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探讨原发性甲状旁腺功能亢进症中敏感且特异的生物标志物对隐匿性肾损伤的作用。

Investigating subtle kidney injury in primary hyperparathyroidism by means of sensitive and specific biomarkers.

机构信息

Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, Rome, Italy.

Faculty of Economics, UNINT University, Rome, Italy.

出版信息

Clin Endocrinol (Oxf). 2019 Nov;91(5):660-668. doi: 10.1111/cen.14064. Epub 2019 Aug 1.

Abstract

OBJECTIVE

Kidney involvement is a common complication in primary hyperparathyroidism (PHPT). No study so far has assessed the prevalence of kidney injury developing before the reduction in glomerular filtration rate (GFR) in PHPT. The study was aimed at establishing the potential role of biomarkers of kidney injury in detecting subtle renal damage in patients with PHPT.

DESIGN

Cross-sectional study.

PATIENTS

A total of 69 postmenopausal patients with PHPT and 41 healthy age- and sex-matched subjects were studied. Exclusion criteria were as follows: GFR < 30 mL/min, chronic inflammatory disease, nephrotic syndrome, infection, malignancy, heart failure, recent exposure to iodinated contrast media or nonsteroidal anti-inflammatory drugs.

MEASUREMENTS

We measured a panel of sensitive biomarkers of kidney injury in PHPT vs controls.

RESULTS

Mean FGF23 and Klotho were higher in PHPT (72 ± 48 and 811 ± 366 pg/mL, respectively) than controls (53 ± 23.5 and 668.6 ± 17; P < .02 and P < .05). Urine KIM-1/uCr was significantly higher in PHPT (1.4  ± 1.3 ) than controls (9.2  ± 7 ; P < .05); this was particularly evident in the CrCl 60-89 mL/min category (1.3  ± 9 vs 8.2  ± 3.6 ; P < .02). Mean values of urine NGAL/uCr were higher in PHPT with (n = 28) compared to those without kidney stones (n = 35; 1.8  ± 1.4 and 1  ± 8 ; P < .0001). We found significant positive associations between urine NGAL/uCr and Ca (R = .292, P < .02) and urine KIM1/uCr and PTH (R = .329, P < .01).

CONCLUSIONS

We propose the utilization of these molecules, particularly urine KIM-1/uCr and urine NGAL/uCr ratios for the assessment of subtle kidney injury in patients with PHPT. These molecules are elevated in tubular necrosis and have potential role in the development of kidney damage in PHPT, according to the severity of the disease.

摘要

目的

肾脏损害是甲状旁腺功能亢进症(PHPT)的常见并发症。目前尚无研究评估 PHPT 患者肾小球滤过率(GFR)降低前肾脏损伤的发生率。本研究旨在确定肾脏损伤生物标志物在检测 PHPT 患者亚临床肾脏损害中的潜在作用。

设计

横断面研究。

患者

共纳入 69 例绝经后 PHPT 患者和 41 例年龄和性别匹配的健康对照者。排除标准如下:GFR<30mL/min、慢性炎症性疾病、肾病综合征、感染、恶性肿瘤、心力衰竭、近期接触碘造影剂或非甾体抗炎药。

检测指标

测量 PHPT 患者与对照组的一组敏感的肾脏损伤生物标志物。

结果

与对照组相比,PHPT 患者的 FGF23 和 Klotho 中位值更高(分别为 72±48pg/mL 和 811±366pg/mL)(P<0.02 和 P<0.05)。PHPT 患者尿 KIM-1/肌酐比值(1.4±1.3)明显高于对照组(9.2±7)(P<0.05);在 CrCl 60-89mL/min 亚组中更为显著(1.3±9 vs 8.2±3.6)(P<0.02)。有肾结石的 PHPT 患者(n=28)尿 NGAL/肌酐比值(1.8±1.4)高于无肾结石的 PHPT 患者(n=35;1.0±8)(P<0.0001)。我们发现尿 NGAL/肌酐比值与 Ca(R=0.292,P<0.02)和尿 KIM-1/肌酐比值与 PTH(R=0.329,P<0.01)之间存在显著正相关。

结论

我们提出利用这些分子,特别是尿 KIM-1/肌酐比值和尿 NGAL/肌酐比值,评估 PHPT 患者的亚临床肾脏损伤。这些分子在肾小管坏死中升高,根据疾病的严重程度,在 PHPT 患者的肾脏损害发展中具有潜在作用。

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