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Biomedical subjects

S Yoshiara

Publications and source records attributed to S Yoshiara.

9 recordsLinked to original sources

Glomerular morphometry in reflux nephropathy: functional and radiological correlations.

Using computerized digitometry, we investigated the relationships between renal size, glomerular filtration rate (GFR), proteinuria, incidence of segmental and global glomerulosclerosis, glomerular size, hilar arteriolar wall thickness and hyaline deposition in renal biopsies obtained from 24 children and adolescents with reflux nephropathy, of whom only 4 were hypertensive. Age-matched controls comprised minimal-change nephrotic syndrome (6) and recurrent haematuria with normal biopsy (13). The mean sectional area of patients' glomeruli was double that of controls. Glomerular size correlated with the amount of proteinuria (measured as protein/creatinine ratios in early morning urine) and inversely with renal size and GFR. Segmental sclerosis, invariably of hilar origin, was observed in 8 patients and the percentage of glomeruli affected correlated strongly with glomerular size and proteinuria. Global sclerosis was found equally in patients and controls, and showed no similar correlations. Compared with controls, patients' hilar arterioles showed increased wall thickness, more intramural hyaline deposits and decreased luminal diameter when related to glomerular size. The proteinuria and glomerular changes are consistent with hyperfiltration, while the previously undescribed hilar vascular changes, which both precede and accompany sclerosis, resemble abnormalities reported experimentally following renal ablation.

Adolescent↗

The glomerular changes in children with reflux nephropathy.

While heavy proteinuria and focal segmental glomerulosclerosis (FSGS) are well-recognized features of progressive reflux nephropathy in adults, little is known of their early evolution. We have studied the glomerular changes in renal biopsy specimens obtained from 24 patients aged 5.2-18.8 years, in whom urinary protein excretion was measured as early morning urine protein creatinine ratios, using the Coomassie blue dye-binding method. Segmental sclerotic lesions were found in eight biopsies and traced through serial sections to a hilar origin in every instance. There was a strong positive correlation between the extent of glomerular involvement and the amount of proteinuria (P less than 0.0001). Parahilar hyaline deposits were observed in 16 biopsies, including five of the eight showing FSGS. All unsclerosed glomeruli were enlarged, and the hilar arterioles showed both enlargement and thickening, their walls frequently containing subendothelial hyaline deposits. Since in most patients renal function was comparatively well preserved, despite extensive loss of renal substances, we believe that these glomerular and vascular changes represent the stages in the evolution of hyperfiltration. Microproteinuria is the earliest clinical manifestation of FSGS, and should be sought routinely in all patients with reflux nephropathy.

Adolescent↗

Focal and diffuse membranoproliferative glomerulonephritis in children.

Characteristic deposition of C3 has been reported in type I membranoproliferative glomerulonephritis (MPGN). Immunofluorescence microscopy shows diffuse granular deposition of C3 along the majority of capillary loops with lobular pattern. To determine the specificity of this immunofluorescence finding which might aid in distinction between type 1 MPGN, particularly focal MPGN, and the other glomerulopathies, 530 renal biopsies from 437 children were studied retrospectively. Nineteen patients showed diffuse granular deposits of C3 along the capillary walls with lobular distribution. Three patients had lupus nephritis. Nine patients showed the light microscopic changes of diffuse type I MPGN with the characteristic double-walled capillaries. Six patients showed the changes of focal MPGN, and 1 had diffuse mesangial proliferation but without double contours, and they were regarded as examples of a mild or early form of MPGN. A similar deposition of C3 was not seen in the 418 patients with other conditions. We concluded that diffuse granular deposits of C3 along the capillary walls with a lobular distribution appear to be confined to type I MPGN and lupus nephritis and are seen in all patients with diffuse and focal type I MPGN.

Biopsy↗

Immunoelectron microscopic study of childhood IgA nephropathy and Henoch-Schönlein nephritis.

Renal biopsy specimens from 11 children with Henoch-Schönlein nephritis and 14 with IgA nephropathy were examined by immunoelectron microscopy. The distribution of IgA reaction product (RP) was found to be similar to that of the electron-dense deposits seen with conventional electron microscopy. Deposits of IgA-RP were present in the mesangium and in the subendothelial region of the peripheral glomerular capillary wall in all patients. Subepithelial deposits of IgA-RP were seen in 12 patients. Deposits of IgG-RP were rare and no deposits of IgM-RP were observed. Deposits of C3-RP were found frequently, although they were smaller and less extensive than deposits of IgA-RP. There was no significant difference between Henoch-Schönlein nephritis and IgA nephropathy with regard to immunoelectron microscopy findings. These observations suggest that Henoch-Schönlein nephritis and IgA nephropathy are both forms of mesangiopathic glomerulo-nephritis caused by immune complexes, mainly composed of IgA.

Adolescent↗

Clinical course of immunoglobulin A nephropathy in children.

The clinical presentation, initial laboratory and renal biopsy findings, and subsequent clinical course of IgA nephropathy were studied retrospectively in 200 children, and findings in those with younger onset and older onset were compared. Eighty-three patients were 8 years of age or younger (group 1) and 117 were 9 years of age or older (group 2) at onset. There were no differences between the two groups with regard to sex, initial renal function, incidence of hypertension and macroscopic hematuria, degree of proteinuria, and pathologic findings. At the latest follow-up, two patients in group 1 and eight in group 2 had chronic renal failure, and five patients in group 1 and 21 in group 2 had heavy proteinuria with or without hypertension (P less than 0.01), whereas 36 (43%) patients in group 1 and 29 (25%) in group 2 had normal urine, blood pressure, and glomerular filtration rate (P less than 0.01); the disease followed a significantly more benign course in children with younger onset than in those with older onset. These observations suggest some age-related differences in the natural history of childhood IgA nephropathy.

Age Factors↗

Mesangial changes in IgA nephropathy in children.

The mesangial changes in 92 renal biopsy specimens from 81 children with IgA nephropathy were correlated with the clinical and the other renal biopsy findings. Three types of mesangial changes were identified: mesangial hypercellularity was predominant compared with the increase in matrix in 34 biopsy specimens (type A), the degrees of mesangial hypercellularity and matrix increase were similar in 36 (type B) and matrix increase was predominant in 22 (type C). The interval between the onset of disease and biopsy was significantly shorter in biopsies with type A mesangial changes (P less than 0.01) and significantly longer in those with type C (P less than 0.01). Serial pathologic observations revealed that predominant mesangial hypercellularity was almost exclusively seen in the initial biopsy but predominant matrix increase was usually seen in the follow-up biopsy. The percentage of glomeruli showing sclerosis was significantly higher in biopsies with type C mesangial changes (P less than 0.05). At the latest follow-up, 58% of the patients showing type A and 57% showing type B lost their proteinuria, whereas only 9% showing type C lost their proteinuria (P less than 0.01). These findings suggest that predominant mesangial hypercellularity is characteristic of the early lesion of childhood IgA nephropathy, and progression of disease leads to gradual decrease of mesangial cellularity and increase of matrix with sclerosis.

Biopsy↗

Henoch-Schoenlein nephritis and IgA nephropathy in children: a comparison of clinical course.

The clinical presentation, initial laboratory and renal biopsy findings, and subsequent clinical course were studied and compared in 128 children with Henoch-Schoenlein (HS) nephritis and in 206 children with IgA nephropathy. The clinical and pathological findings of the two conditions were similar. After a mean follow-up period of 5 years, 72 patients (56%) with HS nephritis and 67 (32%) with IgA nephropathy showed no demonstrable abnormality, 29 (23%) with HS nephritis and 103 (50%) with IgA nephropathy had minor urinary abnormalities, 7 (5%) with HS nephritis and 26 (13%) with IgA nephropathy had heavy proteinuria and/or hypertension, and 20 (16%) with HS nephritis and 10 (5%) with IgA nephropathy had developed chronic renal failure. A worse outcome was significantly associated with the more severe clinical presentations and more severe glomerular changes by light microscopy in HS nephritis, whereas there was no relationship between the severity of clinical presentation and glomerular changes and prognosis in IgA nephropathy. These findings suggest that HS nephritis is an acute disease and prognosis is associated with the severity of glomerular changes at onset, while IgA nephropathy is a chronic, slowly progressive glomerular disease.

Adolescent↗

Lysis of the glomerular basement membrane in children with IgA nephropathy and Henoch-Shönlein nephritis.

An electron-microscopic study of the glomerular basement membrane was made on 242 renal biopsies from 222 children with a variety of renal diseases. Lysis of the basement membrane was observed in 16 of the 25 children with Henoch-Schönlein nephritis, 36 of the 72 with IgA nephropathy and one with acute poststreptococcal glomerulonephritis. Lysis was frequently associated with subepithelial dense deposits and polymorphonuclear leukocytes, and these are thought to play a role in the lytic process. There was a significant correlation between the presence of lysis of the basement membrane, the degree of proteinuria and the severity of glomerular changes by light microscopy. These findings suggest that the degree of lysis is an indication of the severity of the disease and lysis is associated with progressive disease and a worse prognosis in Henoch-Schönlein nephritis and IgA nephropathy.

Adolescent↗

Glomerular electron-dense deposits in childhood IgA nephropathy.

An electron-microscopic study of the glomeruli was made on 154 children with IgA nephropathy and no evidence of systemic disease, in whom immunofluorescence microscopy had shown diffuse mesangial deposition of IgA. Mesangial deposits were observed in all but eight children. Subepithelial deposits were observed in 40 children and were almost always accompanied by both mesangial and subendothelial deposits. Subepithelial deposits were significantly associated with more severe clinical presentations, a worse outcome and more severe light microscopic glomerular changes. These observations support the concept that IgA nephropathy is an immune complex disease.

Adolescent↗