Pretransplant donor biopsy (PTDB)‐based marginal donor allocation systems to single or dual renal transplantation could increase the use of organs with Kidney Donor Profile Index (KDPI) in the ...highest range (e.g. >80 or >90), whose discard rate approximates 50% in the United States. To test this hypothesis, we retrospectively calculated the KDPI and analyzed the outcomes of 442 marginal kidney transplants (340 single transplants: 278 with a PTDB Remuzzi score <4 median KDPI: 87; interquartile range (IQR): 78–94 and 62 with a score = 4 median KDPI: 87; IQR: 76–93; 102 dual transplants median KDPI: 93; IQR: 86–96) and 248 single standard transplant controls (median KDPI: 36; IQR: 18–51). PTDB‐based allocation of marginal grafts led to a limited discard rate of 15% for kidneys with KDPI of 80–90 and of 37% for kidneys with a KDPI of 91–100. Although 1‐year estimated GFRs were significantly lower in recipients of marginal kidneys (−9.3, −17.9 and −18.8 mL/min, for dual transplants, single kidneys with PTDB score <4 and =4, respectively; p < 0.001), graft survival (median follow‐up 3.3 years) was similar between marginal and standard kidney transplants (hazard ratio: 1.20 95% confidence interval: 0.80–1.79; p = 0.38). In conclusion, PTDB‐based allocation allows the safe transplantation of kidneys with KDPI in the highest range that may otherwise be discarded.
This study shows that the standardized assessment of formalin‐fixed pretransplant biopsies helps recover donors with KDPI in the highest range that would be otherwise discarded, and by providing the expected graft outcomes based on KDPI and pretransplant biopsy, it guides the clinician facing the difficult decision whether to accept or reject these organs. See editorial by Gupta et al on page 2444.
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.
This prospective, randomized, PK study in de novo kidney transplant patients showed comparable systemic steady‐state tacrolimus exposure, and a good correlation between trough tacrolimus levels and AUC, for once‐ and twice‐daily tacrolimus formulations.
Abstract Introduction Delayed graft function (DGF) is a common complication in kidney transplantation. We sought to evaluate possible correlates for DGF including intraoperative parameters, focusing ...on fluid replacement and central venous pressure (CVP) values among patients undergoing kidney transplantation at our center. Methods One hundred fifty-five cadaveric donor transplantations performed at our center between 2001 and 2005 were selected for the study. We compared intraoperative parameters together with 15 other clinical and socio-demographic recipient and donor variables among patients experiencing DGF (n = 58) versus those with immediate graft function (IGF; n = 97). All significant variables at P < .05 upon univariate analysis were entered into a multivariate logistic regression model to identify risk factors for DGF. Results CVP at awakening of ≤8 mm Hg (odds ratio OR = 3.53; 95% confidence interval CI, 1.63–7.63), fluid input during surgery ≤2.250 mL (OR = 2.12; 95% CI, 1.00–4.51), and recipient age ≥50 years (OR = 2.72; 95% CI, 1.11–6.68) were the strongest correlates of DGF. Conclusions Our data suggested that reduced intraoperative perfusion as measured using CVP monitoring might increase DGF risk. This study provides the rationale to further investigate the optimal CVP target during this surgery.
Abstract This multicenter, randomized, prospective, controlled trial (EVIDENCE study) aimed to determine short-term effects of early steroid withdrawal in renal transplant patients initially treated ...with everolimus, low-dose cyclosporine (CsA), and steroids. Patients were randomized to standard triple therapy with CsA, everolimus twice daily and steroids (group A), steroid-free immunosuppression (group B), or triple therapy once daily (group C). However, since patient enrollment was slower than expected, group C randomization was prematurely discontinued. The primary end point was treatment failure rate (composite end point of death, graft loss, biopsy-proven acute rejection, and loss to follow-up) between randomization and month 12. Patients evaluable for the primary end point included 139 randomized patients. According to intention-to-treat analysis, 2.8% of patients in group A and 14.7% in group B experienced treatment failure (95% upper confidence limit 19.7%). As this was higher than the predefined noninferiority limit of 10%, noninferiority could not be proved. No conclusive statements can be made on noninferiority of the steroid withdrawal regimen vs the standard regimen in these patients. Additional studies with longer follow-up are required to determine the efficacy of steroid-free immunosuppression in renal transplant recipients receiving everolimus.
Abstract Most of the difficulties when trying to realize the proposal to prescribe physical activity for transplantation patients come from patient attitudes and cultural beliefs that ignore the ...benefits of exercise, but there also are organizational aspects arising from the difficulties that these patients face in accessing supervised exercise facilities. To address these difficulties, the Italian study project “Transplant … and Now Sport” was developed based on a model of cooperation among transplantation specialists, sports physicians, and exercise specialists organized as a team combining their specific skills to effectively actuate the physical exercise programs. This preliminary report is based on 26 patients (16 male, 10 female; 47.8 ± 10.0 years old; 21 kidney and 5 liver transplantations; time from transplantation 2.3 ± 1.4 years) who performed prescribed and supervised exercises consisting of 3 sessions per week of aerobic and strengthening exercises for 1 year. Preliminary results show a significant decrease in body mass index (t = 1.966; P < .05) and a significant increase in peak aerobic power (t = 4.535; P < .01) and maximum workload (t = 4.665; P < .01) on the incremental cycling test. Also maximum strength of knee extensors (t = 2.933; P < .05) and elbow flexors (t = 2.450; P < .05) and countermovement jump performance (t = 2.303; P < .05) significantly increased. Creatinine and proteinuria tended to decrease, but the differences were not significant. In health-related quality of life assessed by the SF-36 questionnaire, the Bodily Pain, General Health, Vitality, Social Functioning, and Role Emotional scale scores showed a significant improvement ( P < .05). Preliminary results of the study protocol “Transplant…and Now Sport” show the positive effects of the model based on cooperation among transplantation centers, sports medicine centers, and gyms in the administration of a supervised exercise prescription. These data should be considered a contribution to developing and promoting further detailed exercise protocols and to fostering improved posttransplantation health and survival, helping to ensure that physical activity becomes a safe routine medical treatment plan of patient management.
Abstract Background Kidney transplant recipients (KTRs) manifest hypercoagulable state that contributes to an increased incidence of deep vein thrombosis (DVT), not only early but also late in their ...course. KTRs display an imbalance of hemostatic mechanisms with a multifactorial rise in procoagulant factors, partly related to traditional risk factors and partly to transplantation. The aim of this study was to evaluate the incidence of first episodes of DVT among KTRs, focusing on risk factors. Methods From 2008 to 2011, we evaluated 30 kidney transplant patients who ≥4 months there after transplantation developed DVT in the lower limbs only, lower limbs complicated by pulmonary embolism or retinal thrombosis. We analyzed causes of primary nephropathy, immunosuppressive regimen, post-transplantation infections, and erythrocytosis. DVT was diagnosed by color Doppler ultrasound or eye examination. Results A significantly increased incidence of DVT was observed among patients receiving cyclosporine or cyclosporine + mammalian target of rapamycin inhibitors, affected by polycystic kidney diseases, systemic lupus erythematosus or nephrotic syndrome, or displaying rapid and/or excessive correction of hematocrit values. DVT was not significantly related to an acute infection (cytomegalovirus) or to the prior dialysis modality. Conclusions Hypercoagulability is a multifactorial condition in KTRs, representing a severe complication in stable patients. Prevention may consist of either accurate pretransplantation screening for thrombophilia or identification of patients at higher DVT risk.
Abstract We analyzed the results of kidney transplantation in autosomal dominent polycystic kidney disease (ADPKD) patients in Italy, including 14,305 transplantations performed from January 2002 to ...December 2010, including: 12,859 first single or double kidneys from cadaveric donors (13% polycystic), 172 combined liver-kidney cases (22% polycystic), and 1,303 living-donor organs (7% polycystic). Among the first transplantations (12,008 single, 851 double), with follow-ups ranging from 16 to 120 months, polycystic patients demonstrated better graft survival compared with other kidney diseases (86% vs 82% at 5 years; P < .01); mortality was not different (92% vs 79% at 1 year). A better trend was obtained also among combined liver-kidney transplantations in ADPKD. Regarding pretransplantation management of polycystic patients, we noticed a conservative attitude in 32/35 transplant centers. The main indication for nephrectomy was for the lack of abdominal space. Regarding instrumental studies, 86% of centers asked for second-level investigations computerized tomography for kidney dimensions. Radiologic investigations for vasculocerebral malformations were required in 97% of the centers: 74% as a routine and 23% in the presence of familial history of cerebral hemorrhage. Polycystic patients are good candidates for kidney transplantation with correct management before transplantation.
Abstract Introduction It is widely accepted that the risk of malignancies is significantly increased among patients with end-stage kidney disease (ESKD) and after kidney transplantation compared with ...the general population. Only a few data are available on kidney transplantation waiting list patients. The aim of this study was to investigate solid organ cancer incidence among subjects on the waiting list at a single center. Materials and Methods We retrospectively reviewed the records of all patients enrolled on our kidney transplantation waiting list between August 1, 2008 and July 31, 2010, seeking to evaluate the causes of withdrawal from the list, incidence of cancer, type of neoplasm, and its correlation with clinical features. We estimated the ratio of observed to expected numbers of cancers, the standardized incidence ratio (SIR). Results Among 1184 patients, we excluded 569 patients from the waiting list including 26 (4.56%) who displayed malignancies. The overall incidence of cancer was 0.11 events/person-months and the overall prevalence of cancer was 2.2%. In 97% of patients, the malignant disease was confined to the primitive organ of origin without secondary dissemination. We observed a prevalence of cancers related to ESKD (17; 65.38%). The SIR for all cancer types in our population compared with the general population was 2.22. The SIR for native kidney and thyroid cancers among our population compared with the general population was >10. Conclusion The incidence of cancer was significantly increased among kidney transplantation waiting list patients compared with the general population. Our study highlighted the importance of a careful, targeted neoplastic screening. It could be particularly important for ESKD-related malignancies like native kidney tumors or thyroid cancers.
Abstract Introduction The use of kidneys from expanded criteria donors (ECD) is an attractive strategy to enlarge the pool of organs available for transplantation. Considering the fact that ECD ...organs have a reduced nephron mass, they are preferentially allocated for dual-kidney transplantation (DKT). Authors have reported excellent results of DKT when pretransplant ECD organs are evaluated for histological scores. The aim of this study was to evaluate DKT donor and recipient characteristics for comparison with DKT posttransplant outcomes versus those of recipients of single-kidney transplantations from expanded criteria (edSKT) and ideal donors (idSKT). We analyzed the potential prognostic factors involved in DKT among a population derived from three transplant centers. Materials and methods Between 2001 and 2007, DKT ( n = 80) were performed based upon the ECD kidney allocation assessed by biopsy. Results The average donor ages for the DKT, edSKT, and idSKT groups were 68.8 ± 7.8, 65.3 ± 7.2, and 40.1 ± 13.8 years, respectively ( P < .001). The number of human leukocyte antigen mismatches was greater in the DKT group (3.1 ± 1.2, P < .05). Patient and graft 5-year survival rates were similar among DKT, edSKT, and idSKT recipients, namely, 97.5% versus 95.8% versus 96.9% and 93.7% versus 87.4% versus 86.9%, respectively. Mean serum creatinine values at discharge were lower in the DKT and idSKT recipients (1.5 ± 0.9 and 1.6 ± 0.7 mg/dL; P < .05) compared with the edSKT group (1.9 ± 0.7 mg/dL). Correlations between supposed prognostic factors and survival among the DKT group noted worse outcomes in reoperation cases ( P < .05). Conclusion We confirmed that DKT produced successful outcomes. An accurate surgical procedure is particularly important to try to avoid reoperations. In our experience, the use of a biopsy as an absolute criterion to allocate ECD kidneys may be too protective.
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