The most remarkable features of the new animal model for accelerated senescence, the senescence accelerated mouse (SAM), developed by the inbreeding of AKR mice are early onset and rapid progression of senescence and a high incidence of amyloid deposition. The kidney was examined histologically and the morphological features of the senility in SAM are described. The main histological findings were: 1) a fairly high incidence (43.6%) of elastofibrosis of the intima in the small arteries, 2) frequent amyloid deposition (64.4%) in the glomeruli, the interstitial tissue around the tubules and the vascular walls, especially the vein walls, and 3) macroscopic evidence of contracted scarred kidney (40.6%), a microscopically irregular kidney surface (52.5%) and colloid casts in the dilated tubules (52.5%), combined with renal amyloid deposition. Arteriosclerotic changes of the medium-sized and larger arteries, sclerosis of the glomeruli and increased interstitial connective tissue were not conspicuous. The amyloid deposition in the kidneys of SAM is considered to be of great importance.

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The senescence accelerated mouse (SAM) is characterized by early onset and fast advance of senility and a high incidence of amyloidosis. Senile amyloidosis was investigated in the kidneys of SAM. Amyloid deposits were present in the mesangial regions and capillary walls of the glomeruli, the interstitium around the tubules and the vascular walls. Amyloid deposition was frequent and prominent in the papillae and in the interstitium around the thin portion of Henle's loop. Greater involvement of the vein walls than the artery walls was one of the features of the senile amyloidosis of SAM. The incidence and degree of amyloidosis of the kidney of SAM were confirmed to be age dependent. The kidney/body weight ratio did not parallel the severity of amyloidosis. The deposited amyloid was potassium permanganate resistant. The incidence of renal amyloidosis was higher in SAM with complications (abscess, lymphoma, skin ulcer and/or gangrene and tumors) than in SAM without them. This fact and the findings for the amyloid kidney tissues stained with p-dimethyl aminobenzaldehyde-nitrite (DAB) suggest that such complications stimulate amyloidosis or superimpose secondary amyloidosis on senile amyloidosis, i.e. AS/SAM and AA can coexist in some kidneys of SAM.

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The management of renal angiomyolipoma, one of the most important benign renal tumors, is discussed on the basis of 12 cases studied. In view of the fact that more accurate diagnosis of renal mass lesions can be expected with the recent progress in image diagnostic modalities, the management of renal angiomyolipoma should be re-evaluated in order to preserve as much renal parenchyma as possible. A policy of management for renal angiomyolipoma is proposed based on the following risk factors: tumor vascularity, size, location, and presence of tuberous sclerosis.

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The case of a 21-year-old male with recurrent Henoch Schoenlein purpura nephritis associated with tuberculous pleuritis is reported. Following tuberculotherapy, polyclonal increases in the serum IgA and IgG were normalized, and proteinuria and hematuria disappeared. These findings suggest that the tuberculous pleuritis might have played a key role in the genesis of the recurrence of Henoch Schoenlein purpura nephritis in this case.

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We investigated the usefulness of oral protein loading tests for evaluating renal functional reserve. Healthy subjects and patients with renal impairment were given protein-rich meals to eat after a night's fast (1 g protein/kg body weight). Later, at hougly intervals, the creatinine clearance (Ccr) was measured and the change compared to the previous value (delta Ccr) was estimated. Boiled lean yellowfin tuna was used as the protein source. The largest delta Ccr in the healthy subjects, 34.4 ± 6.0 ml/min, occurred at the second hour after the protein load. There was a significant correlation between the delta Ccr values and the preceding Ccr values. On the basis of these results, the delta Ccr after oral protein loading was considered to reflect the renal functional reserve, and monitoring of delta Ccr appeared to be useful for evaluating the progression of renal impairment.

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We developd a simple, precise and reliable method for determination of the intracellular sodium and potassium concentrations in erythrocytes. With this method, erythrocytes were washed with cold isotonic MgCl₂ solution to remove plasma trapped between the cells, and a microcapillary tube whose diameter had been predetermined was employed to measure the volume of the cell pellet accurately. Using this method, the extent of the biological variation was analyzed and factors contributing to the intracellular sodium and potassium concentrations were studied in 1046 healthy male adults aged 43.7±8.9 years. The intracellullar sodium concentration was found to be 8.61 ± 1.12 mmol/l cells and the intracellular potassium concentration was 100.5±3.1 mmol/l cells. A significant negative correlation was observed between the intracellular sodium and potassium concentrations (r = -0.22, p<0.01). The intracellular sodium and potassium concentrations did not show any relation to the serum sodium or potassium concentration and did not change with age. The obesity index was negatively linked with the intracellular potassium but not with the intracellular sodium concentration. These results suggest that in healthy male subjects, 1) the regulating factor of sodium transport is, at least in part, linked with potassium transport across the cell membrane. 2) the intracellular sodium concentration is not affected by age or the obesity index, 3) the serum sodium and potassium concentrations may not reflect or affect the state of the intracellular sodium or potassium concentrations, and 4) much of the variation in the intracellular sodium and potassium concentrations among subjects remains unexplained.

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We examined the responses of 8 patients with chronic renal failure (Ccr, 15.4 ± 3.1 ml/min) to oral furosemide (F) (40 mg) in the absence (control) and in the presence of oral hydrochlorothiazide (HCT) (100 mg). In the 24-hour period after oral F, HCT was shown to increase the urine volume, urinary sodium excretion and urinary chloride excretion. The increment was most significant in the 12- to 24-hour period. Enhancement of the diuresis with HCT was associated with neither a significant increase in the area under the curve (AUC) of the plasma F concentration, nor an increase in the urinary F excretion. However, the urinary excretion of glucuronidated furosemide (FG), one of the main metabolites of F, was decreased with HCT. In summary, HCT significantly enhanced the response to F in chronic renal failure patients.

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Administration of cyclosporin A (CYA) (20 mg/kg) at the preimmunization stage prominently inhibited the specific antibody response and the development of glomerulonephritis. In contrast, preimmunized rats showed mild glomerulonephritis with antibody response when CYA was given at the stage of continuous sensitization. Prednisolone (PL) (80 mg/kg) could not suppress the specific antibody response, when it was given in the preimmunization and/or the continuous immunization stage. However glomerulonephritis was found to be milder in terms of tissue damage and proliferation, resulting from its evident antiinflammatory effect.

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The short-term effects of cyclosporin A (CYA) and steroid were analyzed histologically in full-blown proliferative glomerulonephritis in experimental serum sickness of the rat. Administration of CYA (20 mg/kg) for 7 days induced no suppressive effect on glomerular inflammation including cell proliferation, immune deposition and tissue damage. In contrast, treatment with prednisolone (80 mg/kg) for 7 days apparently reduced the glomerular cellularity and destructive changes in spite of diffuse deposition of immune complexes in the glomeruli. These results suggest that CYA may be of limited therapeutic use at the stage of full-blown glomerulonephritis of the immune complex type.

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To evaluate whether salt sensitivity can be predicted by simple variables, several indices during consumption of a regular salt diet (10 g per day) were investigated during hospitalization in 53 patients with essential hypertension using multivariate analysis. Salt sensitivity was defined as the per cent change in mean blood pressure (% Δ MBP) following a change from a week of low salt diet (3 g per day) to a week of high salt diet (20 g per day). Various clinical, biochemical and hemodynamic variables were measured before and after 40 mg of intravenous furosemide during consumption of the regular salt diet. These independent variables were analyzed by a backward elimination procedure employing a Statistical Analysis System Program for salt sensitivity. Salt sensitivity was positively related to age (r = 0.262, p<0.05) and negatively related to plasma renin activity (PRA) and to % Δ MBP with furosemide (r = -0.387 and r = -0.478, respectively; p<0.01 for both) by simple regression analysis. Patients older than 60 years showed a significantly higher salt sensitivity than those below 60 years (11.8 ± 7.96 vs. 5.47 ± 5.80%; p <0.01). % ΔMBP with furosemide was the greatest independent determinant of salt sensitivity (p<0.005), followed by age (p<0.01), the degree of Scheie's funduscopic hypertensive change (p<0.01) and PRA (p<0.05) in that order. A multiple regression analysis equation with these four variables significantly explained about 40% of the salt sensitivity (r = 0.64, p<0.0001). These results suggest that salt sensitivity in patients with essential hypertension can be predicted in the outpatient clinic based on the hypotensive response to furosemide, age, the degree of Scheie's funduscopic hypertensive change and PRA.

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A chronically hemodialyzed patient suffering from multiple bony fractures due to aluminum bone disease, was treated with desferrioxamine. Her subsequent remarkable improvement was interrupted by the development of fulminant hyperparathyroid bone disease with a brown tumor at 9 months after starting the treatment, preceded by marked elevation of the serum alkaline phosphatase level with a concomitant increase in the carboxy-terminal parathyroid hormone concentration. Hyperplasia was found in all the four parathy-roil glands at the time of parathyroidectomy, which again restored her bone disease. These observations strongly suggest that the administration of desferrioxamine could lead to severe hyperparathyroid bone disease which becomes manifest within a short time in patients with aluminium accumulation and coexistent parathyroid hyperplasia.

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Ninety-six patients with IgA nephropathy had persistent proteinuria of 1.0 g/day or more at renal biopsy and were followed up for more than 4 years after the start of therapy. Thirty-six of these patients showed heavy proteinuria of 2.0 g/day or more and the remaining 60 showed moderate proteinuric of 1.0 to 2.0 g/day. Thirty of the 36 heavy proteinuric patients received prednisolone treatment at an initial dose of 40 mg/day followed by gradual tapering of the dose over 18 months on average. Of these patients, 16 with initial Ccr values of more than 70 ml/min maintained 64 ml/min as the final Ccr value after a mean follow-up period of 81 months, while 14 patients with initial Ccr values of less than 70 ml/min showed a rapid deterioration to the range of 56 to 18 ml/min during an average of 52 months follow-up. On the other hand, 18 of the 60 moderate proteinuric patients received the same prednisolone treatment schedule, with the remaining 42 taking non-steroidal anti-inflammatory drugs and/or anti-thrombocyte drugs alone. Fifteen steroid treated, moderate proteinuric patients with initial Ccr values of more than 70 ml/ min maintained a final renal function of 76 ml/min after a mean follow-up period of 95 months, while 31 non-steroid treated, moderate proteinuric patients with the same initial renal function displayed renal functional deterioration to 52 ml/min as the final Ccr value after a mean follow-up period of 90 months. These two groups showed a significant difference in Ccr values at 4 years after therapy (p<0.05). All 14 moderate proteinuric patients with initial Ccr values of less than 70 ml/min, 3 steroid and all non-steroid treated, displayed subsequent severe renal functional deterioration, from a mean of 64 to 31 ml/min in the former group and from 52 to 0 ml/min in the latter. Although the present study was not a controlled one, these results suggest that steroid therapy in progressive IgA nephropathy is beneficial for preserving subsequent renal function for an extended period, particularly in patients with preserved renal function at the start of therapy.

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There is much evidence that renal tubular function is more or less defective in nephrolithiasis. In order to make clear whether tubular dysfunction is a cause or consequence of stone disease, we conducted renal tubular function tests in 9 idiopathic calcium stone patients when the stone seemed to be no longer obstructive to the urinary tract on intravenous pyelographs. All the tests were repeated one month after removal of stones. We compared the values of tubular reabsorption of phosphate, urinary acidification ability and fractional excretion of magnesium, potassium and insulin before and after removal of stones, and found no significant difference. The urinary excretion of gamma-GT was elevated in some cases with calculi. However, after removal of them, it returned to a normal level. We concluded that if tubulopathy is consequent upon the stone disease, it may be caused by obstruction of the involved urinary tract with calculi.

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In an attemt to clarify the regulation mechanisms of intracellular sodium concentration in patients with chronic renal failure on maintenance hemodialysis, the relation between Na pump activity, intraerythrocytic sodium concentration and arterial pH was studied in 20 patients and 26 controls. While the Na pump activity was significantly reduced in the patients, their intraerythrocytic sodium concentration was not different from that of the controls. The intraerythrocytic sodium concentration was negatively correlated with the Na pump activity in each group, but the regression line between these two variables in the patient group was steeper and shifted further downwards than that of the control group. Since the patients showed marked acidosis, in order to clarify the effects of acidosis on the intraerythrocytic sodium concentration and Na pump activity, erythrocytes were incubated in an artificial medium at varying pH values. This incubation study revealed that the intraerythrocytic sodium concentration was increased with elevation in the medium pH, but the Na pump activity was not affected by pH change. Improvement of the marked acidosis after hemodialysis was accompanied by an elevation of the intraerythrocytic sodium concentration but not by an alteration of the Na pump activity. These results suggest that the intraerythrocytic sodium concentration in patients with chronic renal failure on maintenance hemodialysis was not increased in spite of an inhibited Na pump activity, and this phenomenon may be due to changes in other Na transport systems which are affected by pH.

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We performed, for possible therapeutic application, low density lipoprotein apheresis (LDL-A) in conjunction with double filtration plasmapheresis (DEPP) in 5 patients with drug-resistant nephrotic syndrome due to focal glomerular sclerosis (FGS). The possible relationship between changes of renal function and correction of lipid abnormalities was investigated. The creatinine clearance (Ccr) and renal blood flow (RBF) were increased by LDL-A and DFPP in all patients, and the remission of renal function and proteinuria followed a reduction in serum lipid levels. We next followed the changes in putative non-immune parameters of glomerular disease, such as flbrinopeptide A (FPA), fibrinopeptide Bβ15-42 (FPBβ15-42), thromboxane B₂ (TxB₂) and 6-keto-prostaglandin F₁α (6-Keto-PG F₁α). The plasma FPA and FPBIβ15-42 levels, and the TxB₂/6-Keto-PGF₁α ratio were found to decrease followintg plasmapheresis. These results may provide some indication of the beneficial effects of LDL-A and DEPP on glomerular disease. In this report, we present a new approach for the treatment of drug-resistant nephrotic syndrome due to FGS. The data suggest that lipid abnormalities may, at least in part, play a pathogenetic role in progressive renal disease.

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