A Prospective Cohort Study of Mineral Metabolism After Kidney Transplantation.

BACKGROUND: Kidney transplantation corrects or improves many complications of chronic kidney disease, but its impact on disordered mineral metabolism is incompletely understood. METHODS: We performed a multicenter, prospective, observational cohort study of 246 kidney transplant recipients in the United States to investigate the evolution of mineral metabolism from pretransplant through the first year after transplantation. Participants were enrolled into 2 strata defined by their pretransplant levels of parathyroid hormone (PTH), low PTH (\u3e65 to ≤300 pg/mL; n = 112), and high PTH (\u3e300 pg/mL; n = 134) and underwent repeated, longitudinal testing for mineral metabolites. RESULTS: The prevalence of posttransplant, persistent hyperparathyroidism (PTH \u3e65 pg/mL) was 89.5%, 86.8%, 83.1%, and 86.2%, at months 3, 6, 9, and 12, respectively, among participants who remained untreated with cinacalcet, vitamin D sterols, or parathyroidectomy. The results did not differ across the low and high PTH strata, and rates of persistent hyperparathyroidism remained higher than 40% when defined using a higher PTH threshold greater than 130 pg/mL. Rates of hypercalcemia peaked at 48% at week 8 in the high PTH stratum and then steadily decreased through month 12. Rates of hypophosphatemia ( CONCLUSIONS: Persistent hyperparathyroidism is common after kidney transplantation. Further studies should determine if persistent hyperparathyroidism or its treatment influences long-term posttransplantation clinical outcomes.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0

Impact of aprotinin and renal function on mortality: a retrospective single center analysis

<p>Abstract</p> <p>Background</p> <p>An estimated up to 7% of high-risk cardiac surgery patients return to the operating room for bleeding. Aprotinin was used extensively as an antifibrinolytic agent in cardiac surgery patients for over 15 years and it showed efficacy in reducing bleeding. Aprotinin was removed from the market by the U.S. Food and Drug Administration after a large prospective, randomized clinical trial documented an increased mortality risk associated with the drug. Further debate arose when a meta-analysis of 211 randomized controlled trials showed no risk of renal failure or death associated with aprotinin. However, only patients with normal kidney function have been studied.</p> <p>Methods</p> <p>In this study, we look at a single center clinical trial using patients with varying degrees of baseline kidney function to answer the question: Does aprotinin increase odds of death given varying levels of preoperative kidney dysfunction?</p> <p>Results</p> <p>Based on our model, aprotinin use was associated with a 3.8-fold increase in odds of death one year later compared to no aprotinin use with p-value = 0.0018, regardless of level of preoperative kidney dysfunction after adjusting for other perioperative variables.</p> <p>Conclusions</p> <p>Lessons learned from our experience using aprotinin in the perioperative setting as an antifibrinolytic during open cardiac surgery should guide us in testing future antifibrinolytic drugs for not only efficacy of preventing bleeding, but for overall safety to the whole organism using long-term clinical outcome studies, including those with varying degree of baseline kidney function.</p

Complete biopsy-proven resolution of deposits in recurrent proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) following rituximab treatment in renal allograft

Abstract Background Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) is a disease entity classified under the group of “Monoclonal gammopathy-related kidney diseases”, and can recur after transplant. Clinical remission of proteinuria in patients with PGNMIGD has been previously shown following anti-B cell and/or anti-plasma cell therapies. Our case is the first to show complete histologic resolution of the glomerular monoclonal IgG kappa deposits in a case of recurrent PGNMIGD in renal allograft after rituximab and steroid treatment. This is a novel finding and it shows that the deposits are amenable to therapy. This case also highlights the importance of IgG subclass staining in the recognition of the monoclonal nature of the deposits. It is particularly important in PGNMIGD because only 20 to 30% of patients with this disease are reported to have detectable monoclonal gammopathy, and the deposits do not have any organized substructure on electron microscopic examination. Morphologically, they resemble polyclonal immune-type deposits seen in other immune complex glomerulonephritides such as lupus nephritis, infection-associated glomerulonephritis, and membranoproliferative glomerulonephritis (MPGN type I). Case presentation The patient is a 44 year old Caucasian male who received a living unrelated donor kidney transplant for end-stage renal disease diagnosed 7 years before transplant. The reported native kidney biopsy diagnosis was membranoproliferative glomerulonephritis (MPGN) with IgG, C3 and kappa restricted deposits. Fourteen months post-transplant, he presented with abrupt worsening of graft function, proteinuria and serum IgG kappa monoclonal spike. Allograft biopsy was consistent with recurrent PGNMIGD, considering the native kidney diagnosis and interval post-transplant. He underwent plasmapheresis, IV pooled immune globulin, steroid pulse and taper, and anti-CD-20 Rituximab therapy. Patient had gradual decline in proteinuria and complete resolution of the immune deposits on repeat biopsy 3 months later. Unfortunately he subsequently developed chronic antibody-mediated rejection and transplant glomerulopathy and graft failure 34 months post-transplant. Conclusions In a transplant setting, repeat allograft biopsies are frequently performed for graft dysfunction. This provides a good opportunity to study the evolution of the immune deposits following treatment. Our case shows complete histologic resolution of the deposits in allograft PGNMIGD

Multicenter evaluation of a novel endothelial cell crossmatch test in kidney transplantation

BACKGROUND.: Despite their clinical importance, clinical routine tests to detect anti-endothelial cell antibodies (AECA) in organ transplantation have not been readily available. This multicenter prospective kidney transplantation trial evaluates the efficacy of a novel endothelial cell crossmatch (ECXM) test to detect donor-reactive AECA associated with kidney allograft rejection. METHODS.: Pretransplant serum samples from 147 patients were tested for AECA by a novel flow cytometric crossmatch technique (XM-ONE) using peripheral blood endothelial progenitor cells as targets. Patient enrolment was based on acceptance for transplantation determined by donor lymphocyte crossmatch results. RESULTS.: Donor-reactive AECA were found in 35 of 147 (24%) patients. A significantly higher proportion of patients with a positive ECXM had rejections (16 of 35, 46%) during the follow-up of at least 3 months compared with those without AECA (13 of 112, 12%; P\u3c0.00005). Both IgG and IgM AECAs were associated with graft rejections. Mean serum creatinine levels were significantly higher in patients with a positive ECXM test at 3 and 6 months posttransplant. CONCLUSIONS.: XM-ONE is quick, easy to perform on whole blood samples and identifies patients at risk for rejection and reduced graft function not identified by conventional lymphocyte crossmatches. © 2009 by Lippincott Williams & Wilkins