Effects of cimetidine on maintenace hemodiaiysis patients

Six years ago, we administered 1α-hydroxycholecalciferol (1α-OH-D₃) to maintenance hemodialysis patients, using a dialysate with a calcium concentration of 6.0mg/dl for prevention and treatment of disturbance of Ca metabolism and renal osteodystrophy.<br>In these patients, we observed hyper-PTH-nemia and 1α-OH-D₃ hypersensitivity, which were resistant to the above therapy.<br>In the present study we treated these patients by administration of cimetidine (histamine H₂ receptor antagonist). Cimetidine was administered orally at a dose of 400mg/day. For convenience, we divided the patients into three groups: Group I (hyper-PTH-nemia), Group II (hyper-PTH-nemia+1α-OH-D₃ hypersensitivity) and Group III (1α-OH-D₃ hypersensitivity).<br>Group I (3 cases): Cimetidine decreased the PTH level in case 1 from 8.31 to 2.45ng/ml, in case 2 from 7.76 to 3.14ng/ml and in case 3 from 7.31 to 4.81ng/ml. Cimetidine did not change the levels of T-Ca, Ca⁺⁺, P, AI-P or the dose 1α-OH-D₃. In two cases, an increase in MCI and BMC/BW and prolongation of the half-lives of MCI and BMC/BW were observed.<br>Group II (one case): Cimetidine decreased the PTH level from 17.66 to 6.33ng/ml. The dose of 1α-OH-D₃ could be increased from 0.5 to 2.0γ/day, thereby, enabling its stable administration. Bone pain disappeared, enabling the patient to walk independently. However, the decrease in MCI and BMC/BW could not prevented.<br>Group III (4 cases): Cimetidine allowed an increase in the dose of 1α-OH-D₃ from 0.5 to 3.0γ/day in case 1, from 0 to 1.5γ/day in case 2, from 0 to 3.0γ/day in case 3 and from 1.0 to 2.0γ/day in case 4. Thus, stable administration of 1α-OH-D₃ was realized. In cases 3 and 4, bone pain disappeared, thereby enabling independent walking. In both cases, MCI and BMC/BW increased.<br>Conclusion<br>(1) In hyper-PTH-nemia, cimetidine administration decreased PTH levels and did not change the levels of T-Ca, Ca⁺⁺, P, and AI-P or the dose of 1α-OH-D₃. Cimetidine increased MCI and BMC/BW and prolonged the half-lives of MCI and BMC/BW. (2) Cimetidine improved the hypersensitivity to 1α-OH-D₃. Therefore, cimetidine administration could make it possible to increase the dose of 1α-OH-D₃ and 1α-OH-D₃ administration could be stable. (3) In secondary hyperparathyroidism, cimetidine administration may be a more effective treatment than parathyroidectomy.