吴静等
[摘要] 意图 调查碳酸镧联合阿法骨化醇医治保持性腹膜透析患者继发甲状旁腺功用亢进的作用。 办法 选取30例保持性非卧床腹膜透析继发甲状旁腺功用亢进患者,随机分为对照组(n=15,阿法骨化醇 0.5 μg/d)和医治组(n=15,阿法骨化醇0.5 μg、1次/d+碳酸镧500 mg、3次/d),调查医治前及医治后接连3个月的血Ca2+、血P3+及血全段甲状旁腺激素(iPTH)水平改变。 成果 对照组医治2、3个月后,仅血Ca2+有显着改进(P<0.05),血P3+、血iPTH与医治前比较差异无计算学含义(P>0.05)。医治组的血P3+于医治后1个月开端下降,血Ca2+、血iPTH于医治后2个月开端有显着改进(P<0.05);与对照组医治3个月比较,医治组血P3+、血iPTH改进显着,差异有计算学含义(P<0.05)。 定论 在阿法骨化醇基础上加用碳酸镧可显着改进保持性腹膜透析患者钙磷代谢紊乱,有用缓解继发甲状旁腺功用亢进。
[关键词] 阿法骨化醇;碳酸镧;保持性腹膜透析;甲状旁腺功用亢进
[中图分类号] R459.5 [文献标识码] A [文章编号] 1674-4721(2014)08(b)-0096-03
[Abstract] Objective To observe the effect of lanthanum carbonate combined with alphacalcidol in the treatment of continuous peritoneal dialysis patients with secondary hyperparathyroidism. Methods 30 cases of continuous ambulatory peritoneal dialysis patients with secondary hyperparathyroidism were selected and randomly divided into control group(n=15,alphacalcidol 0.5 μg/d)and treatment group(n=15,alphacalcidol 0.5 μg/d+lanthanum carbonate 500 mg,three times a day).In 3 months of treatment,serum calcium(Ca2+),serum phosphate(P3+)and serum intact parathyroid hormone(iPTH)was observed respectively. Results After 2 and 3 months of treatment in control group,only the level of serum Ca2+ increased obviously between before and after treatment,with statistical difference(P<0.05).There was no statistical difference in the change of serum P3+ and iPTH(P>0.05)in control group.In treatment group,serum P3+ began to fall evidently after 1 month of combination therapy with lanthanum carbonate(P<0.05).Serum Ca2+ and iPTH showed significant change after 2 month of treatment(P<0.05).There was statistical difference on the serum P3+ and iPTH between treatment group and control group after 3 months respectively(P<0.05). Conclusion Alphacalcidol combined lanthanum carbonate can obviously improve the calcium and phosphorus metabolism disorder in peritoneal dialysis patients,and relieve secondary hyperparathyroidism effectively.
[Key words] Alphacalcidol;Lanthanum carbonate;Continous peritoneal dialysis;Hyperparathyroidism
缓慢肾脏疾病(chronic kidney disease,CKD)具有高发病率、高住院率、高逝世率及高额医治费用等特色,已成为危害全国际公共卫生健康的严峻疾病[1]。CKD患者约占国际总人口的10%[1],西南地区CKD的患病率高达18.3%,成人中约有1.2亿CKD患者[2],全国约有3600万尿毒症患者需行肾脏代替医治,CKD已成为影响我国人群的重要健康问题。跟着医疗技能的改进,越来越多的尿毒症患者挑选保持性非卧床腹膜透析(CAPD)医治。继发性甲状旁腺功用亢进是CAPD患者常见的并发症,也是其发作肾性骨病及相应靶器官危害的重要病因。研讨发现血P3+每升高1 mg/dl,CKD患者逝世风险升高18%,高磷血症是逝世风险添加的一个独立要素[3-4],所以挑选适宜的药物医治钙磷代谢紊乱显得尤为重要。本研讨调查磷结合剂——碳酸镧联合阿法骨化醇医治CAPD患者继发甲状旁腺功用亢进的临床作用,为临床合理防治甲状旁腺功用亢进供给根据。endprint
1 材料与办法
1.1 一般材料
选取2011年3月~2013年12月本院肾内科行CAPD继发甲状旁腺功用亢进患者30例,随机分为两组,对照组和医治组各15例。对照组:男9例,女6例;年纪22~72岁,均匀(44.7±3.8)岁;保持性腹膜透析1~5年,均匀3.2年;原发病为缓慢肾小球肾炎7例,糖尿病肾病4例,高血压肾危害3例,急进性肾小球肾炎1例。医治组:男8例,女7例;年纪20~78岁,均匀(46.8±4.2)岁;保持性腹膜透析1~6年,均匀3.8年;原发疾病为缓慢肾小球肾炎8例,糖尿病性肾病3例,高血压肾病3例,梗阻性肾病1例。两组患者的一般状况比较差异无计算学含义(P>0.05),具有可比性。
1.2 腹膜透析及医治
两组患者均行CAPD 3~4次/d,透析液为广州百特公司的低钙透析液(碳酸盐-1.5%),对照组给予阿法骨化醇软胶囊(上海信宜延安药业有限公司,批号:05130904,0.5 μg/粒)0.5 μg口服,1次/d,2~4周后根据血Ca2+状况调整剂量,最大剂量为0.5~1 μg/d;医治组在对照组的基础上嚼服碳酸镧咀嚼片[费森尤斯卡比(我国)投资有限公司,批号:H20120055,500 mg/片]500 mg,3次/d,餐中嚼服。根据血P3+状况调整碳酸镧用量,最大日剂量不超越3750 mg,一起给予低蛋白和低磷饮食合作医治,总阶段为3个月。
1.3 调查目标
两组医治前后每隔4周均监测血Ca2+、血P3+,选用双位点免疫放射剖析法测定全段甲状旁腺激素(iPTH),接连调查3个月。
1.4 计算学处理
选用SPSS 17.0计算软件对数据进行剖析和处理,计量材料以x±s标明,选用t查验,以P<0.05为差异有计算学含义。
2 成果
2.1 两组医治前后血Ca2+、血P3+及血iPTH的比较
两组医治后2、3个月的血Ca2+水平与医治前比较,差异有计算学含义(P<0.05);对照组医治后血P3+、血iPTH水平与医治前比较差异无计算学含义(P>0.05);医治组的血P3+水平与医治前比较,医治1个月后开端下降(P<0.05),医治后3个月与对照组比较差异有计算学含义(P<0.05);医治组的血iPTH水平医治后2个月开端下降,差异有计算学含义(P<0.05),且医治后3个月与对照组比较差异有计算学含义(P<0.05)(表1)。
2.2 不良反应状况
在医治期间,一切患者未呈现阿法骨化醇、碳酸镧有关的严峻不良反应(消化道症状、头痛、头晕、肝肾功用危害、皮疹)。对照组1例患者呈现高钙血症,削减阿法骨化醇用量后血Ca2+降至正常。医治组1例呈现厌恶症状,服药2周后消失;1例呈现高钙血症,也于削减阿法骨化醇用量后血Ca2+降至正常。
3 评论
缓慢肾衰竭时,肾脏1α羟化作用的危害及维生素D受体的表达削减,导致相对和肯定1,25-(OH)2D3的缺乏,是CKD患者发作继发性甲状旁腺功用亢进的主要原因[5]。高磷血症不只经过削减骨化三醇的发生和下降血Ca2+浓度直接影响PTH的排泄,并且对甲状旁腺还有直接刺激作用,引起PTH排泄添加,是构成继发性甲状旁腺功用亢进的重要要素[6]。缓慢肾衰竭前期,血P3+仍保持在正常范围内,当肾小球滤过率为20~50 ml/min时,血P3+水平开端升高[7],保持性腹膜透析不能有用铲除血P3+,且高磷血症是心血管疾病的独立风险要素,因而调理CAPD的钙磷代谢紊乱,缓解甲状旁腺代谢紊乱显得尤为重要。
阿法骨化醇口服经小肠吸收后在肝内经25-羟化酶作用转化为1,25-(OH)2 D3而发挥作用,1,25-(OH)2 D3直接按捺PTH组成与排泄,添加甲状旁腺对Ca2+的敏感性,促进肠道吸收Ca2+,纠正低钙血症[8]。本研讨发现使用阿法骨化醇医治CAPD患者低钙血症作用切当,对照组和医治组口服阿法骨化醇2、3个月后血Ca2+均有升高趋势(P<0.05),标明单用阿法骨化醇可显着升高血Ca2+,且不易导致高钙血症。
依照KDOQI攻略引荐的透析患者每日蛋白摄入量1.2 g/kg,长时刻腹膜透析患者的高磷血症简直不可避免[9],虽然能够选用添加透析频率、延伸透析时刻来添加铲除血P3+[10],但由于本钱问题、各个透析中心技能问题,透析铲除的P3+仍是有限。碳酸镧是一种不含钙和铝的磷酸盐结合剂,经过构成高度不溶的磷酸镧复合物来按捺磷酸盐的吸收,然后下降血浆磷酸盐和磷酸钙水平。用于终晚期肾病患者下降血清中磷酸盐浓度,有其共同的医治优越性[11-12]。本研讨发现,碳酸镧的起效时刻较快,大约1个月就体现出了显着下降趋势,3个月医治组患者血P3+大多降至正常,且不升高血Ca2+浓度。本文发现医治组服用碳酸镧加阿法骨化醇后2个月iPTH水平呈现显着下降趋势,3个月后iPTH水平降至正常,考虑与碳酸镧及阿法骨化醇的升高血Ca2+、下降血P3+及改进继发性甲状旁腺功用亢进有关。
我国血液透析展开较快,临床上有较多关于患者钙磷代谢的研讨,而腹膜透析在我国底层医院展开相对较迟,其钙磷代谢紊乱的研讨相对较少[13]。本研讨发现,单用阿法骨化醇医治3个月后血Ca2+水平康复正常,差异有计算学含义,而血P3+、血iPTH水平较医治前差异无计算学含义,可能与医治时刻短及样本量少有关,今后可经过添加样本量及延伸医治时刻进一步调查临床作用。医治组血Ca2+水平康复正常,血P3+、血iPTH水平显着下降,差异有计算学含义,可证明阿法骨化醇联合碳酸镧在纠正低钙、高磷及下降PTH水平,而不升高血Ca2+中作用显着,安全可靠。
综上所述,碳酸镧联合阿法骨化醇能够显着改进保持性血液透析患者钙、磷代谢紊乱,有用缓解继发性甲状旁腺功用亢进,为临床合理防治甲状旁腺功用亢进供给根据。endprint
[参考文献]
[1] 张训.缓慢肾脏病继发性甲状旁腺功用亢进的新知道[J].我国中西医结合肾病杂志,2010,11(4):283-285.
[2] Zhang L,Wang F,Wang L,et al.Prevalence of chronic kidney disease in China:a cross-sectional survey[J].Lancet,2012,379(9818):815-822.
[3] Palmer SC,Hayen A,Macaskill P,et al.Serum levels of phosphorus,parathyroid hormone,and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease:a systematic review and meta-analysis[J].JAMA,2011,305(11):1119-1127.
[4] Hruska KA,Saab G,Mathew S,et al.Renal osteodystrophy,phosphate homeostasis,and vascular calcification[J].Semin Dial,2007,20(4):309-315.
[5] Cozzolion M,Gallieni M,Brancaccio D,et al.Vitamin D retains an important role in the pathogenesis and management of secondary hyperparathyroidism in chronic renal failure[J].J Nephrol,2006,19(5):566-577.
[6] Cunningham J,Locatelli F,Rodriguez M,et al.Secondary hyperparathyroidism:pathogenesis,disease progression,and therapeutic options[J].Clin J Am Soc Nephrol,2011,6(4):913-921.
[7] 王海燕,王梅.缓慢肾脏病及透析的临床攻略[M].北京:公民卫生出版社,2004:141-153.
[8] Francis RM,Boyle IT,Moniz C,et al.A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures[J].Osteoporos Int,1996,6(4):284-290.
[9] Uribarri J.Doqi guidelines for nutrition in long-term peritoneal dialysis patients:a dissenting view[J].Am J Kidney Dis,2001,37(6):1313-1318.
[10] Badve SV,Zimmerman DL,Knoll GA,et al.Peritoneal phosphate clearance is influenced by peritoneal dialysis modality,independent of peritoneal transport characteristics[J].Clin J Am Soc Nephrol,2008,3(6):1711-1717.
[11] Tonelli M,Pannu N,Manns B,et al.Oral phosphate binders in patients with kidney failure[J].N Engl J Med,2010,363(10):1312-1324.
[12] Lloret MJ,Ruiz-García C,Dasilva I,et al.Lanthanum carbonate for the control of hyperphosphatemia in chronic renal failure patients:a new oral powder formulation-safety,efficacy,and patient adherence[J].Patient Prefer Adherence,2013,7:1147-1156.
[13] 瞿金涛,汪玫,郁胜强.1998~2007年国内腹膜透析及血液透析范畴文献回忆与剖析[J].我国全科医学,2010, 13(8):1953-1955.
(收稿日期:2014-06-06 本文修改:李亚聪)endprint
[参考文献]
[1] 张训.缓慢肾脏病继发性甲状旁腺功用亢进的新知道[J].我国中西医结合肾病杂志,2010,11(4):283-285.
[2] Zhang L,Wang F,Wang L,et al.Prevalence of chronic kidney disease in China:a cross-sectional survey[J].Lancet,2012,379(9818):815-822.
[3] Palmer SC,Hayen A,Macaskill P,et al.Serum levels of phosphorus,parathyroid hormone,and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease:a systematic review and meta-analysis[J].JAMA,2011,305(11):1119-1127.
[4] Hruska KA,Saab G,Mathew S,et al.Renal osteodystrophy,phosphate homeostasis,and vascular calcification[J].Semin Dial,2007,20(4):309-315.
[5] Cozzolion M,Gallieni M,Brancaccio D,et al.Vitamin D retains an important role in the pathogenesis and management of secondary hyperparathyroidism in chronic renal failure[J].J Nephrol,2006,19(5):566-577.
[6] Cunningham J,Locatelli F,Rodriguez M,et al.Secondary hyperparathyroidism:pathogenesis,disease progression,and therapeutic options[J].Clin J Am Soc Nephrol,2011,6(4):913-921.
[7] 王海燕,王梅.缓慢肾脏病及透析的临床攻略[M].北京:公民卫生出版社,2004:141-153.
[8] Francis RM,Boyle IT,Moniz C,et al.A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures[J].Osteoporos Int,1996,6(4):284-290.
[9] Uribarri J.Doqi guidelines for nutrition in long-term peritoneal dialysis patients:a dissenting view[J].Am J Kidney Dis,2001,37(6):1313-1318.
[10] Badve SV,Zimmerman DL,Knoll GA,et al.Peritoneal phosphate clearance is influenced by peritoneal dialysis modality,independent of peritoneal transport characteristics[J].Clin J Am Soc Nephrol,2008,3(6):1711-1717.
[11] Tonelli M,Pannu N,Manns B,et al.Oral phosphate binders in patients with kidney failure[J].N Engl J Med,2010,363(10):1312-1324.
[12] Lloret MJ,Ruiz-García C,Dasilva I,et al.Lanthanum carbonate for the control of hyperphosphatemia in chronic renal failure patients:a new oral powder formulation-safety,efficacy,and patient adherence[J].Patient Prefer Adherence,2013,7:1147-1156.
[13] 瞿金涛,汪玫,郁胜强.1998~2007年国内腹膜透析及血液透析范畴文献回忆与剖析[J].我国全科医学,2010, 13(8):1953-1955.
(收稿日期:2014-06-06 本文修改:李亚聪)endprint
[参考文献]
[1] 张训.缓慢肾脏病继发性甲状旁腺功用亢进的新知道[J].我国中西医结合肾病杂志,2010,11(4):283-285.
[2] Zhang L,Wang F,Wang L,et al.Prevalence of chronic kidney disease in China:a cross-sectional survey[J].Lancet,2012,379(9818):815-822.
[3] Palmer SC,Hayen A,Macaskill P,et al.Serum levels of phosphorus,parathyroid hormone,and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease:a systematic review and meta-analysis[J].JAMA,2011,305(11):1119-1127.
[4] Hruska KA,Saab G,Mathew S,et al.Renal osteodystrophy,phosphate homeostasis,and vascular calcification[J].Semin Dial,2007,20(4):309-315.
[5] Cozzolion M,Gallieni M,Brancaccio D,et al.Vitamin D retains an important role in the pathogenesis and management of secondary hyperparathyroidism in chronic renal failure[J].J Nephrol,2006,19(5):566-577.
[6] Cunningham J,Locatelli F,Rodriguez M,et al.Secondary hyperparathyroidism:pathogenesis,disease progression,and therapeutic options[J].Clin J Am Soc Nephrol,2011,6(4):913-921.
[7] 王海燕,王梅.缓慢肾脏病及透析的临床攻略[M].北京:公民卫生出版社,2004:141-153.
[8] Francis RM,Boyle IT,Moniz C,et al.A comparison of the effects of alfacalcidol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures[J].Osteoporos Int,1996,6(4):284-290.
[9] Uribarri J.Doqi guidelines for nutrition in long-term peritoneal dialysis patients:a dissenting view[J].Am J Kidney Dis,2001,37(6):1313-1318.
[10] Badve SV,Zimmerman DL,Knoll GA,et al.Peritoneal phosphate clearance is influenced by peritoneal dialysis modality,independent of peritoneal transport characteristics[J].Clin J Am Soc Nephrol,2008,3(6):1711-1717.
[11] Tonelli M,Pannu N,Manns B,et al.Oral phosphate binders in patients with kidney failure[J].N Engl J Med,2010,363(10):1312-1324.
[12] Lloret MJ,Ruiz-García C,Dasilva I,et al.Lanthanum carbonate for the control of hyperphosphatemia in chronic renal failure patients:a new oral powder formulation-safety,efficacy,and patient adherence[J].Patient Prefer Adherence,2013,7:1147-1156.
[13] 瞿金涛,汪玫,郁胜强.1998~2007年国内腹膜透析及血液透析范畴文献回忆与剖析[J].我国全科医学,2010, 13(8):1953-1955.
(收稿日期:2014-06-06 本文修改:李亚聪)endprint