The Division of Nephrology and Hypertension Diabetes Center Tokyo Women's Medical University School of Medicine Tokyo Japan.
Department of Medicine Diabetes Center Tokyo Women's Medical University School of Medicine Tokyo Japan.
J Diabetes Investig. 2014 Mar 23;5(2):228-35. doi: 10.1111/jdi.12134. Epub 2013 Sep 16.
AIMS/INTRODUCTION: Recent observational studies suggest elevated levels of bilirubin, an endogenous anti-oxidant, might protect against kidney disease. We carried out an observational cohort study to assess whether higher baseline levels of bilirubin, within normal range, could predict the rate of development and progression of diabetic nephropathy in patients with type 2 diabetes.
Japanese type 2 diabetic patients with normo- or microalbuminuria and normal serum bilirubin (<1.2 mg/dL) were recruited from a single center, and categorized according to baseline serum bilirubin levels. Two independent end-points were specified: development or progression of diabetic nephropathy, based on transition to a more advanced stage of albuminuria (albuminuria cohort), and the rate of change in estimated glomerular filtration rate (eGFR cohort).
Albuminuria and eGFR cohorts were constructed consisting of 1,915 patients and 1,898 patients, respectively, with 1,738 patients overlapping. Mean follow up was 4.4 and 5.4 years for the two cohorts, respectively. Within the albuminuria cohort, 132 (9%) of 1,418 patients with normoalbuminuria developed microalbuminuria, and 56 (11%) of 497 patients with microalbuminuria developed macroalbuminuria. Higher baseline bilirubin levels were associated with significantly lower risk of progression from microalbuminuria to macroalbuminuria in both the univariate and multivariate analyses. In normoalbuminuric patients, an inverse association was found when restricted to a subgroup with elevated hemoglobin A1c levels. There was no relationship between bilirubin levels and the rate of change in eGFR.
Higher serum bilirubin levels, within normal range, might be predictive of a lower risk of progression of nephropathy in type 2 diabetic patients.
目的/引言：最近的观察性研究表明，胆红素作为一种内源性抗氧化剂，其水平升高可能有助于预防肾脏疾病。我们进行了一项观察性队列研究，以评估正常范围内的胆红素基线水平升高是否可以预测 2 型糖尿病患者糖尿病肾病的发展和进展速度。
本研究从一家单中心招募了伴有正常或微量白蛋白尿且血清胆红素正常（<1.2mg/dL）的日本 2 型糖尿病患者，并根据基线血清胆红素水平进行分类。指定了两个独立的终点：根据蛋白尿程度的进展（蛋白尿队列）或转变为更严重的白蛋白尿阶段，以及估算肾小球滤过率（eGFR）的变化率（eGFR 队列）来判断糖尿病肾病的发生或进展。
白蛋白尿和 eGFR 队列分别由 1915 例和 1898 例患者组成，有 1738 例患者重叠。两个队列的平均随访时间分别为 4.4 年和 5.4 年。在蛋白尿队列中，1418 例正常白蛋白尿患者中有 132 例（9%）发展为微量白蛋白尿，497 例微量白蛋白尿患者中有 56 例（11%）发展为大量白蛋白尿。在单变量和多变量分析中，较高的基线胆红素水平与从微量白蛋白尿进展为大量白蛋白尿的风险显著降低相关。在正常白蛋白尿患者中，当限制在血红蛋白 A1c 水平升高的亚组中时，发现存在反比关系。胆红素水平与 eGFR 变化率之间没有关系。
正常范围内的血清胆红素水平升高可能预示着 2 型糖尿病患者肾病进展的风险较低。
