Renal function at 12 months of kidney transplantation comparing tacrolimus and mycophenolate with tacrolimus and mTORi in donors with different KDPI ranges. A multicenter cohort study using propensity scoring.

Introduction: The combination of tacrolimus/mTORi compared to tacrolimus/mycophenolate (MMF) was shown to be safe in the TRANSFORM trial. For donors with a high KDPI (Kidney Donor Profile Index), however, there are no data to support the effectiveness of this regimen. The main objective of this study was to explore the influence of the KDPI on 12-month renal function (eGFR) in patients receiving mTORi or MMF. Methods: Multicenter cohort study of four Brazilian services that use the tacrolimus with mTORi as a protocol. Data from 2008 to 2018 of the tacrolimus/mycophenolate (MMF) and tacrolimus/mTORi (mTORi) regimens in renal transplant recipients over 18 years old were collected. For better homogeneity, the propensity score was used. Afterward, the method used for group selection ("match") was the K-nearest neighbor (KNN) method. New analyses were performed on this new balanced sample, and two different subsamples were constituted based on the median KDPI. Results: The global analysis (n = 870) showed that the major determinant of worse kidney function was high KDPI. Afterward, the three strata were analyzed. In the first stratum (KDPI up to 50), 242 patients were evaluated, with 121 in each group. The eGFR was 64 ml/min/1.73 m2 in the mTORi group compared to 63 in the MMF group, p = 0.4, and when imputed eGFR was evaluated, 61 in the mTORi and 53 in the MMF, p = 0.065. In the second stratum (KDPI from 50 to 85), 282 patients were evaluated, with 141 in each group. eGFR was 46 ml/min/1.73 m2 in mTORi compared to 48 in MMF, p = 0.4, and when imputed eGFR was evaluated, 40 mTORi and 41 MMF, p = 0.8. In the last stratum (KDPI higher than 85) with n = 126 and 63 cases per group, eGFR was 36 ml/min/1.73 m2 in mTORi compared to 39 in MMF, p = 0.2, and when imputed eGFR was evaluated, 30 mTORi and 34 MMF, p = 0.2. Discussion: The regimen using mTOR inhibitor is an effective and safe regimen when compared to the standard regimen. In addition, the scheme seems to offer additional protection against infections and may be an important ally in cases of high risk for these pathologies.

Tropical Infections in the Context of Kidney Transplantation in Latin America.

Reports on tropical infections among kidney transplant (KT) recipients have increased in recent years, mainly because of the growing number of KT programs located in tropical and subtropical areas, and greater mobility or migration between different areas of the world. Endemic in emerging and developing regions, like most countries in Latin America, tropical infections are an important cause of morbidity and mortality in this population. Tropical infections in KT recipients may exhibit different pathways for acquisition compared with those in nonrecipients, such as transmission through a graft and reactivation of a latent infection triggered by immunosuppression. Clinical presentation may differ compared with that in immunocompetent patients, and there are also particularities in diagnostic aspects, treatment, and prognosis. KT patients must be screened for latent infections and immunized properly. Last, drug-drug interactions between immunosuppressive agents and drugs used to treat tropical infections are an additional challenge in KT patients. In this review, we summarize the management of tropical infections in KT patients.

Exploring the causes of the high incidence of delayed graft function after kidney transplantation in Brazil: a multicenter study.

This retrospective multicenter (n = 18) cohort study evaluated the incidence, risk factors, and the impact of delayed graft function (DGF) on 1-year kidney transplant (KT) outcomes. Of 3992 deceased donor KT performed in 2014-2015, the incidence of DGF was 54%, ranging from 29.9% to 87.7% among centers. Risk factors (lower-bound-95%CI OR upper-bound-95%CI ) were male gender (1.066 1.2491.463 ), diabetic kidney disease (1.053 1.2961.595 ), time on dialysis (1.005 1.0071.009 ), retransplantation (1.035 1.3971.885 ), preformed anti-HLA antibodies (1.011 1.3831.892 ), HLA mismatches (1.006 1.0661.130 ), donor age (1.011 1.0171.023 ), donor final serum creatinine (sCr) (1.239 1.3171.399 ), cold ischemia time (CIT) (1.031 1.0431.056 ), machine perfusion (0.401 0.5420.733 ), and induction therapy with rabbit antithymocyte globulin (rATG) (0.658 0.8000.973 ). Duration of DGF > 4 days was associated with inferior renal function and DGF > 14 days with the higher incidences of acute rejection, graft loss, and death. In conclusion, the incidence and duration of DGF were high and associated with inferior graft outcomes. While late referral and poor donor maintenance account for the high overall incidence of DGF, variability in donor and recipient selection, organ preservation method, and type of induction agent may account for the wide variation observed among transplant centers.

The Impact of Hypothermic Pulsatile Machine Perfusion Versus Static Cold Storage: A Donor-Matched Paired Analysis in a Scenario of High Incidence of Delayed Kidney Graft Function.

BACKGROUND The present study analyzed the impact of hypothermic pulsatile machine perfusion (MP) following a long period of static cold (SC) storage in the peculiar Brazilian scenario of high incidence of delayed graft function (DGF), despite good donor characteristics. MATERIAL AND METHODS A retrospective analysis, with a 1-year follow-up, of 206 recipients of donor-matched paired kidneys was performed. Of the 206 donor kidneys, 103 were maintained exclusively in static cold storage (SC group) and 103 were kept on machine perfusion after a period of SC preservation (MP group). All donors were brain dead. RESULTS Only 4.9% of the kidneys were from expanded-criteria donors. Static cold ischemia time (CIT) in the SC group was 20.8±4.1 hours vs. 15.8±6.2 hours in the MP group (P<0.001). Dynamic CIT in the MP group was 12.3±5.7 hours. MP significantly reduced DGF incidence (29.1% vs. 55.3%, P<0.001), and this effect was confirmed in multivariable analysis (OR, 1.115; 95% CI, 1.033-1.204, P=0.001). No differences were observed between the groups with regard to DGF duration, length of hospital stay, incidence of primary nonfunction and acute rejection, graft loss, death, or renal function. CONCLUSIONS In this Brazilian setting, MP following a long period of SC preservation was associated with reduced DGF incidence in comparison with SC storage without MP.

The impact of deceased donor maintenance on delayed kidney allograft function: A machine learning analysis.

BACKGROUND: This study evaluated the risk factors for delayed graft function (DGF) in a country where its incidence is high, detailing donor maintenance-related (DMR) variables and using machine learning (ML) methods beyond the traditional regression-based models. METHODS: A total of 443 brain dead deceased donor kidney transplants (KT) from two Brazilian centers were retrospectively analyzed and the following DMR were evaluated using predictive modeling: arterial blood gas pH, serum sodium, blood glucose, urine output, mean arterial pressure, vasopressors use, and reversed cardiac arrest. RESULTS: Most patients (95.7%) received kidneys from standard criteria donors. The incidence of DGF was 53%. In multivariable logistic regression analysis, DMR variables did not impact on DGF occurrence. In post-hoc analysis including only KT with cold ischemia time<21h (n = 220), urine output in 24h prior to recovery surgery (OR = 0.639, 95%CI 0.444-0.919) and serum sodium (OR = 1.030, 95%CI 1.052-1.379) were risk factors for DGF. Using elastic net regularized regression model and ML analysis (decision tree, neural network and support vector machine), urine output and other DMR variables emerged as DGF predictors: mean arterial pressure, ≥ 1 or high dose vasopressors and blood glucose. CONCLUSIONS: Some DMR variables were associated with DGF, suggesting a potential impact of variables reflecting poor clinical and hemodynamic status on the incidence of DGF.

Tuberculosis after kidney transplantation is associated with significantly impaired allograft function.

BACKGROUND: This study aimed to evaluate renal function before, during, and after the course of tuberculosis (TB) disease in kidney transplant recipients, and assess the risk factors for non-recovery of baseline renal function. METHODS: We performed a retrospective, single-center cohort study, including all patients with confirmed or presumed TB diagnosis after kidney transplant (n=34, 2.1%). Renal function was assessed by serum creatinine (Cr) and glomerular filtration rate (GFR) adjusted for deaths and graft losses. RESULTS: A significant increase was seen in serum Cr during TB disease and treatment: 1.5 mg/dL at baseline (Crbase ), 1.7 mg/dL at diagnosis (P<.001 vs. Crbase ), and 2.4 mg/dL during the peak (P<.001 vs. Crbase ). According to acute kidney injury (AKI) Kidney Disease: Improving Global Outcomes (KDIGO) classification, 29 (85%) patients had AKI: 16 stage 1, 2 stage 2, and 11 stage 3. Three months after the end of the TB treatment, five patients (14.7%) had lost their graft and two others (5.9%) had died. The GFR was lower than the baseline (42.4 mL/min vs 51.6 mL/min, P=.007). In the univariate analysis, peak Cr (odds ratio [OR] 1.276, 95% confidence interval [CI] 0.955-1.705, P=.100), AKI KDIGO stages 2 or 3 (OR 4.958, 95% CI 1.062-23.157, P=.042), severe disease (OR 5.700, 95% CI 1.147-28.330, P=.033), and acute rejection (AR) episodes after TB diagnosis (OR 3.937, 95% CI 0.551-28.116, P=.172) were associated with non-recovery of baseline renal function. No variable was identified in the multivariable model. CONCLUSION: Post-transplantation TB was associated with a high incidence of AKI, and complete recovery of baseline renal function was not achieved after treatment. The severity of TB disease, AKI, and AR episodes that occurred after TB diagnosis are potential causes for this outcome.

Dengue Fever Among Renal Transplant Recipients: A Series of 10 Cases in a Tropical Country.

This is a case series of 10 consecutive renal allograft recipients, followed at a tertiary hospital in northeast Brazil, with a confirmed diagnosis of dengue. Five of the patients needed hospitalization. Half of them were males and age ranged from 19 to 60 years with a median of 38.2 years. They had been transplanted for a mean of 5 days to 166 months. Four patients developed dengue hemorrhagic fever (DHF). All patients had myalgia and headache. All of them, except one, had fever. Positive dengue serology (IgM) was found in all patients. No patient died. Dengue is an important infectious disease that can affect renal transplant recipients, mainly in endemic areas. Its presentation seems to be similar to that seen in immunocompetent patients.