Pioglitazone reduces urinary protein and urinary transforming growth factor-beta excretion in patients with type 2 diabetes and overt nephropathy.
OBJECTIVE
Increased urinary excretion of protein and transforming growth factor-beta (TGF-beta) are associated with progression of diabetic nephropathy (DN). Thiazolidinediones (TZD) could reduce urinary protein excretion in patients with microalbuminuric DN. There is little data of patients with macroalbuminuric DN. Also, there are no available clinical data regarding the effect of TZD on TGF-beta and type IV collagen in clinical DN. The present study was carried out to evaluate the effect of pioglitazone (PGZ), a member of TZD, on urinary protein, urinary TGF-beta, and urinary type IV collagen excretion in type 2 diabetic patients with macroalbuminuric DN.


METHODS
Forty patients with type 2 diabetes and overt nephropathy, proteinuria more than 500 mg/day, were randomly assigned to receive PGZ (30 mg/day, n = 24) or placebo (control group, n = 16), for 12 weeks. Blood pressure, plasma glucose, glycated hemoglobin, lipid profile, 24-hour proteinuria, urinary TGF-beta and urinary type IV collagen were determined and compared.


RESULTS
Glycemic control and blood pressure in both groups were not significant different. At baseline, the levels of proteinuria, urinary TGF-beta, and type IV collagen were not significant different between both groups. The geometric mean of urinary protein excretion in the PGZ group was progressively reduced from 1.64 to 0.98 gram/day (g/d), or 40.1% decrease which was significantly different (p < 0.05) from the 4.3% increase (from 1.72 to 1.80 g/d) in the control group. Urinary TGF-beta excretion in the PGZ group was decreased by 47.8% which significantly differed from the 59.7% increase in the control group (p < 0.05). Urinary type IV collagen levels in the PGZ group were decreased by 35% which was slightly, but not significantly, different from the 51.6% elevation in the control group (p = 0.06).


CONCLUSIONS
Besides the effectiveness in blood sugar control, pioglitazone could salutarily reduce proteinuria and synthesis of TGF-beta as well as type IV collagen. These beneficial effects of pioglitazone on diabetic nephropathy are comparable to angiotensin converting enzyme inhibitors and angiotensin receptor blockers
Division of Nephrology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Pisut
P
Katavetin
Somchai
S
Eiam-Ong
Sompongse
S
Suwanwalaikorn
D000284:Administration, Oral; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D011336:Probability; D011507:Proteinuria / Q000503:physiopathology / Q000517:prevention & control*; D012016:Reference Values; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016037:Single-Blind Method; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000187:drug effects*; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D016212:Transforming Growth Factor beta; D000077205:Pioglitazone