Microalbuminuria and the risk for early progressive renal function decline in type 1 diabetes
Microalbuminuria and the risk for early progressive renal function decline in type 1 diabetes
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DOI：
10.1681/asn.2006080872
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发表时间：
2007-04-01
影响因子：
13.6
通讯作者：
Krolewski, Andrzej S.
中科院分区：
文献类型：
--
作者：
Perkins, Bruce A.;Ficociello, Linda H.;Krolewski, Andrzej S.
本研究旨在确定1型糖尿病患者肾功能下降的起始时间和决定因素。到目前为止，这种下降一直被认为是与蛋白尿有关的晚发事件。研究人员对267例正常蛋白尿患者和301例微量蛋白尿患者进行了8 - 12年的随访。通过连续测定血清胱抑素C来估计GFR的线性趋势（斜率）。早期肾功能下降的病例定义为胱抑素C GFR损失超过-3.3%/年，这一阈值对应于独立非糖尿病正常血压人群中GFR斜率分布的第2.5个百分点。正常蛋白尿组早期肾功能下降的发生率为9%（平均斜率为-4.4，范围为-5.9 ~ -3.3%/年），微量白蛋白尿组早期肾功能下降的发生率为31%（平均斜率为-7.1，范围为-23.8 ~ -3.3%/年）（P < 0.001）。早期肾功能下降的风险取决于微量白蛋白尿是否消退、保持稳定或进展，分别从16%上升到32%和68% （P < 0.001）。在多变量分析中，35岁后或糖化血红蛋白超过9%时，下降的风险更高，但与糖尿病病程、吸烟、血压或血管紧张素转换酶抑制剂治疗无关。与现有的糖尿病肾病模式相反，1型糖尿病的进行性肾功能下降是一个早期事件，发生在大量微量白蛋白尿患者中。与微量白蛋白尿检测一起，应该制定使用胱抑素C诊断早期肾功能下降和跟踪治疗干预反应的临床方案。
This study aimed to establish the time of initiation and the determinants of renal function decline in type 1 diabetes. Until now, such decline has been assumed to be a late-occurring event associated with proteinuria. A total of 267 patients with normoalbuminuria and 301 patients with microalbuminuria were followed for 8 to 12 yr. Linear trends (slopes) in GFR were estimated by serial measurement of serum cystatin C. Cases of early renal function decline were defined by loss in cystatin C GFR that exceeded -3.3%/yr, a threshold that corresponds to the 2.5th percentile of the distribution of GFR slopes in an independent nondiabetic normotensive population. Cases of early renal function decline occurred in 9% (mean slope -4.4; range -5.9 to -3.3%/yr) of the normoalbuminuria group and 31% (mean slope -7.1; range -23.8 to -3.3%/yr) of the microalburninuria group (P < 0.001). Risk for early renal function decline depended on whether microalbuminuria regressed, remained stable, or progressed, rising from 16 to 32 and 68%, respectively (P < 0.001). In multivariate analysis, risk for decline was higher after age 35 yr or when glycosylated hemoglobin exceeded 9% but did not vary with diabetes duration, smoking, BP, or angiotensin-converting enzyme inhibitor treatment. Contrary to the existing paradigm of diabetic nephropathy, progressive renal function decline in type 1 diabetes is an early event that occurs in a large proportion of patients with microalburninuria. Together with testing for microalburninuria, clinical protocols using cystatin C to diagnose early renal function decline and track response to therapeutic interventions should be developed.