The Significance Of Urinary Nephrin Excretion In Type 2 Diabetics And Drug Intervention

ObjectiveTo approach the significance of urinary nephrin in diabetic nephropathy by comparing the levels of urinary nephrin which expressed in in type 2 diabetics with the different level of urinaryalbumin. And to observe the changes of urinary nephrin excretion and urinary albumin excretion rate(UAER)in patients with early diabetic nephopathy(DN);intervened by valsartan(an angiotensin receptor blocker) and combination therapy of valsartan and rosiglitazone (peroxisome proliferator- activated receptoryagonist),and to study the possible mechanisms of rosiglitazone protecting the kidney function of early diabetic nephopathy.MethodsTotal 20 normal controls and 79 type 2 diabetics were recruited into the study.The latter were divided into 3 groups according to the urinary albumin excretion rate(UAER):①normal-albuminuria group (UAER<20μg/min,n=15);②micro-albuminuria group (20μg/min≤UAER≤200μg/min,n=48);③macro-albu-minuria group(UAER≥200μg/min, n=16). Urinary nephrin excretion were measured by enzyme linked immunosorbent assay (ELISA).48 patients with early diabetic nephropathy were divided into 3 groups by random.Group A was treated with general treatment, Group B was treated With Valsartan,.Group C was treated with combination of Valsartant and rosiglit-azone.Before treatment and after treatment urinary nephrin excretion were measured by ELISA and UAER Were measured by radioimmunoassay.Results1.There were no significant differences between normal control group and normal-albuminuria group, micro-abuminuria group, macro-albuminuria group in age, sex,waist-hip ratio and body mass index; Compared with control group, There were statistically significant differences between diabetic group in systolic blood pressure,diastolic blood pressure, fasting blood glucose,2-hour postprandial blood glucosr, HbA1c (P<0.01)2.Urinary nephrin didn't be detected in normal control group ,but its excretion was found in the urine of diabetics:Trace urinary nephrin excretion can be detected in normal albuminuria group.24-hour urinary nephrin excretion (ng)of micro-albuminuria group was significantly higher than that of normal albuminuria group (P<0.01). Macro-albuminuria group further increased,the urinary nephrin excretion in macro-albuminuria group was significantly higher than that in micro-albuminuria group (P<0.01)。3.The relative analysis showed urinary nephrin excretion were positively related to UAER,fasting blood glucose,2-hour postprandial blood glucosr, HbAlc and the course of disease and systolic blood pressure. (r=0.726,r=0.414, r=0.325, r=0.486 r=0.526 r=0.358, P均<0.01).4.(1) There were no significantly change in 24h urinary nephrin excretion and UAER of A group before and after treatment (P> 0.05);24h urinary nephrin excretion and UAER were significantly reduced in group B and group C after treatment,the difference was statistically significant (group B,P<0.05; group C, P<0.01);C group decreased more than Bgroup (P<0.05). Scr and Bun had no significant change in three groups before and after treatment.(2) After treatment, SBP, DBP of three groups was lower than before treatment, it was no significant difference among three groups(P> 0.05). (3) After treatment, FBG,2 h PG of three groups was significant lower than before treatment(P<0.01),C group was more obvious. but it was no significant difference among three groups(P> 0.05). After treatment, HbA1C of three groups was significant lower than before treatment(P<0.05),C group was more obvious. but it was no significant difference among three groups(P> 0.05).(4) ALT and blood K+ were not significantly difference among three groups (P> 0.05), during treatment,A group and C group each have one case of mild edema of both lower extremities,these did not affect the experiment, none withdraw from the study.Conclusion(1) Trace urinary nephrin excretion can be detected in normal albuminuria group.Nephrin excretion in urine earlier than the appearance of microalbumin-uria, urinary nephrin excretion may become a new noninvasive marker of early screening DN.(2) Urinary nephrin excretion increases in type 2 dibetics ,which is correlated to the degree of dibetics nephropathy.(3) Rosiglitazone can reduce urinary nephrin excretion,and play a role in kidney protection.(4) Rosiglitazone combined with valsartan may have to play better therapeutic effect on DN.