Viberti G C, Bilous R W, Mackintosh D, Keen H
Am J Med. 1983 Feb;74(2):256-64. doi: 10.1016/0002-9343(83)90624-1.
Glomerular function was monitored prospectively in 13 patients with insulin-dependent diabetes and diabetic nephropathy for up to 51 months. Glomerular filtration rate, measured by 51Cr-EDTA clearance, showed a linear decline in all patients. Rates of fall ranged between 0.63 and 2.4 ml/minute per month (mean +/- SEM 1.2 +/- 0.16). Plasma creatinine concentration proved to be an insensitive marker of glomerular function, especially in the early phase of nephropathy. A good correlation was found between the rate of change of 51Cr-EDTA glomerular filtration rate and that of inverse creatinine levels when plasma creatinine concentrations exceeded 200 mumol/liter. Inverse plasma beta 2-microglobulin concentrations, however, showed a highly significant correlation (r = 0.93; p less than 0.001) with 51Cr-EDTA glomerular filtration rate over the whole range of values, making it sensitive in screening for early impairment of renal function. A significant relationship (r = 0.85; p less than 0.01) was found between the rates of change of the 51Cr-EDTA glomerular filtration rate and of inverse beta 2-microglobulin levels for plasma beta 2-microglobulin concentrations above 3 mg/liter. A progressive increase in the fractional clearance of albumin, IgG, and beta 2-microglobulin was noted as the glomerular filtration rate fell, indicating an evolving defect in the renal handling of proteins. The rate of decline of the glomerular filtration rate was unrelated to age, sex, duration of diabetes, duration of diabetes before onset of proteinuria, glomerular filtration rate, initial albumin clearance, blood glucose control, and arterial pressure, when diastolic values were below 100 mm Hg. The effect of therapeutic intervention (e.g., blood glucose, blood pressure, or diet) on the progression of diabetic nephropathy can be reliably evaluated by precise measures of rate of decline of glomerular filtration rate and changes in fractional clearance of plasma proteins. The factor(s) determining the individual rate of decline of renal function still remain obscure.
对13例胰岛素依赖型糖尿病合并糖尿病肾病患者的肾小球功能进行了长达51个月的前瞻性监测。通过51Cr - EDTA清除率测定的肾小球滤过率在所有患者中均呈线性下降。下降速率在每月0.63至2.4毫升/分钟之间(平均±标准误1.2±0.16)。血浆肌酐浓度被证明是肾小球功能的一个不敏感指标,尤其是在肾病早期。当血浆肌酐浓度超过200微摩尔/升时,51Cr - EDTA肾小球滤过率的变化率与肌酐水平倒数之间存在良好的相关性。然而,在整个数值范围内,血浆β2 - 微球蛋白浓度倒数与51Cr - EDTA肾小球滤过率显示出高度显著的相关性(r = 0.93;p < 0.001),这使其在筛查肾功能早期损害方面具有敏感性。当血浆β2 - 微球蛋白浓度高于3毫克/升时,51Cr - EDTA肾小球滤过率的变化率与β2 - 微球蛋白水平倒数之间存在显著关系(r = 0.85;p < 0.01)。随着肾小球滤过率下降,白蛋白、IgG和β2 - 微球蛋白的分数清除率逐渐增加,表明肾脏对蛋白质的处理存在逐渐发展的缺陷。当舒张压值低于100毫米汞柱时,肾小球滤过率的下降速率与年龄、性别、糖尿病病程、蛋白尿出现前的糖尿病病程、肾小球滤过率、初始白蛋白清除率、血糖控制和动脉压无关。通过精确测量肾小球滤过率的下降速率和血浆蛋白分数清除率的变化,可以可靠地评估治疗干预(如血糖、血压或饮食)对糖尿病肾病进展的影响。决定肾功能个体下降速率的因素仍然不明。