以血清cystatin C評估藥物對第二型糖尿病患腎功能之影響

Application of serum cystatin C for evaluation the influence of different medicines on kidney function in type 2 diabetes patient

胡美黛(Mei-Tai Hu)

指導教授 ： 周芬碧

中山醫學大學/醫學院/生化暨生物科技研究所/碩士(2011年)

摘要

糖尿病腎病變(diabetic nephropathy, DN)是糖尿病最常見的併發症與死因，研究證實血清cystatin-C (胱蛋白C)對早期糖尿病腎病變的敏感性，比血清肌酸酐(creatinine)或以血清肌酸酐計算eGFR公式高1,2。目前關於藥物與早期糖尿病腎病變的文獻資料不多，各種藥物對早期糖尿病腎病變的影響亦不明確；本研究利用血清cystatin C評估第二型糖尿病患，使用降血糖藥物或合併降高血壓藥物後對早期糖尿病腎病變的影響。實驗中共收集125位第二型糖尿病患者，以免疫散射比濁法(immunonephelometry)測定血清cystatin C，計算Cys-eGFR (cystatin-C base estimates glomerular filtration rate)，收集醣化血色素(glycosylated hemoglobin A1c, HbA1c)、腎臟及血脂常規項目及身體質量指數(body mass index, BMI) 等數據。實驗結果顯示男性的Cys-eGFR、尿液白蛋白與肌酸酐比值(albumin creatinine ratio, ACR)及高密度脂蛋白(high density lipoprotein cholesterol, HDL-C)較低；但血清肌酸酐(creatinine)及血清cystatin-C (p= 0.01)則較高，與女性糖尿病族群有明顯差異；年齡與血清cystatin-C呈正相關 (r=0.531, p<0.001)，與Cys-eGFR則為負相關(r=0.549, p<0.001)。Cys-eGFR評估結果顯示，磺胺尿素類(sulfonylurea)的glibenclamide藥物(P = 0.003) 或乙型交感神經阻斷劑類(β1-blocker)降血壓藥物(P= 0.001)使用者的Cys-eGFR較低，與使用其他類別藥物者有顯著差異。以血清cystatin C篩檢糖尿病患腎臟功能，計算Cys-eGFR來評估腎絲球濾過率(glomerular filtration rate, GFR)，應可提早提供初期腎功能減退時的警訊，對高危險群患者所使用藥物的更應謹慎評估。

關鍵字

胱蛋白C ； 糖尿病腎病變

並列摘要

Diabetic nephropathy is the most common complication of diabetes and cause of death. Studies showed that serum cystatin C has higher sensitivity for detection of early diabetic nephropathy than serum creatinine or serum creatinine base formula for calculated eGFR1,2. There are little literatures investigating the relationship between drug utilization and early diabetic nephropathy. The impact of variety of drugs on early diabetic nephropathy is not clear. This study used serum cystatin C to evaluation the impact of hypoglycemic drugs or lowering high blood pressure drugs on early diabetic nephropathy in 125 type II diabetes patients. Serum level of cystatin C was determined by immune nephelometry assay and used for calculation of Cys-eGFR. Usual blood data such as glycosylated hemoglobin, kidney function and blood lipids and body mass index were collected for analysis. The results showed that Cys-eGFR, urinary albumin creatinine ratio and high-density lipoprotein were lower in male than in female. On the other hand serum creatinine and serum cystatin C (p = 0.01) were significant higher in male than in female. The age of patients was positively correlated to serum cystatin C (r = 0.531, p <0.001), and negatively correlated to Cys-eGFR (r = 0.549, p <0.001). The users of sulfonylurea class drug, glibenclamide, and blood pressure lowering drugs of beta blocker class (β1-blocker) had lower Cys-eGFR as compared to those using other types of drugs with significances of P = 0.003 and P = 0.001 respectively. Application serum cystatin C for calculation of glomerular filtration rate (Cys-eGFR) for screening of kidney function in diabetic patients should be able to provide early warning sign of initial renal dysfunction for those drug users at high risk.

並列關鍵字

cystatin C ； diabetic nephropathy

參考文獻

1.Pucci L, Triscornia S, Lucchesi D, Fotino C, Pellegrini G, Pardini E, Miccoli R,Del Prato S, Penno G. Cystatin C and estimates of renal function: searching for a better measure of kidney function in diabetic patients. Clinical chemistry 53, 480-488 (2007).

2.McNamara NV, Chen R, Janu MR, Bwititi P, Car G, Seibel M. Early renal failure detection by cystatin C in type 2 diabetes mellitus: varying patterns of renal analyte expression. Pathology 41, 269-275 (2009).

3.International Diabetes Federation. Diabetes atlas (3rd edition). (2007).

4.Chan JC, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon KH, Hu FB. Diabetes in asia:epidemiology, risk factors, and pathophysiology.The journal of the american medical association 301, 2129-2140 (2009).

5.Chuang L,Tsai, S, Juang J, Tsai W, Tai T. Genetic epidemiology of type 1 diabetes mellitus in taiwan. Diabetes rearch and cinical pactice 50, S41–S47 (2000) .