Background Chronic kidney disease (CKD) has a significant impact on psychological well-being. Here, the psychological evaluation of patients with CKD undergoing replacement treatment (dialysis or kidney transplantation) and conservative therapy (preemptive patients, who are waiting list for kidney transplantation) was analyzed. In addition, serum irisin levels, a protein displaying anxiolytic and antidepressant effects in mice, were measured in dialysis patients. Methods Dialysis (N = 57), non-dialysis (preemptive, N = 31) and kidney transplant patients (N = 33) were enrolled. All participants underwent psychometric tests including State–Trait Anxiety Inventory (STAI-Y 1 and 2 form), Psychological General Well-Being Index (PGWBI), Symptom Checklist-90-R (SCL-90-R), etc. Serum irisin levels in dialyzed patients were measured by ELISA assay. Results Dialysis patient group scored worse on all tests performed than both preemptive and kidney transplant patients. Indeed, dialysis patients displayed the lowest PGWBI score, and higher scores of BDI, and STAY-1 and STAY-2, compared with preemptive and kidney transplant patients. We also found that about 40% of dialysis patients showed significant psychological distress with higher clinical attention values in the somatization, obsessive-compulsive, depression, and anxiety domains assessed by SCL-90. Furthermore, the stratification of all patients into groups younger and older than 50 years showed that the older group of transplanted patients displayed better outcomes than the younger ones. Finally, stratification of dialysis patients according to irisin levels revealed that only those with higher serum irisin levels had better psychological conditions in tests. Conclusions Kidney transplantation as well as conservative therapy were related to a lower prevalence of depressive symptoms and other psychological disorders than dialysis. Furthermore, all transplanted patients over 50 years of age showed better outcomes than the younger ones. However, dialyzed patients with high levels of circulating irisin displayed better psychological conditions. Overall, our findings supported the importance to provide timely access to transplantation and to improve psychological support for dialysis patients.

IgA nephropathy (IgAN) is a leading cause of End-Stage Renal Disease, with kidney transplantation as the preferred treatment, although with unpredictable and diverse outcomes. Mannose-binding lectin (MBL), a key component of the lectin pathway (LP), is associated with IgAN, and both excessive and deficient levels may exacerbate the disease. Genetic variants in MBL2 affect MBL serum levels and function, potentially influencing graft outcomes. We investigated correlations between MBL2 variants, MBL levels, complement system activation, and graft survival in 64 IgAN transplant recipients. The combined impact of MBL2 alleles and delCFHR3-1 status was also evaluated. Patients with the MBL2 "O" allele exhibited significantly lower MBL serum levels (p = 0.0013) and reduced event-free survival (p = 0.024) compared to wild-type "A" allele carriers. This deficiency was associated with increased alternative pathway (AP) activity, suggesting that enhanced complement activation contributes to allograft dysfunction. These findings highlight the role of AP on graft survival of IgAN transplant patients. Therefore, genotyping for delCFHR3-1 and the MBL2 "O" allele and MBL level assessment could provide prognostic insights. Identifying at-risk patients may enable personalised strategies, such as targeting a specific complement pathway, to improve post-transplant outcomes and extend graft survival, thus challenging the universal benefit of complete complement inhibition in this population.

Immunocompromised patients show an impaired vaccine response and remain at high risk of severe COVID-19, despite vaccination. Neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed for prophylaxis and treatment. The combination tixagevimab/cilgavimab (AZD7442) has been authorized for emergency use as pre-exposure prophylaxis for COVID-19, but data on safety and efficacy in kidney transplant recipients during the Omicron period are limited. We conducted a multicenter retrospective cohort study including 253 kidney transplant recipients, of whom 98 were treated with tixagevimab/cilgavimab 150 mg/150 mg and 155 who received only four doses of the BNT162b2 mRNA vaccine. Only 13.3

Abstract Funding Acknowledgements Type of funding sources: None. Background direct oral anticoagulants (DOACs) are a well-known alternative to conventional antagonist of vitamin-K (avK) and have emerged as the preferred choice due to their safety and efficacy profile. However, immune modulating drugs as cyclosporine and tacrolimus, commonly used for transplant recipients, may interfere with DOACs. Aim of this study: evaluate safety and efficacy profile of direct oral anticoagulants (DOACs) compared to warfarin in kidney transplant recipients (KTRs) treated with immune modulating agents. Methods a multi-center study from 4 Italian hospitals enrolling KTRs on DOACs or avK was carried out. Sixty-nine patients on DOACs were compared with fifty patients on avK with mean estimated glomerular filtrate rate (eGFR) > 45 mL/min. Clinical follow-up and serial evaluation of renal function and serum levels of immune modulating drugs during 24 months follow-up (FU) was performed. Results Mean age of DOACs patients was 67±9 and mean eGFR was57±20 mL/min. Immune-modulating therapy included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). There were no changes in Tacrolimus and Cyclosporin serum levels following 14 days therapy with DOACs (+0.5 ±2 and +28 ±31, p=0.52, 0.90, respectively) and only a patient treated with dabigatran 150 mg required a dose adjustment. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during follow-up. At long-term follow-up, there were no thromboembolic events among patients treated with DOACs or avK and no differences in term of mayor bleeding (5.8% vs 4% p=0.99). There was no difference in term of eGFR decline from start therapy to 24 months FU between DOACs or avK therapy (-3.9±1 vs -3.8±2 p=0.82) (FIGURE 1). Conclusion DOACs are a potential therapeutic option among patients with kidney transplant recipients treated with immune modulating drugs. Careful evaluation of immunomodulating agent levels during the first two week of therapy should be recommended. No difference in term of bleeding, renal function decline was found when comparing with avK therapy.

Influenza and Coronavirus Disease 2019 (COVID-19) vaccination are recommended in both solid organ transplant (SOT) candidates and recipients. In Puglia, Southern Italy, an active vaccination offer program has been activated targeting these patients. This study aims at investigating vaccination coverage (VC) for both vaccines in a SOT patients' cohort, as well as at identifying the vaccination compliance determinant. This is a retrospective, population-based study. The study population consists of the SOT patients who accessed Bari's "Policlinico" General Hospital during 2017-2022. Patients were contacted and, after providing their consent, asked their immunization status regarding influenza and COVID-19 and whether they had already undergone transplant or were waiting to do so. Regression models were fitted to investigate the determinants of VCs for influenza vaccination (2021/22 and 2022/23 seasons) and for COVID-19 vaccination (three-dose base cycle, first and second booster doses). Three-hundred and ten SOT patients were identified; 85.2% (264/310) had already undergone SOT. VCs were suboptimal, especially for constant yearly influenza vaccination (17.7%) and COVID-19 vaccination's second booster (1.94%). Logistic regression highlighted that influenza VCs are higher for SOT recipients than SOT candidates, as well as for older patients, although when considering both vaccination seasons only age significantly impact the vaccination uptake. Older age was the only influential variable for COVID-19 VC. VCs for SOT patients seem to be unsatisfying. Stronger interventions are required.

COVID-19 in kidney transplant recipients is associated with high morbidity and mortality. In this study we aimed to evaluate: (i) the seroconversion rate after BNT162b2 (Pfizer-BioNTech) SARS-CoV-2 vaccine, (ii) factors associated with humoral response, (iii) clinical outcome of COVID-19 in kidney transplanted patients. We enrolled a cohort of 743 kidney transplant recipients followed up from March 2020 until April 2022. A subset of 336 patients, who received three-doses of SARS-CoV-2 vaccine, was analyzed in terms of kinetics of humoral immune response and compared to a control group of 94 healthcare workers. Antibody response was tested before vaccination (T0), 15 and 90 days after the second dose (T1 and T2), on the day of the third dose (T3) and one month after the third dose (T4). We observed that 66 out of 743 subjects had COVID-19 infection pre-vaccination: 65.2

Kidney transplant (KT) recipients are known to be at risk of developing several cancer types; however, cancer mortality in this population is underinvestigated. Our study aimed to assess the risk of cancer death among Italian KT recipients compared to the corresponding general population. A cohort study was conducted among 7373 individuals who underwent KT between 2003 and 2020 in 17 Italian centers. Date and cause of death were retrieved until 31 December 2020. Indirect standardization was used to estimate standardized mortality ratios (SMRs) and corresponding 95% confidence intervals (CIs). Cancer was the most common cause of death among the 7373 KT recipients, constituting 32.4% of all deaths. A 1.8-fold excess mortality (95% CI: 1.59-2.09) was observed for all cancers combined. Lymphomas (SMR = 6.17, 95% CI: 3.81-9.25), kidney cancer (SMR = 5.44, 95% CI: 2.97-8.88) and skin melanoma (SMR = 3.19, 95% CI: 1.03-6.98) showed the highest excess death risks. In addition, SMRs were increased about 1.6 to 3.0 times for cancers of lung, breast, bladder and other hematopoietic and lymphoid tissues. As compared to the general population, relative cancer mortality risk remained significantly elevated in all age groups though it decreased with increasing age. A linear temporal increase in SMR over time was documented for all cancers combined (P < .01). Our study documented significantly higher risks of cancer death in KT recipients than in the corresponding general population. Such results support further investigation into the prevention and early detection of cancer in KT recipients.

The crosstalk among the complement system, immune cells, and mediators of inflammation provides an efficient mechanism to protect the organism against infections and support the repair of damaged tissues. Alterations in this complex machinery play a role in the pathogenesis of different diseases. Core complement proteins C3 and C5, their activation fragments, their receptors, and their regulators have been shown to be active intracellularly as the complosome. The kidney is particularly vulnerable to complement-induced damage, and emerging findings have revealed the role of complement system dysregulation in a wide range of kidney disorders, including glomerulopathies and ischemia-reperfusion injury during kidney transplantation. Different studies have shown that activation of the complement system is an important component of tumorigenesis and its elements have been proved to be present in the TME of various human malignancies. The role of the complement system in renal cell carcinoma (RCC) has been recently explored. Clear cell and papillary RCC upregulate most of the complement genes relative to normal kidney tissue. The aim of this narrative review is to provide novel insights into the role of complement in kidney disorders.

IntroductionThe study of immune response to SARSCoV-2 infection in different solid organ transplant settings represents an opportunity for clarifying the interplay between SARS-CoV-2 and the immune system. In our nationwide registry study from Italy, we specifically evaluated, during the first wave pandemic, i.e., in non-vaccinated patients, COVID-19 prevalence of infection, mortality, and lethality in liver transplant recipients (LTRs), using non-liver solid transplant recipients (NL-SOTRs) and the Italian general population (GP) as comparators.MethodsCase collection started from February 21 to June 22, 2020, using the data from the National Institute of Health and National Transplant Center, whereas the data analysis was performed on September 30, 2020.To compare the sex- and age-adjusted distribution of infection, mortality, and lethality in LTRs, NL-SOTRs, and Italian GP we applied an indirect standardization method to determine the standardized rate.ResultsAmong the 43,983 Italian SOTRs with a functioning graft, LTRs accounted for 14,168 patients, of whom 89 were SARS-CoV-2 infected. In the 29,815 NL-SOTRs, 361 cases of SARS-CoV-2 infection were observed. The geographical distribution of the disease was highly variable across the different Italian regions. The standardized rate of infection, mortality, and lethality rates in LTRs resulted lower compared to NL-SOTRs [1.02 (95%CI 0.81-1.23) vs. 2.01 (95%CI 1.8-2.2); 1.0 (95%CI 0.5-1.5) vs. 4.5 (95%CI 3.6-5.3); 1.6 (95%CI 0.7-2.4) vs. 2.8 (95%CI 2.2-3.3), respectively] and comparable to the Italian GP.DiscussionAccording to the most recent studies on SOTRs and SARS-CoV-2 infection, our data strongly suggest that, in contrast to what was observed in NL-SOTRs receiving a similar immunosuppressive therapy, LTRs have the same risk of SARS-CoV-2 infection, mortality, and lethality observed in the general population. These results suggest an immune response to SARS-CoV-2 infection in LTRS that is different from NL-SOTRs, probably related to the ability of the grafted liver to induce immunotolerance.

Abstract Background and Aims Direct oral anticoagulants (DOACs) are a well-known alternative to conventional antagonist of vitamin-K (avK) and have emerged as the preferred choice due to their safety and efficacy profile. However, immune modulating drugs as cyclosporine and tacrolimus, commonly used for transplant recipients, may interfere with DOACs pharmacokinetic. Our study evaluates safety and efficacy profile of direct oral anticoagulants (DOACs) compared to avK in kidney transplant recipients (KTRs) treated with immune modulating agents. Methods A multi-center retrospective observational study from 4 Italian hospitals enrolling KTRs on DOACs or avK was carried out. Sixty-six patients on DOACs were compared with fifty patients on avK with similar clinical features. Serial evaluation of renal function and serum levels of immune modulating drugs during 24 months follow-up (FU) was performed. Results Mean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73 m2. Immune-modulating therapy included tacrolimus (n = 47, 71%), cyclosporin (n = 13, 20%), everolimus (n = 10, 7%) and sirolimus (n = 4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p = 0.80) and cyclosporine (+0.12±0.25 p = 0.94) not statistically significant. Only a patient treated with dabigatran 150 mg required a dose adjustment. Levels of tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or avK and no differences in term of mayor bleeding (5.8% vs 4% p = 0.99), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs or avK therapy (-3.9±1 vs −3.8±2 p = 0.82). Conclusion DOACs are a potential therapeutic option among kidney transplant recipients treated with immune modulating drugs. Careful evaluation of immunomodulating agent levels during the first two week of therapy should be recommended. No difference in term of bleeding, thromboembolic events and renal function decline was found when comparing with avK therapy.

Introduction: Remdesivir (REM) and monoclonal antibodies (mAbs) could alleviate severe COVID-19 in at-risk outpatients. However, data on their use in hospitalized patients, particularly in elderly or immunocompromised hosts, are lacking. Methods: All consecutive patients hospitalized with COVID-19 at our unit from 1 July 2021 to 15 March 2022 were retrospectively enrolled. The primary outcome was the progression to severe COVID-19 (P/F < 200). Descriptive statistics, a Cox univariate–multivariate model, and an inverse probability treatment-weighted (IPTW) analysis were performed. Results: Overall, 331 subjects were included; their median (q1–q3) age was 71 (51–80) years, and they were males in 52% of the cases. Of them, 78 (23%) developed severe COVID-19. All-cause in-hospital mortality was 14%; it was higher in those with disease progression (36% vs. 7%, p < 0.001). REM and mAbs resulted in a 7% (95%CI = 3–11%) and 14% (95%CI = 3–25%) reduction in the risk of severe COVID-19, respectively, after adjusting the analysis with the IPTW. In addition, by evaluating only immunocompromised hosts, the combination of REM and mAbs was associated with a significantly lower incidence of severe COVID-19 (aHR = 0.06, 95%CI = 0.02–0.77) when compared with monotherapy. Conclusions: REM and mAbs may reduce the risk of COVID-19 progression in hospitalized patients. Importantly, in immunocompromised hosts, the combination of mAbs and REM may be beneficial.

This cohort study examined 25-year variations in cancer incidence among 11,418 Italian recipients of kidney transplantation (KT) from 17 Italian centers. Cancer incidence was examined over three periods (1997-2004; 2005-2012; and 2013-2021) by internal (Incidence rate ratio-IRR) and external (standardized incidence ratios-SIR) comparisons. Poisson regression was used to assess trends. Overall, 1646 post-transplant cancers were diagnosed, with incidence rates/1000 person-years ranging from 15.5 in 1997-2004 to 21.0 in 2013-2021. Adjusted IRRs showed a significant reduction in incidence rates across periods for all cancers combined after exclusion of nonmelanoma skin cancers (IRR = 0.90, 95% confidence interval-CI: 0.76-1.07 in 2005-2012; IRR = 0.72, 95% CI: 0.60-0.87 in 2013-2021 vs. 1997-2004; Ptrend < 0.01). In site-specific analyses, however, significant changes in incidence rates were observed only for Kaposi's sarcoma (KS; IRR = 0.37, 95% CI: 0.24-0.57 in 2005-2012; IRR = 0.09, 95% CI: 0.04-0.18 in 2013-2021; Ptrend < 0.01). As compared to the general population, the overall post-transplant cancer risk in KT recipients was elevated, with a decreasing magnitude over time (SIR = 2.54, 95% CI: 2.26-2.85 in 1997-2004; SIR = 1.99, 95% CI: 1.83-2.16 in 2013-2021; Ptrend < 0.01). A decline in SIRs was observed specifically for non-Hodgkin lymphoma and KS, though only the KS trend retained statistical significance after adjustment. In conclusion, apart from KS, no changes in the incidence of other cancers over time were observed among Italian KT recipients.

Oral Abstract/Thursday: Mechanisms and Single-Cell Transcriptional Profiles in Transplant Rejection and Ischemia Reperfusion Injury

Abstract Background and Aims HLA compatibility is a key issue in deceased and living kidney allocation, although the continuous improvement of immunosuppressive protocols might have reduced its relevance. However, an increased immunosuppression is associated with several adverse events, including the development of post-transplant neoplasia. Indeed, several reports demonstrated that the improvement in immunosuppressive drug efficiency corresponded to an increase incidence of malignancies after kidney transplantation. Thus, the aim of our study was to investigate the effect of HLA compatibility on kidney graft survival and incidence of post-transplant neoplasia. Method This is an observational, retrospective, multicenter center study including 1506 patients receiving a single kidney transplant at the Gemelli and Policlinico “Consorziale” kidney transplant centers from 1/1/2000 to 1/2/2022. The primary outcomes were death-censored graft survival and the development of post-transplant neoplasia. HLA compatibility was measured as the number of HLA mismatches (MM) at the three main class I (A and B) and class II (DR) loci. To this purpose, both donor and recipients were genotyped for HLA A, B and DR. We included in the analysis all deceased and living kidney donor transplants and excluded recipients from AB0 incompatible living kidney donors and with pre-transplant donor specific antibodies. Results Based on HLA compatibility, we divided our patients’ population in three groups (0-2 MM, 369 patients 3-4 MM, 856 patients and 5-6 MM, 281 patients). At univariate analysis (Kaplan-Meyer) number of MM were not associate with death-censored graft survival (Logrank p = 0.6) whereas we observed a significant association with the development of post-transplant neoplasia (Logrank p = 0.01). However, multivariate analysis (Cox model including recipient age, induction and maintenance immunosuppressive therapy) demonstrated that patients with 3-4 (HR 1.033, 95% CI 0.676-1.580, p = 0.9) and 5-6 MM (HR 1.342, 95% CI 0.853-2.111, p = 0.2) did not have any statistically significant increase in the risk to develop a post-transplant malignancy. Conclusion In this observational retrospective multicenter analysis, we demonstrated that HLA incompatibility, as indicated by the number of HLA A, B and DR MM, does not predict death-censored graft survival and does not impact the development of post-transplant neoplasia. Our observation would suggest that the missing effect of HLA compatibility on graft outcome is not associated with an increased long-term over-immunosuppression.

BACKGROUND:direct oral anticoagulants (DOACs) are an alternative to conventional antagonist of vitamin-K (AVK). However, immune suppressive drugs (ISDs) may interfere with DOACs pharmacokinetic. AIM OF THIS STUDY:evaluate safety and efficacy profile of DOACs compared to AVK in kidney transplant recipients (KTRs) treated with ISDs. METHODS:a multi-center study from 4 Italian University hospitals enrolling consecutive KTRs on DOACs or AVK was carried out. Sixty-six patients on DOACs were compared with fifty patients on AVK with similar clinical features. Serial evaluation of renal function and serum levels of ISDs during 18 months follow-up (FU) was performed. RESULTS:Mean age of DOACs patients was 67±9 and mean eGFR was 58,3± 30,4mL/min/1.73m2. ISDs included tacrolimus (n=47, 71%), cyclosporin (n=13, 20%), everolimus (n=10, 7%) and sirolimus (n=4, 6%). After 14 days of DOACs therapy initiation there was a slight increase of serum levels of tacrolimus (+0.19±0.67 p=0.80) and cyclosporine (+0.12±0.25 p=0.94) not statistically significant. Levels of Tacrolimus and cyclosporin were stable at serial evaluation during 18-months follow-up. There were no thromboembolic events among patients treated with DOACs or AVK and no differences in term of major bleeding (6% vs 4% p=0.69), at long-term follow-up. There was no difference in term of eGFR decline from start therapy to 18 months FU between DOACs vs AVK therapy (-3.9±1 vs -3.8±2 p=0.82). CONCLUSION:DOACs have similar safety and efficacy than AVK among KTRs treated with ISDs. However, careful evaluation of potential drug interaction and ISDs serum levels is needed.

Background Delayed graft function (DGF) leads to a reduced graft survival. Donors’ features have been always considered as key pathogenic factors in this setting. The aim of our study was to evaluate the recipients’ characteristics in the development of DGF. Methods We enrolled 932 kidney graft recipients from 466 donors; 226 recipients experienced DGF. In 290 donors, both recipients presented with early graft function (EGF, group A), in 50 both recipients experienced DGF (group B), and in 126 one recipient presented with DGF and the other with EGF (group C). In group C, we selected 7 couples of DGF/EGF recipients and we evaluated the transcriptomic profile by microarray on circulating mononuclear cells harvested before transplantation. Results were validated by qPCR in an independent group of 25 EGF/DGF couples. Findings In the whole study group, DGF was associated with clinical characteristics related to both donors and recipient. In group C, DGF was significantly associated with body mass index, hemodialysis, and number of mismatches. In the same group, we identified 411 genes differently expressed before transplantation between recipients discordant for the transplant outcome. Those genes were involved in immune dysfunction and inflammation. In particular, we observed a significant increase in DGF patients in the expression of C–C chemokine receptor type 2 (CCR2), the monocyte chemoattractant protein-1 (MCP-1) receptor. CCR-2 upregulation was confirmed in an independent cohort of patients. Conclusions Our results suggest that recipients’ clinical/immunological features, potentially modulated by dialysis, are associated with the development of DGF independently of donors’ features.

Background The nephrectomy for donation reduces the renal parenchyma and glomerular filtration rate (GFR). It is important to understand the clinical consequences of kidney donation by a living donor. Methods In this single-center, observational, retrospective study, we defined the renal and cardiovascular outcomes of living kidney donors. We analyzed data of 124 donors who donated at the Kidney Transplant Center (TC) of Bari between February 2002 and December 2018. Biometric data collected at visit 0, that is, at the time of the study of the donor candidate, and at visit 1, or rather at the last nephrological checkup (October-2018/August-2019) were compared. Results An overall drop in GFR of 29 mL/min was observed over the analyzed period of 81+/-59 months. At visit 1, two donors developed chronic renal failure, including one in ESKD who underwent a kidney transplant. No relationship between age at donation and GFR drop was found. A trend toward an increase in obese people was reported; 28% of patients had compensated dyslipidemia and 35% were treated for hypertension. During the follow-up time, 3% had major cardiovascular events and 24% were lost to follow-up. One patient died. Conclusion The age of the donor does not represent a basic element for reducing GFR or for the occurrence of major cardiovascular events. Furthermore, older donor candidates, in optimal health, should not be excluded from the donation. It is important to promote careful and timely follow-up of the donor, preventing the most common clinical consequences of nephrectomy, in consideration of the poor compliance of a large part of donors over the long-term post-donation period.

Background/aim:Direct-acting antivirals (DAAs) have improved the treatment of HCV-positive kidney transplant recipients (KTRs). However, their medium-term follow-up effects on graft function are conflicting. This study aimed to analyze how the interplay between DAAs, calcineurin inhibitors (CNI), and HCV eradication impacts 12-month kidney graft function.Methods:This double-center retrospective study with a prospective follow-up enrolled 35 KTRs with HCV treated with DAAs for 12 weeks. We compared three parameters: estimated glomerular filtration rate (eGFR), 24-h proteinuria, and CNI trough levels at three time points: baseline, end of treatment (EOT), and 12 months later.Results:Kidney allograft function remained stable when comparing baseline and 12-month post-treatment values of eGFR (60.7 versus 57.8 ml/min; p = 0.28) and 24-h proteinuria (0.3 versus 0.2 g/24 h; p = 0.15), while tacrolimus (Tac) trough levels underwent a statistically significant decline (6.9 versus 5.4 ng/ml; p = 0.004). Using an ongoing triple Tac-based maintenance therapy as a conservative measure, a dose escalation of Tac was applied only in seven patients. No variation in CyA and mTOR levels was detected.Conclusion:DAA therapy is safe and effective in HCV-positive KTRs. It also produces a persistent significant reduction in Tac trough levels that does not influence graft function at 12 months.