Comparisons of Parathyroid Klotho and FGFR1 Expression Between End-Stage Renal Disease Patients and Renal Transplant Recipients with Hyperparathyroidism

Abstract

Recently, fibroblast growth factor 23 (FGF23), the phosphaturic hormone, has been ascertained to be increased in the patients with chronic kidney disease and end stage renal disease for a compensation of phosphate level. In parathyroid glands, FGF23 exerts its effect by binding to its cognate FGF receptor 1 (FGFR1) in the presence of its co-receptor Klotho, and FGF23 directly inhibit parathyroid hormone. However, in secondary hyperparathyroidism, ‘FGF23 resistance’ aggravates parathyroid cell proliferation. Tertiary hyperparathyroidism means the persistence of severe secondary hyperparathyroidism from dialysis into the post transplant period. We compared with expression of FGFR1 and Klotho in parathyroid tissue after parathryoidectomy owing to severe persistent hyperparathyroidism between renal allograft recipients and end stage renal disease patients. Methods: Hyperplastic parathyroid glands were obtained from dialysis patients and renal allograft recipients who underwent total parathyroidectomy with autotransplantation. We measured the expression of Klotho, FGFR1 by immunohistochemistry in 8 allograft recipients with persistent hyperparathyroidism after transplantation and 11 uremic patients with secondary hyperparathyroidism who underwent dialysis. Immunoreactivity was assessed semiquantitiatively. Results: FGFR1 expression in uremic patients was more decreased than that in renal allograft recipients (6.18 ± 7.26 vs. 3.00 ± 2.97 positive cell per area). But, Klotho expression was increased in uremic patients and renal allograft recipients compared with normal glands. Positive cell area of Klotho expression was 52.42 ± 16.63 % and 47.62 ± 14.04 % in uremic patients and renal allograft recipients. Klotho expression was decreased in renal allograft recipients compared with uremic patients, but there was not significant statistically. (P value 0.29) A significant positive correlation was observed between FGFR1 and serum phosphate level (r2= 0.410, P value 0.035), FGFR1 and serum calcium x phosphate products (r2= 0.509, P value 0.047) in renal allograft recipients. FGFR1 expression was found to be negatively correlated to serum creatinine. (r2= -0.819, P value 0.002). But, Klotho expression on parathyroid hyperplastic tissue in renal allograft recipients was not correlated to the serum phosphate, serum calcium, serum calcium x phosphate products, intact PTH and renal function. Conclusion: Klotho and FGFR1 expression is a discrepancy in hyperplastic glands from patients with secondary and tertiary hyperparathyroidism in this study. Expression of Klotho in parathyroid glands is not different with two groups, and the cause of this result may be explained a pleotrophic effect of Klotho protein. This result also suggested that change of FGFR1 expression in hyperplastic glands can explain ‘FGF23-resistance’ in secondary and tertiary hyperparathyroidism rather than Klotho parathyroid expression.