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Biomedical subjects

Ichiei Narita

Publications and source records attributed to Ichiei Narita.

At least 19 recordsLinked to original sources

Histological differences in new-onset IgA nephropathy between children and adults.

BACKGROUND: It is suggested that IgA nephropathy (IgAN) manifests differently in children vs adults on the basis of biopsy findings. However, this has been difficult to establish owing to the uncertainty of the timing of disease onset in adult IgAN. We addressed this question by comparing both histology and leucocyte accumulation in biopsies of recently diagnosed childhood and adult IgAN. METHODS: Biopsies taken within 2 years from the onset of renal abnormalities in 33 childhood (10 +/- 3 years of age) and 38 adult (35 +/- 6 years) cases of IgAN were examined for histological changes (cellularity in mesangial, endocapillary and extracapillary areas, matrix expansion, adhesions/crescents and interstitial damage), glomerular deposition of immunoglobulin and complement, and the presence of macrophages, activated macrophages and T cells by immunohistochemistry. RESULTS: Glomerular hypercellularity owing to increased cells in mesangial area was prominent in paediatric IgAN and significantly greater than in adult IgAN. In contrast, glomerular matrix expansion, crescent formation and interstitial damage were more severe in adults compared to paediatric IgAN. Indeed, glomerular hypercellularity correlated with proteinuria in paediatric but not in adult IgAN, whereas glomerular matrix correlated with proteinuria and renal function in adult but not in paediatric IgAN. The degree of C3c deposition was significantly greater in paediatric IgAN, while deposition of fibrinogen was greater in adult IgAN. Glomerular and interstitial CD68+ macrophages and a subset of sialoadhesin (Sn)+ activated macrophages were identified in both paediatric and adult IgAN, being significantly greater in number in adult IgAN. Glomerular leucocyte infiltration correlated with proteinuria while interstitial leucocyte infiltration correlated with interstitial damage in both groups. However, only the subset of Sn+ macrophages gave a significant correlation with renal function, glomerular hypercellularity and glomerular matrix. CONCLUSIONS: This study has demonstrated significant differences in the early glomerular lesions of IgAN in children vs adults. Furthermore, Sn+ activated macrophages are implicated in the pathogenesis of IgAN in both patient groups. The prognostic significance of these findings warrants further study.

Adolescent↗

Analysis of the effect of surgical lung biopsy on serum KL-6 Levels in patients with interstitial pneumonia: surgical lung biopsy does not elevate serum KL-6 levels.

OBJECTIVE: It is well known that the serum level of KL-6 can be an indicator of disease activity in patients with interstitial pneumonia (IP). However, surgical lung biopsy is often required for the diagnosis of IP, although this can result in IP exacerbation. METHODS: The effect of surgical lung biopsy on the serum level of KL-6 in patients with IP was analyzed. Thirty-two cases of IP were examined in this study. There were no cases showing exacerbation of IP. RESULTS: The serum level of KL-6 demonstrated 1067+/-550 U/ml (mean+/-SD) before lung biopsy, 991+/-471 U/ml a day, 824+/-377 U/ml 4 days and 826+/-384 U/ml 7 days after lung biopsy. The serum KL-6 levels on the 1st, 4th, 7th day after the lung biopsy were significantly lower than that before the lung biopsy (P<0.05, P<0.01 and P<0.01, respectively). The percent decrease of the serum KL-6 levels on the 4th day (the lowest level) was dependent on the urine volume, and the analysis of the urinary levels of KL-6 showed a transient increase in urinary KL-6 excretion, suggesting that the decrease in serum KL-6 levels associated with surgical lung biopsy may be caused by this increase in urinary KL-6 excretion. CONCLUSION: Surgical lung biopsy of patients with IP has little effect on the increase in serum KL-6 levels. An elevation of serum KL-6 after surgical lung biopsy may indicate exacerbation of IP.

Aged↗

Abeta-2M-amyloidosis and related bone diseases.

Abeta-2M-amyloidosis is a type of systemic amyloidosis that is specifically seen in patients with chronic kidney diseases. The precursor protein of Abeta-2M-amyloid fibril is beta2-microglobulin, and its elevated serum level is the main cause of Abeta-2M-amyloidosis in patients with kidney failure. However, the precise mechanism of Abeta-2M-amyloidogenesis remains unclear. In vitro analyses of Abeta-2M amyloidogenesis are still being actively conducted. Osteolytic lesions are often found around synovial membrane with Abeta-2M-amyloid deposition. Both evident osteoclastogenesis and active osteoclastic bone resorption are found, while osteoblastic bone formation is absent in the lesion most likely associated with the inflammation caused by infiltrating macrophages/monocytes into Abeta-2M-amyloid deposition. The precise cell biological mechanism of this inflammatory change is unknown. Further studies are needed to establish specific treatments against this as yet unsolved problem with long-term dialysis therapy.

Amyloid↗

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↗

SAA1 gene polymorphisms and the risk of AA amyloidosis in Japanese patients with rheumatoid arthritis.

To investigate the precise modality of association between SAA1 gene polymorphisms and the development of AA amyloidosis in patients with rheumatoid arthritis (RA), Japanese patients with RA (n=153), among whom 29 were histologically diagnosed as having amyloidosis, were genotyped for three single nucleotide polymorphisms (SNPs), C-13T, C2995T, and C3010T, in the SAA gene. Pairwise linkage disequilibrium coefficients between each pair of SNPs were calculated and estimated haplotype frequencies were compared between patients with and without amyloidosis. Possible associations between these SNPs and amyloidosis were analyzed by a case-control study and by the Kaplan-Meier method, in which the endpoint was defined as the time of diagnosis of AA amyloidosis. The -13T and 2995C alleles, which were in a tight linkage disequilibrium, were more frequent in the patients with amyloidosis, and the groups with the -13TT and 2995CC genotype had worse survival curves than patients without these genotypes, whereas C3010T was not associated with amyloidosis. Moreover, the haplotype containing -13C and 2995T was found to be protective. Both C-13T and C2995T were associated with the development of amyloidosis. Examining both polymorphisms may be more useful than examining only one of them for estimating the risk of the development of amyloidosis.

Aged↗

Circulating osteoprotegerin affects bone metabolism in dialysis patients with mild secondary hyperparathyroidism.

Osteoprotegerin (OPG) is a soluble glycoprotein which inhibits osteoclastic formation and activity. Circulating OPG levels are elevated in uremia. The role of elevated circulating OPG levels in uremia remains unknown. Blood samples were obtained from 22 non-diabetic dialysis patients who underwent iliac bone biopsy examination. The serum OPG concentration was assayed by ELISA. The circulating OPG levels showed a negative correlation with the ratio of eroded surface/bone surface (ES/BS) in biopsied iliac bone samples among 15 of those with plasma intact PTH levels less than 300 pg/mL (P < 0.05, r(2) = 0.270). Patients with serum OPG levels less than 2.0 ng/mL showed significantly greater ES/BS values than those with levels > or =3.0 ng/mL, while the intact PTH levels were comparable among those groups. These tendencies disappeared when seven patients with plasma intact PTH levels more than 300 pg/mL were included into the analysis. In conclusion, circulating OPG levels showed a significant negative correlation with a bone resorption parameters in dialysis patients with mild secondary hyperparathyroidism. Circulating OPG might have a suppressive effect on osteoclastic bone resorption in dialysis patients.

Adult↗

Renovascular hypertension: a unique cause of unilateral focal segmental glomerulosclerosis.

A 48-year-old man presented with malignant hypertension and massive proteinuria. Renal angiography showed complete obstruction of the left renal artery and 99mTc-mercaptoacetylglycine (MAG3) renography showed a nonfunctioning left kidney. Percutaneous transluminal renal angioplasty of the left renal artery was unsuccessful; hence, the patient underwent left nephrectomy because of uncontrolled hypertension and proteinuria. Histological examination of a right kidney specimen revealed lesions of focal segmental glomerulosclerosis with benign nephrosclerosis. In contrast, histology of the left kidney showed typical ischemic kidney with hypertrophy of arteriolar smooth muscle cells. The patient responded favorably to the nephrectomy, as his blood pressure and urinary protein dramatically decreased with no antihypertensive medication. This case illustrates the heterogeneous effect of the renin-angiotensin system on either kidney in patients with renovascular hypertension due to unilateral renal artery stenosis.

Glomerulosclerosis, Focal Segmental↗

Pretreatment plasma intact parathyroid hormone and serum calcium levels, but not serum phosphate levels, predict the response to maxacalcitol therapy in dialysis patients with secondary hyperparathyroidism.

BACKGROUND: The treatment strategy for secondary hyperparathyroidism is generally determined empirically with regards to present parathyroid function and serum calcium (Ca) and inorganic phosphate (Pi) levels. More evidence is needed to avoid the aimless continuation of active vitamin D therapy. METHODS: Nondiabetic dialysis patients whose plasma intact parathyroid hormone (iPTH) levels were greater than 300 pg/ml were included in the study. Maxacalcitol was intravenously injected three times a week. The treatment was continued for 48 weeks, unless the iPTH level was reduced to less than 300 pg/ml or unfavorable events occurred. The patients whose plasma iPTH levels were below 300 pg/ml within 48 weeks were defined as those who had been successfully treated. RESULTS: Findings for 146 patients were analyzed, and 96 patients were successfully treated. Serum Pi levels did not significantly increase during the therapy. The pretreatment plasma iPTH levels and serum Ca levels were lower in the patients who were successfully treated with maxacalcitol. A logistic regression study and classifying by stratum analyses revealed that the pretreatment serum Ca levels and plasma iPTH levels were significantly related to the result of maxacalcitol therapy, while the serum Pi levels were not. Analyses using a receiver-operating characteristic curve revealed that the areas under curves obtained for iPTH and Ca were significantly greater than those obtained for Pi (P < 0.0001). CONCLUSIONS: Serum Ca levels and parathyroid function were correlated with the results of maxacalcitol therapy. Pretreatment serum Pi levels could not predict the result.

Adult↗

Monocyte chemoattractant protein-1 A-2518G gene polymorphism and renal survival of Japanese patients with immunoglobulin A nephropathy.

BACKGROUND: Monocyte chemoattractant protein (MCP)-1 is closely related to the pathogenesis of the progression of various chronic renal diseases, including IgA nephropathy (IgAN), through its chemoattractant effect on macrophages. However, the correlation of MCP-1 gene polymorphism with the long-term prognosis of Japanese patients with IgAN has not been clearly determined yet. METHODS: We investigated 277 Japanese patients diagnosed with IgAN based on renal biopsy to clarify the association between the progression of IgAN and MCP-1 gene polymorphism at position A-2518G, which regulates the transcription of the MCP-1 gene. RESULTS: The incidence of endstage renal disease was significantly higher in patients with the AA genotype (47.1%) compared to those with the AG (24.1%) or GG (27.4%) genotype (P = 0.024). Moreover, Kaplan-Meier analysis revealed that the AA genotype significantly facilitated the progression of renal disease (log rank; P = 0.0029), and Cox proportional hazards regression model analysis showed that the AA genotype represented a 2.058-fold risk for the progression of renal disease (P = 0.026) compared to the AG/GG genotype. However, when the patients were treated with angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, or corticosteroid, homozygosity for the -2518A allele was not associated with a higher rate of incidence of endstage renal disease. Serum MCP-1 levels were higher although not significantly so, in the patients with IgAN possessing the AA genotype. CONCLUSIONS: The AA genotype at MCP-1 -2518 was an independent risk factor for the progression of renal disease in Japanese patients with IgAN, and was closely associated with renal survival.

Adult↗

Osteopontin expression in acute renal allograft rejection.

BACKGROUND: Osteopontin (OPN) is a potent chemoattractant for mononuclear cells that is up-regulated in various inflammatory states of the kidney. The role of OPN and its expression in human renal allograft rejection are unknown. METHODS: We examined by immunohistochemistry and in situ hybridization, renal biopsies from patients with acute rejection (N= 22), protocol biopsies without rejection (N= 9), and perioperative donor biopsies (N= 35) for intrarenal expression of OPN, and its correlation with clinical, laboratory, and histopathologic parameters. In the rejection biopsies, interstitial monocyte/macrophage infiltration, tubulointerstitial cell proliferation/regeneration and apoptosis were investigated. RESULTS: In the majority of rejection biopsies, OPN expression by proximal tubular epithelium was widespread, and tended to be enhanced in the tubules surrounded by numerous inflammatory cells. Conversely, in patients that did not experience episodes of rejection and in donor biopsies, OPN expression by proximal tubules was nil or weak. OPN mRNA was colocalized with its translated protein in the renal tubular epithelium. OPN expression positively correlated with the degree of interstitial inflammation (P < 0.05), CD68+ monocyte infiltration (P < 0.01), Ki-67+ regenerating tubular and interstitial cells (P < 0.05 and P < 0.005, respectively), but not with terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL)-positive apoptotic tubular cells. CONCLUSION: These data suggest that inducible expression of OPN in the tubular epithelium may have a pathogenic role in acute renal allograft rejection by mediating interstitial monocyte infiltration and possibly tubular regeneration.

Acute Disease↗

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↗

Bezafibrate suppresses rat antiglomerular basement membrane crescentic glomerulonephritis.

BACKGROUND: The immunoregulatory activity of ligands for peroxisome proliferator-activated receptors (PPARs) has been recently paid attention. The regulatory effect of bezafibrate (BZF), a ligand for PPARalpha on glomerulonephritis was investigated using a rat anti-glomerular basement membrane (GBM) glomerulonephritis model. METHODS: The effect on development of anti-GBM glomerulonephritis was examined by treatment with BZF from day -7 to day 7 after intravenous injection of rabbit anti-GBM serum into Wistar Kyoto (WKY) rats. The therapeutic efficacy after onset of the glomerulonephritis was also checked by treatment with BZF from day 3 to 7. On day 7, the condition was evaluated histologically. The expression of a tissue injury molecule, macrophage metalloesterase (MME), was measured by Northern blot analysis. The suppressive effect on immune cells was assessed by proliferation assay with mitogen-stimulated rat spleen cells. RESULTS: Histopathologic changes induced by anti-GBM in rats treated with BZF (day -7 to day 7) were markedly suppressed in a dose-dependent fashion. Infiltration of ED-1+ macrophages in glomeruli, proteinuria, and mRNA expression of MME in kidneys were diminished in parallel with histologic improvement. Moreover, the disease activity was also attenuated even by the treatment after onset of the glomerulonephritis (day 3 to 7). The mitogen-induced proliferation of spleen cells was down-regulated at concentrations of BZF, which were equivalent to those in sera of BZF-treated rats. CONCLUSION: BZF markedly suppresses the activity of rat anti-GBM crescentic glomerulonephritis. Fibrates might serve as a therapeutic option for crescentic glomerulonephritis.

Animals↗

A novel type of encephalopathy associated with mushroom Sugihiratake ingestion in patients with chronic kidney diseases.

BACKGROUND: The etiology of encephalopathy in uremic patients is multiple. We recently encountered a novel type of encephalopathy which occurred exclusively in patients with chronic kidney diseases after ingestion of a mushroom called Sugihiratake. While the exact etiology of this encephalopathy remained mysterious, we aimed to describe its clinical features. METHODS: A total of 32 patients with chronic kidney diseases who had presented with encephalopathy following ingestion of Sugihiratake were enrolled from seven prefectures in Japan., with 24 of the 32 patients undergoing regular hemodialysis. The patient's clinical data were from surveillance by The Japanese Society of Nephrology. RESULTS: There was a significant association between Sugihiratake ingestion and the occurrence of encephalopathy in 524 hemodialysis patients questioned for a recent ingestion of this mushroom (P= 0.0006). The latent asymptomatic period before the onset of symptoms varied from 1 to 31 days (mean 9.1 +/- 7.3) days. The patient's symptoms consisted of disturbed consciousness in 30 patients (93.8%), convulsions in 25 (78.1%), myoclonus in 15 (46.9%), dysarthria in ten (31.3%), ataxia in eight (25.0%), paresis or paralysis in seven (21.9%), and skin parasthesia in two patients (6.3%). Nine (27.2%) patients died, mostly due to respiratory failure. The other patients were either discharged or still in hospitals with various degrees of clinical improvement. CONCLUSION: Patients with chronic kidney diseases are at risk of having serious encephalopathy following Sugihiratake ingestion and must refrain from eating it. Physicians, in those parts of the world, where this mushroom harvesting is common, should be aware of this complication.

Agaricales↗

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↗

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↗