We described a transient low or non-selective proteinuria after forced lordosis as a characteristic of orthostatic proteinuria and the heteroporous theory and sieving function theory which might explain the mechanism of orthostatic proteinuia. The angiogenic action of the renin-angiotensin system played an important part in these theories, Angiotensin II was recognized as the key regulator of renal sodium excretion, because it reduced the urinary Na/K ratio. Since the purpose of this study is to investigate the influence of the renin-angiotensin system on the mechanism of orthostatic proteinuria, proteins and electrolytes in the urine were examined before and after lordosis in 9 healthy children (Group A) and in 6 children with orthostatic proteinuria (Group B). The urinary ratio of protein/creatinine (P/cre) in Group B was already significantly higher than that in Group A before lordosis and significantly increased after lordosis, while P/cre in group A did not increase after lordosis. The urinary Na/K ratio (Na/K) in Group B was already significantly lower than that in Group A before lordosis, and after forced lordosis, Na/K in Group A decrease with no difference between both groups observed. It is suggested that a significant increase on P/cre after lordosis was obtained only in Group A, whereas in both groups the renal vein may be compressed by forced lordosis and as a result angiotensin II may be stimulated, There might be a difference of the responsibility to angiotensin II in glomerular mesangium contraction between both groups.

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Previous studies have suggested that autoimmunity to a number of kidney antigens may exist in glomerular disease. Our own work suggested that sulfatide which is one of the major acidic glycolipids of human kidney may be antigenic. Glycolipids were isolated from lipid extract of human kidney using thin-layer chromatography (TLC), As the major acidic glycolipids, sulfatide, CDH-sulfate, G_M3, G_D3 were identified. Acidic fraction of lipid extract were chromatographed and then tested for antigen by immunostaining. Sera from patients with IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN) contained antibody to the sulfatide of human kidney as determind by the direct binding of antibody to TLC. In addition, we measured the presence of sulfatide antibodies by enzyme linked immunosorbent assay (ELISA) in sera of patients with various glomerular disease: IgAN, HSPN, mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis (MPGN), focal and segmental glomeruosclerosis (FSGS), membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS), acute post streptcoccal glomerulonephritis (PSAGN), and lupus nephritis (LN), IgM class sulfatide antibody were demonstrated in many cases of them. The incidence of IgA class sulfatide antibody in HSPN and IgAN was significantly high, and also the high incidence of IgG class sulfatide antibody occurred in IgAN. On the other hand, we evaluated cellular hypersensitivity to sulfatide in IgAN, HSPN, and FSGS using an active E-rosette assay. Positive results occurred in IgAN and HSPN. It was suggested that delayed hypersensitivity to sulfatide may generate an autoimmune inflammatory process. It has been reported that laminin binds specifically to sulfatide. Autoimmunity to sulfatide may disturbe the laminin binding and consequently interfere with renal function. These results suggested sulfatide antigen may play important role in occurrence and aggravation of glomerular disease.

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Renal nerve and cardiovascular effects of intrarenal veratrine (Ver) were investigated using the cross-perfused kidney preparations of anesthetized dogs. Ver (1 and 3 μg/kg), injected as a bolus, elicited increases in arterial blood pressure (ABP), heart rate (HR) and renal efferent nerve activity (RENA). Ganglion blockade, hexametonium (2 mg/kg) markedly diminisched increases in ABP, HR and RENA induced by Ver. In a separate group of animals, significant increases in renal afferent nerve activity (RANA) occurred after Ver administration. It is concluded that selective intrarenal Ver activates renal nerve afferents, and these results in cardiovascular changes are consistent with efferent sympathetic activation.

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In order to examine the relationship between microscopic findings and the prognosis of patients with IgA nephropathy, a multiple regression lifetable analysis was performed using a Cox's proportional Hazzard model. Histological changes were evaluated on the basis of nine parameters. By using the changes in serum creatinine concentration (S-Cr) as the criterion for assessing the prognosis, calculations were made at two points, the first point of S-Cr reached 2 mg/dl and the second of 4 mg/dl following the biopsy. As a result, the following conclusions were obtained: 1) At the S-Cr value of 2 mg/dl, two regression coefficients for mesangial lesions and crescent formations showed a correlation (P<0.10) with respective risk ratios of 4.517 and 9.970. 2) At the S-Cr value of 4 mg/dl, the regresion coefficient for complete glomerular sclerosis was statistically significant (P<0.05) with a risk ratio of 6.527.Mesangial lesions and tubulo-interstitial lesions had a risk ratio ranging from 3.0 to 4.0 3) In assessing renal histological findings in IgA nephropathy, it is important to take consideration into the variations in the severity and the stage of the renal dysfunction. 4) Although statistical significance of the pathological findings could not be achieved, such speculation as described before was made. More definitive conclusions may be attained by the longer following up on the clinical course, increasing the number of patients to be examined, and devising a more apporopriate mothod for the evaluation of renal tissue lesions.

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The present study was designed to examine the suppressive action of Lipo PGE₁ on the development of accelerated passive Heymann nephritis in rats, Lipo PGE₁, given i. v. twice a day at 20, 40 and 80 μg/kg from the day after immunization with rabbit γ-globulin (γ-G) (the 1st day), remarkably inhibited the urinary protein excretion as well as glomerular histopathological changes such as thickening of basement membrane and spike formation. Lipo PGE₁ at doses which the development of nephritis was suppressed, significantly inhibited the elevation of plasma antibody titer against rabbit γ-G from the day before the appearance of the heavy proteinuria and apparently reduced the deposition of rat IgG in glomeruli. In addition, a single i. v. administration of Lipo PGE₁ remarkably recovered the diminished renal blood flow induced by nephritis. These results suggest that intravenous Lipo PGE₁ is effective in suppressing the development of the experimental membranous nephropathy. This agent may mainly prevent the development of nephritis by reducing the deposition of rat IgG in glomeruli via the suppression of host antibody formation. Furthermore, the increasing action of Lipo PGE₁ on renal blood flow may be also in part related to a beneficial effect of this agent.

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We have studied the influence of exercise on renal function in chronic glomerulonephritis with mesangial proliferation. The mesangial proliferative glomerulonephritis consisted of (1) IgA nephropathy (Mild group), (2) IgA nephropathy (Moderate group), (3) diffuse proliferative glomerulonephritis=DPGN (Mild group), were divided 2 groups between (A) exercise loading groups and (B) control groups, respectively. The period of observation was one or one year 6 months. None of cases deteriorated in the renal function during the period of observation were found in the exercise loading groups. The prescription of exercise for permits with mesangial proliferative glomerulonephritis indicates approximately 130 values of %BMR, which is estimated by calori counter.

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It has been reported that elevation of blood pressure produces a reduction in pain sensitivity. This study was designed to clarify the correlation in spontaneously hypertensive rats (SHR) between fall in blood pressure and pain sensitivity. In seven-weeks-old male SHR, the angiotensin converting inhibitor delapril (10 mg/kg/day) or calcium antagonist nifedipine (3 mg/kg/day) was administered orally every day for 8 weeks. Systolic blood pressure (SBP) pretreatment was significantly higher in the SHR than in normotensive Wistar-Kyoto (WKY) rats and pain sensitivity measured with the hot plate method was significantly lower in the SHR than in the WKY rats. Administration of both drugs produced a significant suppression of elevation of SBP, and produced a significant elevation of pain sensitivity. Furthermore, at 8 weeks after drug administration, urinary norepinephrine (UNE) significantly decreased and plasma β-endorphin (β-end) significantly increased. A significant correlation was noted between pain sensitivity and SBP and also between pain sensitivity and UNE. Of these, pain sensitivity was the more closely correlated to degree of change in UNE than to degree of change in SBP. It appears that elevation of pain sensitivity is due to suppression of the sympathetic nervous system by antihypertensive drugs, but not to elevation of β-end levels. These data suggest that a fall in blood pressure through administration of delapril or nifedipine reverses decrease in pain sensitivity in SHR and that decrease in sympathetic tone plays an important role in the restoration of levels of sensitivity to pain.

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Endogenous creatinine clearance (Ccr) has been much more commonly used to estimate renal function in clinical medicine, in comparison with inulin clearance (Cin) which is more accurate measure of glomerular filtration rate (GFR). There is, however, increasing difference between Ccr and Cin as renal function deteriorates. Since this difference is considered to be resulting from the tubular secretion of creatinine, Cin and Ccr were simultaneously measured in 81 patients with chronic renal disease, as well as 12 control subjects in this study. As Cin decreased, the Ccr/Cin ratio increased and the ratio varied widely even in patients with similar degree of renal impairment. The subjects were classified into 3 groups, group I (Cin>80 ml/min), group II (80 ml/min ≥Cin ≥40 ml/min) and group III (Cin>40 ml/min). The mean values of tubular creatinine secretion (Tcr) were 0.07±0.173 mg/min (±SD) in group I, 0.205±0.136 mg/min in groupII and 0.333 ±0.139 mg/min in group III, respectively. Therefore, Tcr in the group of the severe impairment was the highest. In addition, Ccr and Cin were measured in 15 patients with chronic nephritis before and after an intravenous bolus injection of cimetidine (5 mg/kg BW). Following the injection Ccr/Cin ratio was reduced from an initial value of 1.51±0.23 to 118±0.13 in group II and from 2.00±0.44 to 1.55±0.25 in group III, respectively. Tubular secretion of creatinine appeared to be inhibited by cimetidine even in the patients with severe renal dysfunction. It was concluded that the function of tubular secretion of creatinine was preserved even in patients with moderate to severe decrease in GFR, resulting in a disparity between Ccr and Cin. Therefore, Ccr in the normal range does not necessarily indicate normal glomerular function since there is wide range variety in Ccr and Cmn in the individual patients.

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It is well known that the products of protein catabolism and some of the intermediates including middle molecules (MM) are a biochemical feature of uremic serum and also the activity of serum alanine aminotransferase decreases relatively. To examine the toxicity of MM, we investigate the effect of MM removed by HF on aminotransf erases and peptidases in rat liver cytosol. The following enzymes were selected: aminotransf erases (GOT, GPT), leucine aminopeptidase (LAP), γ-glutamyltranspeptidase (γGTP). MM samples were as follows: preparation of MM fraction from each 10l HF fluid at half intervals of former (F-) and latter (L-) for 5h. HF of two patients (5 weeks) by 1KD ultrafiltration, and group separation into hydrophobic (Mo) and hydrophilic (Mi) by XAD-4 resin (F-Mo, L-Mo, F-Mi, L-Mi). Except for GOT, the effect of MM were found at the activities decreased on LAP (26-30%), on GPT (5-6%), and increased on γGTP (4-23%), as compared to control. We found a little difference in the results by the character of MM (Mo, Mi) and by the intervals of HF (F-, L-). These results suggest that MM might play a role in the formation of uremic peptides.

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Our medical team conducted the percutaneous renal biopsy, using an aspirating biopsy needle (Vacu-Cut) in 101 cases, and an automatic biopsy needle (Biopty-Cut) in 82 cases. Thereafter, we examined the usefulness of the two types of needles in comparison with that of Tru-Cut used in 101 cases. The test confirmed that in the cases of Vacu-Cut, 7.6 glomeruli (p <0.01), on the average, existed in LM specimen; 9.0 glomeruli (ns), Biopty-Cut, and 10.7 glomeruli, Tru-Cut, respectively. However the incidence of cases containing more than 5 glomeruli was not significant statiscally between Vacu-Cut/Biopty-Cut and Tru-Cut. The incidence that each type of needles obtained more than one glomerulus in IF specimen was as follows: 73.3%, Vacu-Cut (p<0.05), 81.7%, Biopty-Cut (ns), 87.1%, Tru-Cut, respectively. As for in EM specimen, 61.4%, Vacu-Cut (ns), 67.1%, Biopty-Cut (ns), and 70.3%, Tru-Cut, respectively. As for complications, in the cases of Vacu-Cut and Biopty-Cut, gross hematuria and post-biopsy pain occured in 6.9 to 9.8% (p<0.01-p<0.05), whereas in Tru-Cut, they occured in 20.7 to 24.8%. As for blood pressure lowering (less than 90 mmHg) and anemia (the cases in which blood transfusion was required), 0%, Vacu-Cut and Biopty-Cut, 2 to 3%, Tru-Cut, respectively. As for fever, Vacu-Cut 0%, Vacu-Cut (p<0.01), 3.7%, Biopty-Cut (ns), and 7.9%, Tru-Cut, respectively. The above findings lead to conclusion that both Vacu-Cut and Biopty-Cut are useful instruments for renal biopsy.

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The effects of internal treatment were compared with those of surgical procedures on secondary hyperparathyroidism as a complication of chronic renal failure patients in order to study their applications and problems. Maintenance hemodialysis patients complicated with 2HPT were selected as test subjects. The following internal treatment was administered. 1) Elcitonine to 6 cases and 2) Ipriflavon to 5 cases respectively and applied 3) pulse therapy of 1.25 (OH) ₂D₃ to 12 cases. On the other hand, total parathyroidectomy and autotransplantation were carried out as surgical procedures. The results of the treatment were evaluated by comparing serological data including tartrate resistant acid phosphatase (TAP) measured with the passage of time, bone scintigram findings, and change of bone mineral content (BMC) measured by single photon absorptiometry and dual photon absorptiometry. In the pulse therapy group, an oral tolerance test of 6μg of 1.25 (OH) ₂D₃ was carried out to investigate its relation to long term prognosis. Futhermore, in both the pulse therapy group and PTX group, serum aluminum (Al) and ΔAl calculated by Defferoxamine (DFO) tolerance test were measured. The results are as follows. 1) In Elcitonine and Ipriflavon administration groups, increase of ALP and PTH and decrease of BMC (p<0.05) were recognized. 2) In the pulse therapy group, although the patients with PTH-C less than 30 ng/ml showed decrease in PTH both in short and long terms, cases with PTH-C more than 30 ng/ml kept the same level in PTH. Regardless of the change of PTH and ALP, there was no significant change observed in BMC. 3) In the PTX group, ALP/TAP ratio rose by 900% temporarily and BMC increased (p<0.01) in all regions measured. 4) Serum Al and ΔA1 were decreased (p<0.01) in PTX cases and in the pulse therapy cases in which ALP was decreased. In recent years, internal treatments on 2HPT patients have become diversified, However, exacerbation of 2HPT considered as an escape phenomenon caused the decrease in BMC after exclusive calcitonine preparatives administration. Pulse therapy, which is regarded at present as most effective in reducing PTH, ALP, did not work to increase BMC efficiently. In other word, in order to attain efficient BMC increase action, it is necessary to transfer from bone resorption phase to formative phase rapidly with drastic decrease of PTH and TAP observed in PTX. At present, it is advisable to apply PTX while preventing Al from accumulating and fixing within the bone using Al cherating therapy for patients with PTH-C of more than 30 ng/ml and significant decrease in BMC.

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A 26-year-old female patient complicated with reflux nephropathy and pheochromocytoma is reported. We could not find either intrinsic or extrinsic factor of urinary tract obstruction. The open bilateral renal biopsy was performed at the time of resection of the tumor. The renal biopsy specimen demonstrated minor glomerular change, severe tubular "thyroid-like" appearance and cast formation in the obvious reflux side. Otherwise focal glomerular sclerosis (FGS) lesion was found in less reflux side. In reflux nephropathy, FGS lesion is reported as main cause of progression, but mechanism of FGS lesion is unknown. This case which has both vesicoureteral reflux the high plasma nor-epinephrine concentration was considered to be important to emphasize circulative factor in the pathogenesis of FGS like lesion.

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We examined fresh urine samples from patients with hematuria using flow cytometry to evaluate its clinical usefulness and accuracy in objectively identifying glomerular and non-glomerular hematuria. Two parameter analysis was applied for forward light scattering (OLS), chiefly representing cell volume and perpendicular light scattering (90LS), chiefly representing cell structure. In patients whose diagnosis were established by renal biopsy or diagnostic procedures, the patterns of the distribution curves of OLS and 90LS were divided into three groups; (1) glomerular, (2) non-glomerular and (3) debris patterns. After a prospective blind study was undertaken, the results of flow cytometry were later compared with the results of clinical diagnosis. Glomerular hematuria above 30/high power field could be detected with high sensitivity (92.9%) and specificity (90.5%) . Glomerular diseases showed a significantly lower peak channel number than non-glomerular diseases did (OLS; 53.8± 16.4 versus 97.5± 26.5, p< 0.01, 90LS; 48.4± 17.0 versus 85.5± 32.9, p< 0.01, respectively) . It is suggested that flow cytometric analysis of hematuria is an useful diagnostic procedure as a rapid, non-invasive, accurate and objective test for determination of origin of hematuria.

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Recombinant human growth hormone (r-hGH), 1 U/kg body weight/week, was administered subcutaneously for 2-4 weeks to two end stage renal disease patients with severe malnutrition, Following r-hGH, there were significant increase in hematocrit level and serum conceetration of albumin, IGF-1 and GH, and decrease of urea nitrogen. It was concluded that r-hGH exerts a therapeutic effect to nutritional status in renal failure patients by improving severe hypoalbuminemia, susceptibility to infectious disease, intractable ascites and so on.

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Effect of angiotensin converting enzyme inhibitor (ACEI) and calcium channel blockers (CaB) on renal blood flow (RBF), glomerular filtration rate (GFR), and autoregulation (AR) of RBF were studied on the uninephrectomized spontaneously hypertensive rat (SHR) under the conditions of high (H) and low (L) salt loading. SHR was given with 0.9% or 0.09% NaCl solution as drinking water (GH, GL). Each group was divided into three groups for treatment with enalapril (Enp) and nitredipine (Nit); i. e. Enp group (GHE, GLE), Nit group (GHN, GLN) and control group (GHC, GLC). After 6 weeks, inulin clearance (Cin) was determined and RBF was measured by means of an electromagnetic flow meter. The renal arterial pressure was lowered by clamping and changes in RBF and AR were examined. Cin showed higher values of 1.85 and 1.69 ml/min in GHN and GLN, as compared to be 1.33 and 1.28 ml/min in GHC and GLC (p<0.01). Filtration fraction (FF) showed lower values of 0.18 and 0.20 ml/min in GHE and GLE (p<0.01), whereas 0.29 and 0.30 in GHC and GLC respectively. RBF was markedly lower at 7.4 ml/min in GLC as compared to 9.9 ml/min in GHC (p<0.01). In GH, GHE showed a higher value of 11.6 ml/min, as compared to GHC (p<0.01). In GL, comparing with GLC the value was much higher of 12.1 ml/min in GLE (p<0.01). AR of RBF diminished in GLC at higher blood pressure as compared to GHC (p<0.01). It was maintained at lower blood pressure in GLE (p<0.01), but there were no significant differences between four groups; i. e. GLN, GHC, GHE and GHN. In summary, low salt loading reduced RBF and suppressed AR. Enp elevated RBF, lowered FF and caused AR to be maintained even at lower blood pressure. Nit elevated RBF and GFR without changing FF, and did not suppress AR. These results indicate that, in hypertension complicated with moderate renal dysfuncction, both ACEI and CaB are expected to exhibit the beneficial effects on maintenance of renal circulation, despite though the different mechanism.

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