Eicosapentaenoic Acid and Prevalence of Cardiovascular Disease in Hemodialysis Patients.

Eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio showed inverse associations with cardiovascular disease (CVD) in general population. However, this has not been examined enough in dialysis patients. We cross-sectionally investigated the relationship between EPA/AA ratio and prevalence of CVD in 321 chronic hemodialysis patients (64 ± 11 years old; 110 women; dialysis vintage 10 ± 8 years) in an urban area of Tokyo. CVD was defined as a composite of ischemic heart disease, ischemic stroke and hemorrhagic stroke. The frequency of dietary fish intake was also examined. Logistic regression was used to quantify the association of EPA/AA ratio with CVD. EPA/AA ratio was 0.31 ± 0.19 and 154 patients (48%) consumed fish once or less weekly. One hundred and thirty patients (41%) had CVD, including 65 with ischemic heart disease, 70 with ischemic stroke, and 20 with hemorrhagic stroke. Age (odds ratio [OR], 1.04; P = 0.01), hypertension (OR, 2.25; P = 0.002), and dialysis vintage (OR, 1.04; P = 0.02) were associated with CVD; however, EPA/AA was not after adjustment for other risk factors. A similar relationship was observed between fish intake and CVD prevalence. We did not find any significant association between EPA/AA ratio and prevalence of CVD, although traditional risk factors such as age, hypertension and dialysis vintage were associated with CVD. These results might have been influenced by the fact that only a small proportion of our patients showed a high EPA/AA ratio.

Changes in nephritogenic serum galactose-deficient IgA1 in IgA nephropathy following tonsillectomy and steroid therapy.

BACKGROUND: Recent studies have shown that galactose-deficient IgA1 (GdIgA1) has an important role in the pathogenesis of IgA nephropathy (IgAN). Although emerging data suggest that serum GdIgA1 can be a useful non-invasive IgAN biomarker, the localization of nephritogenic GdIgA1-producing B cells remains unclear. Recent clinical and experimental studies indicate that immune activation tonsillar toll-like receptor (TLR) 9 may be involved in the pathogenesis of IgAN. Here we assessed the possibility of GdIgA1 production in the palatine tonsils in IgAN patients. METHODS: We assessed changes in serum GdIgA1 levels in IgAN patients with clinical remission of hematuria and proteinuria following combined tonsillectomy and steroid pulse therapy. Further, the association between clinical outcome and tonsillar TLR9 expression was evaluated. RESULTS: Patients (n = 37) were divided into two groups according to therapy response. In one group, serum GdIgA1 levels decreased after tonsillectomy (59%) alone, whereas in the other group most levels only decreased after the addition of steroid pulse therapy to tonsillectomy (41%). The former group showed significantly higher tonsillar TLR9 expression and better improvement in hematuria immediately after tonsillectomy than the latter group. CONCLUSIONS: The present study indicates that the palatine tonsils are probably a major sites of GdIgA1-producing cells. However, in some patients these cells may propagate to other lymphoid organs, which may partially explain the different responses observed to tonsillectomy alone. These findings help to clarify some of the clinical observations in the management of IgAN, and may highlight future directions for research.

AP-VAS 2012 case report: two patients with rheumatoid arthritis suspected of relapsed microscopic polyangiitis after initiation of dialysis.

We report two patients with rheumatoid arthritis (RA) who were suspected of microscopic polyangiitis during maintenance dialysis. Case 1 was a 52-year-old woman with RA diagnosed at the age of 38 years and treated successfully with gold compounds. At the age of 43 years, she presented with progressive renal dysfunction and abnormal urine sediments, and a renal biopsy revealed crescentic nephritis with advanced glomerular sclerosis. Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) was not measured on that occasion. She reached end-stage renal failure within 4 months and started peritoneal dialysis. Eight years later, soon after she was switched to hemodialysis, she developed fever of unknown origin. MPO-ANCA was elevated to 37 EU, although there were no other signs or symptoms suggestive of vasculitis. After taking prednisolone orally (10 mg/day), her fever withdrew, and MPO-ANCA became undetectable. Case 2 was a 71-year-old woman with RA diagnosed at the age of 60 years and treated with gold compounds. She developed renal failure of unknown cause (no biopsy was performed), and started hemodialysis at the age of 69 years. One year later, she presented with fever and subsequently developed cough with hemoptysis. MPO-ANCA was elevated to 62 EU. Treatment with azathioprine 50 mg and prednisolone 35 mg daily brought remarkable clinical improvement, and MPO-ANCA became undetectable. These cases highlight the importance of measuring ANCA even in RA patients on dialysis who present with fever of unknown origin or with underlying kidney disease of uncertain etiology.

Experimental evidence of cell dissemination playing a role in pathogenesis of IgA nephropathy in multiple lymphoid organs.

BACKGROUND: Since the pathogenesis of immunoglobulin A (IgA) nephropathy (IgAN) remains unclear, the rationale for current IgAN therapies is still obscure. Recent studies have shown that galactose-deficient IgA1 (GdIgA1) plays a critical role in the pathogenesis of IgAN and can be a non-invasive IgAN biomarker, although the origin of the pathogenic cells producing GdIgA1 is unknown. We examined the cell types and localization of pathogenic cells in IgAN-prone mice. METHODS: We transplanted bone marrow (BM) or spleen cells with or without specific cell types from IgAN-prone mice, which have many features similar to human IgAN, to identify cell types responsible for the IgAN phenotype and to determine their localization. RESULTS: BM transplantation and whole spleen cell transfer from IgAN-prone mice reconstituted IgAN in normal and severe combined immunodeficiency mice. Depletion of CD90(+) spleen cells had no affect on reconstitution, whereas CD19(+) B cells from the spleen were sufficient to reconstitute IgAN in both recipients. CONCLUSIONS: These results indicate that CD19(+) B cells, which can regulate nephritogenic IgA production in a T-cell-independent manner, are responsible for the disease and are disseminated in peripheral lymphoid organs.

Tonsillar TLR9 expression and efficacy of tonsillectomy with steroid pulse therapy in IgA nephropathy patients.

BACKGROUND: Patients with IgA nephropathy (IgAN) often show aggravation of renal injury with macroscopic hematuria after mucosal infections, especially tonsillitis. We previously demonstrated the important role of mucosal Toll-like receptor 9 (TLR9) activation in the pathogenesis of murine IgAN. Moreover, a single nucleotide polymorphism (SNP) in TLR9 was significantly associated with pathological severity in human IgAN. In this study, we investigated correlations between tonsillar TLR9 messenger RNA expression, TLR9 SNP genotypes and clinical outcomes following tonsillectomy with steroid pulse therapy (SPT) in IgAN patients. METHODS: Tonsillar TLR9 expression was examined in IgAN (n = 49) and control (n = 15) patients who had undergone tonsillectomy. The correlations between tonsillar TLR9 expression level, TLR9 SNP genotypes and clinical outcomes after tonsillectomy with SPT were examined. RESULTS: High expression of tonsillar TLR9 was observed in ∼23% of IgAN patients. These patients showed stronger and earlier remission of hematuria and proteinuria than those with low TLR9 expression. Patients with the TT genotype of TLR9 SNP (rs352140) had more severe renal damage than those with other genotypes. Patients whose serum IgA level decreased more than average after tonsillectomy (large ΔIgA) showed higher cumulative remission rates of proteinuria than patients with a smaller decrease in these levels (small ΔIgA). CT/CC genotypes were more dominant and tonsillar TLR9 expressions significantly higher in large ΔIgA patients than in small ΔIgA patients. CONCLUSION: In IgAN patients, expression levels of tonsillar TLR9 and TLR9 SNP were well correlated with the efficacy of tonsillectomy with SPT.