Diabetes and Metabolic Disease Section, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Pisana, University of Pisa, 2 Via Paradisa, 56124, Pisa, Italy.
Diabetologia. 2017 Jun;60(6):1102-1113. doi: 10.1007/s00125-017-4251-1. Epub 2017 Mar 29.
AIMS/HYPOTHESIS: In a retrospective, observational, cross-sectional, single-centre study, we assessed the prevalence and correlates of different CKD phenotypes (with and without albuminuria) in a large cohort of patients of white ethnicity with type 1 diabetes.
From 2001 to 2009, 408 men and 369 women with type 1 diabetes (age 40.2 ± 11.7 years, diabetes duration 19.4 ± 12.2 years, HbA 7.83 ± 1.17% [62.0 ± 12.9 mmol/mol]) were recruited consecutively. Albumin-to-creatinine ratio (ACR) and eGFR (Modification of Diet in Renal Disease) were obtained for all individuals, together with CKD stage. Diabetic retinopathy and peripheral polyneuropathy were detected in 41.5% and 8.1%, respectively, and cardiovascular disease (CVD) occurred in 8.5%. Adjudications of CKD phenotype were made by blinded investigators.
Normo- (ACR <3.4), micro- (ACR 3.4-34) or macroalbuminuria (ACR ≥34 mg/mmol) were present in 91.6%, 6.4% and 1.9% of individuals, respectively. eGFR categories 1 (≥90 ml min [1.73 m]), 2 (60-89 ml min [1.73 m]) and 3 (<60 ml min [1.73 m]) were present in 57.3%, 39.0% and 3.7%, respectively. The majority of participants had no CKD (89.4%), while stages 1-2 and ≥3 CKD were detected in 6.8% and 3.7%, respectively. The albuminuric (Alb) and non-albuminuric (Alb) phenotypes were present in 12 (41.4%) and 17 (58.6%) individuals with stage ≥3 CKD, respectively. Individuals with an ACR <3.4 mg/mmol were subdivided into those with normal albuminuria (<1.1 mg/mmol; 77.2%) and mildly increased albuminuria (1.1-3.4 mg/mmol; 14.4%), and individuals with stage 2 CKD were subdivided into those with eGFR 75-89 ml min [1.73 m] and 60-74 ml min [1.73 m]. ACR <3.4 mg/mmol (88.7%) and even <1.1 mg/mmol (70.4%) were common in individuals with eGFR 60-74 ml min [1.73 m]. The prevalence of ACR <1.1 mg/mmol was lower but still significant (34.5%) in those with stage ≥3 CKD. In logistic regression analysis, stages 1-2 and ≥3 CKD were independently associated with age, HbA, γ-glutamyltransferase, fibrinogen, hypertension, but not with sex, BMI, smoking, HDL-cholesterol or triacylglycerol. Inclusion of advanced retinopathy removed HbA from the model. The CKD Alb phenotype correlated with diabetes duration, HbA, HDL-cholesterol, fibrinogen and hypertension, while the CKD Alb phenotype was associated with age and hypertension, but not with diabetes duration, HbA and fibrinogen.
CONCLUSIONS/INTERPRETATION: The Alb CKD phenotype is present in a significant proportion of individuals with type 1 diabetes supporting the hypothesis of two distinct pathways (Alb and Alb) of progression towards advanced kidney disease in type 1 diabetes. These are probably distinct pathways as suggested by different sets of covariates associated with the two CKD phenotypes.
目的/假设：在一项回顾性、观察性、横断面、单中心研究中，我们评估了白种人 1 型糖尿病患者中不同 CKD 表型（有和无白蛋白尿）的患病率及其相关因素。
2001 年至 2009 年，连续纳入 408 名男性和 369 名女性 1 型糖尿病患者（年龄 40.2±11.7 岁，糖尿病病程 19.4±12.2 年，HbA1c7.83±1.17%[62.0±12.9mmol/mol]）。所有患者均检测白蛋白/肌酐比值（ACR）和肾小球滤过率（肾脏病饮食改良法），并确定 CKD 分期。分别有 41.5%和 8.1%的患者检测到糖尿病视网膜病变和周围神经病变，8.5%的患者发生心血管疾病（CVD）。盲法研究者对 CKD 表型进行了判断。
91.6%、6.4%和 1.9%的个体分别存在正常白蛋白尿（ACR<3.4mg/mmol）、微量白蛋白尿（ACR3.4-34mg/mmol）和大量白蛋白尿（ACR≥34mg/mmol）。eGFR 1 期（≥90ml/min[1.73m]）、2 期（60-89ml/min[1.73m]）和 3 期（<60ml/min[1.73m]）分别占 57.3%、39.0%和 3.7%。大多数患者没有 CKD（89.4%），而 6.8%和 3.7%的患者分别处于 CKD 1-2 期和≥3 期。在≥3 期 CKD 患者中，白蛋白尿表型（Alb）和非白蛋白尿表型（Alb）分别为 12（41.4%）和 17（58.6%）。ACR<3.4mg/mmol 的个体进一步分为正常白蛋白尿（<1.1mg/mmol；77.2%）和轻度白蛋白尿（1.1-3.4mg/mmol；14.4%），eGFR 为 75-89ml/min[1.73m]的患者进一步分为 eGFR 为 60-74ml/min[1.73m]的患者。即使在 eGFR 为 60-74ml/min[1.73m]的患者中，ACR<3.4mg/mmol（88.7%）甚至<1.1mg/mmol（70.4%）也很常见。在≥3 期 CKD 患者中，ACR<1.1mg/mmol 的患病率较低，但仍有显著意义（34.5%）。在 logistic 回归分析中，CKD 1-2 期和≥3 期 CKD 与年龄、HbA、γ-谷氨酰转移酶、纤维蛋白原、高血压独立相关，但与性别、BMI、吸烟、高密度脂蛋白胆固醇或三酰甘油无关。纳入晚期视网膜病变后，HbA 从模型中去除。CKD Alb 表型与糖尿病病程、HbA、高密度脂蛋白胆固醇、纤维蛋白原和高血压相关，而 CKD Alb 表型与年龄和高血压相关，与糖尿病病程、HbA 和纤维蛋白原无关。
结论/解释：1 型糖尿病患者的 Alb CKD 表型占相当大的比例，支持了 1 型糖尿病中两种不同的进展途径（Alb 和 Alb）向晚期肾病进展的假说。这两种途径可能是不同的，这可以从与两种 CKD 表型相关的不同的协变量集来提示。
