Effect of tranilast in early-stage diabetic nephropathy.
BACKGROUND
Tranilast is an antifibrotic drug known to suppress collagen synthesis by fibroblasts by interfering with the effects of TGF-beta. We recently reported that it slowed the progression rate of advanced diabetic nephropathy (DN) by reducing the accumulation of collagens in renal tissue. The present study was undertaken to examine the effect of tranilast on early-stage DN.


METHODS
Among out-patients with diabetes mellitus, we selected patients with (i) urinary albumin excretion of 30-1000 mg/g creatinine (/gCr) in the first morning urine, (ii) serum creatinine (SCr) < or =1.2 mg/dl and no haematuria and (iii) currently taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Twenty patients fulfilled the criteria, of whom 10 were selected at random and commenced on tranilast [100 mg, 3 times daily; T(+) group]. The remaining 10 patients comprised the T(-) group. Excretion of both urinary type IV collagen (U-IV) and albumin (U-A) in the first morning urine was measured every 3 months. The follow-up period was 1 year.


RESULTS
At baseline, no significant differences were observed in SCr, HbA(1c), blood pressure and U-A excretion between the T(+) and T(-) groups, but U-IV excretion in the T(+) group was higher than in the T(-) group (6.4 +/- 0.66 vs 3.7 +/- 0.36 microg/gCr, mean +/- SEM, P < 0.01). At 1 year, SCr was not different from the baseline in either group. In the T(+) group, however, excretion rates of both U-IV and U-A tended to decrease with time, and after 1 year, were significantly decreased compared with excretion at baseline (U-A: 279 +/- 78 to 191 +/- 62 mg/gCr; P = 0.049, U-IV: 6.4 +/- 0.66 to 4.4 +/- 0.99 microg/gCr; P = 0.02). In contrast, in the T(-) group, excretion of both U-A and U-IV tended to increase with time. The changes of both U-A and U-IV excretions in the two groups took statistically different trends through tranilast treatment (P = 0.01 and P = 0.04, respectively).


CONCLUSIONS
Our results suggest that tranilast could be therapeutically beneficial in early-stage DN.
Soma
Jun
J
Department of Nephrology, Iwate Prefectural Central Hospital, 1-4-1 Ueda, Morioka 020-0066, Japan. sjun@chuo-hp.pref.iwate.jp
Sato
Kozo
K
Saito
Harutaka
H
Tsuchiya
Yoshinori
Y
D000368:Aged; D000419:Albuminuria / Q000652:urine; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use; D024141:Collagen Type IV / Q000652:urine; D003404:Creatinine / Q000097:blood; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D016896:Treatment Outcome; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000627:therapeutic use*
D002121:Calcium Channel Blockers; D024141:Collagen Type IV; D062367:ortho-Aminobenzoates; D003404:Creatinine; C012293:tranilast