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1.
Sci Rep ; 13(1): 4506, 2023 03 18.
Article in English | MEDLINE | ID: mdl-36934135

ABSTRACT

Predicting risk factors for death in leptospirosis is challenging, and identifying high-risk patients is crucial as it might expedite the start of life-saving supportive care. Admission data of 295 leptospirosis patients were enrolled, and a machine-learning approach was used to fit models in a derivation cohort. The comparison of accuracy metrics was performed with two previous models-SPIRO score and quick SOFA score. A Lasso regression analysis was the selected model, demonstrating the best accuracy to predict mortality in leptospirosis [area under the curve (AUC-ROC) = 0.776]. A score-based prediction was carried out with the coefficients of this model and named LeptoScore. Then, to simplify the predictive tool, a new score was built by attributing points to the predictors with importance values higher than 1. The simplified score, named QuickLepto, has five variables (age > 40 years; lethargy; pulmonary symptom; mean arterial pressure < 80 mmHg and hematocrit < 30%) and good predictive accuracy (AUC-ROC = 0.788). LeptoScore and QuickLepto had better accuracy to predict mortality in patients with leptospirosis when compared to SPIRO score (AUC-ROC = 0.500) and quick SOFA score (AUC-ROC = 0.782). The main result is a new scoring system, the QuickLepto, that is a simple and useful tool to predict death in leptospirosis patients at hospital admission.


Subject(s)
Leptospirosis , Humans , Adult , ROC Curve , Leptospirosis/diagnosis , Risk Factors , Hematocrit , Machine Learning , Retrospective Studies
2.
Appl Immunohistochem Mol Morphol ; 30(10): 687-693, 2022.
Article in English | MEDLINE | ID: mdl-36251974

ABSTRACT

Few reports assessed endothelial activation biomarkers in kidney allograft biopsies using immunohistochemistry. This retrospective cohort study evaluated the association between posttransplant outcomes and the immunohistochemistry expression of Caveolin-1, Von Willebrand Factor (Vwf), and T-Cadherin in for-cause biopsies diagnosed as interstitial fibrosis and tubular atrophy of unknown etiology. Samples with antibody-mediated changes were excluded. The patients were followed for 3 years after the biopsy or until graft loss/death. Seventy-one (71) samples from 66 patients were included. Eighteen (25.4%) patients lost their grafts, mainly due to chronic rejection (33.3%). Caveolin-1 and T-Cadherin were not associated with graft loss. Vwf had good accuracy in predicting graft failure (AUC 0.637, 95% CI 0.486 to 0.788 P =0.101). The presence of more than 10% of Vwf positivity in the microvasculature (Vwf >10%) was associated with reduced death-censored graft survival (58.2% vs. 85.4% P =0.006), and this result was also observed in the subgroup presenting mild interstitial fibrosis (ci=1) (65.7% vs. 88.6% P =0.033). The multivariate analysis showed that Vwf >10% was an independent risk factor for graft loss (HR=2.88, 95% CI 1.03 to 8.02 P =0.043). In conclusion, Vwf might be an additional tool to predict allograft outcomes in kidney transplant recipients with interstitial fibrosis and tubular atrophy of unknown etiology, probably reflecting immune endothelial activation.


Subject(s)
Kidney Diseases , Kidney Transplantation , Humans , Allografts/pathology , Atrophy/pathology , Biopsy , Caveolin 1 , Fibrosis , Graft Rejection/diagnosis , Kidney/pathology , Retrospective Studies , von Willebrand Factor , Immunohistochemistry
4.
Transplantation ; 106(10): e441-e451, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35765133

ABSTRACT

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.


Subject(s)
COVID-19 , Kidney Transplantation , Azathioprine , Calcineurin Inhibitors/adverse effects , Enzyme Inhibitors , Humans , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Mycophenolic Acid/adverse effects , Sirolimus/adverse effects , TOR Serine-Threonine Kinases
5.
Transpl Int ; 35: 10205, 2022.
Article in English | MEDLINE | ID: mdl-35185380

ABSTRACT

Data from the general population suggest that fatality rates declined during the course of the pandemic. This analysis, using data extracted from the Brazilian Kidney Transplant COVID-19 Registry, seeks to determine fatality rates over time since the index case on March 3rd, 2020. Data from hospitalized patients with RT-PCR positive SARS-CoV-2 infection from March to August 2020 (35 sites, 878 patients) were compared using trend tests according to quartiles (Q1: <72 days; Q2: 72-104 days; Q3: 105-140 days; Q4: >140 days after the index case). The 28-day fatality decreased from 29.5% (Q1) to 18.8% (Q4) (pfor-trend = 0.004). In multivariable analysis, patients diagnosed in Q4 showed a 35% reduced risk of death. The trend of reducing fatality was associated with a lower number of comorbidities (20.7-10.6%, p for-trend = 0.002), younger age (55-53 years, pfor-trend = 0.062), and better baseline renal function (43.6-47.7 ml/min/1.73 m2, pfor-trend = 0.060), and were confirmed by multivariable analysis. The proportion of patients presenting dyspnea (pfor-trend = 0.001) and hypoxemia (pfor-trend < 0.001) at diagnosis, and requiring intensive care was also found reduced (pfor-trend = 0.038). Despite possible confounding variables and time-dependent sampling differences, we conclude that COVID-19-associated fatality decreased over time. Differences in demographics, clinical presentation, and treatment options might be involved.


Subject(s)
COVID-19 , Kidney Transplantation , Cohort Studies , Humans , Kidney Transplantation/adverse effects , Registries , SARS-CoV-2 , Transplant Recipients
6.
J Nephrol ; 35(1): 131-141, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34677805

ABSTRACT

BACKGROUND AND OBJECTIVES: Patients undergoing kidney replacement therapies (KRTs) have a poor prognosis after Covid-19 infection. Few studies have compared the outcomes of such patients in the different KRT modalities. This study aimed to analyze the 30-day Covid-19-associated case-fatality rate of dialysis and kidney transplant patients. METHODS: Retrospective cohort study analyzing data from patients with confirmed Covid-19 between Mar/20 and Jan/21 included in two multicenter studies, the Brazilian Covid-19 Dialysis Study (Dialysis group, n = 703) and the Covid-19-KT Brazilian Study (Transplant group, n = 1907). To assess the risk factors for death, adjusted Cox hazards models were used. A sensitivity analysis was performed using a propensity score analysis to match the groups (n = 587 patients in each group). RESULTS: A higher percentage of transplant patients required hospitalization (68 vs. 51%, p < 0.001), intensive care (37 vs. 30%, p = 0.023), and invasive mechanical ventilation (28 vs. 22%, p = 0.035). Multivariate analysis of the before-matching sample showed that subjects in the transplant group were at a lower death risk at baseline (HR 0.380.560.85). However, they showed higher risk over time (HR 1.031.061.09). Kaplan-Meier analysis after propensity score matching confirmed the inferior 30-day cumulative survival in the transplant recipients (83 vs. 78%, p = 0.0014). CONCLUSION: Both transplant and dialysis patients have high 30-day case-fatality rates after a Covid-19 diagnosis. Despite lower death risk at baseline, transplant patients have an increased death risk of 6% per day than dialysis patients.


Subject(s)
COVID-19 Testing , COVID-19 , Cohort Studies , Humans , Propensity Score , Renal Dialysis/adverse effects , Retrospective Studies , SARS-CoV-2
7.
Am J Transplant ; 22(2): 610-625, 2022 02.
Article in English | MEDLINE | ID: mdl-34416075

ABSTRACT

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.


Subject(s)
COVID-19 , Kidney Transplantation , COVID-19 Testing , Humans , Internet , Kidney Transplantation/adverse effects , ROC Curve , Retrospective Studies , Risk Factors , SARS-CoV-2 , Transplant Recipients
8.
Am J Trop Med Hyg ; 105(3): 564-572, 2021 06 28.
Article in English | MEDLINE | ID: mdl-34181579

ABSTRACT

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.


Subject(s)
Arbovirus Infections/diagnosis , Chagas Disease/diagnosis , Kidney Transplantation , Leishmaniasis/diagnosis , Strongyloidiasis/diagnosis , Tuberculosis/diagnosis , Arbovirus Infections/immunology , Arbovirus Infections/therapy , Chagas Disease/immunology , Chagas Disease/therapy , Chikungunya Fever/diagnosis , Chikungunya Fever/immunology , Chikungunya Fever/therapy , Dengue/diagnosis , Dengue/immunology , Dengue/therapy , Graft Rejection/prevention & control , Humans , Immunocompromised Host , Immunosuppressive Agents/therapeutic use , Latin America , Leishmaniasis/immunology , Leishmaniasis/therapy , Strongyloidiasis/immunology , Strongyloidiasis/therapy , Tuberculosis/immunology , Tuberculosis/therapy , Yellow Fever/diagnosis , Yellow Fever/immunology , Yellow Fever/therapy , Zika Virus Infection/diagnosis , Zika Virus Infection/immunology , Zika Virus Infection/therapy
9.
Transpl Int ; 34(6): 1093-1104, 2021 06.
Article in English | MEDLINE | ID: mdl-33742470

ABSTRACT

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.


Subject(s)
Kidney Transplantation , Brazil/epidemiology , Cohort Studies , Delayed Graft Function/epidemiology , Delayed Graft Function/etiology , Graft Rejection/epidemiology , Graft Rejection/etiology , Graft Survival , Humans , Incidence , Kidney Transplantation/adverse effects , Male , Retrospective Studies , Risk Factors , Tissue Donors
11.
Clin Exp Nephrol ; 25(3): 305-314, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33242156

ABSTRACT

BACKGROUND: There are only a few reports evaluating the applicability of endothelial-damage markers analysis by immunohistochemistry (IHC) in kidney allograft samples. This study analyzed the expression of Caveolin-1 (Cav), von Willebrand factor (Vwf), and T-cadherin (Cad) in kidney biopsies and their association with antibody-mediated injury. METHODS: In this retrospective study, 114 cases with antibody-mediated changes (Banff, 2020) and 72 with interstitial fibrosis/tubular atrophy were selected. IHC for Cav, Vwf and Cad was performed and evaluated according to their qualitative expression in peritubular capillaries. The cases were grouped according to the presence of microvascular inflammation (MVI), donor-specific antibodies (DSA), C4d positivity and antibody-mediated rejection (AMR). A level of significance < 0.05 was adopted. RESULTS: Vwf expression was associated with MVI (p < 0.001), DSA (p = 0.016), C4d (p < 0.001) and AMR (p < 0.001), and was higher in DSA+/C4d+ cases despite MVI (p < 0.001). The expression of Cad correlated with MVI (p = 0.015), C4d (p = 0.005) and AMR (p = < 0.001). Cad was more expressed in chronic AMR compared with acute/active cases (p = 0.001). Cav expression was associated with MVI (p = 0.029) and AMR (p = 0.016) and was also higher in chronic AMR (p = 0.049). A combined score of Vwf and Cad was higher in AMR when compared with C4d without rejection and IF/TA cases (p < 0.001). CONCLUSION: Vwf, Cad and Cav expression shows association with antibody-mediated injury and may be helpful to support AMR diagnosis.


Subject(s)
Cadherins/analysis , Caveolin 1/analysis , Graft Rejection/metabolism , Immunohistochemistry , Isoantibodies/analysis , Kidney Transplantation/adverse effects , Kidney/chemistry , von Willebrand Factor/analysis , Adult , Biomarkers/analysis , Biopsy , Female , Graft Rejection/immunology , Graft Rejection/pathology , Humans , Kidney/immunology , Kidney/pathology , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies , Young Adult
12.
Transplant Proc ; 53(2): 602-606, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33077181

ABSTRACT

BACKGROUND: There are few reports about the usefulness of Maryland Aggregate Pathology Index (MAPI) score in procurement biopsies. This study aimed to evaluate the association between histopathological analysis according to MAPI and unfavorable outcomes in the first year after kidney transplantation (KT). METHODS: This retrospective study included deceased-donor KT patients whose grafts were biopsied before transplantation and had low MAPI scores (<8) in frozen sections (FSs). Paraffin sections (PSs) were analyzed after KT. MAPI parameters were global glomerulosclerosis in more than 15% (2 patients), periglomerular fibrosis (4 patients), wall-lumen ratio of arteries >0.5 (2 patients), arteriolar hyalinosis (4 patients), and interstitial scar (3 patients). Multivariable models were used to analyze risk factors for delayed graft function (DGF), prolonged DGF, inferior renal function, and graft loss (P < .05). RESULTS: One hundred fifty-nine KTs were included. Donors (n = 120) were predominantly men (70%) and young adults (37.68 ± 12.50 years old) who suffered a traumatic death (55.8%). Recipients were predominantly men (62.26%) and adults (45.70 ± 15.80 years old) with kidney disease of unknown etiology (39.6%). Low rates of agreement between FS and PS were observed for all MAPI criteria, with kappa values ranging from 0.28 to 0.51. Using FS, no histologic parameter was independently associated with outcomes. After adjustment, glomerulosclerosis was an independent risk factor for prolonged DGF (odds ratio = 6.18: 95% confidence interval, 1.27-30.18) and wall-lumen ratio >0.5 for inferior renal function at 1 year (odds ratio = 4.08; 95% confidence interval, 1.21-13.76). CONCLUSION: Procurement biopsies can be useful to predict inferior outcomes even in kidneys with low MAPI scores.


Subject(s)
Delayed Graft Function , Kidney Diseases/diagnosis , Kidney Transplantation , Transplants/pathology , Adult , Biopsy , Female , Humans , Kidney/pathology , Kidney Diseases/pathology , Kidney Transplantation/adverse effects , Male , Middle Aged , Odds Ratio , Retrospective Studies , Risk Factors , Tissue Donors
13.
Ann Transplant ; 25: e927010, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-33318465

ABSTRACT

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.


Subject(s)
Delayed Graft Function , Kidney Transplantation , Organ Preservation , Adult , Brazil , Delayed Graft Function/epidemiology , Female , Graft Survival , Humans , Incidence , Kidney , Male , Middle Aged , Organ Preservation/methods , Perfusion , Retrospective Studies , Tissue Donors , Young Adult
14.
Transpl Infect Dis ; 22(6): e13376, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32573894

ABSTRACT

Protecting immunosuppressed patients during infectious disease outbreaks is crucial. During this novel coronavirus disease 2019 pandemic, preserving "clean areas" in hospitals assisting organ transplant recipients is key to protect them and to preserve transplantation activity. Evidence suggests that asymptomatic carriers might transmit the SARS-CoV-2, challenging the implementation of transmission preventive strategies. We report a single-center experience using universal SARS-CoV-2 screening for all inpatients and newly admitted patients to an Organ Transplant Unit located in a region with significantly high community-based transmission.


Subject(s)
COVID-19/diagnosis , Carrier State/diagnosis , Cross Infection/prevention & control , Organ Transplantation , Adult , Aged , Brazil , COVID-19/complications , COVID-19/physiopathology , COVID-19/prevention & control , COVID-19 Nucleic Acid Testing , Child , End Stage Liver Disease/complications , Female , Hospital Units , Humans , Kidney Failure, Chronic/complications , Kidney Transplantation , Liver Transplantation , Male , Mass Screening , Middle Aged , Patient Isolation , Personal Protective Equipment , SARS-CoV-2 , Waiting Lists
15.
Transpl Int ; 31(12): 1345-1356, 2018 12.
Article in English | MEDLINE | ID: mdl-29969826

ABSTRACT

There is no evidence of whether everolimus (EVR) reduces cytomegalovirus (CMV) events in patients receiving steroid-free regimens. Besides, studies evaluating a tacrolimus (TAC) and EVR regimen are limited to 1-year follow-up. In this single-center prospective randomized trial, the incidence of CMV and 3-year efficacy and safety outcomes of EVR were compared to those of mycophenolate sodium (MPS) in a steroid-free regimen based on low-exposure TAC. Both groups received rabbit anti-thymocyte globulin (r-ATG) induction (6 mg/kg) and the steroids were withdrawn at day 7. Maintenance immunosuppression consisted of TAC (4-7 ng/ml until month 3 and 2-4 ng/ml thereafter) plus EVR (3-8 ng/ml) in the EVR group (n = 59); and TAC (4-7 ng/ml during all follow-up) plus MPS (1440 mg) in the MPS group (n = 56). The EVR group presented with a lower incidence of CMV events (18.6% vs. 50%, P = 0.001). No differences were observed in biopsy-proven acute rejection (6.8% vs. 3.6%, P = 0.680),graft loss (0.0% vs. 1.8%, P = 0.487),death (6.8% vs. 1.8%, P = 0.365), or estimated glomerular filtration rate at 36 months (61.1 ± 25.4 vs. 66.3 ± 24 ml/min/1.73 m2 , P = 0.369). A higher proportion of patients discontinued MPS treatment (8.5% vs. 26.8%, P = 0.013) for safety issues. In conclusion, EVR was associated with lower rates of CMV events in patients induced with standard dose r-ATG and a maintenance steroid-free regimen based on TAC. This regimen effectively prevented acute rejection and demonstrated a more favorable safety profile. (ClinicalTrials.gov:NCT02084446).


Subject(s)
Cytomegalovirus Infections/complications , Everolimus/therapeutic use , Immunosuppressive Agents/therapeutic use , Kidney Transplantation , Adolescent , Adult , Aged , Cytomegalovirus , Female , Follow-Up Studies , Graft Rejection/prevention & control , Graft Survival/drug effects , Humans , Male , Middle Aged , Prospective Studies , Steroids/therapeutic use , Tacrolimus/therapeutic use , Transplant Recipients , Young Adult
16.
Mycoses ; 61(11): 845-852, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29992629

ABSTRACT

Pneumocystis jirovecii can cause severe potentially life-threatening pneumonia (PCP) in kidney transplant patients. Prophylaxis of patients against PCP in this setting is usually performed during 6 months after transplantation. The aim of this study is to describe the molecular epidemiology of a cluster of PCP in renal transplant recipients in Brazil. Renal transplant patients who developed PCP between May and December 2011 had their formalin-fixed paraffin-embedded (FFPE) lung biopsy samples analysed. Pneumocystis jirovecii 23S mitochondrial large subunit of ribosomal RNA (23S mtLSU-rRNA), 26S rRNA, and dihydropteroate synthase (DHPS) genes were amplified by polymerase chain reaction (PCR), sequenced, and analysed for genetic variation. During the study period, 17 patients developed PCP (only four infections were documented within the first year after transplantation) and six (35.3%) died. Thirty FFPE samples from 11 patients, including one external control HIV-infected patient, had fungal DNA successfully extracted for further amplification and sequencing for all three genes. A total of five genotypes were identified among the 10 infected patients. Of note, four patients were infected by more than one genotype and seven patients were infected by the same genotype. DNA extracted from FFPE samples can be used for genotyping; this approach allowed us to demonstrate that multiple P. jirovecii strains were responsible for this cluster, and one genotype was found infecting seven patients. The knowledge of the causative agents of PCP may help to develop new initiatives for control and prevention of PCP among patients undergoing renal transplant and improve routine PCP prophylaxis.


Subject(s)
Genetic Variation , Kidney Transplantation/adverse effects , Pneumocystis/isolation & purification , Pneumonia, Pneumocystis/microbiology , Postoperative Complications/microbiology , Adult , Brazil , Cross-Sectional Studies , DNA, Fungal/genetics , Female , Genotype , Humans , Male , Middle Aged , Phylogeny , Pneumocystis/classification , Pneumocystis/genetics , Pneumonia, Pneumocystis/diagnosis , Postoperative Complications/diagnosis , Retrospective Studies , Ribosome Subunits, Large/genetics , Young Adult
17.
Ann Transplant ; 23: 166-175, 2018 Mar 09.
Article in English | MEDLINE | ID: mdl-29519995

ABSTRACT

BACKGROUND Initially described as a relatively benign condition, recent studies report graft loss in up to 50% of the patients with post-transplant IgA nephropathy. There is no evidence for the best therapeutic approach, and prognostic factors remain to be elucidated. MATERIAL AND METHODS Single center retrospective analysis of patients >12 years old, with clinically relevant post-transplant IgA nephropathy (proteinuria ≥1.0 g/g and/or graft dysfunction) and ≥6 months follow-up after diagnosis (n=47). RESULTS Living donor transplants represented 85% of cases. Dysmorphic hematuria (100%), blood pressure elevation (95.7%), renal dysfunction (70.2%) and subnephrotic proteinuria (60.6%) predominated at presentation. Using the Oxford Classification, mesangial proliferation was the main histological lesion (91%). Treatment consisted mostly of blockade of the renin angiotensin system (89.4%) and modification of immunosuppression (85.1%), mainly by increasing oral steroids dose (83%), with venous pulse therapy in 63.8% of cases. Partial and complete remission occurred in 48.9% and 17% of cases, respectively. One patient died (sepsis) and 15 patients (31.9%) lost their grafts due to nephropathy. The percentage of decrease in glomerular filtration rate at diagnosis was independently associated with partial remission (HR 0.97, 95% CI 0.94-0.99, p=0.01) and graft loss (HR 1.13, 95% CI 1.06-1.20, p<0.001). Deceased donor (HR 28.04, 95% CI 4.41-178.39, p<0.001) and donor age (HR 1.1, 95% CI 1.04-1.16, p=0.001) were also risk factors for graft loss. CONCLUSIONS Despite treatment, most patients with post-transplant IgA nephropathy in this cohort study presented unfavorable outcomes, and graft dysfunction at diagnosis appeared to be the main prognostic marker.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Glomerulonephritis, IGA/diagnosis , Hematuria/diagnosis , Kidney Transplantation/adverse effects , Adult , Female , Glomerulonephritis, IGA/drug therapy , Glomerulonephritis, IGA/etiology , Hematuria/drug therapy , Hematuria/etiology , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Treatment Outcome , Young Adult
18.
Transpl Infect Dis ; 19(5)2017 Oct.
Article in English | MEDLINE | ID: mdl-28714235

ABSTRACT

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.


Subject(s)
Acute Kidney Injury/etiology , Antitubercular Agents/therapeutic use , Kidney Transplantation/adverse effects , Tuberculosis/complications , Adult , Female , Glomerular Filtration Rate , Humans , Kidney Function Tests , Male , Middle Aged , Retrospective Studies , Risk Factors , Tuberculosis/drug therapy , Tuberculosis/etiology
19.
J Thorac Dis ; 9(1): 166-175, 2017 Jan.
Article in English | MEDLINE | ID: mdl-28203420

ABSTRACT

BACKGROUND: The purpose of this study was to assess the efficacy of open lung biopsy (OLB) in determining the specific diagnosis and the related complications in patients with undiagnosed diffuse pulmonary infiltrates. METHODS: This single center, retrospective study included adult kidney transplant patients who underwent OLB. The patients had diffuse pulmonary infiltrates without definitive diagnoses and failed to respond to empiric antibiotic treatment. We analyzed the number of specific diagnoses, changes in treatment and the occurrence of complications in these patients. A logistic regression was used to determine which variables were predictors of hospital mortality. RESULTS: From April 2010 to April 2014, 87 patients consecutively underwent OLB. A specific diagnosis was reached in 74 (85.1%) patients. In 46 patients (53%), their therapeutic management was changed after the OLB results. Twenty-five (28.7%) patients had complications related to the OLB. The hospital mortality rate was 25.2%. Age, SAPS3 score and complications related to the procedure were independent predictors of all-cause mortality. CONCLUSIONS: OLB is a high-risk procedure with a high diagnostic yield in kidney transplant patients with diffuse pulmonary infiltrates who did not have a definitive diagnosis and who failed to respond to empiric antibiotic treatment. Complications related to OLB were common and were independently associated with intra-hospital mortality.

20.
PLoS One ; 10(12): e0144188, 2015.
Article in English | MEDLINE | ID: mdl-26679933

ABSTRACT

It is unclear if there is an association between the duration of delayed graft function (DGF) and kidney transplant (KT) outcomes. This study investigated the impact of prolonged DGF on patient and graft survivals, and renal function one year after KT. This single center retrospective analysis included all deceased donor KT performed between Jan/1998 and Dec/2008 (n = 1412). Patients were grouped in quartiles according to duration of DGF (1-5, 6-10, 11-15, and >15 days, designated as prolonged DGF). The overall incidence of DGF was 54.2%. Prolonged DGF was associated with retransplantation (OR 2.110, CI95% 1.064-4.184,p = 0.033) and more than 3 HLA mismatches (OR 1.819, CI95% 1.117-2.962,p = 0.016). The incidence of acute rejection was higher in patients with DGF compared with those without DGF (36.2% vs. 12.2%, p<0.001). Compared to patients without DGF, DGF(1-5), DGF(6-10), and DGF(11-15), patients with prolonged DGF showed inferior one year patient survival (95.2% vs. 95.4% vs. 95.5% vs. 93.4% vs. 88.86%, p = 0.003), graft survival (91% vs. 91.4% vs. 92% vs. 88.7% vs. 70.5%, p<0.001), death-censored graft survival (95.7% vs. 95.4% vs. 96.4% vs. 94% vs. 79.3%, p<0.001), and creatinine clearance (58.0±24.6 vs. 55.8±22.2 vs. 53.8±24.1 vs. 53.0±27.2 vs. 36.8±27.0 mL/min, p<0.001), respectively. Multivariable analysis showed that prolonged DGF was an independent risk factor for graft loss (OR 3.876, CI95% 2.270-6.618, p<0.001), death censored graft loss (OR 4.103, CI95% 2.055-8.193, p<0.001), and death (OR 3.065, CI95% 1.536-6.117, p = 0.001). Prolonged DGF, determined by retransplantation and higher HLA mismatches, was associated with inferior renal function, and patient and graft survivals at one year.


Subject(s)
Delayed Graft Function , Graft Survival , Kidney Transplantation , Adult , Female , Humans , Kidney Function Tests , Male , Middle Aged , Risk Factors , Treatment Outcome , Young Adult
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