Urinary Transforming Growth Factor-beta1 is a Robust Predictor of Kidney Disease Progression / 대한신장학회잡지

BACKGROUND: TGF-beta1 is the main fibrogenic cytokine associated with human glomerulonephritis. TGF-beta1 levels were found to be significantly increased in the urine of patients with IgA nephropathy. However, urinary TGF-beta1 excretion has so far not been evaluated with respect to the risk of kidney disease progression. METHODS: In the current study, urine samples were taken for TGF-beta1 protein analysis from 37 patients diagnosed with IgA nephropathy on the day of renal biopsy, and patients were followed until either the date of serum creatinine doubling or until the end of the follow-up period. RESULTS: The median follow-up was 3.6 years (range, 0.4-6.2 years). Urinary TGF-beta1/creatinine ratios (TGF-beta1/Cr, pg/mg) were significantly higher in IgA nephropathy patients than in normal controls (10.7+/-1.92 versus 2.38+/-0.52). The area under the receiver-operating-characteristics curve was 0.78 (P<0.05, 95% confidence interval 0.61-0.90), indicating that urinary TGF-beta1/Cr is an excellent predictor of kidney disease progression. Univariate Cox regression analysis showed that urinary TGF-beta1/Cr was the most powerful predictor of serum creatinine doubling (p=0.0026, relative risk 1.09, 95% confidence interval 1.03-1.15). Furthermore, multivariate Cox regression analysis adjusted for other confounders revealed that urinary TGF-beta1/Cr was the only significant predictor of serum creatinine doubling. In contrast, serum TGF-beta1 levels were not found to be a risk factor of kidney disease progression. CONCLUSION: Our findings provide new evidence of a robust association between urinary TGF-beta1 and kidney disease progression in patients with IgA nephropathy.

Effect of Losartan Treatment on Proteinuria and Urinary Transforming Growth Factor-beta1 in Human Chronic Glomerulonephritis / 대한신장학회잡지

BACKGROUND: Urinary TGF-beta1 reflects intrarenal TGF-beta1 production and is increased in patients with progressive nephropathies. We studied the effects of angiotensin receptor blocker (ARB) on serum and urinary TGF-beta1 excretion in chronic glomerulonephritis patients with proteinuria. Also the role of urinary TGF-beta1 in ARB induced antiproteinuric responses was evaluated. METHODS: Patients with non-diabetic chronic renal disease with proteinuria of 1 g or more were enrolled in this open, prospective study. After four weeks of washout period, the patients received losartan 50 mg daily followed by 100 mg in two treatment periods each lasting 12 weeks. Clinical parameters and urinary indices including proteinuria and urinary TGF-beta1 were measured at baseline and after each 12 week treatment period. RESULTS: Among the 42 patients who completed the study, 31 responded to ARB therapy determined as a decrease in proteinuria by 30% (responders), and 11 did not respond (non-responders). ARB treatment controlled blood pressure to a similar degree in both responders and non-responders. Renal function and other biochemical parameters did not change during the study period. Both doses of losartan significantly lowered proteinuria and urinary TGF-beta1 excretion in responders (50 mg: 33.4% and 29.0%, 100 mg: 64.1% and 45.8%, respectively, p<0.05). In contrast, non-responders showed no significant reduction in proteinuria and no further decrease in urinary TGF-beta1 after 100 mg treatment. Urinary TGF-beta1 excretion lacked any correlation between clinical parameters such as proteinuria or renal function. Responders were younger, showed lower baseline proteinuria and urinary TGF-beta1 excretion and greater reduction in urinary TGF-beta1 excretion after ARB treatment. However, lower baseline urinary TGF-beta1 excretion was the only significant predictor of response to ARB therapy. CONCIUSION: Our data suggest that ARB therapy in nondiabetic proteinuric chronic glomerulonephritis patients reduces proteinuria and urinary TGF-beta1 excretion and baseline urinary TGF-beta1 excretion may predict antiproteinuric response to ARB therapy.