SARS-CoV-2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID-19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID-19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti-COVID-19 treatment in the second wave (July-December) than in the first one (March-June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post-KT should be considered when selecting recipients for transplantation in the COVID-19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.

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.

To increase the number of kidney donors, new strategies are needed such as living donor programs, expanded criteria donors, or donors after circulatory death (DCD) kidney transplantation programs. The GEODAS group has started an observational, prospective, multicenter clinical study, collecting data from all DCD type-3 kidney transplantations performed in seven Spanish hospitals from January 2012 to January 2014. The preliminary results have shown a delayed graft function of 40.4% and graft survival of 93.7% with a nadir creatinine of 1.3 mg/dL. From all 33 potential donors included in the study, 32 were effective and 63 kidney grafts were transplanted with a utilization rate of 98.5%. Creatinine evolution (median [range]) was in the first month: 2.1 [0.6-5.6]; third month: 1.6 [0.8, 4.2]; first year: 1.6 [0.9-2.2]. These results are similar to kidney transplantation from donors after brain death as shown in the literature, especially in the graft and recipient survival rates. In addition, the controlled programs are easier and less expensive than uncontrolled DCD programs with a higher rate of graft use.

Introduction: Nephrectomy is usually specified after the loss of a graft when there are signs of intolerance or resistance to erythropoietin. However, the influence of the first graft nephrectomy in the evolution of the second graft is less known. Materials and methods: We conducted a multicenter study of all second transplants performed between January 2001 and December 2005 in 15 centers in our country. Were analyzed: Data from the first graft (donor and recipient age, pretransplant antibody(Ac) titres, rejection acute rate, acute tubular necrosis(ATN), immunosupression, causes of graft loss) Indication of nephrectomy, second transplant data (pretransplant Ac title, acute rejection rate, inmunospresión, ATN, yearly development of proteinuria and renal function and patient and graft survival. The minimum follow-up period is 5 years Results: The sample consists of 525 patients who received a second kidney transplant, 243 had been nephrectomized, in 25 had been performed an embolization and 258 continued with the first graft. The indication for nephrectomy/embolization was 31.5% for graft intolerance in 38.16% by early nephrectomy and required rest from other causes.No nephrectomy for resistance to erythropoietin were made. In the first graft did not find significant differences in donor age, the title of Ac at transplantation, acute rejection rate or frequency of ATN among patients with or without nephrectomy. The duration of first graft was 31.8 months in patients nephrectomized and 94.9 in which nephrectomy was not required. The waiting time for the second transplant was higher in patients nephrectomized (33 vs 23 months, p< 0,01) In the second graft did not find significant differences in donor age, cause of donor death, recipient age or number of HLA incompatibilities in patients with or without prior nephrectomy. The nephrectomized patients had a significantly higher second pretransplant Ac (15.7 vs. 11.8%, p < 0.001), increased frequency of NTA (54% vs. 39%, p < 0.001) and higher rate of acute rejection (24, 7 vs. 17.1%, p < 0.001), as well as more frequently required the use of induction therapy (55 vs 41%, p < 0.01). There were no significant differences in patient survival or graft survival after 5 years of follow-up Conclusions: Nephrectomy was performed in 50.9% of grafts lost. It is indicated by early nephrectomy and graft intolerance syndrome. It is associated with: Increased waiting on dialysis, increased pre-second transplant antibodies, more NTA, more acute rejection, further immunosuppression. No impact on graft and patient survival was observed at 5 years of follow-up.

To the Editor: We have read the article by Touzot et al. (1Touzot M Pillebout E Matignon M et al.Renal transplantation in HIV-infected patients: The Paris experience.Am J Transplant. 2010; 10: 1-7Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar) with great interest. They present the results of a study on kidney transplantation in HIV-infected patients in France. The authors state in the Discussion section that, to their knowledge, their study is the first one describing a European cohort of HIV-positive kidney transplant recipients. However, in 2006, we published an initial study that analyzed the outcomes of all the HIV-infected patients who had undergone kidney transplantation in the high-activity antiretroviral therapy era in another European country, Spain (2Mazuecos A Pascual J Gomez E et al.Renal transplantation in HIV-infected patients in Spain.Nefrologia. 2006; 26: 113-120PubMed Google Scholar). Recently, and almost simultaneously with Touzot et al., we have also reported the results of a case-control study that is an extension of our previous study (3Mazuecos A Fernandez A Andres A et al.HIV infection and renal transplantation.Nephrol Dial Transplant. 2010; (doi: 10.1093/ndt/gfq592.)PubMed Google Scholar). In this recent paper, we compare 20 HIV-positive renal transplant patients with a matched cohort of 40 HIV-negative recipients who received a kidney graft in our country. Almost all the reported experience on this topic comes from the Unites States (4Kumar MSA Sierka DR Damask AM et al.Safety and success of kidney transplantation and concomitant immunosuppression in HIV-positive patients.Kidney Int. 2005; 67: 1622-1629Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar,5Stock PG Barin B Murphy B et al.Outcomes of kidney transplantation in HIV-infected recipients.N Engl J Med. 2010; 363: 2004-2014Crossref PubMed Scopus (376) Google Scholar). In Spain, the HIV-positive transplant patients present some epidemiological characteristics, which could influence their posttransplant outcome. In the American and French studies, the majority of patients are Afro-American or African recipients, whereas almost all of our patients are Caucasian. Among our patients, HCV coinfection is very prevalent because drug addiction background is frequent. However, in spite of these differences, the results have been similar to those reported in the USA: 1-year graft-survival rates were 85% in the Spanish study (2Mazuecos A Pascual J Gomez E et al.Renal transplantation in HIV-infected patients in Spain.Nefrologia. 2006; 26: 113-120PubMed Google Scholar) and 90.4% and 75% in the two most relevant American studies (4Kumar MSA Sierka DR Damask AM et al.Safety and success of kidney transplantation and concomitant immunosuppression in HIV-positive patients.Kidney Int. 2005; 67: 1622-1629Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar,5Stock PG Barin B Murphy B et al.Outcomes of kidney transplantation in HIV-infected recipients.N Engl J Med. 2010; 363: 2004-2014Crossref PubMed Scopus (376) Google Scholar) (median follow-up: 36.2, 19.2 and 20.4 months, respectively). The GFR were also similar [at 1 year: 54 mL/min, Spanish study; 55 mL/min, Kumar et al. (4Kumar MSA Sierka DR Damask AM et al.Safety and success of kidney transplantation and concomitant immunosuppression in HIV-positive patients.Kidney Int. 2005; 67: 1622-1629Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar); 51.8 or 60.5 mL/min in recipients with or without rejection, Stock et al. (5Stock PG Barin B Murphy B et al.Outcomes of kidney transplantation in HIV-infected recipients.N Engl J Med. 2010; 363: 2004-2014Crossref PubMed Scopus (376) Google Scholar)]. In our experience, as in many of the large American studies, the incidence of acute rejection has been high [40%, Spanish study; 29%, Kumar et al. (4Kumar MSA Sierka DR Damask AM et al.Safety and success of kidney transplantation and concomitant immunosuppression in HIV-positive patients.Kidney Int. 2005; 67: 1622-1629Abstract Full Text Full Text PDF PubMed Scopus (188) Google Scholar); 41%, Stock et al. (5Stock PG Barin B Murphy B et al.Outcomes of kidney transplantation in HIV-infected recipients.N Engl J Med. 2010; 363: 2004-2014Crossref PubMed Scopus (376) Google Scholar)]. In contrast, the rejection rate in the French study is low (15%). Almost all our patients were treated with tacrolimus but only 35% of them received induction therapy. We agree with those authors that these different rejection rates could be due to changes in the immunosuppressive regimens, among other causes. We have also observed that graft survival was worse in our experience in HIV–HCV coinfected patients. However, in our study, graft survival was similar in HIV-positive and HIV-negative patients when we exclude from both groups the patients with HCV infection (1-year graft-survival: 100% in HIV-positive, 96.8% in HIV-negative recipients). The higher prevalence of HIV–HCV coinfection among our patients (40%, Spanish study; 19%, Stock et al. (5Stock PG Barin B Murphy B et al.Outcomes of kidney transplantation in HIV-infected recipients.N Engl J Med. 2010; 363: 2004-2014Crossref PubMed Scopus (376) Google Scholar); 7%, Touzot et al. (1Touzot M Pillebout E Matignon M et al.Renal transplantation in HIV-infected patients: The Paris experience.Am J Transplant. 2010; 10: 1-7Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar) could also explain the differences observed in the results between the different studies. The good results in a large number of studies indicate that the kidney transplantation is a suitable treatment for HIV-infected patients. The long-term follow-up and detailed analysis of particular aspects associated with this population (rejection, HIV–HCV coinfection and others) should continue to be a principal focus of research. The authors of this manuscript have no conflicts of interest to disclose as described the American Journal of Transplantation.

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

The shortage of organ availability in recent years has made it necessary to use grafts from advanced-aged donors to maintain the rate of renal transplantation in our country. The objective of this study was to evaluate the graft function and patient survival using kidneys from deceased donors of over 65 year of age. From 2005 until 2010, we compared the outcomes of patients who received grafts from donors over 65 years old vs less than 65 years. We observed no significant difference in sex, time on dialysis, or cold ischemia time between the groups. As expected the recipient age was significantly different. For the analysis of survival, we used the Tablecloth-Haenzel test and the Kaplan-Meier survival estimator. Actuarial survivals at 3 years after transplantation showed 84.8% among patients transplanted with kidneys from donors over 65 years old versus 97.5% in the control group. The graft survival was 78.8% among expanded criteria versus 86.85% in the control group. When we analyzed graft survival using an "exitus-censured" analysis, we obtained graft survivals of 89.1% in the expanded criteria kidney group versus 88.6% among the controls. We concluded that the use of kidney from donors over 65 years of age allows us to increase the rate of renal transplantation to about 15 to 20 per million population, with good graft and patient survivals provided that the protocol for expanded criteria organs ensured proper macroscopic and microscopic evaluation of the organ for transplantation.

Mazuecos, A.; Marcén, R.; Andrés, A.; Gómez, E.; Zárraga, S.; Burgos, D.; Jiménez, C.; Paul, J.; Rodríguez-Benot, A.; Fernández, C. Author Information

BACKGROUND:A prospective study was performed in kidney transplant patients at risk of developing cytomegalovirus (CMV) infection (CMV D+/R-). They were treated with valganciclovir (VGC) for 3 months as prophylactic therapy. The aim was to determine the safety and efficacy of prophylactic therapy with VGC.METHODS:Antigenemia and/or polymerase chain reaction CMV was routinely performed every 2 weeks up to month 3, monthly to month 6, and every other month until the end of the first year posttranplantation, as well as when clinically indicated.RESULTS:From July 2007 to April 2010, 366 renal transplantations were performed at our center, including 34 (9%) high-risk patients for CMV infection. The median age was 47 years; 19 were males and 15 females. Twelve (35%) patients developed CMV infections: 10 (34%) gastrointestinal disease and 3 viral syndromes. The timing of the clinical manifestations was 16% (3/12) between months 1 and 3, 75% (8/12) between months 4 and 6, and 8% (1/12) in month 9 posttransplantation.CONCLUSION:Treatment with intravenous ganciclovir followed by oral VGC was successful in all patients. No opportunistic infections or allograft rejection were observed; only 1 patient developed thrombocytopenia as an adverse event to VGC.

Whenever graft function is good and proteinuria is under control, many reports describe the efficacy and safety of the conversion to Everolimus (EVL) among stable kidney recepients, simultaneously withdrawing the calcineurin inhibitor (CNI). However, there are few publications that evaluate the role of EVL in patients with decreased renal function. We describe our experience with 22 stable renal transplant recipients whose serum creatinine concentrations were >2 mg/dL and proteinuria <1000 mg/24 h who underwent an abrupt switch from a CNI to EVL. Conversion was simple, well-tolerated, and safe using an initial dose of 1-3 mg/d that was sufficient to achieve the recommended levels of 3-8 ng/dL. The adverse events were expected; most of them were of medium intensity. Globally, over the 24 months follow-up, there was improved renal function despite the initial creatinine. The improvement was greater when the switch was performed during the first year after transplantation. Two patients lost their grafts after a dramatic evolution with development of nephrotic syndrome and increasing creatinine. In our experience, conversion to EVL is a safe alternative among patients with chronic allograft nephropathy or nephrotoxicity due to CNI, even in patients with significantly decreased renal function at the time of the switch.

OBJECTIVE:Most immunosuppressive protocols in de novo renal transplantation include tacrolimus in combination with mycophenolate mofetil/mycophenolic acid (MMF/MPA) and prednisone. A variable percentage of patients show intolerance to MMF/MPA needing a reduction, interruption, or suspension of the drug, thereby exposing the patient to a greater risk of a rejection episode. The association of everolimus and tacrolimus may prove to be an alternative option in such cases. The aim of this study was to present our clinical experience, evaluating the incidence of graft rejection.PATIENTS AND METHODS:We performed a descriptive study of 19 kidney transplant patients from 2001-2008 who were treated with tacrolimus, MMF/MPA, and prednisone and displayed gastrointestinal or hematological adverse events to MMF/MPA, which were addressed with everolimus. We analyzed parameters up to 2 years after the change.RESULTS:The doses and levels of everolimus were increased progressively. At the same time, we decreased the doses and levels of tacrolimus. Renal function remained stable during the period and there was no case of a rejection episode during the 2 years. Only 5 patients (26%) showed side effects which were attributable to everolimus; 36% of patients required starting and/or increasing the erythropoietin dose, 15% required iron supplements, 15% required diuretics, and 31% began or increased treatment with statins.CONCLUSION:Our experience suggested that a combination of tacrolimus and everolimus may be a safe, effective alternative for kidney transplant patients who show intolerance to MMF/MPA.

Ruiz, J C.1; Sánchez-Fructuoso, A2; Rengel, M3; Ramos, D4; Plaza, J J.5; Zárraga, S6; Andrés, A7; Errasti, P8; Fernández, A9 Author Information

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.

BACKGROUND:Although hyperuricaemia and gout are frequently found in renal transplant recipients, little has been published on the efficacy of urate-lowering therapy (ULT) in this patient population. We therefore examine the effects of allopurinol and benziodarone therapy in a cohort of renal transplant patients.METHODS:We reviewed files from a cohort of 1328 patients that received renal transplantation. The selection criteria included: functioning allograft, hyperuricaemia for >12 months or gout, ULT lasting at least 1 year and at least two control measurements after the onset of ULT. Patients on azathioprine were treated with benziodarone to avoid azathioprine-allopurinol interactions.RESULTS:Two-hundred and seventy-nine patients fulfilled the criteria for review. They were treated with 289 courses of ULT: 100 with allopurinol (mean dose: 376 mg/day/dl/min of creatinine clearance) and 189 with benziodarone (mean dose: 73 mg/day). The mean follow-up was 38 months. Both drugs were effective for the control of hyperuricaemia, but benziodarone caused greater reductions in serum uric acid levels, especially when used at mean doses of >75 mg/day. Severe side effects were uncommon, in both the allopurinol and benziodarone groups.CONCLUSIONS:Both allopurinol and benziodarone were effective for the control of hyperuricaemia in renal transplantation. Benziodarone at doses >75 mg/day was more effective than allopurinol in reducing serum uric acid levels and also reduced the risk of azathioprine-allopurinol interactions.

To evaluate the efficacy and safety of conversion from cyclosporine to tacrolimus, we analyzed 55 kidney transplant patients who were converted due to cosmetic reasons in 42 patients, acute rejection in 2 patients, and other causes in 11 patients. At the doses and levels used, the development of diabetes mellitus was minimized. Disappearance of cosmetic side-effects and improvement of cardiovascular risk factors, together with conservation of renal function, encourage us to use tacrolimus as an efficacious and safe immunosuppressive therapy.