H-D antibodies which were known as antibodies detectable in patients with serum sickness have recently been detected in renal diseases. We attempted to detect IgG, IgA and IgM antibodies to N-glycolyl GM3, among other H-D antibodies, by ELISA in various renal diseases and found increased IgM antibody in mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis, IgA nephropathy, minimal change nephrotic syndrome and Henoch-Schonlein purpura nephritis (HSPN), elevated IgA antibody in IgA nephropathy and HSPN and raised IgG antibody in IgA nephropathy. In 2 cases of IgA nephropathy, there was noted a good correlation between clinical course and anti-N-glycolyl GM3 antibody titers. Measurement by ELISA of IgG antibody to cytomegalovirus (CMV) seemed as one of immune pathogenetic factors of IgA nephropathy showed a high positive rate for this antibody of IgA nephropathy patients and a positive correlation between the antibody and anti-N-glycolyl GM3 antibody. The key molecule of H-D antigens is N-glycolyl neuraminic acid (NGNA) and this sialic acid does not normally exist in humans. One can surmise, therefore, that in those renal diseases in which there was noted an elevation of anti-N-glycolyl GM3 antibody, this antigen is formed or generated by some unknown mechanism. In other words, it may be that humans are not entirely negative for H-D antigens but have a minimum inherent antigenicity and a potential capacity to synthesize these antigens. The present study thus raises the possibility that activation of sialic acid mono-oxygenase, an enzyme that catalyzes the conversion of N-acetyl neuraminic acid to NGNA and can normally occur in man, may take place in renal diseases also, e. g., as a consequence of viral infection serving as a trigger.

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In a study involving 22 cases of nephrotic syndrome in children, investigations were made of growth disturbance caused by corticosteroid in relation to dose of the steroid and age levels at steroid treatment and also of the effects of concomitantly used im-munosuppressive drugs. The final height of frequent relapsing nephrotic syndrome was below M-2SD in approximately 30% of cases. Final heights of boys receiving the steroid from 12 to 16 years of age and of girls treated with the steroid from 10 to 14 years of age were below M-2SD and 10 cm lower than the target height. Final heights of boys and girls who could be withdrawn from steroid therapy by the age of 14 and 12, respectively, were invariably within or above the normal range. The addition of azathioprine therapy resulted in no appreciable reduction of steroid dosage nor improvement of yearly growth rate, although the frequency of relapse for that year was diminished. Under a regimen of concomitant cyclophosphamide the frequency of relapse and steroid dosage was also reduced but the growth rate was accelerated, no significant reduction of steroid consumption was achieved. The administration of cyclosporin A in doses of 1.5-5.0 mg/kg was marked by a reduction in steroid dosage as well as in the frequency of relapse and allowed for near normal growth rate, with no significant differences being observed between the high dose group (3-5 mg/kg/day) and the low dose group (1.5-2.5 mg/kg/day). Prolonged steroid therapy in frequent relapsing nephrotic syndrome may produce dwarfism and other distressing side effects. The present study suggests the potential usefulness of immunosuppressive drugs in the prevention of such distressing end results of steroid therapy. Pediatricians had better use them to gain a positive result in the management of the disease in the hope that every patient will attain a normal height.

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In metabolic disorders such as diabetes mellitus (DM) and obesity, renal abnormalities may also occur even when renal dysfunction is not be detected by conventional urinalysis. By use of immunological technique, an investigation was made on the subclinical abnormality in the excretion of urinary proteins in DM and obese (OB) subjects. Urinary excretion of the proteins (albumin, IgG, IgG4, β2-microglobulin) and fractional clearances (clearance ratios to creatinine clearance) at sitting position were respectively measured. Albumin excretion rate (AER) and fractional albumin clearance were higher in DM and OB than normal controls (NC). In non-diabetic subjects (OB+NC), body mass index (BMI) significantly positively correlated with AER and fractional albumin clearance. In DM, not only AER and fractional albumin clearance but also IgG4 excretion rate and fractional IgG4 clearance positively correlated with BMI. In DM with BMI<22 Kg/m², HbA1C significantly correlated with AER, IgG4 excretion rate, and fractional albumin and IgG4 clearances. The data suggest that microproteinuria in DM and OB may be of glomerular origin. In DM, in the light of an increase in urinary excretion of negatively charged IgG4, it is also suggested that proteinuria is attributed to the alteration of charge barrier as well as to that of glomerular hemodynamics. Lastly but not leastly, obesity-related factor should also be taken into account in the development of microalbuminuria of the diabetic patient.

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We examined the chronic effects of MK954, a novel orally active angiotensin II receptor antagonist, on blood pressure and renal function in 8 patients with essential hypertension for 2-4 weeks. All patients, four men and four women, 48.0±15.3 year-old (mean±SD), were hospitalized and given normal sodium diet (NaC1 10 g/day). After a control period with placebo for one week, MK954 was administered orally at 8 AM every day. The initial dose of MK954 was 12.5 mg/day, then the dose was increased up to 100 mg/day untill diastolic blood pressure fell below 90 mmHg. The average dose was 59.4±43.7 mg/day. Casual blood pressure in supine position decreased significantly from 161.0±6.6/95.0±3.5 mmHg to 145.8±8.1/83.3±3.7 mmHg without any change in pulse rate. Non-invasive ambulatory blood pressure monitoring revealed that once daily administration of MK954 lowered blood pressure for 24 hours but did not affect circadian rhythm or variability of blood pressure. Reduction of blood pressure was slingtly greater during day time than during sleeping time. Unlike a peptide angiotensin II antagonist, there was no pressor action of MK954 as agonist. No significant alternations were observed in body weight, serum electrolytes, creatinine clearance, urine volume or urinary excretion of sodium. Plasma renin activity (PRA) rised significantly after MK954 treatment but plasma aldosterone concentration (PAC) did not change. The reasons why PAC was not reduced are unclear. The doses of MK954 employed in this study might be insufficient to inhibit adrenal angiotensin II receptor. In conclusion, MK954 has long acting hypotensive effect in essential hypertension without affecting renal function.

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We examined the effect of immunosuppresive agent, FK506 (Fujisawa, Co.), on puromycin aminonucleoside (PAN)-induced nephrosis. Single i, p. injection of PAN in a dose of 100 mg/kg was introduced into Munich-Wistar rats weighing about 200 g. Those rats were divided into four groups. PAN-induced nephrosis rats in group 1 (PAN-FK0.1, n=5), group 2 (PAN-FK0.3, n=5), group 3 (PAN-FK1.0, n=5) were treated with i. m. injection of FK506 for 10 days in a dose of 0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg, respectively, and rats in group 4 were treated with FK-placebo (PAN-PL, n=5). The rats in group 5 with Saline+placebo were served as a control (NS-PL, n=5). Among 5 groups, urinary protein, anionic sites (AS) in GBM, and subsets of peripheral lymphocytes through FACS were compared. After 9 days of PAN injection, the rats in PAN-FK0.1 (160.0±38.4), PAN-FK0.3 (118.0±34.4) & PAN-FK1.0 (89.2±40.0) given FK-506 had significantly less proteinuria in a PAN dose dependent manner, compared to those in NS-PL (349±86.8 mg/day). The numbers of AS/1000 mmGBM were more attenuated in FK506-treated PAN rats (PAN-FK1.0; 16.2±3.9) than those in PAN-PL (11.7±4.4). In related to subset of lymphocytes, increased W3/25 in PAN-PL was regressed in PAN-FK0.1, PAN-FK0.3 & PAN-1.0 after 10 days of PAN-injection. W3/25/OX-8 was significantly higher in PAN-PL (3.6) than those in NS-PL (2.4), but not between PAN-1.0 & NS-PL. These data indicate that the mechanism for therapeutic effect of FK506 on PAN-induced nephrosis includes a revision of abnormal cellular immunity, which attenuates the decrease of AS structure and as a result decrease proteinuria.

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This study is aimed to demonstrate that renal impairment caused by administration of amikacin (AMK) alone can be lessened by co-administration of piperacillin (PIPC). The patients in the present study were divided into three groups. In "group P" and "group A", PIPC alone and AMK alone were administered, respectively. In "group P+A", PIPC and AMK were co-administered. Dosage of AMK was individualized based upon the therapeutic drug monitoring method, and that of PIPC was adjusted depending upon the creatinine clearance of a patient. In group A, urinary concentrations of β₂-microglobulin and lysozyme, and urinary excretion of j32-microglobulin, lysozyme and r-GTP per day were significantly higher (p<0.05) than those in group P. These differences were not observed, however, between group P and group P+A. The trough value of AMK, 11 days after AMK administration, was significantly higher in group A (p<0.05) than that in group P+A. Incidence of renal impairment, as judged from urinary excretion of j92-microglobulin per day and urinary lysozyme concentration, was significantly higher in group A (p<0.05) than that in group P+A. These findings indicate that co-administration of PIPC with AMK can lessen the renal impairment caused by administration of AMK alone.

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Active vitamin D (VD) metabolite preparations have been used in the management of secondary hyperparathyroidism (2°HPT) due to impaired calcium and phosphorus meta-bolism and can allegedly be expected to prevent, to some extent, the progression of this pathological condition. Unfortunately, however, it is not uncommon for us in routine clinical practice to find 2° HPT of moderate or greater severity embarrassingly unamenable to treatment with these VD preparations in ordinary oral therapeutic doses. Recent studies have gradually reported that intravenous administration of 1, 25-(OH)₂D₃ and oral active VD pulse therapy has been therapeutic approach to 2°HPT. Methylguanidine (MG) among other GCs, its precursor is already identified as creatinine and activated oxygen as well PTH and VD are known to participate in the process leading to its formation. In the present study, we administered oral 1, 25-(OH)₂D₃ pulse therapy to patients with chronic renal failure for the treatment of 2° HPT in an attempt to assess the effectiveness of this therapeutic regimen and to explore the clinical effect of MG on responsivness to the therapy. The purpose of this paper is to present the results thus obtained. Oral 1, 25-(OH)₂D₃ pulse therapy (6 ug once a week) was administered to 21 hemo-dialysis patients with for 12 weeks. Of these 21, 10 patients responded to the therapy with a more than 20% reduction in serum (PTH) ; (responsive group), whereas the remaining 11 did not (resistant group). Pretreatment serum PTH levels were significantly higher in the latter group than the former. Serum MG levels were found significantly depressed atday 2 and day 4 of initiating therapy in the responsive group, while no such changes were observed in the resistant group. The results of this therapeutic trial indicate that oral active VD pulse therapy is of little value in hemodialysis patients with severe 2°HPT and suggest that measurements of the concentration of MG in serum might be a useful indicator for judging the effectiveness of the therapy.

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Urea kinetic modeling was applied to 19 CAPD patients followed in our outpatient clinics. Serum β₂-microglobulin was also measured as a marker of large molecular weight substances. Clinical conditions of patients were assessed by both doctors and patients. Patient's assessment were done by the questionnaire. Indices of urea kinetics (KT/V, PCR) and biochemical parameters were compared between well-treated and not well-treated patients judging from patient's and doctor's assessment scores. The rate of peritonitis was significantly higher in the latter group. None of the parameters were different between 2 groups except for serum albumin. There was a significant correla-tion between serum concentration of albumin and doctor's assessment score (r=0.52). In conclusion, urea kinetic parameters is not a good indicator for adequacy of dialysis in our CAPD population. Serum albumin seems to be one of the indices for adequate dialysis. However, clinical symptoms and signs are more valuable than biochemical parameters for the assessment of adequancy of dialysis.

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Survival of bacteria and release of the endotoxin from the bacteria with and without ultraviolet irradiation in three kinds of dialysate were investigated. The results obtained are as follows: (1) No growth of S. aureus, E, toll, P. aeruginosa, Aspergillus and C. albicans in the saturated dialysates tested were observed. (2) All of the bacterial cells tested here is gradually, and naturally spontaneously inactivated in all the dialysates. (3) Among the dialysates tested, the saturated dialysate, AF-2, is the most effective for inactivating P, aeruginosa ATCC, but the effect depends upon the isolates of P. aeruginosa. (4) The inactivating effect was somewhat decreased when the saturated AF-2 solution was diluted, but the killing effect was still maintained. (5) The bacterial cells are constantly and significantly inactived by UV irradiation, especially by the direct irradiation. The indirect irradiation, i, e., through glass, has remarkably less effective than the direct one. However, a tendency of the decrease of bacterial cells by the in-direct irradiation is maintained with the killing effect of the dialysated, especially in the case of AF-2 solution. (6) No significant increase of endotoxin was observed, even when the bacterial cells were killed by UV irradiation. Therefore, it is recommended to use UV irradiation for inactivating the bacteria. From the results obtained here, it is indicated that there is no possiblity of the growth of naturally contaminated bacteria in the dialysates, and is an effectiveness of the use of UV irradiation for inactivating the bacteria cells, in terms of release of the endotoxin from the dead cells.

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In order to evaluate the clinical significance of urinary human epidermal growth factor (hEGF) in patients with acute renal failure (ARF), urinary hEGF levels were determined by radioimmunoassay, and were corrected for creatinine (treat.) concentrations in 16 patients with ARF and 12 healthy controls. The urinary hEGF levels significantly decreased in patients with ARF in acute phase compared with normal control subjects (0.98±0.20 vs 13.74±1.18 ng/mg treat. p<0.01), and it subsequently increased during recovery phase (6.10±0.73 ng/mg treat. p<0.01 vs acute phase). A significant correlation between the urinary hEGF levels and creatinine clearance (r=0.712, p<0.001) and an inverse correlation between urinary hEGF levels and fractional excretion of sodium (r= -0.406, p<0.05) was demonstrated. The remarkable decrease of urinary hEGF excretion preceded the increase of urinary j32-microglobulin and N-acetyl-3-D-glucosaminidase levels. Our data suggests that urinary hEGF originates from renal tissues in humans and measurement of urinary hEGF is useful for diagnosing renal damage and recovery of renal tissues from severe tubular injury.

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The influence of renal function on the antihypertensive effect and pharmacokinetics of NZ-105 were studied in 7 patients with essential hypertension (EH) and 6 patients with hypertension having impaired renal function (RH). 1. As for the hypertensive effect, both in EH and RH, the maximum antihypertensive effect was attained 3 to 5 hr after drug administration and there was not significant dif-ference between EH and RH. 2. There was not significant difference in transition of plasma concentration of NZ-105 between EH and RH. 3. Concerning pharmacokinetic parameters of NZ-105, there was significant difference between EH and RH in Tmaxx at 20 mg of NZ-105 administration. However, in regard to Tmax, at 30 mg of NZ-105 administration and Cmax., AUC and t112 at 20 mg, 30 mg of NZ-105 administration, there were not significant differences between EH and RH. 4. There was no correlation between t112 and serum creatinine levels. 5. All cases showed good tolerance without any adverse effect.

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Duplex Doppler sonography (ultrasonic equipment: Toshiba SSA-270A) were per-formed in the patients with various renal disease (male 44, female 32) admitted to our hospital between June 1990 and August 1991. Interlobar arterial blood flow velocity was measured at the side of renal pyramid through a longitudinal scan. Both the maximum blood flow velocity (Vmax) and the minimum blood flow velocity (Vmin) were measured quantitatively and resistive index (RI: defined as (Vmax -Vmin)/Vmax) were calculated. Vmax and Vmin correlated well with the creatinine clearance (Ccr) (r=0.56, r=0.66 res-pectively), whereas RI, by which we can detect Doppler waveform changes, correlated weak with Ccr (r=0.39). We found twenty-nine patients (40%) with an elevated RI (≥0.70). They had severe renal dysfunction and active pathologic findings in the tubuloin-terstitial or vascular compartment of the kidney. Doppler examination of renal blood flow velocity was valuable not only to estimate renal function but also to assess patho-physiology of renal disease.

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This report describes clinical and histopathological findings of a case of a 43-year-old male with granulomatous interstitial nephritis. The patient developed renal failure following renal insufficiency of 4 months duration. The patient presented with lethargy and nocturia. The first renal biopsy revealed granulomatous interstitial nephritis. There was no apparent evidence of a systemic granulomatous disease or drug hypersensitsvity. Therapy with reducting regime of predonisolone produced a marked improvement in symptoms and renal function. Relapse occurred 3 months later in association with early discontinuation of the corticosteroid therapy. Ga-scintigraphy demonstrated an abnormal accumulation of gallium in both kidneys. The second renal biopsy did not show the obvious improvement. With the re-administration of the corticosteroid therapy, renal function rapidly improved again. Twelve months after the re-administration of the steroid therapy, Ga-scintigraphy showed no renal uptake. Corticosteroid therapy yielded a favorable outcome for renal function. The third renal biopsy showed disappearance of the granulomas lesion. Re-administration of the corticosteroid therapy continued for 22 months and the patient has not yet relapsed 9 months after the withdrawal of the steroid therapy.

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A case of idiopathic interstitial nephritis who underwent to chronic renal failure without history of hematuria nor proteinuria is discussed. A 46 years old woman who showed gradually elevation of serum creatinine (1.3-2.5 mg/dl) admitted on our hospital. On occasions of pregnancy, health examination or hospital visit, she has never been pointed out hematuria nor proteinuria. Immunological disorders such as SLE, metabolic diseases, urinary tract obstruction and chronic urinary tract infection were excluded by the examinations after admission. Because of the severe enzymuria (β₂-microglobulin, N-acetyl glucosaminidase), chronic interstitial nephritis was considered, and renal biopsy was performed. Severe tubulointerstitial changes were observed histologically, however, glomerular damage was comparatively mild. From these results, she was diagnosed idiopathic chronic tubulointerstitial nephritis. In this case, hematuria and proteinuria were absent until severe renal dysfunction. This may be caused by that inflammation was located to the tubulointerstitial area. The observation of enzymuria seemed to be important to diagnosis and follow-up of the interstitial nephritis.

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