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R Katafuchi

Publications and source records attributed to R Katafuchi.

29 records · Page 2Linked to original sources

An important role of glomerular segmental lesions on progression of IgA nephropathy: a multivariate analysis.

The independent predictors of progression of IgA nephropathy (IgAN) were investigated by multivariate life table analysis, using Cox's proportional hazard model, in 225 patients with IgAN diagnosed by renal biopsy (Bx). There were 105 men and 120 women. Mean age at Bx was 32.5 years. The follow-up period following Bx was 4.0 +/- 2.6 yrs, ranging from 5 months to 11 yrs. The clinical parameters analyzed were age at the time of discovery of the disease, age at Bx, intervals from discovery to Bx, presence or absence of macrohematuria, and clinical data at Bx such as presence or absence of hypertension, the degree of hematuria, the amount of urinary protein excretion, serum creatinine and serum IgA concentration. The following immunopathological parameters were also examined; glomerular hypercellularity index, percentage of glomeruli associated with segmental lesions such as tuft adhesions, crescents and segmental sclerosis, percentage of obliterated glomeruli by global sclerosis, severity of interstitial infiltration, fibrosis, arterial wall thickening, arterial hyaline changes, and intensity of the depositions of IgG, IgA, IgM, C3, C1q and fibrinogen by immunofluorescent study. Among all clinical and pathologic parameters examined, the following parameters were proved to be significant independent predictors of progression of IgAN: serum creatinine exceeding 1.5 mg/dl in men and 1.3 mg/dl in women, proteinuria over 2 g/day, segmental lesions involving more than 25% of glomeruli and interstitial fibrosis occupying more than 25% of cortical area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Primary hyperoxaluria type I due to a point mutation of T to C in the coding region of the serine:pyruvate aminotransferase gene.

cDNA clones for serine:pyruvate aminotransferase (SPT, alternative name: alanine:glyoxylate aminotransferase) were obtained from a cDNA library constructed from the liver of a primary hyperoxaluria type I (PH1) case in which the SPT activity was approximately one-hundredth that in control liver. Six clones were isolated from 100,000 transformants and all of them contained an approximately 1.5 kbp insert which included the whole coding region for human SPT. Nucleotide sequence analysis revealed a point mutation of T to C at position 634 (relative to the 5'-end of the cDNA) encoding a Ser to Pro substitution at residue 205. The T to C conversion created a new SmaI site, which enabled us to demonstrate that the point mutation had occurred in the patient's SPT gene. SmaI digestion of genomic DNA may be useful for the diagnostic gene analysis of this type of PH1.

Adult↗

Microvascular disease and the progression of IgA nephropathy.

In order to examine the role of microvascular disease in the evolution of IgA nephropathy (IgAN), the interrelationships among vascular sclerosis, glomerular sclerosis, age, and hypertension were determined by morphometric analysis of renal biopsies in 71 patients with IgAN; 63 age- and sex-matched individuals with minimal change nephrotic syndrome (MCNS) served as normal controls. The following parameters in glomeruli and in vessels with an outer diameter of 60 microns or less were analyzed by multiple regression analysis: (1) percentage of glomeruli with segmental and/or global sclerosis; (2) percentage of vessel area in renal cortical tissue measured by the point-counting method; (3) index of hyaline change estimated as the percentage of the number of arteries showing hyaline change; (4) index of vessel wall thickness determined by the ratio of mural thickness to outer diameter of arteries; (5) number of vascular cross sections counted per 6.25 microns2. The results of the multiple regression analysis demonstrate that glomerular and vascular sclerosis are interrelated and that hypertension and vessel area are almost equally important as predictors of glomerular sclerosis. Vessel area proved to be an early marker of vasculopathy, as its values in IgAN, even in the absence of hypertension and/or glomerular sclerosis, exceeded those in age- and sex-matched controls (with MCNS). These data, obtained by the use of quantitative methods, establish a role for vessel disease and hypertension in the progression of IgAN.

Adult↗

Prognostic pathologic markers in IgA nephropathy.

Previous studies have shown that the overall severity of the histologic grade and the extent of glomerular sclerosis are important pathologic markers of prognosis in IgA nephropathy. A previous analysis of the clinical and pathologic parameters in 74 patients at New York University Medical Center revealed that the renal survival (serum creatinine concentration of 2 mg/dL or less) was 100% in patients with mild proteinuria, 87% in those with moderate proteninuria, and 69% in those with heavy proteinuria. The incidence of segmental and global proliferation, glomerular sclerosis, tubulointerstitial damage, and vessel sclerosis increased with levels of proteinuria (P less than 0.01 to 0.05). A comparison of the morphologic parameters in 30 patients with similar initial serum creatinine concentrations (less than or equal to 2 mg/dL) but different outcomes demonstrates a greater incidence and severity of pathologic features, especially glomerular sclerosis in the "nonsurvival" than "survival" groups. Vessel sclerosis as quantitatively measured by a "point-count" technique correlates with the extent of glomerular sclerosis (r = 0.5192; P less than 0.001), suggesting a causal relationship or common basis.

Glomerulonephritis, IGA↗

Hypertension-related aggravation of Iga nephropathy: a statistical approach.

To evaluate the influence of hypertension on human glomerulonephritis, 200 biopsies from 74 patients with Iga nephropathy were examined. Chosen for this study were 28 hypertensive patients and 46 normotensive subjects during an observation period of 3.84 +/- 2.17 years, which extended from the first to the last biopsy. In a comprehensive analysis, the following findings were observed: Glomerular sclerosis was analyzed semiquantitatively and estimated as "glomerular index" (GI). Interstitial volume (IV) was determined by the point-counting method. Mesangial electron dense deposits (MDD) and arteriolar hyaline change (HC) were also analyzed semiquantitatively. Arterial fibroelastic intimal thickening was analyzed morphometrically and estimated as the luminal "occlusive rate" (OR). These morphological parameters including their serial changes were compared between the hypertensives and the normotensives. The serial changes in GI and IV from the first to the last biopsy were significantly greater in the hypertensives than in the normotensives. Both OR and HC, including their serial changes, were significantly higher in the hypertensive subjects. In the study of MDD and its serial changes, no difference was apparent between the two groups. In the study of OR and HC, there was no correlation observed with GI. Our observations show that hypertension accelerates the progression of both glomerular and vascular sclerosis in case of human glomerulonephritis and suggests that this acceleration cannot only be explained by ischemia-related factors resulting from vascular sclerosis.

Adult↗

Morphometrical and functional correlations in benign nephrosclerosis.

To ascertain whether or not vascular lesions lead to renoparenchymal damage through ischemia and to a deterioration of renal function in patients with essential hypertension, correlations among morphometrical findings and renal function were examined in 36 renal biopsies from Japanese patients with a benign nephrosclerosis. The following histological parameters were investigated; glomerular sclerotic index (GS), interstitial volume (IV), measured by the point-counting method, index of arteriolar hyaline change (HC) and intimal thickening (IT), determined by morphometry. Arteries were divided into two groups; those with less than 3 layers of medial smooth muscle cells (SMC less than 3) and those with more than 3 cell layers (SMC greater than or equal to 3). The mean of IT in each size was calculated. IT (SMC less than 3) showed a significant correlation with GS and IV. IT (SMC less than 3), GS and IV significantly correlated with Ccr. On the other hand, IT (SMC greater than or equal to 3) and HC showed no correlation with GS nor Ccr. IT (SMC less than 3) and HC correlated with both blood pressure and the duration of hypertension, and here, IT (SMC greater than or equal to 3) showed no correlation. These data suggest that hyaline change and intimal thickening of small arteries and arterioles (SMC less than 3) are closely related to high blood pressure and that intimal thickening of small arteries rather than hyaline change causes renoparenchymal damage through ischemia and leads to a deterioration of renal function, in those with a benign nephrosclerosis.

Adolescent↗

Structural-functional correlations in serial biopsies from patients with glomerulonephritis.

It has been proposed that interstitial fibrosis is causally related to a progressive decrease in glomerular filtration rate (GFR), in patients with various renal diseases. We examined the relationship between morphological and functional parameters in 200 samples from 74 patients with mesangial proliferative glomerulonephritis. The glomerular lesion was semiquantitatively analyzed using the Glomerular Index (GI). Interstitial volume (IV) was determined by the point-counting method. Both GI and IV showed a significant negative correlation with Ccr and a positive correlation with serum creatinine. The serial change in IV from the first to the last biopsy (delta IV) showed a weak but significant negative correlation with those in Ccr, over the same period (delta Ccr). The serial change in GI (delta GI) did not correlate with delta Ccr. There was a significant positive correlation between GI and IV and between delta GI and delta IV. These data confirmed a cause-and-effect relationship between interstitial damage and GFR and also showed that the glomerular lesion as well as the interstitial change play an important role in the deterioration of renal function. Thus, the interstitial lesion alone should not be emphasized as a determinant of renal function, as we noted a close correlation between the interstitial and glomerular lesion. Interstitial damage is apparently secondary to the glomerular lesion in patients with mesangial proliferative glomerulonephritis.

Adolescent↗

Spectrophotometric determination of oxalate in urine and plasma with oxalate oxidase.

In order to establish a standard procedure for the spectrophotometric determination of urinary and plasma oxalate with oxalate oxidase (Laker, M.F., et al. (1980) Clin. Chem. 26, 827-830; Sugiura, M., et al. (1980) Clin. Chim. Acta 105, 393-399) and to define the limitations of the method, the procedures and reactions involved in the assay have been examined. Among the chromogenic hydrogen donors for peroxidase tested, a combination of 3-methyl-2-benzothiazolinone hydrazone (MBTH) and sodium N-sulfopropylaniline (HALPS) was found to be best for the oxalate determination under the conditions used. Urine contained substance(s) which were inhibitory to the measurement of hydrogen peroxide by the peroxidase-catalyzed oxidative condensation of MBTH and HALPS, but they were largely removed by charcoal treatment at pH 5.6 without significant loss of oxalate. Deproteinization of plasma was carried out by ultrafiltration through a membrane cone (Centriflo CF-25) at neutral pH. The plasma oxalate ultrafiltrability under the conditions employed was calculated to be approximately 95%. A standard assay system for oxalate in these urine and plasma samples was then set up based on a series of studies on the reactions involved in the assay. In the case of normal plasma, however, the absorbance change was very small due to the low concentration of oxalate, and in addition, pretreatment of plasma with excess oxalate decarboxylase followed by the ultrafiltration and oxalate determination did not abolish completely the oxalate oxidase-dependent absorbance increase. It was concluded that the enzymic method was useful for the assay of urinary oxalate and in detecting elevated levels of plasma oxalate such as those in hemodialysis patients but was not sensitive enough to determine accurately the normal or decreased level of oxalate in plasma. The apparent concentration of oxalate in normal human plasma was measured in this work as 3.5 +/- 0.8 microM (mean +/- S.D., n = 8), and this result was interpreted to mean that the concentration of plasma oxalate was less than approximately 3.5 microM, as estimated by the present method.

Blood Proteins↗

Proteinuria in amyloidosis correlates with epithelial detachment and distortion of amyloid fibrils.

To obtain a better understanding of the mechanism of proteinuria in amyloidosis we investigated the ultrastructural distribution and pattern of arrangement of glomerular amyloid fibrils in 15 patients. Clinical data were correlated with the ultrastructural features and with the morphometric indices obtained from composite electron micrographs of whole glomeruli. The epithelial side of amyloid deposits showed spicules (discrete pointed bundles of fibrils) and apparent fraying which we termed tufts (ill-defined and diffuse expansion of fibrils). The extent of mesangial amyloid deposition and total GBM deposition did not correlate with proteinuria. Current data suggest the importance of partial detachment of epithelial cells in pathogenesis of proteinuria, which in turn correlates with distortion of amyloid fibrils, spicules and tufts.

Adult↗