Add-On Effect of Angiotensin Receptor Blockade (Candesartan) on Clinical Remission in Active IgA Nephropathy Patients Treated with Steroid Pulse Therapy and Tonsillectomy: a Randomized, Parallel-Group Comparison Trial.

BACKGROUND/AIMS: Angiotensin receptor blockers (ARBs) may be beneficial for clinical remission during conventional therapy with tonsillectomy and steroid pulse (TSP) for active IgA nephropathy. METHODS: Seventy-seven patients with active IgA nephropathy were randomly assigned to the control arm with conventional regimen (TSP followed by oral prednisolone) (n = 37) or the ARB arm with conventional regimen plus ARB candesartan for the first 6 months (n = 40). Patients not achieving proteinuria remission at 12 months in either arm were administered candesartan, which was titrated until the 24-month follow-up. The primary endpoints were remission of proteinuria (< 0.3 g/gCr) and hematuria at 12 months. RESULTS: Baseline proteinuria (g/g Cr) were comparable between the control and ARB arm (1.02 vs. 0.97, P = 0.97). Similarly, cumulative remission rates at 6, 12, and 24 months were comparable between the control and ARB arms (37.8% vs. 35% [P = 0.80], 48.7% vs. 38.5% [P = 0.37], 71.4% vs. 51.3% [P = 0.08]). Proteinuria, which was slightly worse in the control arm than in the ARB arm at 6 months, was comparable afterwards (0.20 vs. 0.23 g/g Cr at 12 months; 0.12 vs. 0.13 g/g Cr at 24 months). Significant reductions observed in urinary angiotensinogen were almost comparable between the two treatment arms at both 6 and 12 months. CONCLUSION: Early candesartan treatment combined with TSP may not benefit clinical remission regardless of the blood pressure. ARB titration later during the treatment might provide benefit for patients with active IgA nephropathy.

Expression of MRP2 and MRP3 during liver regeneration after 90% partial hepatectomy in rats.

BACKGROUND: Small-for-size grafts often cause persistent conjugated hyperbilirubinemia in the recipient after adult-to-adult living donor liver transplantation, but the cause has not yet been clarified. In physiologic status, bilirubin is excreted from hepatocytes to the bile canaliculus by means of multidrug resistance protein (MRP) 2 and, in particular circumstances, by means of MRP3 to the sinusoidal space. The aim of this study was to research whether there is any change in bilirubin excretion pattern during liver regeneration with reference to expression of MRP2 and MRP3. METHODS: Sprague-Dawley rats underwent sham operation (n=37), 70% hepatectomy (n=38), or 90% hepatectomy (n=37). The degree of liver regeneration, total and direct bilirubin, protein synthesis, and interleukin (IL)-6 were serially assessed. Expression of MRP2 and MRP3 were semiquantified by Western blotting. RESULTS: The proliferating cell nuclear antigen labeling index indicated rapid liver regeneration after 70% and 90% hepatectomy. Serum levels of total and direct bilirubin increased significantly (P<0.05), and conjugated hyperbilirubinemia was proved only in the 90% hepatectomy group. Coagulation factor VII dipped but increased as early as 12 to 24 hr postoperatively in both hepatectomy groups. Plasma IL-6 levels were significantly increased in the 90% hepatectomy group (P<0.05). Expression of MRP2 was decreased and MRP3 was expressed at 36 and 72 hr postoperatively in the 90% hepatectomy group, whereas no change was observed in MRP expression in the 70% hepatectomy group. CONCLUSIONS: During liver regeneration after critical hepatectomy such as 90% hepatectomy, decrease of MRP2 and expression of MRP3 may play an important role in postoperative hyperbilirubinemia.

Influence of cold ischemia time and graft transport distance on postoperative outcome in human liver transplantation.

PURPOSE: The association between hepatic allograft cold ischemia time (CIT) and graft transport distance (GTD) in human liver transplantation was examined by investigating whether extended graft transportation prolongs the CIT and adversely affects graft survival. METHODS: We retrospectively analyzed 186 consecutive orthotopic liver transplants (OLTs) done between May 1997 and July 1998. The number of miles from the donor hospital to the University of Pittsburgh Medical Center in a straight line was measured in each case, and defined as the GTD. The OLTs were divided into two groups according to whether the GTD was 200 miles. The latter group was then subdivided into groups of GTD 200-400 miles, GTD 400-600 miles, and GTD >600 miles. The CIT and graft outcome within 90 days after OLT were assessed. RESULTS: Extended GTD prolonged the CIT ( P < 0.001). The rate of hepatic allograft loss in the long GTD group was significantly higher than that in the short GTD group ( P = 0.018). When the OLTs were subdivided according to GTD, the CIT increased and graft survival decreased as the GTD extended. Hepatic allograft transportation for a long distance prolonged the CIT and decreased the graft survival rate. CONCLUSION: Since prolonged CIT is a major risk factor, avoiding long-distance graft transportation is recommended when the donor risk factors are high.