Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Novel insights into the renal-bone axis in thalassemia major (#115)

Phillip Wong 1 2 3 , Frances Milat 1 2 4 , Peter J Fuller 1 2 3 5 , Matthew T Gillespie 4 , Danielle Oh 6 , Vicky Kartsogiannis 4 , James Doery 7 , Donald Bowden 6 , Sant Rayn Pasricha 6 8 , Ken Lau 2 9
  1. Endocrinology, Monash Health, Melbourne, Victoria, Australia
  2. Medicine, Monash University, Melbourne, Australia
  3. Endocrinology, PHI-MIMR Institute of Medical Research, Melbourne, Victoria, Australia
  4. Endocrinology, PHI-MIMR Institute of Medical Research, Melbourne, Victoria, Australia
  5. Biochemistry and Molecular Biology, Monash University, Melbourne, Victoria, Australia
  6. Thalassaemia Unit, Monash Medical Centre, Melbourne, Australia
  7. Pathology, Monash Health, Melbourne, Victoria, Australia
  8. MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Oxford University, Oxford, United Kingdom
  9. Radiology, Monash Health, Melbourne, Victoria, Australia
β-thalassemia major is a disorder of red blood cell production requiring chronic transfusion and  iron chelation to prevent iron toxicity and multi-organ disease. Bone disease is common with marrow expansion, iron toxicity and endocrinopathies contributing to low bone mineral density (BMD) and fractures.  Recently, reports of renal tubulopathy and hypercalciuria have raised concerns of a renal role in accelerated bone loss in this cohort. In a retrospective study, we reported that 18.1% of patients with β-thalassemia major had symptomatic renal tract calculi and identified an association between urolithiasis and low BMD. To determine the true prevalence and chemical composition of urolithiasis and its association to BMD in patients with β-thalassemia major, we investigated 27 subjects presently asymptomatic for stone disease. All subjects underwent an initial single energy CT of the renal tract, and if a calculus was detected, dual-energy data was acquired, enabling derivation of its chemical composition from a standardised atomic number plot. Synchronous serum and urine biochemistry were measured and BMD determined. Urolithiasis was present in 16/27 (59%). Affected patients generally had multiple stones, often of varying composition, with struvite (33.3%), calcium oxalate (31.3%) and cysteine (21.6%) stones being the most prevalent. Hypercalciuria was present in 77.8% of subjects, and those with calcium-containing urolithiasis had dramatically reduced femoral neck BMD compared to non-calcium stone formers (z score -2.40 vs -0.2, P=0.04). The unusually high prevalence of cysteine stones and its association with renal tubulopathy warrants further investigation. This study confirms the prevalence of urolithiasis in β-thalassemia major to be 10 fold that of the general population. It raises questions about the pathophysiology of urolithiasis and highlights the importance of the renal-bone axis in the management of bone disease in this condition.