Evaluation of FGF-23 and alpha-klotho levels in patients with sarcoidosis

Introduction: Sarcoidosis is a systemic granulomatous disease of unknown origin. The most commonly held structures are the intrathoracic lymph nodes and the lungs, but every organ can be involved. Studies have reported hypercalcemia in 2-10%of patients with sarcoidosis and hypercalciuria in 40%. They have been reported to cause kidney stones, nephrocalcinosis, and kidney damage if not detected and corrected early. In its pathology, it is thought that 1-alpha hydroxylase production and activation as well as 1,25-hydroxy vitamin D production from active macrophages take place. FGF-23 and alpha klotho proteins are proteins that play a key role in the bone-parathyroid-kidney axis, regulation of phosphate and calcium metabolism, and vitamin D metabolism. FGF-23 is a protein mainly expressed in osteocytes and in low amounts in other tissues. Its three main functions are; it inhibits phosphate re-uptake from the proximal tubule, reduces 1,25(OH)2D3 and PTH levels by inhibiting 1-alpha hydroxylase in the kidney and activating 24-hydroxylase. Alfa klotho acts as a cofactor for FGF-23-mediated receptor activation. It also improves the calcium reabsorption by enzymatically modifying the TRPV5 sugar chains in situ. It also plays a direct role in the synthesis of PTH. In this study, we evaluated serum FGF-23 and alpha klotho levels in patients with sarcoidosis. We aimed to demonstrate the effects of pathologic conditions on bone metabolism and the occurrence of vascular calcification since vitamin D can be activated in non-kidney patterns and hypercalcemia and hypercalciuria can be seen in these patients. Materials and Method: The study was designed as a prospective case-control study. The study included 42 patients with an age of 18 years or older diagnosed with sarcoidosis and 42 healthy volunteers who were admitted to the service and outpatient clinics of Pulmonary Diseases, Nephrology and Internal Medicine of Düzce University Medical Faculty Hospital between May 2017 and December 2017. One person from the control group was excluded from the study as one of the exclusion criteria was revealed. The study was completed with 42 patients and a control group of 41 patients. Age, gender, comorbidity informations, BMD measurement data within the last 6 months, 24 hour urine and blood samples were taken from the patient and control groups. Results: The proportion of female to male participants was similar and age was similar. The levels of calcium, phosphorus and calcium in the 24 hour urine were found significantly higher in the patient group in terms of mean values. PTH levels were significantly lower in patients with sarcoidosis. There was no significant difference between the bone mineral density of the study and control groups. FGF-23 and alpha klotho levels were significantly higher in the patient group. There was a positive correlation between FGF-23 and alpha klotho. A negative correlation was found between FGF-23 and urea levels while positive correlation was found between alpha klotho and L1-L4 T-score. Discussion: In our study, serum calcium, 24-hour urine calcium and serum phosphorus levels were found significantly higher in the study group compared to the control group and serum PTH was found significantly lower in the sarcoidosis group. FGF-23 and alpha klotho levels were significantly higher in sarcoidosis group and positive correlations were found between FGF-23 and alpha klotho levels. These results suggested that there may be a relationship between sarcoidosis progression and FGF-23 and alpha klotho levels. Positive correlation between alpha klotho and L1-L4 T score in all groups suggests that alpha klotho may be associated with osteoporosis. Significant values were found in our study that are consistent with current studies. We hope that our work will shed light on the broader and more controlled work to be done in this regard. Keywords: Sarcoidosis, FGF-23, alpha klotho