Ryou Karasawa

Histological Localization of Advanced Glycosylation End Products in the Progression of Diabetic Nephropathy

We studied the immunohistochemical localization of advanced glycosylation end products (AGEs) in the progression of diabetic nephropathy. Fourteen NIDDM patients with diabetic nephropathy were evaluated: 2 patients with normoalbuminuria, 4 with microalbuminuria (MA) and 8 with overt proteinuria (OP). Three patients with minor glomerular abnormalities were used as nondiabetic controls. Immunoreactivity to a monoclonal anti-AGE antibody (6D12) was recognized on the internal elastic membranes of arterial walls in every diabetic group. Hyaline lesions of arterioles of the MA and OP groups demonstrated strong reactions with 6D12. A portion of the nodular and exudative lesions in glomeruli of OP group patients also revealed immunoreactivity to 6D12. No immunoreactivity to 6D12 was observed in nondiabetic control specimens. We confirm that the accumulation of AGEs began in arterial walls of the early stage and presented in glomerular lesions of the late stage of the progression of diabetic nephropathy.

Early Increase of Chondroitin Sulfate Glycosaminoglycan in the Glomerular Basement Membrane of Rats with Diabetic Glomerulopathy

A decrease in anionic change and the loss of heparan sulfate proteoglycan have previously been observed in the glomerular basement membrane (GBM) during diabetic glomerulosclerosis. We studied the chronological changes in the anionic character and the glycosaminoglycan content in the GBM of WBN/ Kob rats with spontaneous diabetes. Two types of cationic probes were used: polyethyleneimine (PEI) and cationic colloidal gold (CCG). Immunogold labeling was performed with anti-monoclonal-heparan-sulfate-glycosaminoglycan (HS-GAG) and anti-chondroitin-sulfate-glycosaminoglycan (CS-GAG) antibodies. The GBM width, the anionic sites and the GAG sites were investigated in diabetic WBN/Kob rats at 2, 10 and 19 months, compared with control rats. Diabetes was confirmed in WBN/Kob rats after 8 months in this study. The GBM width gradually thickened with age. The PEI anionic sites significantly decreased in the lamina rara externa (LRE) at 19 months (vs. 2 and 10 months). The HS-GAG sites also significantly decreased in the LRE at 10 and 19 months (vs. 2 months). However, the CCG anionic sites and the CS-GAG sites significantly increased in the LRE and the lamina densa at 10 months (vs. 2 months) and, after 19 months, returned to the level seen at 2 months. Results indicate that there is an early transient increase in CS-GAG in the GBM while HS-GAG decreases. We noticed a transient increase in the CCG anionic sites at this early stage of diabetic glomerulosclerosis as well. The increase in CS-GAG may provide a marker for early diabetic changes in the GBM.

Morphologic study of the kidney in Japanese non-insulin-dependent patients.

The characteristic histologic finding of nephropathy in patients with diabetes mellitus (DM) has been diabetic glomerulosclerosis (DMGS), either of diffuse or nodular type, which was frequently associated with tubulointerstitial and vascular lesions. Primary glomerulonephritis (GN) has been also reported to be superimposed on DMGS. Most patients with DM in Japan have so-called type II diabetes. In the present study, we attempted to clarify the relationship between morphologic findings and clinical features in DMGS and DM-associated GN of non-insulindependent (NIDDM) patients.

Morphometric study of glomerular basement membrane and proximal tubular basement membrane in adult thin basement membrane disease

AbstractBackground. Thin basement membrane disease (TBMD) is a benign hereditary glomerulopathy with a diffuse attenuation of glomerular basement membrane (GBM). Whether the development of renal basement membranes other than GBM is normal in TBMD has not yet been resolved. Methods. We performed a morphometric study to measure the thickness of GBM and proximal tubular basement membrane (P-TBM) in 44 adult patients with TBMD and in 10 adult diseased controls confirmed to have minor glomerular abnormalities. Results. There was a significant difference between the patients with TBMD and the diseased controls in the thickness of the GBM; however, there was no significant difference between the two groups in the thickness of the P-TBM. In the patients with TBMD, the thickness of the GBM was unchanged with age, but the thickness of the P-TBM increased with age, as did that in the diseased controls. Conclusion. Our morphometric study clarified that the development of P-TBM was normal in the patients with TBMD.

Acute renal failure secondary to rupture of the abdominal aortic aneurysm into the inferior vena cava: Report of two successfully treated cases

Aortocaval fistula is an unusual complication of an abdominal aortic aneurysm. We describe 2 patients with abdominal aortic aneurysms who presented with acute renal failure and hepatic injury secondary to spontaneous aortocaval fistulas. The fistulas were shown by computed tomography, right heart catheterization, and abdominal aortography, and were confirmed at surgery. Increases in the fractional excretion of filtered sodium, the urine sodium concentration divided by the urine-to-plasma creatinine ratio (the renal failure index), and the urine sodium concentration were observed. The patients recovered renal and hepatic function after closure of the fistulas. Increased venous pressure resulting from aortocaval shunt might cause the alteration of renal and hepatic function. Therefore, it is important to accurately diagnose the aortocaval fistula and to close it urgently by surgical methods.