Naoya Toriu1,2, Keiichi Sumida3, Masahiko Oguro3, Yoichi Oshima3, Hiroki Mizuno3, Eiko Hasegawa3, Tatsuya Suwabe3, Masahiro Kawada3, Toshiharu Ueno3, Noriko Hayami3, Akinari Sekine3, Rikako Hiramatsu3, Masayuki Yamanouchi3, Junichi Hoshino3, Naoki Sawa3, Kenmei Takaichi3,4, Kenichi Ohashi5,6, Keiichi Kinowaki5, Takeshi Fujii5, Ryosuke Date7, Yoshifumi Ubara8,9,10. 1. Nephrology Center, Toranomon Hospital, Tokyo, Japan. ntoriu@kuhp.kyoto-u.ac.jp. 2. Nephrology Center, Toranomon Hospital Kajigaya, 1-3-1, Takatsu, Kawasaki, 212-0015, Kanagawa, Japan. ntoriu@kuhp.kyoto-u.ac.jp. 3. Nephrology Center, Toranomon Hospital, Tokyo, Japan. 4. Okinaka Memorial Institute for Medical Research, Tokyo, Japan. 5. Department of Pathology, Toranomon Hospital, Tokyo, Japan. 6. Department of Pathology, Yokohama City Hospital, Kanagawa, Japan. 7. Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan. 8. Nephrology Center, Toranomon Hospital, Tokyo, Japan. ubara@toranomon.gr.jp. 9. Okinaka Memorial Institute for Medical Research, Tokyo, Japan. ubara@toranomon.gr.jp. 10. Nephrology Center, Toranomon Hospital Kajigaya, 1-3-1, Takatsu, Kawasaki, 212-0015, Kanagawa, Japan. ubara@toranomon.gr.jp.
Abstract
INTRODUCTION: 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. MATERIALS AND METHODS: 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). RESULTS: 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. CONCLUSION: 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.
INTRODUCTION: 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 sarcoidosispatients with renal dysfunction. MATERIALS AND METHODS: We enrolled 9 sarcoidosispatients who underwent renal biopsy, and compared the serum 1-25D concentration and eGFR with those in 428 non-sarcoidosispatients who had renal dysfunction (stage 2 or higher CKD with an estimated glomerular filtration rate < 90). RESULTS: Serum calcium and 1-25D levels were significantly higher in the sarcoidosispatients than in the non-sarcoidosispatients (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 sarcoidosispatients was improved by steroid therapy, the serum 1-25D and adjusted serum calcium levels decreased to near the median values in non-sarcoidosispatients. 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. CONCLUSION: 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.