Cohort Of Kidney Transplant Recipients Research Articles

Urinary vitronectin identifies patients with high levels of fibrosis in kidney grafts

BackgroundIn kidney transplantation, fibrosis represents the final and irreversible consequence of the pathogenic mechanisms that lead to graft failure, and in the late stages it irremediably precedes the loss of renal function. The invasiveness of kidney biopsy prevents this condition from being frequently monitored, while clinical data are rather unspecific. The objective of this study was to find noninvasive biomarkers of kidney rejection.MethodsWe carried out proteomic analysis of the urinary Extracellular Vesicles (uEVs) from a cohort of kidney transplant recipients (n = 23) classified according to their biopsy-based diagnosis and clinical parameters as interstitial fibrosis and tubular atrophy (IFTA), acute cellular rejection (ACR), calcineurin inhibitors toxicity (CNIT) and normal kidney function (NKF).ResultsShotgun mass spectrometry of uEV-proteins identified differential expression of several proteins among these different groups. Up to 23 of these proteins were re-evaluated using targeted proteomics in a new independent cohort of patients (n = 41) classified in the same diagnostic groups. Among other results, we found a differential expression of vitronectin (VTN) in patients displaying chronic interstitial and tubular lesions (ci and ct mean > 2 according to Banff criteria). These results were further confirmed by a pilot study using enzyme-linked immunosorbent assay (ELISA).ConclusionUrinary vitronectin levels are a potential stand-alone biomarker to monitor fibrotic changes in kidney transplant recipients in a non-invasive fashion.

Integrative Analysis of Prognostic Biomarkers for Acute Rejection in Kidney Transplant Recipients.

Noninvasive biomarkers may predict adverse events such as acute rejection after kidney transplantation and may be preferable to existing methods because of superior accuracy and convenience. It is uncertain how these biomarkers, often derived from a single study, perform across different cohorts of recipients. Using a cross-validation framework that evaluates the performance of biomarkers, the aim of this study was to devise an integrated gene signature set that predicts acute rejection in kidney transplant recipients. Inclusion criteria were publicly available datasets of gene signatures that reported acute rejection episodes after kidney transplantation. We tested the predictive probability for acute rejection using gene signatures within individual datasets and validated the set using other datasets. Eight eligible studies of 1454 participants, with a total of 512 acute rejections episodes were included. All sets of gene signatures had good positive and negative predictive values (79%-96%) for acute rejection within their own cohorts, but the predictability reduced to <50% when tested in other independent datasets. By integrating signature sets with high specificity scores across all studies, a set of 150 genes (included CXCL6, CXCL11, OLFM4, and PSG9) which are known to be associated with immune responses, had reasonable predictive values (varied between 69% and 90%). A set of gene signatures for acute rejection derived from a specific cohort of kidney transplant recipients do not appear to provide adequate prediction in an independent cohort of transplant recipients. However, the integration of gene signature sets with high specificity scores may improve the prediction performance of these markers.

Acute Kidney Injury in a Predominantly African American Cohort of Kidney Transplant Recipients With COVID-19 Infection.

Renal involvement in severe or critical acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is frequent. Acute kidney injury (AKI) in African American (AA) kidney transplant recipients (KTRs) with COVID-19 is not well described. We report our experience with a predominantly AA cohort (79%) of KTRs with COVID-19 infections in the Detroit Metropolitan area. In this retrospective, single-center study, we identified 39 KTRs who tested positive for SARS-CoV-2 between March 16 and April 25, 2020. Data from electronic medical records were retrieved and compared between KTRs without AKI and KTRs with AKI. One patient was excluded due to delayed graft function. Final analysis of AKI in KTRs with proven COVID-19 was done on 38 patients of which 30 were AA (79%). AKI occurred in 71.1% of COVID-19 KTRs (n = 27), of whom 6 (22.2%) patients required HD. The incidence of AKI in our cohort was 71% (27/38). AKI rate among AA was 76.7% versus 50% in non-AA cohort (P = 0.195). In a univariate logistic regression analysis, AA race was not significantly associated with AKI odds ratio (3.4; CI, 0.68-17.4; P = 0.14). After risk adjustment by race, patients with diabetes showed a significantly higher risk of AKI (adjusted odds ratio, 19.85; CI, 1.65-58.66; P = 0.012). KTRs with AKI had more preexisting renin angiotensin aldosterone system inhibitor use than KTRs without AKI (P = 0.03). KTRs infected with SARS-CoV-2 have a high incidence of AKI, with associated increased morbidity and mortality. Although no racial differences in mortality were noted in our KTRs with AKI, we await data from registries to help elucidate this difference.

Early cytomegalovirus DNAemia and antiviral dose adjustment in high vs intermediate risk kidney transplant recipients.

Cytomegalovirus (CMV) infection continues to negatively affect outcomes for solid organ transplant recipients, despite the advent of strategies for preemptive surveillance and prophylaxis. The impact is especially great for CMV seronegative recipients of donor seropositive organs, who typically lack the ability to control CMV infection at the time of transplantation. We reviewed episodes of CMV DNAemia in a modern cohort of kidney transplant recipients over a 3-year period at a high-volume transplant center to investigate the frequency of DNAemia during antiviral prophylaxis. Despite receipt of antiviral prophylaxis per current guidelines, 75 cases of CMV DNAemia were observed in the first 100days after transplantation. For high risk patients, median time to DNAemia was 75days after transplantation, and the majority of patients had experienced dose-reduction of valganciclovir due to renal insufficiency. Review of CMV seropositive intermediate risk patients demonstrated DNAemia occurring earlier after transplantation compared with high risk patients with a median time of 64days (P=.029). The impact of valganciclovir dose adjustment was less notable in the intermediate risk group. Guidelines recommend beginning routine surveillance for CMV after the completion of antiviral prophylaxis. Our findings suggest that closer monitoring may be beneficial, especially for high risk patients at risk for DNAemia. Patients requiring dose adjustment of valganciclovir due to renal insufficiency may be at increased risk for CMV DNAemia. Improved methods for CMV prophylaxis and evaluation of immunologic risk for CMV DNAemia and disease are needed to improve patient outcomes after kidney transplantation.

Mortality from cancer is not increased in elderly kidney transplant recipients compared to the general population: a competing risk analysis.

The impact of cancer on death of elderly kidney transplant recipients has been extensively investigated, but with conflicting results. Unlike their younger counterparts, in elderly kidney transplant recipients cardiovascular and infectious disease may outweigh cancer in causing the patient's death. Using competing risk analysis on a large retrospective cohort of kidney transplant recipients, we estimated the cause-specific cumulative incidence and hazard of death in different age categories and calculated standardized mortality ratios (SMRs) to compare mortality rates with the general population. Six thousand seven hundred eighty-nine kidney transplant recipients were followed-up for a median of 9years. Ten years after transplantation, in transplant recipients aged 20-39, 40-59, and 60+, the cumulative incidence of cancer-related death was 0.6 (95% confidence interval [CI]: 0.3-1.0), 2.9 (2.3-3.6) and 5.3% (3.5-7.5), whereas the SMR was 9.1 (5.5-15.0), 2.0 (1.6-2.5), and 0.8 (0.6-1.0), respectively. At variance with young recipients, the hazard and the cumulative incidence of cardiovascular-related death in elderly recipients was well above that of cancer-related death. Relative to the general population, cancer-related death is increased in young but not in elderly kidney transplant recipients because of the more marked increased incidence of competing cause of death in the latter category.

Bloodstream infections by gram-negative bacteria in kidney transplant patients: Incidence, risk factors, and outcome.

Kidney transplant recipients (KTRs) are at increased risk of infections. The aims of this study were to describe the incidence of bloodstream infections (BSIs) by gram-negative bacteria in a cohort of KTRs, the risk factors for BSI due to multi-drug-resistant (MDR) gram-negative bacteria, and the predictors for unfavorable outcome, defined as death or nephrectomy or return to dialysis, within 30days from BSI. We conducted a retrospective cohort study at the renal transplant unit of a tertiary care hospital in Athens, Greece. In a total of 1962 KTRs, we recorded 195 BSI episodes in 182 single patients (male/female=97/85), with a median (interquartile range) age of 57.2 (44-64.9) years. The incidence was 1.393/100 patient-years. The most common source of infection was urinary tract (70.9%), and Escherichia coli (63.7%) was the most common pathogen. 19.2% of the infecting organisms were MDR; previous antibiotic use (OR 8.2; CI 2.1-32.9) and previous stay in the intensive care unit (OR 34.2; CI 1.6-730.2) were associated with MDR BSIs. 6% of patients died, and 2.2% underwent nephrectomy, while no patients had to return to dialysis. Diabetes mellitus (OR 8.1; 95% CI 1.3-50.3), Pseudomonas aeruginosa BSI (OR 46.1; 95% CI 3.9-552.3), and septic shock (OR 46.7; 95% CI 1.7-1304.9) were independent predictors of unfavorable outcome. Bloodstream infections in KTRs have a significant impact on allograft and patients outcome.

Characteristics and Outcomes of Kidney Transplant Recipients Requiring High-Acuity Care After Transplant Surgery: A 10-Year Single-Center Study.

ObjectiveTo study the characteristics and outcomes of a cohort of kidney transplant recipients who required high-acuity care after transplant surgery.Patients and MethodsAll adult (aged ≥18 years) solitary kidney transplant recipients from January 1, 2007, through December 31, 2016, were screened and those who required high-acuity care within the same hospitalization were enrolled. Patient demographic and clinical data were collected from the departmental database and electronic DataMart.ResultsOf 1525 patients, 266 (17.4%) required high-acuity care after the kidney transplant operation: 166 (62.4%) directly from the operating room and 100 (37.6%) after an interval during the same hospitalization. Overall, 2 main indications were hypotension (n=87; 32.7%) and cardiac rhythm disturbances (n=83; 31.2%). Recipients in the direct admission group had higher medium body mass index (31.0 [interquartile range, 26.6-36.0] vs 28.0 [interquartile range, 24.3-32.4] kg/m2; P<.001) and were more likely to have undergone a concomitant procedure with the transplant surgery. Overall, in-hospital mortality was 1.9% (n=5).ConclusionIn contemporary practice, patients with higher body mass index are more likely to require high-acuity care immediately after kidney transplant surgery. The most common reasons are hypotension and cardiac rhythm disorders. The overall intensive care unit mortality rate of these patients is low. However, these patients are at risk for graft loss and death in the long term compared with patients who do not require intensive care unit care after transplant surgery.

Respiratory and Gastrointestinal COVID-19 Phenotypes in Kidney Transplant Recipients.

Coronavirus infectious disease 2019 (COVID-19) pandemic has posed at risk the kidney transplant (KT) population. We describe clinical pictures, risk factors for death, and chances to recovery in a large cohort of KT recipients with COVID-19. Inclusion in a Spanish prospectively filled registry was allowed for KT cases with confirmed COVID-19. Outcomes were assessed as in-hospital mortality or recovery. The study population comprised of 414 patients. Fever, respiratory symptoms, and dyspnea were the most frequent COVID-19-related symptoms, and 81.4% of them had pneumonia. More than one-third of patients showed digestive symptoms at diagnosis, combinations of nausea, vomiting, and diarrhea. Most patients were hospitalized, 12.1% in intensive care units, and 17.6% needed ventilator support. Treatment for COVID-19 included frequently hydroxychloroquine, azithromycin, high-dose steroids, lopinavir/ritonavir, and tocilizumab. After a mean follow-up of 44 days, the fatality rate was 26.3%. Pneumonia without gastrointestinal symptoms was associated with a 36.3% mortality (respiratory phenotype), and gastrointestinal symptoms without pneumonia with a 5.3% mortality (gastrointestinal phenotype). The mixed pneumonia and gastrointestinal phenotype showed an intermediate mortality of 19.5% (mixed phenotype). Multivariate Cox regression analysis showed that age and pneumonia were independently associated with death, whereas the gastrointestinal phenotype was associated with recovery. COVID-19 is frequent among the KT population. Advanced age and pneumonia are the main clinical features associated with a high-mortality rate. Gastrointestinal disease is associated with a more benign course and lower mortality.

Outcome implications of benzodiazepine and opioid co-prescription in kidney transplant recipients.

The outcomes of benzodiazepine and opioid co-prescription are not well-defined in transplant populations. We examined linked national transplant registry and pharmaceutical records to characterize benzodiazepine and opioid use in the years before and after transplant in large US cohort of kidney transplant recipients (2007-2016; N=98620), and associations (adjusted hazard ratio, LCL aHRUCL ) with death and graft failure. Among the cohort, 15.6% filled benzodiazepine prescriptions in the year before transplant, and 14.0% filled benzodiazepine prescriptions in the year after transplant (short-acting, 9.5%; long-acting, 3.3%; both 1.1%). Use of short-acting benzodiazepines in the year before transplant was associated with a 22% increased risk of death in the year after transplant (aHR, 1.08 1.221.38 ), while use of all classes in the year after transplant was associated with increased risk of death from >1 to 5years (aHR: short-acting 1.29 1.391.48 ; long-acting 1.12 1.251.40 ; both 1.46 1.742.07 ). Recipients who used benzodiazepines were also more likely to fill opioid prescriptions. Recipients who filled both classes of benzodiazepine and the highest level of opioids had a 2.9-fold increased risk of death compared to recipients who did not use either. Co-prescription of benzodiazepines and opioids in kidney transplant recipients is associated with increased mortality. Ongoing research is needed to understand mechanisms of risk relationships.

Early and recurrent hospitalization after kidney transplantation: Analysis of a contemporary canadian cohort of kidney transplant recipients.

Hospital readmission is a common occurrence following kidney transplantation, but less is known about the predictors of early and recurrent hospitalization. We analyzed a cohort of adult kidney transplant recipients in Nova Scotia, Canada, from January 2010 to December 2015. Readmission rates for 30days, 6months, and 1year were calculated as a proportion of total transplants. Factors independently associated with early readmission were investigated using multivariable Cox hazards models with multivariable Anderson-Gill Cox models being used for factors independently associated with recurrent readmission. Of the 213 patients included, 41 (19.2%), 78 (36.6%), and 88 (41.3%) were readmitted to hospital within 30days, 6months, and 1year, respectively. On multivariable analyses, a history of congestive heart failure (HR 1.741, 95% CI 1.039-2.918), peptic ulcer disease (HR 2.290, 95% CI 1.054-4.973), and liver disease (HR 2.492, 95% CI 1.162-5.344) was associated with higher risk of first rehospitalization. Recurrent hospital admission was associated with initial hospital duration≥8days (HR 2.140, 95% CI 1.265-3.618), congestive heart failure (HR 1.366, 95% CI 1.044-1.787), and liver disease (HR 1.785, 95% CI 1.257-2.534). Increasing duration of initial hospitalization, congestive heart failure, and liver disease are important to consider when evaluating a patient's risk for recurrent readmission following kidney transplant.

Characterization of a Unique γδ T-Cell Subset as a Specific Marker of Cytomegalovirus Infection Severity

Cytomegalovirus (CMV) is a major infectious cause of death and disease after transplantation. We have previously demonstrated that the tissue-associated adaptive Vδ2neg γδ T cells are key effectors responding to CMV and associated with recovery, contrasting with their innatelike circulating counterparts, the Vγ9posVδ2pos T cells that respond to phosphoantigens but not to CMV. A third Vγ9negVδ2pos subgroup with adaptive functions has been described in adults. In the current study, we demonstrate that these Vγ9negVδ2pos T cells are also components of the CMV immune response while presenting with distinct characteristics from Vδ2neg γδ T cells. In a cohort of kidney transplant recipients, CMV seropositivity was the unique clinical parameter associated with Vγ9negVδ2pos T-cell expansion and differentiation. Extensive phenotyping demonstrated their substantial cytotoxic potential and activation during acute CMV primary infection or reinfection. In vitro, Vγ9negVδ2pos T cells responded specifically to CMV-infected cells in a T-cell receptor-dependent manner and through strong interferon γ production. Finally, Vγ9negVδ2pos T cells were the only γδ T-cell subset in which expansion was tightly correlated with the severity of CMV disease. To conclude, our results identify a new player in the immune response against CMV and open interesting clinical perspectives for using Vγ9negVδ2pos T cells as an immune marker for CMV disease severity in immunocompromised patients.

COVID-19 Infection in Kidney Transplant Recipients: A Single-Center Case Series of 22 Cases From Belgium

Rationale & ObjectiveThe world is facing a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although kidney transplant recipients are at increased risk for viral infections, the impact of their chronic immunosuppressed status on the risk for acquiring coronavirus disease 2019 (COVID-19) and disease severity is unknown.Study DesignAll cases of COVID-19 infection in our cohort of kidney transplant recipients were prospectively monitored. Clinical features, management, and outcomes were recorded. A standard strategy of immunosuppression minimization was applied: discontinue the antimetabolite drug and reduce trough levels of calcineurin or mammalian target of rapamycin inhibitors. Unless contraindicated, hydroxychloroquine was administered only to hospitalized patients.Setting & Participants22 COVID-19 infections were diagnosed in our cohort of 1,200 kidney transplant recipients.ResultsMost common initial symptoms included fever, cough, or dyspnea. 18 (82%) patients required hospitalization. Of those patients, 3 had everolimus-based immunosuppression. Computed tomography of the chest at admission (performed in 15 patients) showed mild (n = 3), moderate (n = 8), extensive (n = 1), severe (n = 2), and critical (n = 1) involvement. Immunosuppression reduction was initiated in all patients. Hydroxychloroquine was administered to 15 patients. 11 patients required supplemental oxygen; 2 of them were admitted to an intensive care unit (ICU) with mechanical ventilation. After a median of 10 days, 13 kidney transplant recipients were discharged, 2 were hospitalized in non-ICU units, 1 was in the ICU, and 2 patients had died.LimitationsSmall sample size and short follow-up.ConclusionsThe clinical presentation of COVID-19 infection was similar to that reported in the general population. A standard strategy of immunosuppression minimization and treatment was applied, with 11% mortality among kidney transplant recipients hospitalized with COVID-19 infection.

P0879EARLY STEROID WITHDRAWAL HAS A POSITIVE EFFECT ON BONE KIDNEY TRANSPLANT RECIPIENTS: A PROPENSITY SCORE STUDY WITH INVERSE PROBABILITY-OF-TREATMENT WEIGHTING

Abstract Background and Aims Long-term corticosteroid use after kidney transplantation is associated with a decrease in bone mineral density and a high fracture risk. We hypothesized that patients with early steroid withdrawal (ESW) would display a gain in bone mineral density in the year following kidney transplantation, when compared with patients on long-term corticosteroid therapy (LTCT). Method In a cohort of kidney transplant recipients, 317 patients were included between 2012 and 2018. Dual-energy X-ray absorptiometry was performed 1 and 12 months after transplantation. The data were analyzed using linear regression with inverse probability-of-treatment weighting based on a propensity score. Results One year after transplantation, the gain in bone mineral density was significantly greater in recipients with ESW than in recipients on LTCT for the lumbar spine (+0.027 g/cm, P &amp;lt; 0.001) and the femoral neck (+0.021 g/cm, P = 0.035). Among patients with ESW, (i) none had osteoporosis, (ii) the percentage with normal bone mineral density increased from 35.0% at month 1 to 56.4% at month 12, and (ii) the percentage with osteopenia fell from 52.5% to 43.6%. In patients undergoing LTCT, the fracture incidence was 14.5 per 1000 person-years. None of the patients in the ESW group experienced a fracture. Cardiovascular risk factors were more prominent in the LTCT group relative to the ESW group: patients in LTCT group (i) were more likely to have high blood pressure (p&amp;lt;0.001), (ii) gained more weight gain (p=0.032) and (iii) displayed a greater increase in serum triglyceride levels (p=0.004).The acute rejection rate was similar in the two groups. Conclusion Early steroid withdrawal is associated with a spontaneous increase in bone mineral density at 12 months post-transplantation (relative to patients on long-term steroid therapy), with a reduction in several cardiovascular risk factors and does not appear to harm the graft.

P0653THE USE OF URINARY EPIDERMAL GROWTH FACTOR FOR EVALUATION OF KIDNEY GRAFT FUNCTION

Abstract Background and Aims Follow-up after kidney transplantation requires repeated, reliable glomerular filtration rate (GFR) measurements. Measured GFR (mGFR), using urinary or plasma clearance of an exogenous filtration marker such as iohexol, provides precise measurements but are expensive and time consuming. Instead, estimated GFR (eGFR) based on serum creatinine is most commonly used in clinical practice. Epidermal growth factor is produced in the kidney and promotes tubular cell regeneration and recovery of kidney function after injury. Low levels of urinary epidermal growth factor (uEGF) are linked to progression of chronic kidney disease and increased risk of kidney graft failure. The aim of this study was to investigate uEGF as an additional marker to evaluate graft function in kidney transplant recipients (KTRs). Method Participants in the Omega-3 fatty acids in Renal Transplantation (ORENTRA) trial were examined with mGFR by iohexol clearance at 1 year after kidney transplantation. The concentration of iohexol in serum was measured 3 and 4 hours after iv injection. On the same day, fasting blood and urine samples were obtained in the morning. Serum creatinine was measured and eGFR calculated with the MDRD formula. uEGF and a pre-specified selection of inflammation and fibrosis markers were measured with multiplex immunoassay technique and normalized with urinary creatinine. Principal component analysis (PCA) was used to explore clustering of markers. Correlations were calculated with Pearson’s correlation coefficient R. Results Fifty-nine participants had complete measurements of mGFR (57.2 ± 15.2 mL/min/1.73m2), eGFR (68.6 ± 23.0 mL/min/1.73m2) and uEGF. The correlation between mGFR and eGFR was strong (R=0.783, P&amp;lt;0.001). Measurements of uEGF had a coefficient of variation below 10% for all participants, with a mean value of 22.0 ± 12.1 μg/g creatinine. There was a significant correlation between mGFR and uEGF (R=0.678, P&amp;lt;0.001). The component score of uEGF and eGFR calculated with PCA (74% of variance) had the strongest correlation with mGFR (R=0.845, P&amp;lt;0.001). Conclusion Combining uEGF with eGFR into one component score by PCA gives a greater correlation with mGFR compared to eGFR alone in this cohort of KTRs. These findings need to be validated in other patient populations.

Seeing the Forest for the Trees: Random Forest Models for Predicting Survival in Kidney Transplant Recipients.

Seeing the Forest for the Trees: Random Forest Models for Predicting Survival in Kidney Transplant Recipients.

Use of the Living Kidney Donor Profile Index in the Canadian Kidney Transplant Recipient Population: A Validation Study.

Background:The Living Kidney Donor Profile Index (LKDPI) was derived in a cohort of kidney transplant recipients (KTR) from the United States to predict the risk of total graft failure. There are important differences in patient demographics, listing practices, access to transplantation, delivery of care, and posttransplant mortality in Canada as compared with the United States, and the generalizability of the LKDPI in the Canadian context is unknown.Objective:The purpose of this study was to externally validate the LKDPI in a large contemporary cohort of Canadian KTR.Design:Retrospective cohort validation study.Setting:Toronto General Hospital, University Health Network, Toronto, Ontario, CanadaPatients:A total of 645 adult (≥18 years old) living donor KTR between January 1, 2006 and December 31, 2016 with follow-up until December 31, 2017 were included in the study.Measurements:The predictive performance of the LKDPI was evaluated. The outcome of interest was total graft failure, defined as the need for chronic dialysis, retransplantation, or death with graft function.Methods:The Cox proportional hazards model was used to examine the relation between the LKDPI and total graft failure. The Cox proportional hazards model was also used for external validation and performance assessment of the model. Discrimination and calibration were used to assess model performance. Discrimination was assessed using Harrell’s C statistic and calibration was assessed graphically, comparing observed versus predicted probabilities of total graft failure.Results:A total of 645 living donor KTR were included in the study. The median LKDPI score was 13 (interquartile range [IQR] = 1.1, 29.9). Higher LKDPI scores were associated with an increased risk of total graft failure (hazard ratio = 1.01; 95% confidence interval [CI] = 1.0-1.02; P = .02). Discrimination was poor (C statistic = 0.55; 95% CI = 0.48-0.61). Calibration was as good at 1-year posttransplant but suboptimal at 3- and 5-years posttransplant.Limitations:Limitations include a relatively small sample size, predicted probabilities for assessment of calibration only available for scores of 0 to 100, and some missing data handled by imputation.Conclusions:In this external validation study, the predictive ability of the LKDPI was modest in a cohort of Canadian KTR. Validation of prediction models is an important step to assess performance in external populations. Potential recalibration of the LKDPI may be useful prior to clinical use in external cohorts.

THYROID DISORDERS PREVALENCE IN A COHORT OF KIDNEY TRANSPLANT RECIPIENTS.

As the life expectancy prolongs, malignancy has become an important issue in renal transplant recipients (RTRs). Thyroid cancer is the most common endocrine malignancy with ongoing increase in incidence all over the world. This is a cross-sectional study that investigates the thyroid disorders and the prevalence of thyroid nodule and cancer in RTRs. 204 RTRs were evaluated for the thyroid diseases with ultrasonography, serum thyroid stimulating hormone, free T4, free T3 levels, anti-thyroglobulin antibody and anti-thyroid peroxidase antibody levels; FNAB was carried if required. 191 patients (94.1%) had normal thyroid function. Subclinical hypothyroidism was diagnosed in 11 patients, subclinical hyperthyroidism in 1 patient and low T3 syndrome in 4 patients. The FNAB was performed in 17 (27.9%) from 61 patients with thyroid nodule. The cytological examination of biopsy materials revealed that 2 (11.8%) nodules were suspicious for malignancy, 13 (76.5%) were benign, and 2 (11.8%) with non diagnostic cytology. Thyroid cancer prevalence was 0.2% in Turkey but we detected that 0.98% of RTRs had thyroid cancer. Screening the RTRs for thyroid disorders is necessary, so that early diagnosis and appropriate treatment of thyroid disease and cancer may improve the quality of life.

Early steroid withdrawal has a positive effect on bone in kidney transplant recipients: a propensity score study with inverse probability-of-treatment weighting.

Background:Long-term corticosteroid use after kidney transplantation is associated with a decrease in bone mineral density (BMD) and a high fracture risk. We hypothesized that patients with early steroid withdrawal (ESW) would display a gain in BMD in the year following kidney transplantation, when compared with patients on long-term corticosteroid therapy.Methods:In a cohort of kidney transplant recipients, 356 patients were included between 2012 and 2019. Dual-energy X-ray absorptiometry was performed 1 and 12 months after transplantation. The data were analyzed using linear regression with inverse probability-of-treatment weighting (based on a propensity score).Results:At 1 year after transplantation, the gain in BMD was significantly greater in recipients with ESW than in recipients on long-term corticosteroid therapy for the lumbar spine (+0.036 g/cm2, p < 0.001) and the femoral neck (+0.020 g/cm2, p = 0.035). Among patients with ESW, (i) none had osteoporosis, (ii) the percentage with normal BMD increased from 33.3% at month 1 to 54.4% at month 12, and (iii) the percentage with osteopenia fell from 56.2% to 45.6%. In patients undergoing long-term corticosteroid therapy, the fracture incidence was 13.5 per 1000 person-years. None of the patients in the ESW group experienced a fracture.Conclusion:ESW has a positive effect on bone in kidney transplant recipients.

Renal transplant patients with preformed anti-HLA antibodies: early biopsy findings and clinical outcomes.

Introduction:Renal fibrosis is the end point of a process that begins at transplant, with ischemia reperfusion and early inflammation, and progresses over time with immunological and non-immunological phenomena. Early identification of morphological markers and intervention could improve graft function and survival.Objective:to evaluate the correlation between intensity and specificity of pre-transplant anti-HLA antibodies and kidney allograft pathology in order to identify early risk factors or markers of allograft dysfunction.Methods:A retrospective cohort of kidney transplant recipients with pre-transplant anti-HLA antibodies who underwent graft biopsy within the first two years post-transplant was divided into two groups according to the specificity of anti-HLA antibodies: nonspecific (non-DSA, n = 29) and specific (DSA+, n = 16). Kidney graft pathology, renal function, and proteinuria were analyzed.Results:general characteristics were similar in both groups, except for the higher dose of thymoglobulin in DSA+ group (p < 0.05). The non-DSA group had higher scores for glomerulosclerosis, interstitial inflammation (i) and interstitial fibrosis (ci) (p < 0.05) and higher incidence of cell-mediated acute rejection. No statistical difference in incidence of antibody-mediated rejection, renal function, and proteinuria was observed during follow up.Discussion and conclusions:the difference in inflammation scores and interstitial fibrosis may be associated to the higher incidence of acute cell-mediated rejection and polyomavirus nephropathy in the Non-DSA group. We also should take into account the protective effect of higher doses of thymoglobulin, reducing ischemia reperfusion injury in the DSA+ group. The short follow-up might have been insufficient to detect long-term changes in allograft tissue, renal function, and proteinuria.

BK Polyomavirus‐associated nephropathy managed by screening policy in a real‐life setting

BK polyomavirus-associated nephropathy (PyVAN) is an important complication after kidney transplantation. Prevalence ranges from 1% to 10%, and graft loss occurs in approximately 50% of the cases. There is no effective treatment, so early viral detection with immunosuppression tapering is the current strategy to prevent PyVAN. To verify the frequency of PyVAN in a single center and evaluate the response to immunosuppressive adjustments through graft survival analysis. Retrospective evaluation of a cohort of kidney transplant recipients with biopsy-proven PyVAN, compared with no-PyVAN patients regarding clinical aspects, immunosuppression, and graft survival over at least 2years. There were 1404 kidney transplants analyzed in the study period, 58 with biopsy-proven PyVAN. Cumulative incidence was 4.1%. Median time from transplantation to PyVAN diagnosis was 6 (1-41) months. PyVAN was associated with recipient male gender (P=.041) and deceased donation (P=.005). Graft survival was inferior for PyVAN compared to no-PyVAN patients, 81.8% vs 75.2%, P=.019. Thirteen (22.4%) PyVAN patients lost their grafts, nine (15.5%) losses attributed to BKPyV infection. Three patients with BKPyV-associated graft losses were submitted to a successful second kidney transplant, with no evidence of viral replication during follow-up. PyVAN still is an important cause of kidney graft failure. Even though implementing active vigilance and immunosuppressive adjustment, this real-life single-center study demonstrated inferior graft survival in PyVAN patients compared to non-PyVAN.