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Kidney Transplantation (kidney + transplantation)
Kinds of Kidney Transplantation Selected AbstractsCUMULATIVE SURVIVAL RATE BETWEEN ESRD PATIENTS UNDER TREATMENT HEMODIALYSIS AND KIDNEY TRANSPLANTATIONNEPHROLOGY, Issue 1 2002Aditiawardana [source] De novo Therapy with Everolimus, Low-Dose Ciclosporine A, Basiliximab and Steroid Elimination in Pediatric Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2010L. Pape The number of acute rejections and infections after pediatric kidney transplantation (KTX) could not be reduced in the last years. To reduce these events, we investigated a new immunosuppressive protocol in a prospective trial. After KTX, 20 children (median age 12 years, range 1,17) were initially treated with Basiliximab, ciclosporine A (CsA) (trough-level = C0 200,250 ng/mL) and prednisolone. After 2 weeks, CsA dose was reduced to 50% (C0 75,100 ng/mL, after 6 months: 50,75 ng/mL) and everolimus (1.6 mg/m2/day) was started (C0 3,6 ng/mL). Six months after KTX prednisolone was set to alternate dose and stopped 3 months later. All 20 protocol biopsies 6 months after KTX showed no acute rejection or borderline findings. Indication biopsies resulted in no acute rejections and two borderline findings. Mean glomerular filtration rate (GFR) 1 year after KTX was 71 ± 25 mL/min/1.73 m2. Without cytomegalovirus (CMV)-prophylaxis, only two primary CMV infections were seen despite a donor/recipient-CMV-constellation pos./neg. in 10/20 children. In pediatric KTX, de novo immunosuppression with low-dose CsA, everolimus and steroid withdrawal after 9 months led to promising results according to numbers of acute rejections and infections. Further follow up is needed. Future larger trials will have to confirm our findings. [source] Technical Aspects of Unilateral Dual Kidney Transplantation from Expanded Criteria Donors: Experience of 100 PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010B. Ekser One option for using organs from donors with a suboptimal nephron mass, e.g. expanded criteria donors (ECD) kidneys, is dual kidney transplantation (DKT). In adult recipients, DKT can be carried out by several techniques, but the unilateral placement of both kidneys (UDKT) offers the advantages of single surgical access and shorter operating time. One hundred UDKT were performed using kidneys from ECD donors with a mean age of 72 years (Group 1). The technique consists of transplanting both kidneys extraperitoneally in the same iliac fossa. The results were compared with a cohort of single kidney transplants (SKT) performed with the same selection criteria in the same study period (Group 2, n = 73). Ninety-five percent of UDKTs were positioned in the right iliac fossa, lengthening the right renal vein with an inferior vena cava patch. In 69% of cases, all anastomoses were to the external iliac vessels end-to-side. Surgical complications were comparable in both groups. At 3-year follow-up, patient and graft survival rates were 95.6 and 90.9% in Group 1, respectively. UDKT can be carried out with comparable surgical complication rates as SKT, leaving the contralateral iliac fossa untouched and giving elderly recipients a better chance of receiving a transplant, with optimal results up to 3-years follow-up. [source] Peritransplant Immunoadsorption for Positive Crossmatch Deceased Donor Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010G. 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] Influence of Recipient Race on the Outcome of Simultaneous Pancreas and Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010F. L. Luan Racial differences on the outcome of simultaneous pancreas and kidney (SPK) transplantation have not been well studied. We compared mortality and graft survival of African Americans (AA) recipients to other racial/ethnic groups (non-AA) using the national data. We studied a total of 6585 adult SPK transplants performed in the United States between January 1, 2000 and December 31, 2007. We performed multivariate logistic regression analyses to determine risk factors associated with early graft failure and immune-mediated late graft loss. We used conditional Kaplan,Meier survival and multivariate Cox regression analyses to estimate late death-censored kidney and pancreas graft failure and death between the groups. Although there was no racial disparity in the first 90 days, AA patients had 38% and 47% higher risk for late death-censored kidney and pancreas graft failure, respectively (p = 0.006 and 0.001). AA patients were twice more likely to lose the kidney and pancreas graft due to rejection (OR 2.31 and 1.86, p = 0.002 and 0.008, respectively). Bladder pancreas drainage was associated with inferior patient survival (HR 1.42, 95% CI 1.15, 1.75, p = 0.001). In the era of modern immunosuppresion, AA SPK transplant patients continue to have inferior graft outcome. Additional studies to explore the mechanisms of such racial disparity are warranted. [source] Case Report: Combined Pancreas and En Bloc Kidney Transplantation Using a Bladder Patch Technique From Very Small Pediatric DonorsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010J. Sageshima Very small pediatric donors are underutilized for pancreas and kidney transplantation for the fear of inadequate islet mass and higher incidence of technical complications, and the lower age limit for such donors is not well defined. We present here two cases of combined pancreas and en bloc kidney transplantation from very small pediatric donors (14 and 18 months old) to adult type 1 diabetic and uremic patients. The conventional surgical procedure for simultaneous pancreas and kidney transplantation with systemic venous and bladder exocrine drainage was successfully applied to very small organs. For both, we utilized the recently described bladder patch technique for ureteral reconstruction. One patient developed venous thrombosis (partial thrombosis of the splenic and mesenteric veins) and the other urine leak (from a midportion of the medial ureter without compromising the bladder patch) after the transplants; both were successfully managed and the patients demonstrated immediate and sustained pancreas and kidney graft functions for 12 and 2 months posttransplantation. These cases illustrate the feasibility of combined pancreas and en bloc kidney transplantation from very small pediatric donors using a bladder patch technique to avoid small ureteral anastomosis. [source] Letter to the Editor: Single Kidney Transplantation from Young Pediatric Donors in the United StatesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010D. Tittelbach-Helmrich No abstract is available for this article. [source] Letter to the Editor: Single Kidney Transplantation from Young Pediatric Donors in the United StatesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2010Liise K. Kayler No abstract is available for this article. [source] Recombinant Tissue-Type Plasminogen Activator in the Treatment of Acute Renal Artery Thrombosis After Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010A. Garcia Acute arterial thrombosis is an uncommon but potentially devastating consequence of kidney transplantation. Early recognition followed by thrombectomy may salvage the graft. We present a case of acute renal artery thrombosis after a living-related kidney transplant with successful treatment with operative thrombectomy and intraarterial infusion of recombinant tissue-type plasminogen activator. [source] Thrombotic Microangiopathy After Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010M. Noris Thrombotic microangiopathy (TMA) is a severe complication of kidney transplantation that often causes graft failure. TMA may occur de novo, often triggered by immunosuppressive drugs and acute antibody-mediated rejection, or recur in patients with previous history of hemolytic uremic syndrome (HUS). Recurrent TMA is very rare in patients who had developed end-stage renal failure following HUS caused by Shiga-toxin producing E. scherichia coli, whereas disease recurrence is common in patients with atypical HUS (aHUS). The underlying genetic defect greatly impacts the risk of posttransplant recurrence in aHUS. Indeed recurrence is almost the rule in patients with mutations in genes encoding factor H or factor I, whereas patients with a mutation in membrane-cofactor-protein gene have a good transplant outcome. Prophylactic and therapeutic options for posttransplant TMA, including plasma therapy, combined kidney and liver transplantation and targeted complement inhibitors are discussed in this review. [source] Robotic Transabdominal Kidney Transplantation in a Morbidly Obese PatientAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010P. Giulianotti Kidney transplantation in morbidly obese patients can be technically demanding. Furthermore, morbidly obese patients experience a high rate of wound infections and related complications, which mostly result from the longer length and extent of the incision. These complications can be avoided through minimally invasive surgery; however, conventional laparoscopic instruments are unsuitable for the safe performance of a kidney transplant in morbidly obese patients. Herein, we report the first minimally invasive, total robotic kidney transplant in a morbidly obese patient. A left, deceased donor kidney was transplanted into a 29-year-old woman with a body mass index (BMI) of 41 kg/m2 who had been on hemodialysis for 5 years. The operation was performed intraabdominally using the DaVinci Robotic Surgical System with 4 trocars and a 7 cm midline incision. The operative time was 223 min, and the blood loss was less than 50 cc. The kidney had immediate graft function. No perioperative complications were observed, and the patient was discharged on postoperative day 5 with normal kidney function. Minimally invasive access and robotic technology facilitated the safe performance of a successful kidney transplant in a morbidly obese patient. [source] The Elephant in the Room: Failings of Current Clinical Endpoints in Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010J. D. Schold In this opinion piece, we address the limitations of the two most common clinical endpoints in kidney transplantation trials (acute rejection and renal function) and attempt to offer a reasonable framework by which to find true and reliable early endpoints that reflect long-term outcomes. Other potential endpoints tested in recent years, including the use of genomic and proteomic markers are still in development. Until other reliable endpoints are established, it is important to understand what can be inferred from ongoing studies that utilize these endpoints and what further information we need to derive ,true' surrogate endpoints. We consider evaluation of current markers using the ,Prentice criteria', which bases assessment of endpoints as true surrogates on four primary rules. Based on our assessment, progress in understanding the safety and efficacy of new therapies and interventions in kidney transplantation will remain limited with current makers. Prospectively, we advocate: (i) significant caution in extrapolating long-term outcomes from currently utilized clinical markers, (ii) use of traditional hard endpoints whenever feasible and (iii) dedication of efforts for more data collection on specific disease entities and greater diligence in determining the onset of deleterious processes. [source] Elevated Incidence of Posttransplant Erythrocytosis After Simultaneous Pancreas Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2010G. Guerra Posttransplant erythrocytosis (PTE) poses a potential risk of thrombosis in kidney transplantation. Clinical observation of our systemically drained simultaneous kidney pancreas transplant (S-SPK) patients showed a higher incidence of PTE and need for phlebotomies. To evaluate the incidence of PTE we analyzed hematocrit (Hct) levels and frequency of phlebotomies in 94 SPK as compared to 174 living donor (LD) recipients and 53 type-I diabetic with kidney transplant only. For study purposes we defined PTE as Hct >50% or the necessity for phlebotomies. Kaplan,Meier plots and Cox proportional hazard models were used to examine the association between the transplant type and PTE. We found an increased incidence of PTE in SPK compared to LD (p < 0.001). In the multivariate model, SPK had a 5-fold risk for the development of PTE (AHR 5.3, 95% CI 1.8, 15.9). The incidence of therapeutic phlebotomy was 13% among SPK patients and 4% in LD kidney recipients; 19 patients altogether. A total of 64 units were phlebotomized (48-SPK and 16-LD). Type I diabetic patients with a kidney transplant showed a 0% incidence of PTE. We observed a greater incidence of PTE and phlebotomies in S-SPK compared to LD with kidney only transplant recipients. [source] Geographic Variation in End-Stage Renal Disease Incidence and Access to Deceased Donor Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4p2 2010A. K. Mathur The effect of demand for kidney transplantation, measured by end-stage renal disease (ESRD) incidence, on access to transplantation is unknown. Using data from the U.S. Census Bureau, Centers for Medicare & Medicaid Services (CMS) and the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients (OPTN/SRTR) from 2000 to 2008, we performed donation service area (DSA) and patient-level regression analyses to assess the effect of ESRD incidence on access to the kidney waiting list and deceased donor kidney transplantation. In DSAs, ESRD incidence increased with greater density of high ESRD incidence racial groups (African Americans and Native Americans). Wait-list and transplant rates were relatively lower in high ESRD incidence DSAs, but wait-list rates were not drastically affected by ESRD incidence at the patient level. Compared to low ESRD areas, high ESRD areas were associated with lower adjusted transplant rates among all ESRD patients (RR 0.68, 95% CI 0.66,0.70). Patients living in medium and high ESRD areas had lower transplant rates from the waiting list compared to those in low ESRD areas (medium: RR 0.68, 95% CI 0.66,0.69; high: RR 0.63, 95% CI 0.61,0.65). Geographic variation in access to kidney transplant is in part mediated by local ESRD incidence, which has implications for allocation policy development. [source] The Outcome of Patients with Nephrogenic Systemic Fibrosis after Successful Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010N. Leung Nephrogenic systemic fibrosis (NSF) is a debilitating disease in patients with severely diminished kidney function. Currently, no standard treatment exists but improvement has been reported after restoration of kidney function. We retrospectively studied 17 NSF patients with and without successful kidney transplantation (KTx) to evaluate the effects of KTx on NSF. Nine of the 11 KTx developed NSF pretransplant whereas two developed NSF immediately after KTx with delayed graft function. Two of the six dialysis patients had previous failed kidney transplants. Age and sex were well matched. All but one patient was dialysis dependent at the time of NSF. Median follow-up was 35 months for KTx patients and 9 months for dialysis patients. Kidney transplants achieved adequate renal function with median serum creatinine of 1.4 (0.9,2.8) mg/dL and a glomerular filtration rate of 42 (19,60) mL/min/1.73 m2. NSF improved in 54.6% of the transplanted patients and 50% of the nontransplanted patients (p = 0.86). Two KTx patients had complete resolution of their symptoms whereas four had partial improvement. Improvement in the dialysis patients was all partial. Successful KTx did not insure improvement in NSF and in fact appeared to have no significant benefit over dialysis. [source] Baseline Donor-Specific Antibody Levels and Outcomes in Positive Crossmatch Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010J. M. Gloor Renal transplant candidates with donor-specific alloantibody (DSA) have increased risk of antibody-mediated allograft injury. The goal of this study was to correlate the risk of antibody-mediated rejection (AMR), transplant glomerulopathy (TG) and graft survival with the baseline DSA level (prior to initiation of pretransplant conditioning). These analyses include 119 positive crossmatch (+XM) compared to 70 negative crossmatch (,XM) transplants performed between April 2000 and July 2007. Using a combination of cell-based crossmatch tests, DSA level was stratified into very high +XM, high +XM, low +XM and ,XM groups. In +XM transplants, increasing DSA level was associated with increased risk for AMR (HR = 1.76 [1.51, 2.07], p = 0.0001) but not TG (p = 0.18). We found an increased risk for both early and late allograft loss associated with very high DSA (HR = 7.71 [2.95, 20.1], p = 0.0001). Although lower DSA recipients commonly developed AMR and TG, allograft survival was similar to that of ,XM patients (p = 0.31). We conclude that the baseline DSA level correlates with risk of early and late alloantibody-mediated allograft injury. With current protocols, very high baseline DSA patients have high rates of AMR and poor long-term allograft survival highlighting the need for improved therapy for these candidates. [source] Diabetes Mellitus: A Risk Factor for Delayed Graft Function after Deceased Donor Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010J. Parekh Early graft function is a major determinant of long-term outcomes after renal transplantation. Recently, recipient diabetes was identified as a risk factor for poor initial graft function in living donor renal transplantation. To further explore this association, we performed a paired analysis of deceased donor renal transplants from January 1994 to December 2005. A total of 25,523 transplant pairs were analyzed via conditional logistic regression. Diabetic recipients were older (53.16 vs. 46.75 years, p < 0.01), had a lower average panel reactive antibody (12% vs. 15%, p < 0.01) and fewer prior transplants (0.07 vs. 0.12, p < 0.01). Recipient diabetes, age, male gender, African American race, elevated peak panel reactive antibody and increased cold ischemia time were independent risk factors for delayed graft function. Specifically, diabetic recipients had increased risk of DGF on univariate analysis (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.23,1.42, p < 0.01). Multivariable analysis confirmed this association but the risk differed by recipient gender; with diabetes having a greater effect in women (OR 1.66, 95% CI 1.45,1.91, p < 0.01) compared to men (OR 1.28, 95% CI 1.15,1.43, p < 0.01). It is unknown whether the deleterious impact of recipient diabetes on graft function after renal transplantation results from perioperative hyperglycemia or the chronic sequelae of diabetes. [source] Predicting Coronary Heart Disease after Kidney Transplantation: Patient Outcomes in Renal Transplantation (PORT) StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010A. K. Israni Traditional risk factors do not adequately explain coronary heart disease (CHD) risk after kidney transplantation. We used a large, multicenter database to compare traditional and nontraditional CHD risk factors, and to develop risk-prediction equations for kidney transplant patients in standard clinical practice. We retrospectively assessed risk factors for CHD (acute myocardial infarction, coronary artery revascularization or sudden death) in 23 575 adult kidney transplant patients from 14 transplant centers worldwide. The CHD cumulative incidence was 3.1%, 5.2% and 7.6%, at 1, 3 and 5 years posttransplant, respectively. In separate Cox proportional hazards analyses of CHD in the first posttransplant year (predicted at time of transplant), and predicted within 3 years after a clinic visit occurring in posttransplant years 1,5, important risk factors included pretransplant diabetes, new onset posttransplant diabetes, prior pre- and posttransplant cardiovascular disease events, estimated glomerular filtration rate, delayed graft function, acute rejection, age, sex, race and duration of pretransplant end-stage kidney disease. The risk-prediction equations performed well, with the time-dependent c-statistic greater than 0.75. Traditional risk factors (e.g. hypertension, dyslipidemia and cigarette smoking) added little additional predictive value. Thus, transplant-related risk factors, particularly those linked to graft function, explain much of the variation in CHD after kidney transplantation. [source] Steroids in Pediatric Kidney Transplantation: A Balancing Act in ProgressAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010John C. Magee The issue of steroid withdrawal in pediatric kidney transplantation involves risks as well as benefits, and poses analytical challenges in interpreting studies halted and unblinded prior to enrollment. See article by Benfield et al on page 81. [source] Single Kidney Transplantation from Young Pediatric Donors in the United StatesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009L. K. Kayler Kidney transplantation (KTX) from small pediatric donors is performed as single or en bloc. Criteria to determine when to split pediatric donor kidneys and transplant as singles are not well established. Data reported to the Scientific Registry of Transplant Recipient for donors <10 yrs from 1995 to 2007 were reviewed (n = 5079). Donors were categorized by weight group by 5 kg increments and solitary (n = 3503) versus en bloc (n = 1576). The primary outcome was overall graft survival. Results were compared as adjusted hazard ratios (aHR) relative to ideal standard criteria donors (SCDs) (defined as age 18,39 without other risk factors), non-ideal SCDs (all other SCDs) and expanded criteria donors (age 50,59 with other risk factors or age ,60). Single KTX from donors , 35 kg conferred a similar risk of graft survival as ideal SCDs. Of donors 10,34 kg, risks of en bloc KTX were similar to ideal and risks of single KTX to non-ideal SCDs; single and en bloc KTXs had 7.9 and 5.2 graft losses per 100 follow-up years, respectively. Single KTX from donors >35 kg are similar to ideal SCDs. Single KTX from donors 10,35 kg are similar to non-ideal SCDs. From a resource perspective, pediatric donors 10,35 kg used as singles offer more cumulative graft years than when used en bloc. [source] The Success of Continued Steroid Avoidance After Kidney Transplantation in the USAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009J. D. Schold There has been a significant increase in the use of steroid avoidance regimens as initial treatment for kidney transplant recipients. Early results of the effectiveness of this strategy has been mixed with certain prospective trials indicating increased acute rejection but population-based studies indicating similar or better graft survival as compared to steroid maintenance. We conducted a retrospective study of national registry data to evaluate risk factors for discontinuation of steroid avoidance protocols based on patient characteristics and concomitant immunosuppression. We evaluated 84 647 solitary kidney transplant recipients in the US with at least 6 months graft survival including 24 218 initially discharged without maintenance steroids. We utilized logistic models to assess risk factors for new initiation of steroids after initial steroid-avoidance and survival models to describe graft survival for patients after return to steroids. The most prominent risk factors for new initiation of steroids after deceased donor kidney transplantation included African-American race (AOR = 1.32, p < 0.01), retransplants (AOR = 1.81, p < 0.01), highly sensitized recipients (AOR = 1.29, p < 0.01), recipients with Medicaid (AOR = 1.85, p < 0.01), elevated HLA-MM (AOR = 1.26, p < 0.01) and older donor age (AOR = 1.19, p < 0.01). Concomitant medications were also significantly associated with the propensity to newly initiate steroids. Cumulatively the study suggests that both patient characteristics and concomitant medications are strongly associated with the success of steroid avoidance immunosuppressive regimens. [source] Impact of Medicare Coverage on Disparities in Access to Simultaneous Pancreas and Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009J. K. Melancon In the setting of disparities in access to simultaneous pancreas and kidney transplantation (SPKT), Medicare coverage for this procedure was initiated July 1999. The impact of this change has not yet been studied. A national cohort of 22 190 type 1 diabetic candidates aged 18,55 for kidney transplantation (KT) alone or SPKT was analyzed. Before Medicare coverage, 57% of Caucasian, 36% of African American and 38% of Hispanic type 1 diabetics were registered for SPKT versus KT alone. After Medicare coverage, these proportions increased to 68%, 45% and 43%, respectively. The overall increase in SPKT registration rate was 27% (95% CI 1.16,1.38). As expected, the increase was more substantial in patients with Medicare primary insurance than those with private insurance (Relative Rate 1.18, 95% CI 1.09,1.28). However, racial disparities were unaffected by this policy change (African American vs. Caucasian: 0.97, 95% CI 0.87,1.09; Hispanic vs. Caucasian: 0.94, 95% CI 0.78,1.05). Even after Medicare coverage, African Americans and Hispanics had almost 30% lower SPKT registration rates than their Caucasian counterparts (95% CI 0.66,0.79 and 0.59,0.80, respectively). Medicare coverage for SPKT succeeded in increasing access for patients with Medicare, but did not affect the substantial racial disparities in access to this procedure. [source] Pharmacokinetics for Once- Versus Twice-Daily Tacrolimus Formulations in De Novo Kidney Transplantation: A Randomized, Open-Label TrialAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009Z. Wlodarczyk Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC0,24 of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC0,24 and Cmin for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID. [source] Donor-Estimated GFR as an Appropriate Criterion for Allocation of ECD Kidneys into Single or Dual Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009R. Snanoudj It has been suggested that dual kidney transplantation (DKT) improves outcomes for expanded criteria donor (ECD) kidneys. However, no criteria for allocation to single or dual transplantation have been assessed prospectively. The strategy of DKT remains underused and potentially eligible kidneys are frequently discarded. We prospectively compared 81 DKT and 70 single kidney transplant (SKT) receiving grafts from ECD donors aged >65 years, allocated according to donor estimated glomerular filtration rate (eGFR): DKT if eGFR between 30 and 60 mL/min, SKT if eGFR greater than 60 mL/min. Patient and graft survival were similar in the two groups. In the DKT group, 13/81 patients lost one of their two kidneys due to hemorrhage, arterial or venous thrombosis. Mean eGFR at month 12 was similar in the DKT and SKT groups (47.8 mL/min and 46.4 mL/min, respectively). Simulated allocation of kidneys according to criteria based on day 0 donor parameters such as those described by Remuzzi et al., Andres et al. and UNOS, did not indicate an improvement in 12-month eGFR compared to our allocation based on donor eGFR. [source] Evolution of Coronary Artery Calcifications Following Kidney Transplantation: Relationship with Osteoprotegerin LevelsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009A.-S. Bargnoux We prospectively assessed the evolution of coronary artery calcification (CAC) and osteoprotegerin (OPG) levels after renal transplantation (RT). Eighty-three recipients were followed-up prospectively during 1 year. Blood was collected before (baseline) and after RT for determination of mineral metabolism parameters including OPG. CAC was measured by multidetector computed tomography at transplantation (baseline) and 1 year later. Progression of CAC was defined as a difference between the follow-up square-root transformed volume (SRV) and the baseline SRV , 2.5. By multivariate analysis, baseline OPG level, age and low LDL levels were significantly associated with baseline CAC. RT was accompanied by mineral metabolism improvement with a decrease of OPG from 955 [395,5652] to 527 [217,1818] pg/mL and parathyroid hormone from 94 [1,550] to 62 [16,410] pg/mL. Thirty-one percent of patients did not exhibit CAC at baseline. CAC diminished in 14.5%, stabilized in 59.2% and progressed in 26.3% of patients. Baseline CAC was associated with progression (OR 2.92 [1.02,8.36]). No significant association was found between OPG and CAC progression despite a higher baseline OPG level in progressors (1046 [456,3285]) vs. non-progressors (899 [396,5952] pg/mL). CAC at baseline, but not 1 year after RT, is independently associated with baseline OPG; posttransplant CAC progression is predicted by baseline CAC score. [source] Subgroup Analyses in Randomized Controlled Trials: The Need for Risk Stratification in Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009M. Wagner Although randomized controlled trials (RCT) are the gold standard for establishing causation in clinical research, their aggregated results can be misleading when applied to individual patients. A treatment may be beneficial in some patients, but its harms may outweigh benefits in others. While conventional one-variable-at-a-time subgroup analyses have well-known limitations, multivariable risk-based analyses can help uncover clinically significant heterogeneity in treatment effects that may be otherwise obscured. Trials in kidney transplantation have yielded the finding that a reduction in acute rejection does not translate into a similar benefit in prolonging graft survival and improving graft function. This paradox might be explained by the variation in risk for acute rejection among included kidney transplant recipients varying the likelihood of benefit or harm from intense immunosuppressive regimens. Analyses that stratify patients by their immunological risk may resolve these otherwise puzzling results. Reliable risk models should be developed to investigate benefits and harms in rationally designed risk-based subgroups of patients in existing RCT data sets. These risk strata would need to be validated in future prospective clinical trials examining long-term effects on patient and graft survival. This approach may allow better individualized treatment choices for kidney transplant recipients. [source] Potential Donor,Recipient MYH9 Genotype Interactions in Posttransplant Nephrotic Syndrome After Pediatric Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009B. I. Freedman Recurrence of focal segmental glomerulosclerosis (FSGS) with nephrotic syndrome is relatively common after kidney transplantation in young recipients whose predialysis course consists of heavy proteinuria, hypertension and subacute loss of kidney function. The gene(s) mediating this effect remain unknown. We report an unusual circumstance where kidneys recovered from a deceased African American male donor with MYH9 -related occult FSGS (risk variants in seven of eight MYH9 E1 haplotype single nucleotide polymorphisms) were transplanted into an African American male child with risk variants in four MYH9 E1 risk variants and a European American female teenager with two MYH9 E1 risk variants. Fulminant nephrotic syndrome rapidly developed in the African American recipient, whereas the European American had an uneventful posttransplant course. The kidney donor lacked significant proteinuria at the time of organ procurement. This scenario suggests that donor,recipient interactions in MYH9, as well as other gene,gene and gene,environment interactions, may lead to recurrent nephrotic syndrome after renal transplantation. The impact of transplanting kidneys from donors with multiple MYH9 risk alleles into recipients with similar genetic background at high risk for recurrent kidney disease needs to be determined. [source] Screening to Prevent Polyoma Virus Nephropathy in Kidney Transplantation: A Cost AnalysisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009F. Smith Polyoma virus nephropathy is an important cause of graft dysfunction in kidney transplant recipients and screening to prevent disease has been advocated. Although screening incurs new costs, our hypothesis is that savings from less immunosuppression in those with positive screening tests could pay for overall costs of screening. In 134 consecutive recipients, polyoma virus (positive decoy cells) was detected in the urine of 34 (25.4%) individuals over a 2-year follow-up. Of these 34, 11 had a plasma BK PCR of >7700 copies/mL. Immunosuppression was reduced stepwise in these patients until viral loads fell <1000/mL. Overall screening costs (including extra plasma PCR testing) were estimated at $33 450. Those with positive PCR had greater reductions in annual immunosuppression costs by year 2 ($6452 vs. $2799, p = 0.0015) compared to those with negative screens. At the end of the 2-year period, 61% of the screening costs were covered by less immunosuppressant costs. At the end of 30 months there were net savings. In summary, reductions in immunosuppression cover the cost of screening for polyoma viral infection. Longer-term follow-up is needed to ensure patient outcomes remain acceptable. [source] Asynchronous, Out-of-Sequence, Transcontinental Chain Kidney Transplantation: A Novel ConceptAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009F. K. Butt The organ donor shortage has been the most important hindrance in getting listed patients transplanted. Living kidney donors who are incompatible with their intended recipients are an untapped resource for expanding the donor pool through participation in transplant exchanges. Chain transplantation takes this concept further, with the potential to benefit even more recipients. We describe the first asynchronous, out of sequence transplant chain that was initiated by transcontinental shipment of an altruistic donor kidney 1 week after that recipient's incompatible donor had already donated his kidney to the next recipient in the chain. The altruistic donor kidney was transported from New York to Los Angeles and functioned immediately after transplantation. Our modified-sequence asynchronous transplant chain (MATCH) enabled eight recipients, at four different institutions, to benefit from the generosity of one altruistic donor and warrants further exploration as a promising step toward addressing the organ donor shortage. [source] A Human Anti-CD40 Monoclonal Antibody, 4D11, for Kidney Transplantation in Cynomolgus Monkeys: Induction and Maintenance TherapyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009T. Aoyagi Blockade of CD40,CD154 signaling pathway is an attractive strategy to induce potent immunosuppression and tolerance in organ transplantation. Due to its strong immunosuppressive effect shown in nonhuman primate experiments, anti-CD154 monoclonal antibodies (mAbs) have been tried in clinical settings, but it was interrupted by unexpected thromboembolic complications. Thus, inhibition of the counter molecule, CD40, has remained an alternative approach. In the previous preliminary study, we have shown that 4D11, a novel fully human anti-CD40 mAb, has a fairly potent immunosuppressive effect on kidney allograft in nonhuman primates. In this study, we aimed to confirm the efficacy and untoward events of the 2-week induction and 180-day maintenance 4D11 treatments. In both, 4D11 significantly suppressed T-cell-mediated alloimmune responses and prolonged allograft survival. Addition of weekly 4D11 administration after the induction treatment further enhanced graft survival. Complete inhibition of both donor-specific Ab and anti-4D11 Ab productions was obtained only with higher-dose maintenance therapy. No serious side effect including thromboembolic complications was noted except for a transient reduction of hematocrit in one animal, and decrease of peripheral B-cell counts in all. These results indicate that the 4D11 appears to be a promising candidate for immunosuppression in clinical organ transplantation. [source] | ||||||||||||||||||||||||||||