Mogensen C E, Hansen K W, Nielsen S, Pedersen M M, Rehling M, Schmitz A
Medical Department of Diabetes and Endocrinology, Aarhus Kommunehospital, University Hospitals, Denmark.
Am J Kidney Dis. 1993 Jul;22(1):174-87. doi: 10.1016/s0272-6386(12)70184-1.
The principal end point in the evaluation of treatment in incipient and overt diabetic nephropathy is rate of decline in glomerular filtration rate (GFR). Therefore, information on reproducibility of GFR measurements is essential in the planning and evaluation of clinical trials. We studied reproducibility of GFR measurements in insulin-dependent and non-insulin-dependent diabetes mellitus patients using, respectively, a constant-infusion technique with urine collection and labeled iothalamate as a tracer marker and a single-shot procedure using Cr-EDTA, measuring the GFR from the decline in plasma level after bolus injection. The coefficient of variance in the insulin-dependent patients was from 7.5% to 8.8% with repeated measurements. In longitudinal studies with several measurements the mean coefficient of variances varied between 7.4% and 3.4%. In the non-insulin-dependent patients the coefficient of variances between two tests were 7.0% and 5.3% for normoalbuminuric and microalbuminuric patients, respectively. In cross-sectional studies as well as in longitudinal studies, it has been consistently shown that GFR is well preserved and at a supranormal level in patients with normoalbuminuria and microalbuminuria. A decline in GFR appears to start around the transition from microalbuminuria to overt diabetic renal disease, although more detailed studies are needed to support this finding. With regard to intervention trials, several studies document that microalbuminuria can be reduced by effective antihypertensive treatment, particularly with angiotensin-converting enzyme inhibitors, also in patients with normal or close to normal blood pressure. Preliminary results from long-term studies suggest that reduction in microalbuminuria in these patients is associated with preservation of GFR and, thus, apparently renoprotection. In patients with overt renal disease, it has been consistently shown that antihypertensive treatment reduces albuminuria as well as the rate of decline in GFR. This is also observed with combined treatment regimens, for instance beta blockers or angiotensin-converting enzyme inhibitors combined with diuretics, or the three types of drugs in combination.
在评估早期和显性糖尿病肾病的治疗效果时，主要终点是肾小球滤过率（GFR）的下降速率。因此，GFR测量的可重复性信息对于临床试验的规划和评估至关重要。我们分别采用尿液收集的持续输注技术和以碘他拉酸盐为示踪剂标记物的方法，以及使用Cr-EDTA的单次注射程序，通过测量推注后血浆水平的下降来测定胰岛素依赖型和非胰岛素依赖型糖尿病患者的GFR，研究了GFR测量的可重复性。胰岛素依赖型患者重复测量时的变异系数为7.5%至8.8%。在进行多次测量的纵向研究中，平均变异系数在7.4%至3.4%之间。在非胰岛素依赖型患者中，正常白蛋白尿患者和微量白蛋白尿患者两次检测之间的变异系数分别为7.0%和5.3%。在横断面研究以及纵向研究中，一直表明正常白蛋白尿和微量白蛋白尿患者的GFR得到良好保存且处于超常水平。GFR的下降似乎始于从微量白蛋白尿向显性糖尿病肾病转变之时，不过还需要更详细的研究来支持这一发现。关于干预试验，多项研究表明，有效的降压治疗，尤其是使用血管紧张素转换酶抑制剂，即使在血压正常或接近正常的患者中，也能降低微量白蛋白尿。长期研究的初步结果表明，这些患者微量白蛋白尿的减少与GFR的保存相关，因此显然具有肾脏保护作用。在显性肾病患者中，一直表明降压治疗可降低蛋白尿以及GFR的下降速率。联合治疗方案，如β受体阻滞剂或血管紧张素转换酶抑制剂与利尿剂联合使用，或三种药物联合使用时也观察到了这一点。
