Serum levels of the soluble haemoglobin scavenger receptor CD163 in MPO-ANCA-associated renal vasculitis.

OBJECTIVES: The contribution of infections to the mortality of patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is important, and early and careful infection control is necessary. We investigated the usefulness of the serum-soluble haemoglobin scavenger receptor CD163 for detecting the presence of infectious complications regardless of disease activity. METHOD: Soluble CD163 in serum obtained from 45 Japanese patients with myeloperoxidase (MPO)-AAV was measured by an enzyme-linked immunosorbent assay (ELISA). We evaluated 36 samples from active-vasculitis patients, 36 samples from inactive-vasculitis patients without infection, and 19 samples from inactive-vasculitis patients with infectious complications. Serum-soluble CD163 was also measured in 15 infectious patients without vasculitis and in 30 normal controls. RESULTS: The mean serum-soluble CD163 level was higher in the patients with infectious complications than in the active-vasculitis patients, inactive-vasculitis patients, and normal controls. There were significant positive correlations between serum-soluble CD163 levels and white blood cell (WBC) count, serum C-reactive protein (CRP) levels, and serum albumin levels, but only serum CRP levels were correlated with serum-soluble CD163 levels in a multiple regression analysis. On the receiver-operating characteristic (ROC) curve, serum-soluble CD163 levels had 80.6% sensitivity and 86.7% specificity for differentiating patients with infection from those without infection. Among the active-vasculitis patients, the mean serum-soluble CD163 level of the patients with alveolar haemorrhage was significantly lower than that of the patients with interstitial lung diseases and that of the patients without pulmonary lesions. CONCLUSIONS: The serum-soluble CD163 level may be a useful marker for the detection of infectious complications in MPO-AAV patients.

ECM gene expression and its modulation by insulin in diabetic rats.

The steady-state levels of mRNA encoding for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, basement membrane HSPG, and alpha 1(I) and alpha 1(III) collagen chains were examined in rat glomeruli at 4, 12, and 24 wk after injection of STZ. The mRNA levels for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, and alpha 1(I) and alpha 1(III) collagen chains increased significantly with age in the STZ-induced diabetic rats before morphological thickening of basement membrane occurred. In contrast, the mRNA levels for HSPG decreased markedly 4 wk after STZ injection and then increased with age compared with those for control rats. The mRNA levels for these ECM components showed a continuous decline with age in controls. Treating the diabetic rats with insulin for 4 wk ameliorated the abnormally regulated ECM gene expression in the glomeruli. These data suggest that the abnormal regulation of ECM gene expression in the glomeruli may contribute to the expansion of mesangial matrix and basement membrane thickening in diabetic rats, and that hyperglycemia may play a role in the abnormal ECM gene expression.

Effect of a specific endothelin receptor A antagonist on mRNA levels for extracellular matrix components and growth factors in diabetic glomeruli.

We have previously reported that the mRNA levels of extracellular matrix (ECM) components including alpha 1(I), alpha 1(III), and alpha 1(IV) collagen chains, laminin B1 and B2 chains, and growth factors including tumor necrosis factor (TNF)-alpha, platelet-derived growth factor (PDGF)-B chain, transforming growth factor (TGF)-beta, and basic fibroblast growth factor (FGF) all increase with age in diabetic glomeruli. The present study was designed to assess whether glomerular expression of these mRNAs in rat diabetic glomeruli is affected by a specific endothelin receptor A antagonist, FR139317. Diabetes was produced by streptozotocin injection, and animals were divided into four groups: untreated diabetic rats, FR139317-treated diabetic rats, control nondiabetic rats, and FR139317-treated control rats. FR139317 treatment was continued for 24 weeks. FR139317 attenuated the rise in creatinine clearance (P < 0.01) and reduced urinary protein excretion (P < 0.01) in diabetic rats, but did not affect blood pressure. FR139317 attenuated the increases in glomerular mRNA levels of alpha 1(I) (P < 0.01), alpha 1(III) (P < 0.01), and alpha 1(IV) (P < 0.01) collagen chains, laminin B1 (P < 0.01) and B2 (P < 0.01) chains, TNF-alpha (P < 0.01), PDGF-B (P < 0.01), TGF-beta (P < 0.001) and basic FGF (P < 0.01) in diabetic rats. However, FR139317 did not affect these mRNA levels in glomeruli of control rats. These findings suggest that FR139317 may be useful in the treatment of diabetic glomerulopathy by reducing mRNA levels of ECM components and growth factors.

mRNA expression of growth factors in glomeruli from diabetic rats.

Evaluations of glomerular mRNA levels encoding for PCNA, TNF-alpha, PDGF-A and -B chains, TGF-beta, IGF-I, bFGF, and EGF were made at 4, 12, and 24 wk after injection of STZ in Sprague-Dawley rats. The mRNA levels for PCNA, TNF-alpha, PDGF-B chain, TGF-beta, and bFGF increased with age in STZ-induced diabetic rats. At 24 wk after STZ injection, mRNA levels for PCNA, TNF-alpha, PDGF-B chain, TGF-beta, and bFGF were increased 3.8-fold, (P < 0.01), 4.2-fold (P < 0.01), 4.0-fold (P < 0.01), 5.2-fold (P < 0.001), and 3.6-fold (P < 0.01), respectively, in the glomeruli of diabetic rats when compared with control rats. In contrast, mRNA levels for IGF-I, PDGF-A chain, and EGF were not altered in glomeruli from diabetic and control rats throughout the experimental period. Insulin treatment partially ameliorated the increase in mRNA levels for PCNA, TNF-alpha, PDGF-B chain, TGF-beta, and bFGF in the glomeruli of diabetic rats. These data indicate that alterations in growth factor mRNA levels in glomeruli may be a manifestation of diabetic nephropathy, and that hyperglycemia or insulin deficiency may play a role in abnormal growth factor gene regulation.

Effect of the antiplatelet drug dilazep dihydrochloride on urinary podocytes in patients in the early stage of diabetic nephropathy.

OBJECTIVE: To determine whether the antiplatelet drug dilazep dihydrochloride affects the number of urinary podocytes in diabetic patients with microalbuminuria. RESEARCH DESIGN AND METHODS: Fifty patients with type 2 diabetes and microalbuminuria (30 men and 20 women, mean age 48.6 years) and 30 age-matched control subjects (18 men and 12 women, mean age 49.2 years) were included in the study. No patients showed serum creatinine levels in excess of 2.0 mg/dl. Urinary podocytes were examined by immunofluorescence microscopy with monoclonal antibodies against podocalyxin. RESULTS: Urinary podocytes were detected in 18 of the 50 microalbuminuric diabetic patients (mean, 1.3 cells/ml). Urinary podocytes were not detected in the remaining 32 patients or in the 30 healthy control subjects. Diabetic patients positive for urinary podocytes were divided into 2 treatment groups: a dilazep dihydrochloride treatment group (300 mg/day; n = 9, group A) and a placebo group (n = 9, group B). Treatments were continued for 6 months. In group A, microalbuminuria decreased significantly from 146 +/- 42 to 86 +/- 28 microg/min (P < 0.01) and urinary podocytes also decreased from 1.3 +/- 0.8 to 0.4 +/- 0.2 cells/ml (P < 0.01). However, in group B, microalbuminuria and urinary podocytes changed little over the study period. CONCLUSIONS: Podocyte injury may occur in patients with early diabetic nephropathy, and dilazep dihydrochloride may be useful for preventing glomerular injury.

Increased plasma metalloproteinase-9 concentrations precede development of microalbuminuria in non-insulin-dependent diabetes mellitus.

We determined plasma metalloproteinase-9 (MMP-9) concentrations in 30 patients with non-insulin-dependent diabetes mellitus (NIDDM) at an initial examination (baseline) and on three separate occasions during a 48-month follow-up period. All patients had normal urinary albumin excretion (<20 microg/min) at the first three examinations. At the fourth examination (48 months after the first examination), 22 patients had normal urinary albumin excretion and eight had microalbuminuria (median, 36.4 microg/min; range, 20.2 to 46.6 microg/min). Compared with patients with normal urinary albumin excretion, patients with microalbuminuria had significantly higher plasma levels of MMP-9 at the second (56+/-14 microg/L v36+/-12 microg/L; P < 0.05), third (88+/-23 microg/L v 39+/-14 microg/L; P < 0.01), and fourth (117+/-30 microg/L v 44+/-16 microg/L; P < 0.01) examinations, but not at the first examination (34+/-12 microg/L v 33+/-14 microg/L; P=NS). An increase in plasma MMP-9 concentrations preceded the occurrence of microalbuminuria within 4 years. The groups did not differ with regard to age, sex, duration of NIDDM, blood pressure, or mean glycated hemoglobin. In addition, the eight patients with microalbuminuria were treated with an angiotensin-converting enzyme inhibitor (cilazapril; 0.5 mg once daily) for 6 months. Microalbuminuria was reduced to within the normal range, and plasma MMP-9 concentrations were significantly decreased with the cilazapril treatment (52+/-18 microg/L; P < 0.01). However, serum MMP-1 and tissue inhibitor of MMP-1 showed no change during the study period. These data suggest that plasma MMP-9 concentrations preceded and may predict the development of microalbuminuria in NIDDM.

Effect of hemoperfusion with polymyxin B-immobilized fiber on plasma endothelin-1 and endothelin-1 mRNA in monocytes from patients with sepsis.

Hemoperfusion using polymyxin B-immobilized fiber (PMX-F) is reported to be an effective treatment for sepsis. The aim of the present study is to assess whether plasma endothelin-1 (ET-1) and ET-1 messenger RNA (mRNA) levels in peripheral-blood monocytes are altered in patients with sepsis and whether PMX-F treatment affects plasma ET-1 and monocyte ET-1 mRNA levels. Sixteen patients with sepsis and 20 healthy volunteers were included in this study. Plasma ET-1 concentration was measured by radioimmunoassay (RIA), and plasma levels of transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) were measured by enzyme-linked immunosorbent assay (ELISA). Sixteen patients with sepsis were treated with direct hemoperfusion using PMX-F columns. Blood endotoxin levels decreased significantly from 35 to 10 pg/mL after two treatments of direct hemoperfusion, each for 2 hours. Patients with sepsis showed significantly increased levels of plasma ET-1 (P < 0.001) and monocyte ET-1 mRNA (P < 0.001) compared with healthy volunteers. However, no differences in plasma levels of TGF-beta, TNF-alpha, and IL-1beta existed between patients with sepsis and healthy volunteers. Increased plasma ET-1 levels and monocyte ET-1 mRNA levels in patients with sepsis decreased significantly after PMX-F treatment (P < 0.01). These data suggest that the secretion of ET-1 from peripheral-blood monocytes may be stimulated by endotoxin, and PMX-F treatment may be effective in reducing ET-1 secretion in patients with sepsis.

Increased interleukin 6 mRNA expression by peripheral blood T cells from patients with IgA nephropathy.

We investigated interleukin 6 (IL-6) mRNA expression in peripheral blood T-cells obtained from 36 patients with IgA nephropathy (IgAN), 36 patients with other glomerulonephritides and 24 healthy age-matched controls. The majority of patients with IgAN had increased IL-6 mRNA expression by their T cells; no IL-6 mRNA was detected in T cells obtained from patients with other glomerulonephritides or normal controls. A positive correlation was noted between the IL-6 mRNA level and quantity of protein excretion in the urine, histopathological findings, and renal function. However, there was no significant correlation between IL-6 mRNA expression and the IgA-immune complex titer, serum IgA level or blood pressure. mRNA levels in T cells obtained from patients with grade III or IV renal histopathological findings were significantly higher than in those with grade I or II histopathology. In addition, mRNA levels in T cells obtained from patients with more than 1.0 g/day proteinuria were markedly higher than those with less than 1.0 g/day proteinuria. We also studied the clinical course of 11 patients with IgAN during hospitalization. The IL-6 mRNA levels in these patients decreased gradually, as did proteinuria, after treatment. These studies suggest that abnormally regulated IL-6 mRNA expression in peripheral blood T cells may be associated with disease activity in IgAN.

Changes in plasma erythropoietin and interleukin-6 concentrations in patients with septic shock after hemoperfusion with polymyxin B-immobilized fiber.

OBJECTIVE: To find out whether polymyxin B-immobilized fiber (PMX-F) treatment affects the clinical parameters and plasma concentrations of erythropoietin (EPO) and interleukin (IL)-6. DESIGN: A prospective case series study. SETTING: Intensive care unit of the Department of Internal Medicine, Misato Junshin Hospital, Saitama, and Koto Hospital, Tokyo, Japan. PATIENTS: 17 consecutive patients (10 men, 7 women; mean age 54.6 years) with clinically defined septic shock and 20 healthy volunteers (12 men, 8 women; mean age 52.2 years). MAIN RESULTS: Of the 17 patients with septic shock, 9 (53 %) survived. The systolic blood pressure increased significantly from 78+/-6 to 106+/-8 mm Hg 2 h after PMX-F treatment in patients with septic shock. Plasma endotoxin levels decreased significantly after treatment, from 40+/-6 to 12+/-4 pg/ml. The pretreatment plasma concentrations of EPO and IL-6 were significantly higher in the 8 nonsurviving patients with septic shock (EPO: 400+/-36 mlU/ml; IL-6: 6260+/-1180 pg/ml) than in the 9 surviving patients (EPO: 120+/-22 mlU/ml; IL-6: 680+/-138 pg/ml) and the 20 control subjects (EPO, 12+/-6 mlU/ml; IL-6, 8+/-2 pg/ml). Plasma concentrations of EPO and IL-6 in patients with septic shock decreased significantly after PMX-F treatment (EPO, nonsurviving: 320+/-28 mlU/ml, p < 0.05; survivors: 26+/-8 mlU/ ml, p < 0.001; IL-6, nonsurviving: 3860+/-840 pg/ml, p < 0.01; survivors: 84+/-20 pg/ml, p < 0.001). CONCLUSIONS: Plasma concentrations of EPO and IL-6 may be prognostic indicators in patients with septic shock: PMX-F treatment may be effective in reducing the plasma concentrations of EPO and IL-6 in patients with septic shock.

Comparative effects of pioglitazone, glibenclamide, and voglibose on urinary endothelin-1 and albumin excretion in diabetes patients.

Urinary endothelin (ET)-1 excretion is present in non-insulin dependent diabetes (NIDDM) patients with microalbuminuria, and an increase in circulating ET-1 precedes the microalbuminuric phase of renal injury related to diabetes. The aim of the present study was to determine whether various drugs alter urinary ET-1 levels and urinary albumin excretion (UAE) in NIDDM patients with microalbuminuria. Forty-five NIDDM patients with microalbuminuria were randomly assigned to three groups: those treated with pioglitazone at 30 mg/day (n=15), those treated with glibenclamide at 5 mg/day (n=15), and those treated with voglibose at 0.6 mg/day (n=15). Patients received these drugs for 3 months. UAE, urinary ET-1, and plasma ET-1 levels were measured in these patients before and after treatment. Before treatment, UAE, urinary ET-1, and plasma ET-1 levels differed little among the three groups. UAE in the 45 NIDDM patients (156.2+/-42.8 microg/min) was greater than that in 30 healthy controls (8.2+/-2.6 microg/min) (P<.001). Urinary ET-1 levels in the NIDDM patients (8.7+/-1.3 ng/g urinary creatinine (UC)) were significantly higher than that in the controls (2.4+/-0.2 ng/g UC) (P<.01). Plasma ET-1 levels, however, in the NIDDM patients (1.3+/-0.4 pg/ml) did not differ significantly from the levels in healthy controls (1.0+/-0.6 pg/ml). Pioglitazone but no glibenclamide or voglibose reduced UAE from 142.8+/-42.2 to 48. 4+/-18.2 microg/min (P<.01) and urinary ET-1 levels from 8.6+/-1.3 to 3.4+/-0.5 ng/g UC (P<.01). These data suggest pioglitazone to be effective in reducing UAE and urinary ET-1 concentrations in NIDDM patients with microalbuminuria.

Effects of hemoperfusion with polymyxin B-immobilized fibre on serum neopterin and soluble interleukin-2 receptor concentrations in patients with septic shock.

OBJECTIVE: the aim of the present study was to determine whether serum neopterin and soluble interleukin (IL)-2 receptor levels were related to the development of septic shock and whether polymyxin B-immobilized fibre (PMX-F) treatment affects these levels. METHODS: we examined 24 patients admitted to our intensive care unit with Gram-negative septic shock. Serum neopterin and soluble IL-2 receptor levels were measured using commercially available test kits. Patients were treated with direct hemoperfusion using PMX-F columns. RESULTS: fifteen out of 24 patients (63%) survived and were discharged from our hospitals within 30 days after PMX-F treatment. Blood endotoxin levels decreased significantly from 49.2+/-8.6 pg/ml to 13.2+/-4.4 pg/ml after PMX-F treatment. The pretreatment serum concentrations of neopterin and IL-2 receptor were significantly higher in the nine non-surviving patients with septic shock than in the 15 surviving patients (P<0.01) and 20 control subjects (P<0.001). Serum concentrations of neopterin and IL-2 receptor in patients with septic shock decreased significantly after PMX-F treatment (P<0.01). CONCLUSIONS: these data suggest that serum neopterin and IL-2 receptor concentrations may be prognostic indicators in patients with septic shock. PMX-F treatment may be effective for reducing serum neopterin and IL-2 receptor concentrations.

Increased mRNA expression encoding for medullasin in peripheral blood mononuclear cells from patients with IgA nephropathy.

We investigated mRNA expression for medullasin (an inflammatory serine protease in bone marrow cells) in peripheral blood mononuclear cells (PBMC) obtained from 36 patients with primary IgA nephropathy (IgAN), 30 patients with other types of primary glomerular disease, 18 patients with secondary IgA nephritis including lupus nephritis and hepatic glomerulosclerosis and 24 healthy age-matched controls. The majority of patients with IgAN (86%) showed elevated medullasin expression in PBMC, while no medullasin mRNA expression was detected in PBMC obtained from patients with other types of primary glomerular disease, secondary IgA nephritis or normal healthy controls. A positive correlation was noted between mRNA levels and urinary protein excretion. The medullasin mRNA expression in PBMC also correlated with the severity of the histopathologic changes in renal tissue obtained from patients with IgAN. All the patients with severe proteinuria (more than 3.0 g/day) showed strong [more than (++)] medullasin mRNA expression in their PBMC. In addition, all the patients with more than (++) medullasin mRNA expression are grade III or IV histopathological findings. These studies suggest that abnormally regulated medullasin gene expression in PBMC may be associated with the progression of primary IgAN.

Comparative effects of plasmapheresis and intravenous cyclophosphamide on urinary podocyte excretion in patients with proliferative Lupus nephritis.

Intravenous cyclophosphamide (IVC) in combination with steroids is standard therapy for Lupus nephritis. Reduction of autoantibodies and circulating immune complexes can be used in the treatment of autoimmune diseases. The aim of the present study was to compare the effects of IVC pulse therapy and double-filtration plasmapheresis (DFPP) on proteinuria and urinary excretion of podocytes in adult patients with diffuse proliferative Lupus nephritis (DPLN). Twenty patients were randomly assigned to two groups. Group A (n = 10) was treated with IVC (0.75 - 1.0 g/m2 body surface area) pulse therapy, given as boluses once a month for 6 consecutive months, combined with oral corticosteroid (up to 1 mg/kg/day) administration. Group B (n = 10) was treated with a combination of DFPP (performed 1-2 times weekly) and corticosteroid (up to I mg/kg/ day). The total average number of treatments was 8.4 and the therapeutic efficacies were evaluated after 6 months. Twenty healthy individuals participated as a control group. Urinary podocytes were examined by immunofluorescence with monoclonal antibodies against podocalyxin. Both Group A and Group B reduced proteinuria (p < 0.001) as well as the number of urinary podocytes (p < 0.001). Differences between the 2 treatment outcomes were not statistically significant. Cyclophosphamide pulse therapy and DFPP may be similarly effective in the treatment of podocyte injury in patients with DPLN.

Cytogenetic damage and cell-mediated immunity in pneumoconiosis.

The International Agency for Research on Cancer (IARC) determined that crystalline silica inhaled from occupational sources should be classified as carcinogenic to humans and upgraded it from group 2A to group 1. It has also been found that silicosis may be associated with cancer of various organs and with autoimmune diseases. We studied both the cytogenetic effects and the influence on cell-mediated immunity of mineral dust inhalation in patients with pneumoconiosis, including silicosis. The frequency of sister chromatid exchanges and micronucleus in the pneumoconiosis group were significantly higher than in the controls, suggesting a cytogenetic influence of the occupationally inhaled dust. Alterations in the immunoregulatory T cells were observed in the pneumoconiosis groups, suggesting that inhaled mineral dust may cause immunotoxic effects. Based on these findings, we can consider that cytogenetic damages and immunoregulatory abnormalities in pneumoconiosis patients may play a role in the pathogenesis of various cancers and autoimmune diseases associated with pneumoconiosis.

Mineral dust exposure and systemic diseases.

Based on clinical and immunological studies, we have proposed the hypothesis that occupational dust exposure might cause not only pneumoconiosis but also autoimmune diseases and malignancies of various organs such as neoplasms of lymphatic and hematopoietic tissues and gastric cancer. Evidence from cohort studies of pneumoconiotic patients in Japan, copper miners, and stone masons support our hypothesis. The carcinogenicity and cytotoxic effect of inhaled dust on immune cells are considered to contribute to the development of these diseases.

Elevated levels of erythropoietin in cerebrospinal fluid of depressed patients.

To investigate the role of erythropoietin (EPO) in the central nervous systems, we assayed EPO concentrations in the cerebrospinal fluid (CSF) of patients with depression or old cerebrovascular injuries and controls. Concentrations of EPO in the CSF were significantly higher in 13 patients with depression (3.21+/-0.46 mU/mL) than in 10 patients with old cerebrovascular diseases (1.80+/-0.32 mU/mL, P < 0.01), and in 10 healthy controls (0.98+/-0.26 mU/mL, P < 0.01). Serum EPO concentrations did not differ among these three groups. In the patients with depression, 5 months of treatment with imipramine and/or nortriptyline significantly reduced EPO concentrations in the CSF (1.56+/-0.34 mU/ mL, P < 0.01). Results suggest that the brain of patients with depression may be in an hypoxic state, and that the increased EPO in the CSF may act to limit hypoxia-induced damage to neurons in these patients.

Modulation of plasma metalloproteinase-9 concentrations and peripheral blood monocyte mRNA levels in patients with septic shock: effect of fiber-immobilized polymyxin B treatment.

The authors measured plasma metalloproteinase (MMP)-9 and corresponding monocyte mRNA in 20 patients with septic shock. Plasma MMP-9 concentrations and monocyte MMP-9 mRNA levels were significantly higher in the 10 nonsurviving patients with septic shock than in 10 surviving patients and 25 normal controls. Hemoperfusion using polymyxin B immobilized on fibers (PMX-F), a reportedly effective treatment for septic shock, was studied for effects on MMP-9 in the patients. Increases in plasma MMP-9 concentrations and corresponding monocyte mRNA levels were attenuated significantly by PMX-F treatment in both nonsurviving and surviving patients. These data suggest that plasma MMP-9 concentrations and monocyte MMP-9 mRNA levels may be useful prognostic markers in septic shock, and that PMX-F treatment affects MMP-9.

Increased expression of proliferating cell nuclear antigen mRNA in peripheral blood mononuclear cells from patients with IgA nephropathy.

Proliferating cell nuclear antigen (PCNA)/cyclin is an intranuclear polypeptide antigen whose appearance correlates with the proliferative state of cells. The authors investigated the expression of PCNA from peripheral blood mononuclear cells (PBMC) in 23 patients with IgA nephropathy and 10 healthy age-matched controls, using ribonucleic acid hybridization techniques. The majority of patients with IgA nephropathy (22 of 23 patients) showed elevated PCNA expression in PBMC, while no PCNA expression was detected in PBMC of normal controls. A positive correlation was noted between PCNA expression of PBMC and glomerular injuries and PCNA expression and urinary protein excretion. Sixty-three percent of patients with grade III and IV histological findings showed strong PCNA (more than ) expression in their PBMC. The urinary protein excretion in patients who showed more than ( ) PCNA expression was more than 2.5 g/d, while that in patients with less than (+) PCNA expression was less than 1.0 g/day. These findings indicate that abnormally regulated PCNA expression in PBMC may play an important role in the progression of IgA nephropathy, and that PCNA expression in PBMC may be a useful indicator of disease activity.

Urinary podocytes for the assessment of disease activity in lupus nephritis.

BACKGROUND: Detection of podocytes in the urine indicates that severe injury of podocytes occurred in the glomerulus in children. METHODS: The pathological significance of podocytes in the urine was determined in patients with lupus nephritis. Podocytes were detected by immunofluorescence using a monoclonal antibody against podocalyxin present on the surface of podocytes. Subjects who participated in the present study were of the following types: patients with systemic lupus erythematosus with stable renal function (group A, n = 8; WHO classes IlIa, b, IVb, and IVc at the time of biopsy); patients with clinically active lupus nephritis (group B, n = 8; WHO classes IVb and IVc); and healthy control subjects (group C, n = 10). RESULTS: Podocytes were absent in the urine of subjects in groups A and C. However, podocytes were present in the urine of group B subjects. Patients in group B were examined monthly for urinary podocytes and were treated with methylprednisolone followed by prednisolone. Urinary podocytes were absent in all patients in group B after treatment. CONCLUSIONS: These data indicate that urinary podocytes may be markers of the severity of lupus nephritis and that steroid therapy may be effective for podocyte injury in lupus nephritis.

Increased endothelin-1 mRNA expression in peripheral blood monocytes of dialysis patients.

OBJECTIVE: To compare plasma endothelin (ET)-1 level and ET-1 mRNA level in peripheral blood monocytes of patients undergoing hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). DESIGN: Endothelin-1 mRNA level in peripheral blood monocytes and plasma ET-1 level were studied in 30 HD patients, 15 CAPD patients, 20 chronic renal failure patients not being dialyzed, and 20 normal healthy controls. Hemodialysis patients were dialyzed three times per week with a bicarbonate dialysate. Different types of dialyzer membrane, viz., cellulose triacetate, cuprophane, polysulfone, polyacrylonitrile, and ethylenevinylalcohol were used in 8, 6, 6, 5, and 5 patients, respectively. Continuous ambulatory peritoneal dialysis patients were dialyzed with four daily exchanges of a 2-L dialysate containing glucose at a concentration of 1.5% to 2.5%. RESULTS: Higher levels of ET-1 mRNA in monocytes were observed in HD patients than in CAPD patients (p < 0.01), chronic renal failure patients (p < 0.01), or normal healthy controls (p < 0.001). The level of ET-1 mRNA in monocytes at the end of HD was not significantly higher than that at the start of HD. In addition, these mRNA levels in HD patients showed little difference with different types of dialysis membrane. Plasma ET-1 level in HD patients (10.2 +/- 2.4 pg/mL) was also higher than that in CAPD patients (7.8 +/- 1.6 pg/mL, p < 0.01), in chronic renal failure patients (4.8 +/- 1.2 pg/mL, p < 0.01), or in normal controls (2.6 +/- 0.8 pg/mL, p < 0.001). CONCLUSION: Dialysis itself did not significantly affect ET-1 mRNA levels in monocytes. Chronic stimulation of peripheral blood monocytes may be associated with higher levels of ET-1 mRNA and plasma ET-1 in HD patients than in CAPD patients.