Kidney Transplant Recipients Patients Research Articles

Hybrid and SARS-CoV-2-vaccine immunity in kidney transplant recipients

Kidney transplant recipients (KTR) are at high risk for severe COVID-19 and have demonstrated poor response to vaccination, making it unclear whether successive vaccinations offer immunity and protection. We conducted a serologically guided interventional study where KTR patients that failed to seroconvert were revaccinated and also monitored seroconversion of KTR following the Norwegian vaccination program. We analysed IgG anti-RBD Spike responses from dose 2 (n=432) up to after the 6th (n=37) mRNA vaccine dose. The frequency and phenotype of Spike-specific T and B cell responses were assessed in the interventional cohort after 3-4 vaccine doses (n=30). Additionally, we evaluated the Specific T and B cell response to breakthrough infection (n=32), measured inflammatory cytokines and broadly cross-neutralizing antibodies, and defined the incidence of COVID-19-related hospitalizations and deaths. The Norwegian KTR cohort has a male dominance (2323 males, 1297 females), PBMC were collected from 114 male and 78 female donors. After vaccine dose 3, most KTR developed Spike-specific T cell responses but had significantly reduced Spike-binding B cells and few memory cells. The B cell response included a cross-reactive subset that could bind Omicron VOC, which expanded after breakthrough infection (BTI) and gave rise to a memory IgG+B cell response. After BTI, KTR had increased Spike-specific T cells, emergent non-Spike T and B cell responses, and a systemic inflammatory signature. Late seroconversion occurred after doses 5-6, but 38% (14/37) of KTR had no detectable immunity even after multiple vaccine doses. Boosting vaccination can induce Spike-specific immunity that may expand in breakthrough infections highlighting the benefit of vaccination to protect this vulnerable population. CEPI and internal funds.

BNT162b2 Elicited an Efficient Cell-Mediated Response against SARS-CoV-2 in Kidney Transplant Recipients and Common Variable Immunodeficiency Patients.

SARS-CoV-2 vaccination is the standard of care for the prevention of COVID-19 disease. Although vaccination triggers both humoral and cellular immune response, COVID-19 vaccination efficacy is currently evaluated by measuring antibodies only, whereas adaptative cellular immunity is unexplored. Our aim is to test humoral and cell-mediated response after three doses of BNT162b vaccine in two cohorts of fragile patients: Common Variable Immunodeficiency (CVID) patients and Kidney Transplant Recipients (KTR) patients compared to healthy donors. We enrolled 10 healthy controls (HCs), 19 CVID patients and 17 KTR patients. HC BNT162b third dose had successfully mounted humoral immune response. A positive correlation between Anti-Spike Trimeric IgG concentration and neutralizing antibody titer was also observed. CVID and KTR groups showed a lower humoral immune response compared to HCs. IFN-γ release induced by epitopes of the Spike protein in stimulated CD4+ and CD8+ T cells was similar among vaccinated HC, CVID and KTR. Patients vaccinated and infected showed a more efficient humoral and cell-mediated response compared to only vaccinated patients. In conclusion, CVID and KTR patients had an efficient cell-mediated but not humoral response to SARS-CoV-2 vaccine, suggesting that the evaluation of T cell responses could be a more sensitive marker of immunization in these subjects.

#4448 HUMORAL RESPONSE TO SARS-COV-2 AFTER FIVE SUCCESSIVE DOSES OF MRNA VACCINE AND PASSIVE IMMUNIZATION THERAPY IN STABLE KIDNEY TRANSPLANTATION PATIENTS

Abstract Background and Aims The poor humoral response after vaccination against SARS-CoV-2 in kidney transplant recipients (KT) led to the approval of new doses, the fifth being the last administered, and to the development of drugs for passive immunization. Our aim is to analyze the humoral immune response and the evolution of the antispike (antiS) antibody titer after 5 doses of mRNA vaccine against SARS-CoV-2 and the administration of pre-exposure prophylaxis. Method We performed a prospective cohort study of stable KT patients from our center who received 5 doses of a mRNA vaccine from March 2021 to December 2022. KT recipients with less than 6 months after transplantation and with active oncological or hematologic disease were excluded. We determined antiS titers (Abbott SARS-CoV-2 IgG chemiluminescent microparticle immunoassay) at baseline and one month after the second, third, fourth and fifth doses. We consider seroconversion if antiS titer was greater than 260 BAU/mL. We compared humoral response after 2, 3, 4 and 5 doses. Results We included 18 KT. Mean age was 59.8 years and 72.2% were male. The median time from KT to the first vaccine dose was 45 months, between the second and third 4 months and 6 months between the third and fourth and fourth and fifth doses. Seroconversion rate was 11.1% after 2 doses, 50% after the third, 72% after the fourth, and 94.4% after the fifth (p < 0.001). One TR did not develop antibodies after 5 doses. Two KT that had not seroconverted after the fourth also received passive immunization (tixagevimab-cilgavimab), maintaining high antiS titers 3 and 5 months after administration. The KT who seroconverted after 2 doses doubled the antiS titer after the third (1070 vs. 2168 BAU/mL; p = 0.180), in those who seroconverted after 3 doses it increased by 380% after the fourth (802 [587-2563] BAU/mL vs. 3116 [1004-5680] BAU/mL; p = 0.028) and in those who seroconverted after 4 doses, the antiS titer increased by 60% (1067 [100-2896] BAU/mL vs. 1762 [639-2684] BAU/mL) after the fifth (p = 0.213). No patients had neither acute rejection nor serious adverse effects. Conclusion Successive doses of vaccination increased the development and titer of antibodies against SARS-CoV-2 in KT. However the administration of new doses is necessary, especially bivalent vaccines, which increase protection against new variants of the virus. We should identify those patients who do not generate an adequate humoral response in order to offer them other prevention strategies.

Thyroid, Gonadal and Adrenal Dysfunction in Kidney Transplant Recipients: A Review for the Clinician

While chronic kidney disease-associated mineral and bone disorders (CKD-MBD) prevail in the endocrinological assessment of CKD patients, other endocrine abnormalities are usually overlooked. CKD is associated with significant thyroid, adrenal and gonadal dysfunction, while persistent and de novo endocrinological abnormalities are frequent among kidney transplant recipients (KTR). Low T3 levels prior to transplantation may help identify those at risk for delayed graft function and are often found in KTR. Thyroid surveillance after kidney transplantation should be considered due to structural anomalies that may occur. Despite the rapid recovery of gonadal hormonal secretion after renal transplantation, fertility is not completely restored. Testosterone may improve anemia and general symptoms in KTR with persistent hypogonadism. Female KTR may still experience abnormal uterine bleeding, for which estroprogestative administration may be beneficial. Glucocorticoid administration suppresses the hypothalamic-pituitary–adrenal axis in KTR, leading to metabolic syndrome. Patients should be informed about signs and symptoms of hypoadrenalism that may occur after glucocorticoid withdrawal, prompting adrenal function assessment. Clinicians should be more aware of the endocrine abnormalities experienced by their KTR patients, as these may significantly impact the quality of life. In clinical practice, awareness of the specific endocrine dysfunctions experienced by KTR patients ensures the correct management of these complications in a multidisciplinary team, while avoiding unnecessary treatment.

Abstract #1407860: Rare Cause of Non-PTH Mediated Hypercalcemia Due to Pneumocystis Pneumonia in Renal Transplant Recipient

Hypercalcemia secondary to persistent hyperparathyroidism is common in kidney transplant recipients (KTR). We report a rare cause of non-PTH mediated hypercalcemia in KTR due to pneumocystis jirovecii pneumonia (PJP). The incidence of PJP in KTR is 5-15% in absence of antibiotic prophylaxis. Incidence of hypercalcemia in KTR with PJP is unclear, but scattered case reports are found in literature. The proposed mechanism for hypercalcemia is an infectious granulomatous reaction. PJP induced hypercalcemia needs to be considered in KTR patients with non-PTH mediated hypercalcemia. A 62-year-old male with kidney transplant for renal failure from glomerulosclerosis, three years prior to presentation was admitted for dyspnea and fever. Imaging showed bilateral lung infiltrates, concerning for multifocal infection. Considering his imaging findings and elevated Beta D glucan levels, he was empirically started on PJP treatment with atovaquone on day 4 of admission. Bactrim was not used due to acute renal failure. On day 1, calcium was 10 mg/dL (8.4-10.4), which then progressively increased from 10.7mg/dl on day 4 to a peak calcium level of 14.4 mg/dL on day 12. Further work up showed PTH: 4.7 pg/mL (12-88), PTHrP: 0.6 pMol/L (< /= 4.2), Vitamin D 1, 25: 198 pg/mL (18-72), Vitamin D 25: 79 ng/mL (20-100), SPEP: no M spike, UPEP: no M spike but had a lysozyme band suggestive of granulomatous infection, other fungal studies negative, normal thyroid levels, AFB culture negative. On day 12, he was started on prednisone 60mg presuming hypercalcemia from PJP. On day 13, calcium improved to 11.7 mg/ dL, but his renal function worsened requiring hemodialysis (HD). On day 14, he had respiratory failure requiring intubation and underwent bronchio-alveolar lavage (BAL) which was positive for pneumocystis PCR. He was started on bactrim on day 17 and continued on high dose steroid. By day 19, he was extubated, renal function stabilized without HD and calcium normalized to 8.9 mg/dL. Unfortunately, he had gastrointestinal bleed and refused further procedures eventually opting for hospice on day 23. PJP is a common opportunistic infection in immunosuppressed patients like KTR. The advent of prophylaxis has significantly decreased the incidence of PJP in KTR to 0.3%-2.6%. PJP in KTR is sometimes associated with hypercalcemia. Prevalence of hypercalcemia in KTR with PJP is unclear, but as per a hospital based retrospective study (Hamroun et al., 2019), 37% of PJP patients in KTR (18/49) had hypercalcemia that preceded pneumonia/findings on imaging. The proposed mechanism for hypercalcemia is granulomatous in nature, due to increased extra renal production of 1 alpha hydroxylase enzyme from increased macrophage recruitment in lungs to clear pneumocystis organisms. Hypercalcemia resolved after completion of treatment and resolution of PJP. High dose steroids can be used as hypercalcemia is mediated by a granulomatous reaction. It is crucial for physicians to have a high index of suspicion for PJP as the etiology of pneumonia in immunocompromised organ transplant recipients with non- PTH mediated hypercalcemia, thus ensuring timely diagnosis and treatment.

Efficacy and safety of booster vaccination against SARS-CoV-2 in dialysis and renal transplant patients: systematic review and meta-analysis.

Patients under renal replacement therapy are at an increased risk of severe infection with SARS-CoV-2, and have been known to have impaired response to standard vaccination. This systematic review and meta-analysis aims at evaluating the efficacy of booster dose vaccination in this population. A systematic review has been conducted to find trials on the booster dose vaccination in kidney transplant recipients (KTRs) or patients under dialysis. Data of seroconversion rates at different timepoints, especially 1month prior and post-booster dose vaccination have been collected and analyzed. Effects of different factors including type of renal replacement therapy (RRT), vaccine type and brands, magnitude of response to the standard vaccination, and immunosuppression drugs on the response rates have been investigated. Meta-analyses were performed using software Stata v.17. Overall 58 studies were included. Both RRT patient subgroups represented significant seroconversion, post- (versus pre-) booster dose vaccination, but only in KTRs the booster dose seroconversion surpassed that of the standard protocol. T-cell response was also significantly augmented after booster vaccination, with no difference between the RRT subgroups. mRNA and vector vaccine types had comparable immunogenicity when employed as boosters, both significantly higher than the inactivated virus vaccine, with no significant disparity regarding the vaccine brands. Patients with poor response to standard vaccination had a significant response to booster dose, with dialysis patients having stronger response. The differential effects of vaccine types and brands in the poor responders was similar to that of the overall RRT population. No rejection episodes or graft failure post-booster vaccination was reported. In patients under RRT, booster dose vaccination against SARS-CoV-2 is safe and efficacious determined by significant seroconversion, and therefore, it should be considered to be implemented in all these patients. Since in the KTR patients, the third dose vaccination significantly increased the seroconversion rates even beyond that of the standard protocol, three dose vaccine doses is recommended to be recognized as the standard vaccination protocol in this population. The same recommendation could be considered for dialysis patients, due to their augmented risk of breakthrough infection.

BK virus in kidney transplant recipients with graft dysfunction

ABSTRACT This study was to estimate the viral load of BK virus (BKV) in the urine and blood of Kidney transplant recipients (KTRs) with graft dysfunction and its effect on the development of graft dysfunction. This analysis included all KTR outpatients who visited the clinic at Urology and Nephrology Center during their routine follow-up visits from September 2017 to May 2019. A total of 100 patients were divided into 62 KTR patients with kidney dysfunction (case group) vs. 38 KTR patients without kidney dysfunction (control group). BKV DNA quantification in urine and plasma samples was examined in all patients by the real time PCR method. The BKV DNA was detected in the urine samples of 5 patients, all with kidney dysfunction (8%) vs. none in the control group. The BKV viral load of the 5 cases ranged from 105 to 244000 copies/ml. The BKV DNA was not detected in the blood samples of the 5 urine-positive cases. It was concluded that all patients with kidney dysfunction should be screened for BKV in their urine samples to prevent the development of BKV-caused nephropathy and further graft failure.

SARS-CoV-2-Spike Antibody and T-Cell Responses Elicited by a Homologous Third mRNA COVID-19 Dose in Hemodialysis and Kidney Transplant Recipients.

The effect of a third vaccine dose (3D) of homologous mRNA vaccine on blood levels of SARS-CoV-2-receptor binding domain (RBD)-total antibodies was assessed in 40 hemodialysis patients (HD) and 21 kidney transplant recipients (KTR) at a median of 46 days after 3D. Anti-RBD antibodies were detected in 39/40 HD and 19/21 KTR. Overall, 3D boosted anti-RBD antibody levels (median: 58-fold increase). Neutralizing antibodies (NtAb) against the Wuhan-Hu-1, Delta, and Omicron variants were detected in 14, 13, and 11 out of 14 HD patients, and in 5, 5, and 4 out of 8 KTR patients, respectively. The median fold increase in NtAb titers in HD patients was 77, 28, and 5 and 56, 37, and 9 in KTR patients for each respective variant. SARS-CoV-2-S S-IFN-γ-producing CD8+ and CD4+ T-cell responses were detected in the majority of HD (35 and 36/37, respectively) and all KTR (16/16) patients at 3D. Overall, the administration of 3D boosted T-cell levels in both population groups. In conclusion, a homologous mRNA COVID-19 vaccine 3D exerts a booster effect on anti-RBD antibodies, NtAb binding to Wuhan-Hu-1, Delta, and Omicron variants, and SARS-CoV-2-S-IFN-γ-producing T cells in both HD and KTR patients. The magnitude of the effect was more marked in HD than KTR patients.

P8.054: Out of the Box. Immunosuppressive Therapy With Four Drugs As Rescue Therapy in Kidney Transplant Recipients With Chronic Allograft Rejection

Introduction: Persistent or repeated episodes of acute rejection (AR) may lead to chronic allograft damage. Antibody-mediated rejection (AMR); T-cell mediated rejection (TCMR) and mixed variants (MR) of chronic kidney allograft rejection (CR) are nowadays considered as the main causes of graft loss (GL). This encompasses from endothelial damage up to fibrosis challenging immunosuppressive therapy (IT) management. IT reinforcement with a four-drug scheme (4D) including m-TOR inhibitors, anticalcineurinics, mycophenolate and steroids, could be a good strategy in this scenario, nevertheless there is no consensus about it. We present our experience with 4D in kidney transplant recipients (KT) That presented with CR or recurrent episodes of AR. Objectives: To evaluate kidney graft function (KGF), incidence of rejection and safety of a 4D in KT with CR or recurrent episodes of AR. Methods: KT on treatment with 4D from 2008 to 2021 were included. KGF was evaluated by estimated glomerular filtration rate with CKD-EPI (eGFR) and urinary protein/creatinine ratio (PCR) at 3, 6 and 12 months. Kidney biopsies and panel reactive antibodies (PRA) by Luminex were performed before and after introduction of 4D. BK virus (BKV) incidence, infectious (IE) and neoplastic (NE) events were recorded during the follow up. Results: 16 KT (median age 45 ± 11 years) were treated with 4D during 52.8 (17-106) months. 43.8% of them were women, 50% were deceased KT. The median post transplant time was 108 (60-129) months. Reasons for 4D introduction were CR in 87.4% of the cases (MR 50%; TCMR 31.3%; AMR 6.3%) and in the remaining 12, 6%, recurrent or persistent acute TCMR. Median eGFR was 42 (27-66); 44 (31-62); 48 (33-60) and 48 (32-65) ml/min prior to IT change, at 3, 6 and 12 months respectively. At baseline, mean PCR was 179 (147-664) mg/g without significant changes during follow up. Biopsy proven AR was found in 37% of KT under 4D. No NE were registered. 43% of the patients presented a non major IE, and only one patient was BKV positive during follow up with 4D. There was one GL, one loss of follow up and one death due to sepsis with functioning graft. Conclusions: KT patients with CR or recurrent episodes of AR changed to 4D IT stabilized their renal function and proteinuria. The incidence of new biopsy proven AR was 37%, and no new DSA were found or serious adverse events reported during follow-up. 4D could be a good option to halt the progression of renal damage due to rejection in KT.

P8.155: Current Trends in Anemia Treatment in Kidney Transplant Recipients

Background and Aims: The topic of management of chronic kidney disease (CKD) anemia has constantly been improving. This study aimed to assess the prevalence and current trends in anemia treatment in real-world kidney transplant recipients (KTR). Methods: This cross-section study included 509 KTR patients, mean age – of 53 years, 51.5% male, with functioning grafts in the late post-transplant period in the last quarter of 2021, in an average of 9,4 years post-transplantation. Data were analyzed using SPSS Statistics 27.0. Student’s t-test, Chi-squared test, Pearson correlation tests were used. According to the Kidney Disease: Improving Global Outcomes (KDIGO) definition, anemia was determined as a hemoglobin (Hb) level of <120 g/L for women and <130 g/L for men. CKD stage was determined by the estimated glomerular filtration rate (eGFR) calculated using creatinine in the CKD-EPI equation. Results: The prevalence of anemia in the KTR population was 35% (n=178), increasing from 13% to 96% by progressing CKD from stage 1 to 5 in a transplant (Table 1: The prevalence of anemia depends on the stage of CKD in a transplant.).A moderately strong Pearson correlation was recognized between the stage of CKD and anemia (r=0.441; p<0.001). A statistically significant association (p<0.001) was detected between anemia and the female gender (n=107; 60% of all anemic patients). We found no significant association between anemia and the use of mycophenolate or calcineurin inhibitors. Still, there was a statistically significant association between steroid use and anemia (p=0.041), with a 31% (Odds Ratio = 0.69) less chance of anemia in a group that received steroid therapy. 90% of anemic patients had normochromic, normocytic anemia, 7,8% hypochromic, microcytic, and 2,2% hyperchromic, macrocytic anemia. The treatment involved iron replacement in 29% (n=51) of patients, of whom 92.2% had oral medication and 7.8% intravenous. 54% (n=96) of anemic KTR received treatment with erythropoiesis-stimulating agents (ESAs): 27,1% with darbepoetin alfa and 72,9% with methoxy polyethylene glycol-epoetin beta. Anemia was corrected up to Hb level >110 g/L in 69.7% (n=67) of ESAs receiving KTR. A statistically significant correlation was not detected between the ESAs dosage (µg/kg) and the correction of the anemia (p=0.217). Conclusion: Like in the general CKD population, the prevalence of anemia in KTR increases as CKD progress in a transplant. The extent of anemia correction seems insufficient, although it includes both major components: iron replacement and ESAs. We found anemia more prevalent in female patients and those not receiving steroids in the immunosuppressive regimen. This last unexpected finding needs further exploration. Darja Golubeva for data collection. Ieva Evelina Stolcere for data collection. Liana Linda Lice for data collection.

P16.06: Seroconversion in Pacients After SARS-Cov-2 CHADOX1 NCoV-19/AZD1222 Vaccination in Hemodialysis Patients And Kidney Transplant Recipients

Background: Since December 2019 the world has been affected for Coronavirus SARS-CoV-2 pandemic. In Aguascalientes state at March 13th 2022 has been confirmed a total of 62,440 cases and 3,479 deaths caused by COVID-19. As a combat strategy were developed different kind of vaccines against SARS-CoV-2. The Oxford University developed the vaccine ChAdOx1 nCov-19/AZD1222 which is based in a viral vector which codes the information of the spike protein of SARS-CoV-2. It has been proven that the morbidity and mortality from COVID-19 is higher in hemodialysis (HD) patients and Kidney Transplant (KT) recipients. Objective: Measure and compare the seroconversion level in hemodialysis patients and kidney transplant recipients (KTR), who received two doses of the ChAdOx1 nCov-19/AZD1222 vaccine and identify the factors associated with low response to the vaccine used in our study population. Methods: We performed a prospective, observational, unblinded and comparative analysis. Patients included between 18-80 years old, both genders, that they were in HD or with KTR, and received two doses of the ChAdOx1 nCov-19/AZD1222 vaccine between 2-6 months before sampling. The antibodies level against spike protein of SARS-CoV-2 was determined by the immunoassay Elecsys anti-SARS-CoV-2 and we determined a positive result ≥100 U/mL. Statistical Analysis: iChi2 test with Yates´ correction, Student´s T-Test unpaired and multiple logistic analysis. p<0.05 was considered as significant. Results: 67 patients were included, 49 in HD and 18 with KTR. In the multiple logistic regression analysis, taking the positive seroconversion ≥100 U/mL as the dependent variable, the KT was the risk factor associated with a lower seroconversion frequency, p<0.05 Exp(B) 3.26. Conclusions: The ChAdOx1 nCov-19/AZD1222 vaccine was associated with a higher seroconversion level in HD patients in comparison to KTR. The KTR patients presented a higher frequency of SARS-COV2 infection post vaccination in relation to HD patients. The main risk factor associated with lower seroconversion response was KT in patients who received the ChAdOx1 nCov-19/AZD1222 vaccine. Our population presented a higher seroconversion response that reported in the literature, probably because of the SARS-COV2 infection antecedent prior to vaccination.

Local and Systemic Immunity Are Impaired in End-Stage-Renal-Disease Patients Treated With Hemodialysis, Peritoneal Dialysis and Kidney Transplant Recipients Immunized With BNT162b2 Pfizer-BioNTech SARS-CoV-2 Vaccine.

Vaccination against COVID-19 in patients with end-stage renal disease (ESRD) on replacement therapy and kidney transplant recipients (KTRs) is particularly important due to the high mortality rate. Here, we tested the local and systemic immunity to the novel Pfizer BioNTech (BNT162b2) messenger RNA (mRNA) in ESRD, KTR patients, and healthy individuals (150 subjects). The ESRD group was divided into: hemodialysis (HD) and peritoneal dialysis (PD). We investigated the local and systemic immunity based on anti-N (nucleoprotein) and anti-S (spike1/2) Immunoglobulin A (IgA) and Immunoglobulin G (IgG) antibodies, respectively. Additionally, we performed an Interferon gamma (IFN-γ) release test Interferon-gamma release assay (IGRA) to monitor the cellular component of vaccine response. The control group had the highest level of anti-S IgG antibodies (153/2,080 binding antibody units (BAU)/ml) among all analyzed patients after the 1st and 2nd dose, respectively. The HD group (48/926 BAU/ml) had a diminished antibody level compared to PD (93/1,607 BAU/ml). Moreover, the seroconversion rate after the 1st dose was lower in HD than PD (56% vs. 86%). KTRs had extremely low seroconversion (33%). IgA-mediated immunity was the most effective in the control group, while other patients had diminished IgA production. We observed a lower percentage of vaccine responders based on the IFN-γ level in all research participants (100% vs. 85% in control, 100% vs. 80% in PD, 97% vs. 64% in HD). 63% of seropositive KTRs had a positive IGRA, while 28% of seronegative patients produced IFN-γ. Collectively, PD patients had the strongest response among ESRD patients. Two doses of the Pfizer vaccine are ineffective, especially in HD and KTRs. A closer investigation of ESRD and KTRs is required to set the COVID-19 vaccine clinical guidance.Clinical Trial Registration Number www.ClinicalTrials.gov, identifier: NCT04 905 862

Radiofrequency Echographic Multi-Spectrometry (REMS) technology and DXA for BMD assessment in kidney transplant recipients

Radiofrequency Echographic Multi-Spectrometry (REMS) is a novel ultrasound-based technique that has shown good reliability in the assessment of BMD in women affected by post-menopausal osteoporosis. Data on special populations with secondary osteoporosis are needed. The aim of this study was to compare the performance of the REMS BMD assessment with DXA in a cohort of kidney transplant recipients (KTR). Consecutive patients referring to our KTR clinic were enrolled. All subjects fulfilled the following inclusion criteria: Caucasian population, both genders, age between 40 and 80 years, BMI < 40kg/m2. The enrolled patients underwent a lumbar spine (LS) and femoral neck (FN) examination with DXA and REMS. Differences in DXA vs REMS T-scores were analyzed through Student's t test for independent samples, correlations were tested though Pearson's correlation. Differences in prevalence were tested trough Chi-squared test. Written informed consent was obtained from all participants (protocol 1483CESC). 40 patients were enrolled (table 1). At the LS, BMD was significantly lower when assessed through REMS. The correlation between the T-scores obtained with DXA and REMS are depicted in figure 1. When adopting the worst site, the prevalence of subjects with T-score <-2.5 was 40.5% with DXA and 37.8% with REMS (p=NS) and of subjects with T-score <-1 was 89% with DXA and 97.5% with REMS (p=0.003). These results showed a good reliability of the REMS technology with respect to DXA in the classification of KTR patients as having low bone mass and/or osteoporosis. Furthermore, REMS might be more sensitive than DXA in the detection of early bone impairment and in the classification of KTR patients with low bone mass. Uploaded File(s)

Dengue infection in kidney transplant recipients: clinical course and its impact on renal function.

Introduction:Kidney transplant recipients (KTR) are at increased risk for dengue virus (DENV) infection. The aim of this study was to outline the clinical presentation and laboratory profile of DENV infection in KTR and its impact on renal function.Methods:This was a retrospective study of KTR diagnosed with DENV infection. Adult patients who visited Santa Casa de Belo Horizonte Nephrology Center between April and September 2019 were included. Patients who did not sign the Informed Consent were excluded. Data were collected from the database and medical records. The study was approved by the local Institutional Ethics Committee and the Informed Consent was obtained.Results:Nineteen KTR were evaluated. The main signs and symptoms were myalgia, headache/retro-orbital pain, fever, and gastrointestinal symptoms. Two patients had acute cholecystitis without calculus, three experienced pleural and/or pericardial effusion, and one developed acute myocarditis. All patients were under immunosuppression with prednisone, tacrolimus, and mycophenolate, and most were not receiving induction therapy. Temporary suspension/reduction of immunosuppression was required in 58% of patients and leukopenia was the most common reason. Thrombocytopenia was common and 58% of patients developed acute kidney injury. All patients recovered renal function.Conclusions:DENV infection in KTR patients seems to follow a similar course as in the general population. Although there was no control group, we suspect that immunosuppression, preexisting kidney disease or type of donor was not a determining factor in most patients. Transient renal dysfunction was common but reversible. No patient experienced death or graft loss.

BK Virus and Cytomegalovirus Coinfections in Kidney Transplantation and Their Impact on Allograft Loss.

We aimed to ascertain the interaction and effects of combined reactivations of BK virus and cytomegalovirus on kidney graft function. All consecutive kidney transplant recipients (KTR) between 2003 and 2016 were included. Of 1976 patients who received a kidney transplant, 23 (1.2%) presented BKV-associated nephropathy (BKVAN). Factors independently associated with BKVAN were diabetes mellitus (odds ratios (OR) 3.895%, confidence intervals (CI) (1.4–10.5)), acute allograft rejection (OR 2.8 95%, CI (1.1–7.6)) and nephrostomy requirement (OR 4.195%, CI (1.3–13)). Cytomegalovirus infection was diagnosed in 19% of KTR patients. Recipients with BKVAN presented more frequently with cytomegalovirus (CMV) infection compared to patients without BKVAN (39% vs. 19%, p = 0.02). Acute allograft rejection (OR 2.95%, CI (1.4–2.4)) and nephrostomy requirement (OR 2.95%, CI (1.2–3)) were independently associated with CMV infection. Sixteen patients (69%) with BKVAN had graft dysfunction at one-year post-transplant and eight of them (35%) lost their graft. Patients presenting with BKVAN and graft loss presented more frequently a cytomegalovirus infection (OR 2.295%, CI (1.3–4.3)). In conclusion, we found a relation between CMV infection and graft loss in patients presenting BKVAN, suggesting that patients with CMV reactivation should be actively screened for BKV.

Fatigue in Kidney Transplantation: A Systematic Review and Meta-Analysis.

Fatigue is still present in up to 40–50% of kidney transplant recipients (KTR), the results of studies comparing the prevalence among patients on hemodialysis (HD) and KTR led to conflicting results. Fatigue correlates include inflammation, symptoms of depression, sleep disorders and obesity. Fatigue in KTR leads to significant functional impairment, it is common among KTR poorly adherent to immunosuppressive therapy and is associated with a serious deterioration of quality of life. The following databases were searched for relevant studies up to November 2020: Medline, PubMed, Web of Science and the Cochrane Library. Several studies have compared the prevalence and severity of fatigue between KTR and hemodialysis or healthy patients. They have shown that fatigue determines a significant functional deterioration with less chance of having a paid job and a significant change in quality of life. The aim of the review is to report methods to assess fatigue and its prevalence in KTR patients, compared to HD subjects and define the effects of fatigue on health status and daily life. There is no evidence of studies on the treatment of this symptom in KTR. Efforts to identify and treat fatigue should be a priority to improve the quality of life of KTR.

P0939THE ASSOCIATION BETWEEN MUSCULAR STRENGTH, MUSCLE MASS AND DEPRESSION IN KIDNEY TRANSPLANT RECIPIENTS: A CROSS-SECTIONAL ANALYSIS

Abstract Background and Aims While kidney transplantation (Ktx) offers several advantages in terms of improved clinical outcomes and quality of life compared to dialysis modalities, depressive symptoms are still present in approximately 25% of patients, rates comparable to that of the hemodialysis population. Correlates of depressive symptoms include marital status, income, and kidney function, history of affective illness, malnutrition, and inflammation. The aim of this study was to evaluate possible correlations between nutritional status evaluated through body mass composition parameters, muscle strength and depression in kidney transplant recipients (KtR). Method 115 KtR, 61 (53 %) men and 54 (47 %) women, aged 59.3 (range 25 - 83) years were included. For each patient data about duration after Ktx, duration of dialysis before Ktx, age, gender, body weight and height were collected and body mass index (BMI) was calculated. Tanita MC780 Multi Frequency segmental body composition analyser was used to measure content of body fat, muscle mass, and visceral fat each study subject measured in kilograms (kg) and percentage (%.) Peripheral muscle strength of KtR was measured by using a standardized handgrip dynamometry protocol. The Beck Depression Inventory-Second Edition (BDI-II) was used as an indicator of the severity of depression. Results Out of all 115 KtR patients, according BDI-II score 25 (21.7 %) were depressed; 15 (13 %) had mild, 6 (5.2 %) moderate and 4 (3.5 %) severe depression. Significantly negative correlations between BDI-II scores (higher score – more depressive symptoms) and muscle mass (kg and %) was found (R=-0.205, P=0.032), (R=-0.278, P=0.003), respectively. Therefore, significantly positive correlations between BDI-II scores (higher score – more depressive symptoms), fat mass (%) and age was found (R=-0.24, P=0.012), (R=-0.231, P=0.013), respectively. Those KtR patients with more depressive symptoms (higher BDI-II score) had statistically lower muscle strength (R=-0.205, P=0.032). Significantly correlation between duration after Ktx and duration of dialysis before Ktx with BDI-II score was not found. Conclusion Prevalence rates for depression in this study is similar with previous reports and results have shown that depressive KtR patients were older and had significantly lower muscle mass and muscle strength and significantly higher fat mass content. Possible explanation for this findings might be that depression in KtR is associated with unhealthy behaviours including lower activity levels and worse dietary habits, which may in turn impact body mass composition parameters and upon transplant-related outcomes. Efforts to detect and treat depression should be a priority if one is to improve treatment and dietary adherence, quality of life, and outcomes in KtR.

P0947DIETARY HABITS, BODY COMPOSITION AND MUSCULAR STRENGTH ARE CORRELATED TO COGNITIVE IMPAIRMENT IN DALMATIAN HYPERTENSIVE KIDNEY TRANSPLANT RECIPIENTS (KTRS)

Abstract Background and Aims Cognitive impairment is correlated with increased mortality of chronic kidney disease patients and hypertension is a well known comorbidity. While transplantation offers various general health and cognitive function improvement over dialysis, kidney transplant recipients (KTRs) still show greater cognitive impairment than healthy control. Researched pathophysiological mechanisms in KTR population include infection and immunosuppressive induced neurotoxicity. The aim of this study was to determine what impact do body composition, dietary habits and muscular strength have on cognitive impairment of hypertensive KTRs. Method 48 (52.17 %) men and 44 (47.83%) women, aged 59.7 (range25-83) years were included. For each patient data about duration after Ktx, duration of dialysis before Ktx, age, gender, body weight and height were collected and BMI and waist-to-height ratio (WHtR) were calculated. Tanita MC780 Multi Frequency segmental body composition analyser was used to measure content of body fat, muscle mass, and visceral fat each study subject measured in kilograms (kg) and percentage (%.) Peripheral muscle strength of KtR was measured by using a standardized handgrip dynamometry protocol. The Mini Mental State Exam (MMSE) was used as an indicator of cognitive impairment. Mediterranean Diet Serving Score (MDSS) questionnaire was used to determine adherence to Mediterranean Diet (MeDi) considering the consumption of foods and food groups per meal, day or week. Results Out of 92 KTR patients with hypertension, 5 of them scored ≤ 24 points on MMSE scale implying serious cognitive dysfunction. Mean score of MMSE was 28.2, (range 22-30) Regarding MDSS score, 11 patients scored ≥ 16 meaning highest adherence, while 67 KTRs scored &amp;lt; 16 meaning low adherence to MeDi, (results range 2-18) . Positive correlations were found between MMSE score (higher score meaning better cognitive functioning) and MDSS score ( higher score implying better adherence to MeDi)( R=0,282, p=0,012), consuming 1-2 portions of fruits( R=0,266,p=0,016) or ≥ 2 portions of vegetables ( R=0,241,p=0,03) per main meal, skeletal muscle mass (%) (R=0,278, p=0,008), peripheral muscular strength( R=0,325,p=0,003) and fat free mass (kg)(R=0,212,p=0,045). On the other hand we found statistically significant negative correlation between MMSE score and WHtR ( R=-0,255, p= 0,023) . as well as PWV(R=-0,244, p=0,022). Conclusion Cognitive impairment correlations in this study are similar to ones in general population specially regarding Mediterrranean diet and muscle mass . Possible explanation of positive MeDi impact on cognitive function in KTRs could be its low phosphate intake which prevents vascular calcification and negative effects of hyperparatiroidism. Although benefits of MeDi in CKD patients can be argued due to high pottasium levels, after kidney Tx it should not be an obstacle anymore. These results suggest that lifestyle interventions such as following MeDi, building more muscle and reducing fat could provide hypertensive KTR patients with longer preservation of cognitive function.

Hemodialysis and Kidney Transplantation as Predisposing Conditions to Onychomycosis

Background/Aim: Onychomycosis (OM) is one of the commonest superficial fungal infections. Patients undergoing hemodialysis (HD) treatment and kidney transplant recipients (KTR) are considered at risk of contracting fungal infections, but the few published data do not reach the conclusion of whether they are predisposed to OM. This study aimed to determine the prevalence and etiology of OM in these patients and to determine the antifungal susceptibility profile of the isolated fungal species. Methods: We recruited 149 HD patients, 187 KTR, and a control group comprising 174 patients attending an internal medicine service with other diseases than renal diseases. All patients underwent an examination of all toenails to check for the presence of OM. Antifungal susceptibility tests were performed following the Clinical and Laboratory Standards Institute (CLSI) recommendations. Results: The prevalence rates of OM in HD patients (23.4%) and KTR (23.0%) were significantly higher than those in age- and sex-matched control groups (13.2%). In HD patients, OM was associated with diabetes but not with the duration of dialysis. In KTR, OM was more prevalent in those without diabetes and likely also in those using mycophenolate mofetil or azathioprine but was not associated with the duration of transplantation. Trichophyton rubrum was the most prevalent species (45.9%) followed by T. mentagrophytes (24.5%) and Candida parapsilosis (18.0%). Fluconazole, itraconazole, voriconazole, and terbinafine were all efficient against the isolates of dermatophyte, with terbinafine showing the lowest and fluconazole the highest minimal inhibitory concentrations. All isolates of C. parapsilosis were sensitive to the antifungals according to the CLSI criteria. Conclusion: We found a high prevalence of OM in HD and KTR patients and suggest that these conditions should be considered a risk factor of OM. All 4 antifungals evaluated in the study showed good in vitro activity against the etiologic agents.

Measurement of a 5-gene panel in whole blood in kidney transplant recipients with acute rejection and stable controls

New biomarkers are required to detect acute rejection (AR) in kidney transplant recipients (KTRs) to avoid invasive kidney biopsies. We assess whether a 5-gene panel (DUSP1; NKTR; PBEF1; MAPK9; and PSEN1) in whole blood samples that has previously been shown to identify AR in a paedriatric KTR population is able to distinguish AR in a UK population of adult Caucasian KTR patients.