Nephrology Department, Hospital Clínico Universitario San Carlos, Madrid, Spain.
Nephrol Dial Transplant. 2012 Nov;27(11):4227-35. doi: 10.1093/ndt/gfs409.
The discovery of fibroblast growth factor 23 (FGF23) provides a new conceptual framework that improves our understanding of the pathogenesis of post-transplant bone disease. Excess FGF23 is produced in the early post-transplant period; levels return to normal in the months following transplant. However, few manuscripts discuss FGF23 levels in stable long-term renal transplant recipients.
We performed a cross-sectional observational study of 279 maintenance kidney recipients with chronic kidney disease (CKD) Stages 1-4 and stable allograft function who had received their transplant at least 12 months previously. We calculated the estimated GFR (eGFR) using the MDRD4 equation.
FGF23, parathyroid hormone (PTH) and phosphorus values were higher in more advanced stages, while the serum calcitriol levels and the phosphate reabsorption rate were lower. A significant inverse correlation was found between eGFR and FGF23 (r = -0.487; P < 0.001), PTH (r = -0.444; P < 0.001), serum phosphate levels (r = -0.315; P < 0.001) and fractional excretion of magnesium (r = -0.503; P < 0.001). Multivariable analysis showed that increased time on corticosteroids (P < 0.001), PTH (P < 0.001), serum phosphate (P = 0.003), decreased serum calcitriol (P = 0.049) and estimated glomerular filtration (P = 0.003) rate were associated with high FGF23 levels. In contrast with pre-transplant patients and first year post-transplant patients, higher FGF23 values were not correlated with increased phosphate excretion. An elevated phosphate reabsorption rate was associated with decreased PTH (P < 0.001) and calciuria (P = 0.028) and increased serum calcitriol (P = 0.009), plasma bicarbonate (P = 0.024) and estimated glomerular filtration (P = 0.003).
Serum FGF23 concentrations remain increased in long-term kidney graft recipients, even in the early stages of CKD. It remains to be seen whether measures aimed at reducing serum levels of PTH and phosphate and/or corticosteroid doses might help to lower serum FGF23 and whether this will improve kidney recipient outcomes.
成纤维细胞生长因子 23(FGF23)的发现为我们理解移植后骨病的发病机制提供了一个新的概念框架。移植后早期会产生过量的 FGF23,在移植后数月内恢复正常。然而,很少有文献讨论稳定的长期肾移植受者的 FGF23 水平。
我们对 279 名接受慢性肾脏病(CKD)1-4 期和稳定同种异体移植功能的维持性肾移植受者进行了横断面观察性研究,这些受者至少在 12 个月前接受了移植。我们使用 MDRD4 方程计算估计的肾小球滤过率(eGFR)。
FGF23、甲状旁腺激素(PTH)和磷值在更晚期更高,而血清 1,25-二羟维生素 D3 水平和磷重吸收率更低。eGFR 与 FGF23(r = -0.487;P < 0.001)、PTH(r = -0.444;P < 0.001)、血清磷酸盐水平(r = -0.315;P < 0.001)和镁排泄分数(r = -0.503;P < 0.001)呈显著负相关。多变量分析显示,皮质类固醇(P < 0.001)、PTH(P < 0.001)、血清磷酸盐(P = 0.003)时间增加、血清 1,25-二羟维生素 D3 减少(P = 0.049)和估计肾小球滤过率(P = 0.003)与高 FGF23 水平相关。与移植前患者和移植后 1 年的患者相比,升高的 FGF23 值与磷酸盐排泄增加无关。升高的磷重吸收率与 PTH(P < 0.001)和钙尿(P = 0.028)减少、血清 1,25-二羟维生素 D3 增加(P = 0.009)、血浆碳酸氢盐(P = 0.024)和估计肾小球滤过率(P = 0.003)相关。
即使在 CKD 的早期阶段,长期肾移植受者的血清 FGF23 浓度仍保持升高。降低血清 PTH 和磷酸盐水平和/或皮质类固醇剂量的措施是否有助于降低血清 FGF23 水平,以及这是否会改善肾移植受者的预后,还有待观察。