COMPLICATIONS - METABOLIC

S. Borstnar¹, D. Kovac², B. Erzen³, T. Stopar⁴, T. Kocjan⁵, A. Kandus^6
1Clinical Department Of Nephrology, University Medical Centre Ljubljana, Ljubljana/SLOVENIA, ²Department Of Nephrology, University Medical Centre, Ljubljana/SLOVENIA, ³Department Of Vascular Disease, University Mediacl Centre Ljubljana, Ljubljana/SLOVENIA, ⁴Department For Nuclear Medicine, University Medical Centre Ljubljana, Ljubljana/SLOVENIA, ⁵Department Of Endocrinology, Universty Medical Centre Ljubljana, Ljubljana/SLOVENIA, ⁶Department Of Nephrology, University Medical Centre Ljubljana, Ljubljana/SLOVENIA

Body: Introduction. Hyperparathyroidism can persist for many years in 10-50% of patients after successful kidney transplantation and can harmfully affect graft function and bone metabolism. Calcimimetic cinacalcet offers a new treatment option in hyperparathyroidism after kidney transplantation. It is a well established treatment in the dialysis population but data in kidney transplantation is still sparse, especially regarding its influence on bone mineral density. The aim of this study was to analyze the influence of cinacalcet on hyperparathyroidism, calcemia and bone mineral density in kidney transplant recipients. Methods. Eleven patients (4 men, 7 women, aged 39 to 64 years) were included in this prospective clinical study. The inclusion criteria were intact parathyroid hormone (iPTH) >65 ng/l, serum creatinine concentration <200 μmol/l, stable kidney graft function and more than one year after kidney transplantation. Patients were not treated in the past and during the study with drugs that can have an impact on bone density (bisphosphonates, calcitonine). The study consisted of a 6 month observation period to certify the stability of measured parameters and a 12 month treatment period during which 30 mg/day of cinacalcet was used. Parameters of bone mineral metabolism (serum concentrations of calcium, phosphate, iPTH, 25-OHD3, osteocalcin, collagen degradation fragments, receptor activator of NF-kappa B ligand (RANKL), activity of bone specific alkaline phosphatase (AF), urinary calcium excretion) and bone mineral density (measured by double x-ray densitometry) were followed during the study. Results. During the observation period no measured parameter changed significantly. During the treatment period calcium concentration decreased significantly in the first month (m) of treatment and remained so during the whole study period (from 2.50±0.10 mmol/l at time 0 to 2.32±0.11 mmol/l at 12 m) (p<0.001). Serum iPTH decreased significantly in the first month of treatment (from 275±95 ng/l to 202±56 ng/l) but increased gradually thereafter. Concentration of serum phosphate, osteocalcin, RANKL and activity of AF did not change significantly during the treatment period. Collagen degradation fragments increased significantly during the treatment period (from 6186±3150 pmol/l at time 0 to 9455±7228 pmol/l at 12 m) (p<0.05). The concentration of 25-OH D3 was 51.7±21.7nmol/l and remained unchanged after 12 m. Urinary calcium/creatinine ratio was 0.27±0.23 at time 0 and did not changed significantly during the treatment period. Bone mineral density at lumbar spine, hip and forearm did not change during 12 m of cinacalcet treatment. Serum creatinine remained unchanged during the study period (107±45 μmol/l at time 0 and 115±62 μmol/l at 12 m). One patient stopped taking cinacalcet because of nausea and vomiting and was excluded from the analysis. Conclusions. Treatment with cinacalcet 30 mg/day in kidney transplant recipients resulted in a significant decrease of serum calcium concentration and a transient decrease of iPTH concentration. Collagen degradation products increased during the treatment period but other markers of bone metabolism remained unchanged. Twelve months of treatment with cinacalcet did not result in a significant change of bone mineral density.

Disclosure: All authors have declared no conflicts of interest.