Effect of lanthanum carbonate vs. calcium carbonate on serum calcium in hemodialysis patients: a crossover study.

BACKGROUND: Lanthanum carbonate (LC) is a non-calcium-containing phosphate binder and shows a comparable effect with other phosphate binders on hyperphosphatemia in dialysis patients. LC also contributes to a reduced oral calcium load compared with calcium carbonate (CaC) treatment. However, no crossover studies which compare the influence on serum calcium level between treatments with LC and CaC in hemodialysis (HD) patients have been carried out. METHODS: After washout for 2 weeks, 50 patients on HD were randomized (1 : 1) to receive LC or CaC for 3 months. Thereafter, patients underwent a second 2-week washout period and were switched to the alternative binder for the next 3 months. Mineral and bone metabolism markers were measured with the changes of vitamin D doses. RESULTS: The serum phosphate level showed a similar decrease from baseline to 3 months in both groups. During the study periods, hypercalcemia was observed only in patients taking CaC. The dose of vitamin D analogue was increased more frequently in the patients of the LC group compared with LC group. The iPTH level showed a significant decrease in the CaC group, but not in the LC group. Serum levels of BAP, TRAP5b, and ALP were significantly elevated in the LC group, whereas the FGF-23 level showed a significant decrease. CONCLUSION: LC effectively reduced the serum phosphate level (like CaC) and allowed the vitamin D analogue dosage to be increased without hypercalcemia in HD patients. LC is one of the useful phosphate binders without hypercalcemia. (UMIN-CTR registration number: UMIN000002331).

Comparison of the effects of intravenous methylprednisolone pulse versus oral prednisolone therapies on the first attack of minimal-change nephrotic syndrome in adults.

AIM: Minimal-change nephrotic syndrome (MCNS) is characterized by a good response to corticosteroid, but a high incidence of relapse. We compared the effect of intravenous methylprednisolone pulse plus oral prednisolone therapy (pulse group) with that of conventional oral prednisolone alone therapy (oral group) on the responsiveness and relapse in the first attack of adult-onset MCNS patients. METHODS: Eighty-one adult patients with biopsy-proven MCNS, who were previously untreated and admitted to our hospital with their first attack of nephrotic syndrome, were analyzed retrospectively. They were arbitrarily assigned to either pulse group (n = 29, 1000 mg of methylprednisolone intravenously for 3 days, and then oral prednisolone 30 to 40 mg daily for 4 to 8 weeks) or oral group (n = 52, oral prednisolone 1 mg/kg daily for 4 to 8 weeks). We compared the time to response and relapse between the two groups. RESULTS: Time to steroid response was significantly shorter in the pulse group compared with the oral group (15.2 ± 10.2 vs 26.7 ± 17.6 days, P = 0.03). In 74 patients who reached remission within 12 weeks (pulse vs oral groups; 86.2% vs 96.2%, ns), the time to relapse was not different between two groups but the relapse rate was significantly higher in the pulse group (pulse vs oral groups; 60% vs 35%, P = 0.038). Kaplan-Meier analyses revealed that both complete remission rates within 4 weeks of the initial steroid therapy and relapse rate within 12 months after attaining remission were significantly higher in the pulse group than the oral group. In the Cox regression model, intravenous methylprednisolone pulse therapy had a significant effect on relapse (hazard ratio, 2.39 (95% confidence interval 1.11-5.15), P = 0.026). CONCLUSION: Intravenous methylprednisolone pulse followed by oral prednisolone therapy shows an earlier responsiveness but a much more frequent relapse compared with conventional oral prednisolone alone therapy for the first attack of adult-onset MCNS.

Recent therapeutic strategies improve renal outcome in patients with IgA nephropathy.

BACKGROUND/AIMS: Various treatment options for IgA nephropathy (IgAN) have been developed, particularly over the past decade. Nevertheless, whether such therapeutic interventions improve actual renal outcome as compared with previous therapies remains obscure. METHODS: We examined data from 304 patients with IgAN whose serum creatinine value at renal biopsy was <2.0 mg/dl and who had been followed up for >12 months. We assigned the patients to groups according to the period of diagnosis (group E, between 1981 and 1995, n = 130; group L, between 1996 and 2006, n = 174). RESULTS: Significantly more patients had received steroid therapy and renin-angiotensin system inhibitors (RAS-I) in group L than in group E (steroid 51.7 vs. 15.4%, p < 0.001; RAS-I 42.0 vs. 1.5%, p < 0.001). Forty patients overall reached end-stage renal disease (ESRD) within 81.9 +/- 55.1 months of observation. Kaplan-Meier analysis showed that the 10-year renal survival rate of group L persisted and significantly differed from that of group E (95.7 vs. 75.2%, p = 0.005). The Cox proportional hazards model adjusted for known prognostic markers demonstrated that initial therapeutic interventions in group L prevented ESRD, with a hazard ratio of 0.29 (95% CI 0.11-0.76, p = 0.011). CONCLUSION: Although this study is not a prospective trial, our results indicate that aggressive therapeutic intervention for IgAN over the past decade has improved actual renal outcome.

[Minimal change nephrotic syndrome complicated with recurrence of malignant thymoma: an interesting case with remission due to steroid therapy of both nephrotic syndrome and thymoma].

A 65-year-old man was admitted to our hospital with abdominal fullness and leg edema in April 2005. Diabetes mellitus and hypertension that had been diagnosed in 1990 were well-controlled with oral hypoglucemic drug. He presented with malignant thymoma accompanied by multiple metastases in the right thoracic space in December 2000. He was treated with total thymectomy, combined with chemotherapy (cisplatin + vinorelbin) and hyperthermia. This strategy obviously reduced the tumor mass. However, CT scans showed multiple recurrences of thymoma in December 2004 and abdominal fullness and leg edema appeared shortly thereafter. Laboratory findings revealed proteinuria (over 10 g/day), hypoalbuminemia, hyperlipidemia and renal dysfunction. A kidney biopsy revealed minor glomerular abnormality. He was diagnosed with minimal change nephrotic syndrome (MCNS) complicated with the recurrence of malignant thymoma. Corticosteroid therapy was started, but dialysis was transiently required to protect against oliguric acute renal failure. Three weeks after the initiation of steroid therapy, the proteinuria was improved to less than 1.0 g/day and renal function returned to within the normal range. Subsequent corticosteroid combined with immunosuppressive therapy resulted in good control of his nephrotic syndrome (NS) without recurrence. There have been a few case reports showing NS complicated with malignant thymoma. Among these, several cases with MCNS occurred after thymectomy for malignant thymoma. Interestingly, both the thymoma mass and high pre-treatment vascular endothelial growth factor (VEGF) levels decreased as NS improved with steroid therapy. These findings suggest that VEGF also might have been associated with the onset of NS in this patient.

Outcome of ANCA-associated primary renal vasculitis in Miyazaki Prefecture.

OBJECT: We examined the prognosis of patients with onset of new primary renal vasculitis (PRV) in Miyazaki Prefecture. PATIENTS AND METHODS: We enrolled and followed-up 56 patients (age, 70.4 +/- 10.9 years, mean +/- SD) with onset of new PRV between January 2000 and December 2004, for a median of 24 months. Patients with PRV were defined according to the EUVAS (European Systemic Vasculitis Study Group) criteria. Outcome and factors predicting unfavorable outcome of death were examined. RESULTS: Among the patients, 25% (n=14) required dialysis therapy immediately at the start of immunosuppressive therapy and of these, renal function recovered in only 3 and 6 died during the first admission. On the other hand, 75% (n=42) did not require immediate dialysis, but 8 patients were introduced to dialysis therapy thereafter. At the end of follow-up, 26 (46%) had survived without dialysis, 10 (18%) were dependent on dialysis and 20 (36%) had died. Infection was the major cause of death (n=11) . The Cox proportional hazards model showed that the presence of lung lesions and immediate dialysis therapy conferred poorer survival rates (HR, 3.32, 95% CI, 1.14 to 9.71; HR 2.73, 95% CI, 1.03 to 7.23, respectively). CONCLUSION: A poor survival rate is independently associated with the presence of lung lesions and advanced renal failure at the start of immunosuppressive therapy in patients with PRV. Half of the deaths were due to infection. Thus, PRV should be identified at an early stage and the treatment protocol should prevent infectious complications. These measures should improve the prognosis of patients with PRV.

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 Wegener's 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.

Effect of sevelamer on dyslipidemia and chronic inflammation in maintenance hemodialysis patients.

BACKGROUND: Hemodialysis (HD) patients often experience cardiovascular events, that might be related to altered calcium-phosphate metabolism, dyslipidemia, and chronic inflammation in addition to hypertension. Sevelamer, a non-calcium-containing phosphate binder, may improve the lipid profile of HD patients. However, the influence of sevelamer on chronic inflammation has not been clarified. METHODS: We enrolled 36 maintenance HD patients with a serum calcium (Ca) or phosphate (P) level constantly greater than 9.5 mg/dL and 5.5 mg/dL, respectively. The dose of sevelamer was titrated to achieve a serum Ca and P in the target ranges. The study period was 24 weeks. Patients underwent the following measurements: bone mineral markers, lipids, and a high-sensitivity C-reactive protein (hs-CRP). RESULTS: In the 28 patients who completed the study, sevelamer significantly reduced the mean non-high-density lipoprotein cholesterol (non-HDL-C) level by 15% and 20% (p < 0.0001) after 12 and 24 weeks, respectively, in addition to reducing the serum P level and Ca x P product. Similarly, there was a significant reduction of the serum hs-CRP level after 12 and 24 weeks [median at baseline: 1.03 mg/dL (interquartile range 0.26-3.98 mg/dL) versus 0.57 (0.17-1.47) and 0.38 (0.16-1.03), respectively, p = 0.0259]. The reduction rate of hs-CRP was significantly correlated with those of non-HDL-C (r = 0.451, p < 0.0401) and P (r = 0.453, p < 0.0008) CONCLUSION: Hs-CRP levels were reduced by sevelamer administration, as well as non-HDL-C, P, and the Ca x P product. Sevelamer may have an anti-inflammatory effect, in addition to lowering phosphate and lipid levels in HD patients.