Stable isotope ¹⁵N-compound, ¹⁵N-urea, is useful marker to investigate nitrogen metabolism in clinical nephrology, particularly in chronic renal failure or dialysis. ¹⁵N-urea incorporation into plasma albumin in addition to plasma ¹⁵N disappearance was studied in 6 patients with endstage chronic renal failure. As a result, only minor fraction of administered ¹⁵N-urea was incorporated into albumin in this study. In addition, it was also confirmed that high energy diet may promote protein synthesis through ¹⁵N incorporation to plasma amino acids, such as alanine, in these patients with low protein meal.

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Using the PHA method, streptococcal type-specific antibody was studied in sera from 230 patients with various types of nephritis diagnosed by renal biopsy in order to clarify the relationship between streptococcal infection and the histological types of glomerulonephritis. Two or more serologic types of streptococcal type-specific antibodies with high titers (1:384 or more) were significantly increased in patients with MGA, FGS, PGN, endocapillary proliferative GN, MPGN and IgA GN as compared with those in healthy subjects. Two or more serologic types having high titers (1:384 or more) were significantly increased in MGA, PGN, MPGN and IgA GN as compared with MN. The highest titers (1:768 or more) of streptococcal type-specific antibodies were significantly more frequent in endocapillary proliferative GN as compared with healthy subjects, and such titers were significantly increased in endocapillary proliferative GN and MPGN as compared with MN. The frequency of detection of streptococcal serologic types having high titers (1:384 or more) as found in patients with various nephritis, was in the order of Types 18, 3, 30, 6 and 37, and more than half of the nephritogenic types were included in these serologic types. The above data, which suggest a higher probability of contact with nephritogenic strains during alternative establishment of streptococci by different serologic types, may indicate a close relationship of streptococcal infections with MGA, PGN, MPGN, IgA GN, FGS and endocapillary proliferative GN.

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We examined whether daunomycin rats could be used as an experimental model of human chronic renal failure in terms of their osseous changes and mineral metabolism. The daunomycin rats revealed hyperphosphatemia and osteodystrophic bone changes. In this respect, they were similar to human chronic renal failure. A high calcium level was found in the daunomycin rats at first due to the effect of the daunomycin injection, but later there was a lower calcium level than in the control rats due to chronic renal failure. We conclude that daunomycin rats can be successfully used as an experimental model of chronic renal failure from the standpoint of their osseous changes and mineral metabolism.

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Wistar rats were injected with puromycin aminonucleoside (PAN) to induce massive proteinuria and were raised on a low protein diet to determine whether the urinary protein excretion might be reduced. Although PAN nephrotic rats fed with a normal protein diet containing 20% protein (group A) did not show any reduction of their urinary protein excretion, PAN rats fed with a low protein diet containing 6% protein (group B) revealed a marked reduction at day 9 of the present study in comparison with group A. The total serum protein levels were low in groups A and B as compared to group C, the non-treated control. However, group A recovered to normal levels at day 13. In terms of the absolute amount of oral protein intake, marked differences were observed between groups B and C, but little difference was observed between groups A and C. The body weight in all three groups was decreased at 8 days after the start of this study. The serum levels of creatinine were elevated to 1.1±0.3 mg/dl and 1.0±0.2 mg/dl in groups A and B, respectively, on day 7, but abruptly recovered to normal levels by day 12. These data indicate that the decreased urinary protein excretion in group B might be dependent on the total protein volume intake, and not on the renal function nor serum levels of total protein.

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We report a case showing typical diabetic nodular glomerulosclerosis without retinopathy or other apparent clinical findings of DM except for impaired glucose tolerance. The 57-year-old man had a family history but no personal history of DM. In an extensive examination for DM, the results of funduscopy, daily profile of serum glucose and hemoglobin Alc were entirely within normal limits. However, the oral glucose tolerance test was abnormal. A renal biopsy showed typical nodular lesions (Kimmelstiel-Wilson's lesions). Previously, the interesting feature of transient proteinuria had been recognized. Although hypocellular nodular lesions by light microscopy are characteristic of diabetic nephropathy, renal amyloidosis, carbon disulfide intoxication, multiple myeloma and light chain disease, we concluded that the present lesions had resulted from diabetic nephropathy based on the family history, patient history, impaired glucose tolerance, immunofluorescent findings and electron microscopic observations.

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We investigated the mechanism of uremic neuropathy using experimental acute and chronic renal failure models in rats. After induction of renal failure, the motor nerve conduction velocity, axoplasmic electrolyte content, and cross-sectional area of myelinated fibers in the sciatic nerve were determined. The axoplasmic Na, K, Cl, and Ca contents were measured by electron probe X-ray microanalysis employing thin sections from freshly freeze-dried sciatic nerves. The results obtained for both the acute and chronic renal failure models were similar. The sciatic motor nerve conduction velocity was significantly decreased in both cases as compared to that in the controls. The sciatic nerve axoplasmic Na content was significantly lower than that of the controls in both acute and chronic renal failure, and a significant reduction in the cross-sectional area of the myelinated fibers was observed in both renal failure models. These results suggest that impairment of the axonal membrane Na permeability and shrinkage of the myelinated fibers may play an important role in the decrease of motor nerve conduction velocity in uremic neuropathy.

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The effect of magnesium lithospermate B on the renal responses of rats with renal failure was investigated in the presence and absence of pretreatment with the kallikrein inhibitor, aprotinin. Magnesium lithospermate B caused a marked increase in the levels of the renal functional parameters (glomerular filtration rate, renal plasma flow and renal blood flow), accompanied by significant increases in urinary prostaglandin excretion (increases of prostaglandin E₂ and 6-keto-prostaglandin F_1α excretion by 8210 and 3610, respectively). The urinary excretion of kallikrein was also increased following magnesium litho-spermate B administration. However, pretreatment with aprotinin abolished the renal function-facilitating action of magnesium lithospermate B concomitantly with a markedly increased urinary excretion of prostaglandin E₂, 6-keto-prostaglandin F_1α and kallikrein. These results suggest that the kallikrein-kinin-prostaglandin system is involved in the renal responses elicited by magnesium lithospermate B.

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The effects of CaCO₃ with vitamin D metabolite and without vitamin D metabolite on secondary hyperparathyroidism were investigated in 18 patients undergoing maintenance hemodialysis. 9 patients (Group 1) were treated with 1μg/day 1a (OH)D₃ and 2 g/day Al(OH)₃, and the other 9 patients (Group 2) received 2 g/day Al(OH)₃ without vitamin D metabolite. CaCO₃ at amounts of 3 g/day was subsequently administered to all patients instead of Al(OH)₃. The levels of mid portion-parathyroid hormone (M-PTH) in Group 2 and of 1, 25-dihydroxyvitamin D3 in Group 1 during the baseline period were significantly increased as compared to those in the other group, respectively. In Group 1 only, the level of serum ionized calcium was appreciably elevated at the 4th and 12th weeks as compared to the baseline value, and the level of M-PTH was significantly decreased at the 4th and 12th weeks as compared to the baseline value. The levels of serum phosphate, calcitonin, magnesium and bicarbonate in both groups at the 4th and 12th weeks were not appreciably different from the baseline values. The levels of serum aluminum in all patients of both groups were reduced at the 12th week as compared to the baseline values. A close correlation was recognized between M-PTH and the level of intact parathyroid hormone. It is concluded that prescription of 3g/day CaCO₃, together with adequate doses of vitamin D metabolite, can ameliorate mild secondary hyperparathyroidism.

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The effects of two different H2-receptor antagonists, cimetidine and famotidine, on the acute renal failure induced by 20 min of renal artery occlusion and gentamicin (240mg/kg BW, s. c., for 3 days) were investigated in Sprague-Dawley rats. The animals were treated with either cimetidine (80 or 160 mg/kg BW) or famotidine (4 or 8 mg/kg BW) mixed in the drinking water for 7 days. The low dose of cimetidine and famotidine did not alter the renal function in the absence of renal trauma. However, the high dose of cimetidine or famotidine decreased the GFR by 32% and 22%, whereas RPFR increased by 46% and 6210, and %FENa by 92% and 558%, respectively. The data for the renal function obtained 24 hrs after 20 min of renal ischemia demonstrated a decrease of 54% in GFR, a decrease of 47% in RPFR and an increase of 370% in %FENa over the non-ischemic control values (p <0.05). Cmmetidine (80 mg/kg BW) or famotidine (4 mg/kg BW) did not modify the recovery of renal function following the ischemic insult, showing 55% and 539% decreases in GFR, 74% and 101% increases in RPFR, and 393% and 461% increases in %FENa over the non-ischemic control rats, respectively. Famotidine reduced the decrease in RPFR significantly during the recovery period following ischemia. In the gentamicin study, gentamicin treatment was found to lower the renal function significantly. The GFR was decreased by 45% and the RPFR by 66% of the control values (p <0.05). %FENa and UV were increased 6 fold and 2 fold, respectively. When gentamicin nephrotoxicity was induced in cimetidine (80mg/kg BW) or famotidine (4 mg/kg BW) treated rats, again, no further decrease of the renal functions was observed compared to rats treated with gentamicin alone. There were no significant differences in renal histology between the untreated and H₂-receptor antagonist treated rats in both the renal ischemia and gentamicin studies. In conclusion, the present results demonstrate that despite a dose greater than or equivalent to clinical for the H₂-receptor antagonists being tested, neither cimetidine nor famotidine altered the degrees of renal impairment induced by renal ischemia or gentamicin poisoning.

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Bovine reno-ferredoxin was purified from kidney mitochondria by an improved method that included hydrophobic and ion-exchange chromatography on Toyopearl gels. The optical absorption spectrum of the oxidized reno-ferredoxin revealed two peaks, at 414 and 455 nm in the visible region. The minimum molecular weight of the ferredoxin was 12, 900 Da by SDS-polyacrylamide gel electrophoresis. The amino acid residues of the NH₂-terminal sequence of the ferredoxin were investigated using by a gas-phase sequencer. Bovine reno-ferredoxin and adreno-ferredoxin showed almost identical NH₂-terminal amino acid sequences. Reconstitution of the 25-hydroxyvitamin D₃-1α-hydroxylase system was performed with the following three components: NADPH-ferredoxin reductase from bovine kidney mitochondria, renoferredoxin, and cytochrome P-450(D1α) from bovine kidney mitochondria. The results demonstrated that the reno-ferredoxin was essential for the 1α-hydroxylase activity of 25-hydroxyvitamin D₃.

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A total of 30 patients with urolithiasis underwent 35 sessions of fiberoptic transurethral lithotripsy (f-TUL) involving electrohydraulic lithotripsy. There were 11 patients with nephrolithiasis including 4 with staghorn calculi and 19 patients with ureterolithiasis which were all located above the pelvic brim. A fiberoptic nephroureteroscope (URF-P) was successfully introduced up to the stone in all but 2 cases (93.3%). Of the 28 patients with successful introduction, 21 received a single session of f-TUL for complete fragmentation of their stones, which measured less than 16 × 9 mm by radiography. Three patients with larger renal stones (≥17 × 9 mm) underwent 2 sessions of f-TUL for complete fragmentation. The remaining 4 patients who had staghorn calculi (≥38 × 33 mm) received 1 session of f-TUL with partial fragmentation; then 3 were sent to an ESWL clinic with good results, while the other patient received 2 more sessions of f-TUL and formed a stone street. Attempts were subsequently made to destroy the latter by ESWL but were unsuccessful. In conclusion, f-TUL appears to be most suitable for smaller impacted ureteral calculi above the pelvic brim.

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Three cases of exercise-induced non-oliguric acute renal failure in patients with renal hypouricemia, an isolated defect of the renal urate transport system, are described. During acute renal failure, the serum uric acid levels were 5.6, 2.7 and 5.8 mg/dl, respectively, and were within normal limits. The values representing the fractional excretion of uric acid (FE_UA) were 28.7, 60.0 and 12.7%, with accompanying serum creatinine levels of 8.1, 3.9 and 3.3 mg/dl, respectively. After recovery, the serum uric acid fell to 0.6, 0.7 and 1.0 mg/dl and the FE_UA increased to 79.3, 52.8 and 43.2%, respectively. Two of the patients examined exhibited decreased reabsorption of filtered urate. These 3 examples of renal hypouricemia represented 23% of 13 cases of mild exercise-induced acute renal failure encountered within our experience.

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The kidney volume after transplantation was compared in two groups, one treated by conventional immunosuppression and the other receiving small amounts of ciclosporin (CsA) together with azathioprine and steroid (the so-called triple therapy). Fourteen pairs of donors and recipients were investigated in each group. The kidney volume was measured, using computed tomography (CT scan), before and after transplantation in the donors and after transplantation in the recipients during the allograft rejection-free period. The graft volume at 2-3 months after transplantation was smaller (215.9±30.9 ml, mean±SD) in patients who received small amounts of ciclosporin A (CsA) together with azathioprine and steroid than that (270.9±75.0 ml) in those treated by conventional immunosuppression. The remaining kidney in the donor after transplantation underwent a similar increase in volume in the conventional and triple therapy groups. It is suggested that even a small amount of CsA can significantly limit the compensatory renal growth.

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A 26-year-old male with nephrotic syndrome (NS) due to α-mercaptopropionyl glycine (MPG) is described. In he was diagnosed as having familial cystinuria after receiving urolithiasis treatment since Massive proteinuria and slight pedal edema were noted. Nephrotic syndrome was suggested and renal biopsy was performed. The renal pathological finding demonstrated membranous glomerulonephritis (MN) at stage I. This case was defined as NS clinically associated with MPG, and glucocorticoid intake was initiated. The response to the glucocorticoids was fairly good with no clinical problems after discontinuation of MPG, and the cystinuria was maintained with alkaline medication. The patient's parents and younger brother were suggested and confirmed to have cystinuria based on urinary aminogram analysis, but displayed no symptoms. We present a rare case of NS due to MPG therapy in a patient with familial cystinuria. However, the mechanism of onset remains unclear.

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