Search

Background We aimed to develop an adapted information-motivation-behavioral skills (IMB) model to describe barriers and facilitators for adherence and self-management among kidney transplant recipients. Methods We conducted a review of literature about kidney transplant recipients' knowledge, perceptions, and experiences and organized our results using the IMB framework. We then conducted interviews with transplant recipients and transplant providers to supplement our literature search. Results Our proposed adaption of the IMB model describes informational, motivational, and behavioral skills barriers and facilitators for medication adherence and self-management among kidney transplant recipients. Moderating factors influence not only behavioral skills, but also recipients' understanding of information and motivation to adhere and practice self-management. Conclusion By using the IMB model to organize current research and interviews with recipients and providers, we developed an adapted model for medication adherence and self-management. Results are promising to impact future educational and behavioral interventions for kidney transplant recipients.

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.

Background Endothelial microparticles (EMPs) are membrane vesicles shed from endothelial cell in response to injury, activation or apoptosis. Kidney transplantation (KTx) is the treatment of choice for patients with end stage kidney disease (ESKD). The aim of this study was to analyze changes in EMP and serum creatinine (SCr) in patients following KTx. Methods Blood was periodically collected from patients before (pre-KTx) and after KTx for two months. EMPs were identified as CD31 + /CD42b − microparticles and quantified by fluorescence-activated cell scanning. Results This study included 213 KTx, 14 kidney/pancreas (KPTx) recipients and 60 healthy donors prior to donation. The recipients were divided into 5 groups based on the cause of ESKD. No differences in the quantity of circulating EMP were seen in the pre-KPTx or KTx recipient sera and healthy donor sera. Patients with ESKD secondary to diabetes mellitus, obstructive/inherited kidney disease and autoimmune disease had a decrease in both circulating EMP and SCr by day 60 after KTx. Conclusion Reduction in both circulating EMP and SCr was seen after kidney KTx in patients with selective ESKD.

Proliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMIGD) is a recently recognized glomerular disease. Light microscopy usually resembles membranoproliferative glomerulonephritis. Glomerular deposits are mostly IgG3 κ; however, unlike in the usual forms of monoclonal immunoglobulin deposition disease, extraglomerular deposits are absent. If PGNMIGD is secondary to the glomerular deposition of circulating monoclonal IgG, it is expected to recur in kidney allografts with the same pattern of monoclonal IgG deposition. We reviewed our kidney biopsy files between January 1, 2003, and January 4, 2010, and identified 21 biopsy specimens with PGNMIGD, mostly with glomerular IgG3 κ deposits. Of the 21 biopsy specimens, 4 were from kidney allografts; 2 were recurrent and the other 2 were de novo diseases. Recurrent PGNMIGD develops rapidly, causing proteinuria. This rapid recurrence of PGNMIGD in kidney allografts provides further proof that PGNMIGD is secondary to the glomerular deposition of circulating monoclonal IgG.

This article provides an update of the literature on the use of extended release once-daily tacrolimus in solid organ transplant recipients.Medication nonadherence occurs in a substantial proportion of patients posttransplant and is associated with worse outcomes. Multiple daily dosing is associated with an increased risk for nonadherence. Several studies have indicated once-daily dosing of medications and reduced complexity improve medication adherence. The extended release formulations of tacrolimus have been developed with the potential benefits of improving adherence, and hence safety and outcomes. Astagraf XL™ (Advagraf in Europe) and Envarsus XR. are the two extended release once-daily tacrolimus formulations that have recently become available for clinical use and provide promising alternatives to the treatment choices available for immunosuppression in solid organ transplant recipients.Although extended release tacrolimus shows promise in improving patient adherence to transplant medication therapy, further studies are needed to confirm improved compliance and to assess long-term safety and efficacy.

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 (>65 to ≤300 pg/mL; n = 112), and high PTH (>300 pg/mL; n = 134) and underwent repeated, longitudinal testing for mineral metabolites. Results The prevalence of posttransplant, persistent hyperparathyroidism (PTH >65 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 (, The prevalence of posttransplant hyperparathyroidism was 86% at 12 months (PTH >65 pg/ml) but only 40% (PTH >130 mg/dL) in the absence of cinacalcet, vitamin D sterols, or parathyroidectomy. Intact fibroblast growth factor 23 decreased rapidly to G40 pg/ml by 3 months posttransplant. Supplemental digital content is available in the text.

Background The impact of parathyroidectomy on allograft function in kidney transplant patients is unclear. Methods We conducted a retrospective, observational study of all kidney transplant recipients from 1988 to 2008 who underwent parathyroidectomy for uncontrolled hyperparathyroidism (n = 32). Post-parathyroidectomy, changes in estimated glomerular filtration rate (eGFR) and graft loss were recorded. Cross-sectional associations at baseline between eGFR and serum calcium, phosphate, and parathyroid hormone (PTH), and associations between their changes within subjects during the first two months post-parathyroidectomy were assessed. Results Post-parathyroidectomy, the mean eGFR declined from 51.19 mL/min/1.73 m2 at parathyroidectomy to 44.78 mL/min/1.73 m2 at two months (p

Background: Kidney biopsy is a vital tool in the diagnosis of kidney disease. Although it has become a routine procedure, it is not complication-free. Some serious complications of percutaneous kidney biopsy include retroperitoneal hemorrhage and death. There is an increased belief that smaller biopsy needle size results in a lower complication rate. As renal pathologists, we witness an increased number of kidney biopsies performed with a small needle size (as low as gauge 22), which results in inadequate tissue sampling and often non-diagnostic biopsy results. Herein we report the diagnostic value of kidney biopsies according to the size of the biopsy needles. Methods: We performed kidney biopsies from nephrectomy specimens using biopsy needles of different sizes. Morphologic parameters were analyzed. Results: We found that biopsies performed by small needles (gauges 20 and 22) contain significantly lower numbers of glomeruli and blood vessels, which limits pathologic evaluation. Data from our institution do not show differences in kidney biopsy complication rates between 16- and 18-gauge needles. Conclusions: Our data indicate that small biopsy needles do not provide sufficient material for diagnosis, and they increase the likelihood for a repeat biopsy.

Background 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. Methods 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? Results 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. Conclusions 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.

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

Low molecular weight heparins are now commonly used for systemic anticoagulation. Although elimination is mainly by the renal route, these drugs are being prescribed to patients who are dialysis dependent or have renal failure. We report 3 cases where the use of these drugs in patients with severe renal failure significantly prolonged anti-Xa activity and serious bleeding complications occurred. Concomitant prescription of other anti-thrombotic drugs may have contributed to the bleeding in 2 cases. These cases emphasize the potential toxicity of low molecular weight heparins in patients with severe renal failure and that these drugs should be used with great caution in such patients. If prescribed, doses should be lowered and anti-Xa activity frequently measured. The use of other anti-thrombotic drugs should be minimized.

We have studied the reactive responses of both astrocytes and microglia to dopaminergic denervation of the striatum by MPTP. Following MPTP treatment, increased GFAP immunoreactivity reached a peak at 2 days and persisted for at least 6 weeks. Immunoreactivity to vimentin was also markedly increased in astrocytes 48 h after MPTP treatment. Striatal laminin immunoreactivity, however, appeared to be unaffected by drug treatment. GFAP protein levels increased to 196% and 321% of control 24 and 48 hours after MPTP treatment, respectively. Concomitantly, GFAP mRNA levels increased to 560% and 1620% of control, respectively. These reactive changes in striatal astrocytes in response to MPTP treatment were also accompanied by a reactive microglial response as evidenced by increased immunohistochemical visualization of striatal microglia using antibodies to Mac-1. Our results and those reported previously by O'Callaghan et al., strongly suggest that MPTP-induced reactive gliosis in mouse striatum is associated with reactive microglia, albeit without increased interleukin-1 beta.

An analog of human tumor necrosis factor-alpha (TNF-alpha) was created involving the replacement of Cys69 with Asp and Cys101 with Arg. The solution structure and behavior of this analog were compared with the native protein. The analog exhibited a greatly decreased folding efficiency following dilution from urea, but essentially identical circular dichroic spectra in both the folded and unfolded states. The Stokes radius of the native and analog TNF-alpha in the folded state were identical, with the analog exhibiting a slight broadening of the eluting peak. The fluorescence emission spectrum of the native protein exhibits a plateau from 320 to 328 nm, while the spectrum of the analog consisted of a single peak with a maximum at 335 nm. The analog also had a 1.4-fold increase in the fluorescence intensity. Limited proteolysis of the analog resulted in only one of the two peptides seen following digestion of the native protein, and this product was less stable than the equivalent native protein fragment. The analog exhibited a 10-fold lower cytolytic activity than the native protein. These results demonstrated that the disulfide bond is not necessary for folding and activity, but are consistent with the analog having a looser, more flexible structure in solution than the native TNF-alpha.