慢性肾脏病患者血清骨硬化蛋白与矿物质和骨异常的相关性研究

目的探讨慢性肾脏病（chronic kidney disease，CKD）患者血清骨硬化蛋白（sclerostin，SOST）与CKD矿物质和骨异常（CKD-mineral and bone disorder，CKD-MBD）的相关性。 方法选取CKD 3~5期患者120例，其中CKD 3期、CKD 4期和CKD 5期各40例；另选取同期年龄、性别相匹配的健康体检者40例为对照组。比较各组估算肾小球滤过率（estimated glomerular filtration rate，eGFR）、血肌酐（serum creatinine，SCr）、血尿素氮（blood urea nitrogen，BUN）、血红蛋白（hemoglobin，Hb）水平，对比各组血钙（blood calcium，Ca）、血磷（blood phosphorus，P）、钙磷乘积（calcium phosphorus product，Ca·P）、碱性磷酸酶（alkaline phosphatase，AKP）、白蛋白（albumin，ALB）水平、骨密度（bone mineral density，BMD），观察各组SOST、全段甲状旁腺素（intact parathyroid hormone，iPTH）、25-羟维生素D3［25-hydroxyvitamin D3，25-（OH）D3］水平，并分析SOST与各实验室指标的相关性。 结果CKD 3期组、CKD 4期组和CKD 5期组eGFR、Hb、25-（OH）D3显著低于对照组，SCr、BUN、SOST、iPTH显著高于对照组（P＜0.05）；CKD 4期组和CKD 5期组eGFR、Hb、25-（OH）D3显著低于CKD 3期组，SCr、BUN、SOST、iPTH显著高于CKD 3期组（P＜0.05）；与CKD 4期组比较，CKD 5期组eGFR、Hb、25-（OH）D3显著低于CKD 4期组，SCr、BUN、SOST、iPTH显著高于CKD 4期组（P＜0.05）。CKD 3期组Ca、ALB、BMD显著低于对照组（P＜0.05），CKD 4期组Ca、ALB、BMD显著低于对照组，P、Ca·P显著高于对照组（P＜0.05），CKD 5期组Ca、ALB、BMD显著低于对照组，P、Ca·P、AKP显著高于对照组（P＜0.05）；与于CKD 3期组比较，CKD 4期组Ca、BMD显著低于CKD 3期组，P、Ca·P显著高于CKD 3期组（P＜0.05），CKD 5期组Ca、BMD显著低于CKD 3期组，P、Ca·P、AKP显著高于CKD 3期组（P＜0.05）；CKD 5期组Ca、BMD显著低于CKD 4期组，P、Ca·P、AKP显著高于CKD 4期组（P＜0.05）。CKD 3~5期患者SOST与eGFR、Hb、Ca、25-（OH）D3、BMD呈负相关（r=-0.910、-0.660、-0.426、-0.393、-0.223，P＜0.05），与SCr、P、Ca·P、iPTH呈正相关（r=0.610、0.640、0.548、0.404，P＜0.05）。 结论CKD 3~5期患者血清SOST水平随临床分期增加而升高，且与BMD及矿物质骨代谢指标Ca、P、Ca·P、iPTH、25-（OH）D3密切相关，提示其可作为预测CKD-MBD的可靠指标。

Correlation between serum osteosclerotin and mineral and bone disorder in patients with chronic kidney disease

ObjectiveTo explore the correlation between serum sclerostin(SOST) and CKD-mineral and bone disorder(CKD-MBD) in patients with chronic kidney disease(CKD).MethodsA total of 120 patients with CKD stage 3-5 were selected and divided into CKD stage 3 group(n=40), CKD stage 4 group(n=40) and CKD stage 5 group(n=40) according to different stages of CKD. In addition, 40 age-and gender-matched healthy subjects who underwent physical examination were selected as the control group. The estimated glomerular filtration rate(eGFR), serum creatinine(SCr), blood urea nitrogen(BUN), hemoglobin(Hb) levels were compared in each group. The blood calcium(Ca), blood phosphorus(P), calcium phosphorus product(Ca·P), alkaline phosphatase(AKP), albumin(ALB) levels, and bone mineral density(BMD) were compared. The SOST, levels of intact parathyroid hormone(iPTH), 25-hydroxy vitamin D3［25-（OH）D3］ were observed, and the correlation between SOST and laboratory indexes was analyzed.ResultsCompared with the control group, eGFR, Hb, and 25-（OH）D3 were significantly decreased, while SCr, BUN, SOST, and iPTH were significantly increased in CKD stage 3-5 groups(P＜0.05). Compared with CKD stage 3 group, eGFR, Hb, and 25-（OH）D3 were significantly decreased and SCr, BUN, SOST, and iPTH were significantly increased in CKD stage 4 and 5 groups(P＜0.05). Compared with CKD stage 4 group, eGFR, Hb, and 25-（OH）D3 were significantly decreased and SCr, BUN, SOST, and iPTH were significantly increased in CKD stage 5 group(P＜0.05). Compared with the control group, Ca, ALB and BMD in CKD stage 3 group were significantly decreased(P＜0.05). Ca, ALB and BMD in CKD stage 4 group were significantly decreased, and P, and Ca·P were significantly increased, as compared with the control group(P＜0.05). Ca, ALB and BMD in CKD stage 5 group were significantly lower and P, Ca·P, and AKP were significantly higher than those in the control group(P＜0.05). Compared with CKD stage 3 group, Ca and BMD in CKD stage 4 group was significantly decreased, while P, Ca·P, and AKP were significantly increased(P＜0.05). Ca and BMD were significantly lower and P and Ca·P were significantly higher in CKD stage 5 group than in CKD stage 3 group(P＜0.05). Ca and BMD decreased significantly and P, Ca·P, and AKP increased significantly in CKD stage 5 group, as compared with CKD stage 4 group(P＜0.05). SOST in patients with CKD stage 3-5 groups was negatively correlated with eGFR, Hb, Ca, 25-（OH）D3 and BMD(r=- 0.910, -0.660, -0.426, -0.393, -0.223, P＜0.05), and positively correlated with SCr, P, Ca·P, and iPTH(r=0.610, 0.640, 0.548, 0.404, P＜0.05).ConclusionThe serum level of SOST in patients with CKD stage 3-5 is increased with the increase of clinical stage, and is closely related to BMD and bone mineral metabolism indexes, such as Ca, P, Ca·P, iPTH and 25-（OH）D3, suggesting that it can be used as a reliable index to predict CKD-MBD.