Ryuichiro Kumasaka

Nephrotic syndrome associated with interferon-β-1b therapy for multiple sclerosis

A 43-year-old woman with multiple sclerosis (MS) had nephrotic syndrome 21 months after starting treatment with interferon (IFN)-β-1b (subcutaneous administration). She had taken no drug except for the IFN-β-1b. Because nephrotic syndrome may be induced by IFN therapy, the IFN was stopped. Percutaneous renal biopsy revealed that she had minimal change nephrotic syndrome. As nephrotic-range proteinuria, hypoalbuminemia, and general edema were worsening even 2 weeks after cessation of the drug, oral corticosteroid therapy (prednisolone 40 mg/day) was started. The nephrotic syndrome was treated successfully with prednisolone. The dosage of prednisolone was tapered, without a relapse, and then the corticosteroid therapy was stopped. IFN-β-1b therapy was then resumed, and the patient is in remission for both nephrotic syndrome and MS. Though proteinuria and nephrotic syndrome is a rare adverse effect of IFN-β-1b therapy, physicians treating MS patients with this agent should pay careful attention to new clinical symptoms and laboratory findings.

Extracellular matrix metalloproteinase inducer is expressed in the proximal tubular epithelial cells of the human kidney

Aim:  Matrix metalloproteinases (MMP) affect matrix remodelling, and extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to increase the levels of several MMP. However, the expression of EMMPRIN in the human kidney and its regulatory mechanisms are not well known. In this study, we examined EMMPRIN expression in the human kidney with the biopsied specimens, cultured proximal tubular epithelial cells (PTEC) and human mesangial cells (HMC).

Thrombin enhances the production of monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 in cultured rat glomerular epithelial cells

BACKGROUND Glomerular crescents play an important role in progressive glomerular injury. The lesions consist of epithelial cells, macrophages and deposits of fibrin and extracellular matrix. Monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) are members of chemokine subfamilies. MCP-1 and MIP-2 are potent chemoattractant leukocyte cytokines, and they may be involved in crescent formation. Thrombin participates in fibrin formation. We hypothesized that thrombin stimulates the production of MCP-1 and MIP-2 by glomerular epithelial cells (GECs). METHODS Cultured rat GECs from the 19th to the 24th passage were used. We incubated GECs with or without thrombin to examine the effect of thrombin on the production of MCP-1 and MIP-2. The levels of MCP-1 and MIP-2 were measured in the cell supernatants by enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of MCP-1 and MIP-2 were analysed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). We also examined the inhibitory effect of argatroban, a synthetic thrombin inhibitor, and prednisolone in the production of MCP-1 and MIP-2 stimulated by thrombin. RESULTS Thrombin stimulated the production of MCP-1 and MIP-2 in a dose- and time-dependent manner. Thrombin also enhanced the mRNA expressions of MCP-1 and MIP-2 in the GECs. The stimulating effect of thrombin on the production of MCP-1 and MIP-2 was inhibited by the addition of argatroban or prednisolone. CONCLUSIONS We demonstrated a novel role of thrombin: it stimulates the production of MCP-1 and MIP-2 by GECs. It is clinically important that the inhibition of these chemokines leads to the improvement of crescentic glomerulonephritis. Anti-thrombin drugs and prednisolone may be useful in treating crescentic glomerulonephritis.

Roxithromycin inhibits transforming growth factor-β production by cultured human mesangial cells

Background:  Transforming growth factor‐β (TGF‐β) plays an important role in progression of renal injury. However, few materials which inhibit TGF‐β have been known. Roxithromycin (ROX), macrolide antibiotics, is known to have anti‐inflammatory, immunomodulatory and tissue reparative effects besides its bacteriostatic activity, although the exact mechanism of its anti‐inflammatory and immunomodulatory effects was not defined. We examined the effect of ROX on production of TGF‐β and type IV collagen by cultured human mesangial cells (HMC).

Beneficial effect of neutrophil elastase inhibitor on anti‐Thy1.1 nephritis in rats

Background:  Neutrophil elastase, one of the proteinases released by neutrophils, plays an important role at the sites of inflammation and was reported to be involved in the pathogenesis of glomerulonephritis. Sivelestat is a selective neutrophil elastase inhibitor used for acute lung injury associated with systemic inflammatory response syndrome. There have been few reports on the effects of sivelestat on renal disease.

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.

Systemic lupus erythematosus and blood type

A 26-year-old woman presented with proteinuria and marked oedema. Laboratory test results were indicative of systemic lupus erythematosus with lupus nephritis. Blood typing showed her to have blood type AB (fi gure, A). However, she said that her blood type had been type A. Renal biopsy showed lupus nephritis (type IV) with crescents. She was treated with 0·5 g daily methylprednisolone pulse therapy and 40 mg oral prednisolone daily. Laboratory data (anti-DNA antibody and complements) improved. Blood typing after treatment showed her to have blood type A. We thought that the agglutinin to anti-B antibodies might be a result of her systemic lupus erythematosus. Before treatment, our patient may have had agglutinins that crossreacted to anti-B antibodies to induce agglutination. Lancet 2006; 368: 1022

Acute Tubulointerstitial Nephritis with Antineutrophil Cytoplasmic Antibody

We present a case of acute tubulointerstitial nephritis that developed in a 77-year-old woman who had a high titer of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA). The constellation of clinical, laboratory and histopathologic findings suggested idiopathic acute tubulointerstitial nephritis. Of interest, no drugs were found to be responsible. Therefore, MPO-ANCA itself might play a causative role in the development of acute tubulointerstitial nephritis.

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.