tranilast and Proteinuria

Tranilast, N-(3,4-dimethoxycinnamoyl) anthranilic acid, suppresses collagen synthesis by various cells, including macrophages and fibroblasts, by interfering with the actions of transforming growth factor-beta 1. We investigated the effect of tranilast on progression of diabetic nephropathy (DN), since this process is associated with accumulation of collagens in the glomerulus and interstitium.. Tranilast (100 mg, 3 times daily) was administered to 9 outpatients with advanced DN who were receiving an angiotensin-converting enzyme inhibitor or an angiotensin II receptor antagonist and who exhibited a progressive decline in renal function. The decline in renal function before and during tranilast treatment was evaluated for each patient on the basis of the slope in reciprocal serum creatinine (1/S(Cr)) over time. Urinary type IV collagen (U-IV.C) and protein (U-P) excretions were measured just before commencement of tranilast treatment and every 2 months during the treatment.. One male patient dropped out soon after commencement of tranilast treatment due to development of lung cancer, and hemodialysis was introduced in one female patient 6 months after the start of treatment. In the 8 patients who did not drop out, 1/S(Cr) was significantly less steep during tranilast treatment than before treatment (-0.00748 +/- 0.00700 vs. -0.01348 +/- 0.00636 dl/mg/month, respectively; p = 0.0374). U-IV.C and U-P tended to decrease with time, although the decrease was statistically insignificant.. Our data suggest that tranilast treatment may suppress accumulation of collagens in renal tissue and may be therapeutically useful for reducing the progression of advanced DN.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Collagen Type IV; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Disease Progression; Female; Humans; Male; Middle Aged; ortho-Aminobenzoates; Proteinuria; Treatment Outcome

To investigate the effect and mechanism of tranilast on the adriamycin-induced nephrotic syndrome of rats.. Twenty four rats were randomly divided into 4 groups: normal control group, model group, irbesartan treatment group and tranilast treatment group. The rats in normal control group were injected with normal saline via the tail vein. The rats in the other groups were uninephrectomized and injected with adriamycin 5 mg/kg via the tail vein one week later. Rats in model group underwent gavage to receive the sodium carboxymethylcellulose, rats in irbesartan treatment group to receive the irbesartan with 10 mg/kg x d, and rats in tranilast treatment group to receive the tranilast with 400 mg/kg. Rats were then sacrificed at the end of week 8. The body weight, 24 hours urinary protein, blood urea nitrogen (BUN) and serum creatinine (Scr) of each group rats were measured for the study. Renal pathological changes were evaluated. And immunohistochemistry was used to examine the expression of transforming growth factor beta1 (TGF-beta1) and tissue inhibitor of metalloproteinase 1 (TIMP-1). In situ hybridization was used to measure the expression of a-smooth muscle actin (alpha-SMA) mRNA in the kidney.. Compared with the untreated nephrotic syndrome rats, the proteinuria and Scr of rats treated with tranilast were significantly reduced (P < 0.05); Compared with model group, the renal pathological changes of rats in tranilast treatment group were decreased, with glomerular sclerosis to be markedly lower; Tranilast could decrease the expression of TGF-beta1, TIMP-1 and alpha-SMA mRNA in the kidney of rats with adriamycin nephropathy.. Tranilast has a renoprotective effect on adriamycin-induced nephrotic syndrome in rats, of which the mechanism may be related to that tranilast can depress the expression of TGF-beta1, and TIMP-1 in the kidney, with result in decreasing the synthesis and secretion of extracellular matrix. And tranilast inhibits the transdifferentation of renal primary cells, regulates the synthesis and degradation system of extracellular matrix.

Topics: Actins; Animals; Doxorubicin; Kidney; Nephrotic Syndrome; ortho-Aminobenzoates; Protective Agents; Proteinuria; Rats; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta1

Topics: Adult; Body Weight; Humans; Male; Nephrotic Syndrome; Obesity; ortho-Aminobenzoates; Proteinuria