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Kidney Allograft Recipients (kidney + allograft_recipient)

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Medical Sciences	100%

Selected Abstracts

Calcineurin-Inhibitor-Free Immunosuppression Based on the JAK Inhibitor CP-690,550: A Pilot Study in De Novo Kidney Allograft Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009
S. Busque
This randomized, pilot study compared the Janus kinase inhibitor CP-690,550 (15 mg BID [CP15] and 30 mg BID [CP30], n = 20 each) with tacrolimus (n = 21) in de novo kidney allograft recipients. Patients received an IL-2 receptor antagonist, concomitant mycophenolate mofetil (MMF) and corticosteroids. CP-690,550 doses were reduced after 6 months. Due to a high incidence of BK virus nephropathy (BKN) in CP30, MMF was discontinued in this group. The 6-month biopsy-proven acute rejection rates were 1 of 20, 4 of 20 and 1 of 21 for CP15, CP30 and tacrolimus groups, respectively. BKN developed in 4 of 20 patients in CP30 group. The 6-month rates of cytomegalovirus disease were 2 of 20, 4 of 20 and none of 21 for CP15, CP30 and tacrolimus groups, respectively. Estimated glomerular filtration rate was >70 mL/min at 6 and 12 months (all groups). NK cells were reduced by ,77% in CP-690,550-treated patients. In the CP-690,550 arms, there were modest lipid elevations and a trend toward more frequent anemia and neutropenia during the first 6 months. These data suggest that coadministration of CP-690,550 30 mg BID with MMF is associated with overimmunosuppression. At 15 mg BID, the efficacy/safety profile was comparable to the tacrolimus control group, excepting a higher rate of viral infection. Further dose-ranging evaluation of CP-690,550 is warranted. [source]

Strongyloides Stercoralis Hyperinfection Transmitted by Liver Allograft in a Transplant Recipient

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009
M. J. Rodriguez-Hernandez
We describe a case of Strongyloides stercoralis hyperinfection in a liver allograft recipient 2.5 months after transplantation. The patient lives in Spain, which is not considered an endemic country for strongyloidiasis, and denied prior residence or travel to any known endemic area. The initial symptoms were fever and vomiting, and he subsequently developed a severe respiratory disease. An endoscopic biopsy of ulcerative lesions of the duodenum revealed massive mucosa infiltration by larvae and adult worms, which were also found in respiratory samples. The patient was successfully treated with combined therapy with albendazole and ivermectin. The strongyloides infection was transmitted by the liver allograft. The donor was from Ecuador and, retrospectively, his serum tested positive for S. stercoralis IgG antibodies. Additionally, the pancreas,left kidney allograft recipient from the same donor later developed an intestinal strongyloidiasis without hyperinfection syndrome. To our knowledge, this is the first confirmed case of S. stercoralis infection transmission from the same donor to two solid allograft recipients. [source]

Preemptive lamivudine therapy based on HBV DNA level in HBsAg-positive kidney allograft recipients

HEPATOLOGY, Issue 5 2002
Tak Mao Chan
Hepatitis B surface antigen (HBsAg)-positive kidney transplant recipients have increased liver-related mortality. The impact of lamivudine treatment on patient survival, the optimal time to start treatment, and the feasibility of discontinuing treatment have not been determined. This study examined these issues with a novel management protocol. Serum hepatitis B virus (HBV) DNA levels were measured serially in HBsAg-positive kidney transplant recipients, and lamivudine was administered preemptively to patients with increasing HBV DNA levels with or without elevation of aminotransferase levels. Outcomes of patients who underwent transplantation before or after institution of this preemptive management strategy (in January 1996) were compared. Eleven de novo patients (91.7%) who underwent transplantation between 1996 and 2000 and 15 existing patients (39.5%) who underwent transplantation between 1983 and 1995 received preemptive lamivudine therapy for 32.6 ± 13.3 months. The treatment criteria were met by de novo patients at 8.4 ± 6.2 months (range, 1-18 months) after transplantation. Suppression of HBV DNA and normalization of aminotransferase levels were achieved in all treated patients, and 21.4% had hepatitis B e antigen (HBeAg) seroconversion. The survival of preemptively managed de novo transplant patients was similar to that of HBsAg-negative controls, whereas HBsAg-positive patients who underwent transplantation before January 1996 had inferior survival (relative risk of death, 9.7 [P < .001]; relative risk of liver-related mortality, 68.0 [P < .0001]). Eleven patients (40.7%) developed lamivudine resistance. Discontinuation of lamivudine was attempted in 12 low-risk patients after stabilization and was successful in 5 (41.7%). In conclusion, preemptive lamivudine therapy based on serial HBV DNA levels and clinical monitoring improved the survival of HBsAg-positive renal allograft recipients. Treatment can be discontinued safely in selected patients after stabilization to minimize the selection of drug-resistant HBV mutants. [source]

Mycophenolate mofetil introduction stabilizes and subsequent cyclosporine A reduction slightly improves kidney function in pediatric renal transplant patients: A retrospective analysis

PEDIATRIC TRANSPLANTATION, Issue 3 2006
Kerstin Benz
Abstract: Chronic allograft nephropathy (CAN) is the major cause of late graft loss. Among others, chronic calcineurin inhibitor toxicity (CNI) contributes to the development of CAN. Therefore, reduction in CNI dosage may delay the development of CAN, leading to longer graft survival. It was the aim of the present retrospective analysis to investigate the effect of mycophenolate mofetil (MMF) addition with subsequent cyclosporine A (CSA) reduction on renal function in pediatric kidney allograft recipients. Seventeen patients (aged 8.3,17.6 yr) with monotherapy with CSA and progressive loss of renal function at a median of 3.4 yr after kidney transplantation were enrolled. After at least three months of MMF treatment, CSA dosage was stepwise reduced to trough levels of 100, 80, and 60 ng/mL. In all patients, introduction of MMF prevented a further decrease of glomerular filtration rate (GFR). The mean GFR 12 months before study enrollment was 96.1±24.5 and 71.0±21.0 mL/min/1.73 m2 at start of MMF. After introduction of MMF and unchanged CSA dosage GFR was stabilized to 71.1±23.8 mL/min/1.73 m2. After CSA reduction to trough levels of 60 ng/mL, GFR was slightly ameliorated up to 76.3±24.1 mL/min/1.73 m2. Within the follow-up period, one borderline rejection occurred in a patient in whom the CSA trough level was 60 ng/mL since seven months. In pediatric kidney allograft recipients with progressive loss of renal function reduction of CSA after introduction of MMF may stabilize and even slightly ameliorate renal function. [source]

The Efficacy and Safety of 200 Days Valganciclovir Cytomegalovirus Prophylaxis in High-Risk Kidney Transplant Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010
A. Humar
Late-onset cytomegalovirus (CMV) disease is a significant problem with a standard 3-month prophylaxis regimen. This multicentre, double-blind, randomized controlled trial compared the efficacy and safety of 200 days' versus 100 days' valganciclovir prophylaxis (900 mg once daily) in 326 high-risk (D+/R,) kidney allograft recipients. Significantly fewer patients in the 200-day group versus the 100-day group developed confirmed CMV disease up to month 12 posttransplant (16.1% vs. 36.8%; p < 0.0001). Confirmed CMV viremia was also significantly lower in the 200-day group (37.4% vs. 50.9%; p = 0.015 at month 12). There was no significant difference in the rate of biopsy-proven acute rejection between the groups (11% vs. 17%, respectively, p = 0.114). Adverse events occurred at similar rates between the groups and the majority were rated mild-to-moderate in intensity and not related to study medication. In conclusion, this study demonstrates that extending valganciclovir prophylaxis (900 mg once daily) to 200 days significantly reduces the incidence of CMV disease and viremia through to 12 months compared with 100 days' prophylaxis, without significant additional safety concerns associated with longer treatment. The number needed to treat to avoid one additional patient with CMV disease up to 12 months posttransplant is approximately 5. [source]

Calcineurin-Inhibitor-Free Immunosuppression Based on the JAK Inhibitor CP-690,550: A Pilot Study in De Novo Kidney Allograft Recipients

Homeostatic Repopulation by CD28,CD8+ T Cells in Alemtuzumab-Depleted Kidney Transplant Recipients Treated With Reduced Immunosuppression

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2008
P. Trzonkowski
Alemtuzumab (CAMPATH-1H) is a depleting agent introduced recently in transplantation and often used with reduced maintenance immunosuppression. In the current study we investigated the immune response of 13 kidney allograft recipients treated with alemtuzumab followed by weaned immunosuppression with reduced dose of mycophenolate mofetil (MMF) and tacrolimus. Tacrolimus was switched to sirolimus at 6 months and MMF withdrawn at 12 months after transplantation. We found that after alemtuzumab induction the recovery of CD8+ T cells was much faster than that of CD4+ T cells. It was complete 6 months posttransplant while CD4+ T cells did not fully recover even 15 months posttransplant. Repopulating CD8+ T cells were mainly of immunosenescent CD28,CD8+ phenotype. In a series of in vitro experiments we showed that CD28,CD8+ T cells might suppress proliferation of CD4+ T cells. There were three successfully treated acute rejections during the study (first at +70 day, two others +12 months) that occurred in patients with the lowest level of CD28,CD8+ T cells. We hypothesize that expanded CD28,CD8+ T cells might compete for ,immune space' with CD4+ T cells suppressing their proliferation and therefore delaying CD4+ T-cells recovery. This delay might be associated with the clinical outcome as CD4+ T cells, notably CD4+ T effector memory cells, were shown to be associated with rejection. [source]

Assessment of Changes in Kidney Allograft Function Using Creatinine-Based Estimates of Glomerular Filtration Rate

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2007
M. Gera
These analyses assessed whether creatinine based estimates of glomerular filtration rate (eGFR) accurately represent (1) graft function at different times post-transplant and (2) changes in function over time. These analyses compared iothalamate GFR to eGFR in 684 kidney allograft recipients. Changes in graft function over time (GFR slope) were measured in 360 of 459 recipients (78%) who were followed for at least 3 years. Ninety-five percent of the patients were Caucasians and 72% received kidneys from living donors. All eGFR calculations correlated significantly with GFR at all time points. However, eGFR were less precise and less accurate during the first-year post-transplant than thereafter. The average rate of GFR change (slope) was ,2.93 ± 11.3%/year (,1.06 ± 5.3 mL/min/1.73m2/year). Fifty-four percent of patients had stable or positive GFR slopes. The GFR and eGFR slopes were highly correlated. However, eGFR slope, particularly when calculated by MDRD, significantly underestimated the number of patients with declining graft function. For example, 165 out of 360 patients (46%) lost GFR faster than ,1 mL/min/1.73m2/year. eMDRD identified only 83 of these patients (50%) while the eMayo formula identified 134 (81%). In conclusion, eGFR correlate with GFR but they have relatively low precision and accuracy particularly early post-transplant. eGFR slopes underestimate graft functional loss although some formulas are significantly better than others for this calculation. [source]

Calcineurin Inhibitor-Free Immunosuppression in Renal Allograft Recipients with Thrombotic Microangiopathy/Hemolytic Uremic Syndrome

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2006
O. Øyen
Thrombotic microangiopathy (TMA) and hemolytic uremic syndrome (HUS) represent serious threats to kidney allograft recipients. During a 4-year period, among 850 kidney transplantations, seven recipients with primary HUS and seven recipients (eight transplants) with previous or de novo TMA/HUS were identified and given calcineurin inhibitor (CNI)-free immunosuppression by sirolimus (SRL), mycophenolate mofetil and steroids. Thirteen out of 15 transplantations were successful in the long term; resulting in a mean creatinine of 101 ,mol/L (16.4 months follow-up). In patients maintained on CNI-free regimen, no TMA/HUS recurrences were observed. A high rate of acute rejections (53%) may indicate insufficient immunosuppressive power and/or a causative relationship between TMA/HUS and rejection. Wound-related complications were abundant (60%), and call for surgical/immunosuppressive countermeasures. Our experience supports the idea that CNI's are major offenders in TMA/HUS induction. Total CNI elimination seems essential, as the nephrotoxic combination CNI + SRL may promote TMA. Features of TMA/HUS should be carefully explored in recurrent 'high responders'. [source]

The Relationship Between Donor Age and Cadaveric Renal Allograft Survival Is Modified by the Recipient's Blood Pressure

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2003
Fernando G. Cosio
Increasing donor age correlates with reduced renal allograft survival. In this study we analyzed variables that may modify this relationship. The study included 1285 cadaveric kidney allograft recipients followed for 7.2 + 4.5 years. By Cox, increasing donor age beyond 30 years was associated with significant increases in the hazard ratio for graft loss [age 31,46, hazard ratio (HR) =,1.4, p = 0.02; 46,60, HR = 1.55, p = 0.008; > 60, HR = 1.68, p = 0.03]. Increasing donor age was significantly associated with: older and heavier recipients; higher creatinine and blood pressure (BP) 6 months post-transplant; and lower total cyclosporine dose during the first year. Of interest, the 6-month serum creatinine and the BP level modified significantly the relationship between age and survival. Thus, increasing donor age was significantly related to reduced graft survival only in patients with a 6-month creatinine <,2 mg/dL. Furthermore, donor age related significantly to graft survival only among patients with higher BP levels 6 month post transplant. It is concluded that increasing donor age is associated with reduced cadaveric graft survival, but that relationship is significantly modified by graft function and BP. These data suggest that poorly functioning kidneys have reduced survival irrespective of age. Furthermore, elevated BP levels may have a particularly negative effect on the survival of older grafts. [source]