Subscribe to RSS
DOI: 10.1055/a-1559-6968
CKD-MBD und sekundärer Hyperparathyreoidismus (Teil 2)
Management und neue Therapieoptionen
ZUSAMMENFASSUNG
Der Begriff CKD-MBD (Chronic Kidney Disease – Mineral Bone Disorder) ist seit einigen Jahren für Störungen des Kalzium-Phosphat-Stoffwechsels und der damit verbundenen Risiken für das Mineral-Knochen- und Herz-Kreislauf-System bei chronischen Nierenerkrankungen bekannt. Die Bezeichnung entstand nach einem Paradigmenwechsel in der Pathophysiologie des sekundären Hyperparathyreoidismus und da neue Akteure wie FGF23 und Klotho gefunden wurden, die eine wichtige Rolle bei der Entstehung der Störungen spielen. Das wachsende Verständnis der Zusammenhänge zwischen den neuen Akteuren und Kalzium, Phosphat, Vitamin D und Vitamin K2 sowie der Verkalkung von Gefäßen und Weichteilen beeinflusste unweigerlich unsere Therapien. Dieser zweite Teil des Beitrags verschafft einen Überblick über die Implikationen der neuen pathophysiologischen Erkenntnisse, v. a. im Hinblick auf neue Therapeutika für eine optimale Therapie von Patienten mit CKD-MBD.
Publication History
Article published online:
14 December 2021
© 2021. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
Literatur
- 1 Levin A, Bakris GL, Molitch M. et al 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 2007; 71: 31-38
- 2 Cozzolino M, Ketteler M. Evaluating extended-release calcifediol as a treatment option for chronic kidney disease-mineral and bone disorder (CKD-MBD). Expert Opin Pharmacother 2019; 20: 2081-2093
- 3 Geng S, Kuang Z, Peissig GL. et al Parathyroid hormone independently predicts fracture, vascular events, and death in patients with stage 3 and 4 chronic kidney disease. Osteoporos Int 2019; 30: 2019-2025
- 4 Tentori F, Tu C, Zeppel L. et al Treatments of mineral and bone disorders may be under-utilized in CKD patients. Nephrol Dial Transplant 2017; 32: iii236
- 5 Ennis JL, Worecester EM, Coe FL. et al Current recommended 25-hydroxyvitamin D targets for chronic kidney disease management may be too low. J Nephrol 2016; 29: 63-70
- 6 Ravani P, Alberti F, Tripepi G. et al Vitamin D levels and patient outcome in chronic kidney disease. Kidney Int 2009; 75: 89-95
- 7 Holick MF. Vitamin Deficiency. Engl J Med 2007; 357: 266-281
- 8 Holick MF, Binkley NC, Bischoff-Ferrari HA. et al Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2011; 96: 1911-1930
- 9 National Kidney Foundation K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease. Am J Kidney Dis 2003; 42: S1-S201
- 10 Ross AC, Manson JAE, Abrams SA. et al The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab 2011; 96: 53-58
- 11 Mehotra R, Kerma D, Budoff Met al. Hypovitaminosis D in Chronic Kidney Disease. ClinJ Am Soc Nephrol 2008; 3: 1144-1151
- 12 Nykjaer A, Fyfe JC, Kozyraki Ret al. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitaminD(3). Proc Natl Acad Sci USA 2001; 98: 13895-13900
- 13 Jacob AI, Sallman A, Sanitz Z. et al Defective Photoproduction of Cholecalciferol in Normal and Uremic Humans. J Nutr 1984; 114: 1313-1319
- 14 Krassilnikova M, Ostrov K, Bader A. et al Low Dietary Intake of Vitamin D and Vitamin D Deficiency in HemodialysisPatients. J Nephrol Ther 2014; 4: 166
- 15 Vaziri ND, Hollander D, Hung EK. et al Impaired intestinal absorption of vitamin D3 in azotemic rats. Am J Clin Nutr 1983; 37: 403-406
- 16 Sato KA, Gray RW, Lemann Jr J. Urinary excretion of 25-hydroxyvitamin D in health and the nephrotic syndrome. J Lab Clin Me 1982; 99: 325-330
- 17 Dusso AS. Kidney disease and vitamin D levels: 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and VDR activation. Kidney Int Suppl 2011; 1: 136-141
- 18 Takemoto F, Shinki T, Yokoyama K. et al Gene expression of vitamin Dhydroxylase and megalin in the remnant kidney of nephrectomized rats. Kidney Int 2003; 64: 414-420
- 19 Michaud J, Naud J, Ouimet D. et al Reduced Hepatic Synthesis of Calcidiol in Uremia. J Am Soc Nephrol 2010; 21: 1488-1497
- 20 Mibe Arzneimittel mbH, Dekristol, Fachinformation 09/2015. Im Internet. https://www.mibe.de/tl_files/dp_de/content/produkte_mibe/gebrauchsinformationen/dekristol_20000/GI02913-01_Dekristol_20000_DE.pdf Stand: 22.10.2021
- 21 Roche Pharma AG. Rocaltrol, Fachinformation 11/2018
- 22 LEO Pharma GmbH, EinsAlpha® 2 g/ml Injektionslösung, Fachinformation 06/2016
- 23 AbbVie, Zemplar, Fachinformation 04/2018. Im Internet. https://www.gelbe-liste.de/produkte/Zemplar-5-Mikrogramm-ml-Injektionsloesung-Durchstechflasche_877051/fachinformation Stand: 22.10.2021
- 24 Thadhani R, Appelbaum E, Pritchett Y. et al Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA 2012; 307: 674-684
- 25 Wang A, Fang F, Chan J. et al Effect of Paricalcitol on Left Ventricular Mass and Function in CKD – The OPERA Trial. J Am Soc Nephrol 2014; 25: 175-186
- 26 Bikle D. Vitamin D. Production, Metabolism, and Mechanisms of Action. In: Feingold KR, Anawalt B, Boyce A, et al. (editors). Endotext South Darmouth, Im Internet. https://www.ncbi.nlm.nih.gov/books/NBK278935 Stand: 22.10.2021
- 27 Henry HL. Regulation of vitamin D metabolism. Best Pract Res Clin Endocrinol Metab 2011; 25: 531-541
- 28 Faul C. et al FGF23 induces left ventricular hypertrophy. J Clin Invest 2011; 121: 4394-4408
- 29 Ketteler M, EBlock GA, Evenepoel P. et al Executive summary of the 2017 KDIGO Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) Guideline Update: what’s changed and why it matters. Kidney Int 2017; 92: 26-36
- 30 AMGEN GmbH, Mimpara, Fachinformation 07/2019 Im Internet. https://fachkreise.amgen.de/downloads/f/1/111/mimpara_30_60_90_mg_filmtabletten.pdf Stand: 22.10.2021
- 31 AMGEN GmbH, Parsabiv, Fachinformation 02/2019 Im Internet. https://fachkreise.amgen.de/downloads/f/1/840/parsabiv-25_5_10-mg-injektionsloesung_201902.pdf Stand: 22.10.2021
- 32 KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease – Mineral and Bone Disorder (CKD-MBD). Kidney Int 2017; 7: 1-59
- 33 Westerberg PA, Sterner E, Ljundren Ö. et al High doses of cholecalciferol alleviate the progression ofhyperparathyroidism in patients with CKD Stages 3–4 results of a 12-week double-blind, randomized, controlled study. Nephrol Dial Transplant 2018; 33: 466-471
- 34 Fournier A, Idrissi A, Sebert JL. et al Preventing renal bone disease in moderate renal failure with CaCO3 and 25(OH) vitamin D3. Kidney Int 1988; 24: S178-S179
- 35 Kalantar-Zadeh K, Kovesdy CP. Clinical outcomes with active versus nutritional vitamin D compounds in chronic kidney disease. Clin J Am Soc Nephrol 2009; 4: 1529-1539
- 36 Agarwal R, Georgianos PI. Con: nutritional vitamin D replacement in chronic kidney disease and end-stage renal disease. Nephrol Dial Transplant 2016; 31: 706-713
- 37 Bordier PJ, Marie PJ, Arnaud CD. Evolution of renal osteodystrophy: correlation of bone histomorphometry and serum mineral and immunoreactive parathyroid hormone values before and after treatment with calcium carbonate or 25-hydroxycholecalciferol. Kidney Int Suppl 1975: 102-112
- 38 Antonio L. et al Poster 1044 – Virtual European Congress of Endocrinology 2020 meeting.
- 39 Letteri JM, Kleinmann LM, Ellis KN. et al Effects of 25-hydroxycholecalciferol on calcium metabolism in chronic renal failure. Adv Exp Med Biol 1977; 81: 591-601
- 40 Haddad Jr JG, Rojanasathit S. Acute administration of 25-hydroxycholecalciferol in man. J Clin Endocrinol Metab 1976; 42: 284-290
- 41 Sprague SM, Silva AL, Al Saghir AF. et al Modified-Release Calcifediol Effectively Controls Secondary Hyperparathyroidism Associated with Vitamin D Insufficiency in Chronic Kidney Disease. Am J Nephrol 2014; 40: 535-545
- 42 Sprague SM, Crawford PW, Melnick JZ. et al Use of Extended-Release Calcifediol to Treat Secondary Hyperparathyroidism in Stages 3 and 4 Chronic Kidney Disease. Am J Nephrol. 2016; 44: 316-325
- 43 Petkovich M, Melnick J, White J. et al Modified-release oral calcifediol corrects vitamin D insufficiency with minimal CYP24A1 upregulation. J Steroid Biochem Mol Biol 2015; 148: 283-299
- 44 Sprague SM, Strugnell SA, Bishop CW. Extended-release calcifediol for secondary hyperparathyroidism in stage 3–4 chronic kidney disease. Exp Rev Endocrinol Metab 2017; 12: 289-301
- 45 Strugnell SA, Sprague SM, Ashfaq A. et al Rationale for Raising Current Clinical Practice Guideline Target for Serum 25-Hydroxyvitamin D in Chronic Kidney Disease. Am J Nephrol 2019; 49: 284-293
- 46 Booth SL, Al Rajabi A. Determinants of vitamin K status in humans. Vitam Horm 2008; 78: 1-22
- 47 D’Alessandro AJ. Vitamin K and its role in blood coagulation. Am J Surg 1942; 57: 104-111
- 48 Björklund G, Svanberg E, Dadar M. et al The role of Matrix Gla Protein (MGP) in vascular calcification. Curr Med Chem 2020; 27: 1647-1660
- 49 Ducy P. The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism. Diabetologia 2011; 54: 1291
- 50 Lanham-New SA. Importance of calcium, vitamin D and vitamin K for osteoporosis prevention and treatment. Proc Nutr Soc 2008; 67: 163-176
- 51 Cranenburg EC, Vermeer C, Koos R. et al The circulating inactive form of matrix gla protein (ucmgp) as a biomarker for cardiovascular calcification. J Vasc Res 2008; 45: 427-436
- 52 Fraser J.D, Price PA. Induction of matrix gla protein synthesis during prolonged 1,25-dihydroxyvitamin D3 treatment of osteosarcoma cells. Calcif Tissue Int 1990; 46: 270-279
- 53 Seyama Y, Horiuch M, Hayashi M. et al Effect of vitamin K2 on experimental calcinosis induced by vitamin D2 in rat soft tissue. Int J Vitam Nutr Res 1996; 66: 36-38
- 54 Braam LA, Hoeks AP, Brouns F. et al Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: A follow-up study. Thromb Haemost 2004; 91: 373-380
- 55 Van Ballegooijen AJ, Cepelis A, Visser M. et al Joint association of low vitamin D and vitamin K status with blood pressure and hypertension. Hypertension 2017; 69: 1165-1172
- 56 Van Ballegooijen AJ, Pilz S, Tomaschitz A. The synergistic interplay between vitamins D and K for bone and cardiovascular health: A narrative review. Int J Endocrinol 2017; 2017: 7454376
- 57 Mayer Jr. O, Seidlerova J, Wohlfahrt P. et al Synergistic effect of low K and D vitamin status on arterial stiffness in a general population. J Nutr Biochem 2017; 46: 83-89
- 58 Cozzolino M, Mangano M, Galassi A. et al Vitamin K in chronic kidney disease. Nutrients 2019; 11: 168
- 59 Neradova A, Schumacher SP, Hubeek I. et al Phosphate binders affect vitamin K concentration by undesired binding, an in vitro study. BMC Nephrol 2017; 18: 149
- 60 Susantitaphong P, Jaber PL. Potential Interaction Between Sevelamer and Fat-Soluble Vitamins: A Hypothesis. Am J Kidney Dis 2012; 59: 165-167
- 61 Fusaro M, Cozzolino M, Plebani M. et al Sevelamer use, vitamin K levels, vascular calcifications and vertebral fractures in hemodialysis patients: results from the VIKI study.
- 62 Fraser JD, Otawara Y, Price PA. 1,25-dihydroxyvitamin D3 stimulates the synthesis of matrix gamma-carboxyglutamic acid protein by osteosarcoma cells. Mutually exclusive expression of vitamin K-dependent bone proteins by clonal osteoblastic cell lines. J Biol Chem 1988; 263: 911-916
- 63 Van Ballegooijen AJ, Beulens JWJ, Schurgers LJ. et al Effect of 6-Month Vitamin D Supplementation on Plasma Matrix Gla Protein in Older Adults. Nutrients 2019; 11: 231
- 64 Yasui T, Miyatani Y, Tomita J. et al Effect of vitamin K2 treatment on carboxylation of osteocalcin in early postmenopausal women. Gynecol Endocrinol 2006; 22: 455-459
- 65 Zittermann A, Ernst JB, Prokop S. et al Effect of vitamin d on all-cause mortality in heart failure (EVITA): A 3-year randomized clinical trial with 4000 iu vitamin d daily. Eur Heart J 2017; 38: 2279-2286
- 66 Bolland MJ, Grey A, Avenell A. et al Calcium supplements with or without vitamin d and risk of cardiovascular events: Reanalysis of the women’s health initiative limited access dataset and meta-analysis. BMJ 2011; 342: d2040
- 67 Challoumas D, Stavrou A, Pericleous A. et al Effects of combined vitamin d--calcium supplements on the cardiovascular system: Should we be cautious?. Atherosclerosis 2015; 238: 388-398
- 68 Manson JE, Cook NR, Lee IM. et al on behalf of the VITAL Research Group. Vitamin D Supplements and Prevention of Cancer and Cardiovascular Disease. N Engl J Med 2019; 380: 33-44
- 69 Kohan DE, Fioretto P, Tang W. et al Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int 2014; 85: 962-971
- 70 Watts NB, Bilezikian JP, Usiskin K. et al Effects of Canagliflozin on Fracture Risk in Patients with Type 2 Diabetes Mellitus. J Clin Endocrinol Metab 2016; 101: 157-166
- 71 Blau JE, Taylor SI. Adverse effects of SGLT2 inhibitors on bone. Nat Rev Nephrol 2018; 14: 473-474
- 72 De Jong MA, Petrykiv SI, Laverman GD. et al Effects of Dapagliflozin on circulating Markers of Phosphate Homeostasis. Clin J Am Soc Nephrol 2019; 14: 66-73
- 73 List JF, Woo V, Morales E. et al Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 2009; 32: 650-657
- 74 Kwon H. Canagliflozin: Clinical Efficacy and Safety. Endocrinology and Metabolic Drugs Advisory Committee Meeting, 2013. Im Internet. www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM336234.pdf Stand: 22.10.2021
- 75 Bristol-Myers Squibb Company, Astra Zeneca AB. Background Document: Dapagliflozin. 2011 Im Internet. www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM262996.pdf Stand: 22.10.2021
- 76 Mather A, Pollock C. Glucose handling by the kidney. Kidney Int 2011; 79: S1-S6
- 77 Prasad N, Bhadauria D. Renal phosphate handling: Physiology. Indian J Endocrinol Metab 2013; 17: 620-627
- 78 Lou Y, Yu Y, Duan J. et al Sodium-glucose cotransporter 2 inhibitors and fracture risk in patients with type 2 diabetes mellitus: a meta-analysis of randomized controlled trials. Ther Adv Chron Dis 2020; 11: 2040622320961599