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Background: Eldecalcitol (ELD) is an active vitamin D 3 analog that is widely used in Japan for the treatment of osteoporosis. The most common adverse drug reaction of ELD is hypercalcemia. However, few reports have focused on acute kidney injury (AKI) associated with ELD-induced hypercalcemia., Materials and Methods: We retrospectively reviewed the medical records at our hospital for cases of hypercalcemia-induced AKI between April 2013 and February 2018. Among them, we focused on patients who developed AKI secondary to ELD-induced hypercalcemia., Results: Among 69 patients who developed hypercalcemia-induced AKI, 32 patients (46.4%) developed AKI associated with ELD-induced hypercalcemia. Their mean age was 82 ± 5 years, 97% of them were female, mean corrected serum calcium level was 12.2 ± 1.5 mg/dL, serum creatinine level was 2.5 ± 2.2 mg/dL, and estimated glomerular filtration rate was 23.9 ± 14.4 ml/min/1.73 m 2 on admission. ELD administration was discontinued in all patients and some of them were treated with hydration with or without calcitonin, which was followed by a normalization of serum calcium level. Corrected serum calcium level on admission was significantly higher (p < .05) in patients treated with magnesium oxide. Although there were no significant differences, serum calcium and creatine levels on admission tended to be higher in patients who were treated with other drugs that affect renal hemodynamics and renal calcium metabolism than those not taking these drugs., Conclusions: Prescribers of ELD should regularly monitor serum calcium levels and kidney function to prevent hypercalcemia and AKI associated with ELD and pay more attention to concomitant drugs especially magnesium oxide.

Background: Hypercalcemia (HC) after kidney transplantation (KTx) can deteriorate both graft and patient survival. However, HC as a clinical condition and its clinical significance after KTx remain unknown. We evaluated the prevalence and risk factors of early HC after KTx., Methods: We performed a nested case-control study using a cohort of 100 KTx patients. KTx patients were divided into the HC and normocalcemia (NC) groups based on the baseline serum-corrected calcium (cCa) levels (≥ 10.5 and < 10.5 mg/dL) within 1 year after KTx., Results: Overall, the median value of maximum serum cCa level within 1 year after KTx was 10.1 (9.1-13.8) mg/dL. Of the 100 KTx patients within the cohort, 31 patients (31.0%) were classified as the HC group. The maximum serum cCa level was reached significantly earlier in the HC group compared with the NC group (2 vs. 4 months, p = 0.024). In univariate analysis, the risk factors of early HC after KTx were dialysis duration ≥ 10 years, serum cCa level the day before KTx, and cinacalcet administration before KTx. Among these risk factors, serum cCa level the day before KTx and cinacalcet administration before KTx were identified as significant independent risk factors of early HC after KTx in multivariate analysis., Conclusions: One-third of the KTx patients presented early HC within 1 year after KTx. Early HC after KTx resulted from persistent hyperparathyroidism. Therapeutic strategies to manage HC after KTx must be established.

Excess parathyroid hormone (PTH), known as primary hyperparathyroidism (pHPT), results in hypercalcemia and bone loss. Recent studies have shown that PTH is associated with the occurrence of hypertension in Western countries; however, controversy remains regarding high serum levels of PTH and calcium as risk factors for hypertension in Japanese patients. We retrospectively enrolled 114 consecutive Japanese patients who visited our hospital for examination and treatment of hypercalcemia and/or hypertension with serum calcium levels ≥ 9.8 mg/dL. To estimate the prevalence of hypertension, the patients were categorized according to calcium levels into hypercalcemic (10.2-13.4 mg/dL) and normocalcemic (9.8-10.1 mg/dL) groups, which were further categorized into high PTH (50-440 pg/mL) and low PTH (8-49 pg/mL) groups. The prevalence of hypertension was higher in patients with hypercalcemia than in patients with normocalcemia in both the high and low PTH groups. The prevalence of hypertension was higher in patients with high serum PTH levels than in patients with low serum PTH levels in both the hypercalcemic and normocalcemic groups. Logistic multiple regression analysis determined that serum calcium (P < 0.05) and PTH (P < 0.01) levels were positive contributors to hypertension. In conclusion, high serum levels of PTH and calcium are risk factors for hypertension in Japanese patients.

Deceased donor kidney transplantation in long-term dialysis patients in Japan has been increasing because of a severe lack of donors. Parathyroid glands of long-term dialysis patients often show qualitative morphological changes from diffuse to nodular hyperplasia. Only a few studies have reported the clinicopathological analysis of persistent hyperparathyroidism after kidney transplantation in long-term (>10 years) dialysis patients. This study on consecutive deceased donor kidney transplantation performed from 2002 to 2010 measured biochemical parameters related to bone and mineral disorders and examined parathyroid tissues in parathyroidectomy cases. Thirty-four subjects (22 males; mean age, 53.8 ± 7.9 years; mean dialysis period, 14.4 ± 4.3 years) were enrolled. Multivariate analysis of potential predictors for the hypercalcemia group at 12 months after transplantation showed that pre-transplantation and early post-transplantation calcium and parathyroid hormone levels were significant determinants. Pathological examination showed that a number of glands showed nodular hyperplasia, even in small glands weighing < 100 mg. In long-term dialysis patients, hyperparathyroidism and hypercalcemia developed at an early stage after transplantation and persisted for a long period (>4 years), with nodular hyperplasia being found even in low-weight parathyroid glands. Pre-transplant high calcium and parathyroid hormone levels were the predictors for the prolonged hypercalcemia. Persistent hyperparathyroidism was considered to be caused by remaining nodular hyperplasia, even if the glands were small. Although the best treatment option is to perform a parathyroidectomy in the waiting period before transplantation, we suggest that it be performed in cases with prolonged hypercalcemia of >6 months after transplantation., (© 2013 The Authors. Therapeutic Apheresis and Dialysis © 2013 International Society for Apheresis.)

Background: In patients on continuous ambulatory peritoneal dialysis (CAPD), dialysate calcium concentration has a strong influence on correction of serum calcium, phosphorus, and parathyroid hormone (PTH); however, the optimal concentration of Ca in PD solution is still uncertain. The aim of the survey reported here was to evaluate the prevalence of patients treated with standard- [SCD (approximately 3.25 - 4.0 mEq/L)] or low-calcium [LCD (approximately 1.8 - 2.5 mEq/L)] dialysate and differences in the clinical effects for correction of abnormalities in divalent ions and PTH., Materials and Methods: We used a questionnaire to survey 333 peritoneal dialysis facilities nationwide in Japan. Then, we analyzed serum Ca, P, and PTH levels and the prescription rates for CaCO(3) as a P binder and for vitamin D (VitD) analogs., Results: The 2384 CAPD patients enrolled in this analysis had a mean age of 60.5 +/- 14.2 years and a mean duration of CAPD of 44.1 +/- 39.2 months. The prevalences of SCD, LCD, and combination of SCD and LCD were, respectively, 49%, 50%, and 1% at initiation, and 40%, 38%, and 22% at the time of the survey. In 735 and 876 patients respectively, LCD and SCD had been prescribed from initiation to the time of the survey. In these two groups, we observed no difference in initiation and current serum levels of Ca and P. But prescription rates for CaCO(3) and VitD analogs were higher in the LCD group than in the SCD group, and PTH levels were higher in the LCD group than in the SCD group., Conclusions: A beneficial effect of LCD was revealed in the increased doses of CaCO(3) and VitD analogs seen in that group without the occurrence of hypercalcemia; however, PTH levels in that group were not maintained within an acceptable range. The survey suggests that more serious attention should be paid to the Ca concentration in peritoneal dialysate so as to lessen mineral and PTH disorders in CAPD.

Objective: Our objective was to determine the causes and relative prevalence of hypercalcemia in patients at a major community hospital in Okinawa, Japan. Additionally, we compared these causes of hypercalcemia with the previously published international data., Materials and Methods: We analyzed all patients with hypercalcemia in a community teaching hospital in Okinawa, Japan, from 1999 to 2002 and determined the cause of hypercalcemia in each patient. We also performed a literature review of the original articles describing causes of hypercalcemia in patients from Eastern as well as Western countries., Results: We identified 145 patients with hypercalcemia (median age, 69; range, 22 to 97). Major causes included malignant disorders (n=100; 69%), primary hyperparathyroidism (n=31; 21%), vitamin D-induced (n=4; 3%), and miscellaneous or unknown cause in 11 (8%). Among malignant disorders, adult T cell leukemia was the most frequent (n=35), being followed by lung cancer (n=25). Breast carcinoma was less prevalent (n=4)., Conclusion: The major causes of hypercalcemia are malignancy and primary hyperparathyroidism in Okinawan Japanese patients. Adult T cell leukemia and lung carcinoma are among the top leading malignancies, while breast carcinoma is less frequent in this patient population. The etiologic prevalence of hypercalcemia in the Eastern population including Okinawans is significantly different from that in the Western population.

There have been a number of reports over the last 15 years of patients with cancer who develop both leukocytosis and hypercalcemia, particularly in patients with cancers of the oral cavity. In this study, the authors report the frequency of hypercalcemia and leukocytosis in 225 patients with oral malignancies. Ten patients (4.4%) had hypercalcemia, 11 patients (4.9%) had leukocytosis, and five (2.2%) had both hypercalcemia and leukocytosis. The occurrence of these two distinct paraneoplastic syndromes in the same patients was greater than could have been expected from chance alone (chi-square = 45.8, P less than 0.0001). This study demonstrates that although hypercalcemia and leukocytosis are relatively uncommon in oral cancers, when they do occur they are frequently associated. To the knowledge of the authors, this is the first report in which the frequency of the association hypercalcemia and leukocytosis is studied in detail in large numbers of patients with oral cancer.

We made a retrospective review of the patients with cancer of the digestive organs who died between January 1, 1975 and December 31, 1985, at Shinshu University Hospital. Of 183 patients with such cancers 15 (8.2%) had hypercalcemia. Hypercalcemia was defined as serum calcium level greater than 11.0 mg/dl on at least two determinations. The incidence of hypercalcemia by site was 5 of 74 (6.8%) liver, 1 of 16 (6.3%) biliary tract, 4 of 33 (12.1%) pancreas, 3 of 15 (20.0%) esophagus, 0 of 37 stomach, 0 of 2 duodenum, 2 of 5 colon, and 0 of 1 rectum carcinomas. There was no sexual or age predisposition to hypercalcemia. Bone scans and/or x-ray results were positive in three of eight, negative in five of eight, and were not evaluated in the remaining seven patients. Of five patients tested, four had low to normal serum parathyroid hormone (PTH) levels, and one had a serum PTH level high by C-terminal assay but normal by N-terminal assay. Serum chloride levels at the late stage of hypercalcemia were less than 102 mEq/L in all patients. Therefore, hyperproduction of PTH was unlikely to be a causative factor for hypercalcemia. Indomethacin was given to four patients with hypercalcemia with no effect on serum calcium levels in any cases. Survival from the diagnosis of hypercalcemia ranged from 2 to 96 days (mean 33 days). We conclude that hypercalcemia is a complication not infrequent at the late stages of cancers of the digestive organs, with the exception of gastric cancer, and a portent of a poor prognosis.