Yuko Shimaya

A case of myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis and concurrent membranous nephropathy

BackgroundMyeloperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (MPO-ANCA-GN) and concurrent membranous nephropathy (MN) are very rare combination. Their causal relationship has been suggested, but not determined.Case presentationA 73-years-old male with 5-year history of proteinuria underwent an operation for his sigmoid colon cancer. Seven months later, he was referred to a nephrology division due to an exacerbating renal function and hypoalbuminemia. Laboratory examination revealed positive MPO-ANCA in the serum. A renal biopsy revealed a necrotizing extracapillary proliferative glomerulonephritis with crescents, demonstrating MPO-ANCA-GN. Whereas, immunofluorescent staining documented granular deposition of immumoglobulin (Ig) G and C3 along the capillary wall and electron microscopy showed subepithelial deposits in the glomerular basement membrane demonstrating MN. Immunofluorescent staining of IgG subclass showed positive IgG1, IgG2, negative IgG3 and weak positive IgG4 suggested the possibility of malignancy-associated MN.ConclusionCombination of MPO-ANCA-GN and MN are rare. Although the causal relationship has been suggested in some cases, we should consider all the possibilities including idiopathic MN and secondary MN associated with malignancy, drug use or infection.

Paroxysmal nocturnal hemoglobinuria in systemic lupus erythematosus: a case report

IntroductionParoxysmal nocturnal hemoglobinuria is an acquired disorder of hemopoiesis and is characterized by recurrent episodes of intravascular hemolysis due to an increased sensitivity to complement-mediated hemolysis. Systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. We report a case of paroxysmal nocturnal hemoglobinuria that developed in a patient with systemic lupus erythematosus and lupus nephritis.Case presentationA 29-year-old Mongolian woman had systemic lupus erythematosus, which manifested only as skin lesions when she was 12 years old. She had leg edema and proteinuria when she was 23 years old, and a renal biopsy revealed lupus nephritis (World Health Organization type IV). She had been treated with steroids and immunosuppressant therapy. At 29, she had headaches, nausea, general fatigue, and severe pancytopenia and was admitted to our hospital. A laboratory evaluation showed hemolytic anemia. Further examination showed a neutrophil alkaline phosphatase score of 46 points, a CD55 value of 18%, and a CD59 value of 78.6%. The results of Ham test and sugar water tests were positive. The constellation of symptoms throughout the clinical course and the laboratory findings suggested paroxysmal nocturnal hemoglobinuria.ConclusionsTo the best of our knowledge, systemic lupus erythematosus with paroxysmal nocturnal hemoglobinuria is very rare. Clinicians should be aware of the association between autoimmune and hematological diseases.

Thrombin Stimulates Synthesis of Macrophage Colony-Stimulating Factor, Granulocyte-Macrophage Colony- Stimulating Factor and Granulocyte Colony-Stimulating Factor by Human Proximal Tubular Epithelial Cells in Culture

Background/Aims: Colony-stimulating factors (CSFs) are well-known hematopoietic growth factors. Although recent studies revealed that CSFs are involved in many inflammatory conditions, the local production of CSFs and its regulation in the kidney is not well elucidated. Therefore, using cultured human proximal tubular epithelial cells (PTEC), we examined the effect of thrombin on CSFs production, since thrombin has been suggested to play an important role in tubulointerstitial injury. Methods: PTEC were incubated with thrombin (0.5–5.0 U/ml) and the effects on the production of macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF) were measured in the cell supernatant by enzyme-linked immunosorbent assay, and the expressions of mRNA were analyzed by quantitative real-time reverse transcription polymerase chain reaction. Using argatroban, a direct thrombin inhibitor, we also examined the specific effect of thrombin. Results: Thrombin 5.0 U/ml significantly stimulated the production of M-CSF (p < 0.01) and G-CSF (p < 0.01), and 1.0 and 5.0 U/ml thrombin significantly stimulated GM-CSF (p < 0.02 and p < 0.01) in a dose-dependent manner. Thrombin 5.0 U/ml increased CSFs (M-CSF, p < 0.005; GM-CSF, p < 0.0005; G-CSF, p < 0.005) in a time-dependent manner. Thrombin also significantly enhanced the mRNA expressions of M-CSF (p < 0.01), GM-CSF (p < 0.05) and G-CSF (p < 0.01). These effects of thrombin were significantly reduced by the addition of argatroban (M-CSF, p < 0.01; GM-CSF, p < 0.01; G-CSF, p < 0.05). Conclusion: We demonstrated that thrombin significantly increased the production of CSFs by PTEC. These data suggest that the local production of CSFs in the tubulointerstitium may affect tubulointerstitial lesions in kidney injury.

An adult case of nephrotic syndrome presenting with pulmonary artery thrombosis: a case report

IntroductionPulmonary artery thrombosis is one of the most important complications in patients with nephrotic syndrome. It is well known among nephrologists, however, that this possibly lethal complication very rarely occurs before the diagnosis of nephrotic syndrome.Case presentationA 21-year-old Japanese woman who had no specific medical history consulted a primary care clinic. Although she had been aware of the edema of her lower extremities for 2 weeks, her chief complaints were palpitations and chest pain, which had started the day before. An electrocardiogram and chest radiograph did not reveal any specific abnormalities. Because her etiology was not clear, she was referred to an emergency division in a hospital 2 days later. Although arterial blood gas analysis did not reveal hypoxemia, computed tomography revealed thrombi of the bilateral pulmonary arteries and left iliac vein. At this point, a laboratory examination confirmed the diagnosis of nephrotic syndrome. Subsequently, she was admitted, and anticoagulant therapy was initiated immediately. The next day, oral corticosteroid therapy was initiated, and an inferior vena cava filter was placed internally. Her proteinuria resolved after 3 weeks of treatment. The prompt and complete response to corticosteroid therapy suggested that minimal change disease was the etiology of the nephrotic syndrome and pulmonary artery thrombosis.ConclusionsAn awareness regarding the complication of pulmonary artery thrombosis in nephrotic syndrome is important not only for nephrologists but for all clinicians. Contrast-enhanced computed tomography is crucial to detect pulmonary artery thrombosis.

Effects of Tridocosahexaenoyl-Glycerol Emulsion on Proteinuria in Rats with Nephrotoxic Serum Nephritis

Background: Docosahexaenoic acid (DHA) is one of the n–3 polyunsaturated fatty acids and an important component of cell membrane phospholipids (PL). Nephrotoxic serum (NTS) nephritis was a worldwide model of the Goodpasture syndrome. We investigated the effects of tridocosahexaenoyl-glycerol (DHA-TG) emulsion on proteinuria in rats with NTS nephritis. Methods: Sixteen male Wistar rats weighing approximately 200 g were used. Twelve rats were treated with NTS via the tail vein and divided into 3 groups (groups A, B, and C). Another 4 rats treated with saline served as controls (group D). DHA-TG and soybean oil emulsions were intraperitoneally administered to the rats in groups A and B, respectively, 24 h prior to NTS injection, and 0, 1, 2, 3, 4, and 5 days after the injection. Saline was administered to the rats in groups C and D in the same manner. All rats were sacrificed on day 6 to obtain plasma and kidney samples. Analyses of urinary protein levels and fatty acid composition of plasma and kidney as well as histological examination of the kidneys were performed. Results: Urinary protein levels in group A were significantly lower than those in group C (35.0 ± 13.3 vs. 79.2 ± 11.8 mg/day on day 5, means ± SE, p < 0.05). DHA levels in the PL fraction of the kidneys in group A were significantly increased compared with those in groups B and C. Conclusions: These results suggest that the DHA-TG emulsion may have beneficial effects on NTS nephritis in the rat.