Yoshihiro Fujii

Intraglomerular expression of transforming growth factor-beta 1 (TGF-β1) mRNA in patients with glomerulonephritis: quantitative analysis by competitive polymerase chain reaction

TGF‐β1 is involved in the pathogenesis of glomerular sclerosis. We studied the intraglomerular expression of TGF‐β1 mRNA in patients with glomerulonephritis using competitive polymerase chain reaction (PCR). This method is sensitive enough to quantify cDNA copies of mRNA present in small amounts of samples. Renal biopsy specimens were obtained from 42 patients with various kinds of glomerulonephritis. Ten glomeruli were dissected from renal biopsy specimens. Normal glomeruli were also obtained from the resected kidneys of eight patients with renal cell cancer. Total RNA was extracted from the glomeruli and reverse transcribed into cDNA with reverse transcriptase. To prepare samples containing identical amounts of β‐actin cDNA (8 pg), we performed competitive PCR by co‐amplifying mutant templates of β‐actin with a unique EcoRI site. Next, to measure TGF‐β1 cDNA, we performed competitive PCR by co‐amplifying mutant templates of TGF‐β1. We observed a higher glomerular expression of TGF‐β1 mRNA in cases of mesangial proliferative glomerulonephritis having a moderate increase in mesangial matrix, diabetic nephropathy and diffuse proliferative lupus nephritis, compared with normal glomeruli. Results suggest that the intraglomerular synthesis of TGF‐β1 may be involved in the progression of glomerulonephritis in humans.

Focal and Segmental Glomerulosclerosis in Preeclamptic Patients with Nephrotic Syndrome

Etiology and pathogenesis of focal and segmental glomerulosclerosis (FSGS) in patients with toxemia of pregnancy remain controversial. We examined 15 preeclamptic patients presenting with nephrotic syndrome. None of the patients had urinary abnormalities and hypertension before pregnancy. Clinically, proteinuria first developed during pregnancy and disappeared completely in all but one patient lost to follow-up after 1-30 months from delivery. Renal dysfunction, hypertension and edema rapidly resolved in the postpartum period. None of the patients had a progressive clinical course. Renal biopsy specimens obtained postpartum revealed typical features of preeclamptic nephropathy. In addition, findings compatible with FSGS were observed in 13 patients including 4 in which such lesions were unearthed by additional serial sectioning. These results indicate that FSGS may not only be induced by preeclampsia but also be one of the representative glomerular changes in preeclamptic patients with nephrotic syndrome. A favorable clinical course ensues in a manner similar to that of patients with the garden - variety of preeclampsia.

Alterations in extracellular matrix components and integrins in patients with preeclamptic nephropathy

The glomerular features of patients with preeclapsia consist of swelling of endothelial cells, subendothelial deposits of incompletely defined material, and thickening of the capillary walls. These abnormalities are thought to resolve in the postpartum period. The distribution of extracellular matrix (ECM) components and integrins was investigated in 10 such patients. Frozen sections and paraffin-embedded sections were stained with antibodies to type IV collagen, laminin (LN), fibronectin (FN), vitronectin (VN), tenascin (TN), fibronectin receptor (FNR), and vitronectin receptor (VNR). In preeclamptic nephropathy, the accumulation of type IV collagen, LN, FN, TN, and FNR was observed in the thickened capillary walls, particularly in the subendothelial layer and, to some extent, in the mesangium. However, deposits of VN were sparse and the distribution of VNR was similar to that in normal kidney. In segmental sclerotic lesions, the amounts of type IV collagen, LN, FN, VN, and TN were increased, whereas those of FNR and VNR were markedly decreased. These results suggest that the materials deposited in the subendothelial space consist of ECM components as well as of plasma-derived proteins, and that the deposition of ECM components and of FNR may be involved in the development and the reparative process of the characteristic glomerular lesions. The formation of sclerotic lesions was linked to the accumulation of ECM components, but not to an interaction with integrins.

Relation of glycaemic control and hypertension to progression of glomerular lesions in non-insulin dependent diabetes mellitus

Summary: We investigated the influence of glycaemic control and hypertension on the progression of renal structural changes in 18 patients with non‐insulin dependent diabetes mellitus (NIDDM) who had undergone sequential renal biopsies. Renal biopsies were performed after median interval of 6.0 years (range 2‐11 years). the severity of glomerular diffuse lesions was graded on a 5‐point scale according to Gellmans criteria. Subjects were divided into two groups: (i) patients who showed progression of glomerular diffuse lesions (n= 12); and (ii) patients who showed no change in histological grade (n= 6). Mean arterial blood pressure was significantly higher in group 1. There was no significant difference in the HbA1c between the two groups. These findings suggest that the mean arterial blood pressure is closely related to the progression of glomerular morphological changes regardless of the status of glycaemic control.