Department of Kidney Disease and Hypertension, Osaka General Medical Center, 3-1-56 Bandai-higashi, Osaka, 558-8558, Japan.
Bone. 2012 Oct;51(4):729-36. doi: 10.1016/j.bone.2012.06.027. Epub 2012 Jul 14.
Fibroblast growth factor 23 (FGF23), rather than parathyroid hormone (PTH), has been shown to be the major factor behind hypophosphatemia in the early period after renal transplantation. However, it is not clear whether phosphate wasting persists in the chronic phase. Purpose of our study is to elucidate whether FGF23 can also explain phosphate wasting, if any, in the chronic phase.
In this cross-sectional observational study, we enrolled 247 recipients who had received a graft more than 1 year prior to this study. We compared the phosphate metabolism of recipients and predialysis chronic kidney disease (CKD) patients who are matched on age and estimated glomerular filtration rate (eGFR). We also investigated the determinants of tubular reabsorption of phosphate normalized for glomerular filtration rate (TmP/GFR), as an index of renal threshold for phosphate.
Recipients had a median dialysis vintage of 27.0 months and eGFR 41.2 mL/min/1.73 m(2). Whereas hypophosphatemia (<2.4 mg/dL) was observed in 6.1% of the recipients, 55.2% had TmP/GFR lower than 2.4 mg/dL. Recipients showed significantly lower TmP/GFR in all CKD stages than their predialysis counterparts, indicating that phosphate wasting persists in the chronic phase. Compared to predialysis patients, the recipients in stages 2T and 3T showed lower phosphate and higher intact PTH levels, despite a higher percentage being active vitamin D users. However, in stage 4T, phosphate retention masked relative hypophosphatemia. FGF23 was higher in the recipients across all CKD stages, but adjustment for vitamin D prescription revealed that transplantation had no effect on FGF23. Multiple regression analysis in the recipients showed significant negative associations of intact PTH and dialysis vintage with TmP/GFR.
Renal phosphate wasting persists in the chronic-phase renal transplantation recipients even with normophosphatemia. Persistent hyperparathyroidism and longer dialysis vintage, not FGF23, was associated with renal phosphate wasting in the chronic phase. Such an impact on phosphate metabolism of the factors determined in dialysis period could be called as "uremic memory". This novel finding in the chronic phase is in sharp contrast to the previous finding in the early phase that FGF23 levels are determinants of phosphate wasting.
成纤维细胞生长因子 23(FGF23)而非甲状旁腺激素(PTH)已被证明是肾移植后早期低磷血症的主要原因。然而,在慢性期是否仍存在磷酸盐丢失尚不清楚。本研究旨在阐明 FGF23 是否也能解释慢性期的任何磷酸盐丢失。
在这项横断面观察性研究中,我们纳入了 247 名在研究前 1 年以上接受移植物的受者。我们比较了受者和匹配年龄和估计肾小球滤过率(eGFR)的透析前慢性肾脏病(CKD)患者的磷酸盐代谢。我们还研究了肾小管磷酸盐重吸收率与肾小球滤过率的比值(TmP/GFR)的决定因素,作为磷酸盐肾阈的指标。
受者的中位透析龄为 27.0 个月,eGFR 为 41.2 mL/min/1.73 m²。虽然 6.1%的受者存在低磷血症(<2.4 mg/dL),但 55.2%的受者 TmP/GFR 低于 2.4 mg/dL。与透析前患者相比,所有 CKD 阶段的受者 TmP/GFR 均较低,表明磷酸盐丢失在慢性期仍持续存在。与透析前患者相比,2T 和 3T 期的受者尽管活性维生素 D 使用率较高,但磷酸盐水平较低,而完整 PTH 水平较高。然而,在 4T 期,磷酸盐潴留掩盖了相对低磷血症。所有 CKD 阶段的受者 FGF23 水平均较高,但调整维生素 D 处方后,移植对 FGF23 无影响。受者的多元回归分析显示,完整 PTH 和透析龄与 TmP/GFR 呈显著负相关。
即使血磷正常,慢性期肾移植受者仍存在肾磷酸盐丢失。持续性甲状旁腺功能亢进症和更长的透析龄,而不是 FGF23,与慢性期的肾磷酸盐丢失有关。透析期这些因素对磷酸盐代谢的影响可以称为“尿毒症记忆”。这一在慢性期的新发现与早期 FGF23 水平是磷酸盐丢失决定因素的发现形成鲜明对比。