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Renal Allograft Recipients (renal + allograft_recipient)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

NOVEL SURVEILLANCE AND CURE OF A DONOR- TRANSMITTED LYMPHOMA IN A RENAL ALLOGRAFT RECIPIENT

NEPHROLOGY, Issue 3 2000
Herzig Ka
[source]

Cellulitis Revealing a Cryptococcosis-Related Immune Reconstitution Inflammatory Syndrome in a Renal Allograft Recipient

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2007
F. Lanternier
Immune reconstitution inflammatory syndrome (IRIS) has rarely been described in the course of disseminated cryptococcosis in solid organ transplant recipients. We report here the case of a renal transplant recipient who developed severe cellulitis in the context of Cryptococcus neoformans -associated IRIS while undergoing reduction of his immunosuppressive therapy. IRIS appeared concomitantly with a dramatic increase of blood CD4+ T cells (94,460/mm3) and required the administration of a short-term steroid therapy to resolve. [source]

Mechanisms of Alloantibody Production in Sensitized Renal Allograft Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009
M. D. Stegall
While clinical protocols have been developed to allow for successful kidney transplantation in patients with high levels of donor-specific alloantibody (DSA), significant limitations still exist including high rates of early humoral rejection and decreased long-term graft survival compared to conventional transplants. A better understanding of the mechanisms of alloantibody production at baseline and at various phases posttransplant would be an important step toward the development of improved therapeutic approaches. The goal of this review is to outline recent studies regarding antibody production in general and specific studies that illustrate what is known about alloantibody production in sensitized patients. [source]

Phase 1 Dose-Escalation Study of CP-690 550 in Stable Renal Allograft Recipients: Preliminary Findings of Safety, Tolerability, Effects on Lymphocyte Subsets and Pharmacokinetics

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2008
E. Van Gurp
CP-690 550 inhibits Janus kinase 3 with nanomolar potency. In this dose-escalation study, we assessed the safety, tolerability, effects on lymphocyte subsets, and pharmacokinetics of CP-690 550 when coadministered with mycophenolate mofetil in stable renal allograft recipients for 28 days. Twenty-eight patients were enrolled. Six patients received CP-690 550 5 mg twice daily (BID), 6 patients received 15 mg BID, 10 patients received 30 mg BID, and 6 patients received placebo. The most frequent adverse events were infections and gastrointestinal (abdominal pain, diarrhea, dyspepsia, and vomiting). CP-690 550 15 mg BID and 30 mg BID were associated with a mean decrease in hemoglobin from baseline of 11% and a mean decrease in absolute natural killer cell counts of 50%. CP-690 550 30 mg BID was also associated with a mean increase in absolute CD19+ B-lymphocytes of 130%. There were no changes in the number of neutrophils, total lymphocytes, platelets, or CD4+ or CD8+ T cells; clinical chemistry; vital signs; or electrocardiograms from the pretreatment baseline. Administration of CP-690 550 without a concomitant calcineurin inhibitor resulted in CP-690 550 exposures consistent with previous studies in nontransplant subjects. Additional dose-ranging studies are warranted to evaluate the safety and efficacy of CP-690 550 in renal transplant recipients over longer treatment duration. [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]

Equivalent Pharmacokinetics of Mycophenolate Mofetil in African-American and Caucasian Male and Female Stable Renal Allograft Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2003
Mark D. Pescovitz
African-American (AA) renal transplant recipients require higher doses of mycophenolate mofetil (MMF) than Caucasians. A hypothesized pharmacokinetic (PK) difference was tested in stable renal transplant recipients. Whole blood was collected before, and 20, 40 and 75 min, and 2, 3, 4, 6, 8 and 12 h after the MMF dose. Mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) were analyzed using HPLC. Analysis of variance was performed for the primary end-points of dose-adjusted PK parameters AUC0,12 and Cmax of MPA using log-transformed values. Differences between races and genders were estimated: 90% confidence intervals (CI) were calculated. Back-transformation gave estimates of the race and gender ratio and their CI. Equivalence of the groups was determined if the 90% confidence limits were included in the interval (0.80, 1.25). The calculated PK parameters were comparable among the four subgroups (Caucasian, AA, Male, Female). The 90% CIs for the ratio of dose-adjusted AUC0,12 of MPA between races were between 89.7 and 112.9%. There were no race, gender or race-by-gender effects (p-values = 0.196) nor differences between diabetics and nondiabetics. This study demonstrates that dosing requirement for MMF in AA and Caucasians is unlikely to be related to different exposures to MPA. [source]

The role of calcimimetics in the treatment of hyperparathyroidism

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2007
R. P. Wüthrich
Abstract Calcimimetics reduce serum levels of parathyroid hormone (PTH) and calcium, with a leftward shift in the set-point for calcium-regulated PTH secretion. The aim of this publication is to review the data available for calcimimetics in primary, secondary and tertiary hyperparathyroidism (HPT). Parathyroidectomy (PTX) is currently the only curative treatment for primary HPT, and recommended for patients with moderate-to-severe disease, as defined by a 2002 National Institute's of Health summary statement. In general, patients with primary HPT not meeting these surgical criteria, as well as those with contraindication or refusal for surgery, are monitored for signs and symptoms of primary HPT. There are currently no non-surgical therapies approved for use in primary HPT, although bisphosphonates are used in some patients, in an effort to control serum calcium levels. Calcimimetics decrease PTH and calcium levels and are a potential alternative for patients contraindicated for PTX, or who have failed previous PTX and have recurrent primary HPT. Secondary HPT develops early in chronic kidney disease and is present virtually in all patients with end-stage renal disease (ESRD). Secondary HPT is a progressive disease and is associated with several systemic complications, including renal osteodystrophy, soft tissue and vascular calcifications, and adverse cardiovascular outcomes. In ESRD patients, calcimimetics were shown to simultaneously reduce PTH, calcium, phosphate and calcium × phosphate product. In addition, observational analyses of use of calcimimetics in the ESRD population have shown a reduction of important clinical outcomes. In renal allograft recipients with tertiary HPT and hypercalcaemia, calcimimetics are a promising treatment option to control the parameters of calcium phosphate metabolism and may be a valid alternative to PTX. Based on its unique mechanism of action, the calcimimetic cinacalcet may play a role in the medical treatment of primary and tertiary forms of HPT, in addition to the registered indication for the treatment of secondary HPT. [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]

Pretransplant hepatitis C virus infection and its effect on the post-transplant course of living renal allograft recipients

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7 2003
BEHZAD EINOLLAHI
Abstract Background: Hepatitis C virus infection (HCV) is a main health problem in end-stage renal disease (ESRD) patients. The effect of pretransplant HCV infection on survival among ESRD patients who have undergone renal transplantation is controversial. We report the results of a large monocenter study that evaluated the effect of hepatitis C on the patient, and on graft survival in renal-transplanted patients who received living donated allograft. Methods: A historical cohort study, we investigated all 1006 patients who received a living kidney transplant at Baghiatollah Medical Center in Tehran, Iran, between March 1995 and October 2001 (up to 85 months follow up). Patients' sera had been routinely assayed for anti-HCV antibodies and hepatitis B surface antigen (HBsAg) at the time of transplantation. The HBsAg-positive patients were excluded from the survival analysis. Survivals were examined using Kaplan,Meier analysis and compared using the log,rank test. Multivariate analysis was performed using Cox's model. Results: Forty-five patients (4.5%) were anti-HCV-antibody positive. Anti-HCV-antibody-positive patients spent a longer time on dialysis and had a higher rate of retransplantation. There were no differences in recipients' sex and age and donors' age between the two groups. The 7-year patient survival rate was 89.9% in the anti-HCV-antibody-positive group and 95.5% in the HCV-negative group (P = 0.74). Seven-year graft survival was 82.0% and 75.0% in the anti-HCV-antibody-positive and HCV-negative groups, respectively (P = 0.39). In the multivariate analysis, age was the only significant parameter correlated with patient survival (P = 0.02). Conclusions: HCV infection does not seem to influence patient and graft survival within a medium-time follow up in living allograft recipients, and anti-HCV-antibody positive status (alone) is not a contraindication for renal transplantation. However, further studies are needed to better define the role of HCV infection in long-term prognosis. © 2003 Blackwell Publishing Asia Pty Ltd [source]

Protocol biopsies should be standard of care for pediatric renal allograft recipients!

PEDIATRIC TRANSPLANTATION, Issue 7 2006
Patricia E. Birk
First page of article [source]

Cyclosporine drug monitoring with C0 and C2 concentrations in children with stable renal allograft function

PEDIATRIC TRANSPLANTATION, Issue 2 2006
Mukaddes Kalyoncu
Abstract:, Cyclosporin A (CsA) has a narrow therapeutic window and necessitates monitoring of blood concentration. We aimed to evaluate trough (C0) and second hour (C2) level after ingestion of drug monitoring in renal allograft recipients. In this retrospective study, 12 children eight boys and four girls; mean age at transplantation 14.6 ± 3.7 yr (ranges: 7.0,19.0), mean age post-transtplant 17.8 ± 4.9 yr (ranges: 9.0,24.0) who were transplanted >6 months were enrolled in this evaluation. Ten were recipients of a living related donor and two deceased donor grafts. While six children were receiving CsA, steroids and azathioprine, the other six received CsA, steroids and mycophenolate mofetil. Clinical course, blood pressure, renal and liver function tests were recorded. Mean C0 and C2 were 96.2 ± 59.5 and 504 ± 305.4 ng/mL respectively. Mean serum creatinine level was 1.2 ± 0.45 mg/dL and mean creatinine clearance (CrCl) was 89.2 ± 36.8 mL/min/1.73 m2. There was a correlation between serum creatinine level, CsA dose and C2 levels,whereas,there was no correlation between age, blood pressure, CrCl and C2 levels. However, no correlation was found between C0 levels and any of the above parameters. In conclusion, our data suggest that C2 levels are correlated better with dose and serum creatinine level. [source]

Allograft diabetic nephropathy may progress to end-stage renal disease

PEDIATRIC TRANSPLANTATION, Issue 4 2004
Moro O. Salifu
Abstract:, Mesangial expansion and glomerular basement membrane thickening characteristic of diabetic nephropathy recur in diabetic recipients of renal allografts from non-diabetic donors but progression to renal failure is minimally documented. Three female renal allograft recipients (aged 40, 62 and 73 yr), who developed end-stage renal disease (ESRD) due to recurrent diabetic nephropathy (two patients) and de novo diabetes (one patient) are reported. Onset of proteinuria, uncontrolled hypertension, azotemia, renal allograft pathologic findings and the need for hemodialysis were analyzed. None of the kidney donors (one cadaver, two living related) had known diabetes or perturbed glucose metabolism pre-transplantation. The three patients presented had different varieties of diabetes; type 1, type 2 and new onset diabetes after transplantation (NODAT). In each subject, proteinuria was detected by dipstick at a mean of 8.3 yr (range 8,9) post-transplantation and increased to the nephrotic range (3.7,4.8 g/day) inducing hypoalbuminemia and azotemia. A histopathologic diagnosis of allograft diabetic nephropathy was made in a mean of 11.7 yr (range 10,14), based on glomerular basement membrane thickening, nodular and diffuse intercapillary glomerulosclerosis, arteriolosclerosis, and tubular atrophy with marked tubular basement membrane thickening characteristic of advanced diabetic nephropathy. All three patients manifested uremia and resumed hemodialysis. Two patients died from sepsis within 2 months and one patient died 2.5 yr later after resumption of maintenance hemodialysis. We infer that recurrent or de novo diabetic nephropathy in renal allografts follows a clinical decade-long course irrespective of diabetes. Reports of ESRD due to allograft diabetic nephropathy (ADN) have been limited because of shorter survival of diabetic transplant recipients and few kidney biopsies performed in patients with chronic allograft dysfunction. The occurrence of allograft diabetic nephropathy in some, but not all patients, however, suggests that individual genetic variability modulates disease expression. [source]

Increased expression of cytotoxic effector molecules: Different interpretations for steroid-based and steroid-free immunosuppression

PEDIATRIC TRANSPLANTATION, Issue 1 2003
Thomas Satterwhite
Abstract: Cytotoxic T lymphocyte (CTL) effector molecules have been studied as markers of acute rejection in renal allograft recipients on steroid-based immunosuppression. We hypothesized that basal CTL gene expression may vary with time post-transplantation as well as with different immunosuppression protocols (steroid-based or steroid-free). Variations in CTL gene expression may thus impact on the ability to predict acute allograft rejection. We used the non-invasive method of quantitative competitive-reverse transcription-polymerase chain reaction (QC-RT-PCR) to quantify the amounts of CTL effector molecules (granulysin, GL; perforin, P; granzyme B, GB) in serial peripheral blood lymphocyte (PBL) samples from steroid-free and steroid-based adult and pediatric renal allograft recipients. Patients on both protocols were clinically monitored by protocol biopsies at 1, 3, 6, and 12 months post-transplantation and for graft function at 1 yr post-transplantation in a separate clinical study. Steroid-free patients with stable graft function showed an increase in GL, P, and GB gene expression over time post-transplantation with the increase being seen largely by the first post-transplant month. A further increase in GL expression was noted at the end of the first post-transplant year in the absence of acute rejection, whereas GB and P levels were unchanged. At comparative time-points post-transplantation, CTL genes were found to be higher in steroid-free patients with stable graft function, compared to steroid-based recipients with either clinically stable graft function or acute rejection. This study suggests that levels of CTL gene expression, although important in a steroid-based regimen to monitor the risk of acute rejection, may not be similarly applied in patients on steroid-free immunosuppression. The early increase in levels seen in steroid-free patients appears to correlate with the total absence of steroids. As steroid-free patients seem to have a lower incidence of acute rejection and better long-term graft function at 1 yr, the early increase in CTL genes in the absence of acute rejection may suggest an early adaptive immune activation response, promoting early graft acceptance in this protocol. [source]

Peritransplant Immunoadsorption for Positive Crossmatch Deceased Donor Kidney Transplantation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010
G. Bartel
Various desensitization protocols were shown to enable successful living donor kidney transplantation across a positive complement-dependent cytotoxicity crossmatch (CDCXM). Positive crossmatch transplantation, however, is less well established for deceased donor transplantation. We report a cohort of 68 deceased donor renal allograft recipients who, on the basis of broad sensitization (lymphocytotoxic panel reactivity ,40%), were subjected to a protocol of peritransplant immunoadsorption (IA). Treatment consisted of a single session of immediate pretransplant IA (protein A) followed by posttransplant IA and antilymphocyte antibody therapy. Twenty-one patients had a positive CDCXM, which could be rendered negative by pretransplant apheresis. Solid phase HLA antibody detection revealed preformed donor-specific antibodies (DSA) in all 21 CDCXM-positive and in 30 CDCXM-negative recipients. At 5 years, overall graft survival, death-censored graft survival and patient survival were 63%, 76% and 87%, respectively, without any differences between CDCXM-positive, CDCXM-negative/DSA-positive and CDCXM-negative/DSA-negative recipients. Furthermore, groups did not differ regarding rates of antibody-mediated rejection (24% vs. 30% vs. 24%, p = 0.84), cellular rejection (14% vs. 23% vs. 18%, p = 0.7) or allograft function (median 5-year serum creatinine: 1.3 vs. 1.8 vs. 1.7 mg/dL, p = 0.62). Our results suggest that peritransplant IA is an effective strategy for rapid desensitization in deceased donor transplantation. [source]

Humoral and Cellular Immune Responses after Influenza Vaccination in Kidney Transplant Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009
S Candon
It has been speculated that influenza vaccination of renal allograft recipients could be associated with de novo production and/or increased titers of anti-HLA antibodies (HLA-Ab). To directly address this issue, we recruited 66 stable renal transplant recipients and 19 healthy volunteers during the 2005,2006 vaccination campaign. At day 0 and day 30 following vaccination, HLA-Ab were screened and in parallel influenza-specific antibody and T-cell responses were assessed. Humoral postvaccinal responses to A/H1N1 and A/H3N2 strains, but not B strain, were less frequent in transplanted patients than in control subjects. Significant expansion of influenza-specific IFN-,-producing T cells was observed at similar frequencies in patients and controls. There was no correlation between cellular and humoral postvaccinal responses. No impact of sex, age or immunosuppressive regimen could be evidenced. Vaccination was not associated with any significant change in preexisting or de novo anti-HLA sensitization. No episode of allograft rejection was recorded in any of the patients. Our results suggest that flu vaccination is safe in stable renal transplanted patients. Larger studies are needed for definitive statistical proof of the safety and effectiveness, with regard to the quality of the immune response, of yearly influenza vaccination in immunosuppressed patients. [source]

Early and Limited Use of Tacrolimus to Avoid Rejection in an Alemtuzumab and Sirolimus Regimen for Kidney Transplantation: Clinical Results and Immune Monitoring

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009
S. J. Knechtle
Alemtuzumab induction with 60 days of tacrolimus treatment and continuous sirolimus treatment prevented acute rejection in nine of 10 consecutive renal allograft recipients. All patients are alive with a functioning kidney graft at 27,39 months of follow-up. Extensive immune monitoring was performed in all patients. Alloantibody detection, cytokine kinetics assay (CKA), and trans vivo delayed-type hypersensitivity (DTH) assay were performed every 6 months showing correlation with clinical evolution. Despite alloantibody presence in five patients, eight patients remain without the need for specific treatment and only sirolimus monotherapy in decreasing dosage. Four patients take only 1 mg sirolimus daily with levels of 3,4 ng/mL. One patient showed clinical signs of rejection at month 9 post-transplant, with slow increase in serum creatinine and histological signs of mixed cellular (endarteritis) and humoral rejection (C4d positivity in peritubular capillaries and donor-specific antibody (DSA)). In summary, the addition of tacrolimus therapy for 2 months to a steroid-free, alemtuzumab induction and sirolimus maintenance protocol limited the previously shown acute rejection development. Nevertheless, alloantibody was present in serum and/or C4d present on 1-year biopsy in half the patients. The combination of CKA and DSA monitoring or the performance of transvivo DTH correlated with immune status of the patients. [source]

Phase 1 Dose-Escalation Study of CP-690 550 in Stable Renal Allograft Recipients: Preliminary Findings of Safety, Tolerability, Effects on Lymphocyte Subsets and Pharmacokinetics

CD4+CD25+FOXP3+ Regulatory T Cells Increase De Novo in Kidney Transplant Patients After Immunodepletion with Campath-1H

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2008
D. D. Bloom
Campath-1H (Alemtuzumab) is an effective immunodepletion agent used in renal transplantation. To evaluate its influence on T lymphocytes during repletion, we analyzed peripheral blood from Campath-1H-treated renal allograft recipients for the presence of FOXP3+ regulatory T (Treg) cells. Flow cytometry demonstrated that CD4+CD25+FOXP3+ lymphocytes increased significantly within the CD4+ T-cell population, skewing Treg/Teff (T effector) ratios for up to several years. In contrast, Treg levels in patients treated with anti-CD25 (Basiliximab) and maintained on CsA demonstrated a sustained decrease. The increase in Tregs in Campath-1H treated patients developed independent of maintenance immunosuppression. Importantly, the increase in Tregs was not fully explained by their homeostatic proliferation, increased thymic output, or Treg sparing, suggesting de novo generation/expansion. Consistent with this, in vitro stimulation of PBMCs with Campath-1H, with or without anti-CD3, activation led to an increase in CD4+CD25+FOXP3+ cells that had suppressive capabilities. Together, these data suggest that Campath-1H promotes an increase in peripheral Tregs and may act as an intrinsic generator of Tregs in vivo. [source]

Following Anti-CD25 Treatment, A Functional CD4+CD25+ Regulatory T-Cell Pool Is Present in Renal Transplant Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2007
E. Kreijveld
Daclizumab, a humanized antibody directed against the ,-chain of the interleukin-2 receptor (CD25), has shown efficacy in the prevention of acute rejection following organ transplantation. However, anti-CD25 therapy can be expected to affect not only alloreactive effector T cells, but also CD4+CD25+ regulatory T (Treg) cells that are shown to play an important role in the induction of transplantation tolerance. Therefore, the size and function of the Treg pool in human renal allograft recipients after single-dose daclizumab administration was investigated in this study. Approximately 8 weeks after administration, daclizumab was cleared from the circulation and the Treg population then present appeared not different from that observed before transplantation. Functional analysis revealed that the Treg possessed a normal capacity to suppress mixed lymphocyte reactions in vitro. These data indicate that after daclizumab therapy a Treg population, normal in number and function, is present in the peripheral blood of renal transplant recipients. [source]

Risk Factors and Long-Term Outcome of Transplant Renal Artery Stenosis in Adult Recipients After Treatment by Percutaneous Transluminal Angioplasty

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2006
V. Audard
Transplant renal artery stenosis (TRAS) is a common complication of kidney transplantation but attempts to identify predisposing risk factors for TRAS have yielded conflicting results. In order to determine the predisposing factors for transplant (TRAS), we retrospectively reviewed the records of 29 renal allograft recipients with TRAS treated with percutaneous transluminal angioplasty (PTA). The TRAS group was compared with a case-control group of 58 patients. Predisposing factors for TRAS included CMV infection (41.4% vs. 12.1% p = 0.0018) and initial delayed graft function (DGF) (48.3% vs. 15.5% p = 0.0018), respectively in the TRAS and the control group. Acute rejection occurred more frequently in patients from the TRAS group (48.3%) compared with the control group (27.6%), although the difference was not significant (p = 0.06). In a multivariate analysis, only CMV infection (p = 0.005) and DGF (p = 0.009) appear to be significantly and independently associated with TRAS. The long-term graft survival was significantly higher in the control group, compared with the TRAS group (p = 0.03). Our study suggests that CMV infection and DGF are two reliable risk factors for TRAS. Despite treatment by PTA with primary successful results, TRAS significantly affects long-term graft outcome. [source]

Detection of Acute Tubulointerstitial Rejection by Proteomic Analysis of Urinary Samples in Renal Transplant Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2005
Stefan Wittke
This study investigates proteomic analysis of urinary samples as a non-invasive method to detect acute rejection of renal allografts. Capillary electrophoresis coupled to mass spectrometry (CE-MS) was used to analyze urinary samples in 19 patients with different grades of subclinical or clinical acute rejection (BANFF Ia to IIb), 10 patients with urinary tract infection and 29 patients without evidence of rejection or infection. A distinct urinary polypeptide pattern identified 16 out of 17 cases of acute tubolointerstitial rejection, but was absent in two cases of vascular rejection. Urinary tract infection resulted in a different polypeptide pattern that allowed to differentiate between infection and acute rejection in all cases. Potentially confounding variables such as acute tubular lesions, tubular atrophy, tubulointerstitial fibrosis, calcineurin inhibitor toxicity, proteinuria, hematuria, allograft function and different immunosuppressive regimens did not interfere with test results. Blinded analysis of samples with and without rejection showed correct diagnosis by CE-MS in the majority of cases. Detection of acute rejection by CE-MS offers a promising non-invasive tool for the surveillance of renal allograft recipients. Further investigation is needed to establish polypeptide patterns in vascular rejection and to explore whether changes in the urinary proteome occur before the onset of histologically discernible rejection. [source]

Pharmacokinetics, safety, and efficacy of mycophenolate mofetil in combination with sirolimus or ciclosporin in renal transplant patients

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2007
Mark D. Pescovitz
Aims To compare the pharmacokinetics of mycophenolic acid (MPA) and its metabolite (MPAG) when mycophenolate mofetil (MMF) is administered in combination with sirolimus or ciclosporin (CsA) in renal allograft recipients. Safety and efficacy (biopsy-proven acute rejection (BPAR)) were also assessed. Methods Patients (n = 45) were randomized 2 : 1 to receive treatment with sirolimus (n = 30; dosed to maintain trough concentrations of 10,25 ng ml,1 until week 8, and then 8,15 ng ml,1 thereafter) or CsA (n = 15; administered as per centre practice) both in combination with daclizumab, oral MMF and corticosteroids. Pharmacokinetic assessments were performed at day 7, week 4, and months 3 and 6 post-transplant. The primary endpoint was the AUC(0,12 h) for MPA and MPAG. The pharmacokinetics of sirolimus were also assessed. Results MPA exposure was 39,50% lower (month 6 mean AUC(0,12 h) (95%CI): 40.4 (33.8, 47.0) vs. 68.5 (54.9, 82.0) µg ml,1 h) and MPAG exposure was 25,52% higher (722 (607, 838) vs. 485 (402, 569) µg ml,1 h at month 6) in the presence of CsA compared with sirolimus across visits. BPAR was 40.0% with sirolimus and 13.3% with CsA. The incidence of hypertension, tremors and hirsutism was higher with CsA than with sirolimus, while the incidence of diarrhoea, hyperlipidaemia and impaired wound closure was higher with sirolimus. No deaths, malignancies or graft losses were reported. Conclusions Co-administration of sirolimus with MMF led to greater MPA exposure, but lower MPAG exposure, than co-administration with CsA. As rejection rates were higher in the absence of CsA, further study of calcineurin inhibitor-free regimens is required before general recommendations can be made. [source]

Fever of unknown origin in renal transplant patients with tacrolimus

CLINICAL TRANSPLANTATION, Issue 4 2009
Kathrin Hochegger
Abstract:, The immunosuppressive agent tacrolimus is now widely used for the prevention of acute and chronic rejection in renal allograft recipients. We here report on three patients, who developed drug-induced fever due to tacrolimus one to five months after renal transplantation. Extensive search for a focus, autoantibodies and virus infection remained inconclusive. Therefore, drug-induced fever was suggested. After discontinuing tacrolimus and switching to cyclosporine A fever completely resolved within 24 h. This report demonstrates that tacrolimus-induced drug fever should be included in the differential diagnosis of fever of unknown origin in renal transplant recipients. [source]

Cytomegalovirus prophylaxis with valganciclovir in African,American renal allograft recipients based on donor/recipient serostatus

CLINICAL TRANSPLANTATION, Issue 2 2005
Scott A Gruber
Abstract:, There is a paucity of data examining the efficacy of valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis in kidney transplant patients, particularly with regard to utilization of a risk-stratified dosing regimen. Eighty adult African,American (AA) renal allograft recipients transplanted from November 3, 2001 to May 28, 2003 and followed for 22 ± 8 months received VGC once daily for 90 d post-transplant dosed according to donor/recipient (D/R) serostatus: high risk (D+/R,) received 900 mg (n = 12); moderate risk (D+/R+, D,/R+) received 450 mg (n = 60); and low risk (D,/R,) received no prophylaxis (n = 8). Thymoglobulin or basiliximab was used for induction, and mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus for maintenance immunosuppression. Only six patients (7.5%) developed symptomatic CMV infection diagnosed by pp65 antigenemia, three in the high-risk (25%) and three in the moderate-risk (5%) group (p = 0.02). All patients were on tacrolimus for at least 3 months prior to diagnosis. There were no cases of tissue-invasive disease, resistance to treatment, or recurrence. D+/R, serostatus was the only significant independent predictor for CMV infection using multivariate analysis (odds ratio 10.5; p = 0.04). Thymoglobulin induction was not associated with CMV infection. None of 43 patients who were exposed to sirolimus for >30 d developed CMV infection, vs. six of 37 who were not (p = 0.006). We conclude that VGC dosed according to D/R serostatus provides safe and effective CMV prophylaxis in AA renal allograft recipients. [source]

Angiotensinogen and plasminogen activator inhibitor-1 gene polymorphism in relation to chronic allograft dysfunction,

CLINICAL TRANSPLANTATION, Issue 1 2005
Kadriye Reis
Abstract:, Chronic allograft dysfunction (CAD) is the most common cause of allograft failure in the long-term, and current immunologic strategies have little effect on this condition. The renin-angiotensin system (RAS) plays important roles progression of chronic renal disease. It is thought that plasminogen activator inhibitor-1 (PAI-1) functions in the RAS, in addition to involvement in thrombotic risk and fibrosis. This study investigated possible links between angiotensinogen (AGT) genotypes (M235T/MM, MT, TT) and PAI-1 genotypes (4G4G, 4G5G, 5G5G) and CAD assessments of both types of polymorphism were performed in 82 renal allograft recipients. One hundred healthy subjects were also investigated for AGT polymorphism, and 80 healthy subjects for PAI-1 polymorphism. Genotypes were determined using polymerase chain reaction (PCR) sequence-specific primers, and PCR followed by restriction fragment length polymorphism analysis. Kidney recipients with CAD had significantly lower frequencies of the MM genotype and the M allele than the recipients without CAD (p < 0.05 and <0.001). The transplant recipients with CAD also had significantly lower frequencies of the 5G5G genotype and the 5G allele than those without CAD (p < 0.001 and <0.05). Determination of AGT M235T and PAI-1 genotypes prior to transplantation may help identify patients who at risk for chronic renal transplant dysfunction. [source]

An open-label, pilot study evaluating the safety and efficacy of converting from calcineurin inhibitors to sirolimus in established renal allograft recipients with moderate renal insufficiency

CLINICAL TRANSPLANTATION, Issue 1 2005
V Ram Peddi
Abstract:, This pilot study was designed to evaluate the safety and efficacy of converting from a calcineurin inhibitor (CI) to a sirolimus (SRL)-based regimen in established renal transplant recipients with moderate renal insufficiency. Sixty renal transplant recipients on CI-based immuno-suppression with a serum creatinine (SCr) between 159 and 265 ,M (1.8 and 3.0 mg/dL) and a glomerular filtration rate (GFR) between 30 and 70 mL/min were enrolled. SRL dosing was dependent upon concomitant immunosuppressive therapy. The mean patient age was 45 yr and the mean time from transplant to study enrollment was 60.8 months (range: 7,198). The median SCr was 168 ,M (1.9 mg/dL) and the median GFR was 51 mL/min. Twelve months after conversion the patient and graft survival rates were 96.7% and 95%, respectively. The incidence of biopsy-proven acute rejection was 3.3% (two cases reported, Banff grades IA and IB). The median SCr and median creatinine clearance were 168 ,M (1.9 mg/dL) and 53 mL/min, respectively. Hyperlipidemia, diarrhea, peripheral edema, rash, and anemia were the most commonly reported adverse events. Patients with moderate renal insufficiency can be converted from CI to SRL-based therapy and maintain renal function over a 1-yr period. [source]

Impact of in vivo complement activation and cryoglobulins on graft outcome of HCV-infected renal allograft recipients

CLINICAL TRANSPLANTATION, Issue 1 2004
Stefan M Weiner
Abstract:, Background:, Chronic hepatitis C virus (HCV) infection is closely associated with mixed cryoglobulinemia. Cryoglobulins can activate complement leading to vascular damage. We examined whether cryoglobulinemia and complement turnover is associated with HCV infection in renal transplant recipients and whether this has an adverse effect on graft outcome. Methods:, Sera and fresh plasma from 31 HCV-RNA-positive patients after renal transplantation (group I) were studied for cryoglobulins, complement hemolytic activity (CH50), and complement split product C3d. In total, 80 HCV-negative renal transplant recipients (group II) and 72 untreated patients with chronic hepatitis C (group III) without renal transplantation served as controls. Results:, Cryoglobulins were detected in 45, 28, and 26% of the patients in group I, II, and III, respectively. A high cryocrit (>5%) was present only in patients of group III (p < 0.01%). Mean CH50 values were lower and C3d levels higher in HCV-positive patients (group I and III) compared with HCV-negative patients (p < 0.0001). Cryoglobulins were not associated with extrahepatic manifestations or graft dysfunction, except in five patients of group III demonstrating cryoglobulinemic vasculitis. HCV-positive renal transplant recipients with signs of complement activation showed a significantly greater increase of serum creatinine (0.88 ± 1.14 mg/dL) when compared with baseline than patients without complement activation (0.34 ± 0.37 mg/dL; p = 0.035). There was also a tendency toward a higher extent of proteinuria in patients with complement activation (1.38 ± 2.17 g/d vs. 0.50 ± 0.77 g/d; p = 0.25, NS). Conclusions:, Cryoglobulins are common in renal allograft recipients, but do not affect graft function. However, complement activation appears to be involved in chronic allograft dysfunction in HCV-infected recipients. [source]