Department of Laboratory, Affiliated Houjie Hospital, Guangdong Medical College, Dongguan, 523945, Guangdong, China.
Endocrine. 2012 Feb;41(1):82-8. doi: 10.1007/s12020-011-9509-7. Epub 2011 Jul 21.
The purpose of this study was to investigate the prevalence of tubular damage in short-term (less than five years) type 2 diabetes mellitus (T2DM) patients and to explore the correlation between tubular markers and their relationship with renal indices at different stages of diabetic nephropathy. A group of 101 short-term T2DM patients and 28 control subjects were recruited. Tubular markers, such as neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D: -glucosaminidase (NAG), and kidney injury molecule 1 (KIM-1), as well as urinary albumin excretion were measured in voided urine. Glomerular filtration rate (GFR) was estimated via Macisaac's formula. The patients were further categorized into three groups, namely, the normoalbuminuria, microalbuminuria, and macroalbuminuria groups, according to their urine albumin/creatinine ratio (UACR). Urinary tubular markers were compared and their correlations with renal indices [UACR and estimated GFR (eGFR)] were analyzed among the different diabetic groups. Compared with the control group, Urinary NGAL [median (IQR)][83.6(41.4-138.7) μg/gcr vs. 32.9(26.1-64.5) μg/gcr], NAG [13.5(8.7-17.9) U/gcr vs. 7.6(6.5-13.0) U/gcr] and KIM-1 [120.0(98.4-139.9) ng/gcr vs. 103.1(86.8-106.2) ng/gcr] in the T2DM were all markedly increased. For all patients, urinary NGAL had stronger positive correlations with UACR than NAG (R = 0.556 vs. 0.305, both P < 0.05). In addition, only urinary NGAL showed a negative correlation with eGFR (R = -0.215, P < 0.05). Urinary KIM-1, however, showed no significant difference among the three T2DM groups and did not correlate with either UACR or eGFR. As UACR increased from the normoalbuminuria to the last macroalbuminuria group, all of the markers increased. However, only the concentrations of NGAL were statistically different among the three diabetic groups. The correlation between the tubular markers and their relationships with the renal indices differed markedly among the three T2DM groups. In conclusion, these results suggest that tubular damage is common in short-term T2DM patients. Urinary NGAL may be a promising early marker for monitoring renal impairment in short-term T2DM patients.
本研究旨在探讨短期（<5 年）2 型糖尿病（T2DM）患者肾小管损伤的患病率，并探讨肾小管标志物与不同糖尿病肾病阶段肾指数之间的相关性。研究纳入了 101 例短期 T2DM 患者和 28 例对照组。收集患者的尿液，检测中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、N-乙酰-β-D：-氨基葡萄糖苷酶（NAG）和肾损伤分子 1（KIM-1）等肾小管标志物，同时检测尿白蛋白排泄率。通过 Macisaac 公式估算肾小球滤过率（GFR）。根据尿白蛋白/肌酐比值（UACR），将患者进一步分为三组：正常白蛋白尿组、微量白蛋白尿组和大量白蛋白尿组。比较不同糖尿病组之间的肾小管标志物，并分析其与肾指数[UACR 和估算肾小球滤过率（eGFR）]的相关性。与对照组相比，T2DM 患者的尿 NGAL[中位数（IQR）][83.6(41.4-138.7)μg/gcr 比 32.9(26.1-64.5)μg/gcr]、NAG[13.5(8.7-17.9)U/gcr 比 7.6(6.5-13.0)U/gcr]和 KIM-1[120.0(98.4-139.9)ng/gcr 比 103.1(86.8-106.2)ng/gcr]均显著升高。所有患者中，尿 NGAL 与 UACR 的正相关性均强于 NAG（R=0.556 比 0.305，均 P<0.05）。此外，只有尿 NGAL 与 eGFR 呈负相关（R=-0.215，P<0.05）。然而，尿 KIM-1在三组 T2DM 患者之间无显著差异，且与 UACR 或 eGFR 均无相关性。随着 UACR 从正常白蛋白尿组增加到最后一个大量白蛋白尿组，所有标志物均增加。然而，只有 NGAL 的浓度在三组糖尿病患者之间存在统计学差异。肾小管标志物与肾指数之间的相关性在三组 T2DM 患者之间存在显著差异。总之，这些结果表明短期 T2DM 患者中肾小管损伤很常见。尿 NGAL 可能是监测短期 T2DM 患者肾损害的一种有前途的早期标志物。
