肾小球滤过率估算公式在糖代谢紊乱人群的应用评价
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摘要
目的:分析糖尿病肾病的影响因素,探讨Cockcroft-Gault公式、简化MDRD~*方程及改良简化MDRD方程评价糖代谢紊乱人群肾小球滤过功能的应用价值,并开发适合糖尿病患者的GFR~*估算方程,以指导临床的治疗。
     方法:以2000年1月~2009年1月间,曾经在暨南大学附属第一医院检查~(99m)锝-二乙烯三胺五乙酸肾动态显像法肾小球滤过率的454例患者(材料一)为研究病例,该群体中有188例患者是泌尿系B超检查正常且无肾脏疾病史的糖代谢紊乱患者(材料二)及130例是2007年10月~2009年1月间,在暨南大学附属第一医院住院或门诊就诊的糖尿病患者(材料三)。以~(99m)Tc-DTPA肾动态显像法GFR为金标准,分别比较Cockcroft-Gault公式、简化MDRD方程及改良简化MDRD方程估算GFR值在预测不同糖代谢状态下GFR时与金标准的符合程度,并探讨分析糖尿病患者肾脏滤过功能的影响因素。以糖尿病患者为研究人群,重新引入新的参数,形成新方程,比较在不同GFR水平,新旧方程评估糖尿病及非糖尿病患者的GFR时与金标准的符合程度。
     结果:1.既有公式与金标准的符合程度:①对于混合人群,Cockcroft-Gault公式低估了GFR,简化MDRD方程及改良简化MDRD方程则高估了GFR,差别具有统计学意义;对于CKD5期的患者,3个公式的估测值接近,与金标准比较,差别无统计学意义。②对于非糖代谢紊乱患者,Cockcroft-Gault公式低估了1期及2期的GFR;简化MDRD方程低估了1期的GFR,而高估了3期的GFR;改良简化MDRD方程高估了3期的GFR,差别均具有统计学意义。对于糖代谢紊乱患者,Cockcroft-Gault公式低估了1期及2期的GFR;简化MDRD方程高估了2期及3期的GFR;改良简化MDRD方程高估了1~3期的GFR,差别均具有统计学意义。对于CKD4期以后的患者,无论糖代谢状态如何,3个公式的估测值与金标准的差别无统计学意义。2.糖尿病肾病的影响因素分析:①糖代谢紊乱合并高血压组GFR低于血压正常组,GFR与高血压病程呈负相关;尿白蛋白排泄率高于血压正常组,但CKD各期之间的尿白蛋白排泄率、尿白蛋白/肌酐比值的差别无统计学意义。②GFR与年龄、体表面积、糖尿病病程、视网膜病变程度、收缩压、血肌酐、血尿素氮及血尿酸呈负相关,与糖化血红蛋白、空腹血糖及高密度脂蛋白C呈正相关。③糖代谢紊乱出现非增殖型糖尿病视网膜病变时,其GFR低于正常眼底者,差别具有统计学意义。3.新旧方程的比较:基于糖尿病人群开发的新GFR估算方程具有较高的敏感度(77.62%)和特异度(85.19%),应用于一定范围的糖尿病人群时,其与金标准的符合程度达0.72,优于既有的3个公式;但对于混合人群,新方程的准确性则不及既有的3个公式。
     结论:糖尿病肾病是一多因素疾病,有其独特的致病机制,不同于普通肾脏病患者。既往应用于慢性肾脏病人的GFR估测公式用于评估糖尿病人群的肾小球滤过率欠准确。基于糖尿病人群开发的新方程有较高的敏感度和特异度,可能为临床评估糖尿病人群的GFR带来一定帮助,但本研究受其研究人群的限制,暂适于严格限定范围的糖尿病患者。
Objective:To analyze the influencing factors of diabetic nephropathy and evaluate the applied value of Cockcroft-Gault formula,simplified MDRD formula and modified simplified MDRD formula in glycometabolic disorder subjects.Meanwhile,we tend to develop a new GFR estimated formula specialized for diabetes in order to assist clinical treatment.
     Methods:454 patients(as the First Group) who had accepted examination of ~(99m)Tc-diethylenetriaminepentaacetic acid(~(99m)Tc-DTPA)nephro-dynamic imaging GFR in the first affiliated hospital of JI NAN University during January 2000 to January 2009 were treated as case groups,containing the second Group,which contained 188 diabetes who had normal ultrasound examination result in urinary system and had no history in kidney diseases,and the third Group,which contained 130 diabetes who had been hospitalized in the first affiliated hospital of JI NAN University during January 2000 to January 2009.Using ~(99m)Tc-DTPA nephro-dynamic imaging GFR as gold standard,compare the coincidence of the three known formulae with the gold standard separately at different glycometabolic stations and analyze the influencing factors of the glomerular filtration function of the diabetics.Using the data from diabetic subjects as study cases,to develop a new formula by redrawing into new parameters and compare the coincidence with the gold standard between the new one and the three known formulae at different GFR levels while evaluating the GFR of the diabetics and the non-diabetics.
     Results:1.Coincidence between the known formulae and gold standard:①With regard to the mixed subjects,Cockcroft-Gault formula underestimated the GFR while simplified MDRD formula and modified simplified MDRD formula overestimated the GFR,the difference of which had statistic significance.Regard to the patients after CKD4,the estimated value of the three formulae was near indistinctively,comparing with gold stantard.②Regard to the non-diabetics,Cockcroft-Gault formula underestimated the GFR of the CKD1 and CKD2 patients,simplified MDRD formula underestimated the GFR of CKD1 patients but overestimated the GFR of CKD3,modified simplified MDRD formula overestimated the GFR of CKD3 patients,all of which had statistic significance.For the diabetics,Cockcroft-Gault formula underestimated the GFR of CKD1 and CKD2 patients,simplified MDRD formula overestimated the GFR of CKD2 and CKD3 patients,modified simplified MDRD formula overestimated the GFR of CKD2 to CKD3 patients,all of which had statistic significance.Finally for the CKD4 and CKD5 patients,the estimated value of the three formulae were similar whatever the glycometabolic station,the difference of which had no statistic significance.2.Influencing factors analysis of diabetic nephropathy:①Glycometabolic disorther with hypertension had lower GFR and higher urinary albumin excretion rate,and GFR had negative correlation with hypertension course.But the differences of the urinary albumin excretion rate and the urinary albumin/urinary creatinine ratio between each CKD stage had no statistic significance.②The GFR had negative correlation with age,body surface area,diabetic course,retinopathy level, systolic blood pressure,serum creatinine,blood urea nitrogen and blood uric acid while having positive correlation with glycosylated hemoglobin,fasting plasma glucose and high density lipoprotein C.③The GFR of the diabetics with nonproliferative diabetic retinopathy was lower than the group with normal fundus,the difference of which had statistic significance.3. Comparison between the new formula based on the data from diabetes and the three known formulae:the new one had higher sensitivity(77.62%) and specificity(85.19%).The coincidence of the new formula with the gold standard was 0.72,which was better than the three known formulae when it was applied in a certain diabetic subjects,but was inferior when applied in mixed subjects.
     Conclusions:Diabetic nephropathy is a disease affected by multiple factors,which had distinct pathogenic mechanism.Using the known formulae which was applied to the patients with chronic kidney disease was insufficient when being applied to evaluate the GFR of the diabetics.The new formula based on the diabetics had higher sensitivity and specificity,which may help to more accurately evaluate the GFR of the diabetics in clinical practice.However,this study was limited by the research subjects,thus it can only be applied to the limited diabetics temporarily.
引文
1.Yamagishi S,Fukami K,Ueda S,Okuda S.Molecular mechanisms of diabetic nephropathy and its therapeutic intervention[J].Current Drug Targets,2007 Aug;Vol.8(8):952-959
    2.傅汉菁,袁申元,朱良湘,等.不同时期糖尿病肾病患者的肾小球滤过率的改变以及影响因素[J].基础医学与临床,2000,20(6):36
    3.徐道亮,周海中.糖尿病肾病患者肾小球滤过率测定的临床意义[J].实用临床医药杂志,2004,8(6):96-98
    4.王静,葛家璞,刘芳.GFR与糖尿病肾病尿微量蛋白相关性研究[J].新疆医学,2006,36(1):3-4
    5.王晓军,刘文星,徐丽梅,等.2型糖尿病患者肾小球滤过率的改变及影响因素分析[J].广东医学,2006,27(5):690-692
    6.Grubb A.Diagnostic value of analysis of cystatin C and protein HC in biological fluids[J].Clinical Nephrology,1992,38(Suppl 1):S20-7
    7.Rule AD,et al.Glomerular filtration rate estimated by cystatin C among different clinical presentations[J].Kidney Int,2006(69):399-405
    8.Thomas L,Huber AR.Renal function:estimation of glomerular filtration rate[J].Clin Chem Lab Med,2006(44):1295-1302
    9.Tan GD,et al.Clinical usefulness of cystatin C for the estimation of glomerular filtration rate in type 1 diabetes:reproducibility and accuracy compared with standard measures and iohexol clearance[J].Diabetes Care,2002(25):2004-2009
    10.MacIsaac RJ,et al.Estimating glomerular filtration rate in diabetes:a comparison of Cystatin-C and creatinine-based methods[J].Diabetologia,2006(49):1686-1689
    11.Christensson AG,Grubb AO,Nilsson JA,et al.Serum cystatin C advantageous compared with serum creatinine in the detection of mild but not severe diabetic nephropathy[J].Intern Med,2004,256(6):510-518
    12.Aksun SA,Ozen D,Ozen B,et al.β2-microglobulin and cystatin C in type 2 diabetes:assessment of diabetic nephropathy[J].Exp Clin Endocrinol Diabetes,2004,112(4):195-200
    13.B.-W.Lee,et al.The comparison of cystatin C and creatinine as an accurate serum marker in the prediction of type 2 diabetes nephropathy[J].Diabetes Research and Clinical Practice,2007,78(3):428-134
    14.Itoh K,Tsushima S,Tsukamoto E,et al.Reappraisal of single-sample and gamma camera methods for determination of the glomerular filtration rate with ~(99m)Tc-DTPA[J].Ann Nucl Med,2000,14(3):143-150
    15.Petersen LJ,Petersen JR,Talleruphuus U,et al.Glomerular filtration rate estimateal from the uptake phase of ~(99m)Tc-DTPA renography in chronic renal failure[J].Nephrol Dial Transplant,1999(14):1673-1678
    16.Li Zuo,Hai-Yan Wang.Selection of appropriate glomerular filtration rate estimating equation[J].Hong Kong J Nephrol,April 2007,9(1):15-22
    17.Risch L,Herklotz R,Blumberg A,et al.Effects of glucocorticoid immunosupp ression on serum cystatin C concentrations in renal transplant patients.Clin Chem,2001,47:2055-2059
    18.Bfkenkamp A,van Wijk JA,LentzeMJ,et al.Effect of corticosteroid therapy on serum cystatin C and beta2-microglobulinconcentrations.Clin Chem,2002,48:1123-1126
    19.Wiesli P,SchweglerB,Sp inas GA,et al.Serum cystatin C issensitive to small changes in thyroid function[J].Clin Chim Acta,2003,338:87-90
    20.Le Bricon T,Thervet E,FroissartM,et al.Plasma cystatin C is superior to 24h creatinine clearance and plasma creatinine for estimation of glomerular filtration rate 3 months after kidney transplantation[J].ClinChem,2000,46(8):1206-1207
    21.Biggi A,Vigtietfi A,Farinelli MC,et al.Estimation of glomerular filtration rate using chromium-~(51) ethylene diamine tetra-acetic acid and technetium-~(99m)diethylene triamine penta-acetic acid.Eur Nucl Med[J],1995,22(6):532-536
    22.Rehling M,Moller ML,Thamdrup B,et al.Simultaneous measurement of renal clearance and plasma clearance of ~(99m)Tc-labelled diethylenetri-aminepenta-acetate,~(51)Cr-labelled ethylenediaminetetra-acetate and inulin in man[J].Clin Sci(Lond),1984,66(5):613-619
    23.Itoh K,Tsushima S,Tsukamoto E,et al.Reappraisal of single-sample and gamma camera methods for determination of the glomerular filtration rate with ~(99m)Tc-DTPA[J].Ann Nucl Med,2000,14(3):143-150
    24.Vervoort G,Willems HL,Wetzels JF.Assessment of glomerular filtration rate in healthy subjects and normoalbuminuric diabetic patients validity of a new(MDRD) prediction equation[J].Nephrol Dial Transplant,2002,17(11):1909-1913
    25.Li Zuo,Hai-Yan Wang.Selection of appropriate glomerular filtration rate estimating equation[J].Hong Kong J Nephrol,April 2007,9(1):15-22
    26.Rule AD,et al.Using serum creatinine to estimate glomerular filtration rate:accuracy in good health and in chronic kidney disease[J].Annals of internal medicine,2004,141(12):931-938
    27.Cockcroft DW,Gault MH.Prediction of creatinine clearance from serum creatinine[J].Ne phron 1976(16):31-41
    28.Rigalleau V,et al.A simplified cockcroft-gault formula to improve the prediction of the glomerular filtration rate in diabetic patients[J].Diabetes & Metabolism,2006,32(1):56-62
    29.黎曼,柴华旗,贺丹.Cockcroft-Gault方程和MDRD方程测定肾功能的临床应用[J].苏州大学学报(医学版)2005,252:275-277
    30.周玉红,张京慧,文哲.Cockcroft-Gault公式和肾动态显像法估测老年慢性肾脏病患者肾小球滤过率[J].临床荟萃,2006,21(19):1401-1402
    31.马宏星,等.肾小球滤过测算公式在慢性肾脏病中的应用评估[J].同济大学学报(医学版),2007,28(1):52-55
    32.Levey AS,et al.A more accurate method to estimate glomerular rate from serum creatinine:a new predicition equation.Modification of Diet in Renal Disease Study Group[J].Ann Intem Med,1999,130(6):461-470
    33.Levey AS,et al.A simplified equation to predict glomerular filtration rate from serum creatinine[J].J Am Soc Nephrol,2000(11):A0828.
    34.Rigalleau V,et al.Estimation of glomerular filtration rate in diabertic subjects:Cockcroft formula or Modification of Diet in Renal Disease Study equation?[J].Diabetes Care,2005,28(4):838-843
    35.Julie Lin,et al.A comparison of prediction equations for estimating glomerular filtration rate in adults without kidney disease[J].J Am Soc Nephrol,2003,14(10):2573-2580
    36.马迎春,等.肾小球滤过率评估方程在慢性肾脏病不同分期中的适用性[J].中华内科杂志,2005,44(4):285-289
    37.Gerchman F,et al.Superiority of the Modification of Diet in Renal Disease equation over the Cockcroft-Gault equation in screening for impaired kidney function in Japanese Americans [J].Diabetes Research and Clinical Practice,2007(77):320-326
    38.Jafar TH,Schmid CH,Levey AS.Serum creatinine as marker of kidney function in South Asians:a study of reduced GFR in adults in Pakistan[J].Am.Soc.Nephrol,2005(16):1413-1419
    39.McNeely MJ,Boyko EJ,Shofer JB,et al.Fujimoto,Standard definitions of overweight and central adiposity for determining diabetes risk in Japanese Americans[J].Am.J.Clin.Nutr,2001(74):101-107
    40.梁波,等.探讨并改进Cockcroft-Gault公式的有效性[J].中华肾脏病杂志,2001,17(13):195-196
    41.全国eGFR课题协作组.MDRD方程在我国慢性肾脏病患者中的改良和评估[J].中华肾脏病杂志,2006,22(10):589-595
    42.陆再英,钟南山.内科学.第7版.北京:人民卫生出版社,2008
    43.许曼英.糖尿病学.上海科学技术出版社,2003
    44.Parving HH,Lehnert H,Brochner-Mortensen J,et al.The effect of irbesartan on the development of diabetic nephropathy inpatients with type 2 diabetes[J].N Engl Med,2001(345):870-878
    45.Sasso FC,Carbonara O,Persico M,et al.Irbesartan reduces the albumin excretion rate in microalbuminuric type 2 diabetic patients independently of hypertension[J].Diabetes Care,2002(25):1909-1913
    46.Viberti GC,Wheeldon NM.A blood pressure-independent effect.Circulation,2002(106):672-678
    47.Schrier RW,Estacio RO,Esler A,et al.Effects of aggressive blood pressure control in normotensive type 2 diabetic patients on albuminuria,retinopathy and strokes[J].Kidney Int,2002(61):1086-1097
    48.UK Prospective Diabetes Study Group.Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes:UKPDS 39.BMJ,1998,317:713-720
    49.Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus:results of the HOPE study and MICRO-HOPE substudy.Heart Outcomes Prevention Evaluation Study Investigators[J].Lancet,2000(355):253-259
    50.Siragy HM.Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic.The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial(ALLHAT).Cuur Hypettens Rep,2003(5):293-294
    51.Lindholm LH,Ibsen H,Dahlof B,et al.Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE):a randomized trial against Atenolol[J].Lancet,2002(359):1004-1010
    52.Gross JL,Azevedo M J,Silveiro SP.Diabetic nephropathy:diagnosis,prevention,and treatment[J].Diabetes Care,2005,28(1):164-176
    53.钱孝贤,陈卓铭,曾龙驿.高血压与糖尿病.广州:暨南大学出版社,2006
    54.金秀平,杨春伟,王浩.早期糖尿病肾病相关诊断指标探讨.检验医学与临床[J],2007, 4(4):248-250
    55.Murussi M,et al.Glomerular filtration rate changes in normoalbuminuric and microalbuminuric Type 2 diabetic patients and normal individuals A 10-year follow-up[J].Diabetes and Its Complications,2006(20):210-215
    56.傅汉菁,等.影响糖尿病患者肾小球滤过率危险因素的分析.首都医科大学学报,2001(22):337-339
    57.司徒碧颖,等.老年糖尿病患者的肾功能观察.老年医学与保健,2006(11):108-123
    58.Kopple JD,et al.Observations with regard to the National Kidney Foundation K/DOQI clinical paractice guidelines concerning serum transthyretin in chronic renal failure.Clin Chem Lab Med,2002(40):1308-1312
    59.Fehrman-Ekholm I,Skeppholm L.Renal function in the elderly(>70 years old) measured by means of iohexol clearance[J].Scand Urol Nephrol,2004(38):73-77
    60.Nygaard HA,et al.Clinically important renal impairment in various group of old persons[J].Scand Prim Health Care,2004(22):152-156
    61.Castellani S,et al.Excessive vasoconstriction after stress by the aging kidney:Inadequate prostaglandin modulation of increased endothelin activity[J].J Lab Clin Med,1998(132):186-194
    62.Rimon E,et al.Can creatinine clearance be accurately predicted by formulae in octogenarian in-patients?[J].QJM,2004(97):281-287
    63.Laure P.Epidemiology of the micro-and macro-vascular complication of diabetes in:Georges T.Vascular Complication of Diabetes.Paris:edition-spradel,1994:63-69
    64.蒋国彦.实用糖尿病学[M].第1版.北京:人民卫生出版社,1992:102-213
    65.UK Prospective Diabetes Study(UKPDS) Group:Intensive blood-glucose control with sulphonylureas or insulincompared with conventional treatment and risk of complications in patients with type 2 diabetes(UKPDS 33)[J].Lancet,1998,352:837-853
    66.The Diabetes Control and Complications Trial Research Group:The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus[J].N Engl J Med,1993,329:977-986
    67.Vaag AA.Glycemic control and prevention of microvascular and macrovascular disease in the Steno 2 study[J].Endocrine Practice,2006(12):89-92
    68.Holman RR,et al.10-year follow-up of intensive glucose control in type 2 diabetes J].N Engl Med,2008(359):1577-89
    69.陈文彬,王友赤.诊断学.第五版.北京:人民卫生出版社,2002
    70.周建辉.尿酸在临床疾病中的意义[J].实用医学杂志,2004,20(3):733-734
    71.Bo S,et al.Hypouricemia and hyperuricemia in type 2 diabetes:two different phenotypes[J].Eur J Clin Invest,2001,31(4):318-321
    72.Shichiri M,Iwamoto H,Marumo F.Diabetic hypouricemia as an indicator of clinical nephropathy[J].Am J Nephrol,1990(10):115-122
    73.Golik A,et al.Renal uric acid handling in non-insulin-dependent diabetic patients with elevated glomerular filtration rates[J].Clin Sci,1993(85):713-716
    74.Keane WF.The role of lipids in renal disease:future challenges[J].Kidney Int Suppl,2000(75):S27-31
    75.McGarry JD.Banting lecture 2001:dysregulation of fatty acid metabolism in the etiology of type 2 diabetes.Diabetes,2002(51):7-18
    76.王英,等.血脂异常对2性糖尿病肾病的影响.中国热带医学,2008(8):981-982
    77.Thomas MC,et al.Serum lipids and the progression of nephropathy in type 1 diabetes.Diabetes Care,2006(29):317-322
    78.李博一,等.高密度脂蛋白胆固醇与2型糖尿病肾病的关系.临床荟萃,2007(22):564-565
    79.李青,龚细礼,刘育进.血脂变化与2型糖尿病肾病的关系.医学临床研究,2006(23):184-187
    80.赵亮.糖尿病肾病进展与血脂异常的关系.河北医学,2008(14):317-319
    81.Biesenbach G.Influence of cigarette-smoking on the progression of clinical diabetic nephropathy in type 2 diabetic patients.Clin Nephrol,1997(48):146-50
    82.Ejerblad E,et al.Obesity and risk for chronic renal failure[J].J Am Soc Nephrol,2006(17):1695-1702
    83.Lφkkegaard N.Microalbuminuria in obesity.Scand J Urol Nephrol,1992(26):275-278
    84.Raile K,et al.Diabetic nephropathy in 27,805 children,adolescents,and adults with type 1diabetes:effect of diabetes duration,A1C,hypertension,dyslipidemia,diabetes onset,and sex.Diabetes Care,2007(30):2523-2538

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