<313020BFF8C0FA BFB0C1F6BFAC2DB1E8B1D9C8A32E687770>

Size: px

Start display at page:

Download "<313020BFF8C0FA BFB0C1F6BFAC2DB1E8B1D9C8A32E687770>"

준현 예
5 years ago
Views:

1 대한내과학회지 : 제 81 권제 6 호 2011 혈액투석에서투석액칼슘농도와칼시트리올이골대사에미치는영향 한양대학교의과대학내과학교실 염지연 김현철 이영철 최종욱 박준성 이창화 강종명 김근호 Effects of Dialysate Calcium Concentration and Calcitriol on Bone Metabolism in Hemodialysis Patients Ji-Youn Youm, Hyun-Chul Kim, Young-Chul Lee, Jong-Wook Choi, Joon-Sung Park, Chang-Hwa Lee, Chong-Myung Kang, and Gheun-Ho Kim Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea Background/Aims: Whereas higher dialysate calcium (Ca) levels may pose a risk of hypercalcemia, lower levels may induce a negative Ca balance. We evaluated the effect of lowering dialysate Ca levels from 1.75 to 1.5 mmol/l and explored the appropriate use of calcitriol to regulate bone metabolism in hemodialysis patients. Methods: The dialysate Ca levels of 36 patients were reduced from 1.75 to 1.5 mmol/l. They were divided into three groups according to basal intact parathyroid hormone (ipth) level (group 1, ipth < 150 pg/ml, n = 21; group 2, ipth pg/ml, n = 7; group 3, ipth > 300 pg/ml, n = 8). Data were collected at 3-month intervals for 1 year. Results: Throughout the study period, no significant difference in phosphate binders, serum Ca, phosphorus (P), or Ca P products was observed among groups. However, ipth, alkaline phosphatase (AP), and calcitriol dosage patterns differed among groups. In group 1, ipth and AP increased significantly over 12 months (p = 0.01). In group 2, ipth and AP showed no significant changes. In group 3, ipth and AP declined significantly over 12 months (p = 0.02). Calcitriol dosage did not change in groups 1 and 2, but increased significantly in group 3 (p = 0.001). Conclusions: After converting hemodialysate Ca levels from 1.75 to 1.5 mmol/l, the initially different ipth concentrations converged to a modestly elevated level. The use of 1.5 mmol/l hemodialysate Ca may thus be appropriate for both high- and low-turnover bone disease if phosphate binders and calcitriol are combined appropriately. (Korean J Med 2011;81: ) Keywords: Hemodialysis solution; Calcium; Parathyroid hormone; Calcitriol; Renal osteodystrophy Received: Revised: Accepted: Correspondence to Gheun-Ho Kim, M.D., Ph.D. Department of Internal Medicine, Hanyang University College of Medicine, 17 Haengdang-dong, Seongdong-gu, Seoul , Korea Tel: , Fax: , kimgh@hanyang.ac.kr * This study was supported by a grant from Fresenius Medical Care Korea (2009) and the results were presented in abstract form at the World Congress of Nephrology 2009 in Milan, Italy

2 - The Korean Journal of Medicine: Vol. 81, No. 6, 서 론 대상및방법 만성콩팥병이진행하면고인산혈증이발생하고비타민 D 활성화가감소하여골대사의변화를초래한다. 투석환자에서주로이차성부갑상선기능항진증이문제되었으나, 최근에는칼슘이포함된인결합제와비타민 D 제제사용이증가하면서부갑상선호르몬분비가오히려억제되는 adynamic bone disease 의빈도가점차증가하고있다. 이와관련하여, 투석액의칼슘농도는칼슘평형및골대사에영향미치는주요요소이다. 현재혈액투석에사용하는투석액칼슘농도는 1.25 mmol/l, 1.5 mmol/l, 1.75 mmol/l로구분된다 [1]. 고칼슘 (1.75 mmol/l) 투석액은부갑상선호르몬분비를억제시키고혈역학을안정시켜투석중저혈압을예방하는효과가있으나 [2], 고칼슘혈증에의한전이성석회화우려가있다 [3]. 한편, 저칼슘 (1.25 mmol/l) 투석액은고칼슘혈증의위험을감소시켜칼슘제제나비타민 D를좀더자유롭게사용할수있으므로 adynamic bone disease 의개선효과가있다 [4,5]. 그러나칼슘평형을악화시켜부갑상선호르몬분비를자극하고투석중저혈압을일으킬우려가있으므로적절한투석액칼슘농도를선택하는것이쉽지않다 [6]. 혈액투석이도입된초기에는생리학적수준에맞추어투석액칼슘농도 1.25 mmol/l가사용되었으나, 이차성부갑상선기능항진증이중요한문제로대두되어최근까지고칼슘투석액이주로사용되었다. 그러나칼슘이포함된인결합제와비타민 D 사용이증가하면서고칼슘혈증과 adynamic bone disease 이합병되어다시투석액칼슘농도를낮추어야하는상황이흔히있다. 국내에서도 adynamic bone disease 가있는혈액투석환자에서투석액칼슘농도를표준칼슘 (1.5 mmol/l) 에서저칼슘 (1.25 mmol/l) 으로낮추었을때일부환자에서억제된부갑상선기능이회복되었다고보고된바있다 [7]. 그러나부갑상선호르몬분비가정상이거나높은수준의환자에서도투석액칼슘농도를낮추어유리한효과를기대할수있는지아직분명하지않다. 저자들은부갑상선호르몬수준이다양한혈액투석환자에서고칼슘 (1.75 mmol/l) 투석액을표준칼슘 (1.5 mmol/l) 농도로낮추어사용하였을때 calcitriol 용량변화와아울러골대사에미치는효과를평가하고자하였다. 대상 한양대학교병원에서 1년이상고칼슘투석액 ( 투석액칼슘농도 1.75 mmol/l) 을사용하면서안정적으로혈액투석을받는환자 36명을대상으로하여, 표준칼슘투석액 ( 투석액칼슘농도 1.5 mmol/l) 으로전환한후 1년간경과를추적하였다. 혈청칼슘농도에영향을미칠수있는전신감염증, 악성신생물, 간경변증, 담즙정체성질환, 결핵을포함한육아종증, 부갑상선절제술의경우및신이식혹은투석방법을변경한환자는제외하였다. 방법 표준칼슘투석액사용전 3개월과사용후 1년에걸쳐 3 개월간격으로측정한혈청총칼슘, 인, 알칼리포스파타제 (alkaline phosphatase), 부갑상선호르몬 (intact parathyroid hormone, ipth) 및요소감소율 (urea reduction rate, URR) 을후향적으로수집하여분석하였다. 혈청알부민농도가총칼슘농도에미치는영향을배제하기위하여, 다음공식에따라혈청총칼슘농도를혈청알부민농도로교정하였다 [8]. 교정칼슘농도 (corrected Calcium, c-ca) (mg/dl) = 총칼슘농도 (mg/dl) + [4 - 알부민농도 (g/l)] 0.8 생화학적지표들은표준자동분석기를이용하여측정하였고, 혈청 ipth는면역방사계수측정법 (immunoradiometric assay, 정상치 8-76 pg/ml) 을이용하여측정하였다. 환자들이사용한고칼슘투석액 ( 헤모트레이트비1호, 중외제약, 서울, 한국 ) 과표준칼슘투석액 ( 헤모비덱스 0.1% 1호, 중외제약, 서울, 한국 ) 의조성이표 1에제시되어있다. Table 1. Composition of standard and high-calcium hemodialysates Standard High-calcium Ca ++ (meq/l) Na + (meq/l) K + (meq/l) Mg ++ (meq/l) Cl - (meq/l) CH 3COO - (meq/l) 8 8 Dextrose (g/l)

3 - Ji-Youn Youm, et al. Dialysate calcium and calcitriol in HD - 또한, 표준칼슘투석액으로전환하기 3개월전에측정한기저혈청 ipth 농도에따라, 환자를 1군 (ipth < 150 pg/ml, n = 21), 2군 (ipth pg/ml, n = 7) 및 3군 (ipth > 300 pg/ml, n = 8) 으로구분하여 12개월에걸친혈청총칼슘, 인, ipth, 알칼리포스파타제농도및요소감소율변화를비교하였다. 투석환자진료지침에따라혈청인농도 mg/dl 를목표로칼슘이포함된인결합제 ( 탄산칼슘 500 mg/t 및아세트산칼슘 710 mg/t) 와 sevelamer (800 mg/t) 가사용되었고, ipth pg/ml를유지하고자 ipth 300 pg/ml 이상인경우에경구 (0.25 μg/t) 혹은정주 (1 μg/a) 칼시트리올을투여하였다 [9]. 인결합제와칼시트리올투여용량도 3 개월간격으로후향적으로수집하여분석하였다. 통계분석측정값은평균 ± 표준편차로표시하였고, 통계처리를위해 PASW 통계프로그램윈도우용 18.0 (PASW, Inc., Chicago, IL, USA) 을사용하였다. 표준칼슘투석액으로전환하고 1년에걸쳐 3개월간격으로반복측정한연속변수들의변화여부를검증하기위하여 repeated measures ANOVA를이용하였고, 기저치와전환후 3, 6, 9, 12개월사이의두측정치를비교하고자 Wilcoxon Matched-Pairs Signed-Ranks test을이용하였다. 세군또는두군사이의기저치를비교할때는연속변수의경우 Kruskal-Wallis test 또는 Mann-Whitney U test를각각이용하였고, 카테고리변수의경우 Chi-squared test를이용하였다. p 값 0.05 미만을통계적으로유의하다고판단하였다. 결과고칼슘투석액에서표준칼슘투석액으로전환후변화대상환자 36명중남자 18명, 여자 18명이었고, 연령이 55.6 ± 11.4세였으며, 평균혈액투석기간은 179 ± 79개월 (85-371개월) 이었다. 만성콩팥병의원인은고혈압 12예, 당뇨병 6예, 만성사구체신염 5예및원인불명 5예였다. 전체환자에서표준칼슘투석액으로전환후 3개월간격으로측정한요소감소율, 교정칼슘농도, 혈청인, 교정칼슘 인값, 알칼리포스파타제및 ipth 자료가표 2에제시되어있다. 표준칼슘투석액으로전환후 12개월동안요소감소율, 교정칼슘농도, 혈청인, 교정칼슘 인및알칼리포스파타제의유의한변화는없었다. 그러나혈청 ipth는표준칼슘투석액으로전환후 12개월에걸쳐점차증가하였고 (p = 0.037), 특히 6개월째값이높았다가 (202 ± 238 vs. 391 ± 371 pg/ml, p < 0.05) 약간감소하여안정되었다 (Table 2). 같은기간동안투여된인결합제인칼슘이포함된제제와 sevelamer 모두표준칼슘투석액으로전환후그용량에유의한변화가없었다. 그러나경구혹은정주칼시트리올용량은표준칼슘투석액으로전환후유의하게증가하였다 (p = 0.002, Table 3). 기저부갑상선호르몬수준에따른비교표준칼슘투석액으로전환하기 3개월전에측정한기저혈청 ipth 농도에따라환자를세군으로구분하였을때 1 군, 2군및 3군의 ipth 농도는각각 57 ± 48 pg/ml, 191 ± 46 Table 2. Changes of urea reduction ratio, serum corrected calcium, phosphorus, Ca P product, alkaline phosphatase and parathyroid hormone before and after conversion to hemodialysate calcium 1.5 mmol/l (n = 36) Baseline 3 months 6 months 9 months 12 months p a URR, % 71.4 ± ± ± ± ± c-ca, mg/dl 10.6 ± ± ± ± ± P, mg/dl 4.6 ± ± ± ± ± c-ca P, mg 2 /dl ± ± ± ± ± AP, IU/L 87 ± ± ± ± ± ipth, pg/ml 202 ± ± ± 371 b 329 ± ± Values are expressed as means ± standard deviations. URR, urea reduction ratio; c-ca, corrected calcium; P, phosphate; AP, alkaline phosphatase; ipth, intact parathyroid hormone. a Comparisons were performed using repeated-measures analysis of variance. b p < 0.05 vs. baseline value; Wilcoxon matched-pairs signed-ranks test

4 - 대한내과학회지 : 제 81 권제 6 호통권제 616 호 Table 3. Dosage of phosphate binders (mg/day) and calcitriol (μg/month) before and after conversion to hemodialysate calcium 1.5 mmol/l (n = 36) Baseline 3 months 6 months 9 months 12 months p b Phosphate binders Calcium-based a 1897 ± ± ± ± ± Sevelamer 133 ± ± ± ± ± Calcitriol 0.8 ± ± 4.4 c 3.6 ± 4.5 c 5.4 ± 5.1c 4.5 ± 4.9c Values are expressed as means ± standard deviations. a Calcium carbonate and calcium acetate. b Comparisons were performed using repeated-measures analysis of variance. c p < 0.05 vs. baseline value; Wilcoxon matched-pairs signed-ranks test. Table 4. Comparison of basal characteristics among groups based on parathyroid hormone level Group 1 (n = 21) Group 2 (n = 7) Group 3 (n = 8) p Age, yr a 57.9 ± ± ± 11.4 NS Male, % b 11 (52.3) 2 (28.6) 5 (62.5) NS Dialysis duration, mon a ± ± ± 88.0 NS URR, % 70.7 ± ± ± 5.3 NS Causes of ESRD b NS Diabetes, % 3 (14.3) 2 (28.6) 1 (12.5) Hypertension, % 8 (38.1) 3 (46.9) 1 (12.5) Glomerulonephritis, % 2 (9.5) 0 (0) 3 (37.5) Unknown, % 8 (38.1) 2 (28.6) 3 (37.5) Phosphate binders a Calcium carbonate and acetate, mg/day 1802 ± ± ± 1976 NS Sevelamer HCl, mg/day ± 1697 NS Calcitriol, μg/mon a 0.7 ± ± ± c-ca, mg/dl a 10.6 ± ± ± 0.9 NS P, mg/dl a 4.8 ± ± ± 2.1 NS c-ca P, mg 2 /dl 2 a 47.0 ± ± ± 20.5 NS AP, IU/L a 78 ± ± ± 32 NS ipth, pg/ml a 57 ± ± ± 200 < Continuous data are expressed as means ± standard deviations. NS, not significant; URR, urea reduction ratio; ESRD, end-stage renal disease; c-ca, corrected total calcium; P, phosphorus; AP, alkaline phosphatase; ipth, intact parathyroid hormone. a Comparisons were performed using the Kruskal-Wallis test. b Comparisons were performed using the chi-squared test. pg/ml, 589 ± 200 pg/ml로유의한차이가있었다 (p < 0.001). 한편, 세군사이에연령, 성별, 혈액투석기간, 요소감소율, 원인질환, 교정칼슘농도, 혈청인농도, 교정칼슘 인값 및알칼리포스파타제는세군사이에유의한차이가없었다. 인결합제의용량차이는없었으나, 칼시트리올투여용량이 3군에서많은경향이었다 (p = 0.053, Table 4)

5 - 염지연외 7 인. 혈액투석액칼슘농도와칼시트리올 - Table 5. Calcitriol dosage (μg/month) before and after conversion to hemodialysate calcium 1.5 mmol/l in each group Baseline 3 months 6 months 9 months 12 months p a Group ± ± ± ± ± Group ± ± ± ± 0.1 b 5.6 ± Group ± ± ± 2.9 b 10.9 ± 2.9 b 10.3 ± 2.9 b p c < < < Values are expressed as means ± standard deviations. a Comparisons were performed by repeated-measures analysis of variance. b p < 0.05 vs. baseline value; Wilcoxon matched-pairs signed-ranks test. c Comparisons among groups were performed using the Kruskal-Wallis test. A B C Figure 1. Changes in serum parathyroid hormone (PTH) level after conversion from 1.75 to 1.5 mmol/l hemodialysate calcium. (A) Group 1; (B) group 2; (C) group 3. The results are presented as a box plot (boxes represent median and interquartile ranges, and vertical lines represent the 10 th -90 th percentiles). Comparisons were performed using the Wilcoxon matched-pairs signed-ranks test. 세군에서표준칼슘투석액으로전환후 12개월동안인결합제와칼시트리올투여용량의변화를비교하였다. 칼슘이포함된인결합제 (1군, p = 0.689; 2군, p = 0.858; 3군, p = 0.142) 와 sevelamer (1군, p = 0.089; 2군, p = 0.227; 3군, p = 0.401) 모두 12개월에걸쳐용량의유의한변화는없었다. 경구혹은정주칼시트리올의경우 1군과 2군에서유의한변화가없었으나, 3군에서는 6개월째부터유의하게증가하였고 (4.4 ± 5.1 vs. 9.6 ± 2.9 μg/month, p = 0.023) 나머지기간동안에도증가추세를유지하였다 (p = 0.001). 세군사이에칼시트리올투여용량을비교했을때에도표준칼슘투석액으로전환후 12개월에걸쳐모두 3군에서유의하게많았다 (Table 5). 표준칼슘투석액으로전환하고 12개월에걸쳐 3개월간격으로측정한교정칼슘농도 (1군, p = 0.381; 2군, p = 0.981; 3군, p = 0.064), 혈청인농도 (1군, p = 0.099; 2군, p = 0.706; 3군, p = 0.411) 및교정칼슘 인값 (1군, p = 0.115; 2군, p = 0.719; 3군, p = 0.436) 은세군모두유의한변화가없었다. 그러나혈청 ipth의경우, 1군에서 12개월에걸쳐유의하게증가하였고 (p = 0.013), 특히 3개월째현저하게증가하였다가 (57 ± 48 vs. 287 ± 266 pg/ml, p < 0.01) 나머지기간동안증가추세를유지하였다 (Fig. 1A). 대부분의환자에서혈청 ipth 값이 pg/ml 였으나, 3예에서는 1,000 pg/ml 이상으로증가하였고 4예에서는반대로 150 pg/ml 미만으로유지되었다. 한편, 2군의혈청 ipth는표준칼슘투석액으로전환후유의한변화가없었다 (p = 0.455, Fig. 1B). 이에비해 3군에서는혈청 ipth가표준칼슘투석액으로전환후 12개월에걸쳐유의하게감소하였고 (p = 0.02), 특히 9개월째현저한감소를나타내었다 (589 ± 200 vs. 242 ± 246 pg/ml, p < 0.01, Fig. 1C). ipth 100 pg/ml 이하로감소한경우가 3예에서관찰되었다. 위와같은 ipth 변화양상에부합하여, 혈청알칼리포스파타제가각군사이에서로다른변화양상을보였다

6 - The Korean Journal of Medicine: Vol. 81, No. 6, A B C Figure 2. Changes in serum alkaline phosphatase after conversion from 1.75 to 1.5 mmol/l hemodialysate calcium. (A) Group 1; (B) group 2; (C) group 3. The results are presented as a box plot (boxes represent median and interquartile ranges, and vertical lines represent the 10 th -90 th percentiles). Comparisons were performed using the Wilcoxon matched-pairs signed-ranks test. (Fig. 2). 1군의경우표준칼슘투석액으로전환후 6개월째유의하게증가하였고 (78 ± 31 vs. 90 ± 31 IU/L, p < 0.05), 3군에서는표준칼슘투석액으로전환후 12개월째유의하게감소하였다 (103 ± 32 vs. 88 ± 25 IU/L, p < 0.05). 고찰근래들어혈액투석환자에서사용하는투석액칼슘농도는과거에비해낮아지는경향이다. 국제적인전향적연구였던 Dialysis Outcomes and Practice Patterns Study I (DOPPS I) 에서혈액투석액칼슘농도 1 mmol/l 증가할때마다사망률이 13% 정도증가하는소견이보고되었다 [10]. 다른연구결과에서도투석액칼슘농도를낮출때혈관의탄성도가증가하였고 [11], 칼슘이포함된인결합제를장기간사용하면서유발된고칼슘혈증환자에서근신경계기능이상, 연부조직의석회화및심전도이상등이보고되었다 [12]. 따라서 2009 년에발표된 KDIGO Clinical Practice Guideline 에서는만성콩팥병환자의혈청칼슘농도를정상범위 ( mg/dl) 로유지하고, 투석액칼슘농도 mmol/l를사용하도록권고하였다 [13]. 그러나칼슘농도 1.25 mmol/l인투석액을사용하면이차성부갑상선기능항진증이악화될수있고 [14], 골흡수증가에따른골밀도감소가초래될수있다는보고가있다 [15]. 본연구는혈청 ipth가다양한말기콩팥병환자에서혈액투석액칼슘농도를 1.5 mmol/l으로선택하였을때요독성골질환에미치는긍정적인효과를보여주었다. 투석액의칼슘농도를 1.75 mmol/l에서 1.5 mmol/l로낮 춘후전체환자의혈청 ipth는 12개월에걸쳐유의하게증가하였으나 (Table 2), 기저 ipth 에따라전체환자를세군으로구분하였을때그변화양상은서로달랐다 (Fig. 1). 즉, 기저 ipth가높지않았던 1군에서는투석액의칼슘농도를 1.75 mmol/l에서 1.5 mmol/l로낮춘후혈청 ipth가 12개월에걸쳐유의하게증가하였고, 기저 ipth가중등도로높았던 2군에서는 12개월동안혈청 ipth의유의한변화가없었으며, 기저 ipth가매우높았던 3군에서는혈청 ipth가 12 개월에걸쳐유의하게감소하였다. 따라서최초혈청 ipth 가다양했던혈액투석환자들이혈액투석액칼슘농도를 1.75 mmol/l에서 1.5 mmol/l으로전환하면서혈청 ipth가결국중등도로높은유사한수준에이르는것을보여주었다. 2009년에발표된 KDIGO Clinical Practice Guideline에따르면투석환자가유지해야할 ipth 수준이정상치의 2배내지 9 배이므로, adynamic bone disease 에해당하는 1군과심한이차성부갑상선항진증에해당하는 3군에서긍정적으로호전되는효과를보였다. 혈청칼슘과인의변화는전체환자및군별환자에서모두유의하지않았으나, 기저 ipth > 300 pg/ml이었던 3군에서칼시트리올투여용량이유의하게증가하였다. 투석액칼슘농도를낮추면체내칼슘평형이부족해지고, 따라서이를보상하기위한칼시트리올투여요구가증가했기때문으로해석된다. 전체환자에서혈청알칼리포스파타제의변화는유의하지않았으나, 1군과 3군에서각각 6개월째에증가하고 12개월째에감소한것은 ipth의변화방향에부합하는소견일것이다

7 - Ji-Youn Youm, et al. Dialysate calcium and calcitriol in HD - 다른연구에서도본연구의 1군과같은 adynamic bone disease 환자에서저칼슘투석액을사용하여혈청 ipth와알칼리포스파타제가증가하여 adynamic bone disease 가호전되었다고보고하였다 [16,17]. 한편, 본연구의 3군과같이 ipth 분비가크게증가한이차성부갑상선기능항진증환자에서는저칼슘투석액사용여부에대해명확히연구된바는없다. 일부연구에서는칼슘평형이음성화되면서이차성부갑상선기능항진증이더악화될수있다고하였다 [14,18]. DOPPS 에서는저칼슘투석액사용에의해부갑상선절제술빈도가증가하였다고보고하였고 [10], 심한저칼슘혈증에의해저혈압 [2,6] 혹은부정맥 [19] 등부작용이발생할수도있다. 그러나또다른연구에서는이차성부갑상선기능항진증환자에서투석액칼슘농도를낮춤으로오히려고칼슘혈증빈도가감소하였고, 이로인해비타민 D 제제를적극적으로투여하여부갑상선호르몬분비가감소되었다 [4,16]. 또한부갑상선절제술빈도가감소하였다는보고도있었다 [20]. 본연구에서도이차성부갑상선기능항진증인 3군에서혈청칼슘농도의변화소견은없었지만표준칼슘투석액으로전환후 6개월째부터칼시트리올투여용량이유의하게증가하였다. 그결과, 혈청부갑상선호르몬농도가감소하는골대사의개선효과를유도하였다고생각한다. 흥미롭게도, 투석액칼슘농도감소에따른반응이일정하지않아서일부환자에서는혈청 ipth의과도한증가혹은감소소견이관찰되었다. 1군의경우 3예에서는혈청 ipth가 1,000 pg/ml 이상으로증가하였고, 4예에서는여전히 150 pg/ml 미만으로유지되었다. 투석액칼슘농도저하에도불구하고 1년동안 ipth가 150 pg/ml 미만으로억제된환자들은 1군의다른환자들과비교할때연령, 성별, 혈액투석기간, 요소감소율및원인질환에서차이가없었으며, 기저교정칼슘, 혈청인, 교정칼슘 인값, 알칼리포스파타제뿐만아니라초기에사용된인결합제와칼시트리올용량도다르지않았다. Park 등에따르면, 칼슘감지수용체의유전자형 (Codon 990 G/G vs. non-g/g) 에따라저칼슘투석액에의해나타나는부갑상선의반응에차이가있을수있다 [21]. 본연구는단일기관에서수행되어대상환자수가적었고후향적인연구였다는제한점을가지고있다. 그러나칼슘평형에영향미치는약물요법들이발전하는현실에서투석액칼슘농도의중요성을제시한의의가있다고생각한다. 과거에흔히사용되던 1.75 mmol/l 농도가아닌 1.5 mmol/l 투석 액을사용하면서적절한인결합제와비타민 D 제제를투여하면 adynamic bone disease 및이차성부갑상선기능항진증환자의적어도일부에서는골대사가개선될수있는결과를보여주었다. 한편, 환자의혈압, 동반하는심혈관계질환, 인결합제및비타민 D 제제용량등에따라투석액칼슘농도를개별화할필요도있을것이다. 향후대규모다기관공동연구를통해, 혈액투석환자에서투석액칼슘농도가골대사에미치는영향에대한전향적연구가도움될것이다. 요약목적 : 현재혈액투석에사용중인투석액칼슘농도는 1.25 mmol/l, 1.5 mmol/l, 1.75 mmol/l로구분된다. 고칼슘투석액은부갑상선호르몬의분비를억제시키는효과가있으나고칼슘혈증위험을증가시키고, 저칼슘투석액은 adynamic bone disease 을개선시키는효과가있으나칼슘평형을악화시킬우려가있으므로투석액칼슘농도의적절한선택은쉽지않다. 저자들은표준칼슘농도인 1.5 mmol/l 투석액을사용하였을때칼시트리올용량변화와아울러요독성골질환에미치는효과를평가하고자하였다. 방법 : 투석액칼슘농도 1.75 mmol/l로 1년이상혈액투석중인환자 36명에서투석액칼슘농도를 1.5 mmol/l 로전환후 1년간경과를추적하였다. 투석액칼슘농도를낮추기 3개월전에측정한혈청 ipth 농도에따라환자를 1군 (ipth < 150 pg/ml, n = 21), 2군 (ipth pg/ml, n = 7), 3군 (ipth > 300 pg/ml, n = 8) 으로구분하여혈청칼슘, 인, 알칼리포스파타제, ipth 농도를 3개월간격으로측정하였고, 인결합제및칼시트리올용량변화를조사하였다. 결과 : 투석액칼슘농도 1.75 mmol/l 사용중 1군, 2군및 3군의 ipth 농도는각각 57 ± 48 pg/ml, 191 ± 46 pg/ml, 589 ± 200 pg/ml 로유의한차이가있었다 (p < 0.001). 투석액칼슘농도를 1.5 mmol/l로전환후 1군에서혈청 ipth가 12 개월에걸쳐유의하게증가하였다 (p = 0.01). 3개월째부터증가가현저하여 (57 ± 48 vs. 287 ± 266 pg/ml, p < 0.01) 이후증가세를유지하였다. 그러나 2군에서는유의한변화가없었고, 3군의혈청 ipth는 12개월에걸쳐유의하게감소하였는데 (p = 0.02) 특히 9개월째감소가기저치에비해낮았다 (589 ± 200 vs. 242 ± 246 pg/ml, p < 0.01). 혈청알칼리포스파타제도혈청 ipth와유사한변화양상을보였다. 투석액

8 - 대한내과학회지 : 제 81 권제 6 호통권제 616 호 칼슘농도를 1.5 mmol/l로전환한후 1군과 2군에서인결합제와칼시트리올투여용량의유의한변화는없었으나, 3군에서칼시트리올용량이 6개월째부터유의하게증가하였고 (4.4 ± 5.1 vs. 9.6 ± 2.9 μg/month, p < 0.05) 나머지기간동안증가추세를유지하였다. 결론 : 혈액투석액칼슘농도를 1.75 mmol/l에서 1.5 mmol/l 으로전환한후적절한인결합제와칼시트리올투여용량을조정하면서 adynamic bone disease 와이차성부갑상선항진증환자에서혈청 ipth 측정치가호전되는경향을보였다. 신성골형성장애가있는혈액투석환자에서투석액칼슘농도 1.5 mmol/l를선택하는것이효과적일수있다. 중심단어 : 혈액투석액 ; 칼슘 ; 부갑상선호르몬 ; 칼시트리올 ; 신성골형성장애 REFERENCES 1. Drüeke TB, Touam M. Calcium balance in haemodialysis: do not lower the dialysate calcium concentration too much (con part). Nephrol Dial Transplant 2009;24: Maynard JC, Cruz C, Kleerekoper M, Levin NW. Blood pressure response to changes in serum ionized calcium during hemodialysis. Ann Intern Med 1986;104: Erratum in: Ann Intern Med 1986;105: Toussaint N, Cooney P, Kerr PG. Review of dialysate calcium concentration in hemodialysis. Hemodial Int 2006;10: Lezaic V, Pejanovic S, Kostic S, et al. Effects of lowering dialysate calcium concentration on mineral metabolism and parathyroid hormone secretion: a multicentric study. Ther Apher Dial 2007;11: Spasovski G, Gelev S, Masin-Spasovska J, Selim G, Sikole A, Vanholder R. Improvement of bone and mineral parameters related to adynamic bone disease by diminishing dialysate calcium. Bone 2007;41: Van der Sande FM, Cheriex EC, van Kuijk WH, Leunissen KM. Effect of dialysate calcium concentrations on intradialytic blood pressure course in cardiac-compromised patients. Am J Kidney Dis 1998;32: Chyun JH, Yoon HJ, Kang HJ, et al. Effect of low calcium dialysate on bone markers in hemodialysis patients who may have adynamic bone disease. Korean J Bone metab 2003;10: Ferri FF. Ferri's Clinical Advisor Philadelphia, PA: Elsevier, National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 2003;42(4 Suppl 3):S1-S Young EW, Albert JM, Satayathum S, et al. Predictors and consequences of altered mineral metabolism: the Dialysis Outcomes and Practice Patterns Study. Kidney Int 2005;67: Yoo SJ, Oh DJ, Yu SH. The effects of low calcium dialysate on arterial compliance and vasoactive substances in patients with hemodialysis. Korean J Intern Med 2004;19: Goodman WG, Goldin J, Kuizon BD, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2000;342: Kidney Disease: Improving Global Outcomes (KDIGO) CKD- MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). Kidney Int Suppl 2009;(113):S1-S Yokoyama K, Kagami S, Ohkido I, et al. The negative Ca(2+) balance is involved in the stimulation of PTH secretion. Nephron 2002;92: Sánchez Perales MC, García Cortés MJ, Borrego FJ, et al. Hemodialysis with 2.5 meq/l of calcium in relative hypoparathyroidism: long-term effects on bone mass. Nefrologia 2000;20: Hamano T, Oseto S, Fujii N, et al. Impact of lowering dialysate calcium concentration on serum bone turnover markers in hemodialysis patients. Bone 2005;36: Holgado R, Haire H, Ross D, et al. Effect of a low calcium dialysate on parathyroid hormone secretion in diabetic patients on maintenance hemodialysis. J Bone Miner Res 2000;15: Argilés A, Mion CM. Low-calcium dialysate worsens secondary hyperparathyroidism. J Am Soc Nephrol 1996;7: Severi S, Grandi E, Pes C, Badiali F, Grandi F, Santoro A. Calcium and potassium changes during haemodialysis alter ventricular repolarization duration: in vivo and in silico analysis. Nephrol Dial Transplant 2008;23: Heaf JG, Løkkegård H. Parathyroid hormone during maintenance dialysis: influence of low calcium dialysate, plasma albumin and age. J Nephrol 1998;11: Park TJ, Seo JW, Pack KM, et al. Calcium-sensing receptor gene polymorphism is associated with the parathyroid response to low calcium dialysate in hemodialysis patients with low parathyroid hromone secretion. Korean J Nephrol 2007;26:

05.Kaes001.hwp

05.Kaes001.hwp 혈액투석환자에서삼차성부갑상선기능항진증으로부갑상선절제술후발생한 Hungry Bone Syndrome 1 예 A Case of Hungry Bone Syndrome after Parathyroidectomy in Patient with Tertiary Hyperparathyroidism and Hemodialysis Patient Myoung Won Son, M.D.,