Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY, USA.
Department of Regenerative & Cancer Cell Biology, Albany Medical College, Albany, NY, USA.
Diabetes Res Clin Pract. 2019 Sep;155:107805. doi: 10.1016/j.diabres.2019.107805. Epub 2019 Aug 1.
Intrarenal Aquaporin 5 (AQP5) is upregulated in patients with diabetic nephropathy. Here we investigate whether urinary AQP5 is independently associated with estimated glomerular filtration rate (eGFR) decline in patients with type 2 diabetes and nephropathy.
Baseline urine samples (n = 997) from patients with type 2 diabetes and nephropathy of the sulodexide macroalbuminuria trial were measured for AQP5 through enzyme-linked immunosorbent assays. Pearson correlation and multiple linear regression between AQP5 with eGFR slope (calculated by ≥3 serum creatinine during follow-up) was performed, and association with fast renal function decline, defined as eGFR slope less than 3.0 mL/min/1.73 m/year, was determined by logistic regression.
Follow-up eGFR data >1.4 years from n = 700 were available for analyses. AQP5 was undetectable in 138 patients. Tertiles of AQP5 were 0.4 [0-2.2], 7.3 [5.9-9.1], and 16.0 [13.0-21.6] (ng/mL), respectively (p < 0.01). Patients in the highest tertile of AQP5 had significantly higher total cholesterol, lower baseline eGFR, and higher levels of albuminuria compared to the lowest tertile. AQP5 was inversely correlated with eGFR slope (Pearson's r = -0.12, p < 0.001), and independent of clinical risk factors age, sex, race, and baseline systolic and diastolic blood pressure, hemoglobin A1c, total cholesterol, eGFR, and urine albumin-to-creatinine ratio (β = -0.05, p < 0.004). Furthermore, AQP5 was significantly associated with fast eGFR decline (Odds Ratio = 1.03 (95% Confidence Interval 1.003-1.06), p < 0.03).
Our data suggest that baseline AQP5 is independently associated with the progression of eGFR decline in patients with type 2 diabetes and nephropathy.
肾内水通道蛋白 5（AQP5）在糖尿病肾病患者中上调。在这里，我们研究尿 AQP5 是否与 2 型糖尿病和肾病患者的估算肾小球滤过率（eGFR）下降独立相关。
通过酶联免疫吸附试验测量来自 2 型糖尿病和肾病 sulodexide 大蛋白尿试验的基线尿液样本（n=997）中的 AQP5。进行 AQP5 与 eGFR 斜率（通过随访期间≥3 次血清肌酐计算）之间的 Pearson 相关性和多元线性回归，并通过逻辑回归确定与快速肾功能下降的关系，定义为 eGFR 斜率小于 3.0mL/min/1.73m/year。
n=700 中有超过 1.4 年的随访 eGFR 数据可供分析。138 名患者的 AQP5 无法检测到。AQP5 的三分位为 0.4 [0-2.2]、7.3 [5.9-9.1]和 16.0 [13.0-21.6]（ng/mL）（p<0.01）。AQP5 最高三分位的患者总胆固醇明显较高，基线 eGFR 较低，且尿白蛋白/肌酐比值较高。AQP5 与 eGFR 斜率呈负相关（Pearson r=-0.12，p<0.001），且独立于临床危险因素（年龄、性别、种族以及基线收缩压和舒张压、糖化血红蛋白、总胆固醇、eGFR 和尿白蛋白/肌酐比值）（β=-0.05，p<0.004）。此外，AQP5 与快速 eGFR 下降显著相关（优势比=1.03（95%置信区间 1.003-1.06），p<0.03）。
我们的数据表明，基线 AQP5 与 2 型糖尿病和肾病患者 eGFR 下降的进展独立相关。
