Original Report: Patient-Oriented, Translational Research
Determinants of Fibroblast Growth Factor-23 and Parathyroid Hormone Variability in Dialysis PatientsJia T.a, b · Qureshi A.R.a, b · Brandenburg V.g · Ketteler M.h · Barany P.a · Heimburger O.a · Uhlin F.d, e · Magnusson P.f · Fernström A.d, e · Lindholm B.b · Stenvinkel P.a, c · Larsson T.E.a, c
aDivision of Renal Medicine, Department of Clinical Science, Intervention and Technology, and bRenal Medicine and Baxter Novum, Karolinska Institutet, and cDepartment of Nephrology, Karolinska University Hospital, Stockholm, dDepartment of Medical and Health Science, Faculty of Health Sciences, Linköping University, eDepartment of Nephrology, County Council of Östergötland, and fDivision of Clinical Chemistry, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; gDepartment of Cardiology, Aachen University Hospital, Aachen, and hDivision of Nephrology, Klinikum Coburg, Coburg, Germany
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Article / Publication Details
Background/Aims: Treatment strategies for abnormal mineral metabolism in chronic kidney disease are largely based on achieving target ranges of biomarkers that vary considerably over time, yet determinants of their variability are poorly defined. Methods: Observational study including 162 patients of three dialysis cohorts (peritoneal dialysis, n = 78; hemodialysis, n = 49; hemodiafiltration, n = 35). Clinical and biochemical determinants of parathyroid hormone (PTH) and fibroblast growth factor-23 (FGF23) variability were analyzed in the peritoneal dialysis cohort. All cohorts were used for comparison of PTH and FGF23 intra-subject variability (intra-class correlation), and their intra-subject variability in different modes of dialysis was explored. Results: High PTH variability was independently associated with lower 25-hydroxyvitamin D concentration and factors of lipid and glucose metabolism, whereas high FGF23 variability was mainly associated with lower baseline serum phosphorous. These results were consistent in multivariate and sensitivity analyses. The intra-subject variability of FGF23 was lower than for PTH irrespective of dialysis mode. Conclusions: Baseline vitamin D status and serum phosphorous are independent determinants of the longitudinal variation in PTH and FGF23, respectively. The clinical utility of FGF23 measurement remains unknown, yet it appears favorable based on its greater temporal stability than PTH in dialysis patients.
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- Slatopolsky E, Delmez JA: Pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis 1994;23:229-236.
- Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM: Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004;15:2208-2218.
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;S1-S130.
- K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002;39:S1-S266.
- Stevens LA, Djurdjev O, Cardew S, Cameron EC, Levin A: Calcium, phosphate, and parathyroid hormone levels in combination and as a function of dialysis duration predict mortality: evidence for the complexity of the association between mineral metabolism and outcomes. J Am Soc Nephrol 2004;15:770-779.
- Block GA, Hulbert-Shearon TE, Levin NW, Port FK: Association of serum phosphorus and calcium × phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 1998;31:607-617.
- Shanahan CM, Crouthamel MH, Kapustin A, Giachelli CM: Arterial calcification in chronic kidney disease: key roles for calcium and phosphate. Circ Res 2011;109:697-711.
- Qi Q, Monier-Faugere MC, Geng Z, Malluche HH: Predictive value of serum parathyroid hormone levels for bone turnover in patients on chronic maintenance dialysis. Am J Kidney Dis 1995;26:622-631.
- Larsson TE: The role of FGF-23 in CKD-MBD and cardiovascular disease: friend or foe? Nephrol Dial Transplant 2010;25:1376-1381.
- Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Juppner H, Wolf M: Fibroblast growth factor-23 and mortality among patients undergoing hemodialysis. N Engl J Med 2008;359:584-592.
- Wolf M: Forging forward with 10 burning questions on FGF23 in kidney disease. J Am Soc Nephrol 2010;21:1427-1435.
- Taylor EN, Rimm EB, Stampfer MJ, Curhan GC: Plasma fibroblast growth factor-23, parathyroid hormone, phosphorus, and risk of coronary heart disease. Am Heart J 2011;161:956-962.
- Ix JH, Katz R, Kestenbaum BR, de Boer IH, Chonchol M, Mukamal KJ, Rifkin D, Siscovick DS, Sarnak MJ, Shlipak MG: Fibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS (Cardiovascular Health Study). J Am Coll Cardiol 2012;60:200-207.
Arnlov J, Carlsson AC, Sundstrom J, Ingelsson E, Larsson A, Lind L, Larsson TE: Higher fibroblast growth factor-23 increases the risk of all-cause and cardiovascular mortality in the community. Kidney Int 20113;83:160-166.
- Gardham C, Stevens PE, Delaney MP, LeRoux M, Coleman A, Lamb EJ: Variability of parathyroid hormone and other markers of bone mineral metabolism in patients receiving hemodialysis. Clin J Am Soc Nephrol 2010;5:1261-1267.
- Perrone RD, Madias NE, Levey AS: Serum creatinine as an index of renal function: new insights into old concepts. Clin Chem 1992;38:1933-1953.
- Al-Aly Z: Vitamin D as a novel nontraditional risk factor for mortality in hemodialysis patients: the need for randomized trials. Kidney Int 2007;72:909-911.
- Enia G, Sicuso C, Alati G, Zoccali C: Subjective global assessment of nutrition in dialysis patients. Nephrol Dial Transplant 1993;8:1094-1098.
- Davies SJ, Phillips L, Naish PF, Russell GI: Quantifying comorbidity in peritoneal dialysis patients and its relationship to other predictors of survival. Nephrol Dial Transplant 2002;17:1085-1092.
- Brandenburg VM, Schlieper G, Heussen N, Holzmann S, Busch B, Evenepoel P, Vanholder R, Meijers B, Meert N, Fassbender WJ, Floege J, Jahnen-Dechent W, Ketteler M: Serological cardiovascular and mortality risk predictors in dialysis patients receiving sevelamer: a prospective study. Nephrol Dial Transplant 2010;25:2672-2679.
- Isakova T, Xie H, Barchi-Chung A, Vargas G, Sowden N, Houston J, Wahl P, Lundquist A, Epstein M, Smith K, Contreras G, Ortega L, Lenz O, Briones P, Egbert P, Ikizler TA, Jueppner H, Wolf M: Fibroblast growth factor-23 in patients undergoing peritoneal dialysis. Clin J Am Soc Nephrol 2011;6:2688-2695.
- Guillemant J, Cabrol S, Allemandou A, Peres G, Guillemant S: Vitamin D-dependent seasonal variation of PTH in growing male adolescents. Bone 1995;17:513-516.
- Joly D, Drueke TB, Alberti C, Houillier P, Lawson-Body E, Martin KJ, Massart C, Moe SM, Monge M, Souberbielle JC: Variation in serum and plasma PTH levels in second-generation assays in hemodialysis patients: a cross-sectional study. Am J Kidney Dis 2008;51:987-995.
- Souberbielle JC, Boutten A, Carlier MC, Chevenne D, Coumaros G, Lawson-Body E, Massart C, Monge M, Myara J, Parent X, Plouvier E, Houillier P: Inter-method variability in PTH measurement: implication for the care of CKD patients. Kidney Int 2006;70:345-350.
- Garrett G, Sardiwal S, Lamb EJ, Goldsmith DJ: PTH - a particularly tricky hormone: why measure it at all in kidney patients? Clin J Am Soc Nephrol 2013;8:299-312.
- Smith ER, Cai MM, McMahon LP, Holt SG: Biological variability of plasma intact and C-terminal FGF23 measurements. J Clin Endocrinol Metab 2012;97:3357-3365.
- Krall EA, Sahyoun N, Tannenbaum S, Dallal GE, Dawson-Hughes B: Effect of vitamin D intake on seasonal variations in parathyroid hormone secretion in postmenopausal women. N Engl J Med 1989;321:1777-1783.
- Gupta A, Winer K, Econs MJ, Marx SJ, Collins MT: FGF-23 is elevated by chronic hyperphosphatemia. J Clin Endocrinol Metab 2004;89:4489-4492.
- Imanishi Y, Inaba M, Nakatsuka K, Nagasue K, Okuno S, Yoshihara A, Miura M, Miyauchi A, Kobayashi K, Miki T, Shoji T, Ishimura E, Nishizawa Y: FGF-23 in patients with end-stage renal disease on hemodialysis. Kidney Int 2004;65:1943-1946.
- Bolland MJ, Grey AB, Ames RW, Mason BH, Horne AM, Gamble GD, Reid IR: The effects of seasonal variation of 25-hydroxyvitamin D and fat mass on a diagnosis of vitamin D sufficiency. Am J Clin Nutr 2007;86:959-964.
- Rodriguez-Rodriguez E, Navia-Lomban B, Lopez-Sobaler AM, Ortega RM: Associations between abdominal fat and body mass index on vitamin D status in a group of Spanish schoolchildren. Eur J Clin Nutr 2010;64:461-467.
- Gilsanz V, Kremer A, Mo AO, Wren TA, Kremer R: Vitamin D status and its relation to muscle mass and muscle fat in young women. J Clin Endocrinol Metab 2010;95:1595-1601.
- Grundberg E, Brandstrom H, Ribom EL, Ljunggren O, Mallmin H, Kindmark A: Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women. Eur J Endocrinol 2004;150:323-328.
- Cirillo M, Ciacci C, De Santo NG: Age, renal tubular phosphate reabsorption, and serum phosphate levels in adults. N Engl J Med 2008;359:864-866.
- Ix JH, De Boer IH, Peralta CA, Adeney KL, Duprez DA, Jenny NS, Siscovick DS, Kestenbaum BR: Serum phosphorus concentrations and arterial stiffness among individuals with normal kidney function to moderate kidney disease in mesa. Clin J Am Soc Nephrol 2009;4:609-615.
- De Boer IH, Rue TC, Kestenbaum B: Serum phosphorus concentrations in the third National Health and Nutrition Examination Survey (NHANES III). Am J Kidney Dis 2009;53:399-407.
- Mirza MA, Alsio J, Hammarstedt A, Erben RG, Michaelsson K, Tivesten A, Marsell R, Orwoll E, Karlsson MK, Ljunggren O, Mellstrom D, Lind L, Ohlsson C, Larsson TE: Circulating fibroblast growth factor-23 is associated with fat mass and dyslipidemia in two independent cohorts of elderly individuals. Arterioscler Thromb Vasc Biol 2011;31:219-227.
- Ashikaga E, Honda H, Suzuki H, Hosaka N, Hirai Y, Sanada D, Nakamura M, Nagai H, Matsumoto K, Kato N, Mukai M, Watanabe M, Takahashi K, Shishido K, Akizawa T: Impact of fibroblast growth factor-23 on lipids and atherosclerosis in hemodialysis patients. Ther Apher Dial 2010;14:315-322.
- Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J, Wahl P, Gutierrez OM, Steigerwalt S, He J, Schwartz S, Lo J, Ojo A, Sondheimer J, Hsu CY, Lash J, Leonard M, Kusek JW, Feldman HI, Wolf M: Fibroblast growth factor-23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 2011;305:2432-2439.
- Wolf M, Molnar MZ, Amaral AP, Czira ME, Rudas A, Ujszaszi A, Kiss I, Rosivall L, Kosa J, Lakatos P, Kovesdy CP, Mucsi I: Elevated fibroblast growth factor-23 is a risk factor for kidney transplant loss and mortality. J Am Soc Nephrol 2011;22:956-966.
- Olauson H, Qureshi AR, Miyamoto T, Barany P, Heimburger O, Lindholm B, Stenvinkel P, Larsson TE: Relation between serum fibroblast growth factor-23 level and mortality in incident dialysis patients: are gender and cardiovascular disease confounding the relationship? Nephrol Dial Transplant 2010;25:3033-3038.
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