Urinary Excretion Rate Of Transforming Growth Factor-β₁ In Patients With Diabetic Nephropathy

Diabetic nephropathy(DN) is one of the most common chronic microvascular complications of Non-insulin dependent diabetes mellitus (NIDDM) and it also can lead to chronic renal failure .It's pathological traits are glomerular sclerosis , tubulointerstitial fibrosis and trace protein in urine. The DN in early stage is reversible with timely diagnosis and treatment .If renal function injury exsists,it proceeds quickly and is unreversible.However there are no effective drugs for it, so it is important to diagnose earlier and prevent progressing.Recently ,more and more people regard that transforming growth factor-β1(TGF-β1) plays an important role in DN pathogenesis.In that , we detect the urinary excretion rate of TGF-β1 to find a new way to diagnose early DN. Objective: To explore the clinical significance of microalbumin(mALB) ,β2-microglobulin(β2-M) and TGF-β1 in patients with diabetic nephropathy by investigation of their urinary excretion rates and compared with conventional renal function markers .Methods: Seventy-two cases of NIDDM patients were divided into three groups according to urinary albumin excretion rate (UAER): normoalbuminuric group(Ⅰ)(<20ug /min ,n=22), microalbuminuric group (Ⅱ) (20-200ug/min, n=29), macroalbuminuric group (Ⅲ) (>200ug/min ,n=21).The excretion rates of mALB,TGF-β1and β2-M were detected by ELISA in 72 cases of NIDDM and 16 controls respectively. Fasting blood glucose (FBG),HbA1c,BUN,SCr,and Ccr were simultaneously detected in all cases. Results: The urinary excretion rates of TGF-β1 in various DM groups were markedly higher than those of controls(p<0.05).Moreover ,the excretion rates of TGF-β1 increased with the increase of UAER and there were significant differences among the three groups(p<0.01).Urinary TGF-β1 was also positively correlated with UAER and β2-M (p<0.01).Discussion: The study demonstrated that the urinary excretion rates of TGF-β1 in normoalbuminuric group (Ⅰ) were markedly higher than those of controls (p<0.05).It hinted that urinary excretion rates of TGF-β1 reflected diabetic nephropathy earlier. Moreover ,the excretion rates of TGF-β1 increased with the increase of UAER and there are significant differences among the three groups(p<0.01).Urinary TGF-β1 was also positively correlated with UAER and β2-M,SCr,BUN,LDL-C(p<0.01),which matched reference[7].In that the excretion rates of TGF-β1 was one of the sensitive markers of early DN,and it can reflect various renal injuries.This study also showed that the disturbance of lipoprotein metabolism in DM were the total cholesterol(TC) ,low density lipoprotein (LDL) and lipoprotein A(LPA) increased, and there is positive relation betweeen LDL and TGF-β1 .Under the situation of hyperglycemia, various abnormalities in biological chemistry and microcirculatory disorders take part in DN procession,including the activation of protein kinase C(PKC), protein nonezyme saccharification,oxidative stress,the increase activity of renin-angiotensin.They all accelerated the synthesis and activation of TGF-β1 by all means ,which lead to extracellular matrix accumulation,glomerulosclerosis, tubulointerstitial fibrosis. Among them , hyperglycemia,angiotensinⅡ,nonenzyme saccharification,NO,thrombomodulin and lipoprotein metabolism disturbance regulated the TGF-β1 involving the activity of PKC.Maybe it could increase the synthesis and excretion of TGF-β1,and activated the recessive TGF-β1.The occurrence of urinary TGF-β1 is the premise of DM developing into diabetic renal failure.And the special extracellular protein such as fibronectin proteoglycan and mucoprotein multiplied,which enhanced pathological action of the TGF-β1 on glomerulosclerosis.The increase of ECM acted on glomerular mesangium and renal tubule,resulting in glomerular scleroses proceeding , tubule endothelium fibrosis formation,glomerular filtration rate descending,and finally developing to renal failure. Perhaps TGF-β1 is the last passage of DN pathogenesis.The tubulointerstitial lesion in t...