Comparison of serum alkaline phosphatase levels between two measurement methods in chronic hemodialysis patients in Japan: involvement of ABO blood group system and relationship with mortality risk.

BACKGROUND: Elevated serum alkaline phosphatase (ALP) levels are a risk factor for all-cause mortality in hemodialysis patients. Traditionally in Japan, ALP measurements were conducted using the JSCC method, which yields higher ALP measurement values than the IFCC method, mainly due to its increased sensitivity to intestinal ALP. METHODS: Serum total ALP levels before and after switching the assay method from JSCC to IFCC were compared among different blood types in 521 hemodialysis patients (Study 1). The association between ALP levels measured by the JSCC method and 7-year mortality was analyzed, including blood types and liver function parameters as covariates, in 510 hemodialysis patients (Study 2). RESULTS: ALP levels measured by the JSCC method were approximately three times higher than those measured by the IFCC method, with significant elevation in patients with blood types B and O compared to those with blood types A and AB. Similarly, ALP levels measured by the IFCC method were significantly higher in patients with blood types B and O compared to those with blood types A and AB (Study 1). The highest tertile of ALP levels showed a significantly increased risk of all-cause mortality, even after adjusting for patient background. However, this significance disappeared when serum liver function-related or inflammatory markers were included as covariates (Study 2). CONCLUSION: ALP levels measured by the JSCC method are associated with life prognosis, but caution should be exercised due to their elevation in patients with blood types B and O and in those with hepatic dysfunction or inflammation.

Association between phosphate binder pill burden and mortality risk in patients on maintenance hemodialysis: a single-center cohort study with 7-year follow-up of 513 patients.

BACKGROUND: Dialysis patients often take multiple oral medications, leading to a high pill burden. Phosphate binders (PBs) account for a large proportion of this daily pill burden (DPB). The relationship between DPB and mortality risk remains unclear, and we hypothesized that this relationship might be influenced by the proportion of PBs to all medications. METHODS: We divided DPB into those derived from PBs and non-PB drugs and analyzed the association with mortality risk over a 7-year period in 513 chronic hemodialysis patients using a baseline model. RESULTS: The median (interquartile range) DPB from all drugs was 15.8 (11.2-21.0) pills/day/patient, and the median ratio of PB pills to all drug pills was 29.3 (13.7-45.9)% at baseline. During a median observation period of 5.2 years, 161 patients (31.4%) died. Kaplan-Meier analysis showed no significant difference in all-cause mortality between PB users and non-users. However, a significant survival advantage was observed in the highest tertile of DPB from PBs compared to the lowest tertile. Conversely, the highest tertile of DPB from non-PB drugs was associated with worse survival. Consequently, the highest tertile of the ratio of PBs to all pills was associated with better survival. This association remained significant even after adjusting for patient characteristics in the Cox proportional hazards model. However, when serum nutritional parameters were included as covariates, the significant association disappeared. CONCLUSIONS: Dialysis patients prescribed a higher rate of PB pills to all medications exhibited a lower mortality risk, possibly due to their better nutritional status.

Impact of phosphate binders on medication dosing frequency, timing, and number of prescribed pills in hemodialysis patients.

INTRODUCTION: Phosphate binders (PBs) account for a large proportion of the daily pill burden in hemodialysis patients. However, patients do not take them all at once but at several dosing timings. METHODS: We analyzed the dosing timings of all 322 types of oral drugs prescribed to 533 hemodialysis patients. RESULTS: The median daily dosing frequency for all drugs was 6 (4-7) times/day/patient. Patients prescribed PBs had a markedly higher daily dosing frequency than those not taking PBs (7 [5-8] times/day/patient vs. 4 [3-5] times/day/patient, respectively [p < 0.001]). In addition, the ratio of the number of PB pills to other drugs varied greatly at each dosing timing. Furthermore, it was simulated that the daily dosing frequency could be reduced by approximately two times/day/patient by combining the dosing timings of PBs. CONCLUSION: Changing PB dosing timings can reduce the daily dosing frequency, which may lead to improved medication adherence.

A folded-blister pill pack causes ileal perforation.

Ileal perforation by an accidental ingestion of a blister pill pack is rare. A detailed history of the present illness is the initial key to proceed appropriate investigations. Computed tomography is the gold standard for diagnosis of the disease.

Cardiac involvement in heavy and light chain amyloidosis: A case report and literature review.

INTRODUCTION: Heavy and light chain amyloidosis is an extremely rare condition. There are few reports referring to the clinical impact of cardiac involvement in heavy and light chain amyloidosis, and the significance of myocardial impairment has not yet been completely explained. PATIENT CONCERNS: A 66-year-old Japanese man was admitted to our hospital presenting with nephrotic syndrome and congestive heart failure. DIAGNOSIS: Kidney and endoscopic gastric mucosal biopsy demonstrated congophilic hyalinization in most of the glomeruli and surrounding vessel walls, which were highly positive for immunoglobulin A and lambda. Finally, the patient was diagnosed as an atypical multiple myeloma with systemic heavy and light chain amyloidosis. INTERVENTIONS: The patient was referred to hematology for further treatment and was moved to another hospital for the administration of chemotherapy using melphalan and dexamethasone. OUTCOMES: The patient was still alive after 15-month follow-up from the initial diagnosis. CONCLUSION: Initial screening and follow-up for cardiac involvement are important for heavy and light chain amyloidosis. Further investigation for the prognosis of heavy and light chain amyloidosis is required to improve the strategies of diagnosis and treatment options for patients with this disease.

Phosphate Binders Derived from Natural Ores Contain Many Kinds of Metallic Elements Besides Their Active Ingredient Metals.

Most patients undergoing dialysis are required to take many phosphate binder pills to control hyperphosphatemia. Phosphate binders prescribed in Japan are classified into two types: metal-based binders (Ca carbonate, lanthanum carbonate, ferric citrate hydrate, and sucroferric oxyhydroxide) and chemically synthesized polymers (sevelamer hydrochloride and bixalomer). The raw materials of metal-based phosphate binders are natural ores; thus, such binders may contain several other metallic elements. We measured the elemental contents in six metal-based phosphate binders using an inductively coupled plasma mass - spectrometry (ICP-MS) method. As a result, despite being in small amounts, ore-derived phosphate binders contained various elements besides their active ingredient metals: Na, Mg, P, Mn, Fe, Sr, Y, Ba, La, Nd, and Pb in three Ca-based products; Mg, P, Se, Ce, and Gd in one La-based product; and Na, Mg, Al, P, Ca, Ti, Cr, Mn, Co, Ni, Ge, Ba, and La in two Fe-based products. These elements are considered to have originated from pharmaceutical bulk and from pharmaceutical additives. It is unlikely these elements are immediately harmful to patients. However, it should be emphasized that patients undergoing dialysis do not have a urinary excretion route and are administered many phosphate binder pills every day over a long period of time. In the future, pharmaceutical companies may have to disclose standard amounts and/or analytical values regarding the type and quantity of metallic elements in the final formulation or pharmaceutical bulk derived from natural ores.

[Pharmacological characteristics of drugs targeted on calcium-sensing receptor.-properties of cinacalcet hydrochloride as allosteric modulator].

Calcimimetics act as positive allosteric modulators of the calcium-sensing receptor (CaSR), thereby decreasing parathyroid hormone (PTH) secretion from the parathyroid glands. On the other hand, negative allosteric modulators of the CaSR with stimulatory effect on PTH secretion are termed calcilytics. The calcimimetic cinacalcet hydrochloride (cinacalcet) is the world's first allosteric modulator of G protein-coupled receptor to enter the clinical market. Cinacalcet just tunes the physiological effects of Ca(2+), an endogenous ligand, therefore, shows high selectivity and low side effects. Calcimimetics also increase cell surface CaSR expression by acting as pharmacological chaperones (pharmacoperones). It is considered that the cinacalcet-induced upper gastrointestinal problems are resulted from enhanced physiological responses to Ca(2+) and amino acids via increased sensitivity of digestive tract CaSR by cinacalcet. While clinical developments of calcilytics for osteoporosis were unfortunately halted or terminated due to paucity of efficacy, it is expected that calcilytics may be useful for the treatment of patients with activating CaSR mutations, asthma, and idiopathic pulmonary artery hypertension.

Effect of Polydextrose Intake on Constipation in Japanese Dialysis Patients: A Triple-Blind, Randomized, Controlled Trial.

The objective of the present study was to evaluate bowel habits induced by ingestion of 10 g polydextrose (PDX) fed to Japanese hemodialysis (HD) patients. This was a randomized, placebo-controlled, triple-blind, parallel-group controlled, 8-wk study. A total of 50 HD outpatients capable of self-management (51-79 y of age) were recruited at H Clinic, Japan. Inclusion criteria for participation in the study were ingestion of one or more laxative tablets for more than 3 mo and having received HD for more than 6 mo. The participants were randomly assigned to 2 groups: A (0 g polydextrose/d; control), B (10 g polydextrose/d; PDX). The primary outcome measure was stool frequency. Secondary outcomes were stool consistency, abdominal pain, intestinal bloating and clinical biochemistry indexes. PDX had no significant effect on blood biochemistry indexes. The PDX group showed significant improvements in bowel function (stool frequency increased from 3.0 times per week to 7.5 times per week) and reported no laxation problems (abdominal distention, cramps, and diarrhea) (p<0.01). Regular consumption of the PDX products increased dietary fiber intake to recommended levels and improved bowel habits.