Glutathione, a biological reductant, can affect certain aspects of transport function in renal cortical slices. The influence of glutathione on the rate of sodium-dependent phosphate uptake into renal brushborder membrane (BBM) vesicles was examined. Vesicles were obtained from rat renal cortex by the conventional calcium precipitation method. The amounts of GSH and oxi-glutathione were measured by chromatography. The vesicles were incubated for 15 min with glutathione (10 mM) prior to a 1-min influx of phosphate. The incubation with glutathione reduced the phosphate uptake from 1887 ± 217 to 1496 ± 116 pmol/mg (n=5, p<0.05). A kinetic study revealed that the incubation with glutathione resulted in an increase of Km in the sodium-dependent phosphate transporter from 85 ± 7.9 to 159 ± 18 μM (n= 5, p<0.05). Glutathione was catabolized rapidly by the incubation with BBM, and a concomitant production of oxi-glutathione was recognized. Incubation with oxi-glutathione (10 mM) for 15 min, however, did not affect the phosphate uptake. the present results suggest that incubation with reduced-form glutathione decreases the affinity of the sodium-dependent phosphate transport across the renal brush-border membrane, and that catabolism of glutathione may be linked the inhibitory mechanism.

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To investigate the pathogenesis of phenacetin-induced nephropathy, the influence of aspirin and caffeine on phenacetin metabolism was studied. Eight healthy male volunteers participated in the study after giving written consent. They were randomly divided ino 2 groups. Phenacetin was given to one group, and phenacetin, aspirin and caffeine were given to the other group based on a cross-over design. Blood and urine were collected over a period of 24 hours. The urinary excretion and plasma concentrations of unchanged phenacetin, acetaminophen, acetaminophen glucuronide and acetaminophen sulphate were measured by high performance liquid chromatography. The proportions of urinary excretion of these substances were not significantly different in the two groups. The pharmacokinetic parameters of these substances were also fundamentally indentical. It may be concluded that aspirin and caffeine do not alter the phenacetin metabolism. However, other minor metabolites such as p-phenetidine must be closely investigated before we can draw any final conclusions.

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Nineteen pregnancies in 17 women with IgA nephropathy (IgAGN) were studied in terms of the influence of gestation on the natural course of renal function in IgAGN. We performed serial examinations of the serum creatinine (S-Cr) levels before and during pregnancy and after delivery. Group I comprised 11 pregnancies in 10 gravida who revealed proteinuria (1.1±0.7 g/day; mean±SD) and microhematuria before pregnancy. The S-Cr before pregnancy averaged 0.86±0.13 mg/dl. Group II comprised 8 pregnancies in 7 gravida who showed isolated microhematuria. The S-Cr before pregnancy averaged 0.81±0.06 mg/dl. In group I, S-Cr did not decrease during pregnancy and was elevated at delivery and at 1-4 weeks after delivery (1.03±0.29 mg/dl, p<0.05) in comparison with the level before pregnancy. In group II, S-Cr decreased significantly during pregnancy and was not elevated at delivery or after delivery. The above results suggest that gestation had a slight and transient adverse effect on renal function in IgAGN with proteinuria.

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The lactate dehydrongenase (LDH) activity and LDH isozyme ratio in the perfusate were investigated in perfused dog kidneys, preserved from dogs subjected to warm ischemia of varying duration prior to kidney removal. The length of this warm ischemic time exerted a marked effect on the variations in both the LDH activity and isozyme ratio. Moreover, the variations in LDH activity and isozyme ratio during the preservation were found to correlate well. On this basis, the M-component activity of the LDH isozymes and the activity of the LDH₄ and LDH₅ isoenzymes are proposed to represent more sensitive parameters for evaluating the tissue hypoxic damage. Our data were also analyzed retrospectively, in relation to the ability of the perfused kidney to function on autotransplantation. It was found that the amount of LDH₄ and LDH₅ isoenzyme activity was of great value in determining the viability of the kidney. Thus, an analysis of the LDH activity in the wash solution can provide considerable and precise information about the kidney viability as a graft.

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A 48-year-old man was admitted for treatment of Cushing's syndrome due to right adrenal adenoma, associated with chronic renal failure (CRF) with a blood urea nitrogen level of 64.2 and serum creatinine level of 3.9 mg/dl. After removal of the adrenal adenoma, the CRF deteriorated with progressive symptoms of anorexia, vomiting and hypertension, and the patient was placed on hemodialysis. Prior to adrenalectomy, the 17 OHCS and 17 KGS in the urine were not so high. However, the urinary 17 KS was high with an elevated 11-oxy fraction. In comparison with 2 patients suffering from adrenal Cushing's syndrome with normal renal function, there were no large accumulated quantities of glucuronic conjugated and unconjugated metabolites in the plasma of the CRF Cushing's syndrome, with confirmation ascribable to the radioimmunoassayable cross-reactivity of the cortisol antiserum used in the radioimmunoassay kit. In the Cushing's syndrome with CRF, almost all the cortisol, which was hypersecreted from the adenoma, was presumed to be converted to the 11-oxy fraction of 17 KS, possibly by activation of hepatic enzymes.

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The influence of a small amount of 1α (OH)D₃ on patients with chronic renal failure at the predialytic stage (CRFPS patients) receiving CaCO₃ was investigated. 7 patients given CaCO₃ (3 g/day) were administered 1α (OH)D₃ (0.25μg/day) over a period of 12 weeks. 2 patients were eliminated from the study because of obvious deterioration of renal function. The others revealed no significant changes in levels of serum creatinine, adjusted calcium, phosphate, calcium × phosphate product, alkaline phosphatase, C-terminal parathyroid hormone, pH and bicarbonate. Our results indicated that even 0.25 μg/day 1α (OH)D₃ should not be prescribed to CRFPS patients given 3 g/day CaCO₃. We recommend a little sole use of CaCO₃ in CRFPS patients, paying attention to any exacerbation of renal function due to a rise in serum calcium concentration, when therapy for secondary hyperparathyroidism is required.

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To elucidate the pathophysiological role of atrial natriuretic peptide (ANP) in nephrotic syndrome, the plasma level of ANP and renal response to exogenous human α-ANP (α-hANP) were measured in untreated adult patients with idiopathic nephrotic syndrome (NS) and compared with those of normal volunteers (NL). The plasma concentration of immunoreactive ANP (ir-ANP) in NS (112±9.8 pg/ml, n=9, mean±SE) was not significantly different from that in NL (98±8.0 pg/ml, n=13). However, a significant positive correlation was observed between the plasma it-ANP level and blood volume in NS (r=0.714, p<0.05). In an infusion study with synthetic α-hANP (25 to 100 ng/kg/min), the urine flow rate increased from 0.67±0.08 to 7.11±1.08 ml/min in NL (n=5, p<0.01) and from 0.64±0.16 to 2.88±0.70 ml/min in NS (n=9, p<0.05) and the urinary sodium excretion increased from 115±16 to 466±62 μEq/min in NL (p<0.01) and from 51±8 to 207±58 μEq/min in NS (p<0.01). The absolute and percent changes in urine flow rate and the absolute change in sodium excretion were lower in NS (p<0.05) than in NL. The percent change in sodium excretion in NS did not differ from that in NL. In 2 patients with high plasma it-ANP concentrations, however, infusion of ANP induced poor sodium excretion (59 and 95 μEq/min at 100 ng/kg/min ANP infusion, respectively). Hemodynamic and renal parameters such as blood pressure, pulse rate and creatinine clearance were similarly affected in both NL and NS. We also found that the urinary excretion of protein was significantly increased in NS (p<0.05) during infusion of α-hANP. Our data suggest that the plasma level of it-ANP is regulated by blood volume status, and that the renal responsiveness to ANP, at least in part, contributes to water and sodium retention in NS.

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The glomerular filtration rate (GFR), renal plasma flow (RPF) and renal blood flow (RBF) were all markedly decreased in rats given an adenine diet as the period of adenine administration lengthened. Concurrently, the urinary excretions of prostaglandin E₂ (PGE₂) and 6-keto-prostaglandin F_1α (6-keto-PGF_1α) decreased gradually in parallel with the renal function parameters, whereas the urinary excretion of thromboxane B₂ (TXB₂) increased markedly. These findings suggest the involvement of prostaglandin in the renal circulation.

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To clarify the role of prostacyclin (PG) I₂ and thromboxane (TX) A₂ in the regulation of blood pressure from the standpoint of acquired factors and hereditary factors, the following experiments were carried out. [1] A low salt diet (2 g/day) was given for 7 days, followed by a high salt diet (23 g/day) for 7 days to 34 patients with essential hypertension. The percent change in 6-keto-PGF_1α by salt loading was directly proportional to that in mean blood pressure, but there was no significant relationship between the percent change in TXB₂ and that in mean blood pressure. [2] The aorta was removed from 5-week-old and 20- to 25-week-old spontaneously hypertensive rats (SHRs) and age-matched Wistar Kyoto (WKY) rats. Each aorta was incubated in Tris buffer with and without arachidonic acid (AA). there was no significant difference in 6-keto-PGF_1α production between SHRs and WKY rats at the age of 5 weeks, but the aorta obtained from 20- to 25-week-old SHRs synthesized about 1.5 times as much 6-keto-PGF_1α as did that from age-matched WKY rats with and without AA. The aorta from 5-week-old SHRs synthesized more TXB₂ than did that from age-matched WKY rats with and without AA, but there was no significant difference in TXB₂ production between SHRs and WKY rats at the age of 20-25 weeks. These data suggest that the plasma PGI₂ may have increased as a homeostatic reaction to the elevation of blood pressure induced by salt loading. In hereditary hypertensive models, aortic PGI₂ generation could increase secondarily to the elevation of blood pressure, but TXA₂ might be necessary for the development of hypertension.

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The effects of famotidine on renal function were investigated. Eight healthy men (N) and 8 renal patients with varying degrees of renal failure (R.F.) participated in the trial. They were given either famotidine (40 mg) or cimetidine (800 mg) for 7 days. Cimetidine produced a significant decrease in creatinine clearance (from 131.6 ± 12.9 to 107.7 ± 3.4 ml/min (N), and 22.2 ± 3.9 to 18.1 ± 3.5 ml/min (R.F.)), and increase in serum creatinine (from 0.96 ± 0.05 to 1.09 ± 0.04 mg/dl (N), and 3.46 ± 0.62 to 3.86 ± 0.51 mg/dl (R.F.)), and a decrease in creatinine excretion (from 24.0 ± 1.1 to 22.6 ± 0.8 mg/kg/24 hr (N)), respectively, although the reduction in creatinine excretion in the renal failure group was small. On the other hand, the famotidine treatment produced no significant changes in renal function in both subjects (creatinine clearance, 136.5 ± 5.7 to 133.6 ± 6.0 ml/min (N), and 21.9 ± 3.6 to 20.9 ± 4.1 ml/min (R.F.); serum creatinine, 0.98 ± 0.02 to 0.99 ± 0.02 mg/dl (N), and 3.24 ± 0.43 to 3.46 ± 0.55 mg/dl (R.F.); and urinary creatinine, 25.1 ± 1.0 to 25.3 ± 1.0 mg/kg/24 hr (N), and 17.2 ± 1.4 to 16.6 ± 1.5 mg/kg/24 hr (R.F.)). There were no changes in the percent sodium excretion, or the serum and urinary β₂-microglobulin in both groups.

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A 35-year-old woman at 28 weeks' gestation presented with purpura, arthralgia and proteinuria. After a skin biopsy had suggested necrotizing vasculitis, prednisolone was administered. Renal biopsy following delivery disclosed crescents in about 60% of glomeruli. After stopping prednisolone, purpuric lesions and arthralgia reappeared. A second renal biopsy demonstrated cellular crescents in about 80% of glomeruli. The symptoms disappeared on restarting prednisolone. However, the patient progressed to renal failure in 8 months. Histological examinations of the kidney and skin suggested microscopic PN.

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