磷結合劑在慢性腎臟疾病病人運用的新進展

Recent Advances in the Use of Oral Phosphate Binders in Patients with Chronic Kidney Disease

黃文德(Wen-Te Huang) ； 朱柏齡(Pau-Ling Chu) ； 許育瑞(Yu-Juei Hsu)

《內科學誌》 25卷3期 (2014/06) Pp. 184-194

https://doi.org/10.6314/JIMT.2014.25(3).08

摘要

高血磷症一直是慢性腎臟疾病病人一個普遍常見的併發症，長期的高血磷通常伴隨著低血鈣及活性維生素D3（calcitriol）的不足，甚至誘發次發性副甲狀腺機能亢進（secondary hyperparathyroidism）。但是飲食限制和／或合併目前的透析方式，通常無法有效的控制血中磷離子的濃度，因此大多數慢性腎臟疾病病人仍需服用磷結合劑來改善高血磷症。含鋁的磷結合劑因為藥物嚴重的副作用已逐漸被淘汰，而含鈣的磷結合劑（俗稱鈣片）如碳酸鈣及醋酸鈣為目前最廣泛使用的磷結合劑。然而，隨著越來越多的證據顯示長期使用鈣片可能導致高血鈣，以及心血管及軟組織的鈣化，因此新一代未含鈣的磷結合劑如Sevelamer（磷能解（Sevelamer hydrochloride）；磷減樂（Sevelamer carbonate））及碳酸鑭（Lanthanum carbonate）也相繼問世，皆具有相同的降磷效果，但價格比起傳統鈣片卻相對昂貴許多。Sevelamer除了降磷的作用外，也能減緩冠狀動脈鈣化及降低低密度膽固醇（LDL）。碳酸鑭的長期使用是否會在骨頭以外的人體組織沈積而產生危害，仍需長期的追蹤觀察。近年來由於fibroblast growth factor-23（FGF-23）的發現，使我們對慢性腎臟疾病病人體內鈣磷的平衡有更深入的了解。FGF-23會增加磷酸鹽由尿液排泄，減少副甲狀腺素（parathyroid hormone）的分泌，抑制活性維生素D3的合成。但在慢性腎臟疾病病人，血漿中FGF-23的濃度升高並抑制活性維生素D3的合成與分泌，而長期下來可能造成次發性副甲狀腺機能亢進。在慢性腎臟疾病病人，目前仍無充足證據證明FGF-23可運用於監測磷結合劑的療效，FGF-23是否能發展為慢性腎臟疾病的生物標記或治療藥物，仍有待進一步研究。本文主要是探討慢性腎臟疾病病人高血磷的病理生理機轉和各種磷結合劑運用的新進展。

關鍵字

磷結合劑（Phosphate binders） ； 高血磷症（Hyperphosphatemia） ； 磷能解（Sevelamer hydrochloride） ； 碳酸鑭（Lanthanum carbonate）

並列摘要

Hyperphosphatemia, a nearly universal and common complication in patients with chronic kidney disease (CKD), is frequently accompanied by hypocalcemia and low vitamin D3 (calcitriol) level and eventually contributes to secondary hyperparathyroidism. Dietary restriction of phosphate and/or combined with current dialysis prescription are usually not sufficient to maintain serum phosphate within the recommended range. Thus, the majority of patients with CKD require oral phosphate binders to further lower serum phosphate levels. Aluminum-based phosphate binders are no longer used because of well-established toxicity. Calcium-containing phosphate binders, either calcium carbonate or calcium acetate, have been widely used to control serum phosphate concentration in patients with CKD. However, long-term administration of calcium-containing phosphate binders may result in higher risk of hypercalcemia and vascular and soft tissue calcification. Non-calcium-based phosphate binders (Sevelamer hydrochloride, Sevelamer carbonate and Lanthanum carbonate) appear to have a similar phosphate lowering effect, but these agents are significantly more expensive than traditional calcium-containing phosphate binders. In addition to its phosphate lowering effect, sevelamer appears effective in lowering LDL, which may attenuate coronary artery calcification. However, the long-term safety of lanthanum, particularly its' deposition on bone and other tissues, remains unclear. The recent discovery of fibroblast growth factor-23 (FGF-23) has provided new insight into the regulation of calcium and phosphate metabolism in patients with CKD. FGF-23 has been shown to promote phosphaturia, decreased parathyroid hormone (PTH) secretion and suppress calcitriol synthesis. In patients with CKD, increased circulating FGF-23 levels may reduce calcitriol production and subsequently leading to increased PTH. So far, there is no evidence that FGF-23 can be used to monitor the effectiveness of phosphate binders. Further studies are warranted to investigate whether FGF-23 may emerge as a powerful biomarker or therapeutic target for CKD in the clinical practice. In this review article, we will discuss the pathophysiology of hyperphosphatemia and the recent advances in the use of both calcium-containing and non-calcium containing phosphate binders in patients with CKD.