A New Disease Concept in the Age of Processed Foods—Phosphorus-Burden Disease; CKD–MBD Concrete Analysis and the Way to Solution

In 2012, the Japanese Society for Dialysis Therapy (JSDT) established the order of correction of P, corrected Ca (cCa), and whole PTH (w-PTH) in the treatment of Chronic Kidney Disease-Metabolic Bone Disorder (CKD-MBD) as P-first. However, there is no report that analyzes whether this rule is in line with reality and what the adequate rate of P is. Therefore, we analyzed the test values of our 48 patients during the year of 2019 and examined the validity of the results. The results showed that the adequate range rates were 70.8% for P, 100% for cCa, and 89.6% for w-PTH. This result is better than the JSDT Web-based Analysis of Dialysis Data Archives (WADDA) P adequacy rate of 66.2%. Although the guideline is P-first, it is often the case that we cannot reach the adequate level; therefore, healthcare professionals and patients often blame each other. We believe that this is due to the mismatch between the modern era of processed foods covered with P additives and treatment methods (P intake restriction and P-binders). The development of processed foods with P additives has brought light and darkness to mankind. The light side is freedom from starvation, and the dark side is a new condition caused by P burden: P burden disease (CKD-MBD).

P1402USE OF ROMOSOZUMAB FOR OSTEOPOROSIS IN HEMODIALYSIS PATIENTS

Background and Aims Recently, the importance of osteoporosis and chronic kidney disease-mineral bone disorder (CKD-MBD) has been highlighted as a cause of increased fracture risk in dialysis patients. However, many osteoporosis drugs require careful administration or are contraindicated in dialysis patients, and evidence for their use in dialysis patients is scarce. Here, we administered the new human anti-sclerostin antibody preparation romosozumab to hemodialysis patients with osteoporosis, and examined changes in bone density, bone metabolism markers and other values. Method Romosozumab was administered once per month to 12 hemodialysis patients (mean age: 72.6 ± 9.4 years old; 4 males, 8 females) who were diagnosed with osteoporosis while visiting our hospital and who had no history of cardiovascular complications in the preceding year. Bone density YAM value was measured every 3 months by dual energy X-ray absorptiometry (DXA). TRACP-5b, BAP, P1NP and whole-PTH values were measured every month as bone metabolic markers. Values at the start of observation were regarded as pre-dosing values and the mean values during the 6 months after administration were measured as post-treatment values. The results were then compared. Results At 6 months after the start of treatment, no change was seen in bone density of the proximal femur compared to the pre-dosing value. In contrast, lumbar spine bone density YAM value (%) was significantly improved, from 63.8% ± 9.4% to 70.9% ± 5.2% (P = 0.012). Regarding bone metabolism markers, mean value of bone resorption marker TRACP-5b after the start of administration did not significantly differ from that at the start of observation. BAP value increased significantly from 16.2 ± 8.7 to 25.2 ± 11.0 (p < 0.01) while whole-PTH significantly increased from 103.5 ± 52.8 to 236.1 ± 100.8 (p < 0.01). In addition, serial time changes for each bone metabolic marker, whole-PTH value, and corrected Ca value during the observation period are also reported. Conclusion Romosozumab may improve bone density in dialysis patients with osteoporosis.

P0886EFFICACY AND SAFETY OF EVOCALCET IN PERITONEAL DIALYSIS PATIENTS: A SINGLE CENTER LONGITUDINAL STUDY IN JAPAN

Background and Aims Calcimimetic agent is used for secondaryhyperparathyroidism (SHPT), but it might cause gastrointestinal side-effects. These side effects are severe problem for PD patients with gastrointestinal symptoms due to dialysis fluid storage. Evocalcet is a new calcimimetic agent for SHPT, and expected to reduce gastrointestinal related symptoms. There have been some reports about switching from cinacalcet to evocalcet or administered for HD patients. However, there have been few reports on PD patients. Here, we reported the efficiency and safety of evocalcet in PD patients. Method PD patients who had newly started to treat for SHPT with evocalcet, between August 2018 to August 2019 were selected. Patients who died or transferred to HD within 6 months after administered evocalcet were excluded. We compared the changes in whole PTH level, serum phosphorus level and serum corrected calcium level with baseline and after administration. Moreover, we investigated adverse events of gastrointestinal related symptoms. Results Overall, 34 PD patients were included, (mean age: 67.5 years old, male/female: 23/11, average PD vintage: 39.6 months, serum phosphorus level: 5.1 ± 1.0 mg/dl). There was a significant reduction in whole PTH at week 16 from baseline (346 ± 187 pg/ml vs 258 ± 196 pg/ml, p <0.001), and this relation was continued at week 32. There was no significant change in serum phosphorus level during this study. Serum corrected calcium level was the lowest at week 12 from baseline (9.4±0.7 mg/dl vs 9.0±0.1 mg/dl: p=0.004), thereafter, serum calcium level was not decline with adjustment of vitamin D receptor activators and calcium preparation. Adverse events were observed in 6 patients (18.2 %), nausea occurred in 3 patients, decreased appetite occurred in 2 patients, and diarrhea occurred in 2 patients. Although some adverse events had occurred, all patients continued study. Conclusion These results suggested that evocalcet might be efficient and safety in PD patients with SHPT.

P0894AEFFECTS OF DENOSUMAB ON BONE MINERAL DENSITY AND LOW ENERGY FRACTURES IN KIDNEY TRANSPLANT PATIENTS: SAFE AND EFFECTIVE

Background and Aims Fractures are a disabling clinical outcome after kidney transplantation (KTx), with incidence 5 to 34 times higher expected in males and females, respectively. Denosumab, a fully human monoclonal antibody that binds to RANKL with high affinity and specificity, blocking the interaction of RANKL with RANK, mimicking the endogenous effects of osteoprotegerina, increase bone mineral density; however, its effects to reduce the risk of vertebral fractures and ameliorate BMD remain undefinite in the KTx. Method Thirteen kidney recipients (aged from 50 to 79 yy, 6.2 + 5.5 (SD) yy after KTx), 6 M and 7 F (all postmenopausal) with nearly normal renal function (creat. 1.1+-0.31 mg/dl), affected by low energy vertebral fractures (21 dorsal and 1 lumbar vertebrae), evaluated by morphometric X-ray absorptiometry (Hologic DQR-4500A), were treated with denosumab (four 60-mg doses of denosumab Q6M) over 24 months. Data for vertebral heights and height ratios (P-A), covering 9 vertebral bodies were obtained, besides the data of vertebral, femural and radius BMD.The immunosuppressive regimen consisted of CNI (TAC or CsA), MMF and 8 out of 13 patients were still taking prednisone. Bone mineral metabolism parameters (whole-PTH, 25OHD3 and alcaline phosphatase) were also evaluated. Results No sides effects were observed, and all Patients concluded the study.After two years of denosumab treatment, we observed a significative reduction of vertebral T-score (from -2.12 +- 0.35 (SE) to -1.67+-0.35; p< .02), while T score of femural and radius did not show significative variation (-1.86+-0.21 versus -1.84+- 0.23 and -3.04+-0.42 versus -3.19+-0.45, respectively). The number of low energy vertebral fractures, basal versus two years control, had increased for only two dorsal vertebral fractures. However, to one of two subjects, with new dorsal vertebral fractures, was administered high dose of methylprednison for a severe kidney reject. No variations were observed in whole-PTH (89.31+-19.9 versus 68.38+-9.8 pg/ml), 25OHD3 (24.02+-2.75 versus 26.67+-2.29 ug/dl) and alcaline phosphatase (78.46+-12.73 versus 56.77+-7.14 UI). Conclusion Treatment with denosumab improve BMD at vertebral site in KTx, despite continuous steroid therapy and reduce the risk of new low energy vertebral fractures