for the pooling and comparisons of diagnostic performances. Four electronic databases (PubMed, MEDLINE, Scopus, and the Cochrane Library) were systematically searched for randomized clinical trials of antihypertensive treatments (ACEIs, ARBs, β-blockers, calcium channel blockers [CCBs], diuretics, and their combinations), which reported all-cause death, long-term dialysis, or doubling of serum creatinine. Bayesian network meta-analysis was applied to combine direct and indirect evidence and estimate the relative effects between treatments. Adult patients from the Longitudinal Cohort of Diabetes Patients of the National Health Insurance Research Database were assessed if they received at least 90 days of continuous antihypertensive treatment. Claims data including age, gender, comorbidities, income, occupation, geographic location, and outpatient prescriptions for antihypertensive drugs were obtained for each patient. Cox’s proportional hazard models were used to evaluate (1) ACEIs versus ARBs, and (2) CCBs versus thiazide diuretics as add-on treatment for RAS blockers, for the outcomes of long-term dialysis, acute kidney injury, hyperkalemia, and all-cause death.
Results: Meta-analysis of screening tests for microalbuminuria showed pooled sensitivities of 0.85 and 0.87 for UAC and ACR, respectively, and pooled specificities of 0.88 and 0.88, respectively. No differences in sensitivity or specificity between UAC and ACR were found. Network meta-analysis of antihypertensive treatments showed that only ACEIs significantly reduced the doubling of serum creatinine levels (odds ratio 0.58, 95% credible interval 0.32 to 0.90) compared with placebo. The beneficial effects of ACEIs compared with ARBs did not reach statistical significance. The treatment ranking identified the combination of ACEI plus CCB to have the greatest probability (73.9%) for being the best treatment on reducing mortality, followed by ACEI plus diuretic (12.5%). The nationwide cohort study showed no difference between ACEIs and ARBs for long-term dialysis, acute kidney injury, and hyperkalemia. ACEI users showed a significantly higher mortality than ARB users (hazard ratio 1.20, 95% confidence interval 1.01 to 1.44), but this result is not consistently shown in subgroup analyses. The combination of RAS blocker plus CCB showed significantly higher risks of long-term dialysis (2.12, 1.62 to 2.78) and hyperkalemia (1.32, 1.07 to 1.64) compared with the combination of RAS blocker plus thiazide diuretic.
Discussions and conclusions: UAC and ACR both yielded high sensitivity and specificity for the detection of microalbuminuria. Because the diagnostic performance of UAC is comparable to that of the ACR, we suggest UAC to be the screening tool of choice. As available evidence from experimental and observational studies is not able to clearly differentiate the protective effects of ACEIs and ARBs, we suggest the use of ACEIs as the first line antihypertensive agent in consideration of cost. The superior renoprotective effects of the combination of thiazide diuretic and RAS blocker required additional prospective studies to confirm. CCB therapy is the preferred add-on treatment if adequate blood pressure control cannot be achieved by ACEIs alone.
Subjects
白蛋白尿
血管收縮素轉化酶抑製劑
血管收縮素受體阻斷劑
鈣離子阻斷劑
糖尿病
透析
利尿劑
SDGs
Type
thesis
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