Development and validation of a simple web-based tool for early prediction of COVID-19-associated death in kidney transplant recipients.

This analysis, using data from the Brazilian kidney transplant (KT) COVID-19 study, seeks to develop a prediction score to assist in COVID-19 risk stratification in KT recipients. In this study, 1379 patients (35 sites) were enrolled, and a machine learning approach was used to fit models in a derivation cohort. A reduced Elastic Net model was selected, and the accuracy to predict the 28-day fatality after the COVID-19 diagnosis, assessed by the area under the ROC curve (AUC-ROC), was confirmed in a validation cohort. The better calibration values were used to build the applicable ImAgeS score. The 28-day fatality rate was 17% (n = 235), which was associated with increasing age, hypertension and cardiovascular disease, higher body mass index, dyspnea, and use of mycophenolate acid or azathioprine. Higher kidney graft function, longer time of symptoms until COVID-19 diagnosis, presence of anosmia or coryza, and use of mTOR inhibitor were associated with reduced risk of death. The coefficients of the best model were used to build the predictive score, which achieved an AUC-ROC of 0.767 (95% CI 0.698-0.834) in the validation cohort. In conclusion, the easily applicable predictive model could assist health care practitioners in identifying non-hospitalized kidney transplant patients that may require more intensive monitoring. Trial registration: ClinicalTrials.gov NCT04494776.

An International survey on living kidney donation and transplant practices during the COVID-19 pandemic.

The scope of the impact of the Coronavirus disease 19 (COVID-19) pandemic on living donor kidney transplantation (LDKT) practices across the world is not well-defined. We received survey responses from 204 transplant centers internationally from May to June 2020 regarding the impact of the COVID-19 pandemic on LDKT practices. Respondents represented 16 countries on five continents. Overall, 75% of responding centers reported that LDKT surgery was on hold (from 67% of North American centers to 91% of European centers). The majority (59%) of centers reported that new donor evaluations were stopped (from 46% of North American centers to 86% of European centers), with additional 23% of centers reporting important decrease in evaluations. Only 10% of centers reported slight variations on their evaluations. For the centers that continued donor evaluations, 40% performed in-person visits, 68% by video, and 42% by telephone. Center concerns for donor (82%) and recipient (76%) safety were the leading barriers to LDKT during the pandemic, followed by patients concerns (48%), and government restrictions (46%). European centers reported more barriers related to staff limitations while North and Latin American centers were more concerned with testing capacity and insufficient resources including protective equipment. As LDKT resumes, 96% of the programs intend to screen donor and recipient pairs for coronavirus infection, most of them with polymerase chain reaction testing of nasopharyngeal swab samples. The COVID-19 pandemic has had broad impact on all aspects of LDKT practice. Ongoing research and consensus-building are needed to guide safe reopening of LDKT programs.

A high level of urinary retinol-binding protein is associated with cytomegalovirus infection in kidney transplantation.

The indirect effects of cytomegalovirus (CMV) viremia can be related to chronic changes in renal allograft structure, but its real impact in early and late graft function remains speculative. A total of 159 patients undergoing renal transplantation using a preemptive therapeutic strategy to prevent CMV disease were included in the present study. The patients were prospectively followed, with serial measurements of urinary retinol-binding protein (uRBP), a marker of proximal tubule injury. uRBP levels and their dynamic performance were compared according to CMV viremia and the 5-year estimated glomerular filtration rate (eGFR), as measured with the modification of diet in renal disease (MDRD) equation. CMV viremia was detected in 79.9% of the patients, with high uRBP levels being detected in 76.0% of these patients (compared with 40.7% in CMV-, P=0.005). High uRBP was associated with male recipients (P=0.02), the number of mismatches (P=0.02) and CMV infection (P=0.001). Five-year eGFR was worse in patients with high uRBP levels (50.3 ± 25.8 compared with 59.8 ± 26.4 ml/min, P=0.04). In a multivariate model, eGFR <60 ml/min was associated with donor age (P<0.001), the number of mismatches (P=0.04), thymoglobulin dose (P=0.02), the presence of and time with delayed graft function (DGF) (P=0.005 and P=0.04), 1-month tacrolimus levels (P=0.03), and uRBP levels after CMV treatment (P=0.01). Patients with CMV viremia in whom uRBP levels were normalized up to 3 months after treatment showed significantly better 5-year eGFR than those in whom uRBP remained high: 61.0 ± 24.2 compared with 42.3 ± 23.9 ml/min, P<0.001. CMV viremia was associated with high uRBP levels, which represent a profile of proximal tubule injury, and the dynamic performance of uRBP after treatment was associated with long-term kidney graft function.

Presence of arteriolar hyalinosis in post-reperfusion biopsies represents an additional risk to ischaemic injury in renal transplant.

AIM: The role of post-reperfusion biopsy findings as a predictor of early and long-term graft function and survival is still a target of research. METHODS: We analyzed data from 136 post-reperfusion biopsies performed in deceased donor renal transplanted patients from November 2008 to May 2012. We analyzed the presence of acute tubular necrosis (ATN), arteriolar hyalinosis (AH), intimal thickness (IT), interstitial fibrosis (IF) and glomerulosclerosis (GS). We also analyzed the impact of donor features on the following outcomes: delayed graft function (DGF) and chronic allograft dysfunction defined as eGFR < 60 mL/min at 1 year. RESULTS: The mean donor age was 41 years, 26% of whom were extended criteria donors (ECD), 33% had hypertension and 50% had cerebral vascular accident (CVA) as the cause of death. ATN was present in 87% of these biopsies, AH in 31%, IF in 21%, IT in 27% and GS in 32%. DGF occurred in 80% and chronic allograft dysfunction was present in 53%. AH was the only histological finding associated with DGF and chronic allograft dysfunction at 1 year. Patients with AH had a lower eGFR at 1 year than patients without it (49.8 mL/min × 64.5 mL/min, P = 0.02). In the multivariate analysis, risk variables for development of chronic graft dysfunction were male sex (odds ratio [OR] = 3.159 [CI: 1.22-8.16]; P = 0.018), acute rejection (OR = 8.91 [CI: 2.21-35.92]; P = 0.002), donor hypertension (OR = 2.94 [CI: 1.10-7.84]; P = 0.031), AH (OR = 3.96 [CI: 1.46-10.70]; P = 0.007) and eGFR at discharge (OR = 0.96 [CI: 0.93-0.98]; P = 0.005). In multivariate analysis, risk factors for AH were donor age ≥ 50 years (OR = 2.46 [CI: 1.10-5.44]; P = 0.027) and CVA as the cause of donor death (OR = 2.33 [CI: 1.05-5.15]; P = 0.007). CONCLUSION: The presence of AH in post-reperfusion biopsies is a marker of ageing and vascular disease and was associated with DGF and a one year poorer renal function. AH in donor biopsies superimposed to long ischaemic time is a predictor of renal function. The management of immunosuppression based on the presence of AH in post-reperfusion biopsy could be useful to improve long term graft function.

Long-term Kidney Transplant Survival Across the Globe.

BACKGROUND: The outcomes after kidney transplantation (KT), including access, wait time, and other issues around the globe, have been studied. However, issues do vary from one country to another. METHODS: We obtained data from several countries from North America, South America, Europe, Asia, and Australia, including the number of patients awaiting KT from 2015, transplant rate per million population (pmp), proportion of living donor and deceased donor (LD/DD) KT, and posttransplant survival. We also sought opinions on key difficulties faced by each of these countries with respect to KT and long-term survival. RESULTS: Variation in access to KT across the globe was noted. Countries with the highest rates of KT pmp included the United States (79%) and Spain (71%). A higher proportion of LD transplants was noted in Japan (93%), India (85%), Singapore (63%), and South Korea (63%). A higher proportion of DD KTs was noted in Spain (90%), Brazil (90%), France (85%), Italy (85%), Finland (85%), Australia-New Zealand (80%), and the United States (77%). The 5-y graft survival for LD was highest in South Korea (95%), Singapore (94%), Italy (93%), Finland (93%), and Japan (93%), whereas for DD, it was South Korea (93%), Italy (88%), Japan (86%), and Singapore (86%). The common issues surrounding KTs are access and a limited number of LDs and DDs. Key issues identified for long-term survival were increasing age of donors and recipients, higher recipient comorbidity, and posttransplant events, such as alloimmune injury to the kidney, infection, cancer, and suboptimal adherence to therapy. CONCLUSIONS: A unified approach is necessary to improve issues surrounding KT as the demand continues to increase.

Preemptive kidney transplantation: why, when, and how?

Among renal replacement therapies, preemptive kidney transplantation (PKT) presents the best clinical, social, and economic results. However, it is still infrequently chosen as first therapy for patients with irreversible kidney failure. Initiatives in different parts of the world were developed to identify the reasons why PKT is still not widely used and to facilitate the access of patients with end-stage kidney disease to the advantages associated with it. This article addresses the main advantages and difficulties of PKT and discusses when it should be indicated and how to prepare potential recipients for PKT.

Conversion to mTOR Inhibitor to Reduce the Incidence of Cytomegalovirus Recurrence in Kidney Transplant Recipients Receiving Preemptive Treatment: A Prospective, Randomized Trial.

BACKGROUND: Although mammalian target of rapamycin inhibitors (mTORi) are associated with a lower incidence of the first episode of cytomegalovirus (CMV) infection/disease in kidney transplant recipients receiving calcineurin inhibitors (CNIs), the efficacy and safety of the conversion from the antimetabolite to an mTORi for the prevention of CMV recurrence are unknown. METHODS: In this single-center prospective randomized trial, low-immunological-risk, CMV-positive kidney transplant recipients receiving preemptive therapy were randomized to be converted (sirolimus [SRL]) or not (control [CTR]) immediately after the treatment of the first episode of CMV infection/disease and were followed for 12 mo. A sample size of 72 patients was calculated to demonstrate a 75% reduction in the incidence of CMV recurrence (80% power, 95% confidence level). RESULTS: Of 3247 adult kidney transplants performed between September 13, 2015, and May 7, 2019, 1309 (40%) were treated for the first CMV infection/disease, and 72 were randomized (35 SRL and 37 CTR). In the SRL group, there were no episodes of CMV recurrence, compared with 16 patients in the CTR group (0% versus 43%; P < 0.0001). Four patients had a second and 1 a third recurrent CMV event. Three of them were converted to SRL and did not develop any further CMV events. There were no differences in the incidence of acute rejection, drug discontinuation, kidney function, and patient and graft survival at 12 mo. CONCLUSIONS: These data suggest that, in CMV-positive kidney transplant recipients, the conversion from an antiproliferative drug to SRL after the first CMV episode is an effective and safe strategy for recurrent episodes.

Challenges of Multidrug-resistant New Delhi Metallo-beta-Lactamase (NDM-1)-producing Enterobacteriaceae in Kidney Transplant Patients.

BACKGROUND: The emergence of multidrug-resistant NDM-1-producing enterobacteriaceae strains has become a threat to inpatients, especially to immunosuppressed ones, such as kidney transplant recipients. NDM-1 is a carbapenemase that makes gram-negative bacteria resistant to many types of antibiotics. The incidence of carbapenemase-producing enterobacteria infection in solid organ transplant recipients is around 3 to 10%, with a mortality rate of up to 30%. METHODS: We present a case series of 4 patients with NDM-1-producing enterobacteria isolated in urine cultures or rectal swabs. We also conducted a cross-sectional study 30 days after patient identification, collecting surveillance cultures (rectal swab) from all inpatients to assess the extent of spread of this resistance mechanism; a total of 101 patients were included. RESULTS: Two patients were adequately treated with negative control cultures. The other two patients were not treated because they were asymptomatic and had subsequent negative urine cultures. No new colonization was identified in the cross-sectional screening, and no new cases of urinary NDM-1 infection were recorded after a 4-year follow-up. CONCLUSION: Surveillance for infections caused by multidrug-resistant strains in hospitals treating immunosuppressed patients should be continued and prompt action should be taken in cases of outbreaks of multidrug-resistant infections.

HLA-DPB1 molecular mismatches are risk factors for acute rejection and low 5-year graft function in first kidney transplants.

The study aimed to investigate the impact of HLA-DPB1 allelic and molecular mismatches on the occurrence of acute rejection (AR) and low 5-year graft function (5Y-GF) in first kidney transplant (KT) recipients. This is a single center retrospective study of 130 deceased donor KT recipients transplanted between 2014 and 2016. HLA-DPB1 allelic MM and the following molecular MM (mMM) were analyzed: expression MM with the high expression G allele in the donor; T cell epitope MM (TCE MM); epitope MM (EMM), considering all six hypervariable regions (EMM-ABCDEF HVR), or only ABEF regions (EMM-ABEF HVR); eplet MM (EpMM); antibody-verified eplet MM (AbVer EpMM); and solvent accessible amino acid MM (SAMM). There was no association of allelic MM with AR or 5Y-GF. The variables independently associated (Cox regression analyses) with AR were high donor final creatinine, nonpermissive TCE MM, ABCDEF EMM load ≥6, EpMM load ≥6; SAMM load ≥5, and AbVer EpMM load ≥3. No association between any HLA-DPB1 mMM and 5Y-GF was observed when all 130 transplant recipients were considered. However, when transplants from expanded criteria donors were excluded, independent associations were detected (logistic regression analyses) with AbVerEpMM load ≥2, SAMM load ≥7, cerebro-vascular death, donor age, and AR. To our knowledge, this is the first study that shows that some HLA-DPB1 mMM are associated with AR and low 5Y-GF in a population of exclusively first kidney transplant recipients.

The Association Between Kidney Donor Profile Index and 1-y Graft Function.

The association between Kidney Donor Profile Index (KDPI) and 1-y estimated glomerular filtration rate (eGFR) with long-term kidney graft survival is well known. Yet, the association between KDPI and 1-y eGFR remains uncertain considering the several concurrent competing risk factors. Methods: This single-center, retrospective cohort study analyzed data from 3059 consecutive deceased donor kidney transplant recipients with a 1-y follow-up from January 2013 to December 2017. The aim was to determine the association between the KDPI strata (0%-35%, 36%-50%, 51%-85%, 86%-100%) and 1-y eGFR estimated by the CKD-EPI equation. Results: The incidence of delayed graft function (50.6% versus 59.3% versus 62.7% versus 62.0%; P < 0.001) and cytomegalovirus infection (36.7% versus 36.6% versus 43.3% versus 57.8%; P < 0.001) increased with increasing KDPI strata but not biopsy-proven acute rejection (9.1% versus 9.8% versus 8.4% versus 9.1%; P = 0.736). The median 1-y eGFR decreased with increasing KDPI strata (64.8 versus 53.5 versus 46.9 versus 39.1 mL/min/1.73 m2; P < 0.001). In the Cox regression, the higher the KDPI was, the lower the probability of a lower 1-y eGFR was. Assuming the 0%-35% strata as the reference, the likelihood of eGFR <50 mL/min/1.73 m2 was increased by 76.6% (hazard ratio [HR] = 1.767, 95% confidence interval [CI] = 1.406-2.220), 2.24- and 2.87-fold higher for KDPI higher >35%-50% (HR = 2.239, 95% CI = 1.862-2.691), and >51%-85% (HR = 2.871, 95% CI = 2.361-3.491), respectively. Other variables associated with a lower graft function were donor sex (HR male versus female = 0.896, 95% CI = 0.813-0.989) and cold ischemia time (HR for each hour = 1.011, 95% CI = 1.004-1.019). This association was sustained after the Poisson mediation analysis, including delayed graft function, cytomegalovirus, and acute rejection as mediators. Conclusions: In this cohort of deceased donor kidney recipients, KDPI, and cold ischemia time were the major independent risk factors associated with lower 1-y kidney function.

Paired kidney donation: are we going beyond reasonable limits in living-donor transplantation?

The growing demand for transplant kidneys requires strategies to increase organ supply and avoid long waiting periods on the list. The increase in the number of transplants from living donors involves the growth in the use of unrelated donors and paired kidney donation. Most of these transplants are performed in the USA, where they already represent, respectively, 34% and 16% of total transplants from living donors. In Latin America, and especially in Brazil, there is no collective enthusiasm for these modalities, either at the request of transplanters or that of the community, with the region's priority being to increase transplants from deceased donors, which growth can be up to three-fold. Concerning transplants from matched donors, the possible conflicting results between donors can generate public challenges and they risk compromise the concepts of equal opportunities for transplant candidates, with the possibility of generating resistance to organ donation, especially in regions with socioeconomic limitations and disparities in access to qualified health care and education. This donation model involves challenging ethical and logistical issues, which are subject to questionings, starting with an act of exchange between two pairs until reaching embarrassing proposals, which can compromise the altruistic character of organ donation, and thus not be universally incorporated.

Vascular Calcification Is Associated with Fetuin-A and Cortical Bone Porosity in Stone Formers.

Background: Nephrolithiasis has been associated with bone loss and vascular calcification (VC), reflecting abnormal extraosseous calcium deposition. Fetuin-A (Fet-A) acts as a potent inhibitor of ectopic mineralization. The aim of the present study was to evaluate the prevalence of VC in stone formers (SF) and non-stone formers (NSF) and to investigate potential determinants of VC among SF, including circulating levels of Fet-A and bone microarchitecture parameters. Methods: Abdominal aortic calcification (AAC) was assessed using available computed tomography in SF and in age-, sex-, and BMI-matched NSF (potential living kidney donors). Serum Fet-A was measured in stored blood samples from SF. Bone microarchitecture parameters were obtained as a post hoc analysis of a cross-sectional cohort from young SF evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Results: A total of 62 SF (38.0 [28.0−45.3] years old) and 80 NSF (40.0 [37.0−45.8] years old) were included. There was no significant difference in AAC scores between SF and NSF. However, when dividing SF according to mean AAC score, below <5.8% (n = 33) or above ≥5.8% (n = 29), SF with higher AAC presented significantly higher BMI and tibial cortical porosity (Ct.Po) and significantly lower serum HDL, klotho, Fet-A, and eGFR. Urinary calcium did not differ between groups, but fractional excretion of phosphate was higher in the former. Upon multivariate regression, BMI, serum Fet-A, and tibial Ct.Po remained independently associated with AAC. Conclusions: This study suggests an association between reduced circulating Fet-A levels and increased bone Ct.Po with VC in SF.

Transition from antigenemia to quantitative nucleic acid amplification testing in cytomegalovirus-seropositive kidney transplant recipients receiving preemptive therapy for cytomegalovirus infection.

Due to the high costs, the strategy to reduce the impact of cytomegalovirus (CMV) after kidney transplant (KT) involves preemptive treatment in low and middle-income countries. Thus, this retrospective cohort study compared the performance of antigenemia transitioned to quantitative nucleic acid amplification testing, RT-PCR, in CMV-seropositive KT recipients receiving preemptive treatment as a strategy to prevent CMV infection. Between 2016 and 2018, 363 patients were enrolled and received preemptive treatment based on antigenemia (n = 177) or RT-PCR (n = 186). The primary outcome was CMV disease. Secondarily, the CMV-related events were composed of CMV-infection and disease, which occurred first. There were no differences in 1-year cumulative incidence of CMV-disease (23.7% vs. 19.1%, p = 0.41), CMV-related events (50.8% vs. 44.1%, p = 0.20), neither in time to diagnosis (47.0 vs. 47.0 days) among patients conducted by antigenemia vs. RT-PCR, respectively. The length of CMV first treatment was longer with RT-PCR (20.0 vs. 27.5 days, p < 0.001), while the rate of retreatment was not different (14.7% vs. 11.8%, p = 0.48). In the Cox regression, acute rejection within 30 days was associated with an increased the risk (HR = 2.34; 95% CI = 1.12-4.89; p = 0.024), while each increase of 1 mL/min/1.73 m2 of 30-day eGFR was associated with a 2% reduction risk of CMV-disease (HR = 0.98; 95% CI = 0.97-0.99; p = 0.001). In conclusion, acute rejection and glomerular filtration rate are risk factors for CMV disease, showing comparable performance in the impact of CMV-related events between antigenemia and RT-PCR for preemptive treatment.

Migratory pattern of the coronavirus disease 2019 and high fatality rates among kidney transplant recipients: report from the Brazilian Multicenter Cohort Study.

INTRODUCTION: The unprecedented coronavirus disease 2019 (COVID-19) pandemic has affected kidney transplant (KT) recipients, with worldwide fatality rates around 25%. Considering the well-known Brazilian socio-demographic disparities, this report describes for the first time the main outcomes of COVID-19 in KT recipients according to Brazilian geographic regions. METHODS: This multicenter national retrospective analysis included data from KT recipients with confirmed COVID-19 between March and November 2020. RESULTS: Thirty-five of the 81 centers (57% of KT activity in Brazil) reported 1,680 patients with COVID-19. The Northeast was the first to reach the peak in the number of infections. The Southeast, due to its population density, contributed with the largest number of patients. Patients had a median age of 52 years, 76% had hypertension and 34% diabetes, 75% were recipients of a deceased donor, and the time interval between diagnosis and transplantation was 5.9 years. In 53% of patients, immunosuppression was adjusted, and clinical support varied according to geographic region. Hospitalization was required for 65% of the patients, 35% of them needed intensive care, 25% mechanical ventilation, and 23% renal replacement therapy. The 90-day overall fatality was 21%, being 23% in the Southeast, 16% in the Northeast, and 19% in the Central-west and South regions. CONCLUSION: The migratory pattern of the pandemic among KT recipients followed that of the general population and the outcomes were influenced by regional features. COVID-19 in KT recipients was associated with high utilization of health-care resources and higher fatality rates than those reported in the general population.

Inactivated Whole-virus Vaccine Triggers Low Response Against SARS-CoV-2 Infection Among Renal Transplant Patients: Prospective Phase 4 Study Results.

BACKGROUND: Anti-severe acute respiratory syndrome coronavirus 2 mRNA vaccines elicit lower humoral responses in solid-organ transplant recipients. This is the first prospective trial investigating the effect of an inactivated whole-virion vaccine in kidney transplant recipients. METHODS: Prospective, single-center, phase 4, interventional study. Kidney transplant recipients aged 30-69 y with >30 d of transplantation received two 3 µg intramuscular doses of CoronaVac 28 d apart and are being followed for 6 mo. Primary outcomes: (1) reactogenicity after first dose; (2) antibody responses 28 d after each dose; and (3) incidence/severity of confirmed coronavirus disease 2019 (COVID-19) and 28-d lethality rate. For this analysis, clinical effectiveness was assessed for 3 mo, starting 15 d after the second dose, and compared with 3-mo period before vaccination. RESULTS: Of the 3371 individuals who received the first dose, 99% completed vaccination schedule. Mild/local adverse reactions were reported by 33% of the patients. In the immunogenicity cohort (n = 942), the proportion of patients with IgG antibodies to severe acute respiratory syndrome coronavirus 2 increased from 15.2% after first dose to 43% after second dose. Increase in antibody values after second dose was associated with higher proportion of patients with detected neutralizing antibodies. A significant reduction in the incidence of COVID-19 was observed (6.4% versus 4.2%; P < 0.0001), although the 28-d lethality rate remained unchanged (25% versus 22%; P = 0.534). In 45 patients from the immunogenicity cohort who developed COVID-19, all the 6 deaths occurred among those without antibody response (n = 22; 49%). CONCLUSIONS: CoronaVac vaccine was associated with low reactogenicity, low immunogenicity but reduced incidence of COVID-19 among kidney transplant recipients. The lack of reduction in lethality rates is perhaps associated with the low percentage of patients developing humoral response after the second dose.

The Mycophenolate-based Immunosuppressive Regimen Is Associated With Increased Mortality in Kidney Transplant Patients With COVID-19.

BACKGROUND: The chronic use of immunosuppressive drugs is a key risk factor of death because of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs), although no evident association between the class of immunosuppressive and outcomes has been observed. Thus, we aimed to compare COVID-19-associated outcomes among KTRs receiving 3 different immunosuppressive maintenance regimes. METHODS: This study included data from 1833 KTRs with COVID-19 diagnosed between March 20 and April 21 extracted from the national registry before immunization. All patients were taking calcineurin inhibitor associated with mycophenolate acid (MPA, n = 1258), azathioprine (AZA, n = 389), or mammalian targets of rapamycin inhibitors (mTORi, n = 186). Outcomes within 30 and 90 d were assessed. RESULTS: Compared with patients receiving MPA, the 30-d (79.9% versus 87.9% versus 89.2%; P < 0.0001) and 90-d (75% versus 83.5% versus 88.2%; P < 0.0001) unadjusted patient survivals were higher in those receiving AZA or mTORi, respectively. Using adjusted multivariable Cox regression, compared with patients receiving AZA, the use of MPA was associated with a higher risk of death within 30 d (adjusted hazard ratio [aHR], 1.70; 95% confidence interval [CI], 1.21-2.40; P = 0.003), which was not observed in patients using mTORi (aHR, 0.78; 95% CI, 0.45-1.35; P = 0.365). At 90 d, although higher risk of death was confirmed in patients receiving MPA (aHR, 1.46; 95% CI, 1.09-1.98; P = 0.013), a reduced risk was observed in patients receiving mTORi (aHR, 0.59; 95% CI, 0.35-0.97; P = 0.04) compared with AZA. CONCLUSIONS: This national cohort data suggest that, in KTRs receiving calcineurin inhibitor and diagnosed with COVID-19, the use of MPA was associated with higher risk of death, whereas mTORi use was associated with lower risk of death.

Long-term outcomes after kidney transplant failure and variables related to risk of death and probability of retransplant: Results from a single-center cohort study in Brazil.

BACKGROUND: Returning to dialysis after kidney graft loss (GL) is associated with a high risk of mortality, mainly in the first 3-6 months. The follow-up of patients with GL should be extended to better understand crude patient outcomes, mainly in emerging countries, where the transplantation activity has increased. METHODS: This is a historical single-center cohort study conducted in an emerging country (Brazil) that included 115 transplant patients with kidney allograft failure who were followed for 44.1 (21.4; 72.6) months after GL. The outcomes were death or retransplantation after GL calculated by Kaplan-Meier and log-rank tests. Proportional hazard ratios for death and retransplantation were assessed by Cox regression. RESULTS: The 5-year probability of retransplantation was 38.7% (95% CI: 26.1%-51.2%) and that of death was 37.7% (95% CI: 24.9%-50.5%); OR = 1.03 (95% CI: 0.71-1.70) and P = 0.66. The likelihood of retransplantation was higher in patients who resumed dialysis with higher levels of hemoglobin (HR = 1.22; 95% CI = 1.04-1.43; P = 0.01) and lower in blood type O patients (HR = 0.48; 95% CI = 0.25-0.93; P = 0.03), which was associated with a lower frequency of retransplantation with a subsequent living-donor kidney. On the other hand, the risk of death was significantly associated with Charlson comorbidity index (HR for each point = 1.37; 95% CI 1.19-1.50; P<0.001), and residual eGFR at the time when patients had resumed to dialysis (HR for each mL = 1.14; 95% CI = 1.05-1.25; P = 0.002). The trend toward a lower risk of death when patients had resumed to dialysis using AV fistula access was observed (HR = 0.50; 95% CI 0.25-1.02; P = 0.06), while a higher risk seems to be associated with the number of previous engraftment (HR = 2.01; 95% CI 0.99-4.07; P = 0.05). CONCLUSIONS: The 5-year probability of retransplantation was not less than that of death. Variables related to the probability of retransplantation were hemoglobin level before resuming dialysis and ABO blood type, while the risk of death was associated with comorbidities and residual eGFR.

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.

High mortality among kidney transplant recipients diagnosed with coronavirus disease 2019: Results from the Brazilian multicenter cohort study.

BACKGROUND: Kidney transplant (KT) recipients are considered a high-risk group for unfavorable outcomes in the course of coronavirus disease 2019 (COVID-19). AIM: To describe the clinical aspects and outcomes of COVID-19 among KT recipients. METHODS: This multicenter cohort study enrolled 1,680 KT recipients diagnosed with COVID-19 between March and November 2020, from 35 Brazilian centers. The main outcome was the 90-day cumulative incidence of death, for the entire cohort and according to acute kidney injury (AKI) and renal replacement therapy (RRT) requirement. Fatality rates were analyzed according to hospitalization, intensive care unit (ICU) admission, and mechanical ventilation (MV) requirement. Multivariable analysis was performed by logistic regression for the probability of hospitalization and death. RESULTS: The median age of the recipients was 51.3 years, 60.4% were men and 11.4% were Afro-Brazilian. Comorbidities were reported in 1,489 (88.6%), and the interval between transplantation and infection was 5.9 years. The most frequent symptoms were cough (54%), myalgia (40%), dyspnea (37%), and diarrhea (31%), whereas the clinical signs were fever (61%) and hypoxemia (13%). Hospitalization was required in 65.1%, and immunosuppressive drugs adjustments were made in 74.4% of in-hospital patients. ICU admission was required in 34.6% and MV in 24.9%. In the multivariable modeling, the variables related with the probability of hospitalization were age, hypertension, previous cardiovascular disease, recent use of high dose of steroid, and fever, dyspnea, diarrhea, and nausea or vomiting as COVID-19 symptoms. On the other hand, the variables that reduced the probability of hospitalization were time of COVID-19 symptoms, and nasal congestion, headache, arthralgia and anosmia as COVID-19 symptoms. The overall 90-day cumulative incidence of death was 21.0%. The fatality rates were 31.6%, 58.2%, and 75.5% in those who were hospitalized, admitted to the ICU, and required MV, respectively. At the time of infection, 23.2% had AKI and 23.4% required RRT in the follow-up. The cumulative incidence of death was significantly higher among recipients with AKI (36.0% vs. 19.1%, P < 0.0001) and in those who required RRT (70.8% vs. 10.1%, P < 0.0001). The variables related with the probability of death within 90 days after COVID-19 were age, time after transplantation, presence of hypertension, previous cardiovascular disease, use of tacrolimus and mycophenolate, recent use of high dose of steroids, and dyspnea as COVID-19 symptom. On the other hand, the variables that reduced the risk of death were time of symptoms, and headache and anosmia as COVID-19 symptoms. CONCLUSION: The patients diagnosed with COVID-19 were long-term KT recipients and most of them had some comorbidities. One in every five patients died, and the rate of death was significantly higher in those with AKI, mainly when RRT was required.

Severe Strongyloides stercoralis infection in kidney transplant recipients: A multicenter case-control study.

BACKGROUND: Severe Strongyloides stercoralis infection in kidney transplant recipients is associated with considerable morbidity and mortality, although little is known about the risk factors for such infection. METHODOLOGY/PRINCIPAL FINDINGS: This was a retrospective, multicenter, case-control study in which we assessed the risk factors for and clinical outcomes of severe S. stercoralis infections in kidney transplant recipients in Brazil. We included 138 kidney transplant recipients: 46 cases and 92 controls. Among the cases, the median number of days from transplantation to diagnosis was 117 (interquartile range [IQR], 73.5-965) and the most common clinical findings were gastrointestinal symptoms (in 78.3%) and respiratory symptoms (in 39.1%), whereas fever and eosinophilia were seen in only 32.6% and 43.5%, respectively. The 30-day all-cause mortality among the cases was 28.3% overall and was significantly higher among the cases of infection occurring within the first three months after transplantation (47% vs. 17.2%, P = 0.04). The independent risk factors were receiving a transplant from a deceased donor (odds ratio [OR] = 6.16, 95% confidence interval [CI] = 2.05-18.5), a history of bacterial infection (OR = 3.04, 95% CI = 1.2-7.5), and a cumulative corticosteroid dose (OR = 1.005, 95% CI = 1.001-1.009). The independent predictors of mortality were respiratory failure (OR = 98.33, 95% CI = 4.46-2169.77) and concomitant bacteremia (OR = 413.00, 95% CI = 4.83-35316.61). CONCLUSIONS/SIGNIFICANCE: Severe S. stercoralis infections are associated with considerable morbidity and mortality after kidney transplantation. In endemic areas, such infection may occur late after transplantation, although it seems to be more severe when it occurs earlier after transplantation. Specific risk factors and clinical manifestations can identify patients at risk, who should receive prophylaxis or early treatment.