Esther González

Should asymptomatic bacteriuria be systematically treated in kidney transplant recipients? Results from a randomized controlled trial.

The indication for antimicrobial treatment of asymptomatic bacteriuria (AB) after kidney transplantation (KT) remains controversial. Between January 2011 and December 2013, 112 KT recipients that developed one episode or more of AB beyond the second month after transplantation were included in this open‐label trial. Participants were randomized (1:1 ratio) to the treatment group (systematic antimicrobial therapy for all episodes of AB occurring ≤24 mo after transplantation [53 patients]) or control group (no antimicrobial therapy [59 patients]). Systematic screening for AB was performed similarly in both groups. The primary outcome was the occurrence of acute pyelonephritis at 24‐mo follow‐up. Secondary outcomes included lower urinary tract infection, acute rejection, Clostridium difficile infection, colonization or infection by multidrug‐resistant bacteria, graft function and all‐cause mortality. There were no differences in the primary outcome in the intention‐to‐treat population (7.5% [4 of 53] in the treatment group vs. 8.4% [5 of 59] in the control group; odds ratio [OR] 0.88, 95% confidence interval [CI] 0.22–3.47) or the per‐protocol population (3.8% [1 of 26] in the treatment group vs. 8.0% [4 of 50] in the control group; OR 0.46, 95% CI 0.05–4.34). Moreover, we found no differences in any of the secondary outcomes. In conclusion, systematic screening and treatment of AB beyond the second month after transplantation provided no apparent benefit among KT recipients (NCT02373085).

Progressive increase of resistance in Enterobacteriaceae urinary isolates from kidney transplant recipients over the past decade: narrowing of the therapeutic options

Antibiotic resistance is an emerging phenomenon in kidney transplantation (KT).

Impact of anti-HCV direct antiviral agents on graft function and immunosuppressive drug levels in kidney transplant recipients: a call to attention in the mid-term follow-up in a single-center cohort study

The medium‐term impact on graft function and immunosuppressive drug pharmacokinetics of direct antiviral agents (DAAs) among hepatitis C virus (HCV)‐infected kidney transplant (KT) recipients remain unclear. We compared pre‐ and post‐treatment 12‐month trajectories of estimated glomerular filtration rate (ΔeGFR) and 24‐h proteinuria (Δ24‐h proteinuria) in 49 recipients treated with DAAs (mostly sofosbuvir plus ledipasvir). Among evaluable patients, 66.7% and 100.0% had undetectable viral load by week 4 and end of therapy (EoT). The sustained virologic response rate at 12 weeks was 95.8%. Overall, 80.6% of patients receiving tacrolimus required dose escalation while on DAA‐based therapy (median increase of 66.7%) to maintain target levels. Tacrolimus levels resulted to be higher at 12 months compared to EoT (7.8 ± 2.1 vs. 6.7 ± 2.0 ng/ml; P‐value = 0.002). No changes in graft function during the course of therapy were observed. However, eGFR significantly decreased (P‐value <0.001) throughout the first 12 months after EoT. Median ΔeGFR and Δ24‐h over pre‐ and post‐treatment periods were 3.9% and −6.1% (P‐value = 0.002) and −5.3% and 26.2% (P‐value = 0.057). Caution should be exercised when adjusting immunosuppression in HCV‐infected KT recipients upon initiation of DAAs, followed by mid‐term monitoring of immunosuppressive drug levels and graft function.

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.

Serum iron parameters in the early post-transplant period and infection risk in kidney transplant recipients

The impact of iron metabolism on the risk of infectious complications has been demonstrated in various immunosuppressed populations. However, no previous studies have assessed this potential association in kidney transplant (KT) recipients.

Infection Risk in Kidney Transplantation From Uncontrolled Donation After Circulatory Death Donors

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSION 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.

Pre-transplant dialysis modality does not influence short- or long-term outcome in kidney transplant recipients: analysis of paired kidneys from the same deceased donor.

Previous studies have reported contradictory results regarding the effect of pre‐transplant dialysis modality on the outcomes after kidney transplantation (KT). To minimize the confounding effect of donor‐related variables, we performed a donor‐matched retrospective comparison of 160 patients that received only one modality of pre‐transplant dialysis (peritoneal dialysis [PD] and hemodialysis [HD] in 80 patients each) and that subsequently underwent KT at our center between January 1990 and December 2007. Cox regression models were used to evaluate the association between pre‐transplant dialysis modality and primary study outcomes (death‐censored graft survival and patient survival). To control for imbalances in recipient‐related baseline characteristics, we performed additional adjustments for the propensity score (PS) for receiving pre‐transplant PD (versus HD). There were no significant differences according to pre‐transplant dialysis modality in death‐censored graft survival (PS‐adjusted hazard ratio [aHR]: 0.65; 95% confidence interval [95% CI]: 0.25–1.68) or patient survival (aHR: 0.58; 95% CI: 0.13–2.68). There were no differences in 10‐year graft function or in the incidence of post‐transplant complications either, except for a higher risk of lymphocele in patients undergoing PD (odds ratio: 4.31; 95% CI: 1.15–16.21). In conclusion, pre‐transplant dialysis modality in KT recipients does not impact short‐ or long‐term graft outcomes or patient survival.

Serum sCD30: A promising biomarker for predicting the risk of bacterial infection after kidney transplantation

The transmembrane glycoprotein CD30 contributes to regulate the balance between Th1 and Th2 responses. Previous studies have reported conflicting results on the utility of its soluble form (sCD30) to predict post‐transplant infection.

Experience with miltefosine for persistent or relapsing visceral leishmaniasis in solid organ transplant recipients: a case series from Spain.

The incidence of visceral leishmaniasis (VL) after solid organ transplantation (SOT) is increasing. The optimal therapy for post‐transplant VL remains unclear, as relapses after liposomal amphotericin B (L‐AmB) are common. Miltefosine has been shown to be effective for treating VL in immunocompetent patients, although data in the specific population of SOT recipients are lacking. In the setting of an outbreak of leishmaniasis occurring in Southwest Madrid, we reviewed our experience in 6 SOT recipients with persistent or relapsing VL who received a 28‐day course of miltefosine (2.5 mg/kg/day) as salvage therapy. All patients had been treated previously with L‐AmB as first‐line therapy. The incident episode of VL occurred at a median of 14 months after transplantation. Two patients experienced persistent infection and the remaining 4 had a relapse after a median interval of 168 days since the completion of the course of L‐AmB. All the patients had an apparent initial clinical improvement with miltefosine. However, VL relapsed in 3 of them (after a median interval of 46 days), which required retreatment with L‐AmB‐based regimens. Miltefosine therapy was followed by a prolonged secondary prophylaxis with L‐AmB in the only 2 cases with sustained clinical response and ongoing immunosuppression. No adverse effects associated with miltefosine were observed. Albeit limited, our experience suggests that miltefosine monotherapy likely has a limited utility to obtain a long‐lasting clinical response in complicated (persistent or relapsing) forms of post‐transplant VL, although its role in association with L‐AmB‐based secondary prophylaxis may merit further investigation.

Association between baseline serum hepcidin levels and infection in kidney transplant recipients: Potential role for iron overload

The liver‐synthesized peptide hepcidin is a key regulator of iron metabolism and correlates with total iron stores. We analyzed the association between pre‐transplant hepcidin‐25 levels and infection after kidney transplantation (KT).