Ethnic and seasonal variations in FGF-23 and markers of chronic kidney disease-mineral and bone disorder

Abstract

Background: Fibroblast growth factor 23 (FGF-23) and other markers of chronic kidney disease-mineral and bone disorder (CKD-MBD) provide valuable insights into disease processes, treatment options and patient prognosis. However, limited research has explored potential associations with ethnicity or season, particularly in multi-ethnic populations residing in high-latitude regions.

Methods: We evaluated CKD-BMD markers in a diverse cohort of CKD patients, who were participants of The CANADIAN AIM to PREVENT (the CAN AIM to PREVENT) study. FGF-23, calcium, phosphate, 25-hydroxyvitamin D (25-OHD) and intact parathyroid hormone (iPTH) in 1234 participants with pre-dialysis CKD (mean estimated glomerular filtration rate: 41.8 ± 14.3 mL/min) were analyzed. Mixed-effects general linear regression models adjusted for demographic and biological factors were used to compare repeated measurements across patient groups categorized by ethnicity (East Asian, White, South Asian, Black, Southeast Asian) and seasons.

Results: Compared with other groups, White participants exhibited 8.0%-18.5% higher FGF-23 levels, Black participants had 0.17-0.32 mg/dL higher calcium levels, White participants had 10.0%-20.1% higher 25-OHD levels, South Asian participants had 7.3%-20.1% lower 25-OHD levels and Black participants had 22.1-73.8% higher iPTH levels, while East Asian participants had 10.7%-73.8% lower iPTH levels. Seasonal variations were also observed. FGF-23 levels were 11.9%-15.5% higher in summer compared with other seasons, while calcium levels were 0.03-0.06 mg/dL lower in summer. 25-OHD levels were 5.6%-10.6% higher in summer and autumn compared with other seasons.

Conclusions: This study shows that FGF-23 and CKD-MBD markers in a Canadian pre-dialysis CKD cohort vary independently by ethnicity and season. Further research is needed to understand the reasons and clinical significance of these findings.

Keywords: CKD-MBD; FGF-23; epidemiology; ethnicity; pre-dialysis.

Graphical Abstract

Figure 1:

Derivation of the study cohort.

Figure 2:

Changes in serum FGF-23^* by ethnicity and season. ^*Based on mixed-effects general linear regression model predicting changes in serum natural log FGF-23 adjusted for age, gender, body surface area, visit number (as a proxy for time), eGFR, history of diabetes mellitus, use of vitamin D supplements, urine protein/creatinine ratio, serum calcium, phosphate, 25-OHD and iPTH, ethnicity, and season.

Figure 3:

Changes in serum calcium^* by ethnicity and season. ^*Based on mixed-effects general linear regression model predicting changes in serum calcium adjusted for age, gender, body surface area, visit number (as a proxy for time), eGFR, history of diabetes mellitus, use of vitamin D supplements, urine protein/creatinine ratio, serum FGF-23, phosphate, 25-OHD and iPTH, ethnicity, and season.

Figure 4:

Changes in serum phosphate^* by ethnicity and season. ^*Based on mixed-effects general linear regression model predicting changes in serum phosphate adjusted for age, gender, body surface area, visit number (as a proxy for time), eGFR, history of diabetes mellitus, use of vitamin D supplements, urine protein/creatinine ratio, serum calcium, FGF-23, 25-OHD and iPTH, ethnicity, and season.

Figure 5:

Changes in serum 25-OHD^* by ethnicity and season. ^*Based on mixed-effects general linear regression model predicting changes in serum 25-OHD adjusted for age, gender, body surface area, visit number (as a proxy for time), eGFR, history of diabetes mellitus, use of vitamin D supplements, urine protein/creatinine ratio, serum calcium, phosphate, FGF-23 and iPTH, ethnicity, and season.

Figure 6:

Changes in serum iPTH^* by ethnicity and season. ^*Based on mixed-effects general linear regression model predicting changes in serum iPTH adjusted for age, gender, body surface area, visit number (as a proxy for time), eGFR, history of diabetes mellitus, use of vitamin D supplements, urine protein/creatinine ratio, serum calcium, phosphate, FGF-23 and 25-OHD, ethnicity, and season.