Showing papers by "Anil Chandraker published in 2014"

Efficacy of Levofloxacin in the Treatment of BK Viremia: A Multicenter, Double-Blinded, Randomized, Placebo-Controlled Trial

Abstract: Background and objectives BK virus reactivation in kidney transplant recipients can lead to progressive allograft injury. Reduction of immunosuppression remains the cornerstone of treatment for active BK infection. Fluoroquinolone antibiotics are known to have in vitro antiviral properties, but the evidence for their use in patients with BK viremia is inconclusive. The objective of the study was to determine the efficacy of levofloxacin in the treatment of BK viremia. Design, setting, participants, & measurements Enrollment in this prospective, multicenter, double-blinded, placebo-controlled trial occurred from July 2009 to March 2012. Thirty-nine kidney transplant recipients with BK viremia were randomly assigned to receive levofloxacin, 500 mg daily, or placebo for 30 days. Immunosuppression in all patients was adjusted on the basis of standard clinical practices at each institution. Plasma BK viral load and serum creatinine were measured monthly for 3 months and at 6 months. Results At the 3-month follow-up, the percentage reductions in BK viral load were 70.3% and 69.1% in the levofloxacin group and the placebo group, respectively ( P =0.93). The percentage reductions in BK viral load were also equivalent at 1 month (58% versus and 67.1%; P= 0.47) and 6 months (82.1% versus 90.5%; P =0.38). Linear regression analysis of serum creatinine versus time showed no difference in allograft function between the two study groups during the follow-up period. Conclusions A 30-day course of levofloxacin does not significantly improve BK viral load reduction or allograft function when used in addition to overall reduction of immunosuppression.

Acute rejection in vascularized composite allotransplantation.

Abstract: Purpose of review Acute rejection is the most common complication after vascularized composite allotransplantation (VCA). This review provides a state-of-the-art analysis of prevention, diagnosis and treatment of acute rejection episodes and highlights recent findings with the potential to improve patient care and enhance understanding of the underlying biologic processes. Recent findings Recent reports suggest that maintenance immunosuppression dose reduction and steroid withdrawal are realistic goals in VCA, despite the known high immunogenicity of the skin component. It appears that utilization of sentinel flaps, in-depth histological analyses and application of novel biomarkers have facilitated early diagnosis and characterization of acute rejection episodes, leading to timely institution of appropriate therapy. The successful management of the first highly sensitized face transplant recipient suggests the possibility of carefully considering these high-risk VCA candidates for transplantation. Summary Acute rejection is higher in VCA than in any other organ in the field of transplantation, although most episodes are controlled by high-dose steroids and optimization of maintenance immunosuppression. Because of limitations in patient number and the duration of follow-up, the long-term safety and effectiveness of VCA remain unclear. Moreover, the tests currently used to diagnose acute rejection are of limited value. Better diagnostic tools and a better understanding of the immunologic events during acute rejection are therefore needed to improve diagnosis, treatment and outcomes of this life-changing restorative surgery.

Impact of Pretransplant Anti-HLA Antibodies on Outcomes in Lung Transplant Candidates

Abstract: Rationale: The prevalence of anti-HLA antibodies in lung transplant candidates and their impact on waitlist and transplant outcomes is not known.Objectives: We examined the prevalence of pretransplant anti-HLA antibodies at varying thresholds and evaluated their impact on outcomes before and after lung transplantation.Methods: We performed a single-center retrospective cohort study including all patients listed for lung transplantation between January 2008 and August 2012. Per protocol, transplant candidates were assessed by solid phase LABscreen mixed Class I and II and LABscreen Single Antigen assays.Measurements and Main Results: Among 224 patients, 34% had anti-HLA antibodies at mean fluorescent intensity (MFI) greater than or equal to 3,000 (group III), and 24% had antibodies at MFI 1,000 to 3,000 (group II). Ninety percent of the patients with pretransplant anti-HLA antibodies had class I antibodies, whereas only seven patients developed class II alone. Patients in group III were less likely to rece...

Long-term outcomes of kidney transplantation across a positive complement-dependent cytotoxicity crossmatch.

Abstract: BACKGROUND More than 30% of potential kidney transplant recipients have pre-existing anti-human leukocyte antigen antibodies. This subgroup has significantly lower transplant rates and increased mortality. Desensitization has become an important tool to overcome this immunological barrier. However, limited data is available regarding long-term outcomes, in particular for the highest risk group with a positive complement-dependent cytotoxicity crossmatch (CDC XM) before desensitization. METHODS Between 2002 and 2010, 39 patients underwent living-kidney transplantation across a positive CDC XM against their donors at our center. The desensitization protocol involved pretransplant immunosuppression, plasmapheresis, and low-dose intravenous immunoglobulin±rituximab. Measured outcomes included patient survival, graft survival, renal function, rates of rejection, infection, and malignancy. RESULTS The mean and median follow-up was 5.2 years. Patient survival was 95% at 1 year, 95% at 3 years, and 86% at 5 years. Death-censored graft survival was 94% at 1 year, 88% at 3 years, and 84% at 5 years. Uncensored graft survival was 87% at 1 year, 79% at 3 years, and 72% at 5 years. Twenty-four subjects (61%) developed acute antibody-mediated rejection of the allograft and one patient lost her graft because of hyperacute rejection. Infectious complications included pneumonia (17%), BK nephropathy (10%), and CMV disease (5%). Skin cancer was the most prevalent malignancy in 10% of patients. There were no cases of lymphoproliferative disorder. Mean serum creatinine was 1.7±1 mg/dL in functioning grafts at 5 years after transplantation. CONCLUSION Despite high rates of early rejection, desensitization in living-kidney transplantation results in acceptable 5-year patient and graft survival rates.

Glomerular inflammation correlates with endothelial injury and with IL-6 and IL-1β secretion in the peripheral blood.

Abstract: Background Transplant glomerulitis is an active form of glomerular injury associated with suboptimal graft outcome, inadequate histologic reproducibility, and poorly understood pathogenesis. Using a modified pathologic schema where glomerular inflammation is defined by the presence of five or more leukocytes per glomerulus, we sought to assess the reproducibility of transplant glomerulitis and to prospectively investigate the pathogenesis of glomerular inflammation. Methods Our cohort includes 59 kidney transplant recipients who underwent 60 "for cause" allograft biopsies. In addition to light microscopy, the majority of the biopsies were assessed using immunohistochemistry, immunofluorescence, and electron microscopy studies. Biopsies were classified as noninflamed (n=21), inflamed (borderline changes or above) without glomerulitis (n=21), and transplant glomerulitis (n=18). Peripheral blood was collected on the day of biopsy and cytokines secreted by peripheral blood mononuclear cells (PBMCs) were measured ex vivo. Results Our modified schema had higher inter-observer agreement for detecting glomerulitis than that of the current Banff schema. Biopsies with glomerulitis showed ultrastructural signs of glomerular capillary wall remodeling. In contrast to other anatomic compartments, intraglomerular leukocytes in glomerulitis group consisted largely of monocytes. Patients with glomerulitis had high levels of IL-6 and IL-1β secreted by PBMCs. Furthermore, the percentage of inflamed glomeruli and the number of intraglomerular monocytes showed independent association with IL-6 and IL-1β levels, which tended to correlate with subsequent estimated glomerular filtration rate decline. Conclusions Inter-observer reproducibility of transplant glomerulitis can be improved by using more stringent histologic criteria. Glomerular inflammation correlates with endothelial injury, monocyte influx, and IL-6 and IL-β secretion by circulating immune cells.