Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, Netherlands.
Center for Adults with Rare Genetic Syndromes, Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, Netherlands.
Front Endocrinol (Lausanne). 2023 Jul 21;14:1168648. doi: 10.3389/fendo.2023.1168648. eCollection 2023.
Prader-Willi syndrome (PWS) is a rare, complex, genetic disorder characterized by hyperphagia, hypotonia, delayed psychomotor development, low muscle mass and hypothalamic dysfunction. Adults with PWS often have obesity, hypertension and type 2 diabetes mellitus (DM2), known risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD). Early symptoms of CVD and CKD may be masked by intellectual disability and inability to express physical complaints. Furthermore, kidney diseases are often asymptomatic. Therefore, renal and cardiovascular disease might be missed in patients with PWS. Microalbuminuria is an early sign of microvascular damage in the kidneys and other vascular beds. Therefore, we screened our adult PWS cohort for the presence of elevated urinary albumin and (micro)albuminuria.
We retrospectively collected anthropometric measurements, blood pressure, medical history, medication use, urine dipstick and biochemical measurements form electronic patient files. In addition, we performed a systematic literature review on kidney disease in PWS.
We included 162 adults with genetically confirmed PWS (56% male, median age 28 years), of whom 44 (27%) had DM2. None had known CVD. All subjects had normal estimated glomerular filtration rate (eGFR) according to non-PWS reference intervals. Elevated urinary albumin or (micro)albuminuria was present in 28 (18%); 19 out of 75 (25%) had an increased urinary albumin-to-creatinine ratio (UACR) and 10 out of 57 (18%) had an increased urinary protein-to-creatinine ratio. Elevated urinary albumin was present at a young age (median age 26 (IQR 24-32) years) and was associated with an significantly higher BMI and LDL-cholesterol levels and higher prevalence of DM2, hypertension and dyslipidemia than those with normal UACR (=0.027, =0.019, <0.001, <0.001, =0.011 and respectively).
Upon screening, one in every five adults with PWS had increased urinary albumin or (micro)albuminuria, early signs of microvascular disease. All had normal eGFR, according to non-PWS reference intervals, and none had a formal diagnosis of CVD. As muscle mass is low in PWS, creatinine levels and eGFR may be spuriously normal. Urinalysis in this patient group can be used as a screening tool for microvascular (kidney) disease. We propose an algorithm for the detection and management of microvascular disease in adults with PWS.
普拉德-威利综合征（PWS）是一种罕见的、复杂的遗传性疾病，其特征为食欲过盛、低张力、精神运动发育迟缓、肌肉量低和下丘脑功能障碍。患有 PWS 的成年人通常患有肥胖症、高血压和 2 型糖尿病（DM2），这些都是心血管疾病（CVD）和慢性肾脏病（CKD）的已知危险因素。CVD 和 CKD 的早期症状可能被智力残疾和无法表达身体不适所掩盖。此外，肾脏疾病往往没有症状。因此，PWS 患者可能会漏诊肾脏和心血管疾病。微量白蛋白尿是肾脏和其他血管床微血管损伤的早期迹象。因此，我们对我们的成年 PWS 队列进行了尿液白蛋白和（微量）白蛋白尿升高的筛查。
我们从电子病历中回顾性地收集了人体测量学测量、血压、病史、用药、尿试纸和生化测量值。此外，我们对 PWS 中的肾脏疾病进行了系统的文献回顾。
我们纳入了 162 名经基因证实的 PWS 成年人（56%为男性，中位年龄 28 岁），其中 44 名（27%）患有 DM2。无人患有已知的 CVD。根据非 PWS 参考区间，所有患者的估算肾小球滤过率（eGFR）均正常。28 名（18%）存在尿液白蛋白或（微量）白蛋白尿升高；75 名中有 19 名（25%）的尿白蛋白/肌酐比值（UACR）升高，57 名中有 10 名（18%）的尿蛋白/肌酐比值升高。尿液白蛋白升高出现在年轻年龄（中位数年龄 26（IQR 24-32）岁），与 BMI 和 LDL-胆固醇水平显著升高以及 DM2、高血压和血脂异常的患病率更高相关（=0.027，=0.019，<0.001，<0.001，=0.011，分别）。
在筛查中，每 5 名 PWS 成年人中就有 1 名出现尿液白蛋白或（微量）白蛋白尿升高，这是微血管疾病的早期迹象。根据非 PWS 参考区间，所有患者的 eGFR 均正常，且无人患有 CVD 的正式诊断。由于 PWS 患者的肌肉量较低，肌酐水平和 eGFR 可能会出现假性正常。在该患者组中，尿分析可作为微血管（肾脏）疾病的筛查工具。我们提出了一种用于检测和管理 PWS 成人微血管疾病的算法。
