대한내과학회지 : 제 86 권제 2 호 2014 http://dx.doi.org/10.3904/kjm.2014.86.2.190 다발성골수종에서신부전발생의위험인자및신기능회복예측인자 가톨릭대학교의과대학내과학교실신장내과 황현철 고은실 김정관 정성진 신석준 박철휘 장윤식 Risk Factors and Reversibility of Renal Failure in Patients with Newly Diagnosed Multiple Myeloma Hyun Chul Whang, Eun Sil Koh, Jeong Gwan Kim, Sungjin Chung, Seok Joon Shin, Cheol Whee Park, and Yoon Sik Chang Division of Nephrology, Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea Background/Aims: Multiple myeloma (MM) is frequently accompanied by renal insufficiency, which has been regarded as a poor prognostic factor for MM. It is known that the incidence and characteristics of MM in Asia differ from those in Western countries. The aim of this study was to evaluate risk factors for renal impairment and to investigate reversible factors for renal failure in patients with MM. Methods: Patients newly diagnosed with MM from 2005 to 2008 were included. We investigated factors associated with renal insufficiency and those related to recovery from renal dysfunction after 12 weeks of treatment of MM. Results: Renal failure was recognized in 86 (39%) of 221 patients at diagnosis. In the binary logistic regression analysis, low hemoglobin (odds ratio [OR], 0.813; p = 0.02), high β2microglobulin (OR, 1.006; p < 0.01), and use of angiotensin-converting enzyme inhibitors (ACEi) (OR, 2.783; p < 0.04) at initial presentation were independent risk factors for renal failure in patients with multiple myeloma. After 12 weeks of treatment, 25 of 86 (29%) patients with renal failure had recovered renal function. Good response to chemotherapy (OR, 6.044; p < 0.01) and higher egfr (OR, 1.084; p < 0.01) were associated with renal function recovery. Conclusions: Levels of hemoglobin and β2microglobulin, and use of ACEi were independent risk factors for the development of renal failure in MM patients. The response to chemotherapy and egfr at diagnosis significantly influenced recovery of renal function. (Korean J Med 2014;86:190-197) Keywords: Multiple myeloma; Renal insufficiency; Risk factors Received: 2013. 5. 14 Revised: 2013. 5. 27 Accepted: 2013. 5. 31 Correspondence to Yoon Sik Chang, M.D. Department of Internal Medicine, The Catholic University of Korea Yeouido St. Mary's Hospital, 10 63-ro, Yeongdeungpo-gu, Seoul 150-713, Korea Tel: +82-2-3779-1259, Fax: +82-2-780-3132, E-mail: ysc543@unitel.co.kr Copyright c 2014 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution - 190 - Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
- Hyun Chul Whang, et al. Risk factors of renal failure in patients with multiple myeloma - 서론다발성골수종은단일클론에서유래하는형질세포의악성증식질환으로국내에서는비교적드물었지만최근에는발병률이증가하여혈액암중에서 3번째로많은비율을차지하고있다 [1]. 이형형질세포의단클론성면역글로불린의과도한생산으로인하여골수종원주신병증, 유전분증또는경쇄침착질환등으로인해신손상이일어나며이로인해다발성골수종환자의 20-50% 정도에서신부전이동반된다 [2-4]. 국내의연구자료에따르면다발성골수종으로등록된환자의약 21% 에서신부전이발생한것으로보고된바있다 [5]. 신부전의알려진위험인자로는고칼슘혈증, 고요산혈증, 남성, 빈혈, 높은혈중 M단백농도, 유리경쇄 (free light chain) 형, IgG형, 골병변동반등이있으며 NSAID 및조영제등의신독성물질사용, 안지오텐신전환효소억제제 (angiotensin converting enzyme inhibitor, ACEi) 또는안지오텐신2수용체길항제 (angiotension2 receptor antagonist, ARB) 사용시신부전이발생할가능성이증가한다. 초기에발생한신부전은약 50% 에서회복되는것으로알려져있다. 다발성골수종에서신부전은높은빈도로발생하고환자의예후에영향을미치는중요한합병증이나국내에서는처음진단받은환자에서의신부전발생률및위험인자와신기능회복에관련된인자에대해보고된바가거의없다. 저자는다발성골수종과신부전의관계를확인하기위해후향적연구를통하여다발성골수종환자에서신부전의발생빈도를조사하였으며신부전발생여부에따라두군간의검사실소견과임상경과를비교하였으며신부전발생에영향을주는인자를확인하였으며신기능의회복여부와이에영향을미치는인자를확인하였다. 대상및방법 2005년 1월에서 2008년 12월까지가톨릭대학교여의도성모병원을방문하여다발성골수종으로처음진단받고치료를시행한 221명환자를대상으로하여임상및검사실소견을수집하고신부전의발생률과위험인자를후향적으로분석하였다. 임상적특징은환자의나이, 성별을조사하였고당뇨병, 고혈압등의동반질환을확인하였다. 혈청 M 단백의종류에따라 IgA, IgG, IgM, 유리경쇄, 비분비형 (Non-secretory type) 으로분류하였고, 유리경쇄는카파와람다형으로분류하였다. 혈액검사에서베타-2 마이크로글로불린 (Beta-2 microglobulin), 헤모글로빈 (hemogobiln), 칼슘 (calcium), 크레아티닌 (creatinine), 알부민 (albumin), 혈청총단백 (serum total protein), LDH (lactate dehydrogenase) 를확인하였고 24시간수집소변단백량을분석하였다. 다발성골수종의진단기준은 International Myeloma Working Group (IMWG) 에서제시한기준 [6] 에따랐으며병기분류는 Durie & Salmon 에의한분류법 [7] 을사용하였다. 치료반응의평가는 IMWG 기준에따라 [8] 분류하였으며치료반응군에는완전반응군및부분반응군을포함하였다. 진단당시크레아티닌값을이용하여사구체여과율을 Modification of diet in renal disease (MDRD) 공식으로계산하였고추정사구체여과율 (estimated Glomerular Filtration Rate, egfr) 이 60 ml/min/1.73 m 2 미만인환자를신부전군으로분류하였으며양군간의임상및검사실소견을비교하였으며 3개월후의추적검사에서 60 ml/min/1.73 m 2 이상으로회복된환자를신기능회복군으로구분하여신부전지속군과비교하였다. 통계분석은 SPSS 13.0 (Statistical package for the social science) 를이용하였다. 연속변수의평균치비교는독립표본 t검정, 비연속적변수는교차분석을시행하였고 p 값이 0.05 미만이면통계적으로유의한것으로평가하였다. 신부전의위험인자분석을위해서는로지스틱회귀분석을시행하였고단변량분석에서 p < 0.05인경우다변량분석을시행하였다. 결과대상환자의임상적특성및임상경과대상환자의일반적인특징은다음과같았다 (Table 1). 평균나이는 57 ± 9.8세였으며성별로는남자가 114명, 여자가 107명이었다. 동반질환으로는당뇨 27명, 고혈압 36명으로조사되었다. Durie & Salmons 3병기가가장많았으며 (159명, 71.8%), M단백중 IgG형이 (130명, 58.8%) 가장많았다. 유리경쇄형에서는카파형과람다형의비율이비슷하였다. 다발성골수종치료에대해 156명의환자가완전또는부분반응을보였다. 15명의환자가혈액과점도증후군 (hyperviscosty - 191 -
- 대한내과학회지 : 제 86 권제 2 호통권제 641 호 2014 - Table 1. General characteristics and clinical manifestations of the patients Patient (n = 221) AGE, yr 57 ± 9.77 Male, n (%) 114 (51.6) Diabetes, n (%) 27 (12.2) Hypertension, n (%) 36 (16.2) Hemoglobin, g/dl 9.54 ± 2.17 Creatinine, mg/dl 1.56 ±1.86 Total protein, g/dl 9.01 ± 2.57 Albumin, g/dl 3.36 ± 0.6 LDH, IU/L 457 ± 417 Calcium, mg/dl 8.74 ± 1.38 Beta-2-microglobulin, mg/l 43.91 ± 97.61 24-h collected urine protein, mg/day 1,664.78 ± 8,135.28 Bone marrow plasma, % 57 ± 9.8 Durie-Salmon stage, n (%) I 30 (13.6) II 39 (17.6) III 152 (68.8) M-component type, n (%) IgG 114 (51.8) IgA 61 (27.6) IgM 3(1.3) LCD 38 (17.2) Non-secretory type 5(2.3) Light chain type, n (%) Kappa 99 (44.8) Lambda 85 (38.5) Unknown 37 (16.7) Use of ACEi or ARB, n (%) 30 (13.6) Bone lesion, n (%) 67 (30.3) Values are presented as mean ± SD unless otherwise indicated. LDH, lactate dehydrogenase; LCD, light chain disease; ACEi, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker. syndrome) 으로혈장반출술을시행받았다. 초기검사에서 egfr 60 ml/min/1.73 m 2 미만의신부전을보인환자는 86명 (39%) 이었으며이중 16명은심각한신기능부전을보여혈액투석을시행하였다. 3개월후의추적검사에서신기능이회복된환자는 25 (29%) 명으로총 221명의환자중 61명 (28%) 이신기능을회복하지못하였다. 신부전군과정상신기능군사이의임상소견및검사실소견비교전체 221명의환자를신부전군 (86명) 은정상군 (135명) 으로나누어임상소견과검사실소견을비교하였다. 신부전군은정상군에비해서나이가많았다 (59.43 ± 10.401세대 55.67 ± 9.364세, p = 0.02). 양군간의평균값비교에서는신부전군에서헤모글로빈이낮으며 (10.01 ± 2.08 g/dl vs. 8.81 ± 2.02 g/dl, p < 0.01), 혈청총단백이높았고 (8.53 ± 2.42 g/dl vs. 9.49 ± 2.75 g/dl, p < 0.01) 알부민이낮으며 (3.45 ± 0.60 g/dl vs. 3.22 ± 0.70 g/dl, p = 0.02), 베타-2 마이크로글로불린이높았다 (21.52 ± 48.32 mg/dl vs. 102.50 ± 221.25 mg/dl, p < 0.01). ACEi 또는 ARB를복용한군에서신부전의발생률이높았다 (9% vs. 19%, p = 0.03). 나이, 당뇨, 혈압, 골파괴유무, LDH, 칼슘, 골수내형질세포비율, 혈청내유리경쇄총량, M단백량, 24시간수집소변단백량에따른양군간에유의한차이는없었다. Durie & Salmon 병기 (p = 0.06), 유리경쇄형태 (p = 0.63), M단백형태 (p = 0.07) 에따른통계적유의성은없었지만각각의병기및형태를분석한결과 Durie & Salmon 3병기 (p = 0.04), 및 M단백 IgD형 (p = 0.03) 에서유의한차이를보였다 (Table 2). 신부전발생의독립위험인자분석신손상군과정상신기능군간의차이를보인소견에대해단변량분석을시행하였으며, p < 0.05인경우다변량분석을시행하였다. 헤모글로빈이높을수록신부전의위험성은떨어지며 (odds ratio [OR], 0.813; 95% confidednce interval [CI], 0.686-0.964), 베타-2 마이크로글로빈상승 (OR, 1.006; CI, 1.001-1.011) 및 ACEi 또는 ARB 사용 (OR, 2.873; CI 1.040-7.941) 이신부전발생의위험인자로나타났다 (Table 3). 신기능회복군과신부전지속군사이의임상소견및검사실소견비교 3개월뒤추적검사에서신기능회복군 (25명) 과신부전지속군 (61명) 으로나누어비교분석하였다. 치료반응이좋은경우 (40% vs. 10%, p = 0.02), 혈액투석을시행한경우 (4% vs. 40%, p = 0.03), 및 egfr 의평균값 (29.52 ± 16.31 ml/min/1.73 m 2 vs. 46.88 ± 12.24 ml/min/1.73 m 2, p < 0.01) 에서유의한차이를보였다. 나이, 성별, 당뇨, 고혈압, Durie & Salmon 병기, M단백형태, 골수내형질세포비율, ACEi 또는 ARB의사 - 192 -
- 황현철외 6 인. 다발성골수종에서신부전발생의위험및회복인자 - Table 2. Comparison of baseline characteristics in the normal renal function and renal failure groups Normal (n = 135) Renal failure (n = 86) p value Age, yr 55.67 ± 9.36 59.43 ± 10.41 0.02 a Male, n (%) 69 (51.1) 45 (52.3) 0.86 Diabetes, n (%) 14 (10.4) 13 (15.1) 0.29 Hypertension, n (%) 19 (14.1) 17 (19.8) 0.26 Durie-Salmon stage, n (%) 0.06 I 24 (17.9) 6 (6.9) II 25 (18.3) 14 (16.3) III 86 (63.8) 66 (76.8) M-component type, n (%) 0.07 IgG 71 (52.6) 43 (50.0) IgA 39 (28.9) 22 (25.6) IgD 0 (0.0) 3 (3.4) LCD 24 (17.7) 14 (16.3) Non-secretory type 1 (0.7) 4 (4.6) Light-chain type, n (%) 0.63 Kappa 71 (52.6) 28 (32.6) Lambda 47 (34.8) 38 (44.2) Unknown 17 (12.6) 20 (23.2) Hemoglobin, g/dl 10.01 ± 2.08 8.81 ± 2.02 < 0.01 a Total protein, g/dl 8.53 ± 2.42 9.49 ± 2.75 < 0.01 a Albumin, g/dl 3.45 ± 0.62 3.22 ± 0.72 0.02 a LDH, IU/L 437.8 ± 383.46 508.17 ± 475.27 0.229 Calcium, mg/dl 8.60 ± 0.91 8.97 ± 1.97 0.107 Beta-2-microglobulin, mg/l 21.52 ± 48.32 102.50 ± 221.25 < 0.01 a 24-h collected urine protein, mg/day 1436.69 ± 9673.31 1930.96 ± 3457.40 0.67 Bone marrow plasma, % 45.00 ± 24.25 56.38 ± 30.42 0.12 Total light chain, mg/l 1625.14 ± 7797.16 3021.05 ± 5495.69 0.34 IgG, mg/l 2545.42 ± 2589.10 2973.84 ±2739.84 0.26 IgA, mg/l 457.72 ± 1033.43 402.37 ± 1016.28 0.65 Use of ACEi or ARB, n (%) 13 (7.0) 17 (19.8) 0.03 a Bone lesion, n (%) 40 (29.6) 27 (31.3) 0.78 Values are presented as mean ± SD unless otherwise indicated. LCD, light chain disease; LDH, lactate dehydrogenase; ACEi, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker. a p < 0.05. 용, 조영제의사용, 비스테로이드성항염제 (Non-steroidal anti inflammatory drug) 의사용, 골파괴유무및항암화학요법의종류에따른양군간의유의한차이는없었다 (Tables 4 and 5). 신기능회복에관련된독립인자분석 신기능회복군과신부전지속군간의차이를보인소견에대해단변량분석을시행하였으며 p < 0.05인경우다변량분 - 193 -
- The Korean Journal of Medicine: Vol. 86, No. 2, 2014 - Table 3. Univariate and multivariate analyses of risk factors for renal failure Risk factor Univariate analysis Multivariate analysis B OR (95% CI) p value B OR (95% CI) p value Age 0.040 1.041 (1.011-1.071) < 0.01 a Durie-Salmon stage III 0.631 1.880 (1.021-3.474) 0.04 a Hemoglobin -0.295 0.744 (0.642-0.863) < 0.01 a -0.206 0.813 (0.686-0.964) 0.02 a Total protein 0.146 1.157 (1.039-1.288) < 0.01 a Albumin -0.549 0.578 (0.373-0.894) 0.02 a Beta-2-microglobulin 0.007 1.007 (1.002-1.012) < 0.01 a 0.006 1.006 (1.001-1.011) < 0.01 a ACEi or ARB 0.838 2.312 (1.060-5.045) 0.04 a 1.055 2.873 (1.040-7.941) 0.04 a OR, odds ratio; CI, confidence interval; ACEi, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker. a p < 0.05. 석을시행하였다. 항암치료에반응을보인경우 (OR, 6.044; CI, 1.566-23.331) 와진단당시의높은 egfr (OR, 1.084; CI, 1.038-1.131) 이신부전회복의예측인자로나타났다 (Table 6). 고찰다발성골수종은단일클론에서유래하는형질세포의악성증식질환으로미국에서전체암중 1%, 혈액암중에서 10% 를차지하고있다 [1]. 국내혈액암중에서는 3번째로많은빈도를보이며현재 4,000명에서 5,000명의환자가있으며매년그수가빠르게증가하고있다 [9]. 다발성골수종은피로감, 체중감소등과함께빈혈, 골붕괴, 신부전등의다양한임상증상을보인다. 신부전은감염다음으로환자생존율에큰영향을미치는중요한합병증중에하나이며 [10] 약 20-40% 정도의높은비율로보고되고있다 [3,4] 이렇게발생률의차이가나는것은각연구마다신부전의정의가다르며다발성골수종이지역및인종에따라다른특성을가지고있기때문이다. 다발성골수종에서신부전이발생하는기전은다음과같다. 비정상골수세포에서과잉생산된단일클론성면역글로불린경쇄로인한골수종원주신병증, 유전분증또는경쇄침착질환으로인하여신손상이발생하고이로인해단백뇨부터신부전까지다양한정도로신기능이상을유발한다 [2]. 이와동반되는다양한전신상태는신부전이악화시키는데알려진위험인자로는빈혈, 고칼슘혈증, 고요산혈증, Durie and Salmon 3병기, 남성, 혈중 M단백량, 유리경쇄형, IgD형, 골병변동반, 비스테로이드성항염제의사용, 조영제의사용 등이있다 [10-13]. 본연구에서는이러한요인들중 ACEi 또는 ARB의사용과낮은헤모글로빈, 높은베타-2 마이크로글로빈이신부전발생의위험인자로나타났다. ACEi 또는 ARB의복용은원위세동맥을확장시켜사구체내혈류량감소를가속화하여유리경쇄로인한신손상을악화시킬수있으며 [14], 빈혈은허혈성손상일으켜신부전을악화시킬수있다. 베타-2 마이크로글로불린은다발성골수종진행의중요한표지자이며, 정확한병리학적기전은알려져있지않지만알려진신부전의위험인자이다. 면역글로불린 IgD형은발생빈도가 2% 로드문형태로, 다른형보다예후가좋지않으며신부전발생률이높은것으로보고되고있다 [15,16]. 본연구에서는 3명이 IgD형으로진단되었으며, 모두에서신부전이발생하였다 (p = 0.03). 또한 Durie & Salmon 3병기는심한빈혈, 고칼슘혈증의동반, 혈중높은 M 단백을동반함으로써전반적으로불량한예후를나타내며, 신부전의위험인자중하나이다. Durie & Salmon 3병기환자는 152명이었으며이중 66명이발견당시신부전을동반하였으나 (p = 0.04), 양쪽모두다변량분석시통계적유의성은보이지않았다. 발병초기에발생한신부전은 3주이내에약 50% 에서회복을보이는것으로보고된바있다 [17]. 적절한수분공급을통한저혈량혈증의방지와고칼슘혈증의치료가중요하며 [3,11], 감염의예방및비스테로이드성소염제, ACEi, ARB, 조영제의사용을줄이는것이신기능회복에도움이된다 [18]. 일반적인치료외에혈장반출술이나 HCO (High cut-off) 혈액투석을통해혈중유리경쇄를빠르게제거해주는것이도움이 - 194 -
- Hyun Chul Whang, et al. Risk factors of renal failure in patients with multiple myeloma - Table 4. Comparison of baseline characteristics in the renal function recovery and non-recovery groups Recovery (n = 25) Non-recovery (n = 61) p value Age, yr 62.24 ± 8.35 58.28 ± 10.98 0.11 Male gender, n (%) 8 (32) 40 (65.6) Diabetes, n (%) 3 (12) 10 (16.4) 0.61 Hypertension, n (%) 7 (28) 10 (16.4) 0.22 Durie-Salmon stage, n (%) 0.34 I 3 (12.0) 3 (4.9) II 4 (16.0) 7 (11.5) III 18 (72.0) 51 (83.6) M-component type, n (%) 0.35 IgG 15 (60.0) 32 (52.5) IgA 8 (24.0) 17 (27.9) IgD 1 (4.0) 2 (3.3) LCD 0 (0.0) 9 (14.8) Non-secretory type 1 (4.0) 1 (1.5) Light chain type, n (%) 0.51 Kappa 11 (44.0) 28 (45.9) Lambda 10 (40.0) 24 (39.3) Unknown 4 (4.0) 9 (14.8) Hemoglobin, g/dl 9.26 ± 2.75 8.63 ± 1.62 0.30 Total protein, g/dl 10.10 ± 2.49 9.28 ± 2.84 0.27 Albumin, g/dl 3.10 ± 0.56 3.27 ± 0.76 0.33 LDH, IU/L 395.29 ± 227.81 555.20 ± 541.14 0.16 Calcium, mg/dl 8.95 ± 1.82 9.01 ± 2.33 0.91 Beta-2-microglobulin, mg/l 129.15 ± 257.09 41.16 ± 72.31 0.14 24-h collected urine protein, mg/day 2,263.02 ± 3,932.05 1,173.86 ± 1,846.27 0.19 egfr, ml/min/1.73 m 2 29.52 ± 16.31 46.88 ± 12.24 < 0.01 a Bone marrow plasma, % 62.25 ± 29.03 37.60 ± 29.81 0.12 Use of ACEi, n (%) 6 (24.0) 11 (18.1) 0.53 Use of contrast dye, n (%) 0 (0.0) 4 (6.6) 0.19 Use of NSAID, n (%) 8 (32.0) 10 (16.4) 0.11 Bone lesion, n (%) 10 (40) 17 (27.9) 0.27 Plasmapheresis, n (%) 3 (12.0) 9 (14.8) 0.74 Hemodialysis, n (%) 1 (4.0) 15 (24.6) 0.03 a Response to chemotherapy, n (%) 10 (40.0) 6 (9.8) 0.02 a Values are presented as mean ± SD unless otherwise indicated. LCD, light chain disease; LDH, lactate dehydrogenase; egfr, estimated glomerular filtration rate; NSAID, nonsteroidal anti-inflammatory drug. a p < 0.05. 되며 [19,20], 항암치료약제선택에서 Bortezomib 이나 Lenalidomide 등의새로운약제가신기능회복에도움이된다는 보고가있다 [21-23]. 본연구에서는신부전이발생한 86명의환자중 12명이혈장반출술을시술받았으며, 15명이혈액 - 195 -
- 대한내과학회지 : 제 86 권제 2 호통권제 641 호 2014 - Table 5. Comparisons of chemotherapthy regimens between renal function recovery and non-recovery Recovery (n = 25) Non-recovery (n = 61) p value Type of chemotherpathy, n (%) 0.25 VAD 12 (48.0) 21 (34.4) MP 3 (12.0) 19 (31.1) Thalidomide + Dexamethasone 0 (0.0) 3 (4.9) Velcade based regimen 6 (24.0) 15 (24.6) Others 4 (16.0) 3 (4.9) VAD, Vincristine + Adriamycin + Dexamethasone; MP, Melphalan + Prednisolone. p < 0.05. Table 6. Multivariate analysis of predictive factors for recovery of renal function B Multivariate OR (95% CI) p value egfr 0.080 1.084 (1.038-1.131) < 0.01 a Response to chemotherapy 1.799 6.044 (1.566-23.331) < 0.01 a OR, odds ratio; CI, confidence interval; egfr, estimated glomerular filtration rate. a p < 0.05. 투석을시행하였다. 혈장반출술을시행한환자중 3명이혈액투석을시행한환자중 1명만이신기능회복을보였다. 회복군과지속군간에비스테로이드성소염제의사용, ACEi 또는 ARB의사용및조영제사용에대한차이는없었다. 86 명의환자중 25명의환자 (29%) 만이신부전회복을보였다. 항암제종류에따른차이는없었으나항암치료에좋은반응을보인환자와진단시높은신기능을유지한환자에서신기능의회복을보였다. 본연구의제한점은다음과같다. 첫째, 다발성골수종으로진단되기이전에이미가지고있는기저질환들의영향을완전히배제하지못하였다. 둘째, 후향적으로의무기록을조사하는과정에서정확한수액공급량이나전해질및미네랄교정의노력여부그리고신독성유발가능한약제들의영향력정도를알기어려웠다. 결론적으로 221명의환자중 86명 (39%) 에서발병당시신부전이동반되었으며 61명 (28%) 의환자가만성신부전으로진행되었다. 낮은헤모글로빈, ACEi 또는 ARB의사용, 높은베타-2 마이크로글로불린이신부전의위험인자로확인되었으며항암치료에좋은반응을보인경우및발병당시신기능이높게유지된경우에서신부전의회복을기대할수 있었다. 혈액투석이필요한심한신부전을동반한경우에는대부분신기능이회복되지않았다. 다발성골수종에서신부전은단일원인보다는동반되는다양한전신상태로인한복합적인요인으로발생하기때문에신기능에대한면밀한감시가필요하며각각의위험인자를교정해줌으로써만성신부전으로의진행을막을수있을것이며적합한항암치료를통해신기능의호전을기대할수있을것으로생각된다. 요약목적 : 신부전은다발성골수종에서종종발생하며나쁜예후를보인다. 아시아의다발성골수종의발생빈도와특징은서양과는다른것으로알려져있다. 이연구의목적은다발성골수종환자들에서신부전발생의위험인자및치료후신기능회복인자를찾고자하였다. 방법 : 2005년부터 2008년까지처음다발성골수종을진단받은환자를대상으로하여신부전의발생과관련된인자를조사하였고, 12주간의치료후에신부전의회복과관련된인자를찾았다. 결과 : 진단당시 221명의환자중 86명 (39%) 에서신부전 - 196 -
- 황현철외 6 인. 다발성골수종에서신부전발생의위험및회복인자 - 이발생하였다. 이변량로지스틱회기분석에서낮은헤모글로빈 (OR = 0.813, p = 0.02), 높은베타-2 마이크로글로불린 (OR = 1.006, p < 0.01), ACEi (OR = 2.783, p = 0.04) 사용이신부전발생의독립적인위험인자로나타났다. 12주간의치료후, 86명중에서 25 (29%) 명의신기능이회복되었다. 항암치료에반응을보인경우 (OR = 6.044, p < 0.01) 와높은 egfr (OR = 1.084, p < 0.01) 이회복과연관된인자로나타났다. 결론 : 헤모글로빈수치, 베타-2 마이크로글로불린, ACEi 의사용이한국다발성골수종환자에있어신부전발생의독립적인위험인자이며항암치료에반응여부와진단시의 egfr 이신기능회복의예측인자이다. 중심단어 : 다발성골수종 ; 신부전 ; 위험인자 REFERENCES 1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin 2009;59:225-249. 2. Markowitz GS. Dysproteinemia and the kidney. Adv Anat Pathol 2004;11:49-63. 3. Goldschmidt H, Lannert H, Bommer J, Ho AD. Multiple myeloma and renal failure. Nephrol Dial Transplant 2000; 15:301-304. 4. Kastritis E, Anagnostopoulos A, Roussou M, et al. Reversibility of renal failure in newly diagnosed multiple myeloma patients treated with high dose dexamethasonecontaining regimens and the impact of novel agents. Haematologica 2007;92:546-549. 5. Kim SJ, Kim K, Kim BS, et al. Clinical features and survival outcomes in patients with multiple myeloma: analysis of web-based data from the Korean Myeloma Registry. Acta Haematol 2009;122:200-210. 6. International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol 2003;121:749-757. 7. Durie BG, Salmon SE. A clinical staging system for multiple myeloma: correlation of measured myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer 1975;36:842-854. 8. Durie BG, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple myeloma. Leukemia 2006;20:1467-1473. 9. Lee JH, Lee DS, Lee JJ, et al. Multiple myeloma in Korea: past, present, and future perspectives: experience of the Korean Multiple Myeloma Working Party. Int J Hematol 2010;92:52-57. 10. Uchida M, Kamata K, Okubo M. Renal dysfunction in multiple myeloma. Intern Med 1995;34:364-370. 11. Heher EC, Goes NB, Spitzer TR, et al. Kidney disease associated with plasma cell dyscrasias. Blood 2010;116: 1397-1404. 12. Eleutherakis-Papaiakovou V, Bamias A, Gika D, et al. Renal failure in multiple myeloma: incidence, correlations, and prognostic significance. Leuk Lymphoma 2007;48:337-341. 13. Knudsen LM, Hjorth M, Hippe E. Renal failure in multiple myeloma: reversibility and impact on the prognosis: Nordic Myeloma Study Group. Eur J Haematol 2000;65:175-181. 14. Rabb H, Gunasekaran H, Gunasekaran S, Saba SR. Acute renal failure from multiple myeloma precipitated by ACE inhibitors. Am J Kidney Dis 1999;33:E5. 15. Bladé J, Kyle RA. Nonsecretory myeloma, immunoglobulin D myeloma, and plasma cell leukemia. Hematol Oncol Clin North Am 1999;13:1259-1272. 16. Kim MK, Suh C, Lee DH, et al. Immunoglobulin D multiple myeloma: response to therapy, survival, and prognostic factors in 75 patients. Ann Oncol 2011;22:411-416. 17. Korbet SM, Schwartz MM. Multiple myeloma. J Am Soc Nephrol 2006;17:2533-2545. 18. Dimopoulos MA, Kastritis E, Rosinol L, Bladé J, Ludwig H. Pathogenesis and treatment of renal failure in multiple myeloma. Leukemia 2008;22:1485-1493. 19. Gupta D, Bachegowda L, Phadke G, Boren S, Johnson D, Misra M. Role of plasmapheresis in the management of myeloma kidney: a systematic review. Hemodial Int 2010;14:355-363. 20. Hutchison CA, Bradwell AR, Cook M, et al. Treatment of acute renal failure secondary to multiple myeloma with chemotherapy and extended high cut-off hemodialysis. Clin J Am Soc Nephrol 2009;4:745-754. 21. Roussou M, Kastritis E, Migkou M, et al. Treatment of patients with multiple myeloma complicated by renal failure with bortezomib-based regimens. Leuk Lymphoma 2008;49:890-895. 22. Oehrlein K, Langer C, Sturm I, et al. Successful treatment of patients with multiple myeloma and impaired renal function with lenalidomide: results of 4 German centers. Clin Lymphoma Myeloma Leuk 2012;12:191-196. 23. Dimopoulos MA, Roussou M, Gkotzamanidou M, et al. The role of novel agents on the reversibility of renal impairment in newly diagnosed symptomatic patients with multiple myeloma. Leukemia 2013;27:423-429. - 197 -