Parathyroid hormone and mobilization of circulating bone marrow-derived cells in uremic patients

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.