Fibroblast growth factor 23 in hypophosphataemic HIV‐positive adults on tenofovir

Abstract

Objectives Hypophosphataemia is common in HIV‐positive patients, in particular in those using tenofovir disoproxil fumarate (TDF). Its pathogenesis is not well understood. The importance of fibroblast growth factor 23 (FGF‐23), the most potent phosphaturic hormone known today, has not been studied in these patients. The aim of the study was to investigate whether FGF‐23 might be involved in the aetiology of hypophosphataemia in HIV‐positive patients on tenofovir. Methods Calcium and phosphate metabolism was studied in 36 HIV‐positive patients on TDF. Hypophosphataemia was defined as a serum phosphate level < 0.75 mmol/L. Results Fifteen patients (42%) had hypophosphataemia (group 1), and 21 had a normal serum phosphate level (group 2). The renal phosphate reabsorption threshold [tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/gfr)] was significantly lower in group 1 than in group 2 (0.58 ± 0.04 vs. 0.91 ± 0.03 mmol/L, respectively; P < 0.0001). The serum phosphate concentration was strongly correlated with TmP/gfr (R = 0.71; P < 0.0001). Both groups had normal serum FGF‐23 levels, and serum phosphate and TmP/gfr were not related to serum parathyroid hormone (PTH) or FGF‐23 levels. Conclusion FGF‐23 is not involved in the pathogenesis of hypophosphataemia in HIV‐positive patients on TDF. The data suggest that a PTH‐like factor may be involved.

Association of Higher Plasma Vitamin D Binding Protein and Lower Free Calcitriol Levels with Tenofovir Disoproxil Fumarate Use and Plasma and Intracellular Tenofovir Pharmacokinetics: Cause of a Functional Vitamin D Deficiency?

“…FGF23 concentrations did not differ between TDF treatment groups, consistent with other studies (18,42), but the highest quintile of tenofovir diphosphate was associated with lower FGF23 concentration. FGF23, produced in osteocytes and osteoblasts, is increased in response to elevations in dietary and serum phosphorus (43) and in response to increased 1,25-OH(2)D (44) ( Table 1).…”

“…TDF use is associated with decreased bone mineral density (2)(3)(4)(5)(6), possibly caused by TDF-induced phosphaturia (7)(8)(9)(10)(11)(12)(13)(14) with accompanying hypophosphatemia and osteomalacia (15)(16)(17). The phosphaturic hormone fibroblast growth factor 23 (FGF23) is not altered by TDF use (18,19). TDFassociated bone changes may occur through a TDF effect on parathyroid hormone (16,20), as parathyroid hormone secretion increases soon after initiating TDF (21).…”

“…TDF may induce a state of functional vitamin D deficiency (24), or a parathyroid hormone-like factor may cause these TDF-associated metabolic changes (18) Table 1). The association between TDF use and vitamin D binding protein (VDBP), which could alter free 1,25-OH(2)D and affect circulating parathyroid hormone concentration, total 1,25-OH(2)D, and bone density, has not been assessed.…”

Tenofovir monotherapy for hepatitis B after 1 year does not produce renal dysfunction, but is associated with hyperparathyroidism not related to vitamin D

“…Some studies have associated the presence of high levels of PTH in TDF-treated patients and its relationship with bone metabolism, race, and vitamin D, mainly in HIV patients [11,12,14,48]. Nevertheless, data on the relationship between hepatitis B-infected patients and levels of PTH are scarce, and favor a relationship with hypovitaminosis D rather than TDF alone [49].…”

Avaliação de marcadores de lesão do túbulo proximal renal e incidência de redução da filtração glomerular em pacientes portadores de Hepatite B em uso de tenofovir

“…(Bech et al, 2012). Em um estudo envolvendo 542 pacientes portadores de hepatite B em monoterapia com TDF, onde se avaliou a segurança do uso desta medicação com duração de três anos de seguimento, apenas 0,4% dos pacientes desenvolveram elevação de creatinina sérica superior a 0,5 mg/dl e apenas 0,7% dos pacientes acusaram hipofosfatemia < 2 mg/dl.…”