Department of Nephrology, Erciyes University Medical Faculty, Kayseri, Turkey.
Department of Internal Medicine, Erciyes University Medical Faculty, Kayseri, Turkey.
Clin Exp Nephrol. 2019 Sep;23(9):1130-1140. doi: 10.1007/s10157-019-01748-z. Epub 2019 May 27.
Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested.
Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study. Groups were evaluated at baseline for presence of MS, blood markers of metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) score, and biochemical markers of inflammation (hs-CRP, IL-1β, IL-6, TNF-α and PON-1). MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Patients were followed for 12 months and progression defined as a decrease in baseline eGFR > 10%.
MS and hypertension were more prevalent amongst ADPKD patients than in the control group. Meanwhile, markers of inflammation such as hs-CRP (3.63 [3.45-5.17] vs. 4.2 [3.45-8.99] mg/dL; p = 0.014), IL-6 (21.65 [14.1-27.49] vs. 24.9 [16.23-39.4] pg/mL; p = 0.004) and IL-1β (21.33 [15.8-26.4] vs. 26.78 [18.22-35] pg/mL; p < 0.001) levels were all more elevated in ADPKD patients than in non-diabetic CKD subjects. In multivariate analysis having a truncating PKD1 mutation predicted (OR 1.25 [1.09-1.43]; p = 0.002) fulfilling the MS criteria. Finally, ADPKD patients fulfilling MS criteria had a significantly more rapid progression during 12 months of follow-up than did those that did not (OR 3.28 [1.09-9.87]; p = 0.035).
Our data supports the notion that dysmetabolisms part of the ADPKD phenotype and associated with a poor outcome, especially in patients with a truncating PKD1 mutation.
超重和肥胖最近与常染色体显性多囊肾病（ADPKD）患者的预后不良有关。肥胖的代谢后果，如代谢综合征（MS）所定义的，是否也与疾病进展有关，这一点尚未得到验证。
本研究纳入了不同 CKD 分期的 105 例 ADPKD 患者和 105 例匹配 CKD 分期的非糖尿病对照者。在基线时评估两组患者是否存在 MS、代谢血液标志物、胰岛素抵抗的稳态模型评估（HOMA-IR）评分以及炎症的生化标志物（hs-CRP、IL-1β、IL-6、TNF-α 和 PON-1）。MS 根据国家胆固醇教育计划-成人治疗专家组 III（NCEP-ATP III）进行定义。患者接受了 12 个月的随访，以 eGFR 基线下降>10%定义为疾病进展。
ADPKD 患者中 MS 和高血压的发生率高于对照组。与此同时，炎症标志物如 hs-CRP（3.63[3.45-5.17]比 4.2[3.45-8.99]mg/dL；p=0.014）、IL-6（21.65[14.1-27.49]比 24.9[16.23-39.4]pg/mL；p=0.004）和 IL-1β（21.33[15.8-26.4]比 26.78[18.22-35]pg/mL；p<0.001）水平在 ADPKD 患者中均高于非糖尿病 CKD 患者。在多变量分析中，截短 PKD1 突变的存在预测（OR 1.25[1.09-1.43]；p=0.002）符合 MS 标准。最后，在 12 个月的随访中，符合 MS 标准的 ADPKD 患者的疾病进展速度明显快于不符合 MS 标准的患者（OR 3.28[1.09-9.87]；p=0.035）。
我们的数据支持这样一种观点，即 ADPKD 表型的一部分代谢异常与不良结局有关，特别是在存在截短 PKD1 突变的患者中。
