Unveiling Trichosporon austroamericanum sp. nov.: A Novel Emerging Opportunistic Basidiomycetous Yeast Species.

During an epidemiological survey, a potential novel species within the basidiomycetous yeast genus Trichosporon was observed. The clinical strain was obtained from a urine sample taken from a Brazilian kidney transplant recipient. The strain was molecularly identified using the intergenic spacer (IGS1) ribosomal DNA locus and a subsequent phylogenetic analysis showed that multiple strains that were previously reported by other studies shared an identical IGS1-genotype most closely related to that of Trichosporon inkin. However, none of these studies provided an in-depth characterization of the involved strains to describe it as a new taxon. Here, we present the novel clinically relevant yeast for which we propose the name Trichosporon austroamericanum sp. nov. (holotype CBS H-24937). T. austroamericanum can be distinguished from other siblings in the genus Trichosporon using morphological, physiological, and phylogenetic characters.

Quality of life of patients after kidney transplant: ADHERE Brazil multicenter cross-sectional study.

BACKGROUND: Quality of life (QoL) is a measure to evaluate kidney transplant (KT) results. AIM: To describe the QoL profile in a larger sample of Brazilian patients who underwent KT according to age, sex, and access to KT. METHODS: We conducted a secondary data analysis of the ADHERE BRAZIL multicenter cross-sectional study including 1105 patients from 20 centers, considering KT access region and transplant activity. QoL was assessed by the WHOQOL-BREF. Data was compared using Generalized Estimating Equations. RESULTS: Overall, 58.5 % of the patients were men, mean age of 47.6 ± 12.6 years. The general QoL score was 81 ± 15.1, 58.6 ± 11.6 for physical, 65.5 ± 11.4 for psychological, 68.3 ± 17.1 for social relationships, and 64.2 ± 13.3 for environmental domain. Higher QoL scores were observed in men compared to women in three WHOQOL-BREF domains: psychological (OR:2.62; CI, 1.29 ̶ 3.95, p < 0.0001), social relationships (OR:3.21; CI, 1.2 ̶ 5.23, p = 0.002) and environmental (OR:3.79; CI:2.23 ̶ 5.35, p < 0.0001). Younger patients (18-44 years) had higher scores in the psychological (OR:-2.69; CI, -4.13 ̶ -1.25; p < 0.001; OR:-3.52; CI, -5.39 ̶ -1.66; p < 0.001) and social (OR:-3.46; CI, -5.64 ̶ -1.27; p = 0.002; OR:-7.17; CI, -10 ̶ -4.35; p < 0.0001) domains than older ones (45-59 and > 60 years, respectively). Patients from higher KT access region had higher scores in environmental domain (OR:3.53; CI, 0.28 ̶ 6.78; p = 0.033). CONCLUSIONS: Featuring the results of KT under patient view, the physical and social relationships domains were the most and least affected, respectively. Lower QoL subgroups (females and age > 45 years) should be targeted in future multi-professional interventions.

Sex Differences among Overweight/Obese Kidney Transplant Recipients Requiring Oxygen Support Amid the COVID-19 Pandemic.

Background and Objectives: Overweight/obesity puts individuals at greater risk for COVID-19 progression and mortality. We aimed to evaluate the impact of overweight/obesity on oxygen (O2) requirement outcomes of male and female kidney transplant recipients (KTRs) during the COVID-19 pandemic. Materials and Methods: We conducted a retrospective analysis of a cohort of KTRs diagnosed with COVID-19. Participants were stratified based on BMI categories, and data on the need for O2 therapy outcome were collected and analyzed separately for male and female KTRs. Results: In total, 284 KTRs (97 males and 187 females) were included in the study. Overweight/obesity was observed in 60.6% of male KTRs and 71% of female KTRs. Strikingly, overweight/obese women had a significantly higher requirement for supplemental O2 (63.3% vs. 41.7%, OR = 2.45, p = 0.03), particularly among older individuals (OR = 1.05, p = 0.04), smokers (OR = 4.55, p = 0.03), those with elevated lactate dehydrogenase (LDH) levels (OR = 1.01, p = 0.006), and those with lower admission and basal estimated glomerular filtration rate (eGFR) levels. Within this cohort, the necessity for O2 supplementation was correlated with more unfavorable outcomes. These included heightened mortality rates, transfers to the intensive care unit, employment of invasive mechanical ventilation, and the emergence of acute kidney injury requiring hemodialysis. On the other hand, although overweight/obese male KTRs had a higher prevalence of hypertension and higher fasting blood glucose levels, no significant association was found with COVID-19-related outcomes when compared to lean male KTRs. Conclusions: Overweight/obesity is highly prevalent in KTRs, and overweight/obese women demonstrated a higher need for supplemental O2. Therefore, the early identification of factors that predict a worse outcome in overweight/obese female KTRs affected by COVID-19 contributes to risk stratification and guides therapeutic decisions.

COVID-19 in Kidney Transplant Recipients With Diabetes Mellitus: A Propensity Score Matching Analysis.

Kidney transplant recipients present higher rates of pre-existing comorbidities, in particular diabetes mellitus (DM), hypertension, and cardiac disease. We aimed to verify the main risk factors related to DM that contribute to COVID-19 progression and mortality in a kidney transplant setting. From March to August 2020, we evaluated 300 kidney transplant recipients affected by COVID-19. We used propensity score matching (PSM) to estimate the impact of DM on COVID-19. After matching, all baseline characteristics were well balanced between those with and without DM (n = 100 in each group). Case fatality rate, the requirement of invasive mechanical ventilation (IMV), and acute kidney injury (AKI) were associated with previous fasting blood glucose, and C-reactive protein (CRP), and lactate dehydrogenase (LDH) levels on admission. These findings were similar in kidney transplant patients with and without DM. Glycemia on admission and estimated glomerular filtration rate (eGFR) either on admission or basal correlated to the need of IMV and development of AKI, respectively. Poor glycaemic control, eGFR, markers of inflammation (CRP) and tissue damage (LDH) were indicative of COVID-19 burden in kidney transplant recipients and may be useful tools for risk-stratifying this population, independently of the DM status, during the pandemic.

High soluble HLA-DQB2 levels in posttransplant serum are associated with kidney graft dysfunction.

HLA-DQB2 is a gene of limited polymorphism, with unknown function that presents at least two transcript variants: v1, which encodes the full-length beta-chain, and v2, which lacks exon 4 and could give rise to a soluble protein. We previously showed a strong correlation between high v2 expression in preimplantation biopsies (PIB) of kidneys from young (18- to 49-year olds) but not from old, deceased donors and 1-year posttransplant low (estimated glomerular filtration rate < 45 ml/min/1.73 m2 ) graft function (GF). In this study, we aimed to investigate the impact of posttransplant soluble HLA-DQB2 (sDQB2) serum levels, v1 expression in PIB, and recipient HLA-DQB2 rs7453920 A/G polymorphism on GF. sDQB2 was evaluated by enzyme-linked immunosorbent assay in sera from 114 recipients, collected at least 1 year (median 2.1 years) after transplantation. Higher sDQB2 levels were observed in recipients of kidneys from young, but not from old, donors that had a ≥30% decline in GF within 1 year after blood collection for sDQB2 determination. Among the 15 recipients of kidneys from young donors with sDQB2 ≥ 1.52 ng/ml, 40% presented a ≥30% decline in GF, whereas this occurred in none of the 43 recipients with lower sDQB2 levels (p = 0.007; OR: 36.5). Expression of HLA-DQB2 variant 1, measured by reverse transcription-polymerase chain reaction (RT-PCR) in 92 PIB from young or old donors, did not significantly differ between transplants with high or low 4-year GF. HLA-DQB2 rs7453920 single nucleotide polymorphism (SNP) frequencies did not significantly differ between recipients with low or high 4-year GF. We conclude that HLA-DQB2 variant 1 expression in PIB and recipient rs7453920 SNP polymorphism are not associated with graft outcome. On the other hand, the association, in transplants of kidneys from young donors, between high posttransplant serum sDQB2 levels and decline in GF is a very interesting finding that deserves a validation study in a larger cohort.

Donor-Derived Transmission of Cryptococcus gattii sensu lato in Kidney Transplant Recipients.

We describe cases of donor-derived transmission of Cryptococcus deuterogattii in 2 kidney transplant recipients in Brazil and published information on other cases. Prompt reduction of immunosuppression and initiation of antifungal therapy was required to successfully control the fungal infections and preserve engraftment.

Immunosuppressive Drug-Associated Adverse Event Profiles in De Novo Kidney Transplant Recipients Receiving Everolimus and Reduced Tacrolimus Doses.

BACKGROUND: The safety of immunosuppressive regimens is influenced by the induction agent, maintenance drug combination, and prophylactic strategy for cytomegalovirus (CMV) infection. Herein, this safety analysis compares rabbit antithymocyte globulin (r-ATG) or basiliximab (BAS) combined with everolimus (EVR) versus BAS combined with mycophenolate sodium (MPS) in kidney transplant recipients receiving tacrolimus, prednisone, and preemptive CMV therapy. METHODS: In this single-center, prospective, randomized study, adverse events (AEs), serious AEs (SAEs), viral infections, laboratory abnormalities, dose reductions, and temporary or permanent discontinuation of the immunosuppressant were compared among patients receiving r-ATG/EVR (n = 85), BAS/EVR (n = 102), and BAS/MPS (n = 101). RESULTS: A total of 2741 AEs and 344 SAEs were observed. There were no differences in the proportion of patients with at least one AE (96% versus 98% versus 96%, respectively; P > 0.05). The proportion of patients with at least one SAE was highest in the BAS/MPS group (33% versus 48% versus 69%, respectively; P < 0.05). This difference was due primarily to a high incidence of CMV infection in the BAS/MPS group (4.7% versus 10.8% versus 37.6%, respectively). The incidence of mild/moderate abnormalities in creatinine, cholesterol, and triglyceride levels was higher in both EVR groups. The cumulative freedom from dose reduction or treatment discontinuation due to an AE was higher in both EVR groups than in the BAS/MPS group (89.2% versus 92.8% versus 76.3%, respectively, P = 0.003). There was no difference in the incidence of biopsy-confirmed acute rejection (9.4% versus 18.6 versus 15.8%, respectively; P = 0.403). CONCLUSIONS: This analysis suggests that r-ATG induction combined with EVR is associated with a comparable incidence of acute rejection, lower incidence of CMV infection, and fewer changes in initial immunosuppressive regimen due to AEs in kidney transplant recipients receiving tacrolimus, prednisone, and preemptive CMV therapy.

Pretransplant defunctionalized bladder-overrated condition?

AIMS: The objective of this study was to evaluate the expression of bladder receptors in patients with defunctionalized bladder (DB) and to assess voiding behavior after refunctionalization. METHODS: A total of 68 pretransplant patients were divided in two groups: DB (diuresis <300 mL/24 h; n = 33) and NDB (non-DB; diuresis ≥300 mL/24 h; n = 35). A sample of mucosa and detrusor at the site of the future ureteral implantation was collected. The following receptors were assessed by real-time polymerase chain reaction (qRT-PCR): M2 , M3 , α1D , ß3 , P2X2 , P2X3 , TRPV1, TRPV4, TRPA1, and TRPM8. At 3, 6, and 12 months after transplant patients answered IPSS and ICIQ-OAB questionnaires and filled a 3-day 24 h frequency/volume chart (FVC) at 6 and 12 months. RESULTS: The expression of all receptors in the mucosa and in the detrusor was similar in both groups, except from α1D , which was overexpressed in the detrusor of DB relatively to NDB group. ICIQ-OAB symptom score was similar between the groups at 3, 6, and 12 months. There was a reduction of this score in both groups with time. The same pattern was found for IPSS score. Bother scores were similar between groups. No difference was observed for all FVC parameters between DB and NDB patients. CONCLUSION: Gene expression of bladder receptors involved in micturition control was similar in patients with or without DB. Bladder behavior had a similar pattern independently of pretransplant residual diuresis. These findings question the relevance of the term DB in pretransplant patients.

Limitations of the interpretation and extrapolation of clinical trial data in kidney transplant recipients.

OBJECTIVE: The risks and benefits of the participation of kidney transplant recipients in randomized clinical trials (RCTs) investigating new immunosuppressive therapies are unknown. DESIGN AND SETTING: We included patients from 12 prospective phase II/III RCTs randomized to the experimental (G1, n=319) or standard-of-care internal control group (G2, n=118). We constructed two additional external control groups with (G3, n=319) or without (G4, n=319) matching inclusion/exclusion criteria based on transplant date. The primary outcome analysis was the composite clinical efficacy failure, defined as biopsy-proven acute rejection (BPAR), graft loss, death, or loss to follow-up 12 months after kidney transplantation. RESULTS: Survival free of composite clinical efficacy failure was higher among participants in RCT, without difference between experimental or standard-of-care therapy (80∙3 vs 78∙0 vs 69∙9 vs 66∙1%, P<.001), respectively. Patient (98.1 vs 99.2 vs 96.9 vs 91.8 P<.001) and graft (94.0 vs 98.3 vs 90.9 vs 82.4) survivals were also higher in G1 compared to G4, but no differences in survival free of BPAR were observed (85.3 vs 78.8 vs 82.8 vs 81.2 P>.05), respectively. CONCLUSION: These findings suggested that new treatments investigated in kidney transplant recipients are not associated with detectable harm compared to standard of care.

Regional differences in the management and outcome of kidney transplantation in patients with human immunodeficiency virus infection: A 3-year retrospective cohort study.

BACKGROUND: In the developed world, kidney transplantation (KT) in patients with human immunodeficiency virus (HIV) infection is well established. Developing countries concentrate 90% of the people living with HIV, but their experience is underreported. Regional differences may affect outcomes. OBJECTIVES: We compared the 3-year outcomes of patients with HIV infection receiving a KT in two different countries, in terms of incomes and development. METHODS: This was an observational, retrospective, double-center study, including all HIV-infected patients >18 years old undergoing KT. RESULTS: Between 2005 and 2015, 54 KTs were performed (39 in a Brazilian center, and 15 in a Spanish center). Brazilians had less hepatitis C virus co-infection (5% vs 27%, P=.024). Median cold ischemia time was higher in Brazil (25 vs 18 hours, P=.001). Biopsy-proven acute rejection (AR) was higher in Brazil (33% vs 13%, P=.187), as were the number of AR episodes (22 vs 4, P=.063). Patient survival at 3 years was 91.3% in Brazil and 100% in Spain; P=.663. All three cases of death in Brazil were a result of bacterial infections within the first year post transplant. At 3 years, survival free from immunosuppressive changes was lower in Brazil (56% vs 90.9%, P=.036). Raltegravir-based treatment to avoid interaction with calcineurin inhibitor was more prevalent in Spain (80% vs 3%; P<.001). HIV infection remained under control in all patients, with undetectable viral load and no opportunistic infections. CONCLUSION: Important regional differences exist in the demographics and management of immunosuppression and antiretroviral therapy. These details may influence AR and infectious complications. Non-AIDS infections leading to early mortality in Brazil deserve special attention.

Influence of the CYP3A4/5 genetic score and ABCB1 polymorphisms on tacrolimus exposure and renal function in Brazilian kidney transplant patients.

BACKGROUND: Polymorphisms in genes encoding transport proteins and metabolizing enzymes involved in tacrolimus (TAC) disposition may be important sources of individual variability during treatment. OBJECTIVE: The aim of this study was to investigate the effect of combined CYP3A4 and CYP3A5 variants, using a CYP3A4/5 genetic score, and ABCB1 polymorphisms on therapeutic TAC monitoring and their relationship with clinical outcomes. MATERIAL AND METHODS: Brazilian kidney transplant recipients (n=151), who received TAC over 3 months after transplantation, were genotyped for CYP3A4 rs2242480 (g.20230G>A), CYP3A5 rs15524 (g.31611C>T) and rs776746 (g.6986A>G), ABCB1 rs1128503 (c.1236C>T), rs1045642 (c.3435C>T), and rs2032582 (c.2677G>T/A) polymorphisms. RESULTS: Frequencies of CYP3A4 g.20230A, CYP3A5 g.31611C, and g.6986A were 0.37, 0.26, and 0.28, respectively. These alleles were associated with TAC rapid metabolization and were used for CYP3A4/5 genetic score construction. A higher CYP3A4/5 genetic score was associated with higher TAC dose and lower concentrations for dose administered (Co/D, P<0.05). Ninety days after transplantation, the presence of two or more rapid metabolization alleles contributed toward 27.7% of Co/D variability and was associated with a lower estimated glomerular filtration rate values (P<0.05). For ABCB1, the frequencies of c.1236T, c.3435T, and c.2677T/A alleles were 0.42, 0.42, and 0.33/0.04. At 30 days after transplantation, patients carrying ABCB1 c.1236TT+c.3435TT+(c.2677TT+TA) genotypes had higher TAC Co/D than those with common or heterozygous genotypes (P<0.05). CONCLUSION: The results show the impact of the CYP3A4/5 genetic score on TAC exposure and renal function in Brazilian patients. Furthermore, ABCB1 polymorphisms, in a combined analysis, influenced TAC Co/D at 30 days after transplantation.

Pharmacokinetics and Long-Term Safety and Tolerability of Everolimus in Renal Transplant Recipients Converted From Cyclosporine.

BACKGROUND: Conversion from cyclosporine (CsA) to everolimus (EVR) in kidney transplant recipients receiving mycophenolate sodium (MPS) and corticosteroids has been used to reduce CsA associated toxicities. Nevertheless, exposures produced by the initial EVR dose, the steady state pharmacokinetic and long-term safety and tolerability have not been explored in detail. METHODS: Twenty-four stable kidney transplant recipients receiving CSA, MPS, and corticosteroids were converted from CSA to EVR. The initial EVR dose was 3 mg BID. Weekly monitoring of EVR blood concentrations was followed by a full 12 hour pharmacokinetic profile 28 days after conversion. Therapeutic drug monitoring, safety, and tolerability were analyzed during 5 years of follow-up. RESULTS: The study population was relatively young (mean of 42 years) with a predominance of males (62%) and White (67%) recipients of kidneys from living (54%) or deceased (46%) donors. Mean time of the conversion was 61 months after transplantation. In the first 7 patients, the initial EVR dose of 3 mg BID resulted in mean EVR trough blood concentration of 14.7 ± 3.7 ng/mL at day 7. The initial EVR dose was then reduced to 2 mg BID for the following 17 patients. Four weeks after conversion, mean EVR dose was 1.7 ± 0.5 mg BID (7 patients were receiving 1 mg BID and 17 were receiving 2 mg BID) resulting in mean EVR trough blood concentration of 4.0 ± 1.4 ng/mL. Whereas mean maximum concentration (13.4 ± 2.8 versus 22.9 ± 7.4 ng/mL, P = 0.003) and mean apparent clearance (232 ± 79 versus 366 ± 173 mL/min, P = 0.016) were higher, mean area under the curve (78.2 ± 22.1 versus 102.5 ± 38.5 ng.h/mL, P = 0.067) and mean C0 (3.7 ± 1.3 versus 4.1 ± 1.5 ng/mL, P = 0.852) were no different comparing patients receiving 1 mg and 2 mg EVR BID. Mean inter-subject variability of area under the curve, trough concentration, and maximum concentration was 38%, 36%, and 38%. EVR treatment was discontinued in 29% of patients due to proteinuria (N = 2), pneumonia (N = 2), dyslipidemia (N = 2), and anemia (N = 1) and MPS dose was reduced in 58% of patients. CONCLUSIONS: The initial 3 mg BID dose produced high EVR trough blood concentrations. The 2 mg BID dose appears to be the appropriate initial dose to provide therapeutic concentrations but still requires initial intensive therapeutic monitoring to achieve and maintain blood concentrations within the therapeutic target concentration. The combination of EVR and full dose MPS has limited long-term tolerability and safety.

Jagged2-signaling promotes IL-6-dependent transplant rejection.

The Notch pathway is an important intercellular signaling pathway that plays a major role in controlling cell fate. Accumulating evidence indicates that Notch and its ligands present on antigen-presenting cells might be important mediators of T helper cell differentiation. In this study, we investigated the role of Jagged2 in murine cardiac transplantation by using a signaling Jagged2 mAb (Jag2) that activates recombinant signal-binding protein-Jκ. While administration of Jag2 mAb had little effect on graft survival in the fully allogeneic mismatched model BALB/c→B6, it hastened rejection in CD28-deficient recipients. Similarly, Jag2 precipitated rejection in the bm12→B6 model. In this MHC class II-mismatched model, allografts spontaneously survive for >56 days due to the emergence of Treg cells that inhibit the expansion of alloreactive T cells. The accelerated rejection was associated with upregulation of Th2 cytokines and proinflammatory cytokine IL-6, despite expansion of Treg cells. Incubation of Treg cells with recombinant IL-6 abrogated their inhibitory effects in vitro. Furthermore, neutralization of IL-6 in vivo protected Jag2-treated recipients from rejection and Jagged2 signaling was unable to further accelerate rejection in the absence of Treg cells. Our findings therefore suggest that Jagged2 signaling can affect graft acceptance by upregulation of IL-6 and consequent resistance to Treg-cell suppression.

Blockade of Notch ligand δ1 promotes allograft survival by inhibiting alloreactive Th1 cells and cytotoxic T cell generation.

The Notch signaling pathway has been recently shown to contribute to T cell differentiation in vitro. However, the in vivo function of Notch signaling in transplantation remains unknown. In this study, we investigated the importance of Delta1 in regulating the alloimmune response in vivo. Delta1 expression was upregulated on dendritic cells and monocytes/macrophages upon transplantation in a BALB/c into B6 vascularized cardiac transplant model. Whereas administration of anti-Delta1 mAb only slightly delayed survival of cardiac allografts in this fully MHC-mismatched model, it significantly prolonged graft survival in combination with single-dose CTLA4-Ig or in CD28 knockout recipients. The prolongation of allograft survival was associated with Th2 polarization and a decrease in Th1 and granzyme B-producing cytotoxic T cells. The survival benefit of Delta1 blockade was abrogated after IL-4 neutralization and in STAT6KO recipients, but was maintained in STAT4KO recipients, reinforcing the key role of Th2 cell development in its graft-prolonging effects. To our knowledge, these data demonstrate for the first time an important role of Delta1 in alloimmunity, identifying Delta1 ligand as a potential novel target for immunomodulation in transplantation.

Oxygen Requirement in Overweight/Obese Kidney Transplant Recipients with COVID-19: An Observational Cohort Study.

INTRODUCTION: Obesity is one of the components of the cardiometabolic syndrome that contributes to COVID-19 progression and mortality. Immunosuppressed individuals are at greater risk of the COVID-19 burden. Therefore, we sought to investigate the impact of the combination of overweight/obesity and kidney transplant on oxygen (O2) requirements in the COVID-19 setting. METHODS: Retrospective analysis of 284 kidney transplant recipients (KTRs) from March/2020 to August/2020 in a single center. We investigated the risk factors associated with O2 requirements in overweight/obese KTRs. RESULTS: Overall, 65.1% had a BMI (body mass index) ≥ 25 kg/m2, 52.4% were male, the mean age was 53.3 ± 11 years old, 78.4% had hypertension, and 41.1% had diabetes mellitus. BMI was an independent risk factor for O2 requirements (OR = 1.07, p = 0.02) alongside age, lymphopenia, and hyponatremia. When overweight/obese KTRs were older, smokers, they presented higher levels of lactate dehydrogenase (LDH), and lower levels of estimated glomerular filtration rate (eGFR), lymphocytes, and sodium at admission, and they needed O2 more often. CONCLUSION: Being overweight/obese is associated with greater O2 requirements in KTRs, in particular in older people and smokers, with worse kidney allograft functions, more inflammation, and lower sodium levels. Therefore, the early identification of factors that predict a worse outcome in overweight/obese KTRs affected by COVID-19 contributes to risk stratification and therapeutic decisions.

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.

Unexpected distribution of hepatitis B genotypes in patients with kidney disease: comparison with immunocompetent subjects.

Hepatitis B virus (HBV) infection has a high prevalence among hemodialysis and renal transplant patients. Data regarding genotype distribution in these populations are scarce and are still under investigation. The aim of this study was to evaluate the distribution of HBV genotypes in end-stage renal disease (ESRD)-patients and renal transplant patients and to compare with the distribution observed in immunocompetent patients from the same geographic region. From a population of 213 patients evaluated initially, 120 patients with detectable HBV-DNA were included in the study and submitted to genotype determination by amplification of S gene by nested PCR followed by sequencing method. Among 41 hemodialysis patients the most frequent genotype was D (83%), followed by genotype A (10%), C (5%), and F (2%). Genotype D was also the most prevalent (73%) among 33 renal transplant patients, followed by genotype A (18%), F (6%), and B (3%). This distribution was similar in these two groups of patients and for the comparative analysis they were considered in the kidney disease group. Compared to immunocompetents, patients with kidney disease (ESRD and renal transplant patients) showed a distinct distribution, with a higher prevalence of genotype D (78% vs. 17%, P < 0.001) whereas genotype A was the most prevalent among immunocompetent patients (70% vs. 14%, P < 0.001). In conclusion, the higher frequency of genotype A in immunocompetent patients and of genotype D in patients with renal disease suggest a higher capacity of environmental transmission or a better adaptability of this genotype in patients with a different pattern of immunologic response.

Impact of Hypertension on COVID-19 Burden in Kidney Transplant Recipients: An Observational Cohort Study.

BACKGROUND: COVID-19 severity is determined by cardiometabolic risk factors, which can be further aggravated by chronic immunosuppression in kidney transplant recipients (KTRs). We aimed to verify the main risk factors related to hypertension (HTN) that contribute to COVID-19 progression and mortality in that population. METHODS: Retrospective analysis of 300 KTRs from March 2020 to August 2020 in a single center. We compared the main outcomes between HTN (n = 225) and non-HTN (n = 75), including admission to the intensive care unit (ICU), development of acute kidney injury (AKI), need for invasive mechanical ventilation or oxygen, and mortality. RESULTS: Of the patients in the study, 57.3% were male, 61.3% were white, the mean age was 52.5 years, and 75% had HTN. Pre-existing HTN was independently associated with higher rates of mortality (32.9%, OR = 1.96, p = 0.036), transfer to the ICU (50.7%, OR = 1.94, p = 0.017), and AKI with hemodialysis (HD) requirement (40.4%, OR = 2.15, p = 0.011). In the hypertensive group, age, diabetes mellitus, heart disease, smoking, glycemic control before admission, C-reactive protein, lactate dehydrogenase, lymphocytes, and D-dimer were significantly associated with COVID-19 progression and mortality. Both lower basal and previous estimated glomerular filtration rates posed KTRs with HTN at greater risk for HD requirement. CONCLUSIONS: Therefore, the early identification of factors that predict COVID-19 progression and mortality in KTRs affected by COVID-19 contributes to therapeutic decisions, patient flow management, and allocation of resources.

HLA-A homozygosis is associated with susceptibility to COVID-19.

The purpose of this single center retrospective study was to investigate the relationship between HLA and ABO polymorphisms and COVID-19 susceptibility and severity in kidney transplant recipients. It included 720 recipients who had COVID-19 and 1680 controls composed by recipients in follow-up who did not contact the transplantation center for COVID-19 symptoms, up to the moment of their inclusion in the study. HLA-A, -B, and -DRB1 allele groups and ABO frequencies were compared between recipients with COVID-19 (all cases, or separately mild/moderate and severe disease) and controls. The HLA association study was conducted in two case-control series and only associations that showed a p-value <0.05 in both series were considered. No HLA association regarding COVID-19 occurrence or severity met this criterion. Homozygosity at HLA-A locus was associated with COVID-19 susceptibility (odds ratio 1.4) but not severity. Blood groups A and O were associated with susceptibility and resistance to COVID-19, respectively. COVID-19 severity was associated only with older age and cardiac disease, in a multivariate analysis. We conclude that an influence of HLA on COVID-19 susceptibility is supported by the association with homozygosity at HLA-A locus but that there is no evidence for a role of any particular HLA-A, -B, or -DRB1 polymorphism. Thus, we suggest that what matters is the overall capability of an individual's HLA molecules to present SARS-CoV-2 peptides to T cells, a factor that might have a great influence on the breadth of the immune response.