Cytomegalovirus prevention strategies in seropositive kidney transplant recipients: an insight into current clinical practice.

There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV-seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site. The impact on the 12-month incidence of CMV disease was assessed by Cox regression. Asymptomatic CMV infection, acute rejection, graft function, non-CMV infection, graft loss, and all-cause mortality were also analyzed (secondary outcomes). Models were adjusted for a propensity score (PS) analysis for receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific intervention. Twelve-month cumulative incidences of CMV disease and asymptomatic infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower incidence of CMV disease [PS-adjusted HR (aHR): 0.10; 95% confidence interval (CI): 0.01-0.79] and asymptomatic infection (aHR: 0.46; 95% CI: 0.29-0.72) than those managed preemptively, with no significant differences according to the duration of prophylaxis. All cases of CMV disease in the prophylaxis group occurred after prophylaxis discontinuation. There were no differences in any of the secondary outcomes. In conclusion, antiviral prophylaxis was associated with a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit should be balanced with the risk of late-onset disease.

Sodium-glucose cotransporter-2 inhibitor therapy in kidney transplant patients with type 2 or post-transplant diabetes: an observational multicentre study.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have cardioprotective and renoprotective effects. However, experience with SGLT2is in diabetic kidney transplant recipients (DKTRs) is limited. Methods: This observational multicentre study was designed to examine the efficacy and safety of SGLT2is in DKTRs. The primary outcome was adverse effects within 6 months of SGLT2i treatment. Results: Among 339 treated DKTRs, adverse effects were recorded in 26%, the most frequent (14%) being urinary tract infection (UTI). In 10%, SGLT2is were suspended mostly because of UTI. Risk factors for developing a UTI were a prior episode of UTI in the 6 months leading up to SGLT2i use {odds ratio [OR] 7.90 [confidence interval (CI) 3.63-17.21]} and female sex [OR 2.46 (CI 1.19-5.03)]. In a post hoc subgroup analysis, the incidence of UTI emerged as similar in DKTRs treated with SGLT2i for 12 months versus non-DKTRs (17.9% versus 16.7%). Between baseline and 6 months, significant reductions were observed in body weight [-2.22 kg (95% CI -2.79 to -1.65)], blood pressure, fasting glycaemia, haemoglobin A1c [-0.36% (95% CI -0.51 to -0.21)], serum uric acid [-0.44 mg/dl (95% CI -0.60 to -0.28)] and urinary protein:creatinine ratio, while serum magnesium [+0.15 mg/dl (95% CI 0.11-0.18)] and haemoglobin levels rose [+0.44 g/dl (95% CI 0.28-0.58]. These outcomes persisted in participants followed over 12 months of treatment. Conclusions: SGLT2is in kidney transplant offer benefits in terms of controlling glycaemia, weight, blood pressure, anaemia, proteinuria and serum uric acid and magnesium. UTI was the most frequent adverse effect. According to our findings, these agents should be prescribed with caution in female DKTRs and those with a history of UTI.

mTOR inhibitor monotherapy. A good treatment choice in renal transplantation?

Calcineurin inhibitors have reduced acute rejection rates and improved short-term graft survival, but without any improvement in long-term outcomes, since calcineurin inhibitors cause nephrotoxicity and death with a functioning graft. mTOR inhibitors have antiproliferative and anti-angiogenic effects with no nephrotoxicity. These properties could improve patient and graft long-term survival rates in select transplant recipients. In addition, monotherapy always diminishes the rate of non-compliance in chronic patients. We examined the evolution of 47 low immunological risk kidney transplant recipients with mTOR inhibitor monotherapy. The mean age was 45 ± 10 years (range: 18-69 years), with 25 males y 22 females. We performed an immunological evaluation before and at 3 and 12 months after starting monotherapy by detection of donor-specific antibodies by microsphere cytometry and the determination of lymphocyte activity with production of ATP by CD4+ T-lymphocytes activated by PHA mitogen. We considered patients to be of low immunological risk when the patient had an ATP production less than 520 ng/dl and no history of acute rejection episode or donor-specific antibodies. Initially, 5 patients received immunosuppression induction without calcineurin inhibitors (mycophenolate, prednisone, mTOR inhibitors and anti-CD25), and 42 were converted to mTOR inhibitors due to secondary effects of calcineurin inhibitors or malignancies. A total of 34 recipients had received sirolimus and 13 everolimus. Eighteen out 47 patients (38.2%) received prednisone and 29 (61.7%) mycophenolate with mTor before starting monotherapy. The mean follow-up period after starting monotherapy was 46.9 months (95% CI: 38.8-55.0 months). At the end of the follow-up, 7 out of 47 recipients (11.5%) had to change immunosuppression without losing their grafts after 1 year, due to heavy proteinuria in 2 cases, pulmonary infection in 1, acute rejection in 1, hepatotoxicity in 1, vasculitis in 1 and a temporary inclusion on dialysis after acute pyelonephritis in 1. Four out of 47 patients (8.5%) lost their grafts, as a result of chronic rejection in 3 cases, and as a result of death with a functioning graft in 1. The rate of acute rejection was 2.1%, one episode, which was solved with steroid pulses and switching from mTOR inhibitors to tacrolimus and mycophenolate. No patients developed donor-specific antibodies, and all of them maintained an ATP production less than 520 ng/dl. The rates of graft and recipient survival were both 100% at 1 year, and 88.7% and 95.7% at 5 years. The percentages of patients on monotherapy were 97.9% and 70.5 % at 1 and 5 years, respectively. At the end of the follow-up, 36 out of 47 recipients remained on mTOR inhibitor monotherapy. Serum creatinine and glomerular filtration rates improved significantly, from 2.16 ± 1.05 mg/dl to 1.49 ± 0.56 mg/dl (P=.001) and from 39.23 ± 25.23 ml/min to 52.23 ± 23.20 ml/min (P=.001), respectively. Proteinuria increased but not significantly, from 306.6 ± 400 mg/24h to 418.1 ± 514.1mg/24h (P=.17). The patients treated with mTOR inhibitors received significantly more erythropoietin and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers than before starting mTOR, but there was no change in the treatment with statins or hypotensive agents. Body weight and the percentage of diabetic recipients were similar during the study. No cases of non-compliance were observed during the follow-up. The present study supports the safety and efficacy of monotherapy with mTOR inhibitors in select kidney transplant recipients.

Monoterapia m-TOR. ¿Una buena elección en trasplante renal? / mTOR inhibitor monotherapy. A good treatment choice in renal transplantation?

La inmunosupresión basada en los inhibidores de la calcineurina (INC) ha hecho posible la reducción del rechazo agudo en el trasplante renal y el aumento de la supervivencia del injerto a corto pero no a largo plazo, siendo la muerte del receptor con injerto funcionante y la disfunción crónica del injerto sus principales causas. Los fármacos inhibidores de la m-Tor son inmunosupresores con capacidad antiproliferativa y antimigratoria, lo que les confiere un potencial papel protector en la disfunción del injerto renal, una mejora del perfil cardiovascular y una reducción en el desarrollo de neoplasias; todo ello podría, teóricamente, preservar la función renal y la vida del paciente a largo plazo en un grupo seleccionado de pacientes. Por otro lado, el uso de monoterapia en un paciente facilita su adherencia a cualquier tratamiento crónico. El objetivo del estudio es evaluar el uso de inhibidores de la m-Tor en monoterapia a largo plazo en un grupo seleccionado de receptores de trasplante renal de bajo riesgo inmunológico mediante un estudio observacional y prospectivo, desarrollado en el período 2001-2011. Los pacientes en tratamiento con inhibidores de la m-Tor junto con micofenolato mofetilo o prednisona fueron evaluados inmunológicamente de cara a ser incluidos en el protocolo de monoterapia con inhibidores de la m-Tor. Se incluyeron los pacientes considerados de bajo riesgo inmunológico: sin antecedentes de episodios previos de rechazo agudo, ausencia de anticuerpos antidonante específico y una producción de ATP inferior a 520 ng/dl. La valoración inmunológica se repitió a los 3 y 12 meses del inicio de la monoterapia. La población del (..) (AU)

Calcineurin inhibitors have reduced acute rejection rates and improved short-term graft survival, but without any improvement in long-term outcomes, since calcineurin inhibitors cause nephrotoxicity and death with a functioning graft. mTOR inhibitors have antiproliferative and anti-angiogenic effects with no nephrotoxicity. These properties could improve patient and graft long-term survival rates in select transplant recipients. In addition, monotherapy always diminishes the rate of non-compliance in chronic patients. We examined the evolution of 47 low immunological risk kidney transplant recipients with mTOR inhibitor monotherapy. The mean age was 45±10 years (range: 18-69 years), with 25 males y 22 females. We performed an immunological evaluation before and at 3 and 12 months after starting monotherapy by detection of donor-specific antibodies by microsphere cytometry and the determination of lymphocyte activity with production of ATP by CD4+ T-lymphocytes activated by PHA mitogen. We considered patients to be of low immunological risk when the patient had an ATP production less than 520ng/dl and no history of acute rejection episode or donor-specific antibodies. Initially, 5 patients received immunosuppression induction without calcineurin inhibitors (mycophenolate, prednisone, mTOR inhibitors and anti-CD25), and 42 were converted to mTOR inhibitors due to secondary effects of calcineurin inhibitors or (..) (AU)

Acute rejection and late renal transplant failure: risk factors and prognosis.

BACKGROUND: Acute rejection episodes are a major determinant of renal allograft survival, and the improvement of the transplantation results in the last two decades is largely due to a progressive decrease in the incidence of acute rejection. These results are explained by the incorporation of new immunosuppressive agents since the introduction of cyclosporine. Because the detrimental effect of acute rejection on graft survival is not limited to the early post-transplant period, we have focused on the impact of acute rejection episodes on late transplant failure in patients with the graft functioning 1 year after transplantation. METHODS: We have retrospectively analysed in 3365 renal transplants performed in adults in Spain during 1990, 1994 and 1998 the incidence and severity of the acute rejection episodes, their risk factors, and their influence on graft and patient survival. RESULTS: The incidence of rejection episodes in the whole series was 32.5%, decreasing in 1998 (25.1%) compared with the previous years (38%) (P<0.0001). Corticoid-resistant rejection episodes also decreased from 8% in 1990 and 1994 to 3.4% in 1998 (P<0.0001). Multivariate analysis showed that patients < 60 years old (P<0.0001), sensitized recipients (P = 0.038), patients with delayed graft function (P<0.0001), cytomegalovirus infection (P = 0.0060), and those transplanted in 1990 or 1994 (P<0.0001) had an increased incidence of rejection episodes. In the univariate analysis, induction treatment with antilymphocyte globulines or OKT3 (P = 0.0002), and traumatic donor death (P = 0.042) were associated with a lower incidence of acute rejection. In the univariate analysis of the transplants performed in 1998, addressed to evaluate the effect of the new immunosuppressive agents, treatment with mycophenolate mofetil (P<0.0001) or tacrolimus (P = 0.0067), but not with anti-IL2 antibodies reduced the incidence of acute rejection. Patients with rejection episodes had an increased risk of late graft failure (Cox proportional hazards model, P<0.0001), which was homogeneous in the three periods analysed, with no effect on patient survival (P = 0.13). CONCLUSIONS: Despite a decreased incidence and severity of acute rejections in 1998, compared with the previous years, acute rejection still remains a powerful risk factor for late transplant failure.

Fiebre en paciente con trasplante renal / Fever in a patient with a renal transplant

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