Osamu Saito

Jichi Medical University, Totigi, Tochigi, Japan

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Publications (51)60.84 Total impact

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    ABSTRACT: Peritoneal deterioration causing structural changes and functional decline is a major complication of peritoneal dialysis (PD). The aim of this study was to explore effluent biomarkers reflecting peritoneal deterioration. In an animal study, rats were intraperitoneally administered with PD fluids adding 20 mM methylglyoxal (MGO) or 20 mM formaldehyde (FA) every day for 21 days. In the MGO-treated rats, tenascin-C (TN-C) levels in the peritoneal effluents were remarkably high and a cluster of TN-C-positive mesothelial cells with epithelial-to-mesenchymal transition- (EMT-) like change excessively proliferated at the peritoneal surface, but not in the FA-treated rats. Effluent matrix metalloproteinase-2 (MMP-2) levels increased in both the MGO- and FA-treated rats. In a clinical study at 18 centers between 2006 and 2013, effluent TN-C and MMP-2 levels were quantified in 182 PD patients with end-stage renal disease. Peritoneal function was estimated using the peritoneal equilibration test (PET). From the PET results, the D/P Cr ratio was correlated with effluent levels of TN-C ( ρ = 0.57, p < 0.001 ) and MMP-2 ( ρ = 0.73, p < 0.001 ). We suggest that TN-C in the effluents may be a diagnostic marker for peritoneal deterioration with EMT-like change in mesothelial cells in PD.
    Preview · Article · Dec 2015
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    ABSTRACT: Acute poststreptococcal glomerulonephritis (APSGN) is a well-established disease. Although various immune responses are thought to be involved in the pathogenesis of APSGN, the disease has a self-limiting nature in clinical practice, despite the presence of severe acute symptoms. We herein report the case of a 78-year-old woman with APSGN who developed primary biliary cirrhosis (PBC) after achieving remission of renal manifestations, including anasarca and elevation of serum creatinine, indicating that persistent alterations in the immune system can cause extrarenal disorders. This case provides insights into the appropriate clinical management of ASPGN and pathogenesis of PBC.
    Full-text · Article · Aug 2015 · Internal Medicine
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    ABSTRACT: In Fabry disease, progressive glycolipid accumulation leads to damage in kidney and other organs. This study was designed to determine the prevalence rate of Fabry disease in Japanese dialysis patients. All dialysis patients agreeing to Japan Fabry disease screening study (J-FAST) with informed consent were selected except for Fabry disease. The screening was performed by a method of measuring plasma and/or leukocytes lysosomal α-galactosidase A protein level and α-galactosidase A activity. If positive, genetic analysis was carried out upon patient's agreement. J-FAST dealt with 8547 patients (male 5408, female 3139). At the tertiary examination, 26 out of 8547 patients were found to be positive. Six out of 26 patients could not accept genetic analysis because of death. Remaining 20 patients agreed with genetic analysis; then 2 patients (male 2, female 0) had a variation of the α-Gal gene and 11 patients showed E66Q variations. Therefore, the frequency of Fabry disease in J-FAST was 0.04 % (2/5408) in males and 0 % (0/3139) in females, and then 0.02 % (2/8547) in all patients. The presumptive clinical diagnoses of end-stage kidney disease (ESKD) were 10 chronic glomerulonephritis, 7 diabetic nephropathy, 3 unknown etiology, 3 nephrosclerosis, 1 gouty nephropathy, 1 autosomal dominant polycystic kidney disease and 1 renal tuberculosis among 26 tertiary positive patients. Two male Fabry patients were initially diagnosed as nephrosclerosis and chronic glomerulonephritis. The prevalence rate of Fabry disease in J-FAST was 0.02 %. Moreover, Fabry disease could not be ruled out as the clinical diagnosis of ESKD.
    Full-text · Article · Jul 2015 · Clinical and Experimental Nephrology
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    ABSTRACT: We present the case of a 36-year-old man with type-1 diabetes who was hospitalized with diabetic ketoacidosis (DKA). On admission, he had hypothermia, hypokalemia and combined metabolic and respiratory alkalosis, in addition to hyperglycemia. Hypothermia, hypokalemia and metabolic alkalosis, with a concurrent respiratory alkalosis, are not commonly seen in DKA. After admission, intravenous infusion of 0.45% saline was administered, which resulted in the development of pure metabolic acidosis. After starting insulin infusion, hypokalemia and hypophosphatemia became evident and finally resulted in massive rhabdomyolysis. Hyperkalemia accompanying oliguric acute kidney injury (AKI) warranted initiation of hemodialysis (HD) on Day-five. On the 45th hospital day, his urine output started to increase and a total of 22 HD sessions were required. We believe that in this case severe dehydration, hypothermia and hypokalemia might have contributed to the initial symptoms of DKA as well as the prolongation of AKI.
    No preview · Article · May 2015 · Saudi journal of kidney diseases and transplantation: an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia

  • No preview · Article · Aug 2014 · Internal Medicine
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    ABSTRACT: Renal biopsy is one of the pivotal diagnostic tools used in the field of nephrology. A morphological analysis of the kidney may also be of value for the overall management of patients with diabetic nephropathy. However, the indications for renal biopsy differ considerably among nephrologists, and no global consensus regarding performing this procedure among diabetic patients with various renal manifestations has yet been achieved. In this report, we would like to describe our serendipitous experience with a male type 2 diabetic patient presenting with nephrotic syndrome complicated by concurrent gastric carcinoma. We also discuss several conundrums that arose in the current case, which had an impact on our diagnostic and therapeutic decisions.
    Full-text · Article · Jul 2014 · Clinical Medicine Insights: Case Reports
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    ABSTRACT: Bleeding from the gastrointestinal tract is one of the common determinants of morbidity and mortality in the ordinary clinical setting. The gastrointestinal involvement of Henoch-Schönlein purpura (HSP) has often been described as self-limiting, with no long-term morbidity. In this report, we describe our experience with a male HSP patient who presented with abdominal pain, loss of appetite and deteriorated renal function associated with nephrotic syndrome. Despite the use of aggressive immunomodulatory treatments, including corticosteroids and plasmapheresis, he developed lethal gastrointestinal hemorrhage. We believe that the accumulation of more experience with additional cases similar to ours is mandatory for the establishment of optimal management for HSP patients with severe gastrointestinal manifestations.
    No preview · Article · May 2014
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    ABSTRACT: Mixed cryoglobulinemia is occasionally seen in patients with hepatitis B virus (HBV) infection. This report presents the case of a quiescent HBV carrier who had type II mixed cryoglobulinemia, protracted purpura, ulcerative skin lesions and advanced chronic kidney disease. The cutaneous manifestations of the patient improved along with a decrease in the serum cryoglobulin and HBV-deoxyribonucleic acid levels following the initiation of oral entecavir in combination with plasmapheresis. However, the patient ultimately required prednisolone due to the limited benefits of these treatments. We also discuss various concerns regarding steroid treatment in patients with mixed cryoglobulinemia complicated by HBV infection.
    No preview · Article · Jan 2014 · Internal Medicine
  • Eiji Kusano · Osamu Saito · Tetsu Akimoto · Yasushi Asano
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    ABSTRACT: The prevalence rate for Fabry disease is conventionally considered to be 1 case in 40,000; however, due to increased screening accuracy, reports now suggest that prevalence is 1 case in 1,500 among male children, and it is likely that the clinical importance of the condition will increase in the future. In dialysis patients to date, prevalence rates are between 0.16 and 1.2 %. Globotriaosylsphingosine (Lyso-GL-3), which is a substrate of α-galactosidase A (α-Gal A), has surfaced as a new biomarker, and is also effective in the determination and monitoring of the effects of enzyme replacement therapy. In terms of genetic abnormalities, the E66Q mutation has recently become a topic of discussion, and although doubts have been expressed over whether or not it is the gene responsible for Fabry disease, there is still a strong possibility that it is a functional genetic polymorphism. At present, the standard treatment for Fabry disease is enzyme replacement therapy, and in order to overcome the problems involved with this, a method of producing recombinant human α-Gal A using methanol-assimilating yeast, and chemical or medicinal chaperone treatment are of current interest. Migalastat hydrochloride is known as a pharmacological chaperone, but is currently in Phase III global clinical trials. Adding saposin B to modified α-N-acetyl galactosaminidase is also under consideration as a treatment method.
    No preview · Article · Nov 2013 · Clinical and Experimental Nephrology
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    ABSTRACT: We herein report the case of a 17-year-old man who developed an increased plasma creatinine level (11.1 mg/dL) and oliguria with massive proteinuria (27.3 g/day) four weeks after an abraded wound to his right knee. The histology of the renal biopsy specimens showed diffuse endocapillary proliferative glomerulonephritis with the deposition of nephritis-associated plasmin receptor in the glomerulus. A case of acute kidney injury due to nephrotic syndrome caused by acute post-streptococcal glomerulonephritis was diagnosed. His renal function and proteinuria were improved with supportive care, including hemodialysis, without the administration of immunosuppressive agents.
    No preview · Article · Sep 2013 · Internal Medicine
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    ABSTRACT: We herein report the case of a 75-year-old man who developed an increased serum creatinine level (4.93 mg/dL) and oliguria with massive proteinuria (7.14 g/day) on the second day after a single oral administration of high-dose (56 mg) minodronate. The histology of a renal biopsy showed one area of glomerular sclerosis among 20 glomeruli with global foot process effacement of podocytes and mild infiltration of lymphocytes and eosinophils into the interstitial space. Acute kidney injury in nephrotic syndrome due to focal segmental glomerular sclerosis induced by minodronate was diagnosed. Following cessation of minodronate without the administration of immunosuppressive agents, the patient's renal function and proteinuria markedly improved.
    No preview · Article · Jun 2013 · Internal Medicine
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    ABSTRACT: Klotho, a single-pass transmembrane protein primarily expressed in the kidneys, parathyroid glands, and choroid plexus of the brain, has a short cytoplasmic tail and a long extracellular domain, which can be cleaved and released as a soluble form. However, information regarding the origins and kinetics of soluble serum Klotho remains poorly understood. We evaluated serial changes in serum Klotho levels among living donors before and after retroperitoneoscopic nephrectomy as well as in their renal transplant recipients. The levels of soluble Klotho in serum obtained from 10 living donors and their renal transplant recipients were determined using a sandwich enzyme-linked immunosorbent assay system. Serum soluble Klotho was detectable in all subjects. The baseline serum Klotho concentrations in the living donors ranged from 726.4 to 1417.1 pg/mL (median, 909.8 pg/mL; interquartile ranges [IR], 754.8-1132.4), whereas that in the concomitant renal transplant recipients ranged from 397.5 to 1047.2 pg/mL (median, 613.0 pg/mL; IR, 445.9-750.8; P = .003). The levels of soluble serum Klotho measured 5 days after retroperitoneoscopic nephrectomy (median, 619.0 pg/mL; IR, 544.6-688.5; P = .001) were significantly lower than the baseline values. Among the renal transplant recipients, no significant changes in serum Klotho levels were observed during the observation period. Our data regarding soluble serum Klotho levels obtained from living donors support the idea that the kidneys are a major source of soluble serum Klotho in human subjects without a deterioration of renal function. In recipients, concomitant acute kidney injuries and immunosuppressive protocols might modulate the release of soluble Klotho from the grafts into the circulation.
    No preview · Article · Feb 2013 · Transplantation Proceedings
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    ABSTRACT: Osteoporosis and chronic kidney disease are common conditions in older adults, and often occur concurrently. Bone disease is caused by increased bone turnover accompanying secondary hyperparathyroidism, and by factors such as bone metabolic disorder accompanying kidney disease and postmenopausal or age-related osteoporosis, even in hemodialysis patients. Raloxifene is commonly used for the treatment of postmenopausal osteoporosis in the general population, and may be a treatment option for osteoporosis in hemodialysis patients. However, the effects of raloxifene in hemodialysis patients with type 2 diabetes have not been examined in detail. This study was performed to investigate the effects of raloxifene on bone turnover markers and bone density in postmenopausal women with type 2 diabetes mellitus who were undergoing hemodialysis in Japan. The subjects were 60 female patients on maintenance hemodialysis (non-diabetic, n=30; diabetic, n=30). Raloxifene hydrochloride (60 mg) was administered to 14 diabetic patients and 14 non-diabetic patients for one year, and these patients were compared with control groups (no raloxifene) of 16 diabetic patients and 16 non-diabetic patients. Serum levels of N-terminal cross-linking telopeptide of type I collagen (NTx), bone alkaline phosphatase, and intact parathyroid hormone (iPTH) were measured, and bone density was determined by quantitative heel ultrasound at the speed of sound (SOS) in the calcaneus during this period. There were no significant differences in the levels of bone turnover markers except for iPTH after treatment of diabetic and non-diabetic patients with raloxifene for one year. SOS increased after treatment with raloxifene, but was significantly decreased in the control groups. Treatment with raloxifene resulted in a significant decrease in NTx and a significant increase in SOS in both diabetic and non-diabetic patients. There were no significant differences between the diabetic and non-diabetic patients who received raloxifene. Treatment with raloxifene can suppress reduction in bone density in postmenopausal women with type 2 diabetes who are undergoing hemodialysis.
    Full-text · Article · Dec 2012 · International Journal of Endocrinology and Metabolism
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    ABSTRACT: We report a case of successful treatment with tolvaptan (15 mg/day) in a 73-year-old female patient with chronic kidney disease (CKD) stage 5 due to diabetic nephropathy and renal sclerosis for volume control and loop diuretic-induced hyponatremia. Her creatinine clearance has remained at 7–10 ml/min for the last 6 months. She was treated by dietary and drug therapy, namely, antihypertensives (nifedipine: 40 mg/day, olmesartan: 20 mg/day) and loop diuretics (azosemide: 40–120 mg/day), for CKD and concomitant diseases of hypertension and diabetic mellitus. She developed loop diuretic-induced hyponatremia (120 mmol/l) by increased sodium excretion, but the diuretic was required for the control of volume overload. Hence, azosemide was suspended and tolvaptan (15 mg/day) was administered. After tolvaptan treatment, the plasma sodium level gradually increased to a normal level (135–140 mmol/l) and volume overload was improved. Urine volume was maintained at about 1000 ml/day with low sodium excretion (<40 mmol/day) and increased free water clearance. These results suggest that tolvaptan may be effective for volume control and diuretic-induced hyponatremia in CKD patients.
    Full-text · Article · Nov 2012
  • O. Saito · T. Saito · S. Asakura · E. Kusano
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    ABSTRACT: Osteoporosis and chronic kidney disease (CKD) are common conditions in older adults and often occur concurrently. Hemodialysis patients typically have renal osteodystrophy as the bone-disease component of chronic kidney disease-mineral and bone disorder (CKD-MBD). However, some hemodialysis patients have much lower bone mineral density (BMD), which may be due to postmenopausal or age-related osteoporosis. In this chapter, we evaluated the involvement of estrogen deficiency in bone disease in female hemodialysis patients. The subjects in the first part of the study were 115 adult hemodialysis patients (57 males and 58 females). In April 2006, serum levels of N-terminal cross-linking telopeptide of type I collagen (NTx), bone alkaline phosphatase (BAP), and intact parathyroid hormone (iPTH) were measured as bone turnover markers; and bone density was determined by quantitative heel ultrasound as the speed of sound (SOS) in the calcaneus. A significant positive correlation between age and NTx levels and a significant negative correlation between age and SOS values were found in female subjects; however, neither of these correlations was present in males. Episodes of bone fracture were assessed for 1 year from April 2006 to April 2007. Eight patients (2 males, 6 females) had bone fracture and the NTx levels in April 2006 and age were elevated in these patients. These results suggest that low bone density due to postmenopausal osteoporosis might accelerate bone frailty in female hemodialysis patients and that the NTx level might be an effective marker for postmenopausal osteoporosis. To examine these results, in the second part of this chapter we investigated the effects of raloxifene, a selective estrogen receptor modulator (SERM), on bone turnover markers and bone density in female hemodialysis patients. Raloxifene hydrochloride (60 mg) was administered daily after the evening meal for one year and NTx, BAP, iPTH and SOS were evaluated. NTx significantly decreased after treatment with raloxifene for one year, but significantly increased in the control group; whereas SOS significantly increased after treatment with raloxifene for one year, but significantly decreased in the control group. This chapter indicates that reduction of BMD caused by estrogen deficiency is involved in development of bone disease in female hemodialysis patients, and that raloxifene improves low BMD even in postmenopausal females complicated with CKD-MBD.
    No preview · Article · Oct 2012
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    ABSTRACT: We report membranous nephropathy in a 61-year-old man after allogeneic hematopoietic stem cell transplant without chronic graft-versus-host disease. A diagnosis of acute myeloid leukemia was made, and the patient received hematopoietic stem cell transplants, twice, from different donors. The first donor was his brother and the second donor was an unrelated man. Human leukocyte antigens between donors and recipient were fully matched. His clinical course was stable without acute or chronic graft-versus-host disease or relapse of acute myeloid leukemia with tacrolimus after the second hematopoietic stem cell transplant. Six months after the second hematopoietic stem cell transplant, tacrolimus was decreased gradually and discontinued because of tacrolimus-induced liver dysfunction. Three months after discontinuing the tacrolimus, the patient developed edema in his leg. The results of a blood analysis showed that plasma albumin level was 21 g/L and plasma total cholesterol level was 11.5 mmol/L, while results from a urinalysis showed proteinuria of 5.6 g/d without hematuria. No abnormalities in the skin, mucosal tissues, and other organs suggestive of chronic graft-versus-host disease were seen. A renal biopsy was done to investigate the cause, which revealed renal disease. Electron microscopic analysis showed dense deposits in the subepithelial region in all glomeruli. Immunofluorescence analysis showed the deposition of IgG4 and C3c in the subepithelial space of all glomeruli. Membranous nephropathy was diagnosed. He then was administered prednisolone at a dosage of 45 mg/d (0.7 mg/kg/d). After prednisolone treatment, urine protein and hypoalbuminemia were markedly improved, and his leg edema disappeared. These results suggest that this membranous nephropathy may have been de novo membranous nephropathy after hematopoietic stem cell transplant because it developed after hematopoietic stem cell transplants without chronic graft-versus-host disease.
    No preview · Article · Jul 2012
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    ABSTRACT: A 70-year-old man complained of muscle pain in his neck, shoulders and pelvic girdle. Proteinuria and hematuria subsequently developed. Blood analysis showed increased acute phase reactants. The histology of renal biopsy showed diffuse endocapillary proliferative glomerulonephritis. There were no signs of autoimmune diseases, malignancies and bacterial or viral infections. His extrarenal symptoms and the results of blood analysis fulfilled three different criteria of polymyalgia rheumatica (PMR). Therefore, diffuse endocapillary proliferative glomerulonephritis associated with PMR was diagnosed. After low-dose prednisolone (10 mg/day) treatment, the muscle pain disappeared, acute phase reactants decreased and hematuria and proteinuria improved. The renal complication of PMR is rare but important to be considered early in the right clinical context.
    Full-text · Article · Jul 2012
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    ABSTRACT: We report the case of a 36-year-old Japanese woman with nephrotic syndrome due to membranoproliferative glomerulonephritis (MPGN) Type I diagnosed after a 5-year history of periodic fever syndrome (PFS). Hypocomplementemia and elevation of anti-proteinase 3 anti-neutrophil cytoplasmic autoantibody (PR3-ANCA) were observed. HIV, and hepatitis B and C serology were negative. Nephrotic syndrome and periodic fever did not respond to oral steroid and intravenous steroid pulse therapies combined with cyclosporine, dipyridamole, warfarin and losartan. We tried immunotherapy using rituximab, a human-mouse chimeric monoclonal antibody directed against the CD20 antigen on mature B cells. This therapeutic approach led to improvement of renal function and remission of nephrotic syndrome and hypocomplementemia. However, it did not have a beneficial effect on periodic fever. Suspecting adult-onset hereditary PFS, we analyzed her genetic alteration of MEFV and TNFRSF1A genes. A rare genotype in intron 6 of TNFRSF1A was revealed. The etiological relationship between periodic fever and MPGN is discussed. Rituximab is a hopeful choice of induction therapy for refractory MPGN.
    Full-text · Article · Jul 2012
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    ABSTRACT: We report a case of mesangial proliferative glomerulonephritis with interstitial nephritis associated with multicentric Castleman's disease (MCD) successfully treated with an anti-interleukin-6 receptor antibody (tocilizumab). This mesangial proliferative glomerulonephritis with interstitial nephritis was resistant to methylprednisolone treatment; however, it was markedly improved with tocilizumab, which was administered intravenously at a dose of 8 mg/kg every 2 weeks. These results suggest that tocilizumab is effective for the treatment of mesangial proliferative glomerulonephritis with interstitial nephritis associated with MCD.
    No preview · Article · Jun 2012 · Internal Medicine
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    ABSTRACT: Aim: Low free triiodothyronine (fT3) has been associated with the presence of malnutrition-inflammation syndrome in patients with end-stage renal disease (ESRD) and decreased overall survival in ESRD. Since thyroid hormone has a particular effect on body fluid status, we hypothesized that hemodialysis patients with low-T3 syndrome might have interstitial edema. In this study, we examined the relationship between levels of thyroid hormone and body composition parameters in Japanese hemodialysis patients. Methods: The subjects were 52 patients on maintenance hemodialysis. Serum levels of thyroid hormone and atrial natriuretic peptide (hANP) were measured. Body composition parameters were measured using a bioimpedance body composition analyzer. Results: Serum fT3 had positive correlations with body mass index (BMI), body fat mass (BFM), total body water (TBW) and intracellular water (ICW), and negative correlations with the ratio of extracellular water to total body water (ECW/TBW) and hANP. There were no correlations between serum fT4 and any body composition parameter. The 49 patients with data at baseline and after 1 year were divided into groups with increased (n = 33) and decreased (n = 16) fT3 after 1 year. ΔBMI and ΔBFM were significantly lower and ΔTBW, ΔICW, ΔECW and ΔECW/TBW (changes over 1 year from baseline) were significantly higher in patients with decreased fT3 compared to those with increased fT3. There was no significant difference in ΔhANP or Δcardiothoracic ratio between the two groups. Conclusion: These results show that a decrease in fT3 might be associated with emaciation and interstitial edema in Japanese hemodialysis patients.
    No preview · Article · Jun 2012 · Clinical and Experimental Nephrology