BackgroundThe study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN).MethodsPatients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria.ResultsDuring 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01–8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission.ConclusionsThe results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified.

Our evidence-based histologic classification can identify the magnitude of the risk of progression to ESRD and is useful for predicting long-term renal outcome in IgAN.

SummaryChronic kidney disease (CKD) is a major and serious risk factor for cardiovascular disease (CVD). Continuous hypoxia due to hypoperfusion in peritubular capillaries is one of the factors aggravating CKD, but evaluation of perfusion in this region is difficult using clinically available imaging methods. Since the second-generation ultrasound contrast agent Sonazoid TM has a stable shell, it enables visualization of the renal vasculature for a long period of time. We therefore evaluated changes in contrast-enhanced ultrasound (CEUS) imaging with Sonazoid TM in CKD patients.Sonazoid TM was used in 85 CKD patients and 5 control subjects, and images were recorded for 10 minutes. Time-intensity curves were generated from the images of 62 time points in both cortex and medulla.In control samples, contrast enhancement spread from the hilar portion to the periphery along the direction of arterial flow, and renal cortex and medulla were then enhanced in sequence. Enhancement was maximal soon after, then gradually decreased, but was still visible at 600 seconds. In CKD patients, renal contrast enhancement was attenuated in both cortex and medulla. On time-intensity curves, the attenuation of enhancement was composed of delayed rising, reduction of peak, and acceleration of decay in both cortex and medulla with progression of renal dysfunction. No side effects of the contrast agent were observed in any subjects.The attenuation of renal contrast enhancement observed in CKD patients appears to reflect disturbance of perfusion in peritubular capillaries. CEUS with Sonazoid TM is a useful and safe means of visualizing the renal microvasculature. (Int Heart J 2010; 51: 176-182)

Preprandial administration provided a more stable absorption profile of cyclosporine compared with postprandial administration. From the correlation with AUC 0-4 , we concluded that C 2 , and not C 0 , is a reliable marker for monitoring cyclosporine exposure.

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BackgroundLupus nephritis class III or IV is associated with a poor prognosis for both patient and renal survival. Recommendations for the management of lupus nephritis have recently been established, and changing therapies is recommended for patients who do not respond adequately to induction therapy. However, it remains a major challenge to determine when to switch the treatment. In this study, we identified early prognostic factors capable of predicting poor renal outcome as well as overall damage accrual in patients with lupus nephritis class III or IV.MethodsEighty patients with biopsy-proven lupus nephritis class III or IV were retrospectively recruited and divided into two groups: those with complete renal response (CR) or non-CR at 3 years after induction therapy. We investigated when clinical responses were obtained at each observational period from baseline to year 3. Clinical responses were divided into three groups: CR, partial renal response (PR), and non-PR. Furthermore, patients were assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) and cumulative dose of corticosteroid for 3 years.ResultsForty-four patients with CR and thirty-six with non-CR were enrolled. The cumulative CR rate was 85.0%. PR rates of patients with CR were significantly higher than those with non-CR from week 12 (p < 0.01). We identified the achievement of PR at 12 weeks as an independent predictor (OR 3.57, p = 0.03) by multivariate analysis. We next divided all patients into two groups according to PR achievement at week 12. The cumulative CR rate of the patients who achieved PR at week 12 was significantly higher than that of those who did not (96.5% vs 69.2%, p < 0.001). Furthermore, a significantly higher SDI and cumulative dose of corticosteroid were seen in the patients who did not achieve PR at week 12 than in those who did, regardless of their CR status, at year 3.ConclusionsLack of PR at week 12 predicts a lower likelihood of achieving CR at 3 years and a higher SDI.

Lipoprotein glomerulopathy (LPG) is a hereditary disease characterized by lipoprotein thrombi in the glomerulus, hyperlipoproteinemia, and a marked increase in serum apolipoprotein E (APOE). More than 12 APOE mutations have been identified as causes of LPG, and APOE-Sendai (Arg145Pro) mutation was frequently detected in patients from the eastern part of Japan including Yamagata prefecture. Recently, effective therapy with intensive lipid-lowering agents was established, and epidemiologic data are required for early diagnosis. We determined the haplotype structure of APOE-Sendai in 13 patients from 9 unrelated families with LPG, and found that the haplotype of all APOE-Sendai mutations was identical, suggesting that APOE-Sendai mutation is common in Japanese patients probably through a founder effect. We also studied the gene frequency of APOE-Sendai in 2023 control subjects and 418 patients receiving hemodialysis in Yamagata prefecture using the TaqMan method, but did not identify any subjects carrying the mutation, indicating that it is very rare in the general population even in the eastern part of Japan. In addition to APOE mutation, other genetic and/or epigenetic factors are considered to be involved in the pathogenesis of LPG because of its low penetrance. The patients did not have a common haplotype of the counterpart APOE allele, and some patients had the same haplotype of the counterpart APOE allele as the asymptomatic carriers. These results suggest that the counterpart APOE allele is not likely associated with the onset of LPG. Further study is required to clarify the pathogenesis of LPG.