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Key words: ascites; Crow-Fukase syndrome; immunoadsorption plasmapheresis; interleukin-6 [ABSTRACT FROM PUBLISHER]

Bcl-2 may account in part for the maintenance of hypercellularity in human glomerular diseases through preventing cell death and by counteracting bax which may be expressed to regulate excessive proliferation. This process is associated with the effect of PDGF B-chain expression. Bax expression may be important in the cell loss leading to glomerulosclerosis and TGF-β1 participates in this process by increasing bax expression. Thus, the balance of bcl-2/bax expression may be critical in the course of human glomerular diseases. [ABSTRACT FROM PUBLISHER]

Presents an abstract of a study that examined the effect of the enzyme inhibitor simvastatin on glomerular pathology in a rat mesangial proliferative glomerulonephritis (GN).

Suppression of the renin-angiotensin system is known to slow progression of chronic kidney disease (CKD). However, few trials have been performed with Japanese patients. This study investigated whether the angiotensin receptor blocker (ARB) valsartan would delay the progression of kidney disease more effectively than conventional treatment in Japanese hypertensive patients with advanced, predialysis CKD. In a multicenter, randomized, open-label trial, 303 patients with hypertension and CKD with serum creatinine levels 2.0 mg dl(-1) were assigned to receive either conventional therapy plus valsartan (valsartan add-on group) or conventional therapy without ARB (control group). The primary outcome was a change in serum creatinine levels. Changes in urinary protein levels and time to onset of renal events were analyzed as secondary end points. There were no between-group differences in blood pressure during the study. Changes in serum creatinine and urinary protein levels did not differ between the groups. However, the rate of renal events, including doubling of serum creatinine levels or end-stage renal disease, was significantly lower in the valsartan add-on group than in the control group. The addition of valsartan decreased the risk by 42.6% after adjustment for baseline variables. The addition of valsartan to conventional therapy significantly slowed the rate of renal function decline and delayed the need for renal replacement therapy in Japanese hypertensive patients with advanced CKD.

Background: The factors that predict baseline peritoneal permeability remain largely unknown. We noticed that patients that adhered to a strict low protein diet (LPD) during the predialysis period seldom showed high peritoneal permeability on the peritoneal equilibration test (PET) at the introduction of peritoneal dialysis (PD). Therefore, we investigated whether a strict LPD during the predialysis period affects peritoneal permeability., Method: We retrospectively analyzed 37 patients that started PD in a single Japanese center. Patients were divided into group A and group B by the median amount of daily protein intake (PI) during the predialysis period using urine collected over 24 hours., Results: There were no differences between groups A and B in age, gender, proportion of diabetic nephropathy, blood pressure, body mass index, or body surface area. There were also no differences between the groups in laboratory findings, including hematocrit, serum albumin, and serum creatinine. The PETs showed a significantly lower dialysate-to-plasma ratio of creatinine at 4 hours (Cr D/P) for group A than for group B (p = 0.02). Furthermore, a significant positive correlation between Cr D/P and PI was observed (r = 0.53, p < 0.01)., Conclusion: It is suggested that a strict LPD during the predialysis period may suppress peritoneal permeability at induction of PD.

The BUF/Mna strain of rat is a model of focal and segmental glomerulosclerosis (FSGS) in which a quantitative trait locus (QTL) for proteinuria, Pur1, has been identified. The aim of the present study was to identify candidates for the Pur1 gene. To narrow the Pur1 QTL, we performed fine QTL mapping and single nucleotide polymorphism (SNP) genotyping. To identify candidate genes, sequencing and gene-expression analyses of all genes contained in the narrowed locus were conducted. The narrowed Pur1 region contained 25 genes. Among these genes, only the Arp3 gene was mutated in the BUF/Mna strain; it contained a missense mutation that caused an (L)111(F) substitution. This leucine is conserved across species. Gene-expression analysis failed to identify any other candidate genes for Pur1. Arp3-mediated actin assembly abnormalities were visible in immunohistochemical and electron microscopic examinations of podocytes in old BUF/Mna rats. Taken together, these data suggest that Arp3 is a candidate for the Pur1 gene. This observation is consistent with our growing recognition that abnormal signaling-induced assembly of actin in podocytes leads to the development of FSGS.

Perlecan is a heparan sulfate proteoglycan and a major component of the glomerular basement membrane. To understand the role of heparan sulfate chains of perlecan in glomerular filtration, detailed analyses were performed of the kidneys of Hspg2(Delta)(3/)(Delta)(3) mice, whose perlecan lacks heparan sulfate attachment sites in N-terminal domain I. Macroscopic, histologic, and electron microscopic observations, as well as immunohistochemical and immunoelectron microscopic analyses using specific antibodies against perlecan and agrin core proteins, revealed no significant abnormalities in these mice under physiologic conditions. Polyethyleneimine staining demonstrated no significant changes in charge density in the glomerular basement membrane. Transcripts of other heparan sulfate proteoglycans, agrin, and collagen type XVIII, as well as perlecan, were expressed at similar levels to those in the wild-type littermates. Approximately 40% of the perlecan synthesized by Hspg2(Delta)(3/)(Delta)(3) fibroblasts was substituted with heparin sulfate and 60% was substituted with chondroitin sulfate. All of the perlecan synthesized by wild-type fibroblasts contained heparin sulfate, indicating an altered substitution of glycosaminoglycans on Hspg2(Delta)(3/)(Delta)(3) perlecan. Immunostaining indicated that the level of chondroitin sulfate was actually increased in the Hspg2(Delta)(3/)(Delta)(3) glomerular basement membrane. When administered intraperitoneally with BSA, Hspg2(Delta)(3/)(Delta)(3) mice exhibited remarkable proteinuria. These findings suggest that heparan sulfate chains of perlecan play an important role in glomerular filtration, especially of a large amount of protein.

Objective: To study the effect of once-daily administration of a nitrendipine tablet 10 mg on 24-hour ambulatory blood pressure in inpatients with renal parenchymal hypertension., Methods: Sixteen patients participated in the present study, and one patient was withdrawn because the baseline office blood pressure was less than 140/90 mmHg. In the baseline period, ambulatory blood pressure was monitored every 30 minutes for 30 hours. After the baseline measurement, nitrendipine 10 mg was orally administered once daily every morning for 7 days. The 30-hour ambulatory blood pressure monitoring was repeated after Day 6., Results: Fifteen patients (aged 64.9 +/- 15.0 years) completed the study protocol. Baseline office blood pressure was 157.9 +/- 17.5/84.7 +/- 12.5 mmHg (mean +/- SD). Nitrendipine 10 mg tablets significantly reduced both systolic blood pressure (SBP) and diastolic blood pressure (DBP) at least for 11 hours after administration compared with those at baseline. The rate of "Decrease" (reduction in blood pressure > or = 20/10 mmHg and/or achieved blood pressure < 140/90 mmHg at trough point) was 60.0% (9/15). Eleven patients were considered as effective cases at peak point (maximal reduction in blood pressure > or = 20/10 mmHg). The rate of "Decrease" in effective cases at peak point was 72.7% (8/11)., Conclusion: These results suggest that a once-daily administration of nitrendipine 10 mg tablets is effective for the 24-hour control of blood pressure in patients with renal parenchymal hypertension.

A 12-month, multicenter (57 clinical institutions), randomized, open-labeled trial was undertaken to compare the efficacy of the angiotensin II receptor antagonist losartan and the calcium channel blocker amlodipine in patients with proteinuric chronic kidney disease (CKD) and hypertension. A total of 117 patients (79, chronic glomerulonephritis; 14, diabetic nephropathy; 24, other CKD) were randomly allocated into two treatment groups. Losartan and amlodipine exerted the same efficacy for blood pressure (BP) control; however, losartan significantly reduced the 24-h urinary protein excretion at months 3, 6, and 12, with the reduction of 20.7%, 35.2%, 35.8%, whereas amlodipine did not change the amount of proteinuria over the 12-month study period. When patients were stratified into groups according to the level of BP control at 3 months, the reduction in urinary protein excretion by losartan was evident in the group for which a BP of <140/90 mmHg was achieved, as well as in the group for which the goal BP (<130/85 mmHg) for treatment of CKD was not achieved. When patients were stratified according to baseline urinary protein excretion, those with > or = 2 g/day showed a reduction in proteinuria by losartan of 23.3%, 39.4%, and 47.9% at months 3, 6, and 12, and those with <2 g/day showed a reduction of 18.5% and 31.2% at months 3 and 6, respectively. No fatal adverse events were experienced in either drug group. We conclude that losartan reduced proteinuria in patients with CKD and hypertension. This positive effect may contribute to the renal protective benefit of losartan, and is beyond the magnitude of BP control.

Pulmonary involvement in cryoglobulinemia usually is mild. We present a rare case of severe lung involvement in mixed cryoglobulinemia. A 73-year-old woman with cryoglobulinemic glomerulonephritis was admitted. Dyspnea appeared suddenly two days later. She received the diagnosis of acute lung injury according to the concept proposed by the American-European Consensus Conference. Management required corticosteroid pulse therapy and plasma exchange. This case is the first description of successful early and long-term management of severe lung involvement observed in cryoglobulinemia. Although she has been free of chest symptoms for seven months, further follow-up may be necessary to assess the potential danger of relapse.

Background: Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection., Methods: We examined the effect of the angiotensin (AT)1 receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] > or = 140 mmHg or diastolic blood pressure [DBP] > or = 90 mmHg) and CKD (male, body weight [BW] > or = 60 kg: 1.5 < or = SCr < 3.0 mg/dl; female or male BW < 60 kg: 1.3 < or = SCr < 3.0 mg/dl), manifesting proteinuria of 0.5 g or more/day. Losartan was administered once daily at doses of 25 to 100 mg/day, and amlodipine was given once daily at 2.5 to 5 mg/day. No antihypertensive combination therapy was allowed during the first 3-month period., Results: A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group ( n = 43), but there was no change in the amlodipine group ( n = 43). Analysis of stratified subgroups with proteinuria of 2 g or more/day and less than 2 g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2 g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period., Conclusions: Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.

Background: Percutaneous ethanol injection therapy (PEIT) effectively suppresses PTH secretion, but the change in the serum calcium and phosphorus product (Ca x P) after PEIT has not been fully evaluated., Methods: Twenty-seven haemodialysis patients with severe secondary hyperparathyroidism (2HPT) were divided into two groups according to their intact PTH (i-PTH) concentrations 6 months after PEIT: (i). effective (E) group, i-PTH concentration <360 pg/ml; and (ii). non-effective (N) group i-PTH > or = 360 pg/ml. The changes in serum calcium and phosphorus concentrations and the Ca x P were recorded for the following 2 years under post-PEIT medical treatment with oral calcitriol or intravenous 22-oxacalcitriol (OCT)., Result: In the E group, the i-PTH concentrations decreased to <300 pg/ml 1 year after PEIT (801+/-302 to 280+/-134 pg/ml), then increased to 435+/-201 pg/ml at 2 years. Serum calcium concentration did not show any significant change except for a transient reduction at 1 month after PEIT. The Ca x P decreased for 1 year (from 66.3+/-15.3 to 56.2+/-10.3 mg(2)/dl(2); P<0.05), in agreement with the course of phosphorus concentration, and continued to be <60 mg(2)/dl(2) up to 2 years after PEIT. The Ca x P tended to decrease more with OCT than oral calcitriol. In the N group, calcium and Ca x P increased significantly at 6 months after PEIT and remained at a high value., Conclusion: Treatment with PEIT suppresses serum PTH concentration as well as Ca x P in the long term.

Background: There are few reports of the effect of a low-protein diet on very late-stage chronic renal failure (CRF), eg, serum creatinine level greater than 10 mg/dL (884 micromol/L). In this retrospective study, we examined the effects of a very low-protein diet in patients with very late-stage CRF., Methods: A very low-protein diet (0.25 to 0.54 g/kg body weight/d [0.39 +/- 0.01g/kg body weight/d]) without supplementation of essential amino acids or keto analogues was administered to 76 patients with very late-stage CRF who had serum creatinine levels greater than 10 mg/dL (884 micromol/L). Twenty-one patients with the same serum creatinine level and protein intake of 0.55 to 1.2 g/kg body weight/d (0.68 +/- 0.03 g/kg body weight/d) were observed in lieu of controls., Results: Blood urea nitrogen was significantly suppressed to 43.1 +/- 1.9 g/dL (15.4 +/- 0.7 mmol/L) in the low-protein group compared with 111.2 +/- 7.0 mg/dL (39.7 +/- 2.5 mmol/L; P < 0.001) in the control group. The rate of decline in glomerular filtration rate (creatinine clearance) was 36-fold slower with the low-protein diet (-7.1 +/- 1.0 versus -0.2 +/- 0.4 mL/mon, respectively; P < 0.001). Nutritional state in the low-protein group exceeded that of the control group. Consequently, the renal survival rate improved significantly (P < 0.0001). All patients in the control group were initiated on dialysis treatment within 6 months from a serum creatinine level of 10 mg/dL (884 micromol/L). Conversely, 58% of the low-protein group are still on predialysis treatment., Conclusion: A severe low-protein diet is effective not only in preventing deterioration in renal function, but also in maintaining nutritional state despite no supplementation of essential amino acids or keto analogues, even as serum creatinine level is more than 10 mg/dL (884 micromol/L).

Collagenofibrotic glomerulopathy is considered as a form of glomerulopathy in which organized collagen type III progressively deposits. We report a case of this disease with widespread expression of collagen type V. A 65-year-old woman was admitted to our hospital for further evaluation of nephrotic-range proteinuria. The patient had had anemia and hypertension for 9 years, and proteinuria for 3 years. A renal biopsy specimen showed a remarkable mesangial expansion with Congo red-negative and periodic acid-Schiff-positive deposits. At the ultrastructural level, two forms of bundling fibers were found in the mesangium and subendothelial side of the glomerular basement membranes (GBM). The GBM itself appeared normal. Immunohistochemical investigation showed that the glomerular lesions were strongly reactive with both anti-collagen type-III and -V antibodies. Immunoelectron microscopy demonstrated collagen type V in both forms of bundling fibers. Despite therapy, her renal function declined. The clinical course and renal pathology of this case were in accordance with collagenofibrotic glomerulopathy except for the widespread expression of collagen type V. Collagen type V is a fibrillar collagen capable of forming banding fibrils. This report poses the question whether collagen type V accumulates only in this particular case or whether it is a normal component in collagenofibrotic glomerulopathy.

The basic or h1 calponin gene, which encodes an actin-binding protein involved in the regulation of smooth-muscle shortening velocity, is known to be a smooth-muscle differentiation-specific gene. It was found that basic calponin was expressed by cultured mesangial cells and localized along the actin filaments. Among the growth factors involved in the mesangial cell pathophysiology, including platelet-derived growth factor-BB (PDGF-BB), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta1 (TGF-beta1), TNF-alpha potently downregulates basic calponin expression in both the mRNA and protein levels, whereas TGF-beta1 upregulates the calponin expression. PDGF-BB also reduced its mRNA expression. The half-life of basic calponin mRNA was determined to be similar between TNF-alpha-treated and -untreated mesangial cells, whereas cell transfection assays that used a luciferase reporter gene construct containing the functional basic calponin promoter showed that TNF-alpha and PDGF-BB reduced the transcriptional activity. Because stimulation with TNF-alpha and PDGF-BB was associated with mesangial cell proliferation, basic calponin may play a role in the suppression of mesangial cell proliferation. Treatment with anti-glomerular basement membrane antibody in calponin knockout mice induced more severe nephritis than in wild type mice, as judged from an increase in the urinary protein excretion, glomerular cellularity, and number of proliferating cell nuclear antigen-positive cells in glomerulus. These results suggest that basic calponin expression may serve as one of the intrinsic regulators of glomerular nephritis. Elucidation of the molecular mechanisms for regulation of the basic calponin expression in mesangial cells may improve the understanding of the molecular basis and pathogenesis of the glomerular response to injury.

Secondary hyperparathyroidism (2HPT) is characterized by an abnormal threshold for suppression of parathyroid hormone (PTH) secretion by serum ionized Ca (ICa). It is therefore critical to examine the threshold of PTH secretion in chronic renal failure patients in relation to the physiopathological conditions and the severity of 2HPT. The effect of 1,25-dihidroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) on parathyroid gland function was investigated in six haemodialysis patients with 2HPT. OCT was administered three times a week for 26 consecutive weeks. The maximum serum PTH (PTHmax), the minimum serum PTH (PTHmin), and ICa concentration required to inhibit 50% of PTHmax were estimated based on the model formula of the sigmoid curve describing the relationship between ICa and intact-PTH levels. The sigmoid ICa-PTH curves displayed a downward shift at 12 and 26 weeks of OCT treatment. Parathyroid gland function, as reflected by both PTHmax and PTHmin, decreased over time. A steep slope was found at 12 and 26 weeks, compared with that at the start of OCT treatment. There were no marked changes in the set point of calcium. Hypercalcaemia and elevated creatine phosphokinase, probably due to OCT therapy, were observed during the study period. In view of the findings that the sigmoid ICa-PTH curve displayed a downward shift, that both PTHmax and PTHmin decreased, and that functional mass of the parathyroid gland was reduced, OCT appears to be useful in ameliorating parathyroid gland function, contributing to the management of 2HPT.

The function of intrinsic glomerular cells in active glomerular inflammation may be similar to that of monocytes/macrophages. Mesangial cells have phagocytic properties and release numerous mediators. In this study we examined whether human mesangial cells (hMCs) express a monocyte/macrophage phenotype in active glomerular inflammation. We report that the proto-oncogene c-fms, the macrophage colony-stimulating factor (M-CSF) receptor, which is a characteristic gene of monocytes/macrophages, is expressed in hMCs. Normal unmanipulated hMCs express weak c-fms mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR), and its expression increases after stimulation with platelet-derived growth factor-BB (PDGF-BB) and epidermal growth factor (EGF). The expression of c-fms was also demonstrated by flow cytometry with a specific polyclonal antibody. By immunohistochemistry, c-fms was prominently detected in acute glomerulonephritis, IgA nephritis, and lupus nephritis. These results indicate that hMCs express c-fms in active glomerular inflammation and are consistent with mesangial cells acquiring some macrophage-like characteristics in diseased states.

A common form of methicillin-resistant Staphylococcus aureus (MRSA) associated glomerulonephritis is either an endocapillary proliferative glomerulonephritis or a crescentic glomerulonephritis. This report describes the development of reversible nephrotic syndrome following MRSA infection in a patient with amyloid A amyloidosis. The patient had been diagnosed as having rheumatoid arthritis for 50 years. Suppurative arthritis due to MRSA became complicated 2 years prior to admission to our hospital. In the meantime, a nonnephrotic-range proteinuria developed. Two weeks before admission, nephrotic syndrome developed. The serum creatinine level remained unchanged throughout the course, but common features characteristic of MRSA-associated glomerulonephritis were observed in this patient, such as elevated serum IgG and IgA levels. A renal biopsy specimen showed glomerular amyloid A amyloidosis of a nodular type, infiltrated mononuclear cells in the mesangium, deposition of IgG, IgA, and C3, and swelling of glomerular endothelial cells. There were no crescentic glomeruli. Following surgical eradication of the MRSA focus in the right knee joint, nephrotic syndrome disappeared. Hence, it was highly possible that MRSA infection induced a reversible nephrotic syndrome by causing reversible injuries to glomerular endothelial cells. The description of this case serves to illustrate the range of MRSA infections that may cause various forms of glomerulonephritides., (Copyright 2001 S. Karger AG, Basel.)

A 81-year-old woman was admitted to our hospital because of edema and massive proteinuria on September 26, 1995. On admission, the palpebral conjuctiva were slightly anemic, and edema of the eyelids and legs was observed. Laboratory findings were as follows, urine protein(3+), occult blood(3+), WBC 2,600/microliter, Hgb 10.0 g/dl, reticulocytes 20@1000, TP 5.0 g/dl, Alb 2.7 g/dl, T-Cho 376 mg/dl, TG 194 mg/dl, LDH 763 U/l, haptoglobin < 93 mg/dl, Ham's test(+), sugar water test(+), and indirect coombs (+). The erythrocytes of this patient showed a negative population consisting of double negative erythrocytes evaluated by flow cytometric two-color analysis using monoclonal antibodies specific to CD55 and CD59. From these findings, the diagnosis of paroxysmal nocturnal hemoglobinuria(PNH) was made. The patient showed nephrotic syndrome and a renal biopsy was performed. The histological findings of renal biopsy showed focal and segmental sclerosis and adhesion of glomerular tufts. Interstitial fibrosis with atrophic tubules and lymphocyte infiltration were also observed. There was no specific staining of immunoglobulins and complement by immunofluorescence. The diagnosis of focal segmental glomerular sclerosis(FSGS) was made. There have been only three case reports of glomerular disease in patients with PNH, such as purpura nephritis, IgA nephropathy and membranous nephropathy. The complication of FSGS and PNH is every rare and there has been no report of FSGS in a case with PNH. The onset of PNH resulted from the loss of CD55 and CD59, which was critical in the onset of FSGS in the present case.

Proteinuria is commonly observed in patients with chyluria due to Bancroftian filariasis. However, whether or not hypoalbuminemia is caused by chyluria alone is still a matter of debate. This is because various forms of glomerulonephritis are complicated in such patients. Herein, we report a case we have recently encountered. A 72-year-old male was admitted to our division for further evaluation of nephrotic syndrome. He was from the Southernmost part of Japan, where Bancroftian filariasis has been epidemic, and had developed persistent chyluria over a period of nearly 50 years. There was no other past history of illness except for diabetes mellitus(DM) pointed out 3 months prior to admission. The physical and laboratory examinations on admission fulfilled the diagnostic criteria for nephrotic syndrome. Lymphoscintigraphy showed an intense tracer accumulation in both kidneys. A renal biopsy was performed. At the light microscopic level, the glomeruli looked normal. Edema of the tubulointerstitium was noted. At the electron microscopic level, effacement of podocyte foot processes was not observed. Immunofluorescent study did not show glomerular deposition of immunoglobulins and complements. He also had persistent microscopic hematuria. Automated urinary sediment analysis by real-time confocal scanning laser microscopy revealed red blood cells of the non-glomerular type. Taken together, these findings strongly indicated that hypoalbuminemia of this patient was caused by chyluria alone. In conclusion, a report of the present case provides strong evidence that hypoalbuminemia of a patient with Bancroftian filariasis could be caused by chyluria alone.

Previous reports have clarified that focal and segmental glomerulosclerosis(FSGS) appearing in membranous nephropathy(MN) is associated with a poorer prognosis than that of MN without FSGS. However, the etiology and pathogenesis of such FSGS lesions may show substantial individual differences. In some patients, hemodynamic alterations secondary to hypertension and vascular disorders seem to play a crucial role in the development of such FSGS lesions. In such instances, steady regulation of blood pressure might slow down further progression of FSGS lesions. Here we describe two cases of biopsy-proven MN with FSGS. Case I was a 44-year-old man who had shown massive proteinuria with hematuria at the age of 39 years. Renal biopsy specimens obtained at the age of 40 and 41 years showed MN without FSGS and MN with FSGS, respectively. His blood pressure control was fairly good throughout the course. Although he was on a steroid, an immunosuppressant, a low protein diet, and an ACE inhibitor, his renal function declined in 5 years. Case 2 was a 61-year-old woman who showed nephrotic syndrome at the age of 39 years. A renal biopsy specimen obtained at the age of 58 years showed MN with FSGS and remarkable atherosclerotic changes of the interlobular arteries. Her blood pressure control was rather poor throughout the course. Her renal function gradually declined over 22 years. Since parts of the FSGS lesions of the second case may have been caused by hypertension, it is tempting to speculate that day-to-day control of blood pressure could improve the long-term prognosis. We believe that, at least in some patients of MN with FSGS, careful management may lead to a more favorable course of decline in renal function.

A patient with acquired hemophilia complicated with chronic renal failure and lung tuberculosis was successfully treated by consecutive plasma exchange (PE). A 71-year-old man with serious bleeding tendency showed low coagulation factor levels and a high titer of factor VIII (FVIII) inhibitor, and he was diagnosed with acquired hemophilia. Because of the complication of active lung tuberculosis, instead of immunosuppressive therapy, he undertook a series of PE with fresh frozen plasma replacement for 3 months. After the start of PE, his bleeding symptoms and activated partial thromboplastin time (APTT) improved gradually according to the decrease in FVIII inhibitor levels. These results suggest that PE is an effective therapeutic tool for refractory acquired hemophilia.

A case of hemophagocytic syndrome (HPS) refractory to corticosteroid therapy was successfully treated by plasma exchange. The patient was a 56-year-old woman who had undergone regular hemodialysis for 10 years for complicated myelodysplastic syndrome (MDS) and then had had lung tuberculosis. After the onset of tuberculosis, she suffered from HPS and was treated by antituberculosis agents and high dose corticosteroid administration without any effect on the HPS. After adding a series of plasma exchanges, the HPS improved gradually, and her MDS began to respond to corticosteroid therapy. Plasma hypercytokinemia due to HPS was corrected by plasma exchange, and the correction of a high level of plasma inflammatory cytokine was considered to be one of the contributing factors for the improvement of HPS. These results suggest that therapeutic plasma exchange should be considered as a therapeutic tool for HPS refractory to conventional therapy.