Effect of Thiazolidinediones on Albuminuria and Proteinuria in Diabetes: A Meta-analysis

• Published in: American journal of kidney diseases Vol. 55; no. 5; pp. 835 - 847
• Main Authors: Sarafidis, Pantelis A., MD, MSc, PhD, Stafylas, Panagiotis C., MD, MSc, Georgianos, Panagiotis I., MD, Saratzis, Athanasios N., MD, Lasaridis, Anastasios N., MD, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-05-2010; Elsevier
• Subjects: albuminuria; Albuminuria - prevention & control; Biological and medical sciences; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - prevention & control; Diabetic Nephropathies - urine; diabetic nephropathy; Disease Progression; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Humans; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Medical sciences; Nephrology; Nephrology. Urinary tract diseases; PPAR gamma - drug effects; proteinuria; Proteinuria - prevention & control; Randomized Controlled Trials as Topic; Thiazolidinediones; Thiazolidinediones - pharmacology; Thiazolidinediones - therapeutic use; Urinary system involvement in other diseases. Miscellaneous; Urinary tract. Prostate gland; albuminuria; Thiazolidinediones; proteinuria; diabetic nephropathy; Endocrinopathy; Kidney disease; Nephrology; Urinary system disease; Diabetes mellitus; Thiazolidinedione derivatives; Urology; Metaanalysis; Concomitant disease; Diabetic nephropathy; Proteinuria
• ISSN: 0272-6386; 1523-6838
• DOI: 10.1053/j.ajkd.2009.11.013

Background Because of the major clinical and economic burden of diabetic nephropathy, new therapeutic tools to delay its progression are needed. Recent studies suggest that thiazolidinediones have renal benefits. We aimed to evaluate the effect of thiazolidinediones on urinary albumin and protein excretion in patients with diabetes mellitus. Study Design Systematic review and meta-analysis by searching MEDLINE/PubMed, EMBASE, and Cochrane CENTRAL databases (1991 to September 2009). Setting & Population Patients with diabetes mellitus. Selection Criteria for Studies Randomized controlled trials. Intervention Thiazolidinediones (rosiglitazone and pioglitazone) compared with placebo or other antidiabetic agents. Outcomes Weighted (WMDs) and standardized mean differences (SMDs) for changes in urine albumin or protein excretion between the thiazolidinedione and control groups. Results Of 171 originally identified articles, 15 studies (5 with rosiglitazone and 10 with pioglitazone) involving 2,860 patients were included in the analysis. In participants with baseline normo- or microalbuminuria, the WMD of proportional changes between the thiazolidinedione and control groups in urinary albumin excretion measured using time-specified collections was −64.8% (95% CI, −75.6 to −53.9) and the WMD of changes in albumin-creatinine ratio was −24.8% (95% CI, −39.6 to −10.0). Overall, in participants with normo- and microalbuminuria, thiazolidinedione treatment was associated with a significant decrease in urinary albumin excretion (SMD, −0.6 units of standard deviation [SD]; 95% CI, −0.8 to −0.4). Similarly, thiazolidinediones were associated with a significant decrease in urinary protein excretion in patients with proteinuria (SMD, −1.1 units of SD; 95% CI, −1.8 to −0.4). Limitations Significant heterogeneity across included studies in several subgroup analyses; patient-level data not available. Conclusions Treatment with thiazolidinediones significantly decreases urinary albumin and protein excretion in patients with diabetes. This finding calls for clinical trials with hard renal outcomes to elucidate the potential benefits of thiazolidinediones on diabetic nephropathy.