Fibroblast growth factor-23 and the long-term risk of hospital-associated AKI among community-dwelling older individuals

Abstract

Background and objectives: AKI occurs frequently in older persons. Elevated circulating fibroblast growth factor-23 (FGF-23), a known marker of impaired mineral metabolism, may also reflect tubular dysfunction and risk of AKI. This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-to-creatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFRCrCyC), as risk factors for AKI in elderly individuals.

Design, setting, participants, & measurements: Plasma FGF-23, UACR, and eGFRCrCyC were measured in 3241 community-dwelling elderly individuals in the Cardiovascular Health Study. Hospitalization for AKI was defined by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Associations of each biomarker with AKI were evaluated using Cox proportional hazards models adjusted for demographics, cardiovascular risk factors, and biomarkers of kidney function.

Results: The mean participant age was 78 years; 60% of participants were women and 16% were African American. The median (interquartile range) values of biomarkers were as follows: FGF-23, 70 RU/ml (53, 99); UACR, 8.88 mg/g (4.71, 20.47); and eGFRCrCyC, 71 ml/min per 1.73 m(2) (59, 83). Hospitalized AKI occurred in 119 participants over 10.0 years of median follow-up. In fully adjusted analyses, compared with the lowest quartiles, the highest quartiles of FGF-23 (≥100 RU/ml) and UACR (≥20.9 mg/g) were associated with AKI (FGF-23: hazard ratio [HR], 1.99; 95% confidence interval [95% CI], 1.04 to 3.80; and UACR: HR, 3.35; 95% CI, 1.83 to 6.13). Compared with the highest quartile, the lowest quartile of eGFRCrCyC (<57 ml/min per 1.73 m(2)) was associated with AKI with an HR of 2.15 (95% CI, 1.21 to 3.82).

Conclusions: FGF-23 adjusted for albuminuria, cardiovascular disease risk factors, and baseline eGFR is independently associated with a higher risk of AKI hospitalizations in community-dwelling elderly individuals. Further studies to understand the nature of this association are warranted.

Figure 1.

Annual AKI event rate. The bar chart graphs the annual AKI incidence (number events per person-years at risk) by quartiles of FGF-23, eGFR_CrCyC, and UACR. eGFR_CrCyC, creatinine-cystatin C estimated GFR; FGF-23, fibroblast growth factor-23; UACR, urine albumin-to-creatinine ratio.

Figure 2.

Association of FGF-23, UACR, and eGFR_CrCyC with AKI. Splines plotting the unadjusted and fully adjusted relationship between FGF-23 (A), UACR (B), and eGFR_CrCyC (C) and hospitalization with AKI. Knots were placed at the quartiles. Dotted lines represent the 95% confidence intervals.

Figure 2.

Association of FGF-23, UACR, and eGFR_CrCyC with AKI. Splines plotting the unadjusted and fully adjusted relationship between FGF-23 (A), UACR (B), and eGFR_CrCyC (C) and hospitalization with AKI. Knots were placed at the quartiles. Dotted lines represent the 95% confidence intervals.