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Junichiro J Kazama

Publications and source records attributed to Junichiro J Kazama.

At least 19 recordsLinked to original sources
PubMed2006

Para-capillary electron-dense deposits reduce glomerular filtration in patients with primary glomerular diseases.

BACKGROUND: Electron-dense deposits are often found around glomerular capillary lumens in patients with glomerulonephritis, forming a portion of the blood-urine barrier (BUB). METHODS: Four hundred and four patients with primary glomerular diseases or donors for living-related kidney transplantation who underwent both percutaneous renal biopsy and renal clearance tests were included in the study. Sodium thiosulfate and paraamino hippurate double-clearance studies were performed with catheterized urinary collection. The filtration fraction (FF) was determined as follows: FF = sodium thiosulfate clearance/paraamino hippurate clearance (CPAH: ). Histomorphometric analyses were performed in 53 patients with overt para-capillary electron-dense deposits (PCEDD) by electron microscopic observations. RESULTS: Patients with membranous nephropathy and membranoproliferative glomerulonephritis showed significantly lower levels of FF than the donors for living-rebated kidney transplantation (normal controls). FF levels were significantly lower in patients with PCEDD than in those without (P < 0.001), while the levels of mean blood pressure and CPAH: were comparable in the two groups. The PCEDD/BUB ratio demonstrated a significant negative correlation with FF (P < 0.0001; r(2) = 0.331). Patients with a ratio of 0.5 or more showed significantly lower FF levels than those with a ratio of 0.25 or less. CONCLUSIONS: PCEDD significantly affected FF levels in patients with primary glomerular diseases. FF may not be an accurate indicator of intraglomerular blood pressure in patients with overt PCEDD.

Adult↗
PubMed2005

Evidence for megalin-mediated proximal tubular uptake of L-FABP, a carrier of potentially nephrotoxic molecules.

Liver-type fatty acid binding protein (L-FABP) binds with high affinity to hydrophobic molecules including free fatty acid, bile acid and bilirubin, which are potentially nephrotoxic, and is involved in their metabolism mainly in hepatocytes. L-FABP is released into the circulation, and patients with liver damage have an elevated plasma L-FABP level. L-FABP is also present in renal tubules; however, the precise localization of L-FABP and its potential role in the renal tubules are not known. In this study, we examined the cellular and subcellular localization of L-FABP in the rat kidney and tried to determine from where the L-FABP in kidney tissues had originated. Immunohistochemical studies of kidney sections localized L-FABP in the lysosomes of proximal tubule cells (PTC). In rats with carbon tetrachloride (CCl4)-induced acute liver injury, we detected high levels of L-FABP in the circulation and in the kidney compared with those in the control rat by immunoblotting, while reverse transcription-polymerase chain reaction showed that the level of L-FABP mRNA expression in the kidney of CCl4-treated rats was low and did not differ from that in the control rat. When 35S-L-FABP was intravenously administered to rats, the kidneys took up 35S-L-FABP more preferentially than the liver and heart, and histoautoradiography of kidney sections revealed that 35S-L-FABP was internalized via the apical domains of PTC. Quartz-crystal microbalance analysis revealed that L-FABP bound to megalin, a multiligand endocytotic receptor on PTC, in a Ca2+-dependent manner. Degradation assays using megalin-expressing rat yolk sac tumor-derived L2 cells demonstrated that megalin mediated the cellular uptake and catabolism of 125I-L-FABP. In conclusion, circulatory L-FABP was found to be filtered by glomeruli and internalized by PTC probably via megalin-mediated endocytosis. These results suggest a novel renal uptake pathway for L-FABP, a carrier of hydrophobic molecules, some of which may exert nephrotoxic effects.

Animals↗
PubMed2005

Role of fibroblast growth factor 23 in health and in chronic kidney disease.

PURPOSE OF REVIEW: This review summarizes the molecular properties and biological roles of a new phosphaturic factor, fibroblast growth factor 23 (FGF23). Significant roles of FGF23 are discussed, especially in terms of its effects on the kidney, the main target organ. RECENT FINDINGS: FGF 23 is a recently discovered phosphaturic factor. Several animal experiments including overexpression or ablation of the FGF23 gene have recently revealed the significant effects of this factor on phosphate excretion and on vitamin D synthesis in the kidney. Although FGF23 was originally identified as a factor responsible for several hypophosphatemic disorders, recent data indicate its role in the physiological regulation of phosphate homeostasis. In chronic kidney disease, FGF23 plays a crucial role in the pathogenesis of secondary hyperparathyroidism. Effects of FGF23 on other organs including bone and intestine remain to be elucidated. SUMMARY: FGF23 is a physiological regulator of phosphate homeostasis. Excessive activity of FGF23 with normal renal function results in hypophosphatemia, low 1,25-dihydroxyvitamin D levels, and rickets/osteomalacia. By contrast, excessive FGF23 activity suppresses 1,25-dihydroxyvitamin D synthesis, but may not be sufficient to excrete the phosphate load appropriately with deteriorating renal function, both of which contribute to the development of hyperparathyroidism.

Chronic Disease↗
PubMed2005

Pretreatment serum FGF-23 levels predict the efficacy of calcitriol therapy in dialysis patients.

BACKGROUND: The predictor for the result of calcitriol therapy would be useful in the clinical practice of secondary hyperparathyroidism. Fibroblast growth factor-23 (FGF-23) is a newly found circulating phosphaturic factor. Its circulating level is elevated in uremia. METHODS: Dialysis patients with plasma intact parathyroid hormone (iPTH) levels greater than 300 pg/mL were included in the study. Calcitriol was intravenously injected three times a week. The patients whose plasma iPTH levels dropped below 300 pg/mL within 24 weeks were defined as those who had been successfully treated. A sandwich enzyme-linked immunosorbent assay (ELISA) system that detects human FGF-23 was applied. RESULTS: Sixty-two patients were analyzed. The pretreatment FGF-23 levels were related to the iPTH levels, calcium x phosphate product levels, and history of active vitamin D therapy. The pretreatment FGF-23, iPTH, and calcium levels were lower in the patients who would be successfully treated with calcitriol. A logistic regression study revealed that the pretreatment iPTH and FGF-23 levels significantly affected the therapy results. Analyses using a receiver-operated curve revealed that FGF-23 was the best screening test for identifying patients with future refractory response to calcitriol therapy. The treatment would be successful in 88.2% of those with FGF-23 </=9860 ng/L and iPTH </=591 pg/mL, while it would be successful in only 4.2% of those with FGF-23 >9860 ng/L and iPTH >591 pg/mL. CONCLUSION: Pretreatment serum FGF-23 levels were a good indicator in predicting the response to calcitriol therapy. The measurement of serum FGF-23 levels, especially in combination with iPTH levels, is a promising laboratory examination for the clinical practice of secondary hyperparathyroidism.

Calcitriol↗
PubMed2005

Role of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism.

It would be useful to predict the future development of hyperparathyroidism before treatment with active vitamin D agents. Fibroblast growth factor 23 (FGF23) is a newly identified humoral phosphaturic factor. Positive correlation was found between parathyroid function and serum FGF23 levels in dialysis patients. Interestingly, FGF23 levels showed even better correlation with intact parathyroid hormone (iPTH) levels 2 years after the sample collection for the FGF23 measurement. In long-term dialysis patients with mild secondary hyperparathyroidism, serum FGF23 level was the best screening test to discriminate patients with future advanced secondary hyperparathyroidism within 2 years. In dialysis patients with advanced secondary hyperparathyroidism, the pretreatment FGF23 levels, as well as iPTH levels, significantly affected the outcome of calcitriol therapy. Thus, the measurement of serum FGF23 level is a promising laboratory examination to predict the future development of secondary hyperparathyroidism. The mechanism of this phenomenon, however, remains to be revealed.

Clinical Trials as Topic↗
PubMed2005

Sevelamer hydrochloride and calcium bicarbonate reduce serum fibroblast growth factor 23 levels in dialysis patients.

Fibroblast growth factor 23 (FGF23) is a member of the fibroblast growth factor superfamily which displays a strong phosphaturic action and an inhibition of vitamin D 1-alpha hydroxylase activity. Fourty-six patients undergoing maintenance hemodialysis therapy participated in the study. They were randomly divided into 2 groups, and treated with either 3 g sevelamer hydrochloride+3 g of calcium bicarbonate (CaCO3), or 3 g of CaCO3 alone. Serum FGF23 levels were determined by a sandwich enzyme-linked immunosorbent assay (ELISA) system that detects the intact form of FGF23 molecules. Although the serum inorganic phosphate (Pi) levels were comparable before treatment, the levels were significantly lower in the patients treated with sevelamer hydrochloride+CaCO3 than those with CaCO3 alone after 4 weeks of treatment (P<0.05). Serum FGF23 levels significantly decreased after 4 weeks of the treatment with sevelamer hydrochloride+CaCO3 from the pretreatment levels (P<0.05), while no changes were found in the patients treated with CaCO3 alone. Thus, the use of sevelamer hydrochloride and CaCO3 reduced serum FGF23 levels in dialysis patients presumably through inhibiting phosphate load into the intestine.

Bicarbonates↗
PubMed2005

Maxacalcitol is a possible less phosphatemic vitamin D analog.

The phosphatemic property of maxacalcitol, a newly developed artificial active vitamin D analog, has not been compared with that of calcitriol. Non-diabetic hemodialysis patients with plasma intact parathyroid hormone (PTH) levels greater than 300 pg/mL were included in this analysis. They were treated with either maxacalcitol or calcitriol for 24 weeks. In total, 80 patients were treated with maxacalcitol and 46 were treated with calcitriol. Pretreatment circulating levels of intact PTH, calcium (Ca) and inorganic phosphate (Pi) were comparable in both treatment groups. Both treatments significantly decreased plasma intact PTH levels (P<0.0001) and increased serum Ca levels (P<0.0001). However, the intact PTH levels were significantly lower in the maxacalcitol group after 24 weeks of the treatments (P<0.01). The decreasing tendency of plasma intact PTH level was significantly evident in the maxcalcitol group (P<0.01). However, the increasing tendency of the serum Pi level was significantly greater in the calcitriol group (P<0.05). Thus, maxacalcitol is a possible less phosphatemic active vitamin D agent, if not non-phosphatemic agent, which might reduce the risk of extraskeletal calcification.

Bone Density Conservation Agents↗
PubMed2005

Direct comparison between two 1-84PTH assays in dialysis patients.

BACKGROUND/AIM: Today, two kinds of 1-84PTH assays are available in clinical practice. Few studies have directly compared the results of these assays in the same plasma. METHODS: Plasma samples were collected from 235 dialysis patients and analyzed by the 1-84PTH-IRMA, intact PTH-IRMA, 1-84PTH-CLIA, and intact PTH-CLIA assays simultaneously. RESULTS: The results obtained by the 1-84PTH-IRMA and 1-84PTH-CLIA were highly correlated to each other (r(2) = 0.971, p < 0.0001). In 90.2-92.3% of patients, the assays agreed when classifying them into three categories based on the K/DOQI guidelines. However, the 1-84PTH assays agreed in only 41.3-83.4% of patients when classifying them into two categories by calculating 1-84PTH/(intact PTH - 1-84PTH). CONCLUSION: The results obtained by the two assays could be regarded as comparable in clinical practice. However, the 1-84PTH/(intact PTH-1-84PTH) ratio has to be carefully applied since it amplified the error of these assays.

Adolescent↗
PubMed2004

Evidence indicating that renal tubular metabolism of leptin is mediated by megalin but not by the leptin receptors.

Leptin is secreted by adipocytes and is a circulating factor that regulates food intake and energy expenditure. Its serum level is elevated in patients with renal failure and has been suggested to be associated with malnutritional factors in these patients. Leptin has been suggested to be primarily metabolized by the kidneys, although the precise molecular mechanisms are not known. The purpose of this study was to determine the nephron segments and potential receptors involved in renal leptin metabolism. To determine the segment involved in leptin uptake, we performed histoautoradiography of kidney sections obtained from rats that had been injected iv with (125)I-leptin. The ability of megalin, a multiligand endocytic receptor in the proximal tubules, to bind and endocytose leptin was examined by ligand blotting analysis, quartz-crystal microbalance, and degradation assays using megalin-expressing rat yolk sac L2 cells. Immunohistochemistry was performed to localize leptin receptors (LEP-R) in the rat kidney using two antibodies that recognize different epitopes on the LEP-R proteins. Circulating (125)I-leptin was filtered by glomeruli and internalized by proximal convoluted tubules. Megalin bound leptin in the presence of Ca(2+) and mediated its cellular internalization and degradation. On immunohistochemistry, LEP-R were localized in the proximal straight tubules, loops of Henle, distal tubules, and collecting ducts. In conclusion, circulating leptin was filtered by glomeruli and taken up by proximal convoluted tubules, where megalin likely mediates its binding and uptake. The localization of LEP-R suggests that they are not primarily involved in leptin metabolism in the proximal tubules.

Animals↗
PubMed2004

Short-term use of continuous positive airway pressure ameliorates glomerular hyperfiltration in patients with obstructive sleep apnoea syndrome.

Patients with OSAS (obstructive sleep apnoea syndrome) demonstrate renal signs such as proteinuria, glomerular hypertrophy and focal glomerular sclerosis. We performed a clinical study to investigate the glomerular function in OSAS patients and the short-term effect of CPAP (continuous positive airway pressure) on it. OSAS patients underwent a sodium thiosulphate and p-aminohippurate double clearance test, polysomnography and ambulatory blood pressure monitoring before and a week after the induction of CPAP. Twenty-seven consecutive patients (24 males) with moderate-to-severe OSAS admitted to our hospital for the induction of CPAP, and 32 healthy donors for renal transplantation as controls participated in the study. Before treatment, the glomerular filtration rate, estimated by the sodium thiosulphate clearance test, was within normal range, and the renal plasma flow was significantly lower than normal in the OSAS patients, thus the FF (filtration fraction) value was much higher than normal. FF before CPAP was not significantly correlated with age, body mass index or blood pressure; however, indices of increased hypoxaemia correlated with increased FF values. Polysomnographic variables after CPAP showed significant improvements in all patients, and only the nocturnal blood pressures were slightly lower than before CPAP. In 21 patients who underwent the clearance test after CPAP, FF significantly decreased from 0.26 +/- 0.04 to 0.23 +/- 0.03 (P < 0.001). OSAS patients were generally in a glomerular-hyperfiltrating condition that appeared to cause the renal findings associated with OSAS. CPAP might prevent nephropathy by ameliorating the glomerular hyperfiltration in OSAS patients.

Aged↗
PubMed2004

Intact PTH assay overestimates true 1-84 PTH levels after maxacalcitol therapy in dialysis patients with secondary hyperparathyroidism.

BACKGROUND: Although the so-called intact parathyroid hormone (iPTH) assay detects not only true 1-84 PTH (1-84PTH) but also large C-terminal PTH fragments, it remains inconclusive whether the 1-84PTH assay is more useful in clinical practice. Previous studies have shown that the results of these two PTH assays in dialysis patients are closely correlated. METHODS: Chronic dialysis patients whose plasma iPTH levels were >400 pg/ml were selected for inclusion in the present study. Following a 4 week wash-out time during which all vitamin D administration was halted, maxacalcitol was intravenously injected at the end of dialysis sessions three times per week for 24 weeks, at an initial dosage of 10 micro g. RESULTS: Ninety-seven patients with secondary hyperparathyroidism were included in our analysis. Their serum calcium levels were elevated from the start levels while phosphate levels remained unchanged. The plasma 1-84PTH levels constantly declined throughout the 24 weeks. Although the patients' plasma 1-84PTH and iPTH levels were closely correlated with each other both at the beginning of the study and after 24 weeks of maxacalcitol therapy, the ratio of 1-84PTH/iPTH consistently decreased throughout the study period (P<0.01). The changes in the ratio were significantly correlated with changes in serum calcium levels. CONCLUSIONS: Twenty-four weeks of intravenous maxacalcitol injection therapy significantly reduced the 1-84PTH/iPTH ratio. Estimated 1-84PTH levels from iPTH levels using a conversion formula obtained before the treatment were 21.0+/-20.4% higher than measured 1-84PTH levels after the therapy. Thus, iPTH measurement has a potential risk to overestimate 1-84PTH levels when evaluating the efficacy of maxacalcitol therapy in dialysis patients with secondary hyperparathyroidism.

Calcitriol↗
PubMed2004

Osteoprotegerin and bone mineral metabolism in renal failure.

PURPOSE OF REVIEW: This review focuses on the impact of a recent breakthrough in bone cell biology for understanding the pathophysiology of bone/vascular abnormalities associated with uraemia. RECENT FINDINGS: Osteoprotegerin is a humoral osteoclastogenesis/osteoclast activation inhibitory factor, which belongs to the TNF-alpha receptor superfamily. Serum osteoprotegerin levels are elevated along with the deterioration of the glomerular filtration rate. The circulating osteoprotegerin molecules were likely to preserve the activity of osteoclastogenesis inhibition, and the levels in many dialysis patients were high enough to inhibit osteoclastogenesis. The higher serum osteoprotegerin levels were related to the development of vascular calcification. SUMMARY: Osteoprotegerin is a potential uraemic toxin that increases the skeletal resistance to PTH. However, the roles of increased circulating osteoprotegerin on bone and/or vascular abnormalities in uraemia remain to be clarified.

Bone Density↗
PubMed2003

Skeletal resistance to parathyroid hormone as a background abnormality in uremia.

Skeletal resistance to parathyroid hormone (PTH) is a background abnormality underlying uremic bone disease. This abnormality exists even with high PTH. By the suppression of PTH, it has become uncovered, presenting as adynamic bone disease. Since patients with adynamic bone disease have higher risk of hypercalcemia or lumber fracture, mechanisms of this skeletal resistance to PTH need to be elucidated for the optimal management of bone turnover and parathyroid function in chronic dialysis patients.

Animals↗
PubMed2003

The sequential organ failure assessment score as a useful predictor for estimating the prognosis of systemic inflammatory response syndrome patients being treated with extracorporeal blood purification.

Systemic inflammatory response syndrome (SIRS) is a major cause of morbidity and mortality in critically ill patients. Extracorporeal blood purification procedures are becoming important for treating these patients. However, the cost of these procedures is high. Therefore, a prognostic marker would be helpful. To establish the reliability of the Sequential Organ Failure Assessment (SOFA) score as a prognostic indicator, we evaluated daily changes in the SOFA score of 40 SIRS patients who needed blood purification procedures such as continuous renal replacement therapy (CRRT), endotoxin adsorption, bilirubin adsorption, and/or plasma exchange. Twenty patients survived and 20 died. Although the baseline scores of the two groups (survivors and non-survivors) did not differ, both the maximum value of the SOFA score and the DeltaSOFA score (the difference between the maximum SOFA and baseline SOFA scores) were significantly higher in the non-survivor group. The mortality rate among patients with a maximum SOFA score greater than or equal to 18 or a DeltaSOFA score greater than or equal to 3 was higher than for the rest of the patients. The changes in the SOFA score correlated well with the outcomes of the SIRS patients. The maximum SOFA score and the DeltaSOFA score are therefore likely to be useful prognostic markers.

APACHE↗
PubMed2003

Bioengineered implantation of megalin-expressing cells: a potential intracorporeal therapeutic model for uremic toxin protein clearance in renal failure.

Patients who have renal failure and are on dialysis therapy experience serious complications caused by low-molecular-weight uremic toxin proteins normally filtered by glomeruli and metabolized by proximal tubule cells (PTC). Dialysis-related amyloidosis is one such complication induced by systemic deposition of amyloid proteins derived from 12-kD beta(2)-microglobulin (beta(2)-m). Despite the use of high-flux membrane hemodialysis devices and direct absorbent columns, the removal of beta(2)-m is suboptimal, because the effects are transient and insufficient. Megalin is expressed in the apical membranes of PTC and recognized as a multiligand endocytic receptor that binds numerous low-molecular-weight proteins, including beta(2)-m. This study tested the feasibility of an intracorporeal therapeutic model of continuous beta(2)-m removal using megalin-expressing cell implantation. By cell association and degradation assays, rat yolk sac-derived L2 cells were identified to internalize and degrade beta(2)-m via megalin. The cells were effectively implanted within the subcutaneous tissues of nude mice using a type I collagen scaffold and a method inducing local angiogenesis. After nephrectomy and intraperitoneal injection with (125)I-beta(2)-m, it was found that the implanted cells took up the labeled ligand, efficiently removing it from the blood. Bioengineered implantation of megalin-expressing cells may represent a new supportive therapy for dialysis patients to compensate for the loss of renal protein metabolism and remove uremic toxin proteins.

Animals↗