Therapeutic Apheresis and Dialysis

2018 Therapeutic Apheresis and Dialysis

doi: 10.1111/1744-9987.12622

Fukagawa, Masafumi

2018 Therapeutic Apheresis and Dialysis

doi: 10.1111/1744-9987.12687pmid: 29883063

Ikeda, Shigaku

2018 Therapeutic Apheresis and Dialysis

doi: 10.1111/1744-9987.12691pmid: 29883061

Kakuta, Takatoshi; Ishida, Mari; Fukagawa, Masafumi

2018 Therapeutic Apheresis and Dialysis

doi: 10.1111/1744-9987.12690pmid: 29781225

Measurement of circulating parathyroid hormone (PTH) levels is essential for optimal management of mineral and bone disorders (MBD) in chronic kidney disease (CKD) patients. There are two major types of PTH assays currently in use: intact parathyroid hormone (i‐PTH) and whole PTH (w‐PTH) assays. The i‐PTH assay is the current standard, and considerable information regarding the management of CKD‐MBD has been obtained with this method. However, several limitations have been found with the i‐PTH assay. One limitation is that i‐PTH assay also measures fragments other than full‐length PTH (1‐84). Another limitation is the existence of multiple readout methods of the i‐PTH assay. The w‐PTH assay is theoretically ideal because it exclusively detects full‐length PTH (1‐84). However, clinical data proving the advantages of w‐PTH measurement are not sufficient. For uremic patients, Kidney Disease Improving Global Outcomes suggest that PTH levels should be maintained within approximately two to nine times the upper normal limit of the i‐PTH assays. The most critical issue in the evaluation of PTH levels is the lack of definitive PTH assay method. Evidence‐based recommendations on clinical management goals of PTH are warranted.

Kazama, Junichiro James; Wakasugi, Minako

2018 Therapeutic Apheresis and Dialysis

doi: 10.1111/1744-9987.12678pmid: 29883066

Bone maintains extracellular calcium levels through a system called bone remodeling. Parathyroid hormone (PTH) is the major initiator of this system, which is secreted by the information through calcium sensing receptor in parathyroid cells. PTH modifies calcified bone morphology through a process of its bone action. Therefore, extremely hyperactivated parathyroid function seen in patients with chronic kidney disease has been considered to have a negative impact on the bone mechanical properties. While skeletal deformities and fragility fractures were common among dialysis patients up to the 1970s, after which methods for the treatment of hyperparathyroidism were developed, we now seldom encounter those cases with severe secondary hyperparathyroidism in Japan. In a three‐dimensional morphometry of biopsied iliac bone samples obtained from dialysis patients, PTH level was inversely correlated with cortical bone thickness, however, this relationship disappeared among those with intact PTH < 1000 pg/mL. Higher PTH levels were associated with more complicated and irregular cancellous bone surface, but this change was not accompanied with decreased cancellous bone connectivity. These findings theoretically support the recent clinical study results that PTH levels no longer show a tight correlation with fracture risk in dialysis patients. Nevertheless, the use of calcium sensing receptor agonist is likely to be associated with reduced hip fracture risk in dialysis patients. Further study is needed to reveal its pharmacological mechanism on bone.

Fujii, Hideki

2018 Therapeutic Apheresis and Dialysis

doi: 10.1111/1744-9987.12679pmid: 29707916

Although parathyroid hormone is known to be related with calcium and phosphate metabolism, it has been also reported to have several effects on the cardiovascular system including heart and vessels. However, the detailed pathophysiological mechanisms remain unclear. Clinical studies have indicated that parathyroid hormone is associated with cardiovascular events and mortality not only in patients with chronic kidney disease but also in those without chronic kidney disease. As a possible mechanism, it is thought that parathyroid hormone is associated with the renin‐angiotensin‐aldosterone system and has direct effects on the cardiovascular system. Therefore, we should pay attention to not only the control of serum phosphate and calcium levels but also the control of serum parathyroid hormone levels, especially in patients with chronic kidney disease.

Tanaka, Motoko; Komaba, Hirotaka; Fukagawa, Masafumi

2018 Therapeutic Apheresis and Dialysis

doi: 10.1111/1744-9987.12685pmid: 29767854

Anemia is a common complication of chronic kidney disease (CKD). There are various causes of renal anemia such as decreased production of erythropoietin, resistance to erythropoietin, shortened survival of red blood cells, and bone marrow fibrosis. Secondary hyperparathyroidism (SHPT) is a less recognized, but potentially significant cause of renal anemia in CKD patients. Parathyroid hormone (PTH) has been regarded as a uremic toxin that has multiple adverse effects, and its elevated levels have been associated with renal anemia in hemodialysis patients. Moreover, recent clinical studies have shown that the treatment of SHPT using either vitamin D receptor activators, calcimimetics, or parathyroidectomy leads to improvement of anemia, supporting the role of PTH in renal anemia. Emerging data have also indicated the involvement of bone‐derived fibroblast growth factor 23 in renal anemia. This review summarizes recent insights into the role of PTH in renal anemia and discusses the importance of treating SHPT in improving the control of renal anemia in hemodialysis patients.

Komaba, Hirotaka; Fukagawa, Masafumi

2018 Therapeutic Apheresis and Dialysis

doi: 10.1111/1744-9987.12683pmid: 29707907

Protein‐energy wasting (PEW), a syndrome involving adverse changes in nutrition and body composition, is a serious problem associated with morbidity and mortality in patients with end‐stage renal disease (ESRD). The pathogenesis of PEW is multifactorial, and the underlying mechanisms are not fully understood. However, recent translational work has provided compelling evidence for a causal role of parathyroid hormone (PTH) in the pathogenesis of adipose tissue browning and increased energy expenditure, a critical component of PEW in ESRD. These results provide a biological explanation for the clinical association between secondary hyperparathyroidism (SHPT) and PEW in hemodialysis patients and may serve as an additional rationale for treating SHPT. Large‐scale clinical and epidemiological studies should determine the clinical significance of SHPT as a contributor to PEW and establish the optimal management of SHPT to ameliorate PEW.

Watanabe, Hiroshi; Maruyama, Toru

2018 Therapeutic Apheresis and Dialysis

doi: 10.1111/1744-9987.12686pmid: 29883064

Recent studies demonstrate that parathyroid hormone (PTH) not only maintains mineral homeostasis through targeting the kidneys and bone, but also exerts its effects on other organs. For instance, PTH induces urate accumulation through inhibiting the expression of the ABCG2 in both the intestine and the kidney. In addition, PTH downregulates the expression of cytochrome P450 (CYP) 3A, a major enzyme for drug metabolism in both the intestine and liver, resulting in the increase of substrate drug exposure. These functions of PTH are mediated through the PTH receptor (PTHR) signaling. Since PTHR exists in various organs, PTH may regulate other, still unspecified transporters or enzymes in the organs that express PTHR.

Miyamoto, Satoko; Ohkubo, Atsushi; Seshima, Hiroshi; Yamamoto, Hiroko; Itagaki, Ayako; Maeda, Takuma; Kurashima, Naoki; Mori, Takayasu; Iimori, Soichiro; Naito, Shotaro; Sohara, Eisei; Rai, Tatemitsu; Uchida, Shinichi; Okado, Tomokazu

2018 Therapeutic Apheresis and Dialysis

doi: 10.1111/1744-9987.12692pmid: 29781127

Selective plasma exchange has been shown to be effective in various diseases, but no studies have assessed the benefits of daily treatment. We aimed to investigate the removal dynamics of immunoglobulins, fibrinogen, and factor XIII on three consecutive days in three patients. For mean processed plasma volumes of 1.06 × plasma volume, reductions of 79.6%, 49.3%, and 8.6% were seen for immunoglobulins G, A, and M, respectively. The reductions for fibrinogen and factor XIII were 18.4% and 13.0%, respectively. Removal dynamics were similar for immunoglobulin G‐related autoantibodies and immunoglobulin G when using daily selective plasma exchange. Moreover, daily use effectively removed the immunoglobulin G while retaining the coagulation factors. When disease‐specific autoantibodies are limited to immunoglobulin G, daily selective plasma exchange may be a useful and safe method of intensive induction treatment for plasmapheresis. However, further study is required in larger cohorts to confirm these findings.