[en] ("[en] CONTEXT: Parathyroid hormone (PTH) treatment targets for patients receiving hemodialysis (HD) are lower in Japan than in Europe. Whether this translates to lower bone turnover is unknown and could depend on skeletal PTH responsiveness.
OBJECTIVE: This study investigates whether skeletal PTH responsiveness is better preserved in Japanese vs European patients receiving HD.
METHODS: This is a post hoc analysis of data from 2 prospective cohort studies, using a case-control design. Patients receiving chronic intermittent HD therapy were eligible for inclusion. Participating Belgian and Japanese patients (n = 374) were matched 1:1 by age (59 ± 12 years), sex (66% male), diabetes (34%), and dialysis duration (39 months [22-63 months]). PTH, bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were measured centrally in Liège, Belgium.
RESULTS: Japanese patients had lower levels of iPTH (207 vs 268 pg/mL; P < .001), BALP (15.3 vs 24.5 μg/L; P < .001), and TRAP5b (3.35 vs 5.79 U/L; P < .001). Linear regression analyses revealed lower levels of bone turnover markers for any given level of PTH in Japanese vs Belgian patients, indicating lower skeletal PTH responsiveness. Consistently, bone turnover markers were significantly lower in Japanese vs Belgian patients when stratifying or matching according to PTH levels. Male sex, obesity, and hyperphosphatemia were the main determinants of the bone turnover marker/PTH ratios.
CONCLUSION: Japanese patients receiving HD have lower bone turnover than their European counterparts, even at similar PTH levels. The rationale for the current regional differences in PTH treatment targets remains obscure and deserves further attention.","[en] ","")
Disciplines :
Laboratory medicine & medical technology Urology & nephrology
Author, co-author :
Evenepoel, Pieter ; Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, 3000 Leuven, Belgium ; Department of Medicine, Division of Nephrology, University Hospitals Leuven, 3000 Leuven, Belgium
Jørgensen, Hanne Skou ; Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, 3000 Leuven, Belgium ; Department of Renal Medicine, Aarhus University Hospital, 8200 Aarhus N, Denmark
Komaba, Hirotaka ; Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara 259-1193, Japan
Mazzaferro, Sandro ; Nephrology Unit at Policlinico Umberto I Hospital, 00185 Rome, Italy ; Department of Translation and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy
Vervloet, Marc ; Department of Nephrology, Amsterdam University Medical Center, 1081 HV Amsterdam, the Netherlands ; Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, 1081 HV Amsterdam, the Netherlands
Cavalier, Etienne ; Centre Hospitalier Universitaire de Liège - CHU > > Service de chimie clinique
Fukagawa, Masafumi ; Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, Isehara 259-1193, Japan
Language :
English
Title :
Lower Bone Turnover and Skeletal PTH Responsiveness in Japanese Compared to European Patients on Hemodialysis.
Ketteler M, Block GA, Evenepoel P, et al. Diagnosis, evaluation, prevention, and treatment of chronic kidney disease "mineral and bone disorder: synopsis of the Kidney Disease: Improving Global Outcomes 2017 clinical practice guideline update. Ann Intern Med. 2018;168(6):422-430.
Pazianas M, Miller PD. The CKD-MBD syndrome: hysteresis in PTH involvement and PTH administration for its management. J Bone Miner Res. 2020;35(12):2313-2317.
Duque EJ, Elias RM, Moys (c)s RMA. Parathyroid hormone: a uremic toxin. Toxins (Basel). 2020;12(3):189.
Merle E, Roth H, London GM, et al. French Calcium and Phosphate Observatory. Low parathyroid hormone status induced by high dialysate calcium is an independent risk factor for cardiovascular death in hemodialysis patients. Kidney Int. 2016;89(3): 666-674.
Lamina C, Kronenberg F, Stenvinkel P, et al. Association of changes in bone mineral parameters with mortality in haemodialysis patients: insights from the ARO cohort. Nephrol Dial Transplant. 2020;35(3):478-487.
Iimori S, Mori Y, Akita W, et al. Diagnostic usefulness of bone mineral density and biochemical markers of bone turnover in predicting fracture in CKD stage 5D patients "a single-center cohort study. Nephrol Dial Transplant. 2012;27(1):345-351.
Jansz TT, Goto NA, van Ballegooijen AJ, Willems HC, Verhaar MC, van Jaarsveld BC. The prevalence and incidence of vertebral fractures in end-stage renal disease and the role of parathyroid hormone. Osteoporos Int. 2020;31(3):515-524.
Tentori F, Blayney MJ, Albert JM, et al. Mortality risk for dialysis patients with different levels of Serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis. 2008;52(3):519-530.
Kalantar-Zadeh K, Kuwae N, Regidor DL, et al. Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int. 2006;70(4):771-780.
Chan K, Karaboyas A, Morgenstern H, et al. International and racial differences in mineral and bone disorder markers and treatments over the first 5 years of hemodialysis in the Dialysis Outcomes and Practice Patterns Study. Kidney Med. 2019;1(3): 86-96.
Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Update Work Group. 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 Suppl (2011). 2017;7(1):1-59.
Fukagawa M, Yokoyama K, Koiwa F, et al. CKD-MBD Guideline Working Group; Japanese Society for Dialysis Therapy. Clinical practice guideline for the management of chronic kidney disease "mineral and bone disorder. Ther Apher Dial. 2013;17(3):247-288.
Nakai S, Akiba T, Kazama J, et al. Patient Registration Committee of the Japanese Society for Dialysis Therapy, Tokyo, Japan. Effects of serum calcium, phosphorous, and intact parathyroid hormone levels on survival in chronic hemodialysis patients in Japan. Ther Apher Dial. 2008;12(1):49-54.
Taniguchi M, Fukagawa M, Fujii N, et al. Committee of Renal Data Registry of the Japanese Society for Dialysis Therapy. Serum phosphate and calcium should be primarily and consistently controlled in prevalent hemodialysis patients. Ther Apher Dial. 2013;17(2): 221-228.
Sawaya BP, Butros R, Naqvi S, et al. Differences in bone turnover and intact PTH levels between African American and Caucasian patients with end-stage renal disease. Kidney Int. 2003;64(2): 737-742.
Tominaga N, Yonaha T, Yamanouchi M, et al. Bone responsiveness to parathyroid hormone is negatively associated with parathyroid hormone-lowering drug use in patients undergoing hemodialysis: a cross-sectional study. BMC Nephrol. 2021;22(1):275.
Evenepoel P, Cavalier E, D (tm)Haese PC. Biomarkers predicting bone turnover in the setting of CKD. Curr Osteoporos Rep. 2017;15(3): 178-186.
Nakagawa Y, Komaba H, Hamano N, et al. Interrelationships between sclerostin, secondary hyperparathyroidism, and bone metabolism in patients on hemodialysis. J Clin Endocrinol Metab. 2022;107(1):e95-e105.
Evenepoel P, Claes K, Meijers B, et al. Bone mineral density, bone turnover markers, and incident fractures in de novo kidney transplant recipients. Kidney Int. 2019;95(6):1461-1470.
Payne RB, Little AJ, Williams RB, Milner JR. Interpretation of serum calcium in patients with abnormal serum proteins. BMJ. 1973;4(5893):643-646.
Cavalier E, Delanaye P, Lukas P, Carlisi A, Gadisseur R, Souberbielle JC. Standardization of DiaSorin and Roche automated third generation PTH assays with an international standard: impact on clinical populations. Clin Chem Lab Med. 2014;52(8): 1137-1141.
Cavalier E, Delanaye P, Vranken L, et al. Interpretation of serum PTH concentrations with different kits in dialysis patients according to the KDIGO guidelines: importance of the reference (normal) values. Nephrol Dial Transplant. 2012;27(5):1950-1956.
Jørgensen HS, Behets G, Viaene L, et al. Diagnostic accuracy of noninvasive bone turnover markers in renal osteodystrophy. Am J Kidney Dis. 2022;79(5):667-676.e1.
Evenepoel P, Jørgensen HS, Komaba H, et al. Supplementary data for "Lower Bone Turnover and Skeletal PTH Responsiveness in Japanese Compared to European Patients on Hemodialysis." Zenodo. September 2, 2022. https://zenodo.org/record/7042961
Hernando N, Wagner CA. Mechanisms and regulation of intestinal phosphate absorption. In: Comprehensive Physiology. Wiley; 2018:1065-1090.
Tabibzadeh N, Karaboyas A, Robinson BM, et al. The risk of medically uncontrolled secondary hyperparathyroidism depends on parathyroid hormone levels at haemodialysis initiation. Nephrol Dial Transplant. 2021;36(1):160-169.
Haarhaus M, Evenepoel P. Differentiating the causes of adynamic bone in advanced chronic kidney disease informs osteoporosis treatment. Kidney Int. 2021;100(3):546-558.
Ott SM, Malluche HH, Jorgetti V, Elder GJ. Importance of bone turnover for therapeutic decisions in patients with CKD-MBD. Kidney Int. 2021;100(3):502-505.
Jadoul M, Albert JM, Akiba T, et al. Incidence and risk factors for hip or other bone fractures among hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study. Kidney Int. 2006;70(7):1358-1366.
Drechsler C, Verduijn M, Pilz S, et al. NECOSAD Study Group. Bone alkaline phosphatase and mortality in dialysis patients. Clin J Am Soc Nephrol. 2011;6(7):1752-1759.
Maruyama Y, Taniguchi M, Kazama JJ, et al. A higher serum alkaline phosphatase is associated with the incidence of hip fracture and mortality among patients receiving hemodialysis in Japan. Nephrol Dial Transplant. 2014;29(8):1532-1538.
Tentori F, McCullough K, Kilpatrick RD, et al. High rates of death and hospitalization follow bone fracture among hemodialysis patients. Kidney Int. 2014;85(1):166-173.
Millan JL. Mammalian Alkaline Phosphatases: From Biology to Applications in Medicine and Biotechnology. J.L. Millan: WILEY-VCH Verlag; 2006; 107-108.
Halleen JM, Tiitinen SL, Ylipahkala H, Fagerlund KM, Väänänen HK. Tartrate-resistant acid phosphatase 5b (TRACP 5b) as a marker of bone resorption. Clin Lab. 2006;52(9-10):499-509.
Rissanen JP, Suominen MI, Peng Z, Halleen JM. Secreted tartrate-resistant acid phosphatase 5b is a marker of osteoclast number in human osteoclast cultures and the rat ovariectomy model. Calcif Tissue Int. 2008;82(2):108-115.
Chu P, Chao TY, Lin YF, Janckila AJ, Yam LT. Correlation between histomorphometric parameters of bone resorption and serum type 5b tartrate-resistant acid phosphatase in uremic patients on maintenance hemodialysis. Am J Kidney Dis. 2003;41(5): 1052-1059.
Nenonen A, Cheng S, Ivaska KK, et al. Serum TRACP 5b is a useful marker for monitoring alendronate treatment: comparison with other markers of bone turnover. J Bone Miner Res. 2005;20(10): 1804-1812.
Haarhaus M, Brandenburg V, Kalantar-Zadeh K, Stenvinkel P, Magnusson P. Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD. Nat Rev Nephrol. 2017;13(7): 429-442.
Broyles DL, Nielsen RG, Bussett EM, et al. Analytical and clinical performance characteristics of tandem-MP ostase, a new immunoassay for serum bone alkaline phosphatase. Clin Chem. 1998;44(10): 2139-2147.
Pike AF, Kramer NI, Blaauboer BJ, Seinen W, Brands R. A novel hypothesis for an alkaline phosphatase "rescue" mechanism in the hepatic acute phase immune response. Biochim Biophys Acta. 2013;1832(12):2044-2056.
Szulc P. The role of bone turnover markers in monitoring treatment in postmenopausal osteoporosis. Clin Biochem. 2012;45(12): 907-919.
Cavalier E, Lukas P, Delanaye P. Analytical evaluation of the Nittobo Medical tartrate resistant acid phosphatase isoform 5b (TRACP-5b) EIA and comparison with IDS iSYS in different clinically defined populations. Clin Chem Lab Med. 2022;60(3): 394-400.
Gossiel F, Ugur A, Peel NFA, Walsh JS, Eastell R. The clinical utility of TRACP-5b to monitor anti-resorptive treatments of osteoporosis. Osteoporos Int. 2022;33(6):1357-1363.
Hansen D, Bressendorff I, Nordholm A, Jacobsen AA, Klausen TW, Jørgensen NR. Circadian rhythm of markers of bone turnover in patients with chronic kidney disease. Bone Rep. 2022;16:101593.
Massry SG, Coburn JW, Lee D, Jowsey J, Kleeman CR. Skeletal resistance to parathyroid hormone in renal failure. Ann Intern Med. 1973;78:357-364.
Wesseling-Perry K, Harkins GC, Wang H, et al. The calcemic response to continuous parathyroid hormone (PTH)(1-34) infusion in end-stage kidney disease varies according to bone turnover: a potential role for PTH(7-84). J Clin Endocrinol Metab. 2010;95(6): 2772-2780.
Picton ML, Moore PR, Mawer EB, et al. Down-regulation of human osteoblast PTH/PTHrP receptor mRNA in end-stage renal failure. Kidney Int. 2000;58(4):1440-1449.
Starup-Linde J, Eriksen SA, Lykkeboe S, Handberg A, Vestergaard P. Biochemical markers of bone turnover in diabetes patients "a meta-analysis, and a methodological study on the effects of glucose on bone markers. Osteoporos Int. 2014;25(6):1697-1708.
de Oliveira RA, Barreto FC, Mendes M, et al. Peritoneal dialysis per se is a risk factor for sclerostin-associated adynamic bone disease. Kidney Int. 2015;87(5):1039-1045.
Kitazawa S, Kajimoto K, Kondo T, Kitazawa R. Vitamin D3 supports osteoclastogenesis via functional vitamin D response element of human RANKL gene promoter. J Cell Biochem. 2003;89(4): 771-777.
Debowska M, Dai L, Wojcik-Zaluska A, et al. Association between biomarkers of mineral and bone metabolism and removal of calcium and phosphate in hemodialysis. Blood Purif. 2020;49(1-2): 71-78.
Spalding EM, Chamney PW, Farrington K. Phosphate kinetics during hemodialysis: evidence for biphasic regulation. Kidney Int. 2002;61(2):655-667.
Shidara K, Inaba M, Okuno S, et al. Serum levels of TRAP5b, a new bone resorption marker unaffected by renal dysfunction, as a useful marker of cortical bone loss in hemodialysis patients. Calcif Tissue Int. 2008;82(4):278-287.
