Non-Heart-Beating Donor Kidney Transplantation Survival Is Similar to Donation After Brain Death: Comparative Study With Controls in a Regional Program.

Non-heart-beating donors (NHBD) are an increasing source of organs for kidney transplantation (KT) compared with donation after brain death (DBD), but the results in each regional transplantation program require local analysis. We compared 164 KT from NHBD (83 Maastrich type II A-B [T2] and 81 type III [T3]) with 328 DBD controls. NHBD kidneys were implanted with less cold ischemia, mean time on renal replacement therapy for NHBD recipients before transplantation was less too, and a higher proportion of thymoglobulin was also used. Besides NHBD-T2 more frequently showing the A group and patients being younger (48.9 ± 11 vs DBD 55.2 ± 15 years old; P < .001), there was a lower proportion of retransplant recipients and HLA sensitization; HLA-DR compatibility was slightly worse. Proportion of nonfunctioning allograft and necessity of dialysis after transplantation for NHBD were 4.9 and 68.3% versus DBD 4.3 and 26.9% (P < .001); renal function after a year was significantly less in NHBD (serum creatinine 1.79 ± 0.9 mg/dL vs 1.46 ± 0.5 in DBD; P < .001). NHBD recipient survival rates were 96% and 96% for the 1st and 3rd years, respectively, versus 96% and 94% for DBD, respectively (not significant [NS]). Graft survival rates censored by death were 91% and 89% (1st and 3rd years, respectively) versus 95% and 94% for DBD, respectively (NS). We did not find significant differences about survival between NHBD-T2 and T3. In the multivariable survival study (Cox, covariables with statistical significance demonstrated previously in our region), NHBD is not a prognosis factor for recipient or graft survival. Regarding current criteria for choosing donors and the graft allocation applied in Andalusia, short-term survival for NHBD transplantation is similar to DBD. Renal function in the short term is slightly worse, which is why it is important to monitor results over a long term, especially those from NHBD-T2.

Kidney Transplantation Results in Very Highly Sensitized Patients Included in a Virtual Crossmatch Program: Analysis of Kidney Pairs.

BACKGROUND: Kidney transplantation in highly-sensitized (HS) patients can improve with organ-exchange strategies based on virtual crossmatch (V-XM). Experience in very-HS patients is limited. METHODS: In June 2012, Andalusia started a V-XM protocol for very-HS patients (calculated panel reactive antibodies ≥95%). After organ allocation a cytotoxic-XM performed immediately before transplantation had to be negative for surgery to proceed. We analyzed results up until December 2015. Whenever possible we also compared the course of the recipient (non-HS) of the other kidney from the same donor. RESULTS: Of the 57 grafts, 52 kidney transplantations were performed (the pretransplantation cytotoxic-XM was positive in 5; predictive value 91.3%). Five patients (9.6%) experienced acute rejection (4 antibody-mediated rejections [AMRs]; 7.6%). Donor-specific antibodies developed in 10 patients. No patient died. One-year graft survival was 98%. We compared the course of the non-HS recipient of the other kidney, excluding cases with no pair (n = 5), pairs who were children recipients (n = 3), pancreas-kidney recipients (n = 5), or pairs already included in the V-XM protocol (n = 4). Finally, 35 pairs were studied. More HS-patients developed donor-specific antibodies (P = .016). No significant differences were seen in acute rejection, but AMR was more common (P = .057). No deaths occurred in either group, and there were no differences in graft survival or renal function. CONCLUSIONS: Although a few patients still developed AMR, our V-XM based protocol with a final pretransplantation cytotoxic-XM achieved very satisfactory results. Although the number of patients was limited, the initial survival of these high-risk recipients was comparable to the controls.

Hepatitis C Treatment With Direct-Acting Antivirals in Kidney Transplant: Preliminary Results From a Multicenter Study.

Hepatitis C (HC) is a very relevant negative prognosis factor for graft and transplant recipient survival. New direct-acting antivirals (DAAs) allow us to solve this problem in an effective way. It is crucial to understand their real impact in our daily practice. We analyzed treatment results with DAA, free of interferon, in kidney transplant recipients (KTRs) from 15 Spanish hospitals (Grupo Español de Actualización en Trasplante), regarding effectiveness, tolerance, and impact on immunosuppression, renal function-proteinuria, and diabetes. One hundred nineteen KTRs were included (9 combined liver-kidney transplants). The main DAA used was sofobusvir (91%) combined with ledipasvir (55%), simeprevir (14%), or daclatasvir (13%); in 9 cases (7%), a paritaprevir-ritonavir-ombitasvir-dasabuvir combination (3D) was used; Ribavirin was used as a coadjuvant in 18%. Side effects were limited (23.5%) and without relevance in general, except in 7 patients for whom we needed to interrupt the treatment due to neurotoxicity (1) caused by drug interaction (3D and tacrolimus) or anemia (3) by Ribavirin or others. Ninety-four patients had completed the treatment when data were analyzed: virological response was seen in 97.8% % of cases. Liver function analysis improved: 84% normal versus 21% before starting the treatment (P < .001). Renal function and proteinuria did not change. Tacrolimus level at the end of DAA-treatment was significantly lower with respect to the beginning (5.8 ± 2.1 ng/mL vs. 7.4 ± 1.8 ng/mL, P = .03), despite a slight increase in the dose (2.6 mg/d vs. 2.3 mg/d, P = .17). DAA are highly effective in the treatment of hepatitis C in KTRs with good tolerance in general, making it possible to solve the problem and have a good chance to improve the prognosis in our transplantation patients. The use of these therapies in KTRs requires special control and coordination with digestive professionals, especially if 3D or Ribavirin is used.

Use of antibodies neutralizing epithelial cell infection to diagnose patients at risk for CMV Disease after transplantation.

OBJECTIVES: Although a CMV-specific T-cell response is associated with reduced risk for infection after transplantation, some patients still develop CMV disease. Thus, the characterization of additional parameters of the CMV-specific immune response that correlate with the control of CMV infection and disease and their use in defining thresholds that can be applied to clinical practice is of interest. METHODS: In a cohort of high risk solid organ transplant recipients we characterized CMV-specific T-cell responses using intracellular cytokine staining upon stimulation with pp65 and IE-1 peptides, and levels of CMV-specific antibodies neutralizing infection in fibroblast (MRC-5) and epithelial (ARPE-19) cells using microneutralization assays. RESULTS: Although patients with a positive (≥0.25%CD8(+)CD69(+)IFN-γ+) T-cell response were 6.4 fold more protected (OR 6.4, 95% CI 1.6-25.3; p < 0.001) from CMV infection than patients without a response, 2 (4.2%) patients developed disease. We defined a cut-off titer for epithelial cell neutralizing antibodies of ≥480 that correlated with disease protection. Thus, patients with a CMV-specific T-cell response and titers ≥480 were 14.2 fold more protected from CMV infection (OR 14.2, 95% CI 5-40.2; p < 0.001) and had no episodes of CMV disease. CONCLUSIONS: Our results indicate that antibodies neutralizing epithelial cell infection may have an important role in long-term protection. Quantification of antibodies neutralizing epithelial cells, in addition to the T-cell response, may be useful for identifying patients with lower risk for CMV disease.

Survival of Kidney Allograft of Donors after Circulatory Death Is Similar to Donors after Brain Death: Experience in a Regional Program.

BACKGROUND: Donors after circulatory death (DCD) are an increasingly crucial source of organs to maintain deceased donor kidney transplant activity when faced with a standstill in donors after brain death (DBD). We analyzed the influence on graft survival since the use of DCD organs was implemented in Andalusia (2010-2014). METHODS: We compared 164 kidney transplants from DCD (83 Maastricht type II and 81 type III) and 1488 DBD transplants in recipients over the age of 18, excluding combined transplants. RESULTS: DCD were more frequently men from the A blood group who were younger (48.9 ± 11 vs 55.2 ± 15 years old for DBD, P < .001). Kidneys from DCD were implanted in younger recipients (51.2 ± 11 vs 53.5 ± 13 years old for DBD, P = .03), more frequently in men from blood group A who spent less time in renal replacement therapy (39.8 vs 51.5 months), in a lower proportion of immunized recipients and re-transplant patients, and had worse HLA-DR compatibility. DCD presented a proportion of primary nonfunctional allografts and an initial need for dialysis of 8.8% and 69.6% vs 5.5% and 29.6% for DBD (P < .001). DCD allograft recipient survival was 96% and 96% at the first and third year respectively, vs 96% and 93% with a DBD graft (NS). Survival of the graft was 91% and 86% at the 1(st) and 3(rd) years, vs 90% and 86% with a DBD allograft (NS). No significant difference was found between Maastricht type II and III. DCD were related to lower graft survival versus DBD under the age of 50 (n = 445), 86% vs 92% (P = .02) in the third year, but were similar to DBD from age 50 to 59 (n = 407) and higher than DBD over age 60 (n = 636), 80% at the 3(rd) year (NS). The survival of DCD recipients was not different than DBD in those under 60 and was significantly better than DBD at or over the age of 60 (96% vs 87% in the 3(rd) year, P = .036). In the multivariable survival study (Cox, covariates of influence previously demonstrated in our region) DCD are not a significant survival prognosis factor for the recipient or the allograft. CONCLUSIONS: With the current guidelines of donor selection and allocation of organs applied in Andalusia, the survival of kidney transplants from DCD overall is similar to DBD. The graft performance tends to be better than DBD over the age of 60, the main source of donors at present.

Impact of Asystolic Donations in Kidney Transplant Activity From Cadaveric Donors in Andalusia.

BACKGROUND: Kidneys from donors after brain death (DBD) cannot meet the demand for renal transplants in Andalusia. METHODS: We analyzed the impact of using non-heart-beating donors (NHBD) in Andalusia from the start of this program to the present. RESULTS: From 2010 to 2014, brain-death kidney donations remained at a standstill (1,635 in total) although NHBD increased from 2.4% to 16% annually, to 5% of the total (n = 164: 83 type II Maastricht [NHBD-T2] and 81 type III Maastricht [NHBD-T3]). The donors were more frequently men (T2 80.5% and T3 76.5% vs DBD 58.2%; P < .001). NHBD were younger (48.9 ± 10.8 y vs DBD 53.3 ± 16 y; P < .001); 11.6% of NHBD were >60 and 0% >70 years old, versus 39.4% and 15.2% of DBD, respectively; this is mostly explained by NHBD-T2 (48.9 ± 10.8 y vs DBD 53.3 ± 16 y). NHBD were used much less frequently than DBD in recipients over the age of 65 years or for retransplanted or hyperimmunized patients and never on priority recipients (children and combined transplant patients). Blood groups differed significantly among different donor types (A, O, B, AB): NHBD-T2 65.1%, 27.7%, 7.2%, and 0%, respectively; NHBD-T3 45.7%, 45.7%, 8.6%, and 0%; and DBD 46.5%, 39.4%, 10.2 %, and 3.9% (P = .01). The immediate output of the graft also differed in the proportion of primary nonfunction and delayed graft function: NHBD-T2 9.8% and 70.7%, respectively; NHBD-T3 5.0% and 65.0%; and DBD 5.9% and 28.7%. CONCLUSIONS: The development of an NHBD program allows us to maintain and even increase transplants in our region. The impact on transplant access for O group recipients without priority will depend on the type of NHBD (low proportion of O group in NHBD-T2).

Proteinuria as a predictive factor in the evolution of kidney transplantation.

INTRODUCTION: Certain factors can change the course of renal transplantation, such as acute rejection, ischemia time, and compatibility. Other donor and recipient factors may modify this evolution. Proteinuria modifies glomerular disease progression and may influence renal graft survival. In this study we analyzed proteinuria in patients who received a transplant since 2000 in Andalusia. MATERIAL AND METHODS: We studied the Andalusian Renal Transplant Registry from January 2000 to March 2012, recording data on 1815 patients who had proteinuria, registered at the third month and first year after transplantation. Three groups were formed, including those with proteinuria < 300 mg/24 h, those between 300 and 1000 mg/24 h, and those >1000 mg/24 h. RESULTS: At the third month and the first year after transplantation, 65.7% and 71.6% of patients had proteinuria < 300 mg/24 h, 29.6% and 24.1% had proteinuria between 300 and 1000 mg/24 h, and 4.7% and 4.4% had proteinuria > 1,000 mg/24 h, respectively. We found differences between the three proteinuria groups in panel reactive antibodies (% PRA), serum creatinine at the third month and the first year, the etiology of the donor death, incidence of delayed renal function, and incidence of hypertension. The degree of proteinuria influenced graft and patient survival. In multivariate analysis, proteinuria was an independent risk factor for renal graft loss CONCLUSIONS: The degree of proteinuria at the third month and the first year after transplantation is predictive of graft and patient survival. The patients who had more proteinuria at the third and 12th month after transplantation had worse renal function and more hypertension. Proteinuria is an independent risk factor for renal graft loss.

Impact of cold ischemia time on initial graft function and survival rates in renal transplants from deceased donors performed in Andalusia.

INTRODUCTION: Prolonged cold ischemic time (CIT) in cadaveric renal transplants has been associated with a high rate of delayed graft function, acute rejection, and even reduced graft survival. We analyzed the influence of CIT on both initial graft function (IGF) and survival rate. METHODS: We studied 2525 noncombined cadaveric cases in recipients over 17 years of age between 2000 and 2008, using data from the renal transplant records of Andalusia. We defined IGF as the need to resume dialysis within the first week or a nonfunctional kidney. The multivariate analyses were corrected by center and year of transplantation. RESULTS: The mean and median cold ischemic time was 17 hours. The duration of CIT was significantly associated (P < .001) with older donor and recipient age. The frequency of IGF increased progressively with longer CIT and older donors. However, the influence of CIT persisted among all donor age strata. Logistic regression analysis using both donor and recipient age as covariables showed a relative risk per hour of 1.05 (95% confidence interval = 1.04-1.07; P < .0001). In a univariable study, longer CIT led to a significant reduction in both recipient and graft survival rates. The multivariate study (Cox) using preprocedure covariables, showed CIT to produce significantly worse survival rates for both recipients (relative risk: 1.03, 1.005-1.05, P = .02) and for grafts (relative risk: 1.03, 1.01-1.04, P = .002). However, the survival rates showed no clear progression in terms of CIT within each individual donor age stratum. CONCLUSIONS: A longer CIT was associated with an increase in IGF independent of the age of both the donor and the recipient. Our data also suggested that CIT influenced patient and graft survival rates.

Efficacy and safety of conversion from twice-daily to once-daily tacrolimus in a large cohort of stable kidney transplant recipients.

Prolonged-release tacrolimus was developed to provide a more convenient once-daily dosing that could improve patient adherence. We conducted a multicenter, prospective, observational, 12-month study to describe the efficacy, safety and patient preference of conversion from tacrolimus twice-daily to once-daily formulation in stable kidney transplant recipients in routine clinical practice. Conversion was made on a 1 mg: 1 mg basis (1 mg: 1.1 mg in patients with trough levels <6 ng/mL). The study included 1832 patients (mean age (± SD): 50.0 ± 13.4 years; 62.7% male). After conversion, a modest reduction in tacrolimus trough levels, necessitating an increase in daily dose, was observed (mean changes at 12 months of -9.1% and +1.24%, respectively; p < 0.0001). Mean glomerular filtration rate did not change significantly (56.5 ± 19.7 mL/min at conversion vs. 55.7 ± 20.6 mL/min at 12 months). Proteinuria, blood pressure, lipid, hepatic and glucose parameters remained stable. Eight patients (0.4%) had acute rejection and 34 patients (1.85%) discontinued treatment. Almost all patients (99.4%) preferred the once-daily formulation, because of less frequent dosing (66%) and improved adherence (34%). In conclusion, at similar doses to twice-daily tacrolimus, once-daily formulation provided stable renal function, a low acute rejection rate, and good tolerability in stable kidney transplant recipients in the routine clinical practice setting.

Efficacy of low doses of pamidronate in osteopenic patients administered in the early post-renal transplant.

UNLABELLED: This study evaluates the efficacy of low doses of pamidronate after renal transplantation to prevent bone loss in osteopenic patients. Results show that pamidronate is safe and significantly reduced spinal bone loss when administered immediately after renal transplantation. INTRODUCTION: The purpose of this work is to evaluate the efficacy of two intravenous infusions of pamidronate in the immediate post-transplant period in a renal transplant (RT) population. METHODS: In this 12-month, randomized, double-blind, multicenter trial, 39 kidney recipients with diagnosed osteopenia received two doses of 30 mg of disodium pamidronate (n = 24) or placebo (n = 15), at surgery and 3 months post-RT. All patients received calcium and vitamin D. Bone density of the lumbar spine and total femur was measured by dual-energy X-ray absorptiometry (DXA) and X-rays were performed at RT, 6 and 12 months post-RT. Biochemical and hormonal determinations were performed before and after treatment. RESULTS: Pamidronate significantly reduced spinal bone loss, but no significant benefit was found for the incidence of fractures. Elevated baseline intact parathyroid hormone (iPTH) and bone remodeling markers returned to normal levels 3 months post-RT. However, normal procollagen type I N propeptide (PINP) concentrations were only maintained in the pamidronate group. After RT, a comparable graft function was observed in both groups according to creatinine values, 25-hydroxyvitamin-D (25-OH-D) levels were improved, and serum calcium levels normalized after a transient fall during the first 3 months. CONCLUSION: A low dose of pamidronate prevents bone loss in osteopenic patients when administered immediately after RT.

Erythropoietin resistance as surrogate marker of graft and patient survival in renal transplantation: 3-year prospective multicenter study.

BACKGROUND: Some transplant recipients demonstrate an inadequate response to erythropoiesis-stimulating agents, or so-called erythropoietin (Epo) resistance. The cause is multifactorial. Resistance to EPO may entail a poor prognosis for the graft and the patient, although results in the literature are inconsistent, and long-term follow-up is lacking. OBJECTIVE: To evaluate whether the presence of Epo resistance at the beginning of the study was a predictive factor for graft and patient survival. MATERIALS AND METHODS: From 482 renal transplant recipients (Kidney Disease Outcomes Quality Initiative stage 3-4T) receiving Epo-stimulating agents in the Anemia and Renal Transplantation in Spain study, 101 were selected for the present study. Erythropoietin resistance was defined as a ratio of weekly Epo dosage/hemoglobin concentration>486,94 U/g/dL with a hemoglobin/<11 g/dL. Darbepoetin dosage was calculated in Epo equivalent units, with a 1:200 conversion factor. Patients were grouped as Epo-resistant (ER+) or not Epo-resistant (ER-), to assess whether Epo resistance was predictive of patient and graft survival. RESULTS: There were no differences in demographic data between the 2 groups except for a higher incidence of vascular, interstitial, and diabetes-related causes of chronic renal failure in the ER+ group. At 3 years posttransplantation, graft survival was 33% in the ER+ group vs 58% in the ER- group (P=.06), and patient survival was 52% in the ER+ group vs 88% in the ER- group (P=.008). Using a Cox regression model, at 3 years, the relative risk of graft failure was 1.96 in the ER+ group (95% CI, 0.93-3.12; P=.07), and of patient death was 3.9 (95% confidence interval, 1.30-11.63; P=.01). CONCLUSION: Erythropoietin resistance is an independent risk factor for death after renal transplantation.

Renal Transplant Register of Andalusia, 2010 Report: survival in relation to the factors used in recipient selection.

Kidney transplantation is the best therapeutic alternative for patients suffering from end-stage renal disease (ESRD). In recent years a significant advance has been made in Andalusia in graft and recipient survival as seen in our 2009 publication. In the current work we analyzed 2989 kidney transplantations performed between January 1, 2000 and December 31, 2009 based on data obtained from the Renal Transplant Registry of Andalusia. We studied the influence on graft and patient survival of factors, such as donor and recipient age, HLA matching, HLA immunization, and duration of previous renal replacement therapy. Patient survival was influenced by age at the time of transplantation and by donor age; the younger the donor, the more it was improved. Graft survival was determined by the donor age group, with no differences at each level according to the recipient age group. No significant differences were observed in patient survival or graft or death-censored graft survival according to HLA matching. Patient and graft survivals were significantly affected by the duration of the previous renal replacement therapy. Despite this being a preliminary study, we have shown the importance of nonmodifiable factors in transplant survival, such as donor and recipient age, with HLA matching having a limited effect. These latter findings should be confirmed in the future by multivariate analyses.

Results of living kidney donation in Andalusia: 2006-2009.

Renal transplantation is the best therapeutic choice in patients with end-stage renal disease (ESRD), with donation from living donors the alternative that offers the best medium- and long-term results. Because of the limited number of cadaver donors and the progressive increase in donor age, transplantation from living donors has become the renal replacement treatment of choice. Several studies have demonstrated that donation does not increase the donor's risk of developing ESRD in the long term. Some studies have asserted that a donor's life expectancy increases as a result of the comprehensive study and screening process they must undergo. The objective of the present study was to evaluate the vital status and onset of chronic renal disease in 101 living kidney donors in Andalusia, Spain, during 2006-2009, based on data obtained from the Sistema de Información de la Coordinación Autonómica de Trasplantes de Andalucía (Regional Transplants Coordination of Andalusia). Donor survival was 99%, and the only death, from lung cancer, was not associated with the surgical procedure. Only 5 transplants failed during this period, and no donors developed ESRD. Neither the probability of survival nor the risk of developing ESRD in donors was influenced by kidney donation.

Are we still making progress in patient survival after kidney transplantation? Results of a regional registry.

Many studies have shown a trend to improved long-term survival of renal transplant recipients. We analyzed the survival of recipients in Andalusia, Spain, from 1984-2007. The study included all the deceased donor, non-multiorgan grafts (n = 5599), grouped over successive 6-year periods, compared for corrected recipient survival. Changes were noted in the recipient characteristics: increased age, diabetes, vascular nephropathy, retransplantation, duration of prior replacement therapy, and reduction in positive hepatitis C virus (HCV+) serology. The univariate analysis showed a significantly worse survival associated with increased age (P < .001), diabetes (P < .001), HCV+ serology (P < .01; 1996-2007), and longer times on replacement therapy, but not with sex or retransplantation. The respective survivals at 1, 5, and 10 years in 1984-1989 were 93%, 86%, and 75%; in 1990-1995, 97%, 92%, and 84%; in 1996-2001, 96%, 91%, and 84%; and in 2002-2007, 96% and 92%, respectively. There was a significant improvement between the first and second periods (P < .001), but no change thereafter. The multivariate analysis (Cox) showed, a significant influence of age >40 years, female gender (relative risk [RR] 0.8; 95% confidence interval [CI] 0.7-0.9), diabetes (RR 2.5; 95% CI 1.8-3.4), and duration of prior replacement therapy (RR 1.08; 95% CI 1.05-1.1). The risk varied significantly depending on the period: using 2002-2007 as the reference period, the RR in 1984-1989 was 3.4 (95% CI 2.6-4.5); in 1990-1995, 1.8 (95% CI 1.3-2.3); and in 1996-2001, 1.4 (95% CI 1.1-1.8; all P < .02). The model remained for 1996-2007, though HCV+ serology was not significant. In conclusion, we showed a significant improvement in recipient survival in Andalusia over time. Correction for worse recipient characteristics suggests continued advances.

Regional survey of patient survival after cadaver renal transplant failure.

Graft failure with return to dialysis is associated with higher mortality, but the determining factors have not been completely studied. We determined predictive factors for survival after renal transplant failure by analyzing demographic and clinical data on kidney recipients in a Spanish regional registry (Andalusia). Among 5547 single-organ cadaveric grafts in Andalusia between 1984 and 2007, 1534 patients returned to dialysis and were followed to death (n = 450), retransplantation (n = 574), or the end of the study period. The most frequent cause of death was cardiovascular disease (36.9%). Actuarial survival rates were 89%, 72%, and 51% at 1, 5, and 10 years, respectively. Upon univariate (Kaplan-Meier) analysis, survival was significantly related only to age at return to dialysis and diabetes. Cox forward step wise multivariate regression analysis showed that predictive factors for lower survival (relative risk -95% confidence interval) were: age (per year), 1.05 (1.05-1.06); male sex, 1.33 (1.1-1.6); and duration of pre-graft renal replacement therapy (per year), 1.02 (1.00-1.05). According to Cox backward stepwise regression analysis, a more saturated model, the predictive factors were: age; male sex; duration of pre-graft renal replacement therapy (per year), 1.03 (1.01-1.06); later study period (1996-2007), 0.81 (0.6-1.0); and primary etiology of chronic kidney disease (CKD). Survival after renal transplant failure was lower among male recipients of advanced age or with a long period of prior renal replacement therapy. Time of transplantation and primary etiology of CKD may also play roles.

Increase in malignancies as cause of death in renal transplant patients.

The Andalusian Kidney Transplant Registry is a Public Health Service Regional Registry of Andalusia, Spain. We have analyzed the causes of death among 5599 kidney transplantations performed between January 1, 1984 and December 31, 2007. The total number of patients who died after renal transplantation was 1106. Of these, 656 patients died with functioning renal grafts, which constituted the group analyzed in this study. No significant differences in the causes of death were observed as a function of age, sex, retransplant status, cause of end-stage renal disease, diabetes, and duration of the previous renal replacement therapy. Infections were the most frequent cause of death in the first year posttransplantation (early deaths). A significant difference was observed when these early deaths were compared with those that occurred after the first year posttransplantation (late deaths); there were fewer deaths due to infections (40.4% vs 15.9%, early vs late) and more deaths from cancer (4.9% vs 23.7%). The causes of death in the period 1984-1995 were compared with those in 1996-2007, excluding the deaths that occurred more than 12 years posttransplantation (not possible in the 1996-2007 periods n = 583). The causes of early death did not change. A significant difference was observed among late deaths with an increase in infections (14% vs 17%) and cancers (20% vs 29.7%). Thus, malignancies became the most frequent cause of late death in the 1996-2007 period. In conclusion, in our region, a long-term change in renal transplant patient mortality is taking place, with a significant increase in deaths due to cancer.

Treatment of anemia in renal transplantation: impact of a stricter application of hemoglobin targets.

OBJECTIVE: The CREATE and CHOIR studies showed a higher risk for cardiovascular events associated with hemoglobin (Hb) values >13 g/dL in patients with stage 3-4 chronic kidney disease. In 2007, a stricter policy on the use of erythropoietin (EPO) was adopted at our center, with an Hb target of 11 to 12 g/dL and withdrawal or reduction of EPO when Hb was >12.5 to 13 g/dL. This study was designed to evaluate this new approach. MATERIALS AND METHODS: The study included patients under follow-up at the transplant outpatient clinic on December 31, 2006 (n = 725), and December 31, 2007 (n = 768). Data were compared between the study populations concerning renal function, Hb, use of EPO, and associated costs. RESULTS: No significant differences in creatinine or Hb values were observed between the 2 groups (1.47 +/- 0.6 vs 1.42 +/- 0.9 mg/dL and 13.7 +/- 1.5 vs 13.7 +/- 1.6 g/dL, respectively). After implementation of the new protocol, the frequency of severe anemia (Hb <11 g/dL) increased (2% vs 4%; P = .10), the use of EPO decreased (22.1% vs 17.2%; P = .017), and the mean Hb of EPO-treated patients decreased (12.5 +/- 1.4 vs 11.9 +/- 1.0; P < .001). The Hb target (11-12 g/dL) was met in fewer than one third of patients, with no significant differences between the 2 study times. CONCLUSIONS: A strict policy on EPO application reduces its use and the rate of patients with "excessive" Hb values (which are associated with increased cardiovascular risks), with an acceptable slight increase in severe anemia cases.

Factor deficiency in the anemia of renal transplant patients with grade III-IV chronic kidney disease: baseline results of the ARES Study.

ARES is a multicenter, prospective study of the prevalence, management, and repercussions on the quality of life of anemia in renal transplant patients with a reduced renal function (creatinine clearance according to Cockcroft-Gault: 15 mL/min). The frequency of factor deficiency and its relationship with anemia were analyzed at the baseline time of the study. Of the 500 patients included in the main study, valid data were available for iron metabolism in n = 419 microg/dL; folic acid, n = 205 ng/mL; and vitamin B12, n = 210 pg/mL. Anemia was defined as hemoglobin

Treatment of BK virus-associated nephropathy with Cidofovir in renal transplantation.

BK virus-associated nephropathy (BKVN) has become recognized as an important cause of allograft dysfunction among transplant recipients. Despite reduction in immunosuppression, 30%-40% of recipients progress to allograft loss. Cidofovir is an antiviral agent that has been proposed for treatment of BKVN. We describe the clinical course, renal function, and blood viral measurement in 6 renal transplant recipients with BKVN who were treated with low doses of cidofovir. Administration of cidofovir was associated with clearance of BK virus DNA from blood and stabilization of renal function in 5 cases. These data suggest that cidofovir may be useful as adjuvant therapy for BKVN.

[Daclizumab in combination with mycophenolate mofetil and a late introduction of Tacrolimus at low doses, as a therapeutic approach in the elderly renal transplant donor-recipients pairs in kidney transplant]. / Daclizumab en combinación con Micofenolato Mofetil e introducción tardía de Tacrolimus a dosis bajas, como opción terapéutica en la pareja donante-receptor añoso en trasplante renal.

BACKGROUND: Nowadays, it is more frequent the use of kidneys from older donors in the renal transplantation. Moreover, it is also increasing the age of the recipients due to the ageing of the population treated with hemodialysis. This makes that recipients become older more commonly. This situation raises specific problems in the renal graft and in the recipient as well. In this manuscript we present the results of a multicenter study that analyzed an immunosuppressive strategy specifically designed to elderly renal transplant donor-recipients. METHODS: Patients > or =50 years were transplanted from donors > or =55 years. Immunosuppressive strategy consisted of daclizumab (2 doses of 1mg/Kg) in combination with steroids, mycophenolate mofetil (2g/daily during the first 45 days and then adjusted according to local practice) and Tacrolimus. Tacrolimus was introduced between 5 and 7 day post-transplantation, adjusting the predose levels between 4-8 ng/mL. Mean follow-up was 12 months. RESULTS: A total of 133 patients were included in the study. Mean age of recipients and donors was 61.3+/-6.2 years and 64.4+/-5.3, respectively. 42.9% of patients needed dialysis during the first week (median 4 days). Between first month and first year, serum creatinine improved from 2.0+/-1.0 mg/dl to 1.5+/-0.4 mg/dl. Similar improvements were observed when creatinine clearance (Cockroft-Gault) was calculated. The survival of patient and renal graft at 12 months was 97.7% and 96.1%, respectively. The acute rejection rate was 13.5%. Security profile was good, as expected. CONCLUSIONS: The Daclizumab and mycophenolate mofetil regimen with a late introduction of Tacrolimus at low doses is a good alternative in the elderly renal transplant recipients with a low immunologic risk.