7th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013)


MOPE076 - Poster Exhibition

Effects of renal tubular dysfunction on bone

L. Hamzah1, A. Samarawickrama2, L. Campbell1, M. Pope2, K. Burling3, A. Norden3, B. Hendry1, M. Fisher2, Y. Gilleece2, K. Walker-Bone2, F. Post1

1King's College London, London, United Kingdom, 2Brighton and Sussex University Hospital, Brighton, United Kingdom, 3Cambridge University Hospitals NHS Foundation Trust, Core Biochemical Assay Laboratory, Cambridge, United Kingdom

Background: Renal tubular dysfunction (RTD) is common in HIV positive patients. Impaired renal phosphate reabsorption in patients with RTD may affect bone turnover and bone mineralisation, although this relationship remains poorly defined. We analysed the associations of RTD with bone turnover and bone mineral density (BMD).
Methods: Urinary retinol-binding protein (RBP) was used to quantify RTD. RBP/creatinine ratio (RBPCR, reference range 0.12-2.93 µg/mmol) was measured in stored urine samples from fasted patients. Phosphate reabsorption was assessed by FEPO4, bone turnover by serum type 1 procollagen (P1NP) and carboxy-terminal collagen crosslinks (CTX) concentrations, and BMD by spine (L1-L4) and hip (neck of femur) DXA. Data were log-transformed as appropriate. Correlation coefficients and multivariate linear regression were used to evaluate relationships between variables.
Results: We studied 422 men (94% white ethnicity, 93% MSM, median time since HIV diagnosis 9.2 years, 94% on ARVs, mean CD4 count 621 cells/µL, 89% HIV RNA < 40 copies/mL). 65 patients (15.4%) had mild RTD (RBPCR 1-5xULN) and 22 (5.2%) had moderate/severe RTD (RBPCR >5xULN). RBPCR was associated with tenofovir exposure (β=0.4, p=0.017) and lower eGFR (β=-0.2, p< 0.0001) in analyses adjusted for age, time since HIV diagnosis, prior AIDS, nadir CD4, HIV RNA and other ARV use. RBPCR correlated with phosphate reabsorption (FEPO4, r2=0.26, p< 0.0001), spine BMD (r2=-0.16 p=0.001) and hip BMD (r2=-0.14 p=0.005), but not P1NP (r2=-0.02, p=0.62) or CTX (r2=0.01, p=0.82). Although RBPCR was associated with BMD in univariate analysis (spine: β=-0.018, p=0.002, hip: β=-0.013, p=0.005), adjustment for confounders (smoking status, previous fracture, steroid exposure, body mass index, eGFR and ARVs) weakened this association (spine: β=-0.011, p=0.05, hip: β=-0.008 p=0.05). When RTD was analysed as a categorical variable, moderate/severe RTD, compared to no RTD, was associated with reduced BMD of the spine (β=-0.097, p=0.006) but not of the hip (β=-0.041, p=0.12).
Conclusion: In this cross-sectional analysis, RBP-defined RTD was associated with reduced phosphate reabsorption but not with increased bone turnover. We found limited evidence that RTD associates with lower BMD, with the possible exception of patients with RBPCR >5xULN, in whom lower spinal BMD was observed.

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