Diuretics have been empirically developed. Inorganic mercury was used as diuretics from 16C. Guy's Hospital Pills (containing the equal part of Hg₂Cl₂, digitalis, and squill) was well known in the 19 C. Discovery of the diuresis of merbaphen has led to develop many organomercurial diuretics and to give suggestion of the drug design of ethacrynic acid. Diuresis in patients given sulfonamide was discovered in 1938. Inhibition of carbonic anhydrase by sulfonamide was related to its diuresis. Drug design aimed to enhance the inhibition of this enzyme has obtained acetazolamide, then chlorothazide. But, the discovery of remarkably enhanced diuretic activity (decreased inhibition on the enzyme) of hydrochlorothazide changed this drug design to rondom chemical modification of thiazide ring. Then, furosemide and other loop diuretics were obtained. The sturcture-activity relationship of thiazides using the electronic state and other physico-chemical indices was studied by us. A large hydrophobic center linked to a positive formal charge was assumed to the receptor of thiazide. Binding of thiazide to erythrocyte which gives mild and long acting diuretic property was found by us. Recently, shut down of the tubuloglomerular feedback by loop diuretics was reported. Loop diuretics are metabolized to loss their activity. Therapeutic drug monitoring is necessary to obtain a desirable diuresis. By wide clinical use of thiazides and loop diuretics, patients with hyponatremia with eu-or hypervolemic increased. I have proposed aquaretics since 1976. In 1992, nonpeptide selective vasopressin V₂ receptor antagonist (OPC-31260) was first synthesized in Japan. This has been found to cause hypotonic diuresis and elevation of serum Na level in men. The combined use of loop diuretics and aquaretics should be considered.

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Measurements of protein-to-creatinine ratios (U^p/Cr) in simple voided urine samples were compared with 24-hour urinary protein excretions in order to guantify proteinuria in inpatients and outpatients. A highly significant linear correlation (r=0 .73), was observed between the two variables. A closer correlation was found in the urine samples obtained from outpatients with non-nephrotic syndrome and normal renal function. Furthermore, in the investigation of urine samples from inpatients, there was a significant correlation between the two variables in urine obtained during the morning, but neither in the early morning nor at night. However, there was no significant correlation between males and females. The results of our study indicate that U^p/Cr in urine samples obtained during the morning provides an accurate quantitative estimate of protein excretion . Furthermore, in clinical practice, this is a suitable method of quantifying proteinuria in patients with renal diseases, particularly, non-nephrotic syndrome and normal renal function.

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Blood pressure (BP), plasma active renin concentration (ARC), plasma renin activity (PRA), aldosterone (Aldo), atrial natriuretic peptide (HANP), plasma sodium (Na), plasma potassium (K), total protein (TP), hematocrit (Ht) and body weight (BW) have been measured in 101 patients, including 9 diabetic patients, undergoing hemodialysis for 5 through 278 months. BP, ARC, PRA and HANP correlated inversely with the duration of dialysis. Among 13 patients undergoing hemodialysis for more than 20 years, only one patient received antihypertensive drugs. This finding suggested that relative low ability of renin secretion and a slightly low concentration of HANP causes low blood pressure in long-term dialysis patients. ARC was significantly correlated with PRA, Aldo, Na, TP-A (TP concentration after hemodialysis), Ht Δ% (difference between before and after hemodialysis) and BWΔ%. These investigations suggest that the removal of large quantities of water and salt in each dialysis session may cause excessive secretion of renin. Though no relation was demonstrated between ARC and blood pressure in 101 patients, ARC was correlated significantly with blood pressure in 37 non-DM patients undergoing hemodialysis for less than 10 years and was inversely correlated in 55 non-DM patients undergoing hemodialysis for more than 10 years. Therefore, further analysis of other factors that maintain blood pressure, especially in long-term dialysis patients is required. Multiple regression analysis showed that major factors regulating the levels of blood pressure were duration of dialysis, HtΔ% and BWΔ%. During dialysis, we observed significant correlation between ARCΔ % and HtΔ %, but we did not find any correlation between the change in blood pressure and ARC. Forthermore, we found that caution should be paid to body water control especially in diabetic patients. because of their remarkable fall of BP during dialysis.

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A24-year-old woman was admitted to our hospital because of macroscopic hematuria with clotting. She had been well until two months before admission, when she experienced fever, arthralgia and lethargy and entered another hospital. Laboratory tests showed macroscopic hema-turia, anemia and mild renal dysfunction. Two weeks prior to admission, she had experienced an episode of macroscopic hematuria with clotting followed by severe anemia requiring blood transfusion. Because of the deterioration of her renal function, she was transferred to our hospital. Exa-minations to determine the source of bleeding from the urinary tract, including a renal arteriogram, were negative. Tests for c-anti-neutrophil cytoplasmic antigen (ANCA) and anti-glomerular basement membrane antibody gave negative results, whereas the test for p-ANCA was positive. Renal biopsy revealed crescentic glomerulonephritis with focal necrosis. Therefore, we diagnosed rapidly progressive glomeru lonephritis (RPGN) due to ANCA-associated renal disease. As a result of methypre-dnisolone pulse treatment followed by oral steroid therapy, macroscopic hematuria disappeared with marked improvement of her renal function. We considered this patient to be a rare case of RPGN with blood loss through glomerular lesions resulting in severe anemia.

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A case of a 73-year-old woman with acute renal failure due to toxic shock syndrome (TSS) is reported. The patient was admitted to our hospital with the complaints of high fever, disturbance of consciousness and shock. Laboratory findings on admission were; CRP 25.11 mg/dl, WBC 35000/ μl, Plt 1.6 × 10 4 / μ1, GOT 155 U/l, GPT 65 U/l, CPK 4202 U/l (CPK-MM 96%), BUN 123 mg/dl and SCr 7.0 mg/dl. Because of anuria, hemodialysis was perfomed. This patient was treated with dopamine, methyl prednisolone (MP), frozen fresh plasma, AT III, antibiotics, and platelet transfusion. The bacterial cultures of blood and cerebrospinal fluid were negative, but MRSA was isolated subsequently from the pharynx and vagina. We investigated the production of toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxins (SE). The isolated MRSA produced TSST-1, SEB and SEC. Accordingly, we made the diagnosis of TSS. After improvement of acute renal failure and the patient's general condition, MRSA persisted and TSST-1 was still found in the patient's blood. Finally we eradicated the MRSA and TSST-1 after administration of ciprofloxacin hydrochloride (CPFX) and Rifampicin (RFP).

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A 49-year-old male was admitted to our hospital because of acute renal failure. He had been treated by a local doctor for rheumatoid arthritis (RA) during the past eight years. We treated him with steroid pulse therapy, because of suspected acute interstitial nephritis. We confirmed this diagnosis by renal biopsy and steroid pulse therapy markedly improved his renal dysfunction. Immunohistochemical studies revealed that interstitial infiltrating leukocytes consisted mainly of polymorphonuclear leukocytes (PMNs), macrophages and B lymphocytes, while T lymphocytes were less predominant. ELAM-1 and GMP-140 were expressed in the peritubular capillaries. These findings suggest that endothelial activation of the peritubular capillaries may cause interstitial infiltration of PMNs and macrophages, resulting in the development of acute interstitial nephritis. Four months later, he developed severe interstitial pneumonitis, and his symptoms were not improved by high-dose steroid pulse and cyclophosphamide pulse treatment. Eight weeks after the second admission, cyclosporin A (Cy A) was started. Three weeks after starting Cy A, he was free from symptoms and his chest radiograph was normalized. Renal function was also improved by Cy A. These observations suggest that endothelial activation by adhesion molecules may play an important role in RA-related autoimmune diseases and that Cy A might be efficacious in such cases.

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We have encountered a 49-year-old female with persistent proteinuria and hematuria. Blood pressure, renal function, physical findings and chest X-p showed no abnormality, but blood tests diclosed mild thrombocytopenia, elevated serum ACE activity, serum lysozyme activity and serum IgA concentration. Abdominal echography and CT revealed multiple nodules in her spleen. In order to make a definite diagnosis and exclude the possibilities of malignant lymphoma or metastatic malignant tumor, splenectomy, and open renal biopsy were performed at the same time. On histological examinations, light microscopic appearance of the spleen was characterized by non-caseating granulomas compatible with sarcoidosis. Renal biopsy specimen showed diffuse proliferative glomerulonephritis with positive staining of IgA predominantly located in the mesangial area, compatible with IgA nephropathy. The present case may provide suggestive evidence for a link between sarcoidosis and IgA nephropathy in the pathogenesis. IgA nephropathy complicated by sarcoidosis is rare, and thus is of particular interest because common immunological abnormalities might be considered in the disease process of both diseases. We feel that despite a low index of suspicion, physicians must be alert to the possibility of IgA nephritis associated with sarcoidosis. The literature is reviewed regarding the relationship between IgA nephropathy and sarcoidosis.

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Steroid-resistant nephrotic syndrome (SRNS) is still difficult to treat in spite of the introduction of various immunosuppressive drugs. In recent years, low-density lipoprotein apheresis (LDL-A) has been used to treat SRNS, mainly on focal glomerular sclerosis (FGS), and some cases have shown amelioration of the nephrotic syndrome. We describe here a case of steroid-resistant minimal-change nephrotic syndrome (MCNS), which was also unresponsive to cyclosporin A (CsA), but attained remission after the additional LDL-A treatment. A 20-year-old man with MCNS was treated with prednisolone at the dose of 40 mg/day for 6 weeks, but his nephrosis continued. The administration of CsA (2.5mg/kg/day) induced remission temporarily for 2 months. However his nephrosis soon recurred, and persisted without improvement in spite of an increase in the CsA dose (4.5mg/kg/day). After 6 LDL-A treatments given concomitantly with the administration of CsA (5mg/kg/day), the urinary protein excretion remarkably reduced, and the patient remained free of the disease. Although the precise mechanism of hyperlipidemia on CsA is still unknown, it can be speculated that the rapid improvement of hyperlipidemia by LDL-A might strengthen the effect of CsA, presumably through the increased cellular uptake of CsA. LDL-A might be useful for ameliorating steroid resistant MCNS, which also is unresponsive to immunosuppressive drugs, such as CsA.

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This report described 45-year-old identical twin sisters with IgA nephropathy. Case 1 presented with microscopic hematuria and proteinuria at the age of 39. Case 2 was found proteinuria at the age of 32. Both the physical examination and laboratory data of these cases were normal. Serum level of IgA was not elevated. The renal biopsy specimen of two cases showed slight mesangial proliferation by light microscopy and mesangial IgA deposition by immunofluorescence microscopy. Their serotype for HLA was found to be HLA-A2, A24, Bw35, Cwl, Cw3, DRw8, DRwl2. Several reports indicated the familial occurrence of patients with IgA nephropathy and a strong association with HLA-Bw35 in those patients. The present cases also suggested that an abnormal immune responselinked HLA system may be involved in the development of IgA nephropathy.

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