Tamotsu Matsuo

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.

Focal segmental glomerulosclerosis with and without nephrotic syndrome in children

The clinical presentation, initial laboratory and renal biopsy findings, and course of focal segmental glomerulosclerosis (FSGS) were studied retrospectively in 57 children in order to compare findings in those with and without nephrotic syndrome and to establish factors of prognostic significance. All patients had proteinuria. Eleven patients were otherwise asymptomatic, and nephrotic syndrome did not develop (group 1); 14 patients had asymptomatic proteinuria, but nephrotic syndrome subsequently developed (group 2); 32 patients had nephrotic syndrome (group 3). There were no differences between these three groups with regard to sex, age, initial renal function, incidence of hypertension and hematuria, and pathologic findings. At the latest follow-up, five group 1 patients, six in group 2, and 14 in group 3 had chronic renal failure; the incidence was similar for those with asymptomatic proteinuria and those with nephrotic syndrome. The location of the sclerosis within the glomerulus proved to have prognostic significance. All 12 patients with peripheral FSGS maintained normal renal function, whereas in 25 of the 44 with hilar FSGS chronic renal failure developed.

Glucose, free fatty acid and ketone body metabolism in duchenne muscular dystrophy

We examined how the substances, especially glucose, free fatty acids (FFA) and ketone bodies, and hormones associated with energy metabolism change with the disease progress in Duchenne muscular dystrophy (DMD). Serum creatine kinase (CK) activity was used as an index of the stage of DMD, because this activity is exponentially decreases with the progress of the disease. The glucose concentration in DMD patients with CK activity of less than 1,000 U/l (low CK) was significantly lower than that in controls, although there was no significant difference between that in DMD patients with CK activity of more than 1,00 U/l (high CK) and that in controls. The FFA concentration in both high CK and low CK patients was significantly higher than that in controls. The FFA concentration in low CK patients tended to be higher than that in high CK patients. The ketone body concentration in low CK patients was significantly higher than that in controls and that in high CK patients. The [glucagon]:[insulin] ratio in low CK patients was significantly higher than that in controls and that in high CK patients. It was also observed in a correlational study that the glucose concentration decreased with the age and the decrease in CK activity, i.e., with the progress of DMD. The FFA and ketone body concentrations increased with the decrease in the glucose concentration. The decrease in the glucose concentration may be due to a caloric shortage and/or degenerated muscle, which cannot supply enough gluconeogenic substrates, such as alanine. The kinetics of insulin and glucagon in DMD may help to maintain the glucose metabolism. Increased concentrations of FFA and ketone bodies may be helpful in the advanced stage of DMD, as energy sources and as substrates, sparing muscle protein.

Nonfamilial hematuria associated with glomerular basement membrane alterations characteristic of hereditary nephritis: Comparison with hereditary nephritis *

Characteristic ultrastructural alterations of the glomerular basement membrane (GBM) have been reported in hereditary nephritis and in children without a family history of renal disease. The clinical features, renal biopsy findings, and subsequent course were studied retrospectively in 48 children with such GBM changes to compare findings in those with and without a family history of nephritis and to determine the significance of the GBM changes in patients with nonfamilial disease. All 48 patients had hematuria. For 30, there was hematuria in at least one other member of the family (familial hematuria group); for 18, there was no familial incidence. There were no differences between the two groups with regard to clinical and pathologic findings. At the latest follow-up six boys with familial hematuria and three boys with nonfamilial hematuria had reduced renal function, and nine boys with familial hematuria and four boys and one girl with nonfamilial hematuria had neurosensory deafness. Our study results show that children with these GBM changes, with or without a family history of hematuria, tend to have a progressive course, with frequent occurrence of neurosensory deafness, and that the prognosis is more severe in boys. These observations suggest that such GBM changes in patients with nonfamilial hematuria may represent new mutations for hereditary nephritis.

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.

Insulin-like Growth Factor-I (IGF-I) /Somatomedin C (SMC) の血中存在様式及びそのレセプターに異常を認めたleprechaunism

Leprechaunism is a rare genetic disorder characterized by physical abnormalities, intrauterine and postnatal growth retardation, poorly developed subcutaneous fat and muscle at birth, and early death. This patient, who was a 1.5 year-old female with typical clinical features of leprechaunism, had relatively high levels of plasma GH and IGF-I/SMC but no glucose intolerance or insulin resistance. Studies were undertaken to elucidate (1) the differences among some kinds of methods for IGF-I/SMC measurement, (2) the distribution patterns of IGF-I/SMC between two kinds of its binding protein (SMBP) in plasma, and (3) the dynamics of IGF-I/SMC receptor in her erythrocytes and liver microsomal membranes. The results were as follows: (1) The level of IGF-I/SMC measured by Nichols radioimmunoassay kit was 1.33U/ml, which was higher than that of infants the same age. Conversely, it was lower than that of the control which was measured by radioimmunoassay using recombinant IGF-I/SMC after acid-ethanol or Seppak C18 extraction. (2) By Sephadex G150 gel-chromatography, immunoreactive IGF-I/SMC was eluted predominantly in 150K region, and two apparent peaks of unsaturated somatomedin binding protein (USBP) were determined in a neonatal infant (appropriate to date), a normal adult and an infant of the same age as this patient. On the other hand, immunoreactive IGF-I/SMC was located only in the fractions corresponding to 40K region, and only one peak of USBP could be estimated in the region of 40K dalton. (3) The IGF-I/SMC receptor in the patients erythrocytes possessed significantly lower binding affinity but higher binding capacity in comparison with that of the normal neonate and adult. In addition, the receptor in liver microsomal membranes obtained from this patient at autopsy also indicated lower affinity but higher capacity than that of fetuses at more than 19 weeks of gestation. This was coincident to that of fetuses less than 19 weeks of gestation. These results suggested that this patient resembled the intrauterine fetus before midgestation not only in the co-relationship among GH, IGF-I/SMC and its binding proteins, but also in the characteristics of its receptor. The severe growth retardation existing in this patient may be, at least partly, due to the abnormality and/or immaturity of IGF-I/SMC function. It is speculated that leprechaunism could be classified in relation to fetal growth mechanism by aspects of biological functions of IGF-I/SMC during development.

Impairment of Superoxide Release by Alveolar Macrophage in Rats Exposed to Oxygen and Vitamin E

We examined the digitonin-stimulated release of superoxide by alveolar macrophages (AMs) from young rats exposed to greater than 95% oxygen for 24-168 h. AMS were obtained by lung lavages, and the release of superoxide stimulated by digitonin was measured by using cytochrome C reduction. The total cell count of lung lavages decreased at 24 and 168 h of oxygen exposure (p less than 0.05 for both). The contamination of polymorphonuclear cells (PMNs) was less than 1% up to 120 h of oxygen exposure, and at 168 h PMNs increased to 5% of total cells in lung lavages. The viability of AMs was greater than 95% up to 72 h and then decreased to 90% at 120 h of oxygen exposure and 87% at 168 h. Digitonin-stimulated superoxide release by AMs recovered from lung lavages in rats exposed to hyperoxia showed a slight increase during the first 48 h. However, oxygen exposure for 72 h or more caused a significant decrease of the stimulated superoxide release of AMs compared to AMs from control rats. This decline in stimulated superoxide release of AMs resulting from hyperoxia was not prevented by vitamin E treatment.