Yasuhiro Amagasaki

Angiotensin-Converting Enzyme Polymorphism and Development of Diabetic Nephropathy in Non-Insulin-Dependent Diabetes mellitus

We determined the distribution frequency of angiotensin-converting enzyme insertion/deletion (I/D) polymorphism in 111 Japanese patients with non-insulin-dependent diabetes mellitus (NIDDM) of at least 10 years duration (80 patients with diabetic nephropathy and 31 patients without nephropathy) and 76 healthy Japanese controls. Patients with diabetic nephropathy showed an excess of the ID genotype compared with patients without nephropathy (p < 0.02) and less of the II genotype compared with healthy controls (p < 0.01) and patients without nephropathy (p < 0.01). NIDDM patients with the II genotype have a decreased risk for the development of diabetic nephropathy.

The influence of antecedent renal disease on pregnancy

The influence of antecedent renal disease on pregnancy was studied retrospectively in 72 women with various renal diseases that had been proved by biopsy. Among 105 pregnancies studied, normal deliveries were observed in 74 (71%), abnormal deliveries with live infants in 14 (13%), fetal or neonatal deaths in 11 (10%), and spontaneous abortions in six (6%). The incidence of normal delivery, as well as that of live births, was the highest in the cases of membranous glomerulonephritis, but there was no obvious difference in the incidence among IgA nephropathy and non-IgA proliferative glomerulonephritis. Cases in which there were tubulointerstitial changes of the cortical area or arteriosclerosis in biopsy specimens and cases that included hypertension (greater than 140/90 mm Hg) or decreased renal function (glomerular filtration rate, less than 70 ml/min) were clearly associated with an unfavorable outcome in delivery. It was concluded that assessment of the advisability of pregnancy in nephritic women should be made on the basis of a combination of the clinical and histologic parameters.

Significance of Tubulointerstitial Lesions in Biopsy Specimens of Glomerulonephritic Patients

To evaluate the significance of tubulointerstitial lesions in the cortical area of renal biopsy specimens, clinicopathological studies were performed on 101 cases of IgA nephropathy, 31 cases of IgA-negative (non-IgA) proliferative glomerulonephritis and 75 cases of idiopathic membranous glomerulonephritis. The degree of tubulointerstitial lesions was assessed semiquantitatively by light microscopic observation and was correlated with the several histopathological and clinical parameters at biopsy, as well as with status at final follow-up (average follow-up period: 72 months). In these three types of glomerulonephritis, the degree of tubulointerstitial lesions in the cortical area was clearly correlated with the severity of glomerular injury, the prevalence of segmental sclerosis, global sclerosis, arteriolosclerosis, decreased renal function (GFR less than 70 ml/min) and hypertension (greater than 150/90 mm Hg) at the time of biopsy. The prevalence of stable renal function at final follow-up was statistically higher in the cases without tubulointerstitial lesions or with those whose lesions included less than 20% of the cortical area. From the above data, it was concluded that a semiquantitative evaluation of tubulointerstitial lesions in the cortex would reflect the severity of glomerular injury and also contribute to the assessment of prognosis in such primary glomerulonephritic patients.

A case of collagenofibrotic glomerulopathy associated with hepatic perisinusoidal fibrosis

A patient with collagenofibrotic glomerulopathy associated with hepatic persinusoidal fibrosis is described. Renal biopsy revealed that the glomerular tufts contained homogeneous material that was proved by electron microscopy to be collagen fibers. The material was reactive to anti-type III collagen monoclonal antibody. Liver biopsy also showed an increase of type III collagen fibers in the perisinusoidal area. Since the serum procollagen III peptide level was elevated in this patient, fibrosis may have been simultaneously activated in kidney and liver by some unknown condition.

Vitamin A toxicity secondary to excessive intake of yellow-green vegetables, liver and laver

We report a case of sudden onset of vitamin A poisoning. A 20-year-old Japanese woman had been eating pumpkin and only a very limited amount of other foods on a daily basis for 2 years. She was overly concerned about weight reduction. Aurantiasis cutis and abnormal liver function tests were noted by her family doctor in 1995 when she was 18 years old. At that time, she stopped eating pumpkin. However, she secretly continued an excessive intake of other beta-carotene-rich vegetables, liver and laver for about 2 years. Two and one-half years after being seen by her family physician, she experienced sudden onset of low-grade fever, limb edema, cheilitis, dry skin, and headache. These symptoms worsened daily. A liver needle biopsy was performed, and it showed a normal portal tract along with fat-laden Ito cells in the space of Disse. A final diagnosis of vitamin A poisoning and hepatic injury secondary to an eating disorder was made. Her symptoms and serum beta-carotene levels returned to normal with successful adjustment of her diet.

Hypertension in Unilateral Atrophic Kidney Secondary to Ureteropelvic Junction Obstruction

A patient with atrophic unilateral hydronephrosis due to ureteropelvic junction obstruction associated with hypertension was successfully treated by nephrectomy. Preoperatively, plasma renin activity was elevated in both the peripheral vein and affected renal vein. Renin concentration in the resected kidney was high, and immunohistochemical localization of renin was observed along the afferent arterioles of the juxtaglomerular apparatus and in arterioles at some distance from the glomeruli.

Hypokalemia and prostaglandin overproduction in Bartter's syndrome

In 2 adult patients with Bartters syndrome, in whom chloride reabsorption at the diluting segment of the nephron was markedly reduced, serum potassium concentration could be improved with oral administration of a large amount of potassium chloride. In both cases, improvement of serum potassium levels with oral potassium load resulted in an increase in plasma renin activity (PRA) and plasma aldosterone concentration (PAC), a decrease in urinary excretion of prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha), and an improvement of pressor responsiveness to angiotensin II and norepinephrine. Treatment with indomethacin also improved the pressor responsiveness to angiotensin II and norepinephrine, but this occurred in association with a decrease in PRA, PAC and urinary excretion of PGE2 and PGF2 alpha. These results indicated that an event at the renal tubular level leading to potassium depletion is the most proximal pathogenetic defect in Bartters syndrome, and that this in turn contributes to excessive prostaglandin production leading further to the decreased pressor responsiveness to vasoactive substances.