This review emphasizes our increasing understanding of renal involvements in vasculitic syndromes. Systemic vasculitis of various size vessels (large, medium, and small) can be classified according to the ANCA positivity. Large vessel vasculitides are usually ANCA negative and the occurence of renal vasculitis or glomerulonephritis is rare. Inflammatory aneurysm of abdominal aorta exhibits peculiar renal injury. In this disease, marked fibrosis of periaorta often induces hydronephrosis. On the other hand, ANCA'is positive in most of small vessel vasculitides. C-ANCA is specific for Wegener's granulomatosis and P-ANCA for pauciimmune crescentic glomerulonephritis with or without pulmonary hemorrhage. Pathogenetic role of ANCA in renal involvements in small vessel angitis can be well explained from the standpoint of ANCA-cytokine sequence theory. Another modern topic is lupus vasculopathy. Renal vascular changes in lupus nephritis are various in relation to the presence of anti-DNA antibody, anti-phospholipid antibody, and anti-endothelial cell antibody, or long administration of corticosteroids.

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Membrane attack complex (MAC) inhibitory factor (MACIF) is a 20-kD membrane protein that inhibits MAC formation on homologous cells. Until recently, a functional role of MACIF had been demonstrated in erythrocytes. Therefore, we have focused on the fact that glomerular epithelial cells (GECs) are the primary target of MAC-mediated damage in rat Heymann's nephritis model of human membranous nephropathy. Using immunocytochemistry and western blotting we have shown that MACIF is expressed in cultured human GECs. Phosphatidyl-inositol (PI)-phospholipase C (PLC) reduced MACIF expression in these cells, suggesting that MACIF is a PI-linked membrane protein in GECs. In addition, we elucidated that MACIF protects GECs against complement-mediated lysis. These findings suggest that MACIF expressed on GECs plays an important role in the protection of GECs against complement mediated-cellular damage in vivo.

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The role of cell-mediated immunity in glomerular injury has been extensively studied, but the precise mechanism remains obscure. This study was undertaken to determine whether the homologous glomerular basement membrane (GBM) combined heterogeneous anti-GBM antibody would induce cell-mediated immunity . Wistar-Kyoto rats were divided into three groups; group I rats were immunized with homologous GBM antigen that was derived from Masugi nephritis and emulsified in complete Freund's adjuvant (CFA); group II rats were immunized with homologous GBM antigen that was derived from normal rats and emulsified in CFA; group Ill rats were immunized with CFA only . Group I rats demonstrated proteinuria on days 7 and 10 after immunization. Histologically, mesangial cell proliferation and cell infiltration were observed in the glomeruli . No changes in tubulointerstitial tissue. CD4-positive cells, CD8-positive cells and macrophages were found in the glomeruli, and mononucleor cells were found in the glomerular capillary lumen . Group II and Group IQ rats demonstrated no proteinuria and no histological changes. These findings indicated that the altered GBM obtained antigenicity and induced cell-mediated immunity in the glomeruli .

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The involvement of adhesion molecules in the accumulation of inflammatory cells in the glomeruli and subsequent glomerular injury was examined in accelerated-type anti-GBM nephritis in rats. This animal model is known to be manifested by progressive and irrevers-ible glomerular damage with rapid influx of monocytes/macrophages into the glomeruli. Up-regulated expression of intercellular adhesion molecule-1 (ICAM-1) was observed exclusively in the glomerular endothelial cells in this model. Therefore we examined the effect of ICAM-1 and lymphocyte function-associated antigen -1 (LFA-1) in the pathogenesis of this nephritis. Four groups of rats with accelerated-type anti-GBM nephritis were in-vestigated. The first group was the control group injected with normal mouse IgG 2mg/Kg. The second group was administered mouse anti-rat ICAM-1 monoclonal antibody (1A-29) 2 mg/Kg. The third group was administered mouse anti-rat LFA-1$ monoclonal antibody (WT-3) 2mg/Kg. The fourth group received both 1A-29 lmg and WT-3 1mg/Kg. Proteinuria and the influx of monocytes/macrophage in this model were decreased after the administra-tion of 1A-29 or WT-3. Simultaneous administration of both antibodies showed intense suppression of the proteinuria and marked reduction of the infiltrating cells. These results suggested that the ICAM-1/LFA-1 pathway is critically involved in the pathogenesis of accelerated-type anti-GBM nephritis in rats.

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We studied cytotoxicity in vitro through reduced glutathione (GSH) metabolism by cisplatin (CDDP) and adriamycin (ADM) in rat kidneys. Renal cortical slices of Fischer 344 rats were incubated with Krebs-Ringer buffer containing CDDP (0-5mM) or ADM (0-0.5 mM). GSH and glutathione reductase (GSSG reductase) in these renal cortical slices were determined. Cell viability was assessed by lactate dehydrogenase (LDH) leakage. The following results were obtained. l) Intracellular GSH in renal cortex was decreased by CDDP doseand time-dependently. 2) The activity of GSSG reductase was suppressed by CDDP, but not by ADM. 3) LDH leakage increased significantly with CDDP and ADM respectively. 4) The incubation of renal cortical slices with GSH exogenously protected the increase of LDH leakage induced by CDDP or ADM. 5) The coincubation of renal cortical slices with CDDP and ADM did not increase LDH leakage compared with single administration of ADM. 6) LDH leakage in incubation with ADM after incubation with CDDP increased remarkably. The viability of renal cortical slices was more damaged by ADM under the condition of depleted GSH by CDDP. Therefore, it seemed that the order of administration was very important in combination chemotherapy.

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Cyclosporine A (CYA) a new immunosuppresive drug, has greatly improved the out-come of solid graft transplantation. The nephrotoxicity of CYA, however, is a serious problem, and constitutes the major obstacle limiting the use of CYA as an immunosuppresive agent for renal transplantation. On the other hand, the newly described atrial natriuretic peptide (ANP) hormonal system in both humans and animals appears to play an important role in sodium and water excretion. The present study examined the nephrotoxicity of CYA and the effect of recombinant-ANP (r-ANP) on the damaged kidneys in three groups. Group 1 consisted of rats with 45 minutes warm ischemic left kidney and right nephrectomy [WI rats]; Group 2 consisted of WI rats with oral administration of CYA (100mg/kg/day) for 2 weeks [WI+CYA rats]; Group 3 consisted of WI+CYA rats with intraperitoneal administra-tion of r-ANP (long/kg/day) for 2 weeks. Group 2 had lower glomerular filtration rates (GFR) and renal plasma flow (RPF) than Group 1, but Group 3 had significantly higher GFR and RPF than Group 2. Additionally, in order to demonstrate the change in renal viability among the three groups, the adenosine triphosphoric acid level (ATP) and adenylate energy charge ratio (EC) of renal parenchymal tissue were measured by high performance liquid chromatography (HPLC). Group 2 had lower ATP and EC than Group 1, and Group 3 had higher ATP and EC than Group 2. The results of this study suggest that r-ANP is efficacious on rat kidney damage induced by CYA and WIT.

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This study was designed to evaluate renal functional reserve (RFR)in obstructive nephropathy using amino acid loading and the effect of angiotensin converting enzyme (ACE) inhibitor on RFR. We divided 24 rabbits into 4 groups, consisting of a control, 6-hours-bilateral ureteral obstruction (BUO), 24-hour BUO and 24 hour BUO pretreated with ACE inhibitor. Following the ligation of the bilateral ureters at the vesicoureteral junction, a unilateral ureter was released after a 6-hour or 24 hour duration in the obstructive groups. We measured RFR and renal vascular resistance after releasing a unilateral ureter in BUO. The baseline GFR values in the 6-hour and 24 hour BUO groups were significantly lower than that in the control. RFR were 0.34+0.04 ml/min/kg (control), 0.10+0.03 (6-hour BUO), 0.01+0.03 (24 hour BUO) and 0.10+0.01 (ACE inhibitor), respectively. RFR in the 6 -hour BUO group was well preserved compared with that in the 24-hour BUO group. Pretreatment with ACE inhibitor in the 24 hour BUO group enhanced RFR to the extent of 6 -hour BUO. Our results demonstrated that angiotensin II plays an important role in decre-ased GFR with obstructive nephropathy. Moreover, the present data suggested that evalua-tion of RFR might play a key role in the recovery of the post-obstructive renal function.

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Urinary levels of glycosaminoglycans (U-GAG) were measured in 72 patients with non-insulin-dependent diabetes mellitus, 12 patients with collagen diseases, 14 patients with IgA nephropathy and 35 healthy subjects as controls to investigate the clinical significance of urinary GAG. The mean urinary GAG levels in diabetics and patients with collagen diseases were 72.4±36.2 and 147. 8± 59. 2mg/g ⋅cr, respectively. These were significantly higher than the level in healthy subjects (46. 7± 11. 3mg/g ⋅cr, p<0. 01). The mean urinary GAG level in patients with IgA nephropathy was 56. 4±21. 0mg/g ⋅cr and did not differ from that in healthy subjects. The mean urinary GAG level in 35 normoalbuminuric diabetic patients (U-Alb < 30mg/g ⋅cr) was 64. 4+25. 6mg/g ⋅cr and was significantly higher than that in healthy subjects (p< 0.01). The mean urinary GAG levels in 24 microalbuminuric patients (30 < U-Albs 300mg/g ⋅cr) and 13 patients with overt albuminuria (U-Alb Z 300mg/g ⋅cr) were 71.4±30.1 and 95.8±58. 4mg/g ⋅cr, respectively and were also higher than the level in healthy subjects (both p<0.01). Urinary GAG levels correlated positively with urinary albumin levels (r=0.251, p<0.05) and urinary N-acetyl-β-D-glucosaminidase activities in diabetics (r=0.491, p<0.01). The prevalence of diabetic macroangiopathies in diabetic patients with elevated levels of urinary GAG was siginificantly higher than that in those with normal levels of urinary GAG (p<0.05). These resuls indicate that urinary GAG levels may reflect minor changes in the renal glomerular basement membrane and tubulointerstitial region, and the severity of atherosclerotic changes in diabetics, and also reflect the seventies of angiopathies in patients with collagen diseases.

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Fibrin/Fibrinogen degradation products (FDP) and cross-linked FDP (XLFDP) have been found in the urine of many patients with renal disease. FDP result from fibrinogenolysis and fibrinolysis. It is useful to detect the urinary XLFDP which results from fibrinolysis in order to diagnose intraglomerular coagulation. I investigated urinary FDP and XLFDP in patients with various renal diseases. Urinary FDP and XLFDP were detected by latex aggregation test in the urine of 96 patients. Urinary XLFDP was measured by enzyme-linked immunosorbent assay (ELISA) using monoclonal antibody in the urine of 140 patients. The positive rates of urinary XLFDP were higher in chronic renal failure, membranous nephropathy and membranous-proliferative gromerulonephritis than in other renal diseases. High levels of urinary XLFDP were found in membranous nephropathy, membranous proliferative gromerulonephritis and non-IgA nephropathy. There was an obrious relationship between urinary XLFDP and the degree of proteinuria, hematuria, serum creatinine and intraglomerular fibrin deposits. The high levels of urinary XLFDP were detected in the case of severe proteinuria, normal and mild hematuria, normal and slightly increased serum creatinine and mild intraglomerular fibrin deposits.

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Primary antiphospholipid antibody syndrome (APS) is characterized by abortion, thrombosis, thrombocytopenia and/or valvular disease and it is liable to complicate systemic lupus erythematosus (SLE). We carried out a study to investigate the clinical and renal pathological findings in five patients with APS, but not SLE. In the clinical findings, the patients had negative tests for proteinuria and hematuria, and their renal function and tubular function were within normal limits. In the light microscopic findings, three patients exhibited mild mesangial hypercellularity, and two had minor glomerular abnormalities. In immunofluorescent study, there were Ig M and/or C3 depositions in the mesangial area in some cases, and in electron microscopic study, there were no special findings other than mesangial hypercellularity. In conclusion, nephropathy is a rare complication in patients with APS, unlike systemic lupus erythematosus.

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We analyzed the total number of 42 events of acute exacerbation of chronic renal failure (CRF) in 35 patients who were admitted to the Matsuyama Red Cross Hospital Kidney Center between 1985 and 1990. These patients consisted of 16 males and 19 females with a mean age of 59.8±12.7 years. The most frequent original renal diseases were diabetic nephropathy (DM) and arteriolosclerotic nephrosclerosis (NS). The most frequent acute exacerbation factors were dehydration and infection. Four cases died and one case transferred to chronic hemodialysis, but the other 37 events (88%) in 31 cases recovered to normal renal functioning. Tentative dialysis therapy was performed for 12 events, in which the cases with DM as the original disease and infection as the exacerbation factor were responsive to this therapy. In the analysis of long-term prognosis, 7 out of 26 cases died of non-renal diseases, 15 transferred to chronic dialysis therapy and only 4 remained in a CRF state. The intervals between the date of discharge and that of the start of dialysis therapy was shorter in the cases with DM (mean of 5 months) or chronic glomerulonephritis (mean of 7.6 months) than in cases with chronic interstitial nephritis, polycystic kidney disease and NS (mean of 17.7 months). We concluded that even though many of the cases eventually transferred to chronic dialysis therapy, appropriate therapy during the acute exacerbation period could allow recovery to a natural progressive or nonprogressive course in each case.

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It is known that the earlier the graft begins functioning after cadaver kidney transplanta-tion, the better the graft survival rate and function will be. In order to examine the possibility of shortening the period of acute tubular necrosis (AIN), we retrospectively studied the effect of several factors on the duration of postoperative hemodialysis. The subjects were 27 patients on whom a cadaver kidney transplantation was performed during a 6-year period from July 1, 1986. The mean duration of postoperative hemodialysis was 14.0 days in 26 out of the 27 patients. The remaining patient showed a primary non-functioning kidney. A significant correlation was observed between the anastomosis time and the duration of postoperative hemodialysis. No significant correlations were noted between the duration of postoperative hemodialysis and the age of the donor, renal function during the 24 hours preceding nephrectomy, or cold ischemic time. Moreover, no significant difference was observed in the duration of postoperative hemodialysis between patients using a roller pump for perfusion and patients who did not. The duration of postoperative hemodialysis was significantly shorter in patients using UW solution than in patients using Euro-Collins solution. Graft survival rate 6 months and one year after transplantation was 88.9% and 83.3%, respectively in the EC group, and 100% and 100%, respectively, in the UW group. It was concluded from these results that a short anastomosis time is essential in order to shorten the period of ATN after cadaver kidney transplantation, and that UW solution is effective in shortening the duration of postoperative hemodialysis and improving the graft survival rate thereafter.

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A 52-year-old man was admitted to our hospital because of oliguric renal failure. The patient was well until four weeks earlier, when he developed nausea and anorexia. The urea nitrogen was 179 mg/dl, creatinine 29.2 mg/dl, uric acid 19.0 mg/dl and potassium 8.6 mEq/ 1. Hemodialysis was started immediately after admission. Bone marrow aspiration showed atypical plasma cell infiltration consistent with multiple myeloma. The im-munoelectrophoresis revealed urinary t -type Bence Jones protein and serum IgD-λ -type M protein. The findings of renal biopsy study were consistent with myeloma kidney. On the fourth hospital day, administration of prednisolone 40 mg and melphalan 2 mg was started. The patient also underwent double filtration plasma-pheresis (DFPP). Serum IgD level was decreased from 950 to 113 mg/dl. After a course of chemotherapy, however, he developed severe leukopenia and was complicated with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. This complication was successfully treated with imipenem/cilastation and vancomycin combined with granulocyte colony stimulating factor (G-CSF). The patient was discharged and returned to work on maintenance hemodialysis. Fifteen months after the presentation, he manifested progressive peripheral nerve disturbances. Three months later, the patient died - not from renal failure, but from ventricular arrhythmia. The application of maintenance dialysis therapy to myelomatosis has until now been questioned. The present case, however, suggests that aggressive treatment consisting of chronic dialysis therapy as well as chemotherapy and plasma exchange should be administered even in patients with established renal failure. Maintenance hemodialysis in IgD-λ-type multiple myeloma associated with severe renal failure.

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