Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, PO Box 30.001, 9700 RB Groningen, The Netherlands.
Clin J Am Soc Nephrol. 2011 Feb;6(2):361-8. doi: 10.2215/CJN.04560510. Epub 2010 Oct 7.
Experimental studies suggest a detrimental role for vasopressin in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, it is unknown whether endogenous vasopressin concentration is associated with disease severity in patients with ADPKD.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Plasma copeptin concentration (a marker of endogenous vasopressin levels) was measured in 102 ADPKD patients (diagnosis based on Ravine criteria) by an immunoassay. Plasma and urinary osmolarity were also measured. To assess disease severity, GFR and effective renal blood flow were measured by continuous infusion of 125I-iothalamate and 131I-hippuran, total renal volume by magnetic resonance imaging, and 24-hour urinary albumin excretion by nephelometry.
In these ADPKD patients, copeptin was associated with the various markers of disease severity in ADPKD (positively with total renal volume [R=0.47] and albuminuria [R=0.39] and negatively with GFR [R=-0.58] and effective renal blood flow [R=-0.52], all P<0.001). These associations were independent of age, gender, and use of diuretics. Copeptin was furthermore associated with plasma osmolarity (P<0.001) but not with 24-hour urinary volume, 24-hour urinary osmolarity or fractional urea excretion (P=0.7, 0.9, and 0.3, respectively).
On cross-sectional analysis, copeptin is associated with disease severity in ADPKD patients, supporting the results of experimental studies that suggest that vasopressin antagonists have a renoprotective effect in ADPKD and offering a good prospect for clinical studies with these agents.
实验研究表明,加压素在常染色体显性多囊肾病(ADPKD)的发病机制中起有害作用。然而,目前尚不清楚内源性加压素浓度是否与 ADPKD 患者的疾病严重程度相关。
设计、设置、参与者和测量:通过免疫测定法测量了 102 名 ADPKD 患者(根据 Ravine 标准诊断)的血浆 copeptin 浓度(内源性加压素水平的标志物)。还测量了血浆和尿渗透压。为了评估疾病严重程度,通过连续输注 125I-iothalamate 和 131I-hippuran 测量 GFR 和有效肾血流量,通过磁共振成像测量总肾体积,通过散射比浊法测量 24 小时尿白蛋白排泄量。
在这些 ADPKD 患者中,copeptin 与 ADPKD 的各种疾病严重程度标志物相关(与总肾体积[R=0.47]和蛋白尿[R=0.39]呈正相关,与 GFR[R=-0.58]和有效肾血流[R=-0.52]呈负相关,均 P<0.001)。这些关联独立于年龄、性别和利尿剂的使用。Copeptin 还与血浆渗透压相关(P<0.001),但与 24 小时尿量、24 小时尿渗透压或尿尿素分数无关(分别为 P=0.7、0.9 和 0.3)。
在横断面分析中,copeptin 与 ADPKD 患者的疾病严重程度相关,支持实验研究的结果,即加压素拮抗剂在 ADPKD 中具有肾保护作用,并为这些药物的临床研究提供了良好的前景。