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Background Prognostic biomarkers of acute rejection (AR) in solid organ transplantation have been addressed in multiple small retrospective studies, and there is a critical need for multicenter studies. Because of their tolerogenic properties, regulatory T cells (Tregs) play an important role in transplant outcome. Methods In the present multicenter study, we have retrospectively examined different Treg subpopulations in an independent cohort of kidney transplant patients within first year after kidney transplantation. All participating centers used identical flow cytometry standard operating procedures. Results Seventy-five renal transplant patients were included, and six of them experienced an AR episode. The activated Treg (aTreg) subpopulation (CD4CD25CD62LCD45RO) was increased in the AR group before transplantation, and an aTreg percentage higher than 1.46% before kidney transplantation conferred an increased risk of AR. The univariate logistic regression model achieved an area under the curve of 81.6%. By including recipient age and thymoglobulin induction as variables in a multivariate logistic regression model, the prediction of AR improved to 92.4%. Conclusion The evaluation of CD4CD25CD62LCD45RO aTreg cells may be useful as pretransplantation predictive biomarker of AR in kidney transplant patients. Definitive confirmation of our results awaits tests in validation groups.

Advanced chronic kidney disease (ACKD) has a great impact on health-related quality of life (HRQL). The use of this variable in studies in our field is becoming more frequent, although there has been no comprehensive review of how Spaniards with ACKD are assessed.To offer a contrasted vision of the HRQL assessment tools that are most often used on Spanish ACKD population, also analysing how this population perceive their quality of life.A review was carried out on literature published on studies undertaken in Spain that had used some kind of instrument, either generic or specific, in order to measure HRQL in patients with different stages of ACKD. Studies in kidney transplant patients were excluded when they were independently reviewed. The research was carried out in CINAHL, CUIDEN, DOCUMED, EMBASE, ERIC (USDE), IME, LILACS, MEDLINE, Nursin@ovid, PubMed, Scielo, Web of Science and TESEO.53 articles published between 1995 and May 2014 have been included in this review. Renal replacement therapy is the variable that is most often associated with the study of HRQL, with haemodialysis being the most studied. Most of the studies found are cross-sectional and the Short Form-36 Health Survey is the most used instrument.The majority of the studies show how HRQL is significantly affected in patients who receive renal replacement therapy. These results are independent from the instrument used to measure health-related quality of life and other associated variables throughout the various studies. HRQL has been particularly analysed in patients on haemodialysis, using mainly observational methods and the Short Form-36 Health Survey. There is a need for more studies that address aspects such as HRQL in the pre-dialysis phase, as well as studies with larger samples and longitudinal, analytical and experimental designs.

Background Safety concerns have been raised about the use of adjuvanted vaccines after kidney transplantation. Methods We retrospectively analyzed 65 kidney transplant (KT) recipients who received ≥1 dose of influenza vaccine (pandemic or seasonal) during the 2009–2010 campaign. Participants were classified into 2 groups: those who received a squalene-based AS03- or MF59-adjuvanted vaccine (“adjuvanted vaccination” [AV] group, n = 37) and those who exclusively received non-adjuvanted vaccines (“non-adjuvanted vaccination” [NAV] group, n = 28). Primary outcomes included occurrence of biopsy-proven acute graft rejection (BPAR) and graft function at months 6 and 12 after vaccination. Patients were followed up until graft loss, death, or October 2010. Results Four episodes of BPAR occurred during post-vaccination follow-up, with no differences between the AV and NAV groups, in terms of cumulative incidence (5.4% vs. 7.1%, respectively; P = 0.581), incidence rate (0.22 vs. 0.18 episodes per 1000 transplant-days; P = 0.950), or occurrence of severe episodes (T-cell-mediated BPAR of grade ≥2a) (2.7% vs. 3.6%; P = 0.680). No between-group differences were seen in graft function after vaccination. Conclusion Adjuvanted influenza vaccination in KT recipients seems to be safe regarding graft outcome.

Cholestatic hepatitis and diffuse liver fibrosis have been described in immunosuppressed patients with hepatitis B virus or hepatitis C virus infection as fibrosing cholestatic hepatitis (FCH). FCH is characterized by cholestasis, with only a modest increase in aminotransferase levels. The pathologic picture typically shows periportal and perisinusoidal fibrosis, scarce mixed infiltrates, hepatocellular ballooning, and histologic cholestasis. We report two patients with diffuse fibrosis and cholestasis quite similar to the histologic picture of FCH, but in whom neither hepatitis B virus nor hepatitis C virus infection could be shown, highlighting the potential contribution of cytomegalovirus infection and azathioprine toxicity in the development of this severe complication of solid-organ transplantation. © 2001 by the National Kidney Foundation, Inc.

BACKGROUND: Supplementation of immunosuppressive therapy with mycophenolate mofetil (MMF) has been found to reduce the rate of acute rejection in renal transplantation. We report a dose-finding study for MMF when administered in combination with low-dose tacrolimus and corticosteroid prophylaxis in cadaveric renal transplant recipients. METHODS: Two hundred thirty-two patients at 16 centers were enrolled in this randomized, parallel-group study. The three treatment groups were tacrolimus and corticosteroids (MMF-0 group, n=82); tacrolimus, corticosteroids, and 1 g of MMF daily (MMF-1 g group, n=79); and tacrolimus, corticosteroids, and 2 g of MMF daily (MMF-2 g group, n=71). Study duration was 6 months, and patients were followed up for patient and graft survival for 12 months. RESULTS: At 6 months posttransplantation, daily doses of 1 g and 2 g of MMF were associated with significantly lower rates of acute rejection compared with tacrolimus alone. The Kaplan-Meier rates were 48.5%, 24.9%, and 22.9%, respectively, for the three treatment groups when acute rejection was determined by clinical criteria (P=0.007). At month 12, patient survival rates were 100%, 97.5%, and 97.2% and graft survival rates were 90.2%, 92.4%, and 93.0% for the MMF-0 group, MMF-1 g group, and the MMF-2 g group, respectively. Gastrointestinal adverse events and leukopenia were higher in the MMF groups, especially in the MMF-2 g group (P

Cyclosporin and tacrolimus have improved survival figures in organ transplantation. However, both drugs are potentially nephrotoxic. The immunosuppressive and nephrotoxic effects of both drugs appear to depend on the inhibition of calcineurin. Cyclosporin and tacrolimus cause acute (functional changes) and chronic nephrotoxicity (structural lesions in the kidney). These last important lesions include arteriolar hyalinosis, stripped interstitial fibrosis and tubular atrophy. It is possible that repeated episodes of renal ischaemia contribute to the development of chronic nephrotoxicity and then chronic allograft nephropathy. Cyclosporin and tacrolimus also induce arterial hypertension. Therefore, the beneficial effects of immunosuppression have been limited due to nephrotoxicity and arterial hypertension. Rapamycin, a novel immunosuppressive agent, that does not inhibit calcineurin, provides immunosuppression without nephrotoxicity. In fact, in the trials performed in Europe, sirolimus-treated immunosuppression patients exhibited a much better renal function than cyclosporin-treated patients. However, sirolimus can potentiate the nephrotoxic effect of cyclosporin. Therefore, when cyclosporin and sirolimus are used in combination, a reduction of the cyclosporin dose is desirable.

IgA antibeta 2 Glycoprotein I (β2GPI) antibodies test can identify some patients with antiphospholipid syndrome (APS) that are negative for other isotypes. Controversy exists because some studies have reported a strong association of these antibodies with vascular disease, while others have not confirmed this observation. Our hypothesis is that these contradictory results may be due to differences among commercial diagnostic kits. To answer this question, we have compared the results obtained with several of the most commonly used commercial IgA anti β2GPI antibodies (aβ2GPI) diagnostic assays on specimens from individuals suspected of having APS. Sera from 69 patients (37 positive and 32 negative for IgA aβ2GPI) were analyzed with seven different commercial ELISA kits for IgA aβ2GPI, following instructions and cutoffs provided by the manufacturer. Our results showed important differences in the sensitivity and specificity of the different assays. Two of the seven kits tested had a sensitivity level below 65% for IgA aβ2GPI, and three showed levels of specificity lower than 80%. Some commercial kits to detect IgA aβ2GPI are suboptimal. Variability between kits may account for the discrepancy in results obtained and for the lack of consensus concerning their clinical significance. It is important that the scientific community work to standardize assay performance so that the true clinical significance of this important clinical marker can be clearly established.

Serial monitoring of peripheral blood lymphocyte subpopulations (PBLSs) counts might be useful in predicting post-transplant opportunistic infection (OI) after kidney transplantation (KT). PBLSs were prospectively measured in 304 KT recipients at baseline and post-transplant months 1 and 6. Areas under receiver operating characteristic curves were used to evaluate the accuracy of different subpopulations in predicting the occurrence of overall OI and, specifically, cytomegalovirus (CMV) disease. We separately analyzed patients not receiving (n = 164) or receiving (n = 140) antithymocyte globulin (ATG) as induction therapy. In the non-ATG group, a CD8(+) T-cell count at month 1

Summary Hepatitis C virus (HCV) infection is the most frequent cause of liver disease after renal transplantation. Its clinical course is irrelevant in the short term, except for rare cases of fibrosing cholestatic hepatitis. However, in the long run, HCV infection can lead to major liver complications. Because interferon (IFN) is generally contraindicated in renal transplant patients, the best approach is to treat patients on dialysis. Until more information with pegylated-IFN is available, the use of alpha-IFN monotherapy is recommended. Most of the patients with sustained virological response remain HCV RNA negative after transplantation. HCV-positive renal transplant patients have a higher risk for proteinuria, chronic rejection, infections and post-transplant diabetes (PTDM). Long-term patient- and graft-survival rates are lower in HCV-positive patients. Mortality is higher, mainly as a result of liver disease and infections. HCV can contribute to the development of certain neoplasias such as post-transplant lymphoproliferative disease (PTLD). HCV infection is also an independent risk factor for graft loss. PTDM, transplant glomerulopathy and HCV-related glomerulonephritis can contribute to graft failure. Despite this, transplantation is the best option for end-stage renal disease in HCV-positive patients. Several measures to minimize the consequences of HCV infection have been recommended. Adjustment of immunosuppression and careful follow up in the outpatient clinic for early detection of HCV-related complications are mandatory.

Hyperhomocysteinemia, an independent risk cardiovascular factor, has been reported in renal transplanted patients (RTP). The aim of the present study was to evaluate homocysteine levels in RTP treated with cyclosporine or tacrolimus, and the changes observed in the two groups of patients after treatment with folic acid. Forty-two RTP with stable function (21 treated with cyclosporine and 21 with tacrolimus, matched by gender and age) were studied. Forty healthy control subjects were matched by age and gender with the patients. In RTP, homocysteine was increased compared with the controls (16.4 +/-5.2 vs 8.0 +/- 1.8 micromol/L; p < 0.001), but there was no difference in vitamin B12 and folic acid levels. Thirty-three patients and one control showed hyperhomocysteinemia (78.5 vs 2.5%; p < 0.001). Homocysteine correlated negatively with creatinine clearance in the patients (p = 0.04), but no correlation was found with vitamin B12, folic acid and lipoproteins. By univariate analysis, patients treated with cyclosporine had higher homocysteine than those treated with tacrolimus (p = 0.03), but multivariate analysis did not confirm these results. In 21 patients with hyperhomocysteinemia and folate levels similar to those of the controls, folic acid (5 mg/d for 3 months) was administered. Homocysteine decreased significantly (19.1 +/- 4.8 vs 13.2 +/- 3.4 micromol/L; p < 0.001), with a median reduction of 31% and with no differences observed in patients treated with either cyclosporine or tacrolimus. We concluded that hyperhomocysteinemia is very frequent in RTP, but homocysteine levels are not different in patients treated with cyclosporine or tacrolimus. Folic acid therapy produces a significant decrease in homocysteine concentrations, in the absence of clear folate deficiency, without differences in relation to immunosuppressant therapy.

Renal transplantation procedures in patients older than 60 years of age have clearly improved in recent years. In the cyclosporin era, graft and patient survival are good. However, older patients exhibit a higher mortality, especially from infectious and cardiovascular causes, than young patients. In this article we review the immunosuppressive treatment in older patients, analyse what drugs can be used and finally propose several immunosuppressive combinations to treat this group of patients. Currently, new immunosuppressive drugs enable more flexible immunosuppressive protocols. Nevertheless, to avoid overimmunosuppression, elderly patients should be treated with lower doses and fewer immunosuppressive drugs.

Introduction. A previous trial in renal transplantation comparing sirolimus (rapamycin) to cyclosporine (CsA) ina triple-drug therapy regimen with azathioprine and corticosteroids found that the incidence of acute rejection was similar (approximately 40%) with a trend for better renal function with sirolimus. Methods. In 14 European centers, first cadaveric renal allograft recipients were randomized to receive sirolimus (n=40) or CsA (n=38) in an open-label design. All patients received corticosteroids and mycophenolate mofetil 2 g/day. Sirolimus and CsA were concentration controlled; trough levels of mycophenolic acid and prednisolone were also measured. Results. At 12 months, graft survival(92.5% sirolimus vs. 89.5% CsA), patient survival (97.5% sirolimus vs. 94.7% CsA), and the incidence of biopsy-proven acute rejection (27.5% sirolimus vs. 18.4% CsA) were not statistically different. The use of antibodies to treat suspected rejection episodes was also similar (7.5% sirolimus vs. 5.3% CsA). More sirolimus patients received bolus steroid therapy (20 vs. 11, P=0.068). From month 2 onward, the calculated glomerular filtration rate was consistently higher in sirolimus-treated patients. The adverse events reported more frequently with sirolimus were thrombocytopenia (45% vs. 8%) and diarrhea (38% vs. 11%). In the CsA group, increased creatinine (18% vs. 39%), hyperuricemia (3% vs. 18%), cytomegalovirus infection (5% vs. 21%), and tremor (5% vs. 21%) were observed significantly more often. Discussion. Patient and graft survival and the incidence of biopsy-proven acute rejection at 12 months were comparable between sirolimus and CsA, whereas safety profiles were different. These data suggest that sirolimus may be used as primary therapy for the prevention of acute rejection.

Everolimus (Eve) has shown good efficacy and safety profiles in clinical trials in combination with low doses of cyclosporine but there is limited experience in other modes, especially with calcineurin inhibitor elimination. We developed a retrospective study to analyze its clinical use after approval in Europe in 2005. Herein we have presented the results of a series of 272 patients followed for the first 6 months after Eve introduction. In 93.8% of cases Eve was introduced after the first month posttransplantation (conversion use), and 6 months after introduction, the CNI had been eliminated in 75% of cases. The main indication for Eve introduction was the diagnosis of a malignant neoplasm (42%), whereas the combined indication of prevention and/or treatment of toxicity, especially nephrotoxicity, accounted for 46.3% of cases. Initial doses were low (1.37 mg/d), but were progressively increased up to 2 mg/d at 6 months. Renal function remained unchanged during the follow-up period, whereas proteinuria moderately increased. Only 5 cases (2%) of acute rejection episodes were observed with excellent patient and graft survivals at 6 months after conversion. Further analysis of this extensive series of patients with a longer follow-up is needed.

Mujer de 36 anos de edad, que presenta una tumoracion de 1,5 cm de diametro en conducto auditivo externo (CAE) izquierdo, de coloracion rojo-azulada y aspecto quistico, de un ano de evolucion (fig. 1). Se sospecha la posibilidad de que se trate de un carcinoma basocelular de CAE. Se solicita TAC de penascos previo a intervencion quirurgica para valorar extension. La tumoracion se limita al CAE sin erosiones oseas. Se realiza exeresis de la lesion mediante un abordaje endoaural. El estudio anatomopatologico (AP) descarta basalioma y revela una formacion quistica con revestimiento epitelial bicapa de habito ecrino (fig. 2A y B) compatible con hidrocistoma ecrino.

Publication Types: Clinical Trial Multicenter Study Randomized Controlled Trial

The purpose of this study was to investigate the incidence and risk factors for the development of diabetes mellitus after kidney transplantation (PTDM). A total of 1783 nondiabetic renal allograft recipients transplanted from January 2000 to December 2002 were included. Diabetes was diagnosed following American Diabetes Association criteria. While 1276 patients were treated with tacrolimus (Tac), mycophenolate mofetil (MMF), and steroids, 507 patients received cyclosporine-ME (CsA), MMF, and steroids. PTDM incidence at 6, 12, and 24 months was 14.2%, 12.8%, and 13.3%, respectively. Cumulative incidence during the follow-up was 21.6%. Only 121 of the diabetic patients (47.6%) at 6 months remained diabetic at 24 months. Furthermore, 60 patients of 116 patients on insulin at 6 months (51.7%) remained on treatment at 24 months. The cumulative incidence of PTDM was similar in the two immunosuppressive treatments (19.7% on CsA-MMF vs 22.3% on Tac-MMF; P = NS). However, at 24 months, 14 of 50 diabetic patients on CsA-MMF (28%) and 74 of 161 patients on Tac-MMF (45.9%) were on insulin treatment (P.05). By Cox regression analysis, age older than 60 years (RR 1.61; 95%CI 1.28-2.04; P.001), body mass index (BMI)30 kg/m2 at transplantation (RR 1.66; 95%CI 1.27-2.16; P.001), and immunosuppression with Tac (RR 1.30; 95%CI 1.02-1-66; P = .033) were associated with PTDM. In conclusions, the incidence of PTDM at 24 months in immunosuppressive protocols including MMF is about 22%, and it is associated with older age, increased BMI, and immnunosuppression with Tac.

BACKGROUND Angiotensin-converting enzyme (ACE) inhibitors have an antiproteinuric effect in membranous glomerulonephritis (MGN). However, no studies have investigated whether this antiproteinuric effect is influenced by urinary C5b-9 excretion, a marker of immunological activity in this disease. METHODS Eleven patients with biopsy-proven MGN were treated with captopril for 8 weeks. The evolution of several clinical and biochemical parameters, including 24-h urinary protein excretion was evaluated every 4 weeks. Urinary C5b-9 excretion was measured at the onset and at the end of captopril treatment. RESULTS Patients with MGN had significantly higher C5b-9 excretions than a group of 14 healthy controls (89 +/- 23 vs 3.7 +/- 1.4 ng/mg UCr; P < 0.001). A significant correlation was found between urinary C5b-9 and the magnitude of proteinuria, both at the onset and at the end of treatment. After 8 weeks of captopril treatment, proteinuria had decreased from 8 +/- 1.8 to 5.2 +/- 1.3 g/day (P < 0.05). Four weeks after captopril discontinuation, proteinuria rose to 7.3 +/- 1.7 g/day (P < 0.05). A marked variability in the antiproteinuric response was observed, ranging from 0 to 85% with respect to baseline values. No correlation between decrease in proteinuria and baseline urinary C5b-9 levels was observed. Several patients with elevated urinary C5b-9 levels had captopril-induced decrease in proteinuria. CONCLUSIONS ACE inhibition induces an antiproteinuric effect in patients with MGN. The urinary C5b-9 excretion does not predict the magnitude of this response.

Cyclosporin has been shown to facilitate renal vasoconstriction and to have an antinatriuretic effect. The existence of an interference of cyclosporin with the vasodilating properties of endothelium mediated by nitric oxide production could mediate these effects. On the other hand, the infusion of the nitric oxide precursor L-arginine has been shown to induce renal vasodilatation and to facilitate natriuresis in normal volunteers. We have investigated the renal effects of the administration of an infusion of L-arginine in renal transplant patients chronically treated with cyclosporin. To facilitate the analysis of the data the effects of the administration of a similar dose of cyclosporin on renal function during the infusion of a vehicle were also investigated during the administration of a vehicle of L-arginine.Ten male renal transplant patients, chronically treated with cyclosporin and with a stable renal function were studied during 2 consecutive days after the administration of the usual morning dose of cyclosporin. The first day they received an intravenous infusion of vehicle and the second the infusion of graded doses of L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h.The first day, after cyclosporin administration a significant fall (P0.01) was observed in natriuresis and kaliuresis in the absence of changes in renal plasma flow and glomerular filtration rate. After the administration of L-arginine significant (P0.01) increases of renal plasma flow, glomerular filtration rate, and natriuresis were seen. The increase in blood levels of cyclosporin after its administration did not differ between days 1 and 2.These results indicate that L-arginine facilitates renal vasodilatation and natriuresis in renal transplant patients. Furthermore, the observed increase in sodium excretion could indicate that L-arginine counteracts the antinatriuretic effect of cyclosporin.

Background.Hepatitis C virus (HCV) infection has been described in association with various types of glomerular diseases, usually type I membranoproliferative glomerulonephritis and rarely membranous glomerulonephritis (MGN). In this article, we describe the first series of MGN exhibited in renal transplant patients and associated with HCV infection. Methods. From January 1980 to December 1994, 2045 kidney transplantations were performed in our renal transplant units. A retrospective analysis demonstrated an overall 20% prevalence of HCV virus-positive patients; 409 transplanted patients were HCV positive (ELISA and RIBA). Results. Fifteen patients developed an allograft MGN (3.66%) 24 months after renal transplantation. MGN appeared in the form of significant proteinuria (>1.5 g/24 h) with stable renal function. In all cases, graft biopsy demonstrated a thickening of the capillary wall, subepithelial electron-dense deposits, and IgG and C3 diffuse granular deposits along the basal membrane. Ten cases were considered de novo, two cases were considered recurrent MGN, and three cases were considered undetermined because the primary renal disease was chronic glomerulonephritis. All patients showed negative antinuclear antibodies and cryoglobulins, normal complement, and negative rheumatoid factors. During follow-up (an average of 2 years), 12 patients developed a progressive worsening of renal function, with increased serum creatinine and persistent proteinuria; 8 of the 12 patients returned to dialysis. Of the remaining three cases, two patients showed partial remission of nephrotic syndrome after high doses of steroids, and one patient persisted with stable renal function and proteinuria (

Chronic rejection - also called chronic renal allograft dysfunction (CRAD) - is the main cause of long-term loss of the transplanted kidney, but its pathogenesis is not well known. The aim of this study was to know if lipoproteins, fibrinogen, plasminogen activator inhibitor-1 (PAI-1) and platelet aggregation show more abnormalities in renal transplant patients with CRAD than in those with stable renal function. Sixty patients with renal allograft have been studied; 20 patients with CRAD and 40 controls matched for age, gender and time after transplantation. In a univariate analysis patients with CRAD had higher total serum triglycerides (214+/-153 vs. 133+/-39 mg/dl; p = 0.04) and very-low-density lipoprotein (VLDL) triglycerides (128+/-116 vs. 59+/-29 mg/dl; p = 0.04). Apolipoprotein B levels were also increased in patients with CRAD although this difference was only borderline significant (131+/-58 vs. 98+/-16 mg/dl; p = 0.05). Similarly, there was a trend toward increased total, VLDL, and low-density lipoprotein (LDL) cholesterol and reduced high-density lipoprotein (HDL) cholesterol in CRAD patients, but these differences did not reach statistical significance. Apolipoprotein A-1 and lipoprotein(a) levels were similar in both groups. Neither platelet aggregation nor PAI-1 levels differed between both groups. In contrast, fibrinogen was increased in patients with CRAD (373+/-81 vs. 322+/-62 mg/dl; p = 0.01). In a multivariate analysis triglycerides and fibrinogen were positively correlated to CRAD. These findings add further support to the hypothesis that lipid abnormalities may be involved in the pathophysiology of CRAD. In addition, this is the first report showing that fibrinogen levels are increased in patients with CRAD. Further studies are needed to evaluate a potential role of fibrinogen in the development of CRAD.

Transplant recipients receiving immunosuppressive therapy are at increased risk of active cytomegalovirus (CMV) infection and disease. Without appropriate prophylaxis, as many as 80% of solid organ transplant recipients may experience CMV infection. In addition to the direct effects of CMV, infection may be associated with a range of indirect effects, including an increase in risk of other infections, as well as a higher incidence of rejection, graft loss and death. The indirect effects of CMV infection can vary depending on the transplanted organ. For example, CMV-infected kidney transplant recipients may be at increased risk of cardiovascular disease and diabetes, while CMV infection in liver transplant recipients may potentiate hepatitis C infection and increase the risk of post-transplant lymphoproliferative disease. Indirect effects result from a number of pathological processes, including immune modulation and immunosuppression, generation of cytotoxic, pro-inflammatory responses, and smooth muscle proliferation. Prophylactic treatment with antiviral medication can reduce the risk of CMV disease, thereby improving graft survival and overall outcomes, particularly in kidney and heart transplant recipients. Antiviral prophylaxis should be considered for all patients at risk of CMV infection after solid organ transplantation. In this paper we review the main indirect effects of CMV infection in solid organ transplant recipients, and the impact of CMV prophylaxis on these effects.

BACKGROUND: The association of anemia with outcomes after renal transplantation (RT) is unclear. METHODS: We performed a retrospective study that included patients who received a RT in Spain in 2007. We collected data on anemia (hemoglobin [Hb]

Background Pretransplantation anti-major histocompatibility complex class I chain-related molecule A (MICA) sensitization is an uncommon event and its role on kidney graft evolution is not completely defined. Methods A retrospective study of patients transplanted between 2005 and 2011 in our center (n=727) was performed. Recipients were classified in four groups, according either to multiplexed flow cytometry-recorded anti-human leukocyte antigen (HLA) and anti-MICA antibodies or to percent panel-reactive antibody (PRA; by complement-dependent cytotoxicity) and anti-MICA antibodies. Results In the total cohort, 52 (7.15%) patients had preformed anti-MICA antibodies, and these were not related with anti-HLA, previous transplantations, or recipient female sex (potential pregnancies). Kaplan-Meier curves showed global allograft survival differences (P=0.042) mostly due to pronounced decrease in PRA+MICA+ group early after transplantation. Biopsy-proven allograft rejection rate increased after month 12 in PRA+MICA- group and was higher early after transplantation in PRA+MICA+ group (P=0.033). In paired comparisons, rejection incidence was superior in PRA+MICA- versus PRA-MICA- patients (17% vs. 7%; P=0.007) at 24 months, confirming the widely reported deleterious effect of PRA+ status, but at 3 months rejection was higher in PRA+MICA+ versus PRA-MICA- patients (14% vs. 2%; P=0.009). Among patients categorized according anti-HLA and anti-MICA antibodies, the most striking difference in rejection was observed at 3 months (8% in HLA-MICA+ vs. 2% in HLA-MICA- patients; P=0.032). In the multivariate analysis, HLA-MICA+ status at 3 months independently conferred the highest risk for rejection (odds ratio, 5.07; P=0.049). Conclusions Pretransplantation sensitization against MICA and HLA are independent events. Preformed anti-MICA antibodies independently increase risk for kidney rejection and enhance the deleterious effect of PRA+ status early after transplantation.

Background Epstein-Barr virus (EBV) DNAemia (EBVd) may be a surrogate marker of the net state of immunosuppression after solid organ transplantation (SOT). Methods A sample of 81 SOT recipients (53 renal, 21 liver, and 7 cardiac) from our institution (2003-2004) surviving more than 180 days was analyzed. EBVd was monitored in whole blood within the first 6 months using a real-time polymerase chain reaction assay. Using a Cox proportional hazards model, duration and magnitude of EBVd were assessed as potential surrogate markers for the occurrence of late adverse events (>6 months): graft dysfunction, graft loss, death, and immunosuppression-related adverse events (IRAE), defined by the occurrence of solid organ tumor and opportunistic and severe infections. Results A median of 10 blood samples per patient was screened. A total of 68 (84%) patients had detectable EBVd. Persistent EBVd (>30 days) was found in 40 (49.4%) and high EBVd (>1500 copies/mL) in 35 (43.3%). Multivariate analyses showed that persistent EVBd and high EBVd levels were independently related to the development of IRAE (hazard ratio, 2.95 and 4.32, respectively), whereas no significant associations were observed with late graft dysfunction or graft loss. Conclusions Persistent and high levels of EBVd within the first 6 months after SOT are surrogate markers of increased risk of IRAE.

Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic and cardiovascular complications in the general population and in hemodialysis patients. Increased Lp(a) levels have been also described as a possible predictor of vascular access occlusion in patients on chronic hemodialysis. We have studied prospectively the relationship between vascular access survival and Lp(a) levels in 40 hemodialysis patients. The Lp(a) plasma concentrations were measured by enzyme-linked immunosorbent assay in all patients in April 1993. Throughout the following year, evolution and survival of their vascular accesses were analyzed. Failure of vascular access was established when there were complications requiring surgical repair or transluminal angioplasty. Fourteen patients showed failure of vascular access, and the cumulative survival of vascular accesses after 1 year of follow-up was 63.8%. The Lp(a) levels were higher in patients with failure of vascular access than in the others (35.2 +/- 31 vs. 22.4 +/- 25 md/dl), but this difference did not reach statistical significance (p = 0.064). The vascular access survival in patients with Lp(a) levels75th percentile (52.5 mg/dl) was significantly lower than in the remaining patients (40 vs. 72%; p = 0.045). This difference increased when we analyzed the patients with Lp(a) levels90th percentile (76 md/dl; 25 vs. 68%; p = 0.002). Our results suggest that patients with the highest levels of Lp(a) are at risk of developing complications in their vascular accesses, and they also have lower vascular access survival.

The urinary enzymes alanine aminopeptidase (AAP; EC 3.4.11.2) and N-acetyl-B-D-glucosaminidase (NAG; EC 3.2.1.30) were measured daily in 35 renal transplant recipients during the early postoperative period. Each peak value of fractional excretion was corrected for its baseline value (CFE). CFE values above normal for both NAG and AAP were more frequently found in episodes of acute rejection than in cyclosporine acute nephrotoxicity episodes (76 vs. 0%; p < 0.001). Consequently, a rise in CFE levels for both NAG and AAP is strongly suggestive of acute rejection crisis.

Uncontrolled donations after circulatory death (DCD) present 2 well-established risk factors for infection after kidney transplantation (KT): greater rates of delayed graft function (DGF) and antithymocyte globulin (ATG)-containing sequential therapies.We performed a prospective cohort study of our 291 KT patients between November 2008 and July 2011 to compare the incidences of infection between DCD (n = 87) and donation after brain death (DBD; n = 204) recipients. Most DCD donors were uncontrolled Maastricht categories 1 or 2. Backward stepwise Cox proportional hazards models were used to assess the impact of DCD on the primary study outcome.As compared to the DBD group, DCD recipients were younger, less likely to have undergone previous transplantations, exhibited lower dialysis vintage, and displayed a greater incidence of DGF and graft loss, but lower incidence of acute rejection episodes. There were no differences in the non-death-censored graft survival at 2 years (log-rank P = .835). The DCD group showed lower cumulative incidences of overall, bacterial, cytomegalovirus (CMV), and non-CMV viral infections (P.05 for all). Multivariate analysis, associated DCD with a lower risk of overall infection (hazard ratio: 0.41; 95% confidence interval: 0.28-0.60; P = .012), an effect that remained when the analysis was restricted to patients receiving ATG induction therapy. Finally, there were no differences in the cumulative incidence of overall infection when DCD recipients were compared with age-matched DBD controls: 43.7% vs 47.1% respectively (P = .648).Despite the higher rate of DGF and the use of ATG-containing sequential therapy, uncontrolled DCD policies were safe in terms of the risk of post-transplant infection.

In the follow-up of transplanted patients under immunosupression, the functional assessment of CD4+ T cells activation by measuring intracellular ATP levels in vitro, using the Immuknow test give information on how immune system is functioning. Therefore, it has been reported that low levels of ATP correlate with the risk of opportunistic infection. Although limited, comprehensive results in adult recipients as well as in pediatric transplanted patients have been reported. Forty stable liver pediatric transplanted patients (mean age: 11.0 years [SD 5.65]), within at least 1 year of transplant were selected for a scheduled review, and an unique determination of Immuknow was performed. Average ATP levels were 317 ng/mL (200-400 ng/mL) which were similar to the values observed in adult population. ATP values among patients with monotherapy Cyclosporin A (CSA) or tacrolimus (TAC) were significantly higher (P = .005) than in patients with double immunosupressive therapy using either CSA/TAC + Mycophenolate Mofetil (MMF). In CSA treatment, there are significant differences (P = .0003) between monotherapy and double therapy, but in the case of TAC we did not find differences (P > .1). A single determination of levels of ATP on CD4+ lymphocytes, can provide additional information that could be used as a complementary test to guide immunosuppressive therapy in paediatric liver transplant recipients.

BACKGROUND Seropositivity for hepatitis C virus (HCV) predicts lower patient and graft survival after renal transplantation (RT). However, the influence of viral replication at transplantation on long-term outcome remains to be determined. METHODS This was a retrospective study conducted in four Spanish hospitals, from 1997 to 2006. Data of all patients with RT, who displayed HCV+ (enzyme-linked immunosorbent assay), and with negative viremia at RT (NEG group) were collected (n=41). For each NEG patient enrolled, data of two patients with RT nearest in time, HCV+, and positive viremia (POS group) were also collected (n=78). RESULTS The POS group showed a higher incidence of long-term liver disease (56.4% vs. 24.4%, P=0.0009) and episodes of transaminase elevation (38.5% vs. 7.3%, P=0.0003) and worse renal function (serum creatinine [sCr], 3.0 [2.7] vs. 1.9 [1.6] mg/dl, P=0.032; glomerular filtration rate, 43.7 [22.4] vs. 56.9 [27.9] ml/min, P=0.075). Noteworthy, 24.4% of NEG patients reactivated after RT, showing a worse patient survival (P=0.039). Active viral replication at RT and dialysis requirement in the first week remained as independent predictors of lower graft survival (death censored): hazards ratio, 3.11 (95% confidence interval, 1.34-7.19; P=0.009) and hazards ratio 3.13 (95% confidence interval, 1.53-6.37; P=0.002). CONCLUSIONS This study shows that active viral replication at transplantation is an independent risk factor for graft failure in patients with positive serology for HCV.

Transplantation of kidneys from donors with hepatitis C antibody into recipients pre-transplantation anti-HCV. Hepatitis C virus (HCV) is transmitted by organ transplantation. Consequently, several organ procurement organizations have imposed a moratorium on use of organs from anti-HCV positive donors. Because of the inadequate supply of cadaver kidneys for transplantation, we adopted a policy to transplant kidneys from anti-HCV donors into anti-HCV positive recipients. During the period between March 1990 and December 1992, 24 anti-HCV positive dialysis patients received a kidney from anti-HCV positive donors (group I) and 40 anti-HCV positive patients received a kidney from anti-HCV negative donors (group II). We compared the prevalence of liver disease, anti-HCV, HCV RNA, graft and patient survival between groups.Pre-transplantation 17 of 24 (71%) patients in group I and 31 of 40 (79%) of patients in group II had serum HCV RNA. Post-transplantation follow-up was 26 ± 8 months and 30 ± 10 months in groups I and II, respectively. During follow-up, elevated ALT levels were present in 7 of 24 (29%) and 16 of 40 (40%) of patients in groups I and II, respectively (P > 0.05). Post-transplantation, all patients in both groups retained anti-HCV. The prevalence of HCV RNA post-transplantation was 22 of 23 (96%) patients in group I and 30 of 39 (77%) of patients in group II (P > 0.05). Graft and patient survival in group I (96% and 100%, respectively) were not significantly different from those in group II (93% and 98%, respectively). The results of this study demonstrate the short-term safety of using kidneys from anti-HCV positive donors in anti-HCV positive recipients. However, this policy may not prevent transmission of HCV. A safer strategy would be to transplant kidneys from anti-HCV positive donors into recipients with HCV RNA.

The long-term outcomes of kidney transplantation are suboptimal because many patients lose their allografts or experience premature death. Cross-country comparisons of long-term outcomes of kidney transplantation may provide insight into factors contributing to premature graft failure and death. We evaluated the rates of late graft failure and death among US and Spanish kidney recipients.This is a cohort study of US (n = 9609) and Spanish (n = 3808) patients who received a deceased donor kidney transplant in 1990, 1994, 1998 or 2002 and had a functioning allograft 1 year after transplantation with follow-up through September 2006. Ten-year overall and death-censored graft survival and 10-year overall recipient survival and death with graft function (DWGF) were estimated with multivariate Cox models.Among recipients alive with graft function 1 year after transplant, the 10-year graft survival was 71.3% for Spanish and 53.4% for US recipients (P0.001). The 10-year, death-censored graft survival was 75.6 and 76.0% for Spanish and US recipients, respectively (P = 0.73). The 10-year recipient survival was 86.2% for Spanish and 67.4% for US recipients (P0.001). In recipients with diabetes as the cause of ESRD, the adjusted DWGF rates at 10 years were 23.9 and 53.8 per 1000 person-years for Spanish and US recipients, respectively (P0.001). Among recipients whose cause of ESRD was not diabetes mellitus, the adjusted 10-year DWGF rates were 11.0 and 25.4 per 1000 person-years for Spanish and US recipients, respectively.US kidney transplant recipients had more than twice the long-term hazard of DWGF compared with Spanish kidney transplant recipients and similar levels of death-censored graft function. Pre-transplant medical care, comorbidities, such as cardiovascular disease, and their management in each country's health system are possible explanations for the differences between the two countries.

The development of new immunosuppressants for renal transplantation is aimed not only at improvingnbsp;short-term outcomes, but also at achieving better safety, cardiovascular, and metabolic profiles and at decreasingnbsp;nephrotoxicity. Belatacept is a fusion protein that inhibits T cell activation by binding to CD80 and CD86 antigens. Clinical trials, particularly the BENEFIT and BENEFIT-EXT studies, have shown that belatacept preserves function and structure in renal grafts. The effects of belatacept provide long-term, sustained results, and the safety and efficacy of this drug have been demonstrated in cases of renal transplantation from expanded criteria donors. Compared to calcineurin inhibitors, belatacept is associated with a lower incidence of chronic allograft nephropathy and a more favourable cardiovascular and metabolic profile.

Preface: Morales, J.M. Hepatitis C: Epidemiology, Diagnosis, Natural History and Therapy: Pol, S. Vallet-Pichard, A. Corouge, M. Mallet, V.O. Hepatitis C and Renal Disease: Epidemiology, Diagnosis, Pathogenesis and Therapy: Morales, J.M. Kamar, N. Rostaing, L. Hepatitis C-Induced Renal Disease in Patients with AIDS: An Emergent Problem: Praga, M. Gutierrez Solis, E. Morales, E. Hepatitis C in Hemodialysis: Epidemiology and Prevention of Hepatitis C Virus Transmission: Jadoul, M. Barril, G. Hepatitis C-Related Liver Disease in Dialysis Patients: Fabrizi, F. Dixit, V. Messa, P. Martin, P. Treatment of Hepatitis C in Dialysis Patients: Esforzado, N. Campistol, J.M. Selection and Management of Hepatitis C Virus-Infected Patients for the Kidney Transplant Waiting List: Roth, D. Bloom, R. Kidney Transplantation in the Patient with Hepatitis C Virus Infection: Morales, J.M. Bloom, R. Roth, D. Treatment of Hepatitis C Virus Infection after Kidney Transplantation: Rostaing, L. Weclawiak, H. Izopet, J. Kamar, N. Immunosuppression in Hepatitis C Virus-Infected Patients after Kidney Transplantation: Manuel, O. Baid-Agrawal, S. Moradpour, D. Pascual, M. Impact of Extrahepatic Complications (Diabetes and Glomerulonephritis) Associated with Hepatitis C Virus Infection after Renal Transplantation: Cruzado, J.M. Bestard, O. Grinyo, J.M. Renal Transplantation from Donors with a Positive Serology for Hepatitis C: Dominguez-Gil, B. Esforzado, N. Andres, A. Campistol, J.M. Morales, J.M.

There is an increased evidence for the association between hepatitis C virus (HCV) infection and kidney diseases. Recent epidemiological studies strongly suggest that HCV infection is a risk factor for proteinuria and/or impaired renal function. Type I membranoproliferative glomerulonephritis (MPGN) associated with type II cryoglobulinemia is the most frequent renal disease, and non-cryoglobulinemic MPGN and membranous glomerulonephritis are less frequently associated with active HCV infection. The pathogenesis of these lesions are related to the deposition of immune complexes in the glomeruli, and recently it has been described that toll-like receptor 3 could have a pathogenic role establishing a link between viral infection and glomerulonephritis. Patients with HCV-related glomerulopathies should be treated with angiotensin-converting enzyme inhibitors in association or not with angiotensin receptor blockers, as well as with anti-HCV therapy. The latter relies on a combined antiviral therapy of standard or pegylated interferon-α and ribavirin. We recommend the treatment of patients for at least 48 weeks, and the continuation of antiviral therapy, even in the absence of a decrease in HCV RNA concentration of 2-log at week 12. Ribavirin doses should be adapted according to creatinine clearance in order to avoid its main side effect, i.e. hemolytic anemia. Combined antiviral therapy and immunosuppression (cyclophosphamide or rituximab with steroids) may be the treatment of choice for patients with severe renal disease, i.e. nephrotic syndrome and/or progressive renal failure, or diseases that are refractory to anti-HCV therapy alone.

Liver disease is an important comorbidity following kidney transplantation, and hepatitis C virus (HCV) infection has been demonstrated to be the leading cause of this complication. Anti-HCV-positive kidney transplant recipients have a higher risk for developing proteinuria, chronic rejection, infections, glomerulonephritis and new-onset diabetes after transplantation (NODAT). Together with progressive liver disease in some patients, these complications all contribute to inferior patient and graft survival rates observed in anti-HCV-positive patients when compared to their uninfected counterparts. The increased mortality in the anti-HCV-positive cohort is largely as a result of a higher incidence of cardiovascular disease, liver disease and infections. HCV can also contribute to the development of some extrahepatic neoplasias, such as posttransplant lymphoproliferative disease. HCV infection is also an independent risk factor for graft loss, likely contributed to by the development of NODAT, chronic rejection/transplant glomerulopathy and HCV-related glomerulonephritis. Despite the increased comorbidities associated with kidney transplant in the HCV-infected patient, transplantation offers the best long-term outcomes for the end-stage renal disease patient with HCV infection. Finally, several interventions designed to minimize the potentially adverse consequences of HCV infection should be considered in the posttransplant setting. Adjustment of immunosuppression and careful follow-up in the outpatient clinic for early detection of proteinuria, renal insufficiency, infection, NODAT, neoplasia or worsening of liver disease are important components of the posttransplant care of the patient with HCV infection.

Producción Científica, Background. To describe the causes of graft loss, patient death and survival figures in kidney transplant patients in Spain based on the recipient’s age. Methods. The results at 5 years of post-transplant cardiovascular disease (CVD) patients, taken from a database on CVD, were prospectively analysed, i.e. a total of 2600 transplanted patients during 2000–2002 in 14 Spanish renal transplant units, most of them receiving their organ from cadaver donors. Patients were grouped according to the recipient’s age: Group A: 60 years. The most frequent immunosuppressive regimen included tacrolimus, mycophenolate mofetil and steroids. Results. Patients were distributed as follows: 25.85% in Group A (>40 years), 50.9% in Group B (40–60 years) and 23.19% in Group C (>60). The 5-year survival for the different age groups was 97.4, 90.8 and 77.7%, respectively. Death-censored graft survival was 88, 84.2 and 79.1%, respectively, and non death-censored graft survival was 82.1, 80.3 and 64.7%, respectively. Across all age groups, CVD and infections were the most frequent cause of death. The main causes of graft loss were chronic allograft dysfunction in patients 1 g at 6 months post-transplantation were statistically significant in the three age groups. The patient survival multivariate analysis did not achieve a statistically significant common factor in the three age groups. Conclusions. Five-year results show an excellent recipient survival and graft survival, especially in the youngest age group. Death with functioning graft is the leading cause of graft loss in patients >40 years. Early improvement of renal function and proteinuria together with strict control of cardiovascular risk factors are mandatory.

Transplantation of kidneys from donors with a positive serology for hepatitis C virus (HCVD+) remains controversial as made evident by wide variations in practice. Current knowledge derived from unicenter and registry experiences have demonstrated that the use of HCVD+ kidneys in HCV+ recipients seems to be safe in the long-term. This information, summarized in this chapter, has provided the basis for internationally agreed recommendations which limit the use of these kidneys for transplantation in recipients with a positive HCV RNA while on the waiting list and consenting in advance. Avoiding superinfection might require matching donors and recipients based on the involved HCV genotype, an approach limited by obvious time constraints. Because the incidence and prevalence of HCV infection is decreasing and there is a proactive treatment of patients with end-stage renal disease and HCV infection before being included on the waiting list, kidneys from HCVD+ are becoming surplus organs due to the lack of appropriate recipients. The underutilization of these kidneys at a moment of dramatic organ shortage requires organizational measures, including the offer of these kidneys for preemptive transplantation, besides the need of reviewing the evidence driving local criteria.

To assess the adherence to immunosuppressant therapy (IST) and perceived barriers affecting IST adherence and quality of life (QOL) in patients who had received a renal (RT) or liver transplant (LT), a questionnaire was sent to over 9000 RT and LT recipients in Spain. Questionnaire comprised questions about patient's socio-demographic, organ transplant and medication characteristics; IST adherence and patient's perceived barriers to adherence; and patient's QOL using the EuroQol. Data from 1983 RT patients and 1479 LT patients were analyzed. Self-reported adherence to IST in RT (92.6%) and LT (88.5%) recipients was high. Daily medication intake (mean of 2-3 doses/d per patient) was considered a lifestyle restriction in about 25% of transplant recipients and was the most common barrier to adherence perceived by over 30% of RT and LT patients. Overall, high-intensity treatment regimens were associated with poorer QOL (EuroQol70) compared with low-intensity treatment regimens. Most RT (71.0%) and LT (61.4%) patients would prefer to suppress the evening dose if they were able to. Although high adherence rates to IST were reported in this first large Spanish survey in RT and LT patients, adjustment of daily treatment intensity by less frequent dosing may be an adequate strategy to minimize barriers to adherence and improve QOL.

This multicenter, open, phase IIIb study assessed short-term efficacy, safety and dose adjustments in adult stable renal transplant recipients converted from tacrolimus twice-daily (BID) to once-daily (QD). Patients receiving unchanged tacrolimus BID for ≥ 12 weeks were enrolled, and after 6-weeks, converted from tacrolimus BID to QD (morning dose) on a 1 : 1 (mg : mg) total daily dose basis, for a further 12 weeks. Primary endpoint: change in steady-state creatinine clearance between treatment phases. Secondary endpoints: biopsy-proven acute rejection (BPAR), patient and graft survival, safety. 128 patients enrolled (mean age 48.9 years; time post-transplant 48.9 months); 91 evaluated for the primary endpoint. Mean total daily dose was 0.06 mg/kg (BID) and 0.07 mg/kg (QD); 79.1% required one/no dose changes post-conversion to maintain recommended blood-trough levels; average dose increase was small (0.6-0.7 mg/day) with more dose increases in patients on the lowest tacrolimus BID doses. Renal function remained stable and non-inferiority of tacrolimus QD against tacrolimus BID was demonstrated. There were no BPAR episodes; patient and graft survival were 100%. Adverse events were few; none led to dose modifications/discontinuation. Tacrolimus BID to tacrolimus QD conversion is straightforward and does not compromise renal function in stable kidney transplant patients in the short term.

BACKGROUND: There is scarce information regarding the role of hepatitis C virus (HCV) infection in the development of infectious complications after kidney transplantation (KT). METHODS: We prospectively analyzed all KT recipients included in the Spanish Network for the Research of Infection in Transplantation cohort from September 2003 to February 2005 with a posttransplant follow-up of 3 years and compared the incidence of both overall and specific infections according to the pretransplant anti-HCV antibody status. RESULTS: Of 1302 analyzed recipients, 105 (8.1%) were anti-HCV positive. These patients presented a higher rate of previous transplant (P

One of the key aims of the so-called Information Society is to facilitate the interconnection and communication of sparse groups of people, which can collaborate with each other by exchanging on-line information from distributed sources (Angehrn et al., 2008). In specific contexts, such as in the research and scholarly domain, where many times work is developed relaying on team-based research (Borgman, 2007), finding colleagues and associates to build collaborative relationships has become a crucial matter. Actually, this is one of the pillars of the conduct of research and production of scholarship (Palmer et al., 2009). Nevertheless, this task can be specially difficult when the research activity implies opening new multidisciplinary lines of investigation, since it is hard to know what’s hot and who’s in in a certain domain out of that of this specialization (even if both areas are related or close to each other).

Kidney transplantation from hepatitis C virus (HCV) antibody positive donors (HCVD+) into HCV antibody positive recipients (HCVR+) is controversial. We implemented this policy in our units in 1990. Herein, we report the long-term safety of this strategy. From March 1990 to March 2007, 162 HCVR+ received a kidney from HCVD+ (group 1) and 306 from HCVD− (group 2) in our units. Mean follow-up was 74.5 months. Five-and 10-year patient survival was 84.8% and 72.7% in group 1 vs. 86.6% and 76.5% in group 2 (p = 0.250). Three deaths in group 1 and two in group 2 were liver-disease related. Five- and 10-year graft survival was 58.9% and 34.4% versus 65.5% and 47.6% respectively (p = 0.006) while death-censored graft survival was 69% and 47% versus 72.7% and 58.5% (p = 0.055). Decompensated chronic liver disease was similar: 10.3% versus 6.2%. Cox-regression analysis could not identify the donor's HCV serology as a significant risk factor for death, graft failure and severe liver disease in HCVR+. In conclusion, long-term outcome of HCVR+ transplanted with kidneys from HCVD+ seems good in terms of patient survival, graft survival and liver disease. HCVD+ was not a significant risk factor for mortality, graft failure and liver disease among HCVR+. These data strongly suggest that the use of kidneys from HCVD+ in HCVR+ is a safe long-term strategy that helps to prevent kidney loss.

HCV infection is a very important and common prob- and manage HCV infection in the dialysis period in lem in dialysis patients [1]. The prevalence of HCV order to eliminate HCV RNA. infection in dialysis is variable, depending on the The management of HCV infection in dialysis geographical area, although it is always higher than in patients on the waiting list for renal transplantation the general population [1]. HCV infection and related has not been completely standardized in dialysis units. liver diseases are chronic processes with long-term The high morbidity and mortality of HCV infection evolution. The survival of dialysis patients has mark- after renal transplantation impair patient and graft edly improved during the last decade, although cardio- survival [9]. Two aspects of HCV infection need to be vascular mortality is by far the major cause of death considered in dialysis patients who are candidates for [2]. The prolongation of patient survival on dialysis renal transplantation: (i) evaluation of the severity of will allow us to observe different types of HCV liver HCV infection and (ii) consideration of the treatment diseases in the near future. There are not yet many of HCV infection. studies of liver histology in dialysis patients. Although The evaluation of HCV infection needs to focus on the first reports of liver biopsies suggested that HCV three different items: liver function tests, liver biopsy infection was histologically benign process [3,4], recent and virological tests. Liver function tests include the studies with longer follow-up have demonstrated the classical parameters to define the presence and the presence of different degrees of chronic hepatitis, severity of HCV infection. Transaminases (ALT and including, in some cases, liver cirrhosis [5]. HCV AST ) are helpful markers of the presence of an HCV infection in dialysis patients can, over a sufficient infection, but they are not precise enough to be used period of time, develop into different types of liver to define the grade of liver lesion. Despite the nonlesions, including cirrhosis and hepatocellular specificity of transaminases, the determination of ALT carcinoma.