慢性肾脏病患者血清FGF23水平与钙磷代谢及临床相关性
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摘要
目的探讨血清成纤维细胞生长因子23(FGF23)在慢性肾脏病(CKD)中的变化规律,在慢性肾脏病-矿物质骨代谢异常(CKD-MBD)早期诊断中价值及与临床的相关性。方法选取CKD患者140例,分为3期组、4期组、5期非透析组(5ND)、5期血液透析组(5HD),并将18例健康体检者纳入对照组,完善血钙(Ca)、血磷(P)、血红蛋白(Hb)、白蛋白(ALB)、血肌酐(SCr)、骨源性碱性磷酸酶(BALP)、甲状旁腺激素(PTH)、FGF23等指标及心脏彩色多普勒检查,监测清晨安静状态下血压。根据是否存在左心室肥厚(LVH)分为LVH组和非左心室肥厚(NLVH)组,根据是否存在心脏瓣膜钙化分为心脏瓣膜钙化组和非心脏瓣膜钙化组。结果①3期组(1.83±0.19)、4期组(1.91±0.16)、5ND期组(1.99±0.18)、5HD期组(2.12±0.12)logFGF23均显著高于对照组(1.74±0.14)(P<0.05),且随着CKD进展不断升高;②3期组Ca(2.13±0.19)、P(1.20±0.21)、logPTH(1.74±0.21)均在正常范围内;③5ND组Hb、Ca显著低于其他组(P<0.05),P显著高于其他组(P<0.05);④5ND组和5HD组BALP及logPTH水平显著高于3期组和4期组(P<0.05);⑤FGF23与P、SCr、BALP、PTH、收缩压呈正相关(P<0.05),与Hb呈负相关性(P<0.05);⑥R*C表χ~2检验示CKD分期与LVH存在中等强度相关,Cramer′s V=0.376,P=0.001,与心脏瓣膜钙化存在弱强度相关,Cramer′s V=0.264,P=0.044;⑦年龄、FGF23和收缩压是LVH的独立危险因素,年龄和FGF23是心脏瓣膜钙化的独立危险因素。结论 FGF23随着CKD进展不断升高,其变化早于Ca、P、PTH,且为LVH和心脏瓣膜钙化的独立危险因素,可作为CKD-MBD的预测指标,与临床密切相关。
Objective To investigate the changes of serum fibroblast growth factor 23(FGF23) in patients with chronic kidney disease(CKD), its value in the early diagnosis of chronic kidney disease-abnormal mineral bone metabolism(CKD-MBD) and its clinical relevance.Methods A total of 140 CKD patients were enrolled in this study. CKD patients were divided into 3 stage group, 4 stage group, 5 stage non dialysis group(5 ND) and 5 state hemodialysis group(5 HD). 18 healthy persons were selected as control group. The laboratory indexes such as calcium(Ca), phosphorus(P), hemoglobin(Hb), albumin(ALB), bone alkaline phosphatase(BALP), parathyroid hormone(PTH) and FGF23 were measured, and echocardiography was undergone. Blood pressure was monitored in the morning quiet state. According to the presence or absence of left ventricular hypertrophy(LVH), they were divided into group LVH and group NLVH. According to the presence or absence of cardiac valve calcification, they were divided into cardiac valve calcification group and non cardiac valve calcification group.Results Relationship between Ca, P, Hb, ALB, BALP, PTH, FGF23 and renal function:the logFGF23 of 3 stage group(1.83±0.19), 4 stage group(1.91±0.16), 5 ND group(1.99±0.18) and 5 HD group(2.12±0.12) were significantly higher than those of the control group(1.74±0.14)(P<0.05), and increased with the CKD progressed. Ca(2.13±0.19), P(1.20±0.21), logPTH(1.74±0.21) in the 3 stage group were all within the normal range.Hb and Ca in the 5 ND group were significantly lower than those in other groups(P<0.05). P was significantly higher than those in other groups(P<0.05).BALP and logPTH in the 5 ND group and the 5 HD group were significantly higher than those in the 3 stage group and the 4 stage group(P<0.05). FGF23 was positively correlated with P, SCr, BALP, PTH and SBP(P<0.05), and negatively correlated with Hb(P<0.05). Analysis of risk factors for LVH and cardiac valve calcification:R*C table χ~2 test showed that CKD stage was moderately correlated with left ventricular hypertrophy, Cramer′s V=0.376, P=0.001, and weakly correlated with cardiac valve calcification, Cramer′s V=0.264, P=0.044. ② Age, FGF23 and SBP were independent risk factors for LVH. Age and FGF23 were independent risk factors for heart valve calcification.Conclusion FGF23 is increasing with the progress of CKD, and its change is earlier than Ca, P, PTH.FGF23 is an independent risk factor for LVH and cardiac valve calcification. It can be used as a predictor of CKD-MBD and is closely related to clinical practice.
Objective To investigate the changes of serum fibroblast growth factor 23(FGF23) in patients with chronic kidney disease(CKD), its value in the early diagnosis of chronic kidney disease-abnormal mineral bone metabolism(CKD-MBD) and its clinical relevance.Methods A total of 140 CKD patients were enrolled in this study. CKD patients were divided into 3 stage group, 4 stage group, 5 stage non dialysis group(5 ND) and 5 state hemodialysis group(5 HD). 18 healthy persons were selected as control group. The laboratory indexes such as calcium(Ca), phosphorus(P), hemoglobin(Hb), albumin(ALB), bone alkaline phosphatase(BALP), parathyroid hormone(PTH) and FGF23 were measured, and echocardiography was undergone. Blood pressure was monitored in the morning quiet state. According to the presence or absence of left ventricular hypertrophy(LVH), they were divided into group LVH and group NLVH. According to the presence or absence of cardiac valve calcification, they were divided into cardiac valve calcification group and non cardiac valve calcification group.Results Relationship between Ca, P, Hb, ALB, BALP, PTH, FGF23 and renal function:the logFGF23 of 3 stage group(1.83±0.19), 4 stage group(1.91±0.16), 5 ND group(1.99±0.18) and 5 HD group(2.12±0.12) were significantly higher than those of the control group(1.74±0.14)(P<0.05), and increased with the CKD progressed. Ca(2.13±0.19), P(1.20±0.21), logPTH(1.74±0.21) in the 3 stage group were all within the normal range.Hb and Ca in the 5 ND group were significantly lower than those in other groups(P<0.05). P was significantly higher than those in other groups(P<0.05).BALP and logPTH in the 5 ND group and the 5 HD group were significantly higher than those in the 3 stage group and the 4 stage group(P<0.05). FGF23 was positively correlated with P, SCr, BALP, PTH and SBP(P<0.05), and negatively correlated with Hb(P<0.05). Analysis of risk factors for LVH and cardiac valve calcification:R*C table χ~2 test showed that CKD stage was moderately correlated with left ventricular hypertrophy, Cramer′s V=0.376, P=0.001, and weakly correlated with cardiac valve calcification, Cramer′s V=0.264, P=0.044. ② Age, FGF23 and SBP were independent risk factors for LVH. Age and FGF23 were independent risk factors for heart valve calcification.Conclusion FGF23 is increasing with the progress of CKD, and its change is earlier than Ca, P, PTH.FGF23 is an independent risk factor for LVH and cardiac valve calcification. It can be used as a predictor of CKD-MBD and is closely related to clinical practice.
引文
[1] Zhang L,Wang F,Wang L,et al.Prevalence of chronic kidney disease in China:a cross-sectional survey[J].Lancet,2012,379(9818):815-22.
[2] Kendrick J,Cheung A K,Kaufman J S,et al.FGF-23 associates with death,cardiovascular events,and initiation of chronic dialysis[J].J Am Soc Nephrol,2011,22(10):1913-22.
[3] Tsuchiya K,Nagano N,Nitta K.Klotho/FGF23 axis in CKD[J].ContribNephrol,2015,185:56-65.
[4] Myakala K,Motta S,Murer H,et al.Renal-specific and inducible depletion of NaPi-IIc/Slc34a3,the cotransporter mutated in HHRH,does not affect phosphate or calcium homeostasis in mice[J].Am J Physiol Renal Physiol,2014,306(8):F833-43.
[5] Hu M C,Shiizaki K,Kuro-o M,et al.Fibroblast growth factor 23 and Klotho:physiology and pathophysiology of an endocrine network of mineral metabolism[J].Annu Rev Physiol,2013,75:503-33.
[6] Isakova T,Wahl P,Vargas G S,et al.Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease[J].Kidney Int,2011,79(12):1370-8.
[7] Gutierrez O M,Mannstadt M,Isakova T,et al.Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis[J].N Engl J Med,2008,359(6):584-92.
[8] Jialal I,Camacho F,Nathoo B,et al.Fibroblast growth factor 23 predicts mortality and end-stage renal disease in a Canadian Asian population with chronic kidney disease[J].Nephron,2017,137(3):190-6.
[9] Sardiwal S,Magnusson P,Goldsmith D J,et al.Bone alkaline phosphatase in CKD-mineral bone disorder[J].Am J Kidney Dis,2013,62(4):810-22.
[10] Nakano C,Hamano T,Fujii N,et al.Intact fibroblast growth factor 23 levels predict incident cardiovascular event before but not after the start of dialysis[J].Bone,2012,50(6):1266-74.
[11] Faul C,Amaral A P,Oskouei B,et al.FGF23 induces left ventricular hypertrophy[J].J Clin Invest,2011,121(11):4393-408.
[12] Leifheit-Nestler M,Groβe Siemer R,Flasbart K,et al.Induction of cardiac FGF23/FGFR4 expression is associated with left ventricular hypertrophy in patients with chronic kidney disease[J].Nephrol Dial Transplant,2016,31(7):1088-99.
[13] Grabner A,Amaral A P,Schramm K,et al.Activation of cardiac fibroblast growth factor receptor 4 causes left ventricular hypertrophy[J].Cell Metab,2015,22(6):1020-32.
[14] DeSeigneux S,Martin P Y.Phosphate and FGF23 in the renoprotective benefit of RAAS inhibition[J].Pharmacol Res,2016,106:87-91.
[15] Yilmaz M I,Sonmez A,Saglam M,et al.FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease[J].Kidney Int,2010,78(7):679-85.
[2] Kendrick J,Cheung A K,Kaufman J S,et al.FGF-23 associates with death,cardiovascular events,and initiation of chronic dialysis[J].J Am Soc Nephrol,2011,22(10):1913-22.
[3] Tsuchiya K,Nagano N,Nitta K.Klotho/FGF23 axis in CKD[J].ContribNephrol,2015,185:56-65.
[4] Myakala K,Motta S,Murer H,et al.Renal-specific and inducible depletion of NaPi-IIc/Slc34a3,the cotransporter mutated in HHRH,does not affect phosphate or calcium homeostasis in mice[J].Am J Physiol Renal Physiol,2014,306(8):F833-43.
[5] Hu M C,Shiizaki K,Kuro-o M,et al.Fibroblast growth factor 23 and Klotho:physiology and pathophysiology of an endocrine network of mineral metabolism[J].Annu Rev Physiol,2013,75:503-33.
[6] Isakova T,Wahl P,Vargas G S,et al.Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease[J].Kidney Int,2011,79(12):1370-8.
[7] Gutierrez O M,Mannstadt M,Isakova T,et al.Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis[J].N Engl J Med,2008,359(6):584-92.
[8] Jialal I,Camacho F,Nathoo B,et al.Fibroblast growth factor 23 predicts mortality and end-stage renal disease in a Canadian Asian population with chronic kidney disease[J].Nephron,2017,137(3):190-6.
[9] Sardiwal S,Magnusson P,Goldsmith D J,et al.Bone alkaline phosphatase in CKD-mineral bone disorder[J].Am J Kidney Dis,2013,62(4):810-22.
[10] Nakano C,Hamano T,Fujii N,et al.Intact fibroblast growth factor 23 levels predict incident cardiovascular event before but not after the start of dialysis[J].Bone,2012,50(6):1266-74.
[11] Faul C,Amaral A P,Oskouei B,et al.FGF23 induces left ventricular hypertrophy[J].J Clin Invest,2011,121(11):4393-408.
[12] Leifheit-Nestler M,Groβe Siemer R,Flasbart K,et al.Induction of cardiac FGF23/FGFR4 expression is associated with left ventricular hypertrophy in patients with chronic kidney disease[J].Nephrol Dial Transplant,2016,31(7):1088-99.
[13] Grabner A,Amaral A P,Schramm K,et al.Activation of cardiac fibroblast growth factor receptor 4 causes left ventricular hypertrophy[J].Cell Metab,2015,22(6):1020-32.
[14] DeSeigneux S,Martin P Y.Phosphate and FGF23 in the renoprotective benefit of RAAS inhibition[J].Pharmacol Res,2016,106:87-91.
[15] Yilmaz M I,Sonmez A,Saglam M,et al.FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease[J].Kidney Int,2010,78(7):679-85.