The treatment and renal histopathological characteristics of 24 patients with IgA nephropathy showing urinary excretion of over 3.0 g/day of protein were investigated retrospectively. Clinically, the incidence of hematuria, nephrotic syndrome, renal dysfunction and hypertension was 100%, 54%, 88% and 42% in the patients, respectively. Histopathologically, although various grades of mesangial proliferation and crescent formation were observed, subepithelial dense deposits and mem-branolysis of the glomerular basement membrane were characteristically recognized by electron microscopy in nearly half of the 24 patients. These patients were administrated several kinds of drugs, such as corticosteroids (C), immunosuppressive agents (I) dipyridamole (D), C+D, I+D or C+I+D+heparin. The treatment with C+D or I+D was particularly effective for reducing the urinary protein and preventing deterioration of renal functions. However, none of the treatments were effec-tive in many patients whose creatinine clearance (Ccr) was below 50 ml/min. In conclusion, these results suggest that treatment of patients with IgA nephropathy showing massive proteinuria and a Ccr of above 50 ml/min should be actively attempted by a combination of immunosuppression therapy (C and/or I) and D.

View full abstract

In order to investigate the antigenicities of mesangial cells or mesangial matrix, we prepared monoclonal antibodies by immunization with in vitro cultured mesangial cells from rabbits. Four monoclonal antibodies, reacting mainly with mesangial matrix or mesangial cells, were obtained. One of them, KI-13, was shown to bind to mesangial cells, both the surface and the intracytoplasmic fibrillary structures, appearing to compose the cytoskeleton of cultured mesangial cells, the cytoplasm of smooth muscle cells of various organs, the Z-I bands of striated muscle cells and the intercalated discs of cardiac muscle cells. These observations as well as the results of absorption and blocking studies suggested that KI-13 recognized the cytoskeletal protein of mesangial cells. This monoclonal antibody is expected to provide a valuable tool for studies on the pathological alterations of mesangial cells in both clinical and experimental glomerulonephritis.

View full abstract

A 51-year-old housewife complaining of edema was admitted to our hospital. Investigations revealed proteinuria of nephrotic level and slightly decreased renal function. Renal biopsy was performed and subtle changes which suggested early figures of focal glomerular sclerosis were observed. In spite of steroid therapy, severe proteinuria persisted and renal function gradually decreased. Finally, hemodialysis was performed because of congestive heart failure from the 70th hospital day. The urine output then decreased by degrees and she became anuric in 5 months. The anuric state continued for about 6 months, but she started to excrete urine again about 1 year after the beginning of hemodialysis. Subsequently, the urine volume and creatinine clearance increased gradually and no hemo-dialysis was required on the 700th day after onset of the disease. Renal biopsy was performed again about 3 years after onset of the disease. The specimen showed typical features of focal glomerular sclerosis. We would like to report this rare example of recovery from severe renal failure in spite of apparent progression of the renal histology. This case had taken a longer period than any other re-ported case to recover from severe renal failure.

View full abstract

The effects of ureteral obstruction and its relief on adenine nucleotides and inorganic phosphate were investigated in a series of experiments on Wistar rats. Ureteral obstruction with hydronephrosis was produced by ligation of a unilateral ureter. Measurement of adenine nucleotides and phosphate esters was performed according to the methods of Nagata and Rasmussen before and at 6 months after the' operation. The results revealed that the renal tissue adenine nucleotides, ATP, ADP and AMP decreased to about 60% of normal at one month after ureteral ligation with a further decline continuing up to 6 months. The energy charge levels by Atkinson also decreased. The turnover rate of cell Pi showed a marked increase during these periods. Recovery of the nucleotides after relief of ligation was prominent in the group with one month's ligation. A further longer period of ligation, however, prevented the nucleotides from reaching the former levels.

View full abstract

210 subjects with biopsy-proven IgA nephritis were evaluated for hypertension and intrarenal small vessel lesions. 24 cases (11.4%) had labile and 20 (9.6%) had fixed hypertension, with an overall incidence of 20.9%. Of the 20 fixed hypertensives, 8 (including one with malignant hypertension) were already azotemic. The remaining 12 were nonazotemic, and their ages ranged from 21 to 67 years. They were further separated into 8 cases with a GFR of 70 to 101 ml/min and 4 cases with a GFR of 53 to 63 ml/min. All but one in the former group were characterized by trace to modest proteinuria and hematuria, and only mild mesangial proliferation. In contrast, the arterioles revealed marked hyalinosis, intimal edema, or even arteriolitis. The small arteries when obtained had extensive intimal fibrosis with a high degree of luminal stenosis. The plasma renin activity was higher in 5 out of 7 cases when measured. However, such intrarenal small vessel lesions were seen at the same frequency and severity in the latter group having a reduced GFR and fixed hypertension, together with more conspicuous glomeular involvement. Similar vessel lesions were also observed in those cases with labile hypertension, and even in normotensives although to a lesser degree and at a lower incidence. Thus, the above 7 subjects can be interpreted as representing a subset with more small-vessel and lesser glomerular involvement, and would simulate benign nephrosclerosis if glomerular IgA deposition is not verified. The blood pressure responded promtply to therapy without any decrease in GFR.

View full abstract

Renal functional and morphometric studies were performed in unilaterally nephrectomized rabbits to examine whether or not ischemic or uranium-induced acute renal failure (ARF) affords resistance to a subsequent renal failure challenge. Two-hr renal artery clamping or i.v. injection of uranyl acetate (UA, 0.8 mg/kg) induced ARF, with recovery from renal injury after 2 weeks. UA-induced ARF afforded functional and morphological resistance to a rechallenge with UA (1 mg/kg) in the recovery phase, whereas kidneys recoverying from prior ischemic injury did not show increased resistance to an additional ischemia. Furthermore, partial resistance to UA-mediated nephropathy was conferred by prior ischemic ARF, but UA-induced ARF did not afford resistance to an acute ischemic event. Increased resistance to ARF was not related to renal hemodynamic alterations or to the water and solute excretion. The present findings suggest that the degree of resistance to ARF differs with different models of renal failure, and that cross protection between ischemic and nephrotoxic ARF is modified by the sequence of ischemia and nephrotoxic substance exposure in uninephrectomized rabbits.

View full abstract

Twenty-four hour ambulatory electrocardiagraphic recording, echocardiographic study and analysis of other parameters (blood chemistry, blood gas and neuroendocrinological investigations) were performed in 26 patients with chronic renal failure who were on maintenance hemodialysis. Control groups consisting of 8 patients with high grade arrhythmias (over Lown grade 2) (Group A) and 18 other patients with low grade ventricular arrhythmias (Group B) were also studied. There were no differences in mean age (59.0 vs. 58.6 years), duration of dialysis, CTR and ultrafiltration ratio, and also no differences in blood chemical and neuroendocrinological parameters and free fatty acids. The pO2 at inception of dialysis in Group A (93.7 ± 7.8 mmHg) was lower than that in Group B (106.0 ± 14.2 mmHg). This difference was significant (P < 0.01). In the echocardiographic studies, Group A showed a lower ejection fraction than Group B (50.4 ± 5.99% vs. 64.8 ± 7.44%). This difference was also significant (P < 0.01). In the 24 hours ambulatory electrocardiographic analysis, ventricular premature contraction (VPC) appeared at the start of hemodialysis. The mean hourly frequency of VPC increased during dialysis and at 4 hours after dialysis. The results of the present study suggest that hypoxia and poor cardiac function may be a cause of arrhythmias in patients on hemodialysis, so that 24 hours ambulatory electrocardiographic recordings are warranted during and after the hemodialysis.

View full abstract

In order to investigate the roles of various factors in the pathogenesis of hypertension, we applied an autoregressive approach to the spectral analysis of long term data from 9 hemodialysis patients with anuria. Although the fluctuation of predialysis body weight reflected fairly well that of extracellular fluid volume, the former revealed essentially no correlation with the fluctuation of predialysis blood pressure of the patients while the patients were treated with chronic hemodialysis. However, by introducing the above new approach, we succeeded in detecting the cause and effect relationship between the two variables, blood pressure and body weight. This technique enabled us to decompose the random fluctuations of the above 2 variables into their frequency spectra, and to calculate the relative power contributions of each variable to the other. It was found that the fluctuation of body weight, which reflects that of extracellular fluid volume, contributed significantly to the fluctuation of blood pressure especially at the specific frequency of one cycle per week in most of the patients examined. Furthermore, by applying this appraoch to multivariate metabolic systems, we confirmed the validity of the mosaic hypothesis for hypertension proposed by Page, on condition that the hypothesis is somewhat modified by taking the concept of frequency domain into consideration.

View full abstract

The binding sites of synthetic rat-atrial natriuretic peptide (r-ANP) were examined in five-sixths nephrectomized rats (Nx rats) by immunohistochemistry. Following injection of 5μg r-ANP, frozen sections of the kidney were prepared for immunohistochemical staining by the avidin-biotin complex (ABC) method using monoclonal antibody to r-ANP were identified on the glomerular cells. It is suspected that the diuretic and natriuretic effects were, at least, partly dependent on the specific binding to these sites. The affinity to r-ANP or binding capacity might be enhanced in Nx rats.

View full abstract

The effect of a new oral adsorbent (AST-120) was examined in uremic rats induced by twostage reduction of the kidney mass, by assessing an abnormal peak "2a" on HPLC (high performance liquid chromatography), which has been regarded as a toxin peak. In vitro, the adsorbent showed adsorption of 2a which appeared in the bile of uremic rats. Uremic rats fed with AST-120 showed significantly lower blood creatinine and 2a levels with higherr values for both the creatinine clearance (Ccr) and the renal clearance of 2a (C2a), as compared to control (pair-fed) rats. Intermittent administration of AST-120 (3 weeks) also produced a significant decrease in blood creatinine and 2a levels and an increase in Ccr and C2a. More strikingly, the progressive destructive changes of the glomeruli were prevented in rats fed with AST-120. These results suggest that oral administration of AST-120 may prevent the rapid deterioration of residual renal function, presumably by removing some nephrotoxic substances from the G-I tract, which may be included within peak 2a on HPLC.

View full abstract

To clarify the conditions of the renin-angiotensin-aldosterone system in renal functional distur-bances and renal failure, the responses of renin and aldosterone to the renin secretion-stimulating test were examined in 39 patients who had chronic primary glomerular diseases, with a glomerular filtration rate (GFR) ranging from 4 to 140 ml/min. The test was performed after they had received furosemide and had been walking for one hour. Although no relationship was observed between the basal plasma renin activity (PRA) and GFR, the increased amount of PRA (oPRA) due to secretooy stimulation showed a significant positive correlation with GFR. The plasma aldosterone concentration (PA) also demonstrated a response similar to that of PRA, and aldosterone secretion from the adrenal cortex by the renin-angiotensin system was normally controlled even in patients with chronic renal failure. The present results indicate that the response of renin secretion decreased in proportion to the reduction of GFR and the reduced renin response was associated with a reduced response of aldo-sterone secretion in patients with chronic primary glomerular diseases.

View full abstract

In the present study, exogenous aldosterone (Aldo) and adrenocorticotropic hormone (ACTH) which stimulates endogenous Aldo were infused into patients with essential hypertension (EH) and the changes in urinary kallikrein excretion (U-Kall) and other factors before and after the infusions were investigated. Under the basal condition before infusion, U-Kall was significantly correlated with the urinary aldosterone excretion (U-Aldo) (r = 0.50, p < 0.05) and glomerular filtration rate (GFR) (r = 0.60, p <0.02). In Aldo infusion, U-Kall was significantly increased from 25.2 ± 3.3 × 10^-4 EU/min at the baseline level to 31.4 ± 3.5 × 10^-4 (p < 0.05) at 90 min but returned to near the baseline level (27.9 ± 3.6 × 10-4) at 180 min in spite of the remarkable increments in U-Aldo and plasma aldosterone concentration (P-Aldo), and there was no correlation between U-Kall and U-Aldo or P-Aldo. On the other hand, the changes in urine volume (UV) and GFR were similar to those in U-Kall. The changes in UV were significantly correlated with those in U-Kall within 90 min (r = 0.87, p <0.01) and 180 min (r = 0.72, p < 0.05) after the infusion. The changes in GFR were significantly correlated with those in U-Kall within 180 min (r = 0.76, p < 0.02) after the infusion. In ACTH infusion, U-Kall was unchanged during the infusion period in spite of the remarkable increments in U-Aldo and P-Aldo, and there was no correlation between U-Kall and U-Aldo or P-Aldo. As regards UV and GFR, no changes were observed during the infusion period, but there was a significant correlation between U-Kall and UV within 120 min (r = 0.88, p < 0.01) after the infusion. These results suggest that Aldo and./or a renal hemodynamic mechanism involving GFR affect U-Kall under physiological conditions, but under the condition of acute infusion, Aldo does not affect U-Kall in spite of the remarkable increments in exogenous or endogenous Aldo.

View full abstract

In the present study, we reinvestigated the effect of bovine serum albumin on dog renin activity. Dog active renin was partially purified from crude renal extract by Pepstatin AH-Sepharose, DEAL Cellulose and Sephacryl S-200 column chromatography. Synthetic tetradecapeptide was employed as substrate. Bovine serum albumin was obtained from 3 different commercial sources, and one of them was partially purified by defatting with charcoal, Sephacyl 5-200, PBE-94 and Blue Sepharose column chromatography. The optimum pH of the renin-substrate reaction was between 6.0 and 6.5 without albumin. When one of the commercial albumin preparations was added, the reaction not only increased at all pHs, but revealed a different pH optimum in the acidic region below 4.5. This suggested that the albumin was contaminated with aspartyl protease(s). A blank experiment was therefore run for each determination to correct for the effect of the protease(s). Although the apparent effects of these commercial and partially purified albumins on the reaction were not always the same, no difference was noted among the effects after correction for the blanks. It appeared therefore that both the activating effect at lower concentrations of the albumins and the inhibiting effects at higher concentrations were caused by the bovine serum albumin itself. The mechanisms of these effects are not yet known.

View full abstract

The precise cellular mechanism of chronic renal allograft rejection is unknown. However, the substantial mononuclear cellular infiltration, which occurs in the rejected graft, suggests that the cellular immune response may be critically involved in graft survival and/or rejection. According to the clinical course of rejection, 13 cases were divided into two groups: Type I and Type II. The Type I group included 8 cases of typical chronic rejection; these cases showed a slowly progressive rise in serum creatinine with hypertension and/or proteinuria. The Type II group included 5 cases, which showed an abruptly irreversible elevation of serum creatinine level (more than 1.0 mg/ dl/month) during the course of Type I chronic rejection. In all 13 cases (Types I and II), pathological examinations revealed evidence of chronic rejection. In Type I, the Leu 2a/3ab ratio was below 1.0 in 7 of the 8 cases; in Type II, it was over 1.0 in 4 of the 5 cases. There was a statistically significant difference between Type I and Type II rejection as regards the ratio of Leu 2a/3ab (P <0.05). The present results demonstrate that T cells are the major infiltrating cells in chronically rejected renal allografts. Helper/inducer T cells were the most frequent cells in Type I cases, whereas cytotoxic/suppressor T cells were predominant in Type II cases of chronic rejection. This difference suggests that a different cellular mechanism may be involved in these two types of chronic renal allograft rejection.

View full abstract

It is extremely rare to diagnose bilateral multiple renal adenomas clinically. We have recently experienced such a case and its details are reported herein. A 53-year-old male with bilateral renal calculi underwent left nephrolithotomy and renal adenoma (18 × 16 mm) was found incidentally and resected. Renal biopsy which was performed simultaneously revealed multiple small adenomas. The right kidney had become contracted as a result of repeated acute pyelonephritis. One year after the left nephrolithotomy, right nephrectomy was performed and multiple adenomas were again found. This condition could be diagnosed as renal adenomatosis.

View full abstract

In February 1984, questionnaires were dispatched in order to determine the incidence and recent trends of renal adenocarcinoma in patients who underwent dialysis between March 1982 and February 1984 in Japan. In addition to 10 reported cases, 27 adenocarcinomas were found by the above survey. The mean age of the 37 (31 males and 6 females) dialysis patients with renal adenocarcinoma was 49.6 years. The mean duration of dialysis was 71.7 months. The clinical diagnosis of adenocarcinoma was based on CT scan (17 cases) and sonographic examinations (4 cases). In 30 cases, the original kidney disease was chronic glomerulonephritis. Eight out of the 37 cases had metastasis. Compared to 34 cases collected in 1982, more of the recent 37 cases were discovered through CT examination than by autopsy and the curative rate was higher. Since the incidence of adenocarcinoma in chronic dialysis patients is 1.5%, it is concluded that many adenocarcinomas in dialysis patients may remain "undiscovered".

View full abstract

Monitoring of urine volume and urinary frequency in rats was performed on a 24-hour basis utilizing a strain gauge to determine the weight of the voided urine. Spontaneously hypertensive rats (SHR) were found to have a stable urinary frequency, averaging 6-8 times a day, regardless of age. In contrast, the urinary frequency of Wistar Kyoto rats (WKY) and Wistar rats (WIS) was higher. Pollakisuria was observed more often in WIS in the dark phase of the day, and when SHR and WKY were diuretic after administration of saline. Young SHR were more liable to show an increase in freequency following saline administration than WKY. Alpha-blockers such as phenoxybenzamine, and prazosin, cause an increase in the frequency of urination or a decrease in the single voiding volume, probably due to sphincteric relaxation, in SHR.

View full abstract