7 CKD に伴う骨ミネラル代謝異常 ステートメント 1 CKD に伴う骨ミネラル代謝異常 (mineral and bone disorder:mbd) (CKD-MBD) の疾患概念 CKD 患者における骨ミネラル代謝異常は, 腎性骨異栄養症に加えて血管の合併症を含む, 生 命予後に影響する全身性疾患 (CKD-MBD) として捉える a). 2 CKD-MBD における Ca と P の管理目標 CKD 患者において, 血清 P 濃度が高いと腎機能障害が進行し, 生命予後は不良となるが 1, 2), ステージ 5D を除く CKD 患者の血清 Ca 濃度や P 濃度の至適管理目標値は明らかではない. 3 CKD-MBD における二次性副甲状腺機能亢進症の治療 ステージ 3~5(5D を除く ) の CKD 患者の二次性副甲状腺機能亢進症に対し, 活性型ビタミン D 製剤を使用した際の腎機能障害の進行抑制効果は明らかではないが 3-8), 生命予後を改善する 可能性がある 9). 解説 1 CKD-MBD の概念 CKD CKD CKDMBD a renal osteodystrophy ROD D 35 CKD 1,814 10 1,25OH2D3 22 pgml intact PTH 65 pgml egfr 60 ml1.73 m 2 CKD P 4.6 mgdl egfr 40 CKD 1,25OH2D3 Cr egfr 10 2 CKD-MBD の治療 P 1 CKDMBD 5D CKD 82
表 K/DOQI ガイドラインに示された骨ミネラル代謝マーカーの管理目標値 CKD P mg/dl Ca mg/dl 7.CKD に伴う骨ミネラル代謝異常 ipth pg/ml 3 2.74.6 3570 4 2.74.6 70110 5 3.55.5 8.49.5 150300 KDOQI 表 b Alb 4.0 gdl Payne Ca mgdl CamgdL4 Alb gdl Ca c KDIGO P P Ca P P Ca ipth D 5D CKD Ca P P D ipth 35 9 69 CKDMBD KDOQI KDIGO 83
エビデンスに基づく CKD 診療ガイドライン 2009 アブストラクトテーブル 論文コード対象方法結果 1.Kestenbaum B, J Am Soc Nephrol 2005 95,619 6,730 CKD P 3.5mgdL P P CKD P 2.Schwarz S, Clin J Am Soc Nephrol 2006 155D CKD 985 Ca P CaP CKD Cr Cox P CaP CKD 3.Ritz E, Nephrol Dial Transplant 1995 Cr 1.46.5 mg dl 1,84PTH 6 pmol CKD 66 0.125 g P 1.7 mmoll Ca 12 Ca P 1,84 PTH 4.Coyne D, Am J Kidney Dis 2006 5.Agarwal R, Kidney Int 2005 GFR 1560 ml 1.73 m 2 ipth 150 pgml, Ca 8.010.0 mgdl P 5.2 mgdl 34 CKD 220 GFR1560 ml 1.73 m 2 34 CKD 220 3 ipth, Ca, P, Cr 24 30% ipth 91% 13% ipth CKD 34 CaP ipth 9.5 g 52 25 24 51% 61 15 25% 6.Rix M, Nephrol Dial Transplant 2004 CCr 1060 ml 36 GFR BMDosteocalcinBAPPICP 18 7.Panichi V, Clin Nephrol 1998 CCr 832 ml A 0.5 g ipth150 pgml B 2 g3 CKD 16 C 2 g ipth1,25 DALPCCr 3 8.Hamdy NA, BMJ 1995 CCr 1550 ml CKD 176 0.25 g 2 84
7.CKD に伴う骨ミネラル代謝異常 論文コード対象方法結果 9.Shoben AB, J Am Soc Nephrol 2008 34 CKD Ca 1,418 D 1.9 408 29% 217 16% CaP D 26% 20% 10.Levin A, Kidney Int 2007 横断研究 35 CKD 1,814 P 4.6 mgdl D egfr 40 ml1.73 m 2 D ipth 65 pgml1,25 OH2D3 egfr 60 85
エビデンスに基づく CKD 診療ガイドライン 2009 文献 1. Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, Sherrard DJ, Andress DL. Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 200516520528. 2. Schwarz S, Trivedi BK, KalantarZadeh K, Kovesdy CP. Association of disorders in mineral metabolism with progression of chronic kidney disease. Clin J Am Soc Nephrol. 20061825831. 3. Ritz E, Küster S, SchmidtGayk H, Stein G, Scholz C, Kraatz G, Heidland A. Lowdose calcitriol prevents the rise in 1,84iPTH without affecting serum calcium and phosphate in patients with moderate renal failureprospective placebocontrolled multicentre trialnephrol Dial Transplant 19951022282234. 4. Coyne D, Acharya M, Qiu P, Abboud H, Batlle D, Rosansky S, Fadem S, Levine B, Williams L, Andress DL, Sprague SM. Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD. Am J Kidney Dis 200647263276. 5. Agarwal R, Acharya M, Tian J, Hippensteel RL, Melnick JZ, Qiu P, Williams L, Batlle D. Antiproteinuric effect of oral paricalcitol in chronic kidney disease. Kidney Int 20056828232828. 6. Rix M, Eskildsen P, Olgaard K. Effect of 18 months of treatment with alfacalcidol on bone in patients with mild to moderate chronic renal failure. Nephrol Dial Transplant 200419870876. 7. Panichi V, Andreini B, De Pietro S, Migliori M, Taccola D, Giovannini L, Ferdeghini M, Palla R. Calcitriol oral therapy for the prevention of secondary hyperparathyroidism in patients with predialytic renal failure. Clin Nephrol 199849245250. 8. Hamdy NA, Kanis JA, Beneton MN, Brown CB, Juttmann JR, Jordans JG, Josse S, Meyrier A, Lins RL, Fairey IT. Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure. BMJ 1995310358363. 9. Shoben AB, Rudser KD, de Boer IH, Young B, Kestenbaum B. Association of oral calcitriol with improved survival in nondialyzed CKD. J Am Soc Nephrol 20081916131619. 10. Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL. Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 200771 3138. 参考にしたガイドラインなど a. Moe S, Drüeke T, Cunningham J, Goodman W, Martin K, Olgaard K, Ott S, Sprague S, Lameire N, Eknoyan G. Kidney DiseaseImproving Global Outcomes KDIGO. Definition, evaluation, and classification of renal osteodystrophya position statement from Kidney DiseaseImproving Global OutcomesKDIGO. Kidney Int 200669 19451953. b. National Kidney Foundation. KDOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 200342Suppl 3S1S201. c. Payne RB, Little AJ, Williams RB, Milner JR. Interpretation of serum calcium in patients with abnormal serum proteins. Br Med J 19734 643646. 86