Fibrosis is a major driver of chronic kidney disease, and epithelial-mesenchymal transition (EMT) may contribute to its development. A polyubiquitinated form of phosphatase and tensin homolog (PTEN) promotes EMT in vitro. Thus, it is a potentially useful biomarker of progressive kidney fibrosis and may predict loss of kidney function. Observational cohort study. Southwest United States, American Indians (154 women, 80 men) with or at high risk for diabetic kidney disease (DKD). Serum level of PTEN. ≥40% loss of glomerular filtration rate (GFR) or onset of kidney failure. Kidney structural measures in a subset of study participants who underwent research kidney biopsies (n = 77). Cox proportional hazards models adjusted for age, sex, diabetes duration, hemoglobin A (HbA), blood pressure, use of renin angiotensin system (RAS) blockers, measured GFR, and albuminuria. Spearman correlations for associations with structural measures. At baseline, the participants’ mean age was 42.8 ± 10.5 (SD) years, diabetes duration 11.5 ± 7.1 years, mean arterial pressure 90.5 ± 9.5 mm Hg, HbA 9.3 ± 2.4%, GFR 152 ± 45 mL/min, and median urinary albumin-creatinine ratio 38 (interquartile range, 14-215) mg/g. RAS blockers were being used by 64 participants (27.4%). A higher PTEN value was associated with a greater risk of ≥40% loss of GFR during a median follow-up period of 6.3 years (HR for quartile 4 [Q4] vs Q1, 3.95 [95% CI, 2.23-6.98], < 0.001). Serum PTEN was associated with an increased risk of kidney failure over a median follow-up period of 15.8 years (HR for Q4 vs Q1, 5.66 [95% CI, 1.99-16.13], = 0.001). Baseline serum PTEN in the biopsy subset correlated with structural measures including glomerular basement membrane width (ρ = 0.370, < 0.001) and mesangial fractional volume (ρ = 0.392, < 0.001). Small study in single population. Higher serum PTEN is associated with increased risk for GFR decline and kidney failure in American Indians with type 2 diabetes.

中文翻译：

---

患有 2 型糖尿病的美洲印第安人的血清多泛素化 PTEN 水平与肾功能丧失


纤维化是慢性肾脏病的主要驱动因素，上皮间质转化 (EMT) 可能有助于其发展。磷酸酶和张力蛋白同源物 (PTEN) 的多泛素化形式可在体外促进 EMT。因此，它是进行性肾纤维化的潜在有用的生物标志物，并且可以预测肾功能的丧失。观察性队列研究。美国西南部的美洲印第安人（154 名女性，80 名男性）患有糖尿病肾病 (DKD) 或具有高风险。 PTEN 的血清水平。肾小球滤过率 (GFR) 损失≥40% 或出现肾衰竭。接受研究性肾活检的一部分研究参与者的肾脏结构测量（n = 77）。 Cox 比例风险模型根据年龄、性别、糖尿病病程、血红蛋白 A (HbA)、血压、肾素血管紧张素系统 (RAS) 阻滞剂的使用、测量的 GFR 和蛋白尿进行调整。与结构性指标关联的 Spearman 相关性。基线时，参与者的平均年龄为 42.8 ± 10.5 (SD) 岁，糖尿病病程 11.5 ± 7.1 年，平均动脉压 90.5 ± 9.5 mm Hg，HbA 9.3 ± 2.4%，GFR 152 ± 45 mL/min，中位尿尿白蛋白-肌酐比率 38（四分位数范围，14-215）mg/g。 64 名参与者 (27.4%) 使用 RAS 阻滞剂。较高的 PTEN 值与中位随访期间 6.3 年期间 GFR 损失 ≥40% 的风险较高相关（四分位数 4 [Q4] 与 Q1 的 HR，3.95 [95% CI，2.23-6.98]，< 0.001）。在中位随访期 15.8 年中，血清 PTEN 与肾衰竭风险增加相关（Q4 与 Q1 的 HR，5.66 [95% CI，1.99-16.13]，= 0.001）。活检子集中的基线血清 PTEN 与结构测量相关，包括肾小球基底膜宽度 (ρ = 0.370，< 0.001) 和系膜体积分数 (ρ = 0.392，< 0.001）。单一人群的小型研究。在患有 2 型糖尿病的美洲印第安人中，较高的血清 PTEN 与 GFR 下降和肾衰竭的风险增加相关。