Perkins Bruce A, Ficociello Linda H, Silva Kristen H, Finkelstein Dianne M, Warram James H, Krolewski Andrzej S
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Boston, MA 02215, USA.
N Engl J Med. 2003 Jun 5;348(23):2285-93. doi: 10.1056/NEJMoa021835.
In the present study, we aimed to determine the frequency of a significant reduction in urinary albumin excretion and factors affecting such reduction in patients with type 1 diabetes and microalbuminuria.
The study included 386 patients with persistent microalbuminuria, indicated by repeated measurements of urinary albumin excretion (estimated on the basis of albumin-to-creatinine ratios) in the range of 30 to 299 microg per minute during an initial two-year evaluation period. Subsequent measurements during the next six years were grouped into two-year periods, averaged, and analyzed for regression of microalbuminuria, which was defined as a 50 percent reduction in urinary albumin excretion from one two-year period to the next.
Regression of microalbuminuria was frequent, with a six-year cumulative incidence of 58 percent (95 percent confidence interval, 52 to 64 percent). The use of angiotensin-converting-enzyme inhibitors was not associated with the regression of microalbuminuria. However, microalbuminuria of short duration, salutary levels of glycosylated hemoglobin (less than 8 percent), low systolic blood pressure (less than 115 mm Hg), and low levels of both cholesterol and triglycerides (less than 198 mg per deciliter [5.12 mmol per liter] and 145 mg per deciliter [1.64 mmol per liter], respectively) were independently associated with the regression of microalbuminuria. Patients with salutary levels of all modifiable factors had a hazard ratio for regression of 3.0 (95 percent confidence interval, 1.5 to 6.0), as compared with patients with no salutary levels of any modifiable factor.
Frequent regression of microalbuminuria in patients with type 1 diabetes indicates that elevated urinary albumin excretion does not imply inexorably progressive nephropathy. Identification of the multiple determinants of the regression of microalbuminuria has implications for current theories about the mechanisms of early diabetic nephropathy.
在本研究中，我们旨在确定1型糖尿病合并微量白蛋白尿患者尿白蛋白排泄显著减少的频率以及影响这种减少的因素。
该研究纳入了386例持续性微量白蛋白尿患者，这些患者在最初两年的评估期内，尿白蛋白排泄量（根据白蛋白与肌酐比值估算）反复测量结果在每分钟30至299微克之间。接下来六年中的后续测量结果按两年为一个周期进行分组、求平均值，并分析微量白蛋白尿的消退情况，微量白蛋白尿的消退定义为尿白蛋白排泄量从一个两年周期到下一个两年周期减少50%。
微量白蛋白尿的消退很常见，六年累积发生率为58%（95%置信区间为52%至64%）。使用血管紧张素转换酶抑制剂与微量白蛋白尿的消退无关。然而，病程短、糖化血红蛋白水平良好（低于8%）、收缩压低（低于115毫米汞柱）以及胆固醇和甘油三酯水平低（分别低于每分升198毫克[5.12毫摩尔/升]和每分升145毫克[1.64毫摩尔/升]）与微量白蛋白尿的消退独立相关。所有可改变因素水平良好的患者与任何可改变因素水平都不佳的患者相比，消退的风险比为3.0（95%置信区间为1.5至6.0）。
1型糖尿病患者中微量白蛋白尿频繁消退表明尿白蛋白排泄升高并不意味着不可避免地会发生进行性肾病。确定微量白蛋白尿消退的多个决定因素对当前关于早期糖尿病肾病机制的理论具有重要意义。
