A case of focal segmental glomerulosclerosis with myeloid bodies.

The presence of myeloid bodies in electron microscopy is a characteristic finding of Fabry's disease. Here, we present a male patient, whose renal biopsy findings suggested the coexistence of focal segmental glomerulosclerosis and Fabry's disease, because of the presence of segmental hyalinosis and/or sclerosis in glomeruli and myeloid bodies in electron microscopy. But finally, Fabry's disease was excluded as a diagnosis because the α-galactosidase A activity in leukocyte and plasma in this patient was within normal limits. After renal biopsy, although he received medication including steroid therapy, his renal function gradually decreased to end-stage renal failure and hemodialysis was initiated. Until now, he does not exhibit any specific symptoms. In conclusion, our case suggests that occasional myeloid bodies in renal biopsy specimens should be interpreted with caution.

Voriconazole-associated salt-losing nephropathy.

A 74-year-old man was diagnosed with nephrotic syndrome due to focal segmental glomerulosclerosis, and steroid therapy was initiated. Subsequently, he was affected by deep mycosis, and hence, voriconazole (VRCZ) was administered. On the 16th day, he was transferred to our hospital because of somnolence and malaise. His systolic blood pressure was approximately 80 mmHg, and he showed decreased skin turgor, indicating volume depletion. Laboratory analysis revealed hyponatremia and liver dysfunction. Discontinuation of VRCZ and drip infusion of normal saline improved the consciousness disorder, hyponatremia, and liver dysfunction. The levels of antidiuretic hormone (ADH) and plasma renin activity were elevated. This patient showed high excreted urine sodium, despite volume depletion and low serum osmolality. Therefore, this patient was diagnosed with salt-losing nephropathy (SLN). SLN should be considered for treatment of VRCZ-associated hyponatremia, together with syndrome of inappropriate secretion of ADH.

Analysis of T-cell receptor usage in myeloperoxidase--antineutrophil cytoplasmic antibody-associated renal vasculitis.

BACKGROUND: Bacterial superantigens produced by Staphylococcus aureus may be associated with the onset of proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA)-associated vasculitis, including Wegener's granulomatosis. We investigated T-cell subsets to assess the superantigens present in patients with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis. METHODS: Peripheral-blood mononuclear cells (PBMC) obtained from 40 normal controls and ten patients with MPO-ANCA-associated vasculitis were stained with fluorescence-labeled monoclonal antibodies against T-cell markers, including 17 variable regions of T-cell receptor beta-chains (TCR-Vbeta) and were then analyzed using flow cytometry. RESULTS: Among PBMCs, the percentage of CD3(+) cells from patients with MPO-ANCA-associated vasculitis was significantly lower than that from normal controls, but there were no differences between the two groups in the percentage of CD19(+) cells or CD16(+) cells. Although there were no differences regarding the overall percentage of CD4(+) cells between the two groups, the percentage of CD4(+)CD45RO(+) cells in patients with MPO-ANCA-associated vasculitis was significantly higher than that in normal controls, and percentages of CD4(+)CD45RO(+)HLA-DR(+) and CD4(+)CD45RO(+)CD62L(low) cells in patients with MPO-ANCA-associated vasculitis were also significantly increased. There was no significant difference between the two groups in terms of the usage of the 17 different TCR-Vbeta regions. CONCLUSION: There was no difference in bacterial superantigens between controls and MPO-ANCA-associated vasculitis patients because of the absence of specific usage of TCR-Vbeta regions. Given the elevated levels of memory T cells, conventional antigens rather than superantigens may be associated with the pathogenesis of MPO-ANCA-associated vasculitis.

Antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis with membranous nephropathy treated using thiamazole.

A 21-year-old woman with nephrotic syndrome was referred to our hospital. She had congenital diaphragmatic hernia, hypoxic ischemic encephalopathy, and mental retardation, and had been treated for hyperthyroidism with thiamazole in another hospital. Serum creatinine was 37.8 µmol/L and antineutrophil cytoplasmic antibody against myeloperoxidase (MPO-ANCA) was 39 EU. Urinalyses were 3+ for proteins and 3+ for occult blood. A renal biopsy was performed. An examination using light microscopy (LM) revealed necrotizing glomerulonephritis with crescent formation. Immunofluorescence microscopy showed granular staining with immunoglobulin G and complement component 3 along the capillary walls. Electron microscopy (EM) disclosed subepithelial dense deposits. A renal biopsy suggested necrotizing glomerulonephritis with membranous nephropathy (MN) in stages I or II. Since many cases of drug-induced ANCA-associated glomerulonephritis (AAG) have been reported, we stopped thiamazole and treated with corticosteroid. The MPO-ANCA titer became negative 49 days after the initiation of treatment. Two years after the first treatment, the MPO-ANCA titer became elevated again and was 82 EU. The patient was administered cyclophosphamide and prednisone. However, the MPO-ANCA titer did not decrease. A renal biopsy was performed again 3 years after the first renal biopsy. LM revealed no crescentic formation but demonstrated spike formations along the glomerular basement membrane. EM also disclosed subepithelial dense deposits, but less than the first biopsy. The renal biopsy suggested MN in stages II or III. AAG was regarded as inactive after corticosteroid treatment. Therefore, ciclosporin administration was started. In conclusion, we experienced a rare case of AAG complicated with MN. The histopathologic results showed that immunosuppressive therapy seemed to be effective in treating crescentic glomerulonephritis; furthermore, it reduced proteinuria but could not reduce the MPO-ANCA titer.

Serum TNF-related and weak inducer of apoptosis levels in septic shock patients.

Capillary permeability is a tightly regulated feature of microcirculation in all organ beds. In sepsis, this feature is fundamentally altered. We have previously reported elevated levels of angiopoietin-2 in patients with septic shock, and have investigated tumor necrosis factor (TNF)-related and weak inducer of apoptosis (TWEAK), which mediates both angiogenesis and inflammation, in those patients. Enzyme-linked immunoassay was used to measure serum TWEAK levels in 20 patients with septic shock, all of whom were treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX), and in 20 non-septic controls. The TWEAK levels were higher in patients with septic shock (192.8 ± 230.5 pg/mL) than in controls (84.1 ± 28.7 pg/mL, P = 0.043). Between 11 survivors and 10 non-survivors, there was no significant difference in the serum TWEAK levels before the DHP-PMX therapy. During DHP-PMX therapy, however, the serum TWEAK levels were significantly increased in non-survivors (142.2 ± 88.1 pg/mL to 399.0 ± 307.1 pg/mL, P = 0.022). There was a significant correlation between the serum TWEAK levels and white blood cell counts (r = 0.393, P < 0.001), platelet counts (r = 0.418, P < 0.001), or serum CRP levels (r = 0.259, P = 0.029), but there was no correlation between the serum TWEAK levels and blood pressure. The serum TWEAK levels were also correlated with the ratio of angiopoietin-2 to -1 (r = 0.464, P < 0.001). TWEAK may be a suitable marker of disease severity and mortality in septic patients, and TWEAK levels may be associated with vascular permeability via angiopoietin balance.

Angiopoietin balance in septic shock patients with acute lung injury: effect of direct hemoperfusion with polymyxin B-immobilized fiber.

Acute lung injury (ALI) in sepsis is characterized by an increase in microvascular permeability, resulting in pulmonary edema. Several studies have suggested that angiopoietin-1 and -2 play a contributory role in the pathogenesis of ALI. Polymyxin B-immobilized fiber column hemoperfusion is effective for sepsis-induced ALI. We investigated the angiopoietin levels before and after direct hemoperfusion with polymyxin B-immobilized fiber column (PMX) therapy. Enzyme-linked immunoassay was used to measure the serum angiopoietin-1 and -2 levels in 25 patients with septic shock treated with PMX. Eleven of the 25 patients were diagnosed with ALI. There was a significant positive correlation between the angiopoietin-1 level and the PaO(2) /FiO(2) ratio, but there was a significant inverse correlation between the angiopoietin-2 level and the PaO(2) /FiO(2) ratio. The mean angiopoietin-1 level before PMX therapy in the ALI group was significantly lower and the mean angiopoietin-2 level was significantly higher than in the non-ALI group. The mean angiopoietin-1 level of the ALI patients in response to PMX therapy was increased during PMX therapy, but that of the non-ALI patients with newly occurring ALI showed a decreased angiopoietin-1 level. On the other hand, the mean angiopoietin-2 level of the responders was decreased during PMX therapy, but that of patients with newly occurring ALI showed an increased angiopoietin-2 level. This result suggested that each angiopoietin-1 and -2 level may play a role in the pathogenesis of ALI and that PMX therapy ameliorates the angiopoietin balance in patients with ALI in sepsis.

Coincidental finding of Fabry's disease in a patient with IgA nephropathy.

We present the case of a woman with IgA nephropathy and concomitant Fabry's disease. She was referred to our hospital with proteinuria and haematuria. A renal biopsy showed findings indicating IgA nephropathy under light and immunofluorescence microscopy. Electron microscopy, however, showed laminated inclusion bodies characteristic of Fabry's disease. The α-galactosidase activity in her serum was low, and the diagnosis of Fabry's disease was confirmed by genetic analysis. Fabry's disease in a patient with IgA nephropathy is a very rare occurrence, and Fabry's disease diagnosed only by electron microscopy has not been previously reported.

Angiopoietin balance in septic shock patients treated by direct hemoperfusion with polymyxin b-immobilized fiber.

Capillary permeability is a tightly regulated feature of microcirculation in all organ beds; however, in sepsis this feature is fundamentally altered. We previously reported elevated levels of vascular endothelial growth factor and its receptor (fms-like tyrosine kinase-1) in patients with septic shock, then investigated two kinds of angiopoietins in those patients. An enzyme-linked immunoassay was used to measure serum angiopoietin-1 and -2 levels in 12 patients with septic shock who were treated by direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX). The angiopoietin-1 level was lower in patients with septic shock (7.01 +/- 10.08 ng/mL) than in controls (28.24 +/- 11.61 ng/mL, P < 0.001), but the angiopoietin-2 level was higher in septic shock patients (40.83 +/- 30.13 ng/mL vs. 2.47 +/- 1.78 ng/mL, P < 0.001). Between seven survivors and five non-survivors there was no significant difference in angiopoietin-1 levels before DHP-PMX therapy. During DHP-PMX therapy, however, the angiopoietin-2 level was significantly decreased in survivors (31.52 +/- 26.15 ng/mL vs. 17.32 +/- 22.46 ng/mL, P = 0.035). Moreover, at the end of the therapy, the angiopoietin-1 level was significantly lower in non-survivors (1.14 +/- 1.30 ng/mL vs. 10.43 +/- 13.56 ng/mL, P = 0.042), but the angiopoietin-2 level in non-survivors was significantly higher (70.79 +/- 40.47 ng/mL vs. 17.32 +/- 22.46 ng/mL, P = 0.019). The angiopoietin-2 level may be associated with vascular permeability in septic patients, and angiopoietins may be suitable markers of disease severity and mortality.