24-25-dihydroxyvitamin-d-3 and Sarcoidosis

Excessive vitamin D causes marked and prolonged hypercalcemia by accelerating intestinal calcium absorption and bone resorption. Vitamin D induced hypercalcemia includes the toxic ingestion of excessive amount of vitamin D preparations, granulomatous diseases and lymphoproliferative malignancies. In vitamin D toxicity, the clinical courses vary depending on the vitamin D preparation responsible for the hypercalcemia. Hypercalcemia state continues for several months when D2 or D3 are responsible for the toxicity whereas the hypercalcemia would subside in a week when 1 alpha(OH) D3 or 1,25 (OH)2D3 are responsible for the toxicity. Abnormal calcium metabolism can be treated by hydration and glucocorticoids. Hypercalcemia is associated with variety kinds of granulomatous diseases, including sarcoidosis and tuberculosis. The granulomatous tissue is believed to be the site of the ectopic production of 1,25(OH)2D3 in which the regulation of the synthesis is quite different from that in the normal kidney. Glucocorticoid markedly diminishes the synthesis. Hypercalcemia associated with elevated serum 1.25(OH)2D3 levels is also found in patients with lymphomas and some other malignancies. However, there still are not sufficient evidences to prove that the excessive amount of endogenous 1.25(OH)2D3 is the primary cause of the hypercalcemia.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Humans; Hypercalcemia; Sarcoidosis; Tuberculosis; Vitamin D

In sarcoidosis, renal involvement includes hypercalcemia-related nephrocalcinosis and granulomatous tubulointerstitial nephritis. Hypercalcemia is thought to be due to increased production of 1,25 dihydroxyvitamin D (1-25D), but 1-25D levels have not been evaluated in sarcoidosis patients with renal dysfunction.. We enrolled 9 sarcoidosis patients who underwent renal biopsy, and compared the serum 1-25D concentration and eGFR with those in 428 non-sarcoidosis patients who had renal dysfunction (stage 2 or higher CKD with an estimated glomerular filtration rate < 90).. Serum calcium and 1-25D levels were significantly higher in the sarcoidosis patients than in the non-sarcoidosis patients (p < 0.01 and p = 0.01, respectively). There was a positive correlation between 1-25D and eGFR in the patients without sarcoidosis (r = 0.693; p < 0.01). As the renal function of sarcoidosis patients was improved by steroid therapy, the serum 1-25D and adjusted serum calcium levels decreased to near the median values in non-sarcoidosis patients. On renal biopsy, CD68 staining was positive for tissue macrophages in all 8 patients who had tubulointerstitial nephritis (with or without typical granulomas), while Von Kossa staining showed calcification of tubules near or inside granulomas in 6 of these 8 patients.. While tissue macrophages promote development of tubulointerstitial nephritis and 1-25D overproduction in renal sarcoidosis, hypercalcemia secondary to elevation of 1-25D may be related to renal calcification and granuloma formation.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biopsy; Calcium; Cohort Studies; Female; Glomerular Filtration Rate; Humans; Hypercalcemia; Kidney; Kidney Diseases; Macrophages; Male; Middle Aged; Nephritis, Interstitial; Retrospective Studies; Sarcoidosis; Steroids; Young Adult