Expression and localization of fibroblast growth factor (FGF)23 and Klotho in the spleen: its physiological and functional implications.

The FGF23-Klotho signaling axis is known to exert anti-aging effects via calcium-phosphorus metabolism. In mice deficient in FGF23-Klotho signaling, however, the number of splenocytes is reduced. FGF23 is expressed in both bone and spleen, with regulation of its production differing in these organs. As FGF23-Klotho signaling may play an immunological role in the spleen, splenocytes in male C57BL/6J mice were assayed for expression of Klotho or FGF23 by flow cytometry and immunohistochemistry. Cells that expressed Klotho included CD45R/B220+ CD21/CD35+ CD1d+ CD43- marginal zone B cells. These cells also expressed FGF receptor 1, indicating that Klotho-positive B cells could respond to FGF23. Plasmacytoid dendritic cells (pDCs) with CD11c+ CD45R/B220+ CD11b- CD8α- were found to produce FGF23. Klotho-positive cells and FGF23-producing cells were present in close proximity to each other, suggesting that FGF23 produced by pDCs may act within a limited area. These findings indicate that FGF23-Klotho signaling could play a biological or immunological role in the spleen.

Effects of Cyclophosphamide Pulse Therapy on the Clinical and Histopathological Findings, Particularly Crescent Formation, in a Patient with Adult-onset Steroid-refractory Henoch-Schönlein Purpura Nephritis.

A 29-year-old woman was diagnosed with Henoch-Schönlein purpura nephritis (HSPN) based on the presence of purpura and histopathological findings showing crescent formation, mesangial proliferation and IgA deposition in the glomerular mesangium. She was treated with high-dose steroids; however, the nephritic syndrome persisted. Therefore, we diagnosed her with steroid-resistant HSPN and decided to add treatment with cyclosphamide pulse therapy. After one year of treatment, the histopathological findings, including crescent formation and IgA deposition, improved, as confirmed on a renal biopsy, and the patient fulfilled the criteria for complete remission. Cyclophosphamide pulse therapy may be considered an effective treatment for intractable HSPN.

[Kidney and bone update : the 5-year history and future of CKD-MBD. Progress of phosphate binders].

Hyperphosphatemia is a serious complication which has been linked with an increased risk of cardiovascular mortality in patients with chronic kidney disease. Especially in end stage renal disease (ESRD) patients, the nutritional disturbance due to strict phosphate restriction with protein restriction is certainly associated with patients' survival. Firstly, the aggressive phosphorus removal by blood purification modality is also important for the good control in serum phosphate level. Secondary, the active phosphate binder therapy is actual effective treatment for ESRD patients with hyperphosphatemia. Until recently, none of the available agents fulfilled the criteria of an ideal phosphate binders. However, several phosphate binder such as calcium carbonate, sevelamer hydrochloride, lanthanum carbonate and so on, are available in Japan. This review work is describing about the history and clinical manifestation of these phosphate binders.

The management of hyperphosphatemia by lanthanum carbonate in chronic kidney disease patients.

Hyperphosphatemia has been shown to be involved not only in the onset and progression of secondary hyperparathyroidism but also in vascular calcification. In addition, it influences the clinical course of patients with chronic kidney disease. Phosphate (Pi) binder is required in the management of hyperparaphosphatemia, because dietary Pi restriction and Pi removal by hemodialysis alone are insufficient. Lanthanum carbonate, a powerful Pi binder, has a similar effect to aluminum hydroxide in reducing serum Pi levels. As it is excreted via the liver, lanthanum carbonate has an advantage in patients with renal failure. The effect of lanthanum carbonate on serum Pi levels is almost two times higher than that of calcium (Ca) carbonate, which is commonly used. Lanthanum carbonate and Ca carbonate have an additive effect. Worldwide, there is 6 years worth of clinical treatment data on lanthanum carbonate; however, we have 3 years of clinical use in Japanese patients with hyperphosphatemia. No serious side effects have been reported. However, the most important concern is bone toxicity, which has been observed with use of aluminum hydroxide. For this study, clinical research involved analysis of bone biopsies. Although osteomalacia is the most noticeable side effect, this was not observed. Both the high- and the low-turnover bone disease concentrated into a normal bone turnover state. However, as the authors have less than 10 years' clinical experience with lanthanum carbonate, patients should be monitored carefully. In addition, it is necessary to demonstrate whether potent treatment effects on hyperphosphatemia improve the long-term outcome.

Reduced expression of perlecan in the aorta of secondary hyperparathyroidism model rats with medial calcification.

BACKGROUND: Vascular calcification is an important complication that worsens the prognosis for dialysis patients, although its detailed molecular mechanisms are still unknown. METHODS: We produced a rat model for vascular calcification with hyperphosphatasemia and hyperparathyroidism, performing a 5/6 nephrectomy and providing a high-phosphorus, low-calcium diet for eight weeks. We examined mRNA obtained from the calcified aortae using microarray analysis, and searched for alterations in gene expression specifically in the calcified lesions. RESULTS: Medial calcification was demonstrated in the abdominal aorta of 12 out of 42 hyperparathyroidism rats. In the aortae of hyperparathyroid rats with vascular calcification, the genes for heparan sulfate proteoglycans, including perlecan, were found to be down-regulated using microarray analysis and real time PCR. Immunohistochemistry also demonstrated reduced production of perlecan in the aortae of hyperparathyroid rats. DISCUSSION: Perlecan is a major component of the vascular wall basement membrane and may play a role in protecting vascular smooth muscle cells from inflammatory cells and various toxins. It has also been reported that heparan sulfate chains may inhibit osteogenesis. Our findings indicate that perlecan may protect vascular smooth muscle cells from various factors that promote vascular calcification. CONCLUSIONS: It may be that reduced expression of perlecan in the calcified aortae of hyperparathyroid rats is a risk factor for vascular calcification.

[Basic and clinical aspects of calcimimetics. The clinical effect and usefulness of Cinacalcet as a calcimimetics on three CKD-5D patients undergoing hemodialysis with refractory secondary hyperparathyroidism].

In this part, we reports the experience of treatment by calcimimetics for 3 hemodialyzed patients with refractory secondary hyperparathyroidism. They purchased own expense, and used "Cinacalcet" as calcimimetics (Sensipar(R) 30 mg/tablet, by AMGEN co. Ltd. in USA) . Serum Ca, P, and intact-PTH decreased certainly in 3 cases after cinacalcet therapy. Especially the reduction of intact-PTH is obviously. The any adverse effect did not observed by 30 mg/tablet/day prescription except mild epigastralgia in a case. We were able to experience the marked suppressive effect on parathyroid gland by cinacalcet as calcimimetics in Japanese patients with refractory secondary hyperparathyroidism undergoing hemodialysis.

Study of plasma exchange for liver failure: beneficial and harmful effects.

Plasma exchange (PE) is often performed in combination with hemodialysis (HD) or hemodiafiltration. However, most methods were developed for the treatment of renal failure, so various problems may arise during treatment of liver failure (LF). In this study, we investigated the impact of PE alone and in combination with HD, and we assessed the complications of using PE + HD for the treatment of LF. After the exchange of 1 L of fresh frozen plasma (FFP), we measured serum electrolytes, HCO(3) (-), citrate, and acetate at 3 points in the circuit: A) the plasma separator inflow; B) after mixing of FFP/the dialyzer inflow; and C) the dialyzer outflow. Serum levels of human hepatocyte growth factor (HGF), acetate, and citrate were also measured before and after PE + HD. The levels of K(+), Ca(++), HCO(3) (-), and acetate were significantly decreased, and citrate was increased, between A and B. K(+) and citrate were decreased, while Ca(++), HCO(3) (-), and acetate showed an increase between B and C. Comparison of A with C revealed insufficient correction of the Ca(++) and citrate levels by HD. After PE + HD, serum levels of acetate and citrate were increased, while HGF was decreased. We concluded that i) when PE is performed, HD is also necessary for correction, but achieves insufficient correction of Ca(++) and citrate, ii) PE is non-selective and not only removes toxins but also beneficial substances such as HGF, iii) accumulation of acetate occurred, even with bicarbonate dialysate, since it also contains acetate for acidification.