Creatinine clearaece (Ccr) has been used to evaluate glomerular filtration rate (GFR) in patients with various kinds and grade of renal disease. It is quite useful in terms of simplicity, accuracy and convenience in clinical medicine. However, for the purpose of clinical research, it is not adequate to assess GFR, since a significant quantity of creatinine is secreted in the renal tubule. The secretion rate is rather increased in the endstage chronic renal disease, misleading the true GFR. It also induces an error to calculate the progression rate of a patient with chronic renal failure or to evaluate the effect of the drugs or diet therapy. Therefore, some other indices should be, in future, investigated in order to establish the quantitative evaluation of GFR in patients with chronic renal failure in stead of Ccr or serum creatinine.

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Samples from seventy autopsy cases ranging from 27 to 79 years of age who had shown no evidence of renal or malignant diseases were examined histologically to clarify renal changes with age. We evaluated scores for renal histological change and referred the scores to clinical laboratory data ; blood pressure, complete blood counts (RBC count, hematocrit, hemoglobin), serum chemistry values (creatinine, urea nitrogen, total chol-esterol, total protein, sodium, potassium, chloride) and urinalysis (protein, sediment). We found the score to be related to serum creatinine level, blood urea nitrogen level and the degree of hematuria but not related to the other factors. The progression of arteriosclerosis, tubulo-interstitial change and global sclerosis were found to be severe with ageing. Also renal weight decreased with increasing age. However there were great differences among individuals in the extent of changes. We could not assume histological changes were generally severe in those of more than 55-65 years of age. It was impossible to clarify renal states only with clinical findings. Some kidneys had severe histological changes though less than 2.0 mg/dl of serum creatinine level. It suggests that living relatives and cadavers over 60 years old can be donors for renal transplantation when there are no significant findings of abnormality in preoperative evaluations of their physical state. If insufficient examinations are done, we cannot determine which of them will be good donors. Therefore preoperative biopsy is the best way to evaluate donor suitability. To evaluate only clinical data, it is necessary that serum creatinine level be less than 1.2 mg/dl, blood urea nitrogen level be less than 23 mg/dl and there be no hematuria.

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It has been known that morphological changes are predominant at the site of intercalated cells (IC-cells) of the rat outer medullary collecting duct (OMCD) under K depletion. The changes are characterized by an increase in microplica and the stud of the apical plasma membrane in association with a decrease in the tubulovesicular membrane compartment of the apical region of the cells. It has also been shown that significant K reabsorption and acceleration of H secretion are taking place in these cells of OMCD under the K depletion. In order to clarify whether the changes are directly related to K reabsorption or H secretion, the animal experiment was carried out under any condition. In the control group, G-I, rat was fed with standard diet of normal K content (serum K ; 4.5±0.2 mEq/1), whereas K content was decreased in the K depletion group, G-II, (serum K ; 2.7±0.6 mEq/l). In the acid loaded group, G-III, 4mEq/100g BW of 2N ammonium chloride was given every day (serum K; 4.0±0.2 mEq/l). Animals were sacrificed after 14 days and kidneys were removed for morphological and biochemical examinations. As a result, a significant cell proliferation and interstitial PAS positive granules are observed in K-depleted rats under the light microscopic study. Under the electron microscope, the changes of the intracellular ultrastructure are predominant in the IC-cells of OMCD, such as 'membrane recycling'. On the contrary, no particular changes are seen in acid loaded rats under the light microscope. However, similar ultrastructural changes in IC-cells of OMCD are observed in acid loaded rats as well as in K-depleted rats under the electron microscope. These results suggest that intracellular ultrastructural change in IC-cell of OMCD under K depletion are more likely related to H secretion rather than K reabsorption.

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It was examined whether superoxide dismutase (SOD) had protective effects in puro-mycin aminonucleoside nephrosis (PAN). Nephrotic rats were induced by a single intraperitoneal injection of puromycin aminonucleoside (PA, 60 mg/kg). Subcutaneous administration of SOD (30 mg/kg) was started the day before PA injection and continued every 24 hours. Animals were sacrificed 10 days later to assess the morphologics and glomerular basement membrane anionic charge sites (CSs). GBM CSs were stained in vitro with polyethyleneimine (PEI) and studied by electron microscopic examination. The SOD-injected group had a significant reduction of urinary protein excretion compared to the PA-treated group. Light microscopy revealed that vast majority of glomeruli in PA-treated group had segmental mesangial expansion and epithelial cell adhesions of the glomerular tuft to Bowman's capsule. Contrasted to these changes in the PA group, glomeruli from SOD-treated group showed less severe morphologic changes. On electron microscopy, the PA-treated rats exhibited marked glomerular epithelial loss of foot processes, epithelial attenuation, cytoplasmic vacuolization and protein reabsorption droplets. The SOD-treated animals demonstrated a lesser degree of epithelial loss of foot processes with a few protein reabsorption droplets. There was also a significant decrease in GBM lamina rara externa CSc stained with PEI in PAN compared to the control. The SOD-treated rats had a significant increase in GBM CSs compared to those of the PAN rats. SOD has protective effects in urinary protein excretion, the morphologics and GBM CSc in PAN, which indicate indirect evidence that superoxide and/or its metabolites are responsible for glomerular injury.

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To evaluate the influence of Coxsackie B4 virus (Cox. 134 virus) on the clearing function of the mesangium, colloidal carbon and Cox. B4 virus were intravenously injected into five groups of female Swiss albino mice. Group I received carbon and no Cox. B4 virus; group II, carbon and live Cox. B4 virus; and group III, carbon and inactivated Cox. B4 virus. Group IV and V received live and inactivated Cox. B4 virus, respectively, first, followed by carbon. Semiquantitative analysis of the distribution of carbon particles within glomeruli revealed that in groups II and III disappearance of intracapilary carbon particles was delayed significantly, and that in group II mesangial transport of carbon particles in the direction of the vascular pole of the glomerulus was suppressed. In Groups IV and V, when the interval between carbon and virus injections was shorter than 24 hours, many carbon particles were observed within glomerular capillary lumina compared with Group I. The mechanism of suppressed mesangial uptake of carbon particles may be explained by change of the charge barrier of the glomerular capillary walls and the expansion of the subendothelial space observed after Cox. B4 virus injection. The suppressed mesangial transport of macromolecules appears to be intimately related to be effect of substances produced in viremia and to impairment by viral infection of the function of mononuclear cells infiltrating glomeruli. These results suggest that mesangial uptake and transport of carbon particles are suppressed in transient glomerular changes due to direct injury by the live virus. This means that the biologic property of Cox. B4 virus may be a very important determinant of the clearing function of the mesangium.

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To determine indications for treatment with high-dose intravenous methylprednisolone pulse therapy in lupus nephritis, we retrospectively assessed the response to pulse therapy over oral prednisolone administration in 120 biopsy proven lupus nephritis patients according to WHO morphologic classification. In the pulse group, 1 g of methylprednisolone was administered on three consecutive days and oral steroid therapy (40-30 mg) was started. In many occasions in treating class III and IV-b, repeated pulse therapy was performed. In control oral prednisolone group, middle-dose steroid therapy (50-30 mg) was started. In patients with minor glomerular abnormalities and mesangial lupus nephritis, rapid improvement of serological activities was observed in pulse group assessed by serum complement level, anti-DNA antibodies, and anti-nuclear antibodies. In patients with focal lupus nephritis, rapid rise in serum complement level and fall in proteinuria was observed in the pulse group. In patients with diffuse proliferative lupus nephritis with active necrotizing lesions, faster rise in serum complement level and proteinuria were observed in the pulse group. In patients with membranous lupus nephritis there was no significant difference between two groups. In comparison with the effect of pulse therapy among each morphologic class, the rise of serum complement level was slowest in class IV-b. Both group of IV-b and V manifested nephrotic syndrome and by pulse therapy the decrease in urinary protein was faster and more significant in class IV-b compared with class V. No significant adverse effect of methylprednisolone was observed during about 150 times of pulse therapy. Bacterial, viral infections such as herpes zoster and fungal infections were observed in pulse group as often as control group.

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The effects of a new angiotensin converting enzyme inhibitor, delapril hydrochloride, (delapril) on renal function, and the renin-angiotensin-aldosterone and kallikrein-kinin prostagrandin systems were studied in 10 hypertensive patients. After 4 to 12 months (7.6±0.9 ‹SE›) of treatment with 15-60 mg/day (36±6.8) of delapril (b. i. d.), mean arterial pressure was decreased from 126±3.0 to 110±4.4 mmHg (p<0.01). Although renal blood flow (RBF), assessed by PAH clearance and hematocrit, was increased from 437±51 to 490±49 ml/min (p<0.05) and renal vascular resistance was decreased (p<0.05), glomerular filtration rate, measured by endogenous creatinine clearance, did not change significantly. Thus, filtration fraction was reduced (p<0.01). Plasma renin activity was increased from 1.5±0.3 to 4.4±1.1 ng/ml/hr (p<0.01). Plasma aldosterone concentration tended to decrease (p<0.1), and urinary aldosterone excretion showed on significant change. Although urinary kallikrein and prostagrandin E2 excretions were increased (p<0.05), urinary throm boxane B₂ excretions was reduced (p<0.05). In addition, the changes in RBF were significantly correlated with those in urinary PGE₂ excretion (r=0.63, p<0.05). These results suggest that the antihypertensive effect of delapril is multifactorial and that the improvement of RBF seen during delapril administration in the present study may be partly due to the suppression of the renin-angiotensin-aldosterone system and the activation of kallikrein-kinin-prostagrandin system.

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Effects of metabolic acidosis were compared between bicarbonate dialysis (BCD) and acetate-free biofiltration (AFB). Three stable dialysis patients (1M, 2F, mean age 30 yrs) were selected for the study because their bicarbonate (BC) pre-dialysis plasma concentration were always under 16 mmol/l while they were on 33 mmol/l-BCD thrice weekly for 12 months. They were switched to a 6 months period of AFB. Pre- and post-dialysis BC plasma concentration, other blood chemical parameters and mass removal (total collection of used dialysate) of urea (U), creatinine (Cr), uric acid (UA), and phosphate (P) were measured during the last week of each period, including 3 dialysis sessions. Mean calorie and protein intake were 29.4 KCal/kgod and 1.5 g/Kgad (BCD period) and 38.2 Kcal/Kg·d and 1.5 g/Kg·d (AFB period) respectively. BC plasma concentration (Mean±SE, mmol/l) at the pre and post-dialysis in AFB were significantly higher than those in BCD (16.6±0.7 vs 20.8±0.6; p<0.001, 22.7±0.8 vs 25.8±0.8; P<0.02). Pre-and postdialysis U plasma concentration (Mean±SE, mmol/l) in AFB were significantly lower than those in BCD (34.3±2.51 vs 20.8±0.59, 10.5±1.32 vs 7.5±0.92; P<0.001). Predialysis P plasma concentration (Mean±SE, mmol/l) in AFB was significantly lower than that in BCD (1.85±0.09 vs 1.50±0.15; P<0.01). Cr, UA and P mass removal in BCD and AFB were not significantly different. However U mass removal in AFB was signi-ficantly lower than that in BCD. It is concluded that control of acidosis in dialysis patients resulted in improvement of nitrogen balance due to reduction of the catabolic state, and better control of pho-sphatemia due to concomitant redistribution of P into bone tissue.

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A case of bucillamine-associated membranous nephropathy in a patient with rheumatoid arthritis was reported. A 34 year-old woman was admitted to our hospital because of proteinuria in Rheumatoid arthritis had been diagnosed in and had been treated with bucillamine (disease modifying anti rheumatic drug) and amfenac (nonsteroidal antiinflamatory drug). The renal biopsy specimens showed Stage I membranous nephropathy, on both electron and immunofluorescence microscopy. Proteinuria decreased after the drugs were withdrawn despite continued RA symptoms. These results were consistent with druginduced nephropathy. Since bucillamine has some resemblances in its structure and pharmacologic action to D-penicillamine, which sometimes induces membranous nephropathy, it is thought that the nephropathy in this case was caused by an adverse reaction to bucillamine.

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We studied the effect of high salt intake on blood pressure in two cases with renovascular hypertension. They had hypertension with hyperreninemia and marked difference in plasma renin activity between both renal veins. Blood pressure significantly decreased after single oral administration of captopril. Renal arteriogragm revealed significant stenosis in the main artery to the left (case 1) and right (case 2) kidney. Bood pressure response was evaluated after seven (case 1) and five (case 2) days of low salt and seven days (both cases) of high salt intake. Mean blood pressure in two patients was significantly decreased (case 1; 118±5.5 to 108±6.1 mmHg and case 2 ; 150±3.8 to 138±3.1 mmHg). Plasma renin activity was also decreased (case 1; 6.25 to 0.77 ng/ml/hr and case 2 ; 22, 8 to 6.3 ng/ml/hr). In case 2, blood pressure elevated markedly during low salt intake, compared with blood pressure level during normal salt intake. The results suggest that excessive salt intake in patients with unilateral renovascular hypertension produces blood pressure reduction because of suppression of renin-angiotensin system. We concluded that in patients with unilateral renovascular hypertension dietary sodium depletion may be harmful, whereas salt supplement may have a beneficial effect.

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We report a case of 47-year-old woman with an isolated deficiency of adrenocortico-tropic hormone. She was admitted complaining of fatigue and frequent loss of consciousness. The patient developed severe hyponatremia (100 mEq/1) after five days of the admission. Her plasma renin activity and plasma aldosterone concentration were low though she was dehydrated. After the treatment of dehydration, plasma osmolality was low but high plasma antidiuretic hormone (ADH) level sustained. Both high urinary sodium excretion and low urinary aldosterone excretion still remained after one month of replacement therapy with prednisolone. But, glomerular filtration rate and a response of urinary volume to acute water loading were normalized. These results suggested that severe hyponatremia of the patient was caused by an inappropriate secretion of ADH and suppression of renin-aldosterone system. We consider the suppression of renin-aldosterone system was partially independent of an inappropriate secretion of ADH.

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A case of paroxysmal nocturnal hemoglobinuria (PNH) associated with acute renal failure (ARF) is described. A 57-year-old female, who had been diagnosed as having PNH in 1983 at Kochi Medical School, was admitted to our hospital in April 1989, because of ARF with dark urine after a common cold. Hemodialysis was performed 5 times for ARF, and after almost completely recovering from ARF, she was discharged. The renal biopsy showed the deposition of hemosiderin in the proximal tubular cells. We surveyed fourteen case reports of PNH associated with ARF in Japan including our case. Ten cases developed ARF after infection causing hemolytic attack. Twelve of 14 cases were treated by hemodialysis and 13 cases were reversible. The histopathology of their renal biopsies revealed the deposition of hemosiderin in the proximal tubular cells in six of seven cases and tubular necrosis in three cases. These data showed that hemolytic attack and dehydration related to infection facilitated the induction of ARF.

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We experienced two cases with renal cell carcinoma who showed enlargement of the contralateral adrenal gland. In case 1, the enlarged adrenal gland was a non-functioning adrenal adenoma, and in case 2, it was a metastatic adrenal tumor. Non-functioning adrenal adenomas are benign tumors of the adrenal cortex often found incidentally at autopsy or on computed tomography (CT) studies of the upper abdomen. Adrenal adenomas have been reported to occur in 9.5-14% of patients with renal cell carcinoma, while the incidence being 1.5-8, 7% in the general population. Since metastases of renal cell carcinoma to the adrenal glands are not uncommon, it is important to distinguish between non-functioning adrenal adenomas and metastatic tumors. Therefore, we studied the incidence of adrenal tumors (including metastatic tumors and benign tumors) in patients with renall cell carcinoma who underwent the abdominal CT study in our hospital. From 1982 to 1939, CT had been performed in 67 patients with renal cell carcinoma. Six adrenal masses were identified with CT in these patients. Three out of the 6 patients probably had metastatic tumors and one of the 3 adrenal masses was pathologically diagnosed as metastatic tumor. The other three masses were benign on pathology and only one of them was pathologically diagnosed as non-functioning adrenal adenoma. The incidence of adrenal adenomas on the CT study was lower than that of previous studies based on autopsy. The reasons of this difference in results between their studies and ours are not clear. One of the possible reasons is that microscopical adenomas that can be diagnosed in the autopsy studies may be overlooked in the CT studies since the minimum size of an adrenal mass that can be resolved by the CT is between 5 and 10 mm. The other possibility is that the number of patients of our study may not be enough to estimate the precise incidence of adrenal adenomas. Further studies are needed to clarify the clinical interaction between renal cell carcinoma and adrenal tumors.

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