Abstract
Fibroblast growth factor23 (FGF23), an early marker of kidney dysfunction, is associated with cardiovascular death. Its role in HIV-positive individuals is unknown. We measured FGF23 in 100 HIV-negative and 191 HIV-positive nondiabetic adults with normal baseline estimated glomerular filtration rate (GFR). We measured GFR by iohexol annually, albumin-creatinine ratio (ACR) every 6 months, as well as pulse wave velocity, carotid plaque, and carotid intima media thickness (IMT) at baseline and 2 years. Progressive albuminuria was defined as follow-up ACR ≥2-fold than baseline and ≥30 mg/g. Regression models assessed associations of FGF23 with baseline factors and longitudinal changes in disease markers. FGF23 levels were similar in HIV serostatus. Among HIV-positive persons, factors independently associated with higher baseline FGF23 levels included female (adjusted ratio of geometric means [95% CI],1.46 [1.21,1.76]), serum phosphorus (1.20 [1.03,1.40]), HCV (1.31 [1.10,1.56]) and non-suppressed HIV RNA (1.27 [1.01,1.76]). At baseline, FGF23 was not associated with GFR, albuminuria, carotid plaque, or carotid IMT in cross-sectionally adjusted analysis of HIV-positive individuals. However, higher baseline FGF23 was associated with progressive albuminuria (odds ratio1.48 [95% CI]:1.05,2.08) and a more rapid increase in IMT (13 μm/year, 95% CI,3,24). These findings suggest a role for FGF23 in HIV-positive populations in identifying patients at greater risk for cardiovascular and kidney disease.
Highlights
Fibroblast growth factor-23 (FGF23) is a 32-kDa glycoprotein secreted by bone osteocytes and osteoblasts to circulate as an active full-length protein and shorter, inactive fragments [1,2]
CI, confidence interval; measured GFR (mGFR), glomerular filtration rate measured by iohexol disappearance from plasma; intima media thickness (IMT), intima-media thickness. a Estimates adjusted for sex, race, age, smoking, hypertension diagnosis, systolic blood pressure, and total cholesterol/high-density lipoprotein cholesterol ratio. b Carotid plaque defined as a focal area of intima-media thickening ! 1.5 mm or 50% thicker than the neighboring wall. c Progressive albuminuria defined as an albumin-creatinine ratio during follow-up that is at least 2-fold higher than the baseline values and ! 30 mg/g d Carotid plaque progression defined as detection of plaque in at least one new segment compared to baseline. doi:10.1371/journal.pone.0155312.t004. In this longitudinal study of non-diabetic individuals with clinically normal kidney function at baseline, we found no difference in baseline FGF23 levels in HIV-positive and demographically and clinically similar HIV-negative participants
We found that that among HIV-positive participants that higher FGF23 levels at baseline were associated with more rapid carotid IMT progression and with progressive albuminuria
Summary
Fibroblast growth factor-23 (FGF23) is a 32-kDa glycoprotein secreted by bone osteocytes and osteoblasts to circulate as an active full-length protein and shorter, inactive fragments [1,2]. It plays a central role in phosphate homeostasis by stimulating renal phosphate excretion via downregulation of sodium-dependent phosphate transporter 2a and 2c (NPT2a and NPT2c) in the renal proximal tubule [3,4].
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