[Elderly male patient with central nervous system lupus undergoing hemodialysis].
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Aged↗
Biomedical subjects
Shouichi Fujimoto
Publications and source records attributed to Shouichi Fujimoto.
Increased production of adrenomedullin in glomeruli from anti-glomerular basement membrane glomerulonephritis rats treated with methylprednisolone.
BACKGROUND/AIMS: Adrenomedullin (AM) has anti-proliferative and apoptotic effects on mesangial cells (MCs). Both effects play an important role in the progression of glomerulonephritis (GN). Glucocorticoids are widely used for the treatment of GN; however, the relationship between AM regulation in MCs or glomeruli and glucocorticoid treatment has not been clarified. METHODS: Using the cultured rat MCs, AM secretion induced by methylprednisolone (m-PSL), and MC proliferation and apoptosis caused by AM were examined. In addition, the role of AM receptor antagonist, AM(22-52), was also investigated. Then, we made an anti-glomerular basement membrane (GBM) GN rat model and compared the AM expression and production in each glomeruli obtained from the control or m-PSL-treated anti-GBM GN rats. RESULTS: In the cultured rat MCs, AM secretion was increased by m-PSL. MC proliferation was inhibited, while MC apoptosis was increased by AM. MC apoptosis was inhibited by the addition of AM(22-52). M-PSL therapy ameliorated the progression of anti-GBM GN rats. AM expression and production were increased in the glomeruli from m-PSL-treated rats compared to the controls. CONCLUSION: Considering the anti-proliferative and apoptotic effects of AM on MCs, increased AM in the glomeruli might participate in the improvement of glomerular lesions in anti-GBM GN rats treated with m-PSL.
Adrenomedullin↗
Renal biopsy in elderly patients: a clinicopathological analysis.
As the numbers of aging patients with manifestations of renal disease increase, the elderly must frequently undergo renal biopsies. This study examined the characteristics of clinicopathological correlations in elderly patients. Medical and clinical records from renal biopsies registered in two hospitals between January 2000 and December 2004 were reviewed. Among 406 patients (female: male 224/182; age 43.9 +/- 18.8 years, mean +/- SD) who underwent renal biopsies, 61 (15.1%) who were aged 65 years and older (female: male, 29/32; age 72.8 +/- 5.2 years) were selected. The elderly usually underwent percutaneous renal biopsies for renal diseases such as nephrotic syndrome (43%) and acute or rapidly progressive renal failure (A/RPRF, 39%). Focal/segmental glomerulosclerosis (23%), minimal change disease (19%), and membranous nephropathy (15%) are frequently diagnosed based on biopsy specimens from patients with nephrotic syndrome. Among patients presenting with A/RPRF, 17 (71%) and 4 (17%) had pauci-immune, MPO-ANCA positive, crescentic glomerulonephritis and interstitial nephritis, respectively, and benefited from therapeutic intervention. Histopathological and pre-biopsy clinical diagnoses differed in nine (15%) patients. The complication rate after biopsy was low (3%). Primary glomerular diseases presenting with nephrotic syndrome and primary crescentic glomerulonephritis associated with rapidly progressive renal failure were the most frequently diagnosed among the elderly who underwent renal biopsy. Percutaneous renal biopsy provides clinically useful information about the elderly because clinical presentation and the predicted diagnosis sometimes vary.
Aged↗
Leukocytapheresis for ulcerative colitis: a comparative study of anticoagulant (nafamostat mesilate vs. dalteparin sodium) for reducing clinical complications.
Leukocytapheresis (LCAP) is a therapeutic strategy for extra corporeal immunomodulation that has been used to treat several immunological disorders, including ulcerative colitis (UC), with encouraging results, inducing remission in steroid-resistant patients. However, we have experienced some complications during or after LCAP therapy. Common adverse effects include fever, chills, nausea, vomiting, and hypotension. One of the reasons for these adverse effects might be the use of nafamostat mesilate (NM) as an anticoagulant. In the present study, 75 patients with UC were divided into two groups, an NM group and a dalteparin sodium (DS) group. The clinical efficacy of these treatments, improvement after treatment, changes in leukocyte differential count, and adverse effects after LCAP therapy were then compared. The clinical efficacy, improvement after treatment, and changes in leukocyte classification were not significantly different between the two groups, while some adverse effects were observed in the NM group but not in the DS group. In conclusion, LCAP therapy is a useful therapy for patients with moderate to severe UC who fail to respond to glucocorticoid therapy, however, a safe anticoagulant should be used to avoid its related adverse effects.
Adolescent↗
A rare case of alveolar haemorrhage due to malignant hypertension.
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Adult↗
Multivariate analysis of prognostic factors and effect of treatment in patients with IgA nephropathy.
BACKGROUND: Although the clinical and histological prognostic factors of IgA nephropathy have been investigated in detail, the value of treatment in terms of renal outcome is not well understood. METHODS: The authors examined data from 237 patients with IgA nephropathy (age 31.4+/-13.5 years, mean+/-SD) who had been followed-up for at least six months (follow-up periods, 62.3+/-45.5 months). The authors initially tested the significance of prognostic factors (age, sex, systolic blood pressure, proteinuria, serum creatinine, and histological severity) and treatment strategies (steroid therapy, renin-angiotensin system inhibitors and tonsillectomy) on renal outcome with univariate analysis, then evaluated the findings using the Cox proportional hazards model. RESULTS: Univariate and multivariate analyses showed that among the prognostic variables, a high level of serum creatinine at renal biopsy, large amounts of proteinuria, and extensive histological injury were significant risk factors for end-stage renal failure. Kaplan-Meier analysis showed that the renal survival rates associated with these factors were significantly poorer depending on their severity. Univariate analysis revealed that tonsillectomy was the only significant treatment that contributes to the maintenance of renal survival. Moreover, urinary abnormalities disappeared at a significantly higher frequency when patients were treated by tonsillectomy. The Cox proportional hazards model showed that steroid therapy independently contributed to improve renal prognosis in addition to tonsillectomy, and the hazard ratios were 0.26 (95% CI, 0.07 to 0.93) and 0.37 (95% CI, 0.14 to 0.99), respectively. CONCLUSION: Steroid therapy and tonsillectomy can independently improve renal outcome in patients with IgA nephropathy.
Adolescent↗
Effect of sevelamer on dyslipidemia and chronic inflammation in maintenance hemodialysis patients.
BACKGROUND: Hemodialysis (HD) patients often experience cardiovascular events, that might be related to altered calcium-phosphate metabolism, dyslipidemia, and chronic inflammation in addition to hypertension. Sevelamer, a non-calcium-containing phosphate binder, may improve the lipid profile of HD patients. However, the influence of sevelamer on chronic inflammation has not been clarified. METHODS: We enrolled 36 maintenance HD patients with a serum calcium (Ca) or phosphate (P) level constantly greater than 9.5 mg/dL and 5.5 mg/dL, respectively. The dose of sevelamer was titrated to achieve a serum Ca and P in the target ranges. The study period was 24 weeks. Patients underwent the following measurements: bone mineral markers, lipids, and a high-sensitivity C-reactive protein (hs-CRP). RESULTS: In the 28 patients who completed the study, sevelamer significantly reduced the mean non-high-density lipoprotein cholesterol (non-HDL-C) level by 15% and 20% (p < 0.0001) after 12 and 24 weeks, respectively, in addition to reducing the serum P level and Ca x P product. Similarly, there was a significant reduction of the serum hs-CRP level after 12 and 24 weeks [median at baseline: 1.03 mg/dL (interquartile range 0.26-3.98 mg/dL) versus 0.57 (0.17-1.47) and 0.38 (0.16-1.03), respectively, p = 0.0259]. The reduction rate of hs-CRP was significantly correlated with those of non-HDL-C (r = 0.451, p < 0.0401) and P (r = 0.453, p < 0.0008) CONCLUSION: Hs-CRP levels were reduced by sevelamer administration, as well as non-HDL-C, P, and the Ca x P product. Sevelamer may have an anti-inflammatory effect, in addition to lowering phosphate and lipid levels in HD patients.
Aged↗
[Three patients with nephrotic syndrome due to membranous nephropathy complicated by Sjögren's syndrome].
We describe three females patients (age 40, 62 and 63 y) with nephrotic syndrome due to membranous nephropathy complicated by Sjögren's syndrome(SS). The patients satisfied the criteria for SS, but not those for systemic lupus erythematosus(SLE). All of them developed nephrotic syndrome, and light immunofluorescence as well as electron microscopy of renal biopsy specimens revealed membranous nephropathy. Two were positive for the SS-A antibody, and the other was positive for the SS-B antibody. Two were complicated with primary biliary cirrhosis (PBC) and autoimmune thyroiditis, whereas the other was complicated with interstitial pneumonia, but not with either PBC or autoimmune thyroiditis. Prednisolone (PSL) with or without cyclophosphamide improved the nephrotic syndrome in two of the patients. In conclusion, some patients with SS might become complicated with nephrotic syndrome due to membranous nephropathy if another systemic autoimmune disease exists.
Adult↗
Role of uroguanylin, a Peptide with natriuretic activity, in rats with experimental nephrotic syndrome.
Uroguanylin induces natriuresis and diuresis in vivo as well as in vitro and is found mainly in the intestine and the kidney. However, the roles of uroguanylin in nephrotic syndrome, which is associated with sodium and water retention, have not been determined. Therefore, changes in the urine and plasma concentration of immunoreactive uroguanylin (ir-uroguanylin) and its mRNA expression in the kidney and intestine were examined using rats with puromycin aminonucleoside (PAN)-induced nephrosis. Male Sprague-Dawley rats were separated into control and nephrotic groups, and then the urinary excretion of sodium, protein, and ir-uroguanylin was examined over time. The plasma levels and renal and intestinal mRNA expression of uroguanylin at the periods of sodium retention and remarkable natriuresis also were evaluated. The sequential changes of urinary ir-uroguanylin excretion in the nephrotic group were similar to those of urinary sodium excretion. When the urinary excretion of ir-uroguanylin and sodium peaked, the plasma level of ir-uroguanylin also increased compared with that of the control group. Uroguanylin mRNA expression in the kidney increased during the period of sodium retention and then decreased during the period of remarkable natriuresis. Uroguanylin mRNA expression in the small intestines of control and nephrotic rats were identical. However, in a unilateral PAN-induced proteinuria, uroguanylin expression significantly increased in the PAN-perfused kidney compared with that in the opposite kidney. Considering the natriuretic effect of uroguanylin, these results suggested that uroguanylin plays an important role as a natriuretic factor in nephrotic syndrome via both the circulation and the kidney itself.
Animals↗
Adrenomedullin (AM) and receptor-activity-modifying proteins in glomeruli with Thy.1 glomerulonephritis.
BACKGROUND: Adrenomedullin (AM) has antiproliferative and proapoptotic effects on mesangial cells in culture, but the regulation of AM and its receptors in glomeruli with glomerulonephritis have not been clarified. METHODS: We examined sequential changes in the mRNA expression of AM and its receptors (receptor-activity-modifying proteins; RAMPs), and AM production in the glomeruli of Thy.1 glomerulonephritis, using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunoradiometric assay (IRMA). RESULTS: Both the mRNA and the protein levels of AM in glomeruli isolated from rats 7 days after injection with anti-thymocyte serum (ATS), when mesangial cell proliferation peaked, were unchanged compared with those in control rats. However, on day 14, when almost all glomeruli had appeared to return to normal, AM mRNA expression was significantly increased (day 14 vs control: 51.2 +/- 9.1 vs 28.4 +/- 7.1 (mmol/mol glyceraldehyde-3-phosphate dehydrogenase; GAPDH); P < 0.05), as was the AM concentration (12.0 +/- 0.8 vs 8.4 +/- 0.4 fmol/10(4) glomeruli; P < 0.01). Subsequently, by 28 days after ATS injection, both levels decreased to the control ones. The mRNA expression of AM and RAMP2, in the glomeruli of Thy.1 glomerulonephritis changed similarly over time. Immunohistochemical staining revealed that AM production in mesangial cells was increased predominantly on day 14. CONCLUSIONS: AM and RAMP increased during the reso-lution phase of increased mesangial proliferation in Thy.1 glomerulonephritis, but not during the mesangial proliferative phase. Considering the antiproliferative and proapoptotic effects of AM, its action on mesangial cells may be related to the amelioration of glomerulonephritis.
Adrenomedullin↗
Development of an ultrasensitive enzyme immunoassay for human proadrenomedullin N-terminal 20 peptide and direct measurement of two molecular forms of PAMP in plasma from healthy subjects and patients with cardiovascular disease.
OBJECTIVE: Proadrenomedullin N-terminal 20 peptide (PAMP) processed from an adrenomedullin precursor is a potent hypotensive peptide. It was anticipated that a mature form of PAMP (m-PAMP) and an intermediate PAMP-gly existed together in the blood. To measure concentrations of PAMPs in human plasma directly, we have developed a highly sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay, ICT-EIA). DESIGN AND METHODS: PAMP was reacted simultaneously with 2,4-dinitrophenyl (DNP)-biotinyl-bovine serum albumin (BSA)-anti-PAMP Fab' conjugate and anti-PAMP Fab'-beta-D-galactosidase conjugate. The immune complex that was formed was initially trapped onto a polystyrene bead coated with anti-DNP IgG, and then transferred onto a second polystyrene bead coated with streptavidin. The resulting three-component complex was then assayed fluorometrically. RESULTS: The detection limits of ICT-EIA for both m-PAMP and PAMP-gly were 0.1 pmol/l with as little as 10 microl of plasma, and were a hundred times higher than with conventional radioimmunoassay (RIA). Using ICT-EIA, we determined that the plasma concentrations of m-PAMP and PAMP-gly in 51 healthy volunteers were 0.51 +/- 0.19 and 1.15 +/- 0.38 pmol/l (mean +/- SD), respectively. Both plasma m-PAMP and PAMP-gly concentrations in patients with a variety of diseases, including hypertension, heart failure, chronic renal failure, and hemodialysis, were significantly higher than those in healthy subjects. In addition, both plasma m-PAMP and PAMP-gly concentrations in patients with New York Heart Association (NYHA) class I-IV heart failure were increased in proportion to clinical severity. CONCLUSIONS: These sensitive and specific ICT-EIAs may be used as a powerful tool for investigating the cardiovascular system in patients with heart failure.
Adrenomedullin↗
Relationship between serum IgA/C3 ratio and progression of IgA nephropathy.
OBJECTIVE: The serum IgA/C3 ratio might be considered to serve as a diagnostic marker for patients with IgA nephropathy (IgAN), but its value as a marker of the severity of histological lesions or prognosis is unknown. METHODS: We studied the serum IgA/C3 ratio, using standardized reference material, in 86 patients with IgAN and in 32 with non-IgAN. The patients with IgAN were divided according to the severity of histological lesions (mild IgAN, n=29 and severe IgAN, n=57) based on Japanese clinical guidelines. RESULTS: The serum IgA level was significantly higher, while its C3 level was lower in patients with severe IgAN compared to those with non-IgAN. However, these levels were not different between patients with mild IgAN and non-IgAN. In contrast, the serum IgA/C3 ratio obviously differed among the three groups (2.47+/-0.96 vs. 3.63+/-1.44 vs. 4.72+/-1.86; p<0.01, ANOVA). Kaplan-Meier analysis of the patients with IgAN classified according to the mean serum IgA/C3 ratio revealed that the group with high serum IgA/C3 (4.5 and above) had a significantly poorer renal outcome (p<0.05, log-rank test), since the cumulative renal survival rate at 5 years was 84.4% vs. 100%. The ratio (%) of patients with severe IgAN in whom hematuria disappeared, was significantly higher in the low, than in the high serum IgA/C3 group (41.9% vs. 15.4%; p<0.05, t-test). CONCLUSION: The serum IgA/C3 ratio appears to reflect the histological severity of IgAN and could serve as a marker of the progression of IgAN.
Adult↗
Nephrotic syndrome caused by membranous nephropathy: response to a short course of cyclophosphamide alternating with prednisolone.
OBJECTIVE: The optimal duration of immunosuppressive therapy and the timing of treatment for treating membranous nephropathy (MN) have yet to be established. We examined outcomes of a short course of cyclophosphamide alternating with prednisolone for MN patients with nephrotic syndrome. METHODS AND PATIENTS: Cyclophosphamide (2 mg/kg/day for 8 weeks) combined with prednisolone (1 mg/kg every 48 hours for 8 weeks, then tapering off for 1 year) was prescribed for 28 MN patients (12 men and 16 women; mean age 52.4+/-2.25 years SEM). We first evaluated the response rates to this combined therapy, then compared the clinical characteristics of those who achieved remission (group A) with those who did not (group B) within 6 months of the start of treatment. RESULTS: The incidences of complete and partial remission increased with the follow-up period; 32 and 21% by 6 months, 54 and 29% by 12 months, and 79 and 11% by 24 months, respectively. Serum IgG (906+/-100.8 versus 562+/-66.1 mg/day; p<0.01) was significantly higher in group A, and the selectivity index (C(IgG)/C(albumin) 0.16+/-0.015 versus 0.30+/-0.040; p<0.01), significantly lower. Nephrotic syndrome persisted in 3 group B patients (23%), who finally had impaired renal function. CONCLUSION: MN patients with nephrotic syndrome responded favorably to a short course of cyclophosphamide combined with prednisolone. The serum IgG level and selectivity index may serve as markers of early response to this treatment.
Biopsy, Needle↗
Minimal change nephrotic syndrome after allogenic hematopoietic stem cell transplantation.
We describe a 24-year-old man who developed minimal change nephrotic syndrome after allogenic hematopoietic stem cell transplantation (HSCT). One year after undergoing allogenic peripheral blood stem cell transplantation (PBSCT), this patient presented with proteinuria. He also presented with skin and lip lesions considered to be chronic graft-versus host disease. Observation of renal biopsy specimens by light microscopy revealed minor glomerular abnormalities. However, electron microscopy disclosed focal mesangial interposition, irregular thickening of the glomerular basement membrane and subendothelial loosening. Two years after HSCT, the patient developed nephrotic syndrome. Long use of cyclosporine improved the proteinuria and hypoalbuminemia within 12 months.
Adult↗
Plasma levels of proadrenomedullin N-terminal 20 peptide and adrenomedullin in patients undergoing hemodialysis.
BACKGROUND: Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide present in the precursor of adrenomedullin (AM), a vasodilative and natriuretic peptide. However, the profile of PAMP in hemodialyzed (HD) patients has not been determined. METHODS: We measured plasma levels of PAMP, total AM (tAM) and a mature form of AM (mAM, the biologically active form) in HD patients (n = 31) and in normal controls (n = 21). RESULTS: Plasma concentrations of PAMP before HD were significantly higher than those in controls (4.02 +/- 0.24 vs. 1.64 +/- 0.12 fmol/ml, p < 0.001) and decreased to the control level after HD (2.17 +/- 0.18 vs. 1.64 +/- 0.12 fmol/ml; NS). The plasma PAMP level before HD significantly correlated with weight gain during HD sessions (r = 0.41, p < 0.05), but not with predialysis blood pressure. The concentrations of mAM before and after HD were significantly higher than those in controls. The plasma mAM level before HD significantly correlated with weight gain during HD sessions, but not with predialysis blood pressure. The plasma level of PAMP did not correlate with that of mAM in HD patients. CONCLUSION: PAMP and AM may be involved in the regulation of blood volume in patients undergoing HD.
Adrenomedullin↗
[Analysis of factors affecting the course of renal disease progression in patients with established renal insufficiency].
All renal diseases ultimately progress to end-stage renal disease after renal dysfunction develops except for acute renal failure or rapidly progressive glomerulonephritis. However, renal function can be preserved for long periods in patients with mild renal insufficiency. We examined the factors affecting the progression of renal disease in patients with established renal insufficiency. We enrolled 38 patients with renal insufficiency diagnosed at the first visit and who were followed up for at least 3 years. We retrospectively recorded all information relating to serum creatinine and blood pressure levels during the follow-up periods. The patients were categorized as group A(n = 11), long-term renal survivors(at least 8 years), group B(n = 22), short-term renal survivors(3 to 8 years) and others(n = 5). Basal renal diseases were variable, and included IgA nephropathy, membranous nephropathy, focal segmental glomerulosclerosis, hypertensive glomerulosclerosis, tubulo-interstitial disease and lupus nephritis. Except for the degree of urinary occult blood, no other clinical data obtained at the first visit differed between groups A and B. Overall blood pressure levels throughout the entire clinical course also did not differ between the two groups. However, mean blood pressure levels before serum creatinine had reached the level of 2.0 mg/dl were significantly lower in group A compared with group B (96 +/- 7.8 vs. 103 +/- 6.3 mmHg, p < 0.05). We considered that the serum creatinine level of the so-called "point of no return" might be 2.0 mg/dl. In conclusion, blood pressure should be strictly controlled before serum creatinine levels reach 2.0 mg/dl.
Adult↗
[Two cases of interstitial nephritis with primary Sjögren's syndrome successfully treated by steroid therapy].
We have experienced two cases of interstitial nephritis with Sjögren's syndrome successfully treated by steroid therapy. Case 1. A 50-year-old woman was admitted because of rash and arthralgia of the limb. Although her renal function was normal, serum IgG was extremely high and gallium-67 scintigrams indicated abnormal uptake in both kidneys with swelling on CT scans. Renal biopsy specimens showed a patchy dense interstitial infiltration of lymphocytes, monocytes and partly plasma cells with tubular cell atrophy. To suppress an excessive immune reaction, oral prednisolone was administrated at a dose of 30 mg/day. Six weeks after inception of the therapy, re-biopsy specimens showed a decrease in interstitial infiltration, particularly plasma cells, and interstitial fibrosis did not progress. After 8 weeks, the serum IgG level was normalized. Case 2. A 57-year-old woman was found to have renal involvement(serum creatinine level: 2.2 mg/dl) and anemia. Clinical findings suggested primary Sjögren's syndrome with renal tubular acidosis. Renal biopsy specimens showed a moderate to severe interstitial infiltration of inflammatory cells. After inception of steroid therapy(prednisolone 40 mg/day), renal involvement and renal anemia gradually improved. The renal function has been kept stable(serum creatinine level: 1.5 mg/dl) for 9 years by low-dose steroid therapy. These two cases suggest that steroid therapy plays two important roles: controlling of the acute immune reaction that causes renal fibrosis to progress in case 1, and long-term preservation of the renal function by the continuous use of low-doses in case 2.
Anti-Inflammatory Agents↗