U. O. C. di Nefrologia e Dialisi, Azienda Ospedaliera "Pugliese-Ciaccio," Catanzaro, Italy.
J Investig Med. 2011 Jun;59(5):823-8. doi: 10.2310/JIM.0b013e318214edf8.
Parathyroid hormone (PTH) revealed a positive action on progenitor cells released from bone marrow, and many mechanisms supported PTH as a tool to improve stem cell-based therapy in experimental models of ischemia. Elevated PTH resulted in increased mobilization of progenitors into the peripheral blood of patients affected by untreated primary hyperparathyroidism. A frequent finding in uremic patients is a higher PTH level, and different therapeutic strategies are adopted and implemented to achieve an intermediary PTH level. On the contrary, the amount of progenitors commonly results to be extremely reduced.
In the present study, we investigated, in a cohort of uremic patients, the effect of different levels of PTH on mobilization of progenitor cell populations.
Eighty patients (26 women, 54 men) were enrolled. Following the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, patients were divided in 3 groups for PTH levels: low-PTH group with a PTH level lower than 150 pg/mL (n = 25), KDOQI-PTH group with a PTH level between 150 and 300 pg/mL (n = 37), and high-PTH group with a PTH level higher than 300 pg/mL (n = 18). Patients with high levels of PTH were treated differently to achieve KDOQI targets: 5 received intravenous calcitriol and P binders, 3 received intravenous paracalcitriol, and 10 received cinacalcet. We quantified, by the combination of surface markers (CD45(+), CD34(+), CD31(+), and c-kit(+)), the number of hematopoietic and endothelial progenitor cells.
High-PTH group demonstrated a significantly higher level of CD45(+)/CD34(+)/c-kit(+) with respect to low-PTH and KDOQI-PTH groups (1.02 [SD, 0.12] vs. 0.56 [SD, 0.14] cells/uL, P < 0.01; and 1.02 [SD, 0.12] vs. 0.46 [SD, 0.20] cells/uL, P < 0.05). CD45(+)/CD34(+)/CD31(+) levels resulted significantly increased in the KDOQI-PTH group compared with those observed in the low- (1.83 [SD, 0.72] vs 1.26 [SD, 0.83] cells/μL, P = 0.04) and high-PTH groups (1.83 [SD, 0.72] vs 1.20 [SD, 1.15] cells/μL, P = 0.04). Receiver operating characteristic analyses were performed to define the ability of CD45(+)/34(+)/31(+) to identify the presence of an optimal PTH status (>150 but <300 pg/mL) among all hemodialysis patients. The area under the curve of CD45(+)/34(+)/31(+) was 0.674 (95% confidence interval [CI], 0.501-0.819) with a best cutoff level of 1.36 cells/μL (sensitivity, 80.0; specificity, 59.1; P < 0.05). After 4 months, we demonstrated an increase in endothelial progenitor cell number in 13 patients with secondary hyperparathyroidism that achieved KDOQI targets in PTH levels after pharmacological treatment.
Our data confirm, with acknowledged limitations due to the low number of patients, the effect of PTH on bone marrow-derived progenitor cells emphasizing that, in our cohort, an intermediary PTH level, achieved following specific guidelines, results in an equilibrate balance between different subsets of progenitor cells.
甲状旁腺激素（PTH）对骨髓释放的祖细胞有积极作用，许多机制支持 PTH 作为改善缺血实验模型中基于干细胞的治疗的工具。甲状旁腺激素升高会导致祖细胞更多地动员到未经治疗的原发性甲状旁腺功能亢进症患者的外周血中。尿毒症患者的一个常见发现是 PTH 水平较高，并且采用了不同的治疗策略来实现中间 PTH 水平。相反，祖细胞的数量通常会极度减少。
在本研究中，我们在一组尿毒症患者中研究了不同水平的 PTH 对祖细胞群动员的影响。
共纳入 80 例患者（26 名女性，54 名男性）。根据肾脏疾病结果质量倡议（KDOQI）指南，患者根据 PTH 水平分为 3 组：低 PTH 组（PTH 水平低于 150 pg/mL，n=25）、KDOQI-PTH 组（PTH 水平在 150 至 300 pg/mL 之间，n=37）和高 PTH 组（PTH 水平高于 300 pg/mL，n=18）。高 PTH 组患者接受不同的治疗以达到 KDOQI 目标：5 例接受静脉注射骨化三醇和 P 结合剂，3 例接受静脉注射帕立骨化醇，10 例接受西那卡塞。我们通过组合表面标志物（CD45(+)、CD34(+)、CD31(+)和 c-kit(+)）来量化造血和内皮祖细胞的数量。
高 PTH 组与低 PTH 和 KDOQI-PTH 组相比，CD45(+)/CD34(+)/c-kit(+)水平显著升高（1.02 [SD，0.12] 比 0.56 [SD，0.14] 细胞/μL，P<0.01；1.02 [SD，0.12] 比 0.46 [SD，0.20] 细胞/μL，P<0.05）。KDOQI-PTH 组的 CD45(+)/CD34(+)/CD31(+)水平与低 PTH 组（1.83 [SD，0.72] 比 1.26 [SD，0.83] 细胞/μL，P=0.04）和高 PTH 组（1.83 [SD，0.72] 比 1.20 [SD，1.15] 细胞/μL，P=0.04）相比，显著升高。进行了受试者工作特征分析，以确定 CD45(+)/34(+)/31(+)是否能够识别所有血液透析患者中存在最佳 PTH 状态（>150 但<300 pg/mL）。CD45(+)/34(+)/31(+)的曲线下面积为 0.674（95%置信区间 [CI]，0.501-0.819），最佳截断值为 1.36 细胞/μL（灵敏度，80.0；特异性，59.1；P<0.05）。在接受药物治疗后达到 KDOQI 目标的甲状旁腺激素水平的 13 例继发性甲状旁腺功能亢进症患者中，我们在 4 个月后证明了内皮祖细胞数量的增加。
我们的数据证实了 PTH 对骨髓来源的祖细胞的作用，由于患者数量有限，存在一些局限性，但这些数据得到了确认。强调了在我们的队列中，遵循特定指南达到的中间 PTH 水平会导致不同祖细胞亚群之间达到平衡。
