To clarify a clinical significance of urinary methylguanidine (U-MG, μg/dl) in nondialyzed patients with chronic renal failure, we measured U-MG, urinry creatinine (U-Cr, mg/dl) and serum creatinine (S-Cr, mg/dl), concurrently and continually in 36 out-patients whose S-Cr was over 4.0 mg/dl. Fresh urine sample was obtained and U-MG was measured by an enzymic method. S-Cr concentrations (mean±SD) at the initiation of dialysis therapy were comparable in non-diabetics and in diabetics, being 13.4±4. 54mg/dl and 8.23±1.96mg/dl, respectively, with statistical significance (p<0.01). U-MG/Cr (μg/mg. Cr) values were also different between them, being 9.28±4.97 in non-diabetics and 5.19±1.29 in diabetics, but with lesser statistical significance (p<0.05) than S-Cr. U-MG/Cr correlated well with the terms till the initiation of dialysis therapy (r=0.7189, p<0.001), more significantly than S-Cr (r=0.5506, p<0.001) in parabolic regression analysis. U-MG/Cr were greatly varied among the 7 patients, although whose S-Cr was nearly the same level (6.0-6.9mg/dl). Most importantly, the tendency was found in these patients that the higher U-MG/Cr, the earlier the renal replacement therapy instituted. These results suggests that U-MG/Cr can be reliable parameter to predict the progression rate of renal failure and to help to hnow when renal replacement therapy should be instituted.

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In order to elucidate the diagnostic significance of urinary apolipoprotein H (apo H), known as β₂-glycoprotein I, urinary apo H levels were measured by a non-competitive enzyme immunoassay in diabetics without hypertension and Albustix-positive proteinuria. The relationships between urinary apo H levels and urinary albumin (Alb) levels as well as clinical profiles in diabetics were investigated. The mean urinary apo H level in 45 diabetics was 264.2±189.5μg /g⋅cr, and significantly higher than that in 41 healthy subjects (120.6±84.8μg/g⋅cr, p<0.01). Diabetics were classified into three groups based on urinary Alb levels; 17 group I patients with normoalbuminuria (U-Alb<15mg/g⋅cr), 12 group II patients, whose urinary Alb levels were in between normo and microalbuminuria (15≤ U-Alb < 30mg/g⋅cr) and 16 group III patients with microalbuminuria (30 < U-Alb ≤ 300mg/g ⋅cr). The mean urinary apo H level in group I patients, who were regarded as without nephropathy, was 199.2 ± 109.0μg/g⋅cr, significantly higher than that in normal subjects (p <0.01). The mean urinary apo H levels in group and III were 271.4±177.1 and 327.8±246.1 μ g/g ⋅cr, respectively. These values were also higher than in normal subjects (both of p<0.01). Urinary apo H levels correlated positively with urinary levels of glycosaminoglycan (r=0.382, n=45, p<0.01), which was regarded as an indicator of the anion loss from glomerular basement membrane to urine, and with urinary N-acety1-β-D-glucosaminidase activities (r=0.378, n=37, p<0, 05). These results indicate that urinary apo H levels may be a new sensitive marker for minor changes of glomerular basement membrane and minor tubulointerstitial lesions in diabetics.

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The decreases of glomerular filtration rate (GFR) and renal blood flow (RBF) after acute administration of cadmium have been reported. The recent studies about renal failure induced by heavy metals revealed that the decrease of glomerular ultrafiltration coefficient is an important contributing factor in the onset of acute renal failure and that the changes of renal hemodynamics are less prominent factors. To clarify whether the changes of renal hemodynamics contribute to the decrease of GFR caused by cadmium, we evaluated the changes of renal hemodynamics and inulin clearance after acute intravenous infusion of cadmium chloride in rats. Cadmium chloride was continuously infused at the rate of 3.0 μmol/kg/min into SD rats. Mean arterial pressure was significantly increased immediately after the infusion of cadmium and unchanged during the experiment. 20 minutes after the infusion of cadmium, inulin clearance was decreaed by 70% of the control value but RBF and renal vascular resistance (RVR) were unchanged. Filtration fraction was significantly decreased. 30 minutes after the infusion of cadmium, inulin clearance was further decreased by 51% of the control value. At the period, significant decrease of RBF (72% of control value) and increase of RVR (156% of control value) were observed. Urinary excretion of sodium and the ratio of urinary sodium to urinary inulin excretion were unchanged until 20 minute and were significantly decreased 30 minuts after the infusion of cadmium. Urinary volume was not changed throughout the experiment. These data indicate that the initial decrease of GFR after the infusion of cadmium is resulted from the decrease of filtration fraction but not RBF, suggesting the contribution of tubuloglomerular feed-back system and that the changes of renal hemodynamics contributes to the following further decrease of GFR.

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In order to clarify the pathogenesis of hypotension seen in the patients on chronic hemodialysis, we studied the vascular reactivity to exogenous vasoactive substances and the change of plasma ANP level during hemodialysis treatment. The vascular responsiveness to intravenously infused norepinephrine was decreased in hemodialysis patients, particularly in hypotensive group, compared with healthy controls (< 0.05). The blood pressure response to angiotensin II was also diminished significantly in hypotensive patients, compared with normotensive patients (p <0.05). The plasma ANP concentration before and after each hemodialysis treatment was not different statistically between hypotensive and normotensive patients. Furthermore, the change of plasma ANP concentration was not correlated with the blood pressure change during each hemodialysis procedure. These findings suggest that the decrease of vascular responsiveness may be a factor for causing persistent hypotension in patients on chronic hemodialysis, and that the plasma ANP level is not responsible for the pathogenesis of hypotension.

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Circadian blood pressure pattern in the patients with chronic glomerulonephritis was studied by ambulatory 24-hour blood pressure monitoring (ABPM). Subjects were 32 patients and were divided into three groups with various renal function; Ccr of 10 patients were normal (Ccr≥70ml/min), 10 patients 30≤Ccr<70ml/min and the Ccr were below 30ml/min in the other 12 patients. Blood pressure levels were significantly higher in reduced Ccr groups as compared with normal Ccr cases. The blood pressure gradient between day-time (7:00-19:00) and sleeping time (1:00-5:00) significantly decreased in the patients with renal impairment as compared with normal Ccr cases. And it positively correlated with Ccr (r=0.51, p<0.01). These results indicate that the patients with reduced renal function in chronic glomerulonephritis show abnormal circadian blood pressure pattern and nocturnal hyperten sion, which may reqire novel modification of antihypertensive treatment.

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Lipid metabolism in tissues and HDL were examined in daunomycin-induced nephrotic rats.1) Daunomycin-induced nephrotic rats showed the decreased phospholipids, the increased cholesterol content in heart. Phospholipids, triglycerides and cholesterol content in brain, lung and spleen were similar in daunomycin-induced nephrotic rats and control rats.2) Triglycerides content in hepatocytes was decreased in daunomycin-induced nephrotic rats. But, cholesterol esters content in hepatocytes was higher in daunomycin-induced nephrotic rats than control rats.3) LCAT activity in serum was increased in daunomycin-insuced nephrotic rats.4) Apolipoproteins composition of HDL in daunomycin-induced nephrotic rats showed the increased apoA-Iand the decreased apo E. These results show that the increased cholesterol esters in liver tissue are due to hepatocytes in daunomycin-induced nephorotic rats. The increased HDL cholesterol content may contribute to the increase of LCAT activity in daunomycin-induced nephrotic rats. The increase of LCAT activity in serum results in the increased apo A-I content in daunomycininduced nephrotic rats. No direct evidence about the incorporation of HDL into liver is obtained from the present exp riments and further study will be necessary to clarify this evidence.

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It was previously demonstrated that initial kidney hypertrophy has been seen in diabetic animals and somatostatin infusion suppresses GFR and serum insulin like growth factor (1GF-1) in diabetic patients. I studied the effects of somatostatin analogue (octreotide) on glomerular hypertrophy in diabetic rats. The animals were randomized into six groups: two groups of streptozocin (STZ) induced diabetic, insulin-treated diabetic and non-diabetic rat groups. One of these three groups were treated with two daily subcutaneous injections of octreotide (10μg × 2) for a period of five weeks. In diabetic rats, body weight, blood sugar, glucose excretion, serum insulin, urinary volume, urinary protein, serum creatinine or creatinine clearance did not differ in diabetic rats with vs. without octreotide injection, but kidney weight (2.97 ± 0.12 vs. 3.28 ± 0.08 mg, P < 0.05; mean ± SEM) and estimated glomerular volume (9.13±0.22 vs. 12.77±0.34×105μm3. P<0.001) were all reduced in diabetic rats with octreotide when compared with untreated diabetic rats. In non-diabetic rats, octreotide reduced body weight (340.3±6.5 vs. 367.1±3.8g, P<0.01) and kidney weight (2.29 ± 0.08 vs. 2.51 ± 0.04 g, P < 0.05) when compared with non-diabetic rats without octreotide. Urinary protein excretion (8, 57±1.39 vs. 14.29±1.53 mg/day, P<0. 05), serum 1GF-1 concentration (956.3 ± 180.7 vs. 1546.1 ± 88.1mg/day, P < 0.05) and estimated glomerular volume (7.69±0.16vs.9, 72±0.15×105 μm3, P<0. 001) significantly differed in insulin treated diabetic rats with vs. without octreotide. In conclusion, subcutaneous infusion of octreotide for five weeks prevents renal hypertrophy or glomerular hypertrophy in diabetic rats with and without insulin treatment. The suppressive effects of octreotide on glomerular hypertrophy may be in part due to reduction of 1GF-1.

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We observed that administration of exogenous glycerol reduces β-ATP level and increases glycerophosphate level using magnetic resonance spectroscopy (MRS) of the kidney. A new "glycerol-loading test" for use with MRS in rats was developed. Sprague-Dawley rats were anesthetized and the left kidney was exposed and placed on surface coil. 31P-MRS (109.25MHz) of the kidney was performed using 10μsec, 90' pulse width and 2.308 sec repetition time with an accumulation of 200 times. MRS was performed 24 hours after induction of acute renal failure in each model of acute renal failure. Glycerol-loading test was performed by the intravenous infusion of 10% glycerol through jugular vein over a 60 min period. MRS was recorded every 10 min during glycerol infusion and for 60 min after cessation of infusion. In normal rats, β-ATP level in the kidney was decreased to 52.0% of the pre-loading value at 55 min glycerol infusion and recovered to 66.7% 55 min after glycerol infusion was stopped. In the cisplatinum model, the reduction of β-ATP and the increase of glycerophosphate levels following glycerol-loading was similar to that in normal rats; however, the recovery of β-ATP level after infusion was stopped was weaker. Rats treated with glycerol and HgC1₂ showed rather severe acute renal failure, but the β-ATP level at 55 min glycerol infusion was 87.3% and 92.4%, respectively, showing difference from that in normal rats. No uptake of glycerol was observed 3 hours after 45 min pedicle clamping. These results revealed that even when the MRS pattern in groups of rats is similar before glycerol-loading test, glycerol infusion affects it under some conditions and not under others. Furthermore, the recovery pattern may be affected by some conditions. This glycerol-loading test may therefore be useful in the evaluation of intracellular energy metabolism with renal 31P-MRS.

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Experiments were undertaken to study whether progressive processes of bovine serum albumin (BSA) nephritis in C57BL/B10-BR mice could be prevented by the treatment with methylprednisolone (MPSL), a glucocorticoid. Crescentic glomerulonephritis could be in duced in 22 mice with high 95 per cent reproducibility by preimmunization of 0.2 mg of BSA four times every 2 weeks, follwed by daily intraperitoneal injections of 50 mg/kg of BSA for 4 weeks (group IV, a control). In groups of 8 mice each, intraperitoneal injection of 50 mg/kg of MPSL was initiated 3 days before premmunization (group I), before daily intraperitoneal injection of BSA (group II), and after daily intraperitoneal injection of BSA (group II), and after daily intraperitoneal injection of BSA (group III). In each group, the treatment was continued until the final day of the experiment. In group I, anti-BSA antibody titers, the levels of circulating immune complexes (CIC) and urinary protein were significantly suppressed in comparison with those in group IV. Histologically, diffuse intra-and extra-capillary proliferation observed in group IV was appar ently inhibited. In group II and III, urinary protein and intra-/extracapillary proliferation were significantly diminished compared with those of group IV in spite of minor or no decrease in antibody titers and the CIC levels. These results suggest that MPSL has a suppressive effect on the progressive processes of immune complex mediated glomerulonephritis through both its immunosuppressive and antiinflammatory actions, especially when used in the early stage of immune reaction.

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Fourty-four Japanese patients with IgA nephropathy and their relatives were typed for HLA-A, B, C, DR and DQ antigens and their HLA haplotypes were determined. The frequency of DQ4 increased significantly in the patients as compared with that in 100 healthy control persons (Pc<0.01). DR4 frequency was higher than in the control subjects but revealed no significant difference (p<0.05, Pc>0.05). The incidence of DR4-DQ4 haplotype was increased in the patients (54.5%) and A24Cw-B52DR2DQ1 haplotype which is very common in the Japanese population was decreased as compared with controls of general Japanese population. Thirty-nine cases of 44 (88.6%) had DR4 or DR9 and HLA genotypes of DR4/DR 5, 6, 8 and DR9/DR5, 6, 8 were significantly increased as compared with those in the control subjects (P<0.001). The incidence of DR4 was significantly higher in the patients with macroscopic hematuria as compared with those without (P<0.01). No specific HLA antigens or HLA haplotypes were related to the prognosis of IgA nephropathy. These findings suggested that HLA haplotypes associated with DR4-DQ4, DR4-DQ3 and DR9-DQ3 as well as those associated with DR5, 6, 8 might be involved in susceptibility to IgA nephropathy, while A24Cw-B52DR2DQ1 haplotype migtht be resistant to the disease development.

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The validity of preoperative localizing procedures was studied in 36 patients with primary aldosteronism due to adrenal adenoma, all of whom were confirmed surgically. Adrenalectomy resulted in normalization of blood pressure and serum potassium . Further more, we reviewed the correlation between mass size and some clinical parameters as well as the accuracy of localization pocedures. Adopted localization procedures included imaging techniques such as abdominal ultrasonography, computed tomography (CT), adrenal scintiscan, magnetic resonance imaging (MRI) and adrenal venography, and as a functional diagnostic procedure, adrenal venous sampling. Among imaging procedures, CT was the most effective to detect adrenal mass with as high accuracy as 88%, adrenal venography following with 83%. The correct localization was obtained in 60% by adrenal scintiscan and only 39% by ultrasonography . Although MRI was performed only in 2 cases, the smallest adenoma could be detected only by MRI, suggesting that MRI might be useful to detect microadenoma by increased signal intensity . Although adrenal scintiscan had been considered to be useful because of its functional diagnostic characteristics, the correct localization was as low accurecy as 60%, which was not improved by the administration of dexamethasone. To assess the accuracy of lateralization for adrenal venous sampling, we calculated the ratio of aldosteron concentration in adrenal vein to inferior vena cava. When the ratio was more than 10 or less than 1, the correct localization was made. That is, when the ratio was more than 10, we can predict the mass of the same side, and when the ratio was less than 1, the mass of the opposite side can be predicted, indicating the usefulness of venous sampling even if unilateral sampling was only performed. No correlation was observed between mass size and some clinical parameters such as blood pressure, duration of hypertension, plasma aldosterone concentraion or serum potassium.

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We evaluated the formulas of urine-free prediction of creatinine clearance (CCr) for clinicat use in the patients with chronic glomerulonephritis (CGN). Subjects were 246 patients with CGN diagnosed by renal biopsy with range from normal renal function to end stage renal failure. CCr were measured exactly with urine collections more than 2 times and compared with the values calculated using four urine-free mathematical formulas of Cockc roft et al, Mawer et al, Konishi et al, and Tozune et al. Strong, statistically significant correlations were observed between CCr estimated with each prediction method and measured CCr (r0. 946). However, the latter two formulas tended to overestimate the values. Predicted errors more than 20% of the formula of Cockcroft et al, were the least. And their formula was the easiest for clinical use because of the simplicity for learning by heart. We conclude that these four formulas can be used with reasonable accuracy in the patients with CGN from normal renal function to end stage renal failur, and the formula of Cockroft et al, is the most recommendable for clinical use.

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Pneumatosis cystoides intestinalis (PCI) is a relatively rare, benign condition characterized by multiple subserosal or submucosal gas-filled cysts in the bowel wall . The cause and incidence of PCI are uncertain, but the condition is most commonly diagnosed in patients who have chronic obstructive pulmonary disease, gastrointestinal disease (e . g. Crohn's disease, peptic ulcer disease) or collagen disease (e . g. scleroderma, systemic lupus erythematosus). The report of PCI associated with nephrotic syndrome has not be known as far as we have referred. We first experienced a case of PCI with nephrotic syndrome . The patient was a 28-year-old female who had developed nephrotic syndrome in 1977. Although she had been treated by steroid since the onset of the nephrotic syndrome, she was a frequent relapser. She was hospitalized to our hospital on November 1988, due to fourth relapse of the disease. The increasing dosage of steroid (60mg/day) improved general edema and decreased urinary protein, but abdominal pain and fullness occurred seven weeks after the admission . The abdominal radiographs showed air accumulations in the wall of the intestine (probably right sided colon) and retroperitoneum . That finding was confirmed by Barium enema and abdominal computed tomography. We diagnosed the lesions as PCI from the above findings, and high flow oxygen and hyperbaric oxygen therapy improved the symptom of PCI. The etiology of PCI in this case was thought to be mainly a long term steroid treatment.

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Analysis of the factors influencing the prognosis of acute renal failure was carried out in cases experienced during the past 10 years. The factors presumed directly affecting the renal function (acute insults) and coexistent predisposing factors (risk factors) were analysed. The followings were considered to be acute insults : surgery/trauma/burn, drug intoxication, sepsis, hypotension, dehydration, rhabdomyolysis, hepatorenal syndrome, and hyperca lcemia/hyperuricemia. Suspected risk factors included age, urine volume, underlying disor ders/complications. Risk factors rather than acute insults were related to the outcome of acute renal failure. The mortality rate increased as the associated risk factors increase in number. In non-oliguric cases, maximum serum creatinine level was lower than the anuric cases, however there was no difference in the duration of the impaired renal function between 2 groups. In survival cases, the factors affecting the time for the recovery of renal function were also studied, but no definite factors could be determined.

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