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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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

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., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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)., (Copyright © 2015 Elsevier Inc. All rights reserved.)

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., (Copyright © 2013. Published by Elsevier Inc.)

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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., (Copyright © 2010 Elsevier Inc. All rights reserved.)

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., (Copyright © 2010 Elsevier Inc. All rights reserved.)

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., (Copyright © 2010 Elsevier Inc. All rights reserved.)

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.

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.

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.

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.

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

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.

Introduction: Simultaneous pancreas-kidney (SPK) transplantation is the best therapeutic option for correctly selected diabetic patients with advanced chronic kidney disease (CKD)., Objectives: The objectives of this study were to quantify in a Spanish province the prevalence and incidence of type 1 and 2 diabetics with stage IV-V CKD who are potential candidates for SPK, and to analyze the selection for SPK in clinical practice., Materials and Methods: All patients with diabetic neuropathy (DN) in predialysis, hemodialysis, or peritoneal dialysis (PD) in our transplantation referral area (population, 1.8 million; data collection ended December 7, 2005) were examined for basic SPK criteria (NTO 2005 Consensus). A new assessment was performed 9 months later, including new possible recipients, and patients were classified as: follows in study, excluded after study, added to SPK waiting list, or SPK-transplanted., Results: In 2005, there were 1371 patients in dialysis or predialysis, including 179 (13%) with DN (41 type 1 and 138 type 2 DM); only 16 of these patients (8.9% of DN patients), 8.9 per million population (PMP), met the basic criteria for SPK transplantation. There were 68 with DN in predialysis, including 8 (11.7%) possible SPK candidates; 7 with DN in PD, no candidates for SPK; and 104 patients with DN in hemodialysis, including 8 (7.2%) SPK candidates. After 9 months, 7 new potential candidates were identified (incidence of 5.1 PMP/y). Of 23 possible candidates, 3 refused SPK, 7 awaited completion of study, 8 were excluded after study, 1 was on the SPK waiting list, and 7 underwent SPK transplantation., Conclusions: In our setting, approximately 9% of DN patients with stage IV-V CKD were potential SPK candidates in 2005 and 2006. After completion of studies, less than half were eventually included on the waiting list, generating an effective demand for SPK of 2-4 new patients PMP/y.

Urinary tract infection (UTI) remains a significant cause of infectious complications in renal transplant recipients. We evaluated prospectively all the UTIs in 161 kidney recipients transplanted between July 2003 and July 2005. All patients received prophylaxis with sulfadoxine-pyrimethamine. We excluded asymptomatic bacteriuria. Forty-one patients (25%) suffered at least one UTI episode. Ninety-two episodes of infection were confirmed with an incidence rate of 97 UTI episodes per 100 patient-years. The most common clinical features were uncomplicated acute bacterial cystitis, 71 episodes (77%), and acute pyelonephritis, 21 episodes (23%). Microbiological isolation was confirmed in 58 episodes (63%). Bacterial infections were the most frequent etiologies: gram-negative bacilli in 52 (90%), gram-positive cocci in 4 (7%), fungal in 2 (3%), and one viral BK virus (2%) infection. The causative microorganisms were E. coli as the principal isolated agent in 41 cases (71%), including 10 (24%) that were extended-spectrum betalactamases (ESBLEC). All episodes showed a favorable course. The survival rate of the graft at the end of the study period was 90.7%, and the survival rate of the transplant recipients was 97.5%. The incidence of UTI in transplant patients who received antibiotic prophylaxis was high. E. coli (ESBLEC) was the main agent isolated. Uncomplicated UTI, the most frequent post transplantation infection, showed a good prognosis.

Mycophenolate mofetil (MMF) is an immunosuppressant that is widely used for prophylaxis of rejection in solid organ transplantation. In this study, we examined the effect of renal insufficiency on the pharmacokinetics of MMF, particularly on the free fraction of drug in renal transplant patients. Our study was performed on 10 patients with severe renal insufficiency (creatinine clearance [CrCl] <30 mL/min), and 10 control patients with preserved renal function (CrCl >90 mL/min). All the patients had received a cadaveric donor graft at least 1 year prior and were clinically stable under treatment with MMF and cyclosporine. For each patient, we determined 12-hour areas under the curve (AUC(0-12 h)) for the metabolites: mycophenolic acid (MPA), 7-O-mycophenolic acid glucuronide (MPAG), and the free non-protein-bound fraction of MPA (f-MPA). The two groups were matched for age, sex, and MMF dose. Mean AUC(0-12 h) values for MPA were similar in both groups. The renal insufficiency group showed a significantly increased AUC(0-12 h) for MPAG (1550 +/- 392 vs 3527 +/- 1130 microg.h/mL, P < .001) and increased trough and AUC(0-12 h) values for f-MPA (0.023 +/- 0.02 vs 0.094 +/- 0.07 microg/mL, P = .003, and 0.87 +/- 0.3 vs 1.52 +/- 0.8 microg . h/mL, P = .016, respectively). We proposed that these differences should be taken into account when deciding upon the dose of this drug for the subset of patients with impaired transplant function.

The use of mycophenolate mofetil (MMF) and renin-angiotensin system blockers (RAB) to prevent and treat chronic graft nephropathy may affect the incidence of anemia in renal transplant recipients. We compared 2 sets of cadaver-donor recipients, namely those followed at the end of 1995 (group 1; n = 252) versus 2003 (group 2; n = 530) in terms of general characteristics, incidence of anemia (hemoglobin [Hb] < or =13 g/L males, 12 g/L females) or severe anemia (Hb < or =11 g/L males, 10 g/L females) and use cost of treatment with erythropoietin (EPO). Group 2 was significantly older, heavier and longer since grafting. Fifty-seven percent received MMF, 21% received azathioprine, and 5% received rapamycin. In group 1, 83% were given azathioprine. RAB were administered to 35.1% in group 2 versus 14.7% in group 1 (P < .001). Mean blood pressure was identical in the 2 groups, but graft function was worse in group 2 (Cockroft, 62 vs 74 mL/min; P < .001). Mean Hb levels (13.66 + - 3.1 vs 13.82 + - 1.7 g/L) and prevalence of anemia (36.9% vs 34.5%) for groups 1 and 2, respectively, were similar. The rate of severe anemia, however, was lower in group 2 (2.3% vs 8.7%; P < .001). The use of EPO increased from 2.8% (group 1) to 8.7% (group 2; P < .01). In 2003, the cost of EPO was calculated at 1982 Euros/patient-year and 91,150 Euros per year for the whole patient group. Despite accumulation of predisposing factors, the control of anemia in our patients has improved due to the expanded use of EPO. Along with its high cost, EPO therapy has potential positive repercussions on the quality of life and patient prognosis. Therefore, we need to precisely define the optimal use of EPO in renal transplant recipients.

Introduction: Hepatitis C virus (HCV) infection is associated with worsening disease progression after renal transplant, and to date there is no available treatment for use at this stage. It has therefore been recommended to treat HCV infection with interferon (IFN) during the dialysis period while the patient is on the waiting list for transplantation., Methods: We analyzed data from 27 patients on hemodialysis awaiting transplant, who were under IFN treatment for chronic HCV infection (dominant genotype, 1b). The starting regime was IFN alpha-2b, 3 MU x 3/week (n = 20) or pegylated IFN alpha-2a, 135 mg/week (n = 7). If there was clearance of HCV RNA in the first 3 to 6 months, we attempted to prolong IFN treatment for 1 year, although in many patients the dose had to be reduced. A sustained response was defined as viral clearance for at least 12 months after the end of treatment., Results: Viremia was negative in 13 patients (48.1%) at the end of treatment, but two of these patients relapsed, to give an overall long-term response rate of 11 patients (40.7%) and incomplete follow-up in three patients. Viral clearance was not achieved in 11 patients. In three patients (12%), IFN had to be suspended before finishing the third month of therapy due to side effects (mainly pancytopenia and intolerance of a previous kidney graft). Seven patients showing a sustained response underwent transplant, maintaining a negative viremia result., Conclusions: IFN treatment was effective in a high proportion of dialysis patients with HCV infection, with response rates possibly even higher than for the general population. However, its use is restricted by a high incidence of side effects.

Background: Renal transplants from elderly donors have a high incidence of delayed graft function, which can be increased by the initial use of calcineurin inhibitors. Our purpose was to assess the safety and efficacy of an immunosuppressive regimen using anti-IL-2R antibodies and MMF that allows delayed introduction of low-dose tacrolimus using elderly donors to elderly recipients., Methods: This observational study involved 13 transplant centers. In total there were 119 patients (age 60.5 +/- 6.6 years, range 50 to 77) who received a kidney from a donor of mean age 64 +/- 5 years (range 55 to 76), 94% of whom died from a CVA. Immunosuppression consisted of daclizumab (1 mg/kg in two doses; preoperatively and on day 14) combined with steroids, mycophenolate mofetil (initial dose of 2 g/d), and tacrolimus (0.1 mg/kg per day). Tacrolimus was introduced before day 7 (mean 5.5 days) and adjusted to a target level of 5 to 8 ng/mL. The mean follow-up was 8 months., Results: Two grafts were lost due to primary nonfunction and acute rejection and 48 patients (40%) required dialysis due to delayed graft function, although it was generally of short duration (median 4 days; only 2 cases >2 weeks). Acute rejection occurred in 16 patients (13.4%), of whom 13 were biopsy-confirmed (10.9%; Banff 1997 grades I and II). Three patients withdrew from the study, and three died (sepsis, accident, and cardiovascular event). The remaining 111 patients continued follow-up, with a median creatinine value of 1.5 mg/dL at 12-months. Eighty-six percent of patients had at least one episode of infection, half of which were urinary tract infections. There were 16 cases of CMV infection., Conclusions: Based on the initial results, our immunosuppressive regimen seems to offer good short-term renal function while maintaining an acceptable rejection rate and a low incidence of serious infections.

We evaluated 10 patients with primary focal segmental glomerulosclerosis (FSGS) treated with plasmapheresis (PS) following renal transplantation. Three patients lost their first graft due to FSGS recurrence. In seven patients, PS was indicated as treatment for probable recurrence defined as the onset of proteinuria above 1 g/24 hours. In the remaining three patients, treatment was started in the first week posttransplant as prophylaxis against recurrence. The PS protocol was 17 sessions with the exchange of 2.5 L of plasma for 5% albumin over 10 to 12 weeks. Losartan (25 to 100 mg/d) was given to most patients at the end of PS treatment. The mean follow-up time after PS was 10 months. All patients currently have a functioning graft. A full response to treatment, defined as persistently reduced proteinuria to less than 500 mg/24 hours or the lack of recurrence in prophylactic treatment, was achieved in six patients. Three patients showed a partial decrease in proteinuria (to less than 1 g/24 hours). One patient failed to respond and still has nephrotic range proteinuria. No adverse effects of PS were recorded. A prompt start of PS combined with the use of losartan yields good results in the prophylaxis and treatment of recurrent FSGS following renal transplant in terms of quickly reduced proteinuria. Given the natural course of FSGS, a longer follow-up is needed to estimate the impact of PS on graft survival.

The aim of the present study was to determine whether a kidney graft expressing the glutathione S-transferase T1 enzyme (GSTT1) could cause an alloimmune response in a recipient with the null GSTT1 genotype that was similar to that observed in liver transplant. We have found anti-GSTT1 antibodies in the sera of a number of patients and confirmed that only one of the four possible genetic combinations--positive donor/null receptor--could lead to the production of these antibodies. Nevertheless, the main finding of this study is that in kidney transplantation, this mismatch was not sufficient to trigger an immune reaction. Longer follow-up of the posttransplant evolution of the patients is required in order to clarify the contribution of the factors involved in this process.

In 3 renal transplant cohorts treated in Spain in 1990, 1994, and 1998 (total number, 3279), we studied the frequency of certain cardiovascular risk factors. Their effect on the cost of drugs was assessed from the data from 1 center; the mean cost of antihypertensive agents per patient-year was 349 euros, and of lipid-lowering drugs was 294 euros. Between 1990 and 1998 the frequency of use of antihypertensive agents at 2 years increased from 70% to 80%, and that of lipid-lowering agents from 12% to 46% (P < .001). Patients received various regimens of immunosuppression at the second year, as follows: (1) steroid-free: cyclosporine, 2.3%; tacrolimus, 9.9%; cyclosporine plus mycophenolate, 16.2%; and tacrolimus plus mycophenolate, 11.8% (P < .001); (2) antihypertensive agents: 74.9% of patients receiving tacrolimus, with or without mycophenolate, versus 80.7% of those receiving cyclosporine (P = .022); (3) lipid-lowering drugs: 28.4% of patients receiving tacrolimus, with or without mycophenolate, versus 51.1% of those receiving cyclosporine (P < .001). The increase in associated drug costs must be added to the recent large increase in the cost for immunosuppressive agents, which rose from 3854 euros per year, in 1990 to 5374 euros per year in 1998. A lower cost of associated drugs tends to lessen the overall cost of therapies with tacrolimus. Because cardiovascular disease is the main cause of death, these findings should be taken into account in the assessment of the long-term cost-benefit ratio.

Introduction: Osteoporosis following a renal transplant is an important cause of morbidity. Several studies have demonstrated the efficiency of diphosphonates for the prevention and treatment of osteoporosis., Methods: We evaluated the effect of alendronate treatment on bone mineral density (BMD) in patients with osteoporosis (lumbar spine and/or hip t-scores < or = -2.5). Two study groups were established: group A (n = 13), patients treated orally with vitamin D, calcium, and alendronate (70 mg/week) and group B (n = 12) patients receiving only vitamin D and calcium. The immunosuppression regimen mostly used was steroids and cyclosporine. BMD was determined at the lumbar spine and hip using a Hologic 4500 QDR densitometer at the start of treatment and after 1 year., Results: The study groups showed no significant differences in age, sex, menopause, or transplant time. Group A received a mean of 1.80 +/- 1.3 microg vitamin D/week and 1.3 +/- 2.1 g calcium/d, compared to 1.1 +/- 1 microg and 1.25 +/- 2.3 g, respectively for group B (NS). After a mean of 411.15 +/- 107.75 days of treatment, a significant increase in BMD at the femoral neck was recorded in group A, but not at the level of the spine (+5.57% +/- 3.5%, P < .05 and -0.42% +/- 12%, NS, respectively). No significant changes were observed in group B (-1.45% +/- 8% femoral neck and +1.69% +/- 3.5% hip, NS). Dyspepsia was reported by 7% of patients., Conclusions: In this preliminary analysis, alendronate produced, improvements are so far limited to an increased BMD in the hip.

Introduction: Epidemiological data suggest that hepatitis C virus (HCV) infection may contribute to the development of posttransplantation diabetes mellitus (PTDM)., Methods: We investigated the glucose metabolism in 19 renal transplant recipients with antiHCV antibodies and without DM according to World Health Organization criteria before or after transplantation. We measured insulin sensitivity (SI), glucose effectiveness (SG), and pancreatic insulin response using the frequently sampled intravenous glucose tolerance test (FSIGTT). SI and SG were estimated using the Bergman minimal model method and pancreatic insulin response was expressed as the area under insulin curve (AUIC) between 0 and 19 minutes., Results: Impaired glucose tolerance was shown in 42% of patients, some (31.5%) in the range of glucose intolerance (KG: 1-1.5) and others (10.5%) in the diabetes range (KG < 1). SI and SG were decreased in 39% and 63% of patients, respectively. Pancreatic insulin response revealed high variation among patients although showing a tendency to be enhanced., Conclusions: A high number of HCV-positive renal transplant recipients without clinically manifest PTDM have impaired glucose tolerance, which suggests the future development of diabetes in these patients.

Although newer immunosuppressive drugs control acute rejection better and have short-term economic advantages, their long-term cost-effectiveness is unknown. We studied the frequency with which different maintenance immunosuppression regimens were used in 3 renal transplantation cohorts treated in 1990, 1994, and 1998 (total number, 3279). We calculated the mean annual immunosuppressive costs based on the true costs in a medium-sized hospital. Cyclosporine, with or without azathioprine, was used almost exclusively as the initial maintenance immunosuppressive therapy in 1990-1994. In 1998, 65% of patients received mycophenolate mofetil (MMF), and 20% received tacrolimus (Tac). A growing number of patients from 1990-1994 were converted to MMF (12%-17%) and Tac (4%-8%), while treatment of those from the 1998 cohort remained stable. According to year 2000 costs, the mean immunosuppressive cost at 1 year in 1998 (5380 euros) was almost twice that of 1994 (2902 euros) or 1990 (2855 euros). In these 2 groups the mean cost was stable until 1996, then increased faster in the 1994 cohort (24.8%) than in the 1990 cohort (17.3%), although it remained significantly lower than that in 1998. Correction of the evolution of drug prices and the purchasing value of the peseta greatly absorbed these changes. The MMF and Tac regimens showed greater mean graft life, but without reaching statistical significance in a multivariate study. The introduction of new immunosuppressive drugs has had an important economic effect since 1996; its cost-effectiveness is still pending confirmation in Spain.

Background: Renal transplants (RTs) from elderly donors show a high incidence of delayed graft function, which may be increased by the initial use of calcineurin inhibitors., Objectives: The purpose of this study was to assess the safety and efficacy of an immunosuppressive regimen using anti-IL-2R antibodies and mycophenolate mofetil (MMF) with delayed introduction of low-dose tacrolimus in RT from elderly donors to elderly recipients., Methods: This observational study in 13 centers included 78 patients, aged 61+/-7 years (range, 50-77), who received a kidney from a donor with a mean age of 64+/-5 years (range, 55-76), 94% of whom had died from a cardiovascular accident (CVA). Immunosuppression consisted of 1 mg/kg daclizumab in two doses (pre-RT and on day 14) combined with steroids, mycophenolate mofetil (initial dose of 2 g/d), and tacrolimus (0.1 mg/kg per day). Tacrolimus was introduced before day 7 (mean, 5.5 days) and adjusted to a target level of 5 to 8 ng/ml. The mean follow up was 27 weeks., Results: One graft was lost due to primary renal failure and 28 patients (36.4%) required dialysis due to delayed graft function, although it was generally of short duration (median, 4 days; only 2 cases >2 weeks). Acute rejection was seen in 11 patients (14%), with 9 of these confirmed by biopsy (11%, Banff 1997 grade I or II). Three patients withdrew from the study and two patients died (sepsis and accident). The remaining 72 patients continued follow up with a median 6-month creatinine value of 1.6 mg/dL. Sixty-seven percent of patients had at least one episode of infection, half of which were of urinary tract infections. There were nine cases of CMV infection., Conclusions: These initial results suggest that this immunosuppressive regimen offers good efficacy with regard to short-term renal function, while maintaining both an acceptable low rejection rate and incidence of serious infections.

Background: Hepatitis C has been associated with an increased incidence of diabetes mellitus (DM) following renal transplantation (RT)., Methods: Patients who underwent RT between 1985 and 2001 were excluded if they showed DM prior to RT, graft survival of less than 90 days, and unknown anti-HCV status (n=15). Two groups (G1 and G2) were distinguished according to the immunosuppressive regimen: G1 (transplanted 1985-1996) received steroids, azathioprine, and cyclosporine (n=330), whereas G2 (1997-2000) received new drugs in several combinations (MMF in 87% and/or tacrolimus in 35% [n=240]). Patients with HCV antibodies pre- and/or post-RT were considered HCV-positive. Post-RT DM requiring prolonged treatment with oral antidiabetics or insulin (>1 month) was assessed using Kaplan-Meier curves and Cox analysis., Results: G2 patients were significantly older, had a greater body mass index (BMI), and suffered significantly less from acute rejection episodes during the first year than G1 patients. Furthermore, fewer required maintenance steroids. HCV-positivity was more common in G1 than in G2 (n=96, 29.1% vs n=27, 11.3%). Six G2 patients were successfully treated with interferon pre-RT, achieving negative PCR-HCV status (maintained post-RT). DM incidence at 4 years was similar in G1 and G2 (8.8% and 8.2%). G1 HCV-positive patients showed a greater risk of developing DM than HCV-negative patients (28.0% vs 6.2% at 10 years; P=001). In G1, multivariate analysis showed that age, BMI, and HCV-positivity were significant risk factors predicting DM (relative risk, 5.7; 95% confidence interval 2.7-12). In G2 patients, HCV was not associated with an increased risk of DM; in the multivariate analysis only age appeared to be a risk factor., Conclusions: The reported relationship between hepatitis C and post-RT DM was not observed among patients receiving new immunosuppressive treatments. Confirmation of this finding requires extended follow up. The reduced use of steroids and effective pre-RT use of interferon may also be responsible for the benefit.

Hepatitis C virus (HCV) infection represents an important problem for hemodialysis patients especially following renal transplantation. We assessed the outcome of HCV-positive patients undergoing renal transplantation after treatment during the pretransplant period with alpha-interferon 2b (alpha-IFN2b). Data from all HCV-infected patients (n=38) undergoing renal transplantation from a cadaveric donor between January 1997 and June 2002 were retrospectively reviewed. Viral clearance was achieved in 7 of 13 patients receiving alpha-IFN2b monotherapy during the pretransplant period. Controls were HCV-negative renal transplantation recipients operated during the same period (n=273). HCV-positive compared to HCV-negative patients showed no differences in age, gender, underlying disease, donor type, or immunosuppressive regimen, but there were significant differences (P<.001) in the mean (+/-SD) time on dialysis (155+/-70 versus 43+/-47 months), retransplant incidence (26% versus 5%), immunization rate as assessed by panel reactive antibodies (PRA) peak >50% (55% versus 18%), or 1-year survival of recipients (88% versus 97%) and of grafts (76% versus 89%). In contrast, all seven HCV RNA-negative patients who were before transplantation survived to the end of follow up with functioning grafts in six subjects and remained with normal liver function and clearance of HCV RNA. We conclude that kidney transplantation in HCV-positive compared with HCV-negative patients shows lower recipient and graft survival rates, possibly due to the higher incidence of risk factors, such as duration of hemodialysis, higher retransplantation rate, or hyperimmunization. Responders to pretransplantation IFN therapy show an excellent prognosis of liver function and overall outcome close to HCV-negative renal transplant recipients.

Objective: The objective of this study is to assess a Simulect (basiliximab) regimen in routine clinical practice in the Spanish kidney transplantation units to evaluate efficacy and safety., Methods: In this prospective, observational study, data on demographics, parameters of efficacy, and safety in patients who under with kidney transplantation treated with Simulect (basiliximab) were collected through an on-line collection system., Results: One hundred sixty three patients at 18 kidney transplant units included 12 months follow-up. The patient mean age was 52 years (DS 13,67) including 96 (58.90%) men and 67 (41.10%) women. Cold ischemia time was 19 hours (DS 6,79). Only 2 patients presented with PRA >50%. For prophylactic immunosuppression, 67.13% of patients received triple therapy with CNI (cyclosporine 49.65% or tacrolimus 17.48%), MMF (66.43%) or AZA (10.49%), and steroids. Incidence of acute rejection (AR) at 12 months was 12.27% (1.84% steroid-resistant). In subgroup analysis, AR was 13.5% in nondiabetics and 4.5% in diabetics, including 3 steroid-resistant episodes (1.84%) in nondiabetics and none in diabetics. In relation to donor age, AR was incidence 10.3% in patients with kidneys from donors aged 50 years or younger and 10.6% when donors were older than 50 years, including 1 (1.73%) and 2 (1.93%) steroid-resistant episodes, respectively. The graft and patient survival rates at 12 months were 90% and 98%, respectively., Conclusions: Simulect (basiliximab) used in routine clinical practice provided good prophylaxis against acute rejection in several kidney transplant patient populations, similar to that observed in randomized clinical studies with excellent tolerability and safety.

Introduction: The reduction of bone mineral density (BMD) levels is an important complication after renal transplantation. The prevalence of nontraumatic lesions may reach 22%. Patients with lower osseous mass suffer the highest number of lesions., Objective: Evaluate BMD in patients over 30-years old who have undergone renal transplantation more than 1 year prior, who attend a medical facility complaining of osteoarticular pain and were prescribed rest or any analgesia., Patients and Methods: One hundred twenty-three patients who received a renal transplant from a cadaveric donor from 1980 through 2000 were included in the present study to measure BMD levels in the hips and the vertebral column using a densitometer (Hologic 4500 QDR). Our study complied with WHO recommendations, which define normal values as a T score >-1 SD osteopenia as a (T score between <-1 and >-2.5 SD), and osteoporosis as a T score <-2.5 SD. Patients were divided into three groups according to gender and hormonal status. The following clinical and analytic data were collected: age, gender, race, age at onset of menopause, diabetes mellitus (DM), weight, size, retransplantation, period of evolution after transplantation, and parathormone (PTH), creatinine, and renal clearance values., Results: There were 51 men (41.1%) included. Forty postmenopausal (32.5%) and premenopausal women (26%) were also included. In all patients we observed a correlation between a reduction in BMD values and age, duration post-transplantation, and body weight (P<.05). Reduced BMD levels in premenopausal women were related with lower body weight, (P<.05) and elevated PTH levels (P<.024)., Conclusions: We observed that patients who had undergone transplantation displayed a moderately higher risk of suffering a fracture. Such risk increased in the case of women with more frequent fractures in the vertebral column. In 23.8% of patients reporting osseous pain, there was no reduction in BMD levels. Therefore, we must look for other disorder, responsible for the pain and prescribe adequate treatment.