Shigehiro Uezono

Incidence of ANCA-Associated Primary Renal Vasculitis in the Miyazaki Prefecture: The First Population-Based, Retrospective, Epidemiologic Survey in Japan

Clinicoepidemiological manifestations of the vasculitides differ geographically. According to a nationwide, hospital-based survey in Japan, the prevalence of microscopic polyangiitis (MPA) and/or renal-limited vasculitis (RLV) is much higher than that of Wegeners granulomatosis (WG). However, little is known about the incidence of antineutrophil cytoplasmic autoantibodies (ANCA)-associated primary renal vasculitis (PRV) in Japan. The incidence of PRV was retrospectively determined by a population-based method in Miyazaki Prefecture in Japan between 2000 and 2004. PRV was defined according to the following criteria from the European Systemic Vasculitis Study Group: (1) new patients with WG, MPA, Churg-Strauss syndrome (CSS), or RLV, (2) renal involvement attributable to active vasculitis, and (3) ANCA considered positive if the disease was not histologically confirmed. The numbers of patients with PRV in the years 2000, 2001, 2002, 2003, and 2004 were 9, 9, 9, 16, and 13, respectively. The male to female ratio was 24:32 and the average age was 70.4 +/- 10.9 (mean +/- SD) yr. The estimated annual incidence of PRV was 14.8 (95% confidence interval [CI] 10.8 to 18.9) and 44.8 (95% CI 33.2 to 56.3) per million adults (>15 yr old) and seniors (>65 yr old), respectively. Ninety-one percent of the patients were myeloperoxidase (MPO)-ANCA positive, but none were positive for proteinase 3 (PR3)-ANCA. There were no WG or CSS patients. The incidence of PRV did not differ between Japan and Europe, but WG was not widespread in Japan. Furthermore, the ratio of serum MPO to PR3-ANCA among Japanese with PRV was much higher than that found among European and US patients.

Renal Biopsy in Elderly Patients: A Clinicopathological Analysis

As the numbers of aging patients with manifestations of renal disease increase, the elderly must frequently undergo renal biopsies. This study examined the characteristics of clinicopathological correlations in elderly patients. Medical and clinical records from renal biopsies registered in two hospitals between January 2000 and December 2004 were reviewed. Among 406 patients (female: male 224/182; age 43.9 ± 18.8 years, mean ± SD) who underwent renal biopsies, 61 (15.1%) who were aged 65 years and older (female: male, 29/32; age 72.8 ± 5.2 years) were selected. The elderly usually underwent percutaneous renal biopsies for renal diseases such as nephrotic syndrome (43%) and acute or rapidly progressive renal failure (A/RPRF, 39%). Focal/segmental glomerulosclerosis (23%), minimal change disease (19%), and membranous nephropathy (15%) are frequently diagnosed based on biopsy specimens from patients with nephrotic syndrome. Among patients presenting with A/RPRF, 17 (71%) and 4 (17%) had pauci-immune, MPO-ANCA positive, crescentic glomerulonephritis and interstitial nephritis, respectively, and benefited from therapeutic intervention. Histopathological and pre-biopsy clinical diagnoses differed in nine (15%) patients. The complication rate after biopsy was low (3%). Primary glomerular diseases presenting with nephrotic syndrome and primary crescentic glomerulonephritis associated with rapidly progressive renal failure were the most frequently diagnosed among the elderly who underwent renal biopsy. Percutaneous renal biopsy provides clinically useful information about the elderly because clinical presentation and the predicted diagnosis sometimes vary.

Increased plasma levels of mature adrenomedullin in chronic glomerulonephritis.

Adrenomedullin (AM) is a potent vasodilative and natriuretic peptide that is processed from its precursor as the intermediate form, AM-glycine-COOH (iAM). Subsequently, iAM is converted to the biologically active mature form, AM(1-52)-CONH2 (mAM), by enzymatic amidation. Using immunoradiometric assays that recognize total AM (tAM) and only mAM, we determined the plasma and urinary levels of mAM and iAM in patients with chronic glomerulonephritis (CGN). The plasma mAM concentration was significantly higher in the patients than in the controls (1.8 ± 0.1 vs. 1.3 ± 0.1 fmol/ml, p < 0.01), whereas the plasma iAM concentration of the CGN patients did not significantly differ from that of the controls (9.4 ± 0.5 vs. 8.9 ± 0.5 fmol/ml). Levels of urinary mAM excretion in the patients did not statistically differ from those of the controls (1.6 ± 0.4 vs. 2.0 ± 0.3 fmol/mg creatinine), whereas urinary iAM excretion was significantly lower in the CGN patients (3.7 ± 0.7 vs. 5.6 ± 0.8 fmol/mg creatinine, p < 0.05). Urinary excretion levels of mAM significantly correlated with those of sodium (r = 0.47, p < 0.05), whereas those of iAM did not. In conclusion, the plasma ratio of mAM to iAM is augmented in CGN patients, and mAM appears to be involved in the regulation of sodium. Therefore, determination of the mAM in addition to the tAM concentration is essential in CGN patients.

Factors affecting outcome of intracerebral hemorrhage in patients undergoing chronic hemodialysis.

To date, despite a markedly high incidence of intracerebral hemorrhage (ICH) in patients with end-stage renal disease, only few studies have focused on factors that affect patients prognosis. To elucidate these factors, we retrospectively investigated 22 consecutive patients who had chronic renal failure, were maintained by hemodialysis (HD), had suffered from ICH, and were hospitalized and treated in our institute from 2006 to 2008. Hematoma volume, blood pressure on admission, blood pressure 3 days after ICH onset, and neurological deterioration significantly affected patient mortality. Progression of neurological symptoms during HD was observed often in patients with hematoma of more than 60 mL or in patients with pontine hemorrhages. Age, gender, duration of HD, anti-platelet or anticoagulant therapies, or maximal dose of nicardipine did not affect patients prognosis. Based on this study we conclude that controlling blood pressure on admission and within 3 days after onset of ICH may be the most important factor that would improve patients prognosis. Further, special care might be required for patients with large hematomas (more than 60 mL) or those with brainstem hemorrhages, because progression of neurological symptoms occurs often in such patients.

Four cases of MPO-ANCA-positive vasculitis with otitis media, and review of the literature

Otitis media is one of the common organ injuries that appear during the course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We experienced four patients with myeloperoxidase (MPO)-ANCA-positive AAV with otitis media. All were elderly Japanese women. MPO-ANCA in our patients was reminiscent of microscopic polyangiitis (MPA), although chest computed tomography (CT) scans revealed characteristics of both granulomatosis with polyangiitis (GPA), showing bronchial lesions and nodule formation, and MPA, showing interstitial changes. Whether our cases should be classified as GPA or MPA is a matter of discussion. We detail their profiles, and review previous literature on MPO-ANCA-positive AAV with otitis media.

Successful treatment of non-Hodgkin’s lymphoma with rituximab and dose-adjusted CHOP therapy in a patient with concomitant end-stage renal disease requiring haemodialysis

Although malignancy is a fatal complication of end-stage renal disease (ESRD) requiring haemodialysis, successful treatment of haematological malignancies has been rarely reported. We describe the case of a 64-year-old man who presented with non-Hodgkin’s lymphoma (NHL; clinical stage, IVB) concomitant with ESRD. Before chemotherapy, haemodialysis was initiated, and one course of dose-adjusted CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) therapy followed by eight courses of rituximab therapy were administered according to the performance status and degree of organ dysfunction. Consequently, the patient was disease free for 27 months. Thus, rituximab plus CHOP combination therapy was effective for NHL concomitant with ESRD.

Glycaemic control is a predictor of infection-related hospitalization on haemodialysis patients: Miyazaki Dialysis Cohort study (MID study).

Although infection is the second leading cause of death in maintenance haemodialysis patients, the effects of glycaemic control on infection in diabetic haemodialysis patients have not yet been examined in detail. We examined the relationship between diabetes or glycemic control and infection‐related hospitalization (IRH) in haemodialysis patients.

Risk of Cerebral Infarction in Japanese Hemodialysis Patients: Miyazaki Dialysis Cohort Study (MID study).

Background/Aims: Predictors including the preventive effects of antiplatelet and anticoagulant drugs on cerebral infarction (CI) events have not yet been clarified in dialysis patients. The aim of the present study was to examine the risk of CI and preventive effects of these drugs in Japanese hemodialysis patients. Methods: Patients receiving maintenance hemodialysis (n=1,551, median age (interquartile range), 69.0 (59.0-78.0) years; 41.5% female) were enrolled in the Miyazaki Dialysis Cohort Study and prospectively followed-up for 3 years. Kaplan-Meier and Coxs regression analyses were used to clarify the risk of CI. Results: Eighty-four patients developed CI at an incidence of 21.5/1000 patients per year. The presence of a previous history of CI, atrial fibrillation (AF), and diabetes mellitus in addition to age were also identified as predictive factors for new CI, whereas no relationship was observed between antiplatelet and/or anticoagulant usage and CI. Furthermore, no significant difference was noted in the frequency of CI events between patients with AF who received warfarin and those who did not. Conclusions: The incidence of CI was higher in dialysis patients with a previous history of CI and AF; however, the preventive effects of antiplatelet/anticoagulant drugs on the development of CI were not evident.