Friday, November 30, 2012

Donor-Specific Antibodies Adversely Affect Kidney Allograft Outcomes


Donor-Specific Antibodies Adversely Affect Kidney Allograft Outcomes

The effect of low titers of donor-specific antibodies (DSAs) detected only by sensitive solid-phase assays (SPAs) on renal transplant outcomes is unclear. We report the results of a systematic review and meta-analysis of rejection rates and graft outcomes for renal transplant recipients with such preformed DSAs, defined by positive results on SPA but negative complement-dependent cytotoxicity and flow cytometry crossmatch results. Our search identified seven retrospective cohort studies comprising a total of 1119 patients, including 145 with isolated DSA-SPA. Together, these studies suggest that the presence of DSA-SPA, despite a negative flow cytometry crossmatch result, nearly doubles the risk for antibody-mediated rejection (relative risk [RR], 1.98; 95% confidence interval [CI], 1.36–2.89; P<0.001) and increases the risk for graft failure by 76% (RR, 1.76; 95% CI, 1.13–2.74; P=0.01). These results suggest that donor selection should consider the presence of antibodies in the recipient, identified by the SPA, even in the presence of a negative flow cytometry crossmatch result.


Página original: http://jasn.asnjournals.org/cgi/content/short/23/12/2061?rss=1


Association of HLA Mismatch With Death With a Functioning Graft A...

Association of HLA Mismatch With Death With a Functioning Graft After Kidney Transplantation: A Collaborative Transplant Study Report

Authors: Opelz, G.; Döhler, B.

Source: American Journal of Transplantation, Volume 12, Number 11, 1 November 2012 , pp. 3031-3038(8)

Abstract:

HLA mismatches may correlate with risk of death with a functioning graft (DWFG) because of requirement for higher immunosuppression doses and more antirejection therapy. Deceased-donor kidney transplants (n = 177 584) performed 1990-2009 and reported to the Collaborative Transplant Study were analyzed. The incidence of DWFG was found to be 4.8% during year 1 posttransplant and 7.7% during years 2-5 (Kaplan-Meier estimates). Most frequent causes of DWFG were infection, cardiovascular disease and malignancy (32.2%, 30.9% and 3.6% in year 1; 16.4%, 29.6% and 15.9% in years 2-5). HLA-A + B + DR mismatches were significantly associated with DWFG during year 1 (p < 0.001), a correlation that diminished but persisted during years 2-5 (p < 0.001). HLA mismatch was associated with DWFG because of infection (p < 0.001 during year 1, p = 0.043 during years 2-5) or cardiovascular disease (p < 0.001 during year 1, p = 0.030 during years 2-5) but not malignancy. There was also a significant association between HLA mismatch and hospitalization for viral (p < 0.001) or bacterial (p = 0.002) infection. Multivariable analysis showed that mismatches for HLA class II were more strongly associated with both hospitalization and DWFG than mismatches for HLA class I.

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1600-6143.2012.04226.x

Affiliations: 1: Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany

Página original: http://www.ingentaconnect.com/content/mksg/ajt/2012/00000012/00000011/art00021


Thursday, November 29, 2012

Increased Urinary CCL2: Cr Ratio at 6 Months is Associated With Late Renal Allograft Loss


Increased Urinary CCL2: Cr Ratio at 6 Months is Associated With Late Renal Allograft Loss

Background: Early noninvasive markers that identify patients at risk of renal allograft loss may stratify patients for more intensive monitoring or therapy. CCL2 is a CCR2 receptor chemokine that is a chemoattractant protein for monocytes/macrophages, T cells, and natural killer cells. We have previously demonstrated in a multicenter cohort that urinary CCL2 at 6 months is an independent predictor for the development of IFTA at 24 months. The goal of this study was to determine if early urinary CCL2 is a predictor of graft loss in an independent patient cohort. Methods: A prospective, observational cohort study was conducted in the Transplant Manitoba Adult Kidney Program (n=231 patients) from 1997 to 2008. Six-month urinary CCL2 was measured by ELISA, corrected for urinary creatinine, and correlated with long-term graft outcomes. Results: Urine CCL2: Cr at 6 months was significantly associated with death-censored graft loss (HR, 2.42; 95% CI, 1.54-3.82, P<0.0001). On multivariate analysis, urinary CCL2: Cr at 6 months remained an independent predictor of death-censored graft loss (HR, 2.20; 95% CI, 1.18-4.10, P=0.01) after adjustment for pretransplant/de novo donor-specific antibody and delayed graft function. An early posttransplant (<=6 months) multivariate model of CCL2, recipient age, and delayed graft function yielded an AUC 0.87 for prediction of death-censored graft loss. A cutoff value of urinary CCL2: Cr 34.8 ng/mmol yielded a strong positive predictive value of 0.96. Conclusions: This study confirms in an independent prospective cohort that early urinary CCL2 at 6 months is a noninvasive, independent predictor for late renal allograft loss. (C) 2012 Lippincott Williams & Wilkins, Inc.

Página original: http://pdfs.journals.lww.com/transplantjournal/9000/00000/Increased_Urinary_CCL2___Cr_Ratio_at_6_Months_is.98797.pdf


Sunday, November 25, 2012

Renal Function and NODM in De Novo Renal Transplant Recipients Treated with Standard and Reduced Levels of Tacrolimus in Combination with EC-MPS


Renal Function and NODM in De Novo Renal Transplant Recipients Treated with Standard and Reduced Levels of Tacrolimus in Combination with EC-MPS

Information is lacking concerning concomitant administration of enteric-coated mycophenolate sodium with tacrolimus (EC-MPS+Tac) in renal transplant recipients (RTxR). In this 6-month, prospective, open-label, multicenter study, de novo RTxR were randomized (1 : 1) to low-dose (LD) or standard-dose (SD) Tac with basiliximab, EC-MPS 720 mg bid, and steroids. Primary objective was to compare renal function at 6-month posttransplantation. Secondary objectives were to compare the incidences of biopsy-proven acute rejection (BPAR), graft loss and death, and new-onset diabetes mellitus (NODM). 292 patients (LD , SD ) were included. Mean Tac levels were at the low end of the target range in standard-exposure patients (SD, ) and exceeded target range in low-exposure patients (LD = 151) throughout the study. There was no significant difference in mean glomerular filtration rate (GFR) between treatments (ITT-population: 63.6 versus 61.0 mL/min). Incidence of BPAR was similar (10.6% versus 9.9%). NODM was significantly less frequent in LD Tac (17% versus 31%; ); other adverse effects (AEs) were comparable. EC-MPS+Tac (LD/SD) was efficacious and well tolerated with well-preserved renal function. No renal function benefits were demonstrated, possibly related to poor adherence to reduced Tac exposure.

Página original: http://www.hindawi.com/journals/jtran/2012/941640/


Wednesday, November 21, 2012

Cinacalcet for the Treatment of Hyperparathyroidism in Kidney Transplant Recipients: A Systematic Review and Meta-analysis


Cinacalcet for the Treatment of Hyperparathyroidism in Kidney Transplant Recipients: A Systematic Review and Meta-analysis

imageBackground: Hyperparathyroidism is present in up to 50% of transplant recipients 1 year after transplant, often despite good graft function. Posttransplant patients frequently have hypercalcemia-associated hyperparathyroidism, limiting the role of vitamin D analogues and sometimes requiring parathyroidectomy. Multiple observational studies have investigated treatment of posttransplant hyperparathyroidism with the calcimimetic agent cinacalcet. Methods: We performed a systematic review and meta-analysis of prospective and retrospective studies from 2004 through January 26, 2012, using MEDLINE. We identified studies evaluating treatment with cinacalcet in renal transplant recipients with hyperparathyroidism. We performed random effects meta-analysis to determine changes in calcium, phosphorus, parathyroid hormone, and serum creatinine. Results: Twenty-one studies with 411 kidney transplant recipients treated with cinacalcet for hyperparathyroidism met inclusion criteria. Patients were treated for 3 to 24 months. By meta-analysis, calcium decreased by 1.14 mg/dL (95% confidence interval, −1.00 to −1.28), phosphorus increased by 0.46 mg/dL (95% confidence interval, 0.28–0.64), parathyroid hormone decreased by 102 pg/mL (95% confidence interval, −69 to −134), and there was no significant change in creatinine (0.02 mg/dL decrease; 95% confidence interval, −0.09 to 0.06). Cinacalcet resulted in hypocalcemia in seven patients. The most common side effect was gastrointestinal intolerance. Conclusions: From nonrandomized studies, cinacalcet appears to be safe and effective for the treatment of posttransplant hyperparathyroidism. Larger observational studies and randomized controlled trials, performed over longer follow-up times and looking at clinical outcomes, are needed to corroborate these findings.

Página original: http://journals.lww.com/transplantjournal/Fulltext/2012/11270/Cinacalcet_for_the_Treatment_of.10.aspx


Posttransplant Malignancies in Solid Organ Adult Recipients: An Analysis of the U.S. National Transplant Database


Posttransplant Malignancies in Solid Organ Adult Recipients: An Analysis of the U.S. National Transplant Database

imageBackground: De novo posttransplant malignancy (PTM) is a serious complication of transplantation. Incidences may vary among solid organ transplantations (SOTs) and may take to particular screening recommendations and posttransplantation care. Methods: Adult recipients, from the U.S. Organ Procurement Transplant Network/United Network for Organ Sharing database (data as of September 3, 2010), of a primary kidney transplantation (KT), liver transplantation (LT), heart transplantation (HT) or lung transplantation (LuT) performed in the United States between 1999 and 2008 were selected. Multiple-organ recipients and those whose grafts failed within 2 weeks after transplantation were excluded. The incidence of PTM (in 1000 person-years) was estimated using the Kaplan-Meier product-limit method and compared with SOT and the general population. Results: The cohort included 193,905 recipients (123,380 KT; 43,106 LT; 16511 HT; and 10,908 LuT). PTM incidence was 8.03, 11.0, 14.3, and 19.8 in KT, LT, HT, and LuT, respectively. In general, PTM recipients were 3 to 5 years older, mostly whites, and are males in all SOTs. In KT, the type of cancer with the highest incidence was posttransplant lymphoproliferative disorder (PTLD, 1.58%), followed by lung (1.12%), prostate (0.82%), and kidney (0.79%) cancers; in LT, PTLD (2.44%), lung and bronchial (2.18%), primary hepatic (0.91%), and prostate (0.88%) cancers; in HT, lung and bronchial (3.24%) and prostate (3.07%) cancers, and PTLD (2.24%); and in LuT, lung and bronchial cancers (5.94%), PTLD (5.72%), and colorectal cancer (1.38%). PTLD, Kaposi sarcoma, and lung and bronchial cancers were increased in all SOTs, when compared with an older (55- to 59-year-old) population. Conclusions: Cancer incidence is different among solid organ transplantations, and ratios may be higher than those in the 55- to 59-year-old population.

Página original: http://journals.lww.com/transplantjournal/Fulltext/2012/11270/Posttransplant_Malignancies_in_Solid_Organ_Adult.3.aspx


Tobacco Smoking and Solid Organ Transplantation


Tobacco Smoking and Solid Organ Transplantation

imageSmoking, both by donors and by recipients, has a major impact on outcomes after organ transplantation. Recipients of smokers' organs are at greater risk of death (lungs hazard ratio [HR], 1.36; heart HR, 1.8; and liver HR, 1.25), extended intensive care stays, and greater need for ventilation. Kidney function is significantly worse at 1 year after transplantation in recipients of grafts from smokers compared with nonsmokers. Clinicians must balance the use of such higher-risk organs with the consequences on waiting list mortality if the donor pool is reduced further by exclusion of such donors. Smoking by kidney transplant recipients significantly increases the risk of cardiovascular events (29.2% vs. 15.4%), renal fibrosis, rejection, and malignancy (HR, 2.56). Furthermore, liver recipients who smoke have higher rates of hepatic artery thrombosis, biliary complications, and malignancy (13% vs. 2%). Heart recipients with a smoking history have increased risk of developing coronary atherosclerosis (21.2% vs. 12.3%), graft dysfunction, and loss after transplantation. Self-reporting of smoking is commonplace but unreliable, which limits its use as a tool for selection of transplant candidates. Despite effective counseling and pharmacotherapy, recidivism rates after transplantation remain high (10–40%). Transplant services need to be more proactive in educating and implementing effective smoking cessation strategies to reduce rates of recidivism and the posttransplantation complications associated with smoking. The adverse impact of smoking by the recipient supports the requirement for a 6-month period of abstinence in lung recipients and cessation before other solid organs.

Página original: http://journals.lww.com/transplantjournal/Fulltext/2012/11270/Tobacco_Smoking_and_Solid_Organ_Transplantation.1.aspx


Inferior Early Posttransplant Outcomes for Recipients of Right Versus Left Deceased Donor Kidneys: An ANZDATA Registry Analysis


Inferior Early Posttransplant Outcomes for Recipients of Right Versus Left Deceased Donor Kidneys: An ANZDATA Registry Analysis

Anatomical differences between right and left kidneys could influence transplant outcome. We compared graft function and survival for left and right kidney recipients transplanted from the same deceased organ donor. Adult recipients of 4900 single kidneys procured from 2450 heart beating deceased donors in Australia and New Zealand from 1995 to 2009 were included in a paired analysis. Right kidneys were associated with more delayed graft function (DGF) (25 vs. 21% for left kidneys, p < 0.001) and, if not affected by DGF, a slower fall in serum creatinine. One-year graft survival was lower for right kidneys (89.1 vs. 91.1% for left kidneys, p = 0.001), primarily attributed to surgical complications (66 versus 35 failures for left kidneys). Beyond the first posttransplant year, kidney side was not associated with eGFR, graft or patient survival. Receipt of a right kidney is a risk factor for inferior outcomes in the first year after transplantation. A higher incidence of surgical complications suggests the shorter right renal vein may be contributory. The higher susceptibility of right kidneys to injury should be considered in organ allocation.


Página original: http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fj.1600-6143.2012.04312.x


Effect of Corticosteroid Withdrawal on Tacrolimus and Mycophenolate Mofetil Exposure in a Randomized Multicenter Study


Effect of Corticosteroid Withdrawal on Tacrolimus and Mycophenolate Mofetil Exposure in a Randomized Multicenter Study

As corticosteroid-sparing protocols are increasingly utilized in kidney transplant recipients, it is crucial to understand potential drug interactions between tacrolimus (TAC) and the effect of corticosteroid withdrawal as well as to characterize dose adjustments of mycophenolate mofetil (MMF) in this setting. This prospective, multicenter, randomized, double-blind study included 397 patients who were randomized on posttransplant day 8 to receive either placebo (CSWD) or corticosteroid continuance (CCS). TAC trough levels at week two posttransplant were significantly greater in the CSWD group whereas TAC doses were comparable to the CCS group. This interaction was not observed in the African American subgroup. Higher serum creatinine and potassium levels were also observed in the CSWD group. MMF dose was significantly reduced in the CSWD group by the investigators because of decreased WBC counts, mostly outside of study protocol criteria, despite similar incidence of neutropenia and reported cytomegalovirus infection. Understanding TAC and MMF exposure in the context of corticosteroid-sparing protocols should allow for improved dosing of immunosuppressants and better management of posttransplant patients.


Página original: http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fj.1600-6143.2012.04327.x

Enviado desde Feeddler RSS Reader



Enviado desde mi iPhone

Treatment of Steroid-Resistant Acute Renal Allograft Rejection With Alemtuzumab


Treatment of Steroid-Resistant Acute Renal Allograft Rejection With Alemtuzumab

Steroid-resistant renal allograft rejections are commonly treated with rabbit antithymocyte globulin (RATG), but alemtuzumab could be an effective, safe and more convenient alternative. Adult patients with steroid-resistant renal allograft rejection treated with alemtuzumab (15–30 mg s.c. on 2 subsequent days) from 2008 to 2012 (n = 11) were compared to patients treated with RATG (2.5-4.0 mg/kg bodyweight i.v. for 10–14 days; n = 20). We assessed treatment-failure (graft loss, lack of improvement of graft function or need for additional anti-rejection treatment), infections during the first 3 months after treatment and infusion-related side effects. In both groups, the median time-interval between rejection and transplantation was 2 weeks, and approximately 75% of rejections were classified as Banff-IIA or higher. Three alemtuzumab-treated patients (27%) experienced treatment failure, compared to eight RATG treated patients (40%, p = 0.70). There was no difference in the incidence of infections. There were mild infusion-related side-effects in three alemtuzumab-treated patients (27%), and more severe infusion-related side effects in 17 RATG-treated patients (85%, p = 0.013). Drug related costs of alemtuzumab-treatment were lower than of RATG-treatment (€1050 vs. €2024; p < 0.01). Alemtuzumab might be an effective therapy for steroid-resistant renal allograft rejections. In contrast to RATG, alemtuzumab is nearly devoid of infusion-related side-effects. These data warrant a prospective trial.


Página original: http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fj.1600-6143.2012.04328.x


Saturday, November 17, 2012

Factors Predictive of Medication Nonadherence After Renal Transplantation: A French Observational Study


Factors Predictive of Medication Nonadherence After Renal Transplantation: A French Observational Study

Background: There have been few prospective studies on the natural history of nonadherence (NA) in kidney transplant recipients (KTRs) over time. The objective of this study was to prospectively evaluate the rate of and risk factors for NA in a French cohort of KTRs. Method: A total of 312 KTRs from eight French transplantation centers were included in this prospective, noninterventional cohort study. A computer-learning software package (the Organ Transplant Information System) was made available to all patients. Results: Using the four-item Morisky scale, we showed that 17.3%, 24.1%, 30.7%, and 34.6% of patients were nonadherent at posttransplant month 3 (M3), M6, M12, and M24, respectively. Young age was predictive of NA at M6, M12, and M24. Surprisingly, simple treatment regimens including a small number of doses per day and a small number of tablets per day were associated with NA at M3 and M12, respectively. Other factors predictive of NA included failure to use the Organ Transplant Information System software package at M6 and patient reports of adverse events at M12 and M24. Importantly, we observed that physicians underestimated the prevalence of adverse events when compared to patient self-reporting. Conclusion: Our observed rate of medication NA in France is consistent with rates reported in previous studies. We found variability in NA risk factors over time as well as an unexpected risk factor (simple treatment regimens). These findings will be useful in developing effective adherence-promoting interventions. (C) 2012 Lippincott Williams & Wilkins, Inc.

Página original: http://pdfs.journals.lww.com/transplantjournal/9000/00000/Factors_Predictive_of_Medication_Nonadherence.98812.pdf


Cancer Transmission From Organ Donors-Unavoidable but Low Risk


Cancer Transmission From Organ Donors-Unavoidable but Low Risk

Background: Donor origin cancer (DOC) in transplant recipients may be transmitted with the graft (donor-transmitted cancer [DTC]) or develop subsequently from the graft (donor-derived cancer [DDC]). Methods: Recipients with DOC between January 1, 2001, and December 31, 2010, were identified from the United Kingdom Transplant Registry and database search at transplantation centers. Results: Of 30,765 transplants from 14,986 donors, 18 recipients developed DOC from 16 donors (0.06%): 3 were DDC (0.01%) and 15 were DTC (0.05%). Of the 15 DTCs, 6 were renal cell cancer; 5, lung cancer; 2, lymphoma; 1, neuroendocrine cancer; and 1, colon cancer. Recipients with DTC underwent explant/excision (11), chemotherapy (4), and radiotherapy (1). Of 15 recipients, 3 (20%) recipients with DTC died as a direct consequence of cancer. Early DTC (diagnosed <=6 weeks of transplantation) showed a better outcome (no DTC-related deaths in 11 cases) as opposed to late DTC (DTC-related deaths in 3 of 4 cases). Five-year survival was 83% for kidney recipients with DTC compared with 93% for recipients without DTC (P=0.077). None of the donors resulting in cancer transmission was known to have cancer at donation. Conclusions: DTC is rare but frequently results in graft loss and death. The risk of cancer transmission cannot be eliminated because, in every case, the presence of cancer was not known at donation. This information will allow informed consent for prospective recipients. Explantation/excision is likely to benefit recipients with localized cancer, but in transplants other than kidney/pancreas, the benefits should be balanced against the risks of retransplantation. (C) 2012 Lippincott Williams & Wilkins, Inc.

Página original: http://pdfs.journals.lww.com/transplantjournal/9000/00000/Cancer_Transmission_From_Organ_Donors_Unavoidable.98807.pdf

Tuesday, November 13, 2012

BK Virus Replication and Nephropathy After Alemtuzumab-Induced Kidney Transplantation.


BK Virus Replication and Nephropathy After Alemtuzumab-Induced Kidney Transplantation.

BK virus nephropathy (BKVN) is a recognized cause of graft failure in kidney transplant recipients. There are limited data on the epidemiology of BK virus (BKV) infection after alemtuzumab induction. By clinical protocol, the kidney transplant recipients at our center were screened with BKV plasma PCR monthly for the first 4 months posttransplant then every 2-3 months for 2 years. A single center retrospective cohort study of all kidney transplant recipients from January 2008 to August 2010 was conducted to determine incidence and outcomes of BKV infection. Descriptive statistics and Kaplan-Meier analysis was performed. Of 666 recipients, 250 (37.5%) developed viruria, 80 (12%) developed viremia and 31 (4.7%) developed BKVN at a median of 17, 21 and 30 weeks, respectively. Induction with alemtuzumab did not significantly affect incidence of BKVN. Increased recipient age, African American race, acute graft rejection and CMV infection were significantly associated with the development of BKVN in multivariate analysis. The incidence of BK viruria, viremia and nephropathy was not significantly different among kidney transplant recipients who received alemtuzumab induction compared to patients receiving less potent induction.

Página original: http://www.unboundmedicine.com/medline/citation/23136975/BK_Virus_Replication_and_Nephropathy_After_Alemtuzumab_Induced_Kidney_Transplantation_

Enviado desde Feeddler RSS Reader



ALBERTO REINO BUELVAS
Enviado desde mi iPad

Polyomavirus BK Replication in De Novo Kidney Transplant Patients Receiving Tacrolimus or Cyclosporine: A Prospective, Randomized, Multicenter Study.


Polyomavirus BK Replication in De Novo Kidney Transplant Patients Receiving Tacrolimus or Cyclosporine: A Prospective, Randomized, Multicenter Study.

Polyomavirus BK (BKV)-associated nephropathy causes premature kidney transplant (KT) failure. BKV viruria and viremia are biomarkers of disease progression, but associated risk factors are controversial. A total of 682 KT patients receiving basiliximab, mycophenolic acid (MPA), corticosteroids were randomized 1:1 to cyclosporine (CsA) or tacrolimus (Tac). Risk factors were analyzed in 629 (92.2%) patients having at least 2 BKV measurements until month 12 posttransplant. Univariate analysis associated CsA-MPA with lower rates of viremia than Tac-MPA at month 6 (10.6% vs. 16.3%, p = 0.048) and 12 (4.8% vs. 12.1%, p = 0.004) and lower plasma BKV loads at month 12 (3.9 vs. 5.1 log(10) copies/mL; p = 0.028). In multivariate models, CsA-MPA remained associated with less viremia than Tac-MPA at month 6 (OR 0.60; 95% CI 0.36-0.99) and month 12 (OR 0.33; 95% CI 0.16-0.68). Viremia at month 6 was also independently associated with higher steroid exposure until month 3 (OR 1.19 per 1 g), and with male gender (OR 2.49) and recipient age (OR 1.14 per 10 years) at month 12. The data suggest a dynamic risk factor evolution of BKV viremia consisting of higher corticosteroids until month 3, Tac-MPA compared to CsA-MPA at month 6 and Tac-MPA, older age, male gender at month 12 posttransplant.

Página original: http://www.unboundmedicine.com/medline/citation/23137180/Polyomavirus_BK_Replication_in_De_Novo_Kidney_Transplant_Patients_Receiving_Tacrolimus_or_Cyclosporine:_A_Prospective_Randomized_Multicenter_Study_

Enviado desde Feeddler RSS Reader



ALBERTO REINO BUELVAS
Enviado desde mi iPad

Estimating Glomerular Filtration Rate in Kidney Transplant Recipients: Performance Over Time of Four Creatinine-Based Formulas


Estimating Glomerular Filtration Rate in Kidney Transplant Recipients: Performance Over Time of Four Creatinine-Based Formulas

imageBackground. The management of kidney transplant recipients requires accurate estimate of glomerular filtration rate (GFR). This study aims at evaluating the performance of four creatinine-based formulas for estimating the GFR (estimated GFR) in this population. Methods. Performances of Cockcroft and Gault formula, Modification of Diet in Renal Disease (MDRD) simplified formula, Chronic Kidney Disease Epidemiology Collaboration formula, and Nankivell formula were assessed compared with inulin clearance taken as the gold standard for measuring GFR (measured GFR). Performances were assessed using the first measurements of GFR obtained in 1249 subjects. How estimated GFR tracks changes in measured GFR over time since transplantation in those patients with repeated measures was also assessed. Results. The MDRD formula provided the best estimate of GFR with a mean bias of −0.5 mL/min/1.73 m2, a standard deviation of bias of 12 mL/min/1.73 m2, and a 30% accuracy at 85%. The MDRD formula also seemed to provide the best performance for estimating GFR, irrespective of age, stage of renal failure, and in people whose body mass index was more than 18.5 kg/m2. This robustness is important in clinical practice. The performance of the four formulas was not modified by the posttransplant period. Conclusion. Even if 30% accuracy was suboptimal in the Kidney Disease Outcomes Quality Initiative guidelines, our results, obtained in a large number of patients, lead us to recommend using the MDRD formula to monitor GFR in kidney transplant recipients.

Página original: http://journals.lww.com/transplantjournal/Fulltext/2011/11150/Estimating_Glomerular_Filtration_Rate_in_Kidney.9.aspx

Enviado desde Feeddler RSS Reader



Enviado desde mi iPhone

Friday, November 9, 2012

Ciprofloxacin Prophylaxis in Kidney Transplant Recipients Reduces BK Virus Infection at 3 Months but not at 1 Year


Ciprofloxacin Prophylaxis in Kidney Transplant Recipients Reduces BK Virus Infection at 3 Months but not at 1 Year

Background: BK polyomavirus (BKV) infection remains a significant cause of nephropathy and graft loss. Fluoroquinolones inhibit BKV replication in vitro, and small studies suggest in vivo benefit. A strategy of fluoroquinolone prophylaxis directed specifically against BKV has not been formally tested against a control group in kidney transplant recipients. Methods: We retrospectively compared the impact of a change in antibiotic prophylaxis practice from no BKV prophylaxis (Group 1, n=106, July-December 2009) to BKV prophylaxis with ciprofloxacin 250 mg twice daily for 30 days (Group 2, n=130, January-June 2010) on the rate of BKV infection during the first 12 months after kidney transplantation. Results: Baseline demographics, transplant characteristics, induction immunosuppression, and 1-year incidence of acute rejection were similar between groups. Group 1 had fewer patients on maintenance corticosteroids (65.1% vs. 83.2%, P=0.002). At 3 months, Group 1 had a significantly higher risk of developing BK viremia (0.161 vs. 0.065, P=0.0378) and viruria (0.303 vs. 0.146, P=0.0067) compared with Group 2, but this difference disappeared at 12 months for both viremia (0.297 vs. 0.261, P=0.6061) and viruria (0.437 vs. 0.389, P=0.5363). Adjusting for the difference in steroid use did not change the results. There was a trend toward higher incidence of biopsy-proven BKV nephropathy in Group 1 (4.7% vs. 0.8%, P=0.057). Conclusion: Thirty-day ciprofloxacin prophylaxis in kidney transplant recipients is associated with a lower rate of BKV infection at 3 months but not at 12 months. The long-term effectiveness and optimal duration of fluoroquinolone prophylaxis against BKV infection remain unknown. (C) 2012 Lippincott Williams & Wilkins, Inc.

Página original: http://pdfs.journals.lww.com/transplantjournal/9000/00000/Ciprofloxacin_Prophylaxis_in_Kidney_Transplant.98855.pdf

Enviado desde Feeddler RSS Reader



Enviado desde mi iPhone

Kidney Graft Survival in Europe and the United States: Strikingly Different Long-term Outcomes


Kidney Graft Survival in Europe and the United States: Strikingly Different Long-term Outcomes

Background: Kidney graft survival has never been systematically compared between Europe and the United States. Methods: Applying period analysis to first deceased-donor (DD) and living-donor kidney grafts from the United Network for Organ Sharing/Organ Procurement and Transplantation Network for the United States and the Collaborative Transplant Study for Europe, we compared overall and age-specific 1-, 5-, and 10-year graft survival for Europeans and white, African, and Hispanic Americans for the 2005 to 2008 period. A Cox regression model was used to adjust for differences in patient characteristics. Results: For the 2005 to 2008 period, 1-year survival for DD grafts was equal (91%) between Europeans and white and Hispanic Americans, whereas it was slightly lower for African Americans (89%). In contrast, overall 5- and 10-year graft survival rates were considerably higher for Europe (77 and 56%, respectively) than for any of the three U.S. populations (whites, 71 and 46%, Hispanic, 73 and 48%, and African American, 62 and 34%). Differences were largest for recipient ages 0 to 17 and 18 to 29 and generally increased beyond 3 to 4 years after transplantation. Survival patterns for living-donor grafts were similar as those seen for DD grafts. Adjusted hazard ratios for graft failure in United Network for Organ Sharing white Americans ranged between 1.5 and 2.3 (all P<0.001) for 2 to 5 years after transplantation, indicating that lower graft survival is not explained by differences in baseline patient characteristics. Conclusions: Long-term kidney graft survival rates are markedly lower in the United States compared with Europe. Identifying actionable factors explaining long-term graft survival differences between Europe and the United States is a high priority for improving long-term graft survival. (C) 2012 Lippincott Williams & Wilkins, Inc.

Página original: http://pdfs.journals.lww.com/transplantjournal/9000/00000/Kidney_Graft_Survival_in_Europe_and_the_United.98853.pdf

Enviado desde Feeddler RSS Reader



Enviado desde mi iPhone

Intravesical Versus Extravesical Ureteroneocystostomy in Kidney Transplantation: A Systematic Review and Meta-Analysis


Intravesical Versus Extravesical Ureteroneocystostomy in Kidney Transplantation: A Systematic Review and Meta-Analysis

Background: Urologic complications are still a major problem postoperatively with a reported incidence of up to 30%, associated with significant morbidity, mortality, prolonged hospital stay, and high medical costs. To date, there is no evidence favoring either an extravesical or an intravesical approach. The purpose of this systematic review and meta-analysis is to determine if an intravesical or an extravesical anastomosis in kidney transplantation is to be preferred. Methods: Comprehensive searches were conducted in PubMed, Embase, and the Cochrane Library. Reference lists were searched manually. The methodology was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement. Two randomized controlled trials and 17 cohort studies were identified. Results: Based on the meta-analysis, outcome was in favor of the extravesical anastomosis. A relative risk of 0.67 (95% confidence interval [95% CI], 0.48-0.93; P=0.02) for stenosis, 0.55 (95% CI, 0.39-0.80; P=0.001) for leakage, 0.56 (95% CI, 0.41-0.76; P<0.001) for the total number of urologic complications, and 0.41 (95% CI, 0.22-0.76; P=0.005) for hematuria was demonstrated. Conclusion: Based on our results, we conclude that there is evidence in favor of the extravesical ureteroneocystostomy for having a smaller amount of urologic complications in kidney transplantation. (C) 2012 Lippincott Williams & Wilkins, Inc.

Página original: http://pdfs.journals.lww.com/transplantjournal/9000/00000/Intravesical_Versus_Extravesical.98851.pdf

Enviado desde Feeddler RSS Reader



Enviado desde mi iPhone

Cinacalcet for the Treatment of Hyperparathyroidism in Kidney Transplant Recipients: A Systematic Review and Meta-analysis


Cinacalcet for the Treatment of Hyperparathyroidism in Kidney Transplant Recipients: A Systematic Review and Meta-analysis

Background: Hyperparathyroidism is present in up to 50% of transplant recipients 1 year after transplant, often despite good graft function. Posttransplant patients frequently have hypercalcemia-associated hyperparathyroidism, limiting the role of vitamin D analogues and sometimes requiring parathyroidectomy. Multiple observational studies have investigated treatment of posttransplant hyperparathyroidism with the calcimimetic agent cinacalcet. Methods: We performed a systematic review and meta-analysis of prospective and retrospective studies from 2004 through January 26, 2012, using MEDLINE. We identified studies evaluating treatment with cinacalcet in renal transplant recipients with hyperparathyroidism. We performed random effects meta-analysis to determine changes in calcium, phosphorus, parathyroid hormone, and serum creatinine. Results: Twenty-one studies with 411 kidney transplant recipients treated with cinacalcet for hyperparathyroidism met inclusion criteria. Patients were treated for 3 to 24 months. By meta-analysis, calcium decreased by 1.14 mg/dL (95% confidence interval, -1.00 to -1.28), phosphorus increased by 0.46 mg/dL (95% confidence interval, 0.28-0.64), parathyroid hormone decreased by 102 pg/mL (95% confidence interval, -69 to -134), and there was no significant change in creatinine (0.02 mg/dL decrease; 95% confidence interval, -0.09 to 0.06). Cinacalcet resulted in hypocalcemia in seven patients. The most common side effect was gastrointestinal intolerance. Conclusion: From nonrandomized studies, cinacalcet appears to be safe and effective for the treatment of posttransplant hyperparathyroidism. Larger observational studies and randomized controlled trials, performed over longer follow-up times and looking at clinical outcomes, are needed to corroborate these findings. (C) 2012 Lippincott Williams & Wilkins, Inc.

Página original: http://pdfs.journals.lww.com/transplantjournal/9000/00000/Cinacalcet_for_the_Treatment_of.98848.pdf

Enviado desde Feeddler RSS Reader



Enviado desde mi iPhone

Effects of HLA-Matched Blood Transfusion for Patients Awaiting Renal Transplantation


Effects of HLA-Matched Blood Transfusion for Patients Awaiting Renal Transplantation

Background: HLA sensitization in potential renal transplant recipients hinders opportunities of receiving suitable organs. To alleviate this, we sought to determine if supplying closely HLA Class I matched leukodepleted blood would minimize sensitization. Methods: Patients received HLA selected or random units of packed red cells. Selected units were sourced from blood donors included in the British Bone Marrow Registry and had no HLA-A and HLA-B mismatches where available, or alternatively, no HLA antigens with more than five immunogenic triplet mismatches as determined by the HLAMatchmaker algorithm. Posttransfusion antibody screening confirmed development of de novo Class I and Class II HLA-specific IgG antibody(s) or increases in preexisting antibody levels of at least 20%. Results: Thirty-seven and 31 patients received HLA selected (mean, 2.5 units) and random (mean, 3.4 units) blood, respectively. A total of 20 of 37 (54.1%) patients receiving selected units and 10 of 31 (32.3%) patients receiving random units were previously sensitized. No patient receiving HLA selected units demonstrated any change in antibody levels. In patients who received random units, 7 of 31 demonstrated changes in antibody levels with three developing de novo HLA-specific antibodies and four an increase in panel reactive antibody (PRA) of at least 20% (P=0.002). Conclusions: The risk of developing HLA-specific antibody is significantly reduced in renal patients awaiting transplantation when transfused with HLA selected units of blood compared with random units. With planning, access to HLA typed blood is achievable as many blood transfusion centers recruit donors for stem cell donor registries. (C) 2012 Lippincott Williams & Wilkins, Inc.

Página original: http://pdfs.journals.lww.com/transplantjournal/9000/00000/Effects_of_HLA_Matched_Blood_Transfusion_for.98830.pdf

Enviado desde Feeddler RSS Reader



Enviado desde mi iPhone

Posttransplant Malignancies in Solid Organ Adult Recipients: An Analysis of the U.S. National Transplant Database


Posttransplant Malignancies in Solid Organ Adult Recipients: An Analysis of the U.S. National Transplant Database

Background: De novo posttransplant malignancy (PTM) is a serious complication of transplantation. Incidences may vary among solid organ transplantations (SOTs) and may take to particular screening recommendations and posttransplantation care. Methods: Adult recipients, from the U.S. Organ Procurement Transplant Network/United Network for Organ Sharing database (data as of September 3, 2010), of a primary kidney transplantation (KT), liver transplantation (LT), heart transplantation (HT) or lung transplantation (LuT) performed in the United States between 1999 and 2008 were selected. Multiple-organ recipients and those whose grafts failed within 2 weeks after transplantation were excluded. The incidence of PTM (in 1000 person-years) was estimated using the Kaplan-Meier product-limit method and compared with SOT and the general population. Results: The cohort included 193,905 recipients (123,380 KT; 43,106 LT; 16511 HT; and 10,908 LuT). PTM incidence was 8.03, 11.0, 14.3, and 19.8 in KT, LT, HT, and LuT, respectively. In general, PTM recipients were 3 to 5 years older, mostly whites, and are males in all SOTs. In KT, the type of cancer with the highest incidence was posttransplant lymphoproliferative disorder (PTLD, 1.58%), followed by lung (1.12%), prostate (0.82%), and kidney (0.79%) cancers; in LT, PTLD (2.44%), lung and bronchial (2.18%), primary hepatic (0.91%), and prostate (0.88%) cancers; in HT, lung and bronchial (3.24%) and prostate (3.07%) cancers, and PTLD (2.24%); and in LuT, lung and bronchial cancers (5.94%), PTLD (5.72%), and colorectal cancer (1.38%). PTLD, Kaposi sarcoma, and lung and bronchial cancers were increased in all SOTs, when compared with an older (55- to 59-year-old) population. Conclusions: Cancer incidence is different among solid organ transplantations, and ratios may be higher than those in the 55- to 59-year-old population. (C) 2012 Lippincott Williams & Wilkins, Inc.

Página original: http://pdfs.journals.lww.com/transplantjournal/9000/00000/Posttransplant_Malignancies_in_Solid_Organ_Adult.98841.pdf

Enviado desde Feeddler RSS Reader



Enviado desde mi iPhone

Tobacco Smoking and Solid Organ Transplantation


Tobacco Smoking and Solid Organ Transplantation

Smoking, both by donors and by recipients, has a major impact on outcomes after organ transplantation. Recipients of smokers' organs are at greater risk of death (lungs hazard ratio [HR], 1.36; heart HR, 1.8; and liver HR, 1.25), extended intensive care stays, and greater need for ventilation. Kidney function is significantly worse at 1 year after transplantation in recipients of grafts from smokers compared with nonsmokers. Clinicians must balance the use of such higher-risk organs with the consequences on waiting list mortality if the donor pool is reduced further by exclusion of such donors. Smoking by kidney transplant recipients significantly increases the risk of cardiovascular events (29.2% vs. 15.4%), renal fibrosis, rejection, and malignancy (HR, 2.56). Furthermore, liver recipients who smoke have higher rates of hepatic artery thrombosis, biliary complications, and malignancy (13% vs. 2%). Heart recipients with a smoking history have increased risk of developing coronary atherosclerosis (21.2% vs. 12.3%), graft dysfunction, and loss after transplantation. Self-reporting of smoking is commonplace but unreliable, which limits its use as a tool for selection of transplant candidates. Despite effective counseling and pharmacotherapy, recidivism rates after transplantation remain high (10-40%). Transplant services need to be more proactive in educating and implementing effective smoking cessation strategies to reduce rates of recidivism and the posttransplantation complications associated with smoking. The adverse impact of smoking by the recipient supports the requirement for a 6-month period of abstinence in lung recipients and cessation before other solid organs. (C) 2012 Lippincott Williams & Wilkins, Inc.

Página original: http://pdfs.journals.lww.com/transplantjournal/9000/00000/Tobacco_Smoking_and_Solid_Organ_Transplantation.98836.pdf

Enviado desde Feeddler RSS Reader



Enviado desde mi iPhone

Management and Outcome of BK Viremia in Renal Transplant Recipients: A Prospective Single-Center Study


Management and Outcome of BK Viremia in Renal Transplant Recipients: A Prospective Single-Center Study

imageBackground: BK viremia can lead to nephritis, which can progress to irreversible kidney transplant failure. Our prospective study provides management and outcome of BK viremia in renal transplant recipients. Methods: Two hundred forty de novo kidney-only recipients were enrolled from July 2007 to July 2010 and followed for 1 year. Standard immunosuppression with Thymoglobulin/interleukin 2 receptor blocker and mycophenolate mofetil/tacrolimus (Tac)/prednisone was employed. Quantitative BK virus (BKV) DNA surveillance in plasma/urine was performed at 1, 3, 6, 12, and 24 months after transplantation. Patients with significant viremia (defined as ≥10,000 viral copies/mL) underwent renal biopsy and treated with 30% to 50% reduction in doses of both mycophenolate mofetil and Tac without antiviral therapy. The target 12-hr Tac trough levels were lowered to 4 to 6 ng/mL in the significant viremia group, whereas the target levels remained unchanged at 5 to 8 ng/mL for all other groups. Results: Sixty-five patients (27%) developed BK viremia; 28 (12%) of whom had significant viremia. A total of five (21%) of the 23 (of 28) patients who underwent biopsy presented with subclinical BKV nephritis. The mean plasma BKV DNA declined by 98% (range, 76%–100%) at 1 year after peak viremia. Acute cellular rejection seen in four (14%) of 28 patients, responded to bolus steroids. There was no decline in estimated glomerular filtration rate over time from 1 month after transplantation to 1 year after peak viremia (P=0.57). Conclusion: Reduction in immunosuppression alone resulted in the successful resolution of viremia with preservation of renal function and prevention of clinical BKV nephritis and graft loss.

Página original: http://journals.lww.com/transplantjournal/Fulltext/2012/10270/Management_and_Outcome_of_BK_Viremia_in_Renal.6.aspx

Enviado desde Feeddler RSS Reader



Enviado desde mi iPhone

BK Virus Replication and Nephropathy After Alemtuzumab-Induced Kidney Transplantation

BK Virus Replication and Nephropathy After Alemtuzumab-Induced Kidney Transplantation

BK virus nephropathy (BKVN) is a recognized cause of graft failure in kidney transplant recipients. There are limited data on the epidemiology of BK virus (BKV) infection after alemtuzumab induction. By clinical protocol, the kidney transplant recipients at our center were screened with BKV plasma PCR monthly for the first 4 months posttransplant then every 2–3 months for 2 years. A single center retrospective cohort study of all kidney transplant recipients from January 2008 to August 2010 was conducted to determine incidence and outcomes of BKV infection. Descriptive statistics and Kaplan–Meier analysis was performed. Of 666 recipients, 250 (37.5%) developed viruria, 80 (12%) developed viremia and 31 (4.7%) developed BKVN at a median of 17, 21 and 30 weeks, respectively. Induction with alemtuzumab did not significantly affect incidence of BKVN. Increased recipient age, African American race, acute graft rejection and CMV infection were significantly associated with the development of BKVN in multivariate analysis. The incidence of BK viruria, viremia and nephropathy was not significantly different among kidney transplant recipients who received alemtuzumab induction compared to patients receiving less potent induction.

Thursday, November 8, 2012

Concurrent Acute Cellular Rejection Is an Independent Risk Factor for Renal Allograft Failure in Patients With C4d-Positive Antibody-Mediated Rejection

Concurrent Acute Cellular Rejection Is an Independent Risk Factor for Renal Allograft Failure in Patients With C4d-Positive Antibody-Mediated Rejection

Background: Identification of risk factors for renal allograft failure after an episode of acute antibody-mediated rejection (AMR) may help the outcome of this difficult-to-treat complication. Methods: During December 2003 to February 2011, 833 kidney graft recipients underwent 1120 clinically indicated biopsies at our center. We reviewed the biopsy results and identified 87 biopsy specimens from 87 patients positive for the degradation product of complement component 4 (C4d) and acute AMR. We generated Kaplan-Meier survival curves and performed a multivariable analysis using the Cox proportional hazards regression model to identify risk factors for allograft failure after C4d+ acute AMR. Results: Among the 87 patients, 26 had a diagnosis of acute AMR according to the Banff ’09 classification schema, 29 had acute AMR and chronic active AMR, 18 had acute AMR and acute T-cell mediated rejection (TCMR), and 14 had acute AMR, chronic active AMR, and acute TCMR. Kaplan-Meier survival estimates showed that concurrent acute TCMR (P=0.001, Mantel-Cox log-rank test), concurrent chronic active AMR (P=0.03), and time to biopsy (P=0.04) are associated with graft survival. The Cox proportional hazards regression analysis identified that concurrent acute TCMR (hazard ratio, 2.59 [95% confidence interval, 1.21–5.55]; P=0.01) and estimated glomerular filtration rate (hazard ratio, 0.65 [95% confidence interval, 0.48–0.88]; P=0.01) are independent risk factors for allograft loss. Concurrent chronic active AMR or time to biopsy was not associated with graft failure by the multivariable Cox analysis. Conclusions: Our single-center study has elucidated that concurrent acute TCMR in kidney transplant recipients with C4d+ acute AMR is an independent risk factor for graft failure. Level of allograft function at the time of diagnosis was also an independent predictor of graft loss.

Late Calcineurin Inhibitor Withdrawal Prevents Progressive Left Ventricular Diastolic Dysfunction in Renal Transplant Recipients

Late Calcineurin Inhibitor Withdrawal Prevents Progressive Left Ventricular Diastolic Dysfunction in Renal Transplant Recipients

Background: Calcineurin inhibitor (CNI)–based therapy is associated with adverse cardiovascular effects. We examined the effects of late CNI or mycophenolate mofetil (MMF) withdrawal on echocardiographic parameters. Methods: This study was conducted as a substudy of a randomized trial in stable renal transplant recipients who were on a triple CNI-based regimen with prednisone and MMF that evaluated late concentration-controlled withdrawal of CNI or MMF on renal function. A total of 108 patients (age, 52.3±11.5 years; 67% male; at a median of 2.0 years post-transplantation, (interquartile range 1.3–3.3 years); estimated glomerular filtration rate, 57±16 mL/min/1.73 m2; 66% on cyclosporine and 34% on tacrolimus) entered the cardiovascular substudy examining echocardiographic parameters at baseline and 2 years after randomization. In all patients, traditional cardiovascular risk factors were treated according to predefined targets. Results: Late CNI withdrawal prevented progressive development of left ventricular (LV) diastolic dysfunction, as assessed by markers of LV diastolic function (mitral deceleration time and mitral annular e′ velocity). Conversely, in the MMF-withdrawal group, the left atrial volume index (an indicator of chronic LV diastolic dysfunction) was significantly increased at 2 years (from 24.1±6.7 to 27.0±7.0 mL/m2, P<0.05). In addition, CNI withdrawal resulted in a higher proportion of patients achieving the predefined blood pressure targets (<130/85 mm Hg: 41.5% vs. 12.7%, P=0.001) at 2 years while requiring less antihypertensive drugs. Changes in the left atrial volume index were significantly associated with treatment arm (P=0.03) and changes in systolic (P=0.005) and diastolic (P=0.005) blood pressure. Conclusions: Late CNI withdrawal, from a triple-drug regimen in stable renal transplant recipients, prevented progressive deterioration of LV diastolic function and facilitated better blood pressure control.

Early Posttransplantation Hyperglycemia in Kidney Transplant Recipients Is Associated With Overall Long-term Graft Losses

Early Posttransplantation Hyperglycemia in Kidney Transplant Recipients Is Associated With Overall Long-term Graft Losses

Background: The association of early-onset posttransplantation hyperglycemia with long-term renal allograft survival is unknown. Methods: Seventy-one (SD 9) days after transplantation, 1410 first-time kidney transplant recipients without diabetes underwent an oral glucose tolerance test and were observed until primary outcome (graft loss) or December 31, 2008 (median [range], 6.0 years [0.3–13.8 years]). We used multivariable Cox regression analysis adjusted for age, gender, body mass index, creatinine level, donor age, preemptive transplantation, deceased donor, early rejection, and early cytomegalovirus infection to estimate hazard ratios for overall and death-censored allograft survival. Results: A total of 392 (28%) recipients experienced graft failure, and 235 (60%) were induced by death. Each 1 mmol/L increase in 2-hr plasma glucose (2hPG) was associated with 7% and 3% increased risk of unadjusted and adjusted overall graft failure (hazard ratio [95% confidence interval], 1.07 [1.04–1.10] and 1.03 [1.00–1.07]). Fasting plasma glucose was associated with unadjusted but not adjusted overall graft failure (1.09 [1.01–1.18] and 1.07 [0.98–1.17]). Neither 2hPG nor fasting plasma glucose was associated with death-censored graft loss (P=0.578 and P=0.896). Compared with recipients with normal glucose tolerance, recipients with posttransplantation diabetes mellitus showed a tendency toward increased overall multiadjusted graft failure (1.30 [0.98–1.73]). This was not observed in patients with impaired fasting glucose or impaired glucose tolerance. Conclusions: In this study, 2hPG was associated with overall graft failure but not death-censored graft failure. The link between 2hPG and graft failure may be explained by the association with mortality.

Polyomavirus BK Replication in De Novo Kidney Transplant Patients Receiving Tacrolimus or Cyclosporine: A Prospective, Randomized, Multicenter Study

Polyomavirus BK Replication in De Novo Kidney Transplant Patients Receiving Tacrolimus or Cyclosporine: A Prospective, Randomized, Multicenter Study

Polyomavirus BK (BKV)-associated nephropathy causes premature kidney transplant (KT) failure. BKV viruria and viremia are biomarkers of disease progression, but associated risk factors are controversial. A total of 682 KT patients receiving basiliximab, mycophenolic acid (MPA), corticosteroids were randomized 1:1 to cyclosporine (CsA) or tacrolimus (Tac). Risk factors were analyzed in 629 (92.2%) patients having at least 2 BKV measurements until month 12 posttransplant. Univariate analysis associated CsA-MPA with lower rates of viremia than Tac-MPA at month 6 (10.6% vs. 16.3%, p = 0.048) and 12 (4.8% vs. 12.1%, p = 0.004) and lower plasma BKV loads at month 12 (3.9 vs. 5.1 log10copies/mL; p = 0.028). In multivariate models, CsA-MPA remained associated with less viremia than Tac-MPA at month 6 (OR 0.60; 95% CI 0.36–0.99) and month 12 (OR 0.33; 95% CI 0.16–0.68). Viremia at month 6 was also independently associated with higher steroid exposure until month 3 (OR 1.19 per 1 g), and with male gender (OR 2.49) and recipient age (OR 1.14 per 10 years) at month 12. The data suggest a dynamic risk factor evolution of BKV viremia consisting of higher corticosteroids until month 3, Tac-MPA compared to CsA-MPA at month 6 and Tac-MPA, older age, male gender at month 12 posttransplant.