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肥胖和FGF23反应迟钝与甲状旁腺功能减退患者的肾功能损害相关。

Obesity and blunted FGF23 response associate with kidney impairment in patients with hypoparathyroidism.

作者信息

di Filippo Luigi, Allora Agnese, Formenti Anna Maria, Ferrari Francesca, Villanova Marta, Russo Antonino, Presciuttini Barbara, Locatelli Massimo, Brandi Maria Luisa, Vezzoli Giuseppe, Marelli Claudio, Giustina Andrea

机构信息

Institute of Endocrine and Metabolic Sciences, Università Vita-Salute San Raffaele, IRCCS Ospedale San Raffaele, Milan, Italy.

Internal Medicine Division, Santa Chiara Hospital, Provincial Health Care Agency (APSS), Trento, Italy.

出版信息

Endocrine. 2025 Apr 16. doi: 10.1007/s12020-025-04221-y.

Abstract

PURPOSE

Chronic kidney disease (CKD) is a common complication of patients affected by chronic hypoparathyroidism managed with conventional therapies. However, no data are currently available regarding the endocrine and metabolic determinants of renal function in these patients.

METHODS

This was a multicenter observational study performed in three health-care centres. Patients with hypoparathyroidism were consecutively enrolled during follow-up visits in 2022-2023. These exclusion criteria were adopted: patients managed with dialysis, proteinuria (>200 mg/24 h), use of antihypertensive drugs including thiazides, ACE-inhibitors, angiotensin-II-receptor antagonists, alpha-beta blocking-agents, aldosterone-antagonists, and insulin-treated diabetes.

RESULTS

A total of 46 patients were enrolled. Median age was 53 years, 34 (74%) were female and the median disease duration was 11 years. In all patients, the calcium-phosphate product was within the normal range. The 23.7% of patients was obese (BMI ≥ 30) and CKD (defined with an eGFR < 60 mL/min1.73m) was found in the 21.7% of patients. Patients with CKD were older, affected by a longer-disease, more frequently obese and with higher BMI. In multivariate analyses, obesity resulted as the only significant independent risk factor associated with CKD. In addition, a significant negative correlation was found between BMI and eGFR, and ROC analyses showed a significant global-performances of BMI to predict CKD. Patients with CKD were characterized also by higher FGF23 levels. A significant negative correlation was found between FGF23 and eGFR, however, evaluating separately those with and without CKD, this correlation remained significant only in the second group.

CONCLUSIONS

For the first-time, obesity was demonstrated to be independently associated with CKD in patients with hypoparathyroidism, and a blunted eGFR-related response of FGF23 was shown in patients with CKD potentially worsening the renal function in the context of hypoparathyroidism.

摘要

目的

慢性肾脏病(CKD)是接受传统疗法治疗的慢性甲状旁腺功能减退患者的常见并发症。然而,目前尚无关于这些患者肾功能的内分泌和代谢决定因素的数据。

方法

这是一项在三个医疗中心进行的多中心观察性研究。甲状旁腺功能减退患者在2022年至2023年的随访期间连续入组。采用以下排除标准:接受透析治疗的患者、蛋白尿(>200mg/24h)、使用包括噻嗪类、血管紧张素转换酶抑制剂、血管紧张素II受体拮抗剂、α-β阻滞剂、醛固酮拮抗剂在内的降压药物以及接受胰岛素治疗的糖尿病患者。

结果

共纳入46例患者。中位年龄为53岁,34例(74%)为女性,中位病程为11年。所有患者的钙磷乘积均在正常范围内。23.7%的患者肥胖(BMI≥30),21.7%的患者患有CKD(定义为估算肾小球滤过率[eGFR]<60mL/min/1.73m²)。患有CKD的患者年龄更大、病程更长、肥胖更为常见且BMI更高。在多变量分析中,肥胖是与CKD相关的唯一显著独立危险因素。此外,BMI与eGFR之间存在显著负相关,ROC分析显示BMI预测CKD具有显著的整体性能。患有CKD的患者还具有较高的成纤维细胞生长因子23(FGF23)水平。FGF23与eGFR之间存在显著负相关,然而,分别评估有和没有CKD的患者时,这种相关性仅在第二组中仍然显著。

结论

首次证明肥胖与甲状旁腺功能减退患者的CKD独立相关,并且在CKD患者中显示出FGF23与eGFR相关的反应减弱,这可能会在甲状旁腺功能减退的情况下使肾功能恶化。

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