Renal Recipients Research Articles

Comparison of the Charlson comorbidity index, the modified Charlson comorbidity index, and the recipient risk score in prediction of the graft and patient survival among renal graft recipients: historical cohort in a single center.

To compare the predictive values of Charlson comorbidity index (CCI), modified Charlson comorbidity index kidney transplant (mCCI-KT) and recipient risk score (RRS) indices in prediction of patient and graft survival in kidney transplant patients. In this retrospective study, all patients who underwent a live-donor KT from 2006 to 2010, were included. Demographic data, comorbidities and survival time after KT were extracted and the association between above indices with patient and graft survival were compared. In ROC curve analysis of 715 included patients, all three indicators were weak in predicting graft rejection with the area under curve (AUC) less than 0.6. The best models for predicting the overall survival were mCCI-KT and CCI with AUC of 0.827 and 0.780, respectively. Sensitivity and specificity of mCCI-KT at cut point of 1 were 87.2 and 75.6. Sensitivity and specificity of CCI at cut point of 3 were 84.6 and 68.3 and for RRS at cut point of 3 were 51.3 and 81.2, respectively. The mCCI-KT index followed by the CCI index provided the best model in predicting the 10-year patient survival; however, they were poor in predicting graft survival and this model can be used for better stratifying transplant candidates prior to surgery.

Early Cytomegalovirus Reactivation in Renal Recipients Is Associated with High Levels of B Cell Maturation Antigen Transcript Expression Prior to Transplantation.

Cytomegalovirus (CMV) infection is the most frequent infection episode in kidney transplant (KT) recipients. Reactivation usually occurs in the first three months after transplantation and is associated with higher cellular and/or antibody-mediated rejection rates and poorer graft performance. CMV induces the expression of BAFF (B-cell-activating factor, a cytokine involved in the homeostasis of B cells), which communicates signals for survival and growth to B cells and virus-specific plasma cells via the R-BAFF (BAFF receptor), TACI (the calcium modulator, the cyclophilin ligand interactor), and BCMA (B cell maturation antigen) receptors. These molecules of the BAFF system have also been suggested as biomarkers for the development of alloantibodies and graft dysfunction. This prospective study included 30 CMV-IgG seropositive KT recipients. The expression levels of the genes BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA) in peripheral blood leukocytes (PBL) pre-KT were determined using qPCR. qPCR was also used to monitor CMV reactivation in the first three months following KT. The remainder of the KT recipients were classified as CMV- reactivation, and those with more than 500 copies/mL in at least one sample were classified as CMV+ reactivation. There were no discernible variations in the BAFF-R and TACI transcript expression levels. In the CMV+ group, we examined the relationship between the transcript levels and peak viremia. Peak viremia levels and BCMA transcript levels showed a strong correlation. BAFF-R and TACI expressions showed no measurable differences. In patients with early CMV reactivation, high BCMA receptor expression was associated with increased plasmablast, lymphocyte B cell class-switched levels (LBCS), and viral load. Our findings demonstrate that pre-KT BCMA transcript levels increased in KT recipients with early CMV reactivation. These transcript levels positively correlate with peak viremia and weakly with plasmablast and LBCS levels in PBLs.

Current Status Regarding Immunosuppressive Treatment in Patients after Renal Transplantation.

Renal transplantation is now the best treatment for end-stage renal failure. To avoid rejection and prolong graft function, organ recipients need immunosuppressive therapy. The immunosuppressive drugs used depends on many factors, including time since transplantation (induction or maintenance), aetiology of the disease, and/or condition of the graft. Immunosuppressive treatment needs to be personalised, and hospitals and clinics have differing protocols and preparations depending on experience. Renal transplant recipient maintenance treatment is mostly based on triple-drug therapy containing calcineurin inhibitors, corticosteroids, and antiproliferative drugs. In addition to the desired effect, the use of immunosuppressive drugs carries risks of certain side effects. Therefore, new immunosuppressive drugs and immunosuppressive protocols are being sought that exert fewer side effects, which could maximise efficacy and reduce toxicity and, in this way, reduce both morbidity and mortality, as well as increase opportunities to modify individual immunosuppression for renal recipients of all ages. The aim of the current review is to describe the classes of immunosuppressive drugs and their mode of action, which are divided by induction and maintenance treatment. An additional aspect of the current review is a description of immune system activity modulation by the drugs used in renal transplant recipients. Complications associated with the use of immunosuppressive drugs and other immunosuppressive treatment options used in kidney transplant recipients have also been described.

#4699 QUALITY OF LIFE AS REPRESENTED BY PHYSICAL ACTIVITY WAS IMPROVING AFTER FULL CORRECTION OF POST-TRANSPLANT ANEMIA

Abstract Background and Aims Recent studies showed positive impact of correction of post-transplant anemia (PTA) on general health, exercise capacity, and physical scores. So we conducted this prospective randomized controlled trial (RCT) to assess quality of life after full correction of post-transplant anemia in renal recipients receiving erythropoietin stimulating agents. Method We recruited 247 kidney transplant recipients with stable graft function in this RCT with 2 groups according to their target hemoglobin (11-12 g/dl, group 1, n = 183) and (13:15 g/dl (group 2, n = 64) which was achieved using erythropoietin stimulating agents (ESA). Monthly clinical and laboratory evaluation of kidney graft function was carried out. Quality of life (QOL) was assessed –using 25 and 36 questionnaires-at the start and 12 months. Results We observed more females in group 1 and the original kidney disease was chronic glomerulonephritis was significantly higher in group 2 (37.5%) followed by diabetic nephropathy (15.7%) while in group 1 it came as 25.7% and 22.4% respectively (p<0.05).The studied groups were comparable regarding pre-transplant co-morbidities. Most patients received thymoglobulin as induction and most of them were maintained on cyclosporine. We did not find any significant difference between the two groups concerning post-transplant co-morbidities (p >0.05), however better graft function was observed in group 2 at 6 months (p< 0.05). At 12 months, the assessment of QoL using the Medical Outcomes Study 36-Item Short-Form Health Survey, group 1 showed better post-transplant physical features and higher emotional factors related inactivity at 12 month (p<0.05), while group 2 showed significantly higher basal and 12 months activity state (p = 0.05). Basal inactivity was comparable in group 2 with that at 12 months (p>0.05), emotional factors related inactivity was significantly higher at 12 months in group 1. Graft outcome was comparable between both groups (p = 0.125), (p = 0.005). Conclusion Quality of life as represented by physical activity was improving by full correction of PTA in renal transplant recipients receiving ESA.

#3143 MEASURING CLINICAL JUDGEMENT IN PROSPECTIVE KIDNEY TRANSPLANT RECIPIENTS: A FEASIBILITY STUDY

Abstract Background and Aims Exercising clinical judgement is becoming more challenging in the context of ageing populations, increasing prevalence of multimorbidity and frailty, and insufficient evidence regarding how best to manage increasing complexity in clinical practice. Measures of clinical judgement are surprisingly absent from health information systems despite their clear importance and the potential costs of poor decisions. Suitability for kidney transplantation is a high-stake clinical judgement, requiring consideration of complex biopsychosocial patient and organ-utilisation factors. This study aimed to test if it is feasible to assess clinical judgement quantitatively from routine clinical documentation in kidney transplant recipients. Method Participants were identified from a regional register of patients on haemodialysis, who underwent deceased donor kidney transplantation (KTR) and had at least 1 year of follow-up. We identified 15 KTR who had poor outcomes, defined as more than 6 hospital admissions or death within one-year of transplantation. Fifteen KTR controls were matched using the United Kingdom Renal Recipient Index (UKRRI: a composite score of age, dialysis requirement at listing, wait time on dialysis and diabetes status). Six blinded raters (two nephrologists, two transplant surgeons and two kidney transplant coordinators) scored clinical letters written at the time of transplant assessment across four domains (Clinician Belief of Appropriateness [CBA] for perceived suitability, perceived benefit, predicted short-term harm, predicted long-term harm: from 1 = worst, to 5 = best). The total CBA score was calculated as the mean score across the 4 domains. CBA scores were compared between raters using the intra-class correlation coefficient (ICC: for two-way agreement). Logistic regression models tested odds of poor outcome by CBA scores across 4 domains. Results Practicing clinicians were eager to participate, suggesting this type of research will be worthwhile and feasible. Among 30 KTR, the median total CBA transplant suitability score was 3 (IQR 3-4, range 1-5). Overall agreement was moderate (ICC for the total CBA score: 0.63, 95% CI 0.51-0.74; p < 0.001), but with substantial variation in CBA scores across the domains and between raters (Figure 1). In 3 of the 4 domains (perceived suitability: OR 0.91, 95% CI 0.48-1.73; predicted short-term: OR 0.70, 95% CI 0.33-1.51; and predicted long-term harms: OR 0.82, 95% CI 0.35-1.91), CBA scores adjusted for UKRRI were associated with poor outcome after transplantation in the expected direction. For predicted benefit, the point estimate was not in the expected direction; individuals with greater predicted benefits were more likely to have poor outcomes (OR 1.46, 95% CI 0.28-7.47). Unsurprisingly, given the small numbers in this pilot and the substantial influence of the donor organ on outcomes in kidney transplantation, all the confidence intervals were wide and crossed the null, indicating considerable uncertainty. Conclusion In patients undergoing assessment for kidney transplantation, measuring clinical judgement retrospectively is feasible, though subject to variability across domains and between raters. We did not identify any clear associations between retrospective assessment of CBA and outcome after kidney transplantation in this small pilot. In future work, we will develop and validate measures of clinical judgement, collect these measures prospectively, and examine the relationship of measured clinical judgement with health outcomes.

The Halifax flow Crossmatch Protocol Results According to the HLA Class and MFI of the DSA

Introduction: The main strategy to reduce the immunogenicity of transplanted grafts is to seek maximum compatibility between alloantigens in the donor-recipient pair. It is understood that the virtual crossmatch (VXM) can be a good tool in the evaluation of the donor / recipient pair and that a broader application of these protocols will improve the pre-transplant immunological risk assessment. The aim of this study was to correlate the physical flow crossmatches results, looking at different mean fluorescence intensity (MFI) values of the donor specific antibodies (DSA), and the probability of a positive crossmatch. We also aimed to validate this tool using a well standardized flow crossmatch protocol. Methods: We performed a total of 15,217 FCXM between 2015 and 2019. All were tested by the Halifax Flow Cytometer Crossmatch (FCXM) protocol, with cells from deceased donors and serum from renal recipients. For this analysis we selected only samples that had one or two DSA per locus (N = 1,081), when the MFI was above 1,000, and they were divided according to the allelic group recognized by the antibody (anti-HLA-A, B, C, DR or DQ) looking at the probability of a positive crossmatch with different MFI values of the DSAs. Combinations among them were also analyzed in the same way (N=175). Results: In the presence of an exclusive DSA against the allelic groups A, B and DR, with an index MFI above 5,000, all the FCXM were positives. With exclusively antibodies against groups C or DQ, all cases with DSAs above 15,000 MFIs were positives. With two or more DSAs anti A and/or B, and/or DR, when their MFIs sums exceeded 5,000, all FCXM results against B cells were positive. The presence of anti-Class I DSAs (A, B and A+B), regardless of the MFI value, was responsible for 71% (N=424 of 601) of the T cell positivity and 77% (N=460 of 661) in the B cell crossmatches. The presence of only anti-Class II DSAs (DR and DQ) accounted for 55% (N=168 of 303) of FCXM positivity in B cells. The overall mean of the MFI of the DSAs was higher in the FCXM positive group when compared to negative crossmatch. The group with sum of DSAs A (N=217) showed that when the sum was 4,000 MFI or higher, there was a 24 times higher probability for a positive B cell crossmatch when compared with lowers MFIs. Conclusions: Our results show a strong association between the DSA MFI and the FCXM result. The data here presented confirm the results of our previous studies, justifying the VXM standard used by our center, proving to be a good tool to streamline the selection of transplant recipients and facilitate the sharing of organs from national donors.

A Case Report of Successful Renal Transplantation After Surgically Treated Type A Aortic Dissection

BackgroundAortoiliac lesions can influence the results of kidney transplantation and increase technical difficulties during surgery. Aortic dissection (AD) is a rare and infrequently reported event before transplantation, whereas immediate optimal perfusion is paramount for kidney transplantation. Thus, adequate blood flow imposed by the flow from the true lumen must be considered when choosing a target inflow vessel. Case presentationA 67-year-old man on dialysis with end-stage renal disease caused by immunoglobulin A nephropathy was referred for kidney transplantation. He had successfully undergone conventional Stanford type A AD surgery 3 years ago. Pretransplant contrast-enhanced computed tomography angiography revealed termination of the distal intimal flaps within the common iliac arteries. Dilation of the descending aorta was also observed. Based on the meticulous vascular assessment, including consultation with the cardiovascular surgery department, the right internal iliac artery (IIA) was considered usable for anastomosis. He underwent living unrelated kidney transplantation from his 66-year-old wife. The patency and blood flow in the right IIA were also verified using intraoperative findings. Without any special procedure, we used a side-to-end arterial anastomosis between the donor renal artery and recipient IIA. After vascular clamp removal, the allograft was perfused homogeneously and immediately functioned. ConclusionPatients receiving previous surgery for type A AD can successfully undergo kidney transplantation if the patency of the iliac arteries from the true lumen is confirmed by perioperative evaluation, and the artery can be carefully clamped to avoid possible further dissection.

A Lesson of Immunosuppression in Renal Transplant: Retreat or Hold?

Background: Aiming at understanding whether there are cases of near-tolerance among long-term surviving kidney transplant recipients in our center, or even operant tolerance can be attempted based on their immune status, we analyzed changes of immune cell subsets and cytokines in various groups, and evaluated immune status of long-term survival recipients. Methods: A real-world, observational, retrospective cohort study was conducted in our hospital. Twenty-eight long-term recipients were selected as study subjects, 15 recent postoperative stable recipients, and 15 healthy subjects as controls. T and B lymphocyte subsets, MDSCs, and cytokines were detected and analyzed. Results: Treg/CD4 T cells, total B and B10 cells in long-term and recent renal recipients were lower than healthy controls (HC). The level of IFN-γ and IL-17A in long-term survival patients was obviously higher than that in recent postoperative stable recipients and HC, while TGF-β1 level was significantly lower in long-term survival group than in short-term postoperative group and HC. Notably, compared with short-term recipients, it has been found that the IL-6 level in both positive and negative HLA groups were obviously lower (all P<0.05). In the long-term survival group, 43% of recipients were positive for urinary protein and 50% were positive for HLA antibody. Conclusion: This "real-world" study validates the findings of real status of long-term survival recipients observed in clinical trials. Contrary to a state of proper tolerance as expected, the group recipients in long-term survival were accompanied by the increased indicators of immune response, while those related to immune tolerance were not significantly increased. Long-term survival recipients with stable renal function may be in an immune equilibrium state where immunosuppression and rejection coexist under the action of low-intensity immune agents. If immunosuppressive agents are reduced or even removed, rejection may occur.

Pattern of urinary tract and surgical site infection in allograft renal recipient during early postoperative period

A kidney transplant (KT) offers a significant survival benefit and is the only curative treatment for patients with ESRD. Infectious complications are still a leading cause of morbidity and death among transplant patients. This study aimed to assess the organisms and risk factors responsible for urinary tract and surgical site infection in allograft live-related renal transplant recipients during the early post-transplant period. This observational follow-up study was conducted among 20 purposively selected patients who underwent renal allograft transplant surgery from July 2019 to December 2020 in the Department of Urology, BSMMU, Dhaka. Patients with a history of renal transplant recipients or congenital renal anomalies and any urological malignancy were excluded from the study. After kidney transplant, UTI developed in 6 (30%) renal transplant recipients where all were complicated types and occurred between 10 to 14 days postoperatively. UTI was caused by E. coli in 3 (15%) patients, while Klebsiella and Enterococci were causative organisms for 1 (5%) and 2 (10.0%) patients, respectively. SSI developed in 3 (15%) renal transplant recipients where two were superficial, and one was deep. SSI occurred between 5-8 days postoperatively. SSI was caused by S. aureus in 2 (10%) patients and Pseudomonas in 1 (5%) patient. UTI was significantly more in older patients and the patients with a longer duration of catheterization. Older patients and overweight patients had significantly higher rates of SSI. In total, 33% of the recipient during the early hospital stay developed UTIs, all of which were complicated types. SSI developed in 15%, where 2/3rd was superficial and 1/3rd was deep. Older age with a longer duration of catheterization and DJ stent was found to be associated with the occurrence of UTI, while older age and high BMI were related to the event of SSI. BSMMU J 2022; 15(2): 127-131

Antiphospholipid Syndrome in Renal Allograft Recipients-A Long-Term Multicenter Analysis.

The aim of the study was to assess renal allograft function and survival in recipients with APS. Retrospective, multicenter study included 19 adult renal recipients with definite APS (primary or lupus-related) from three Polish transplant centers. Renal allograft function was assessed using serum creatinine concentration (SCr1) at 3rd month post-transplant and at the end of the observation (SCr2) and glomerular filtration rate (GFR) was estimated based on modification of diet in renal disease (MDRD) formula. General linear model was used to assess 12 month GFR change over time. Kaplan-Meier curves and restricted mean survival time were used for allograft survival. Matched control group consisted of 21 stable renal recipients without history of thrombosis and without anticoagulation/antiplatelet treatment. The study group differs in induction therapy (p = 0.019), high-urgency procedure (p = 0.04), proteinuria (p = 0.0058), primary disease (lupus) (p &lt; 0.0001), re-transplantation in primary APS (p = 0.0046) and shorter time since engraftment to SCr2 (p = 0.016). Primary APS was more often diagnosed post-transplant (p = 0.0005). Allograft biopsy revealed thrombotic microangiopathy (TMA) with acute rejection (AR) or isolated AR vs AR or chronic rejection in controls but did not reach significance (p = 0.054). Renal allograft function was inferior in the study group but did not reach significance: mean SCr2 (mg/dL) was 2.18 ± 1.41 and 1.5 ± 0.68 in controls, respectively, p = 0.27; mean GFR2 (ml/min/1.73m2) was 39.9 ± 20.83 and 51.23 ± 19.03, respectively, p = 0.102. Renal allograft duration was inferior in patients with APS and was (in years) 11.22 ± 1.44 vs. 14.36 ± 0.42, respectively, p = 0.037, in patients with primary APS (p = 0.021), in patients with APS diagnosed post-transplant (p = 0.012) but not in lupus-related APS (p = ns). Fifteen year renal allograft survival was inferior in APS vs. controls (73,86% vs. 90.48%, respectively, p = 0.049). Recipients with APS are at higher risk for allograft loss due to immune and non-immune causes. Renal allograft survival was inferior in recipients with APS and renal function remains impaired but stable.

Wide-spectrum antibiotic prophylaxis guarantees optimal outcomes in drowned donor kidney transplantation

ABSTRACT Background Drowned victims possibly obtain various pathogens from drowning sites. Using drowned renal donors to expand the donor pool still lacks consensus due to the potential risk of disease transmission. Research design and methods This retrospective study enrolled 38 drowned donor renal recipients in a large clinical center from August 2012 to February 2021. A 1:2 matched cohort was generated with donor demographics, including age, gender, BMI, and ICU durations. Donor microbiological results, recipient perioperative infections, and early post-transplant and first-year clinical outcomes were analyzed. Results Compared to the control group, drowned donors had significantly increased positive fungal cultures (36.84% vs.13.15%, p = 0.039). Recipients in the drowned group had significantly higher rates of gram-negative bacteria (GNB) and multidrug-resistant GNB infections (23.68% vs.5.26%, 18.42% vs. 3.95%, both p < 0.05). Other colonization and infections were also numerically more frequent in the drowned group. Drowned donor recipients receiving inadequate antibiotic prophylaxis had more perioperative bloodstream infections, higher DGF incidences, and more first-year respiratory tract infections and recipient loss than those receiving adequate prophylaxis (all p < 0.05). Clinical outcomes were similar between the adequate group and the control group. Conclusions Drowned donors could be suitable options under wide-spectrum and adequate antimicrobial prophylaxis.

Post-Transplant Diabetes Mellitus in Renal Transplant Recipients, Single-Centre Data: Incidence, Risk Factors, and Effect on Graft Function and Mortality

Background: De novo post-transplant diabetes mellitus (PTDM) is a frequent complication among renal transplant recipients; it confers a high risk for graft failure and patient mortality. This single-centre study aimed to determine the incidence and risk factors of PTDM and its effects on graft outcome and mortality. Methods: In a single-centre longitudinal cohort analysis of 383 non-diabetic renal transplant follow-up recipients, outcomes were analysed through a detailed chart review. We hypothesized that different donor and recipient characters such as age, gender, and HLA mismatch would affect PTDM development in renal transplant recipients. PTDM is defined on basis of fasting plasma sugar (≥7 mmol/L or ≥126 mg/dL), random plasma sugar (≥11.1 mmol/L or ≥200 mg/dL), and glycated haemoglobin (HBA1C: >6.5% or 48 mmol/mol). We assessed PTDM incidence, risk factors, and its effect on patient mortality and graft outcome using Cox regression. Results: The mean age at the time of transplantation was 35.70 (±14.27) years, and 50.91% were male. PTDM incidence in the study period was 23.30%. Independent risk factors include older age at the time of transplantation, cyclosporine immunosuppression, cytomegalovirus, and hepatitis C virus infection. PTDM is not associated with graft dysfunction, whereas it significantly carries high mortality. Conclusion: PTDM is common among renal transplant recipients. Older age at the time of transplantation, cyclosporine immunosuppression, cytomegalovirus, and hepatitis C virus are risk factors. PTDM carries high mortality but is not associated with graft failure.

The Optimization of Renal Graft Preservation Temperature to Mitigate Cold Ischemia-Reperfusion Injury in Kidney Transplantation.

Renal transplantation is the preferred treatment for patients with end-stage renal disease. The current gold standard of kidney preservation for transplantation is static cold storage (SCS) at 4 °C. However, SCS contributes to renal ischemia-reperfusion injury (IRI), a pathological process that negatively impacts graft survival and function. Recent efforts to mitigate cold renal IRI involve preserving renal grafts at higher or subnormothermic temperatures. These temperatures may be beneficial in reducing the risk of cold renal IRI, while also maintaining active biological processes such as increasing the expression of mitochondrial protective metabolites. In this review, we discuss different preservation temperatures for renal transplantation and pharmacological supplementation of kidney preservation solutions with hydrogen sulfide to determine an optimal preservation temperature to mitigate cold renal IRI and enhance renal graft function and recipient survival.

Influence of CYP3A5, IL-10 polymorphisms and metabolism rate on tacrolimus exposure in renal post-transplant recipients.

Aim: To investigate the influence of CYP3A5 and IL-10 polymorphisms on tarcolimus metabolism and renal function for renal transplantation recipients at astable period. Methods: CYP3A5 and IL-10 polymorphisms, together with other clinical factors, were collected for 149 renal transplantation patients at postoperative stable period. Statistics analysis was performed to explore key factors affecting tarcolimus metabolism. Results: CYP3A5 6986A >G and IL-10 -819C >T significantly impacted tacrolimus metabolism (p<0.001). CYP3A5 6986A >G G allele and IL-10 -819C >T T allele were associated with poorer tacrolimus metabolic capability. Patients with various tacrolimus metabolism rates presented little difference in renal functions at stable period. Conclusion: Genotyping of CYP3A5 andIL-10 might benefit the precision dosage of tacrolimus for renal transplantation recipients.

Effect of Carbapenem-Resistant Klebsiella pneumoniae Infection on the Clinical Outcomes of Kidney Transplant Recipients.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has proven to be difficult to control and typically presents with devastating effects. This retrospective study was conducted on the renal recipients at our institution between January 2021 to January 2022. Clinical data was collected to identify factors associated with CRKP infection and clinical outcomes. There were 104 cases out of 186 total renal recipients who presented with at least one infection within 3 months after KT, and 14 cases developed unfavorable clinical outcomes. We identified 16 confirmed CRKP infected cases with the incidence of 8.60%. Possible donor derived infection (DDI) (OR = 6.743; 95% CI: 1.477-30.786; P = 0.014) were independent risk factors for the occurrence of CRKP infection of renal recipients in our analysis, CRKP infection (OR = 20.723; 95% CI: 3.448-124.547; P = 0.001) and pneumonia (OR = 28.458; 95% CI: 1.956-413.984 P = 0.014) were independent risk factors for the occurrence of unfavorable clinical outcomes following KT, and the occurrence of unfavorable clinical outcomes following KT were significantly associated with CRKP infection (r = 0.535; P < 0.001) and antibiotic regimen containing ceftazidime/avibactam (CZA) (r = -0.655; P = 0.006). The use of CZA was significantly different in the comparison of antibiotic regimens between the CRKP infected renal recipients with unfavorable outcomes and CRKP infected patients with favorable outcomes. It is possible that DDI can lead to CRKP infection, and CRKP infection and pneumonia were closely correlated with poor prognosis. The use of CZA may play a role in avoiding the unfavorable outcomes of CRKP infected recipients.

Should the First Rejected Kidney Implant be Removed?

Renal transplantation (TX) is widely used as a definitive therapy for chronic, end-stage organ failure. T cells are pivotal in rejection (RX), and RX is a process whereby donor tissue is recognized and destroyed by the host immune system. Within a rejecting graft it is likely that high concentrations of IL-2 are present. The binding of interleukin 2(IL-2) to its receptor (IL-2R) on human T cells constitutes the key regulatory event in the initiation and maintenance of the immune response. The receptor, IL-2R, is found in two forms: cellular and soluble. The surgical removal of a transplanted kidney following RX or failure can be hazardous. Two surgical techniques were applied: extracapsular and intracapsular removal. The technique of kidney transplant removal by either the intra- or extra-capsular route of the exact timing of the operation are important features for safe treatment of patients with end-stage graft failure. The results of the report are a prospective study on 21 renal TX recipients, and show that nephrectomy of previous TX kidney will reduce the levels of four markers in serum and urine.

Monitoring of Soluble Forms of BAFF System (BAFF, APRIL, sR-BAFF, sTACI and sBCMA) in Kidney Transplantation.

BAFF system plays an essential role in B cells homeostasis and tolerance, although it has widely not been tested in transplantation with doubtful results. The main purpose was to study the BAFF soluble forms and their correlation with acute rejection (AR) and donor-specific antibodies production. Serum levels of BAFF, APRIL, and soluble forms of their receptors were analyzed in renal recipients with and without acute rejection (AR/NAR) appearance. All molecules were evaluated at pre- and post-transplantation. sTACI showed a significant correlation with BAFF and sR-BAFF levels, and sBCMA also showed a positive correlation with sAPRIL levels. A significant increase in sAPRIL levels in patients suffering AR was also found, and ROC curves analysis showed an AUC = 0.724, a concentration of 6.05ng/ml (sensitivity: 66.7%; specificity: 73.3%), the best cutoff point for predicting AR. In the post-transplant dynamics of sAPRIL levels in the longitudinal cohort, we observed a significant decrease at 3 and 6 month post-transplantation compared to pretransplantation status. We also observed that recipients with high pre-transplant levels of sAPRIL generated antibodies earlier than those with lower sAPRIL levels, although their long-term post-transplantation was not different. Our results show that elevated serum levels of APRIL may be helpful as a biomarker for the diagnosis of AR, although the longitudinal study shows that it is not helpful as a prognostic biomarker.

P181 Mucor in the land of the liver: a case report

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM Introduction and ObjectivesMucormycosis is a rare, highly lethal opportunistic fungal infection affecting immune-compromised patients. It accounts for about 2% of invasive fungal infections occurring within 1 year after solid organ transplantation. Among renal recipients, Rhinocerebral is the commonest manifestation and Rhizopus species is the most frequent pathogen.The objectives are:To report a case of Hepatic mucormycosis in a renal transplant recipient.To resolve the dilemma in identification of Mucorale species detected on microscopy but culture negative.MethodA 29-year-old male patient was admitted with severe abdominal pain on day 28 post-live related renal transplantation. Patient was hypertensive, on oral steroids for idiopathic thrombocytopenic purpura, chronic kidney disease with venous thromboembolism-presumed chronic interstitial nephritis, and maintained on hemodialysis for the last 1 year. Post-transplant he was on triple immunosuppressants.Initial ultrasound of abdomen and transplant doppler were normal. CT of abdomen in view of worsening hypotension and non-resolving abdominal pain, revealed hepatomegaly with multiple discrete, coalescing hypodense areas in both lobes of liver with minimal subcapsular extension. Initial cultures included interventional radiology-guided liver aspirate and blood culture. Patient was started on antibiotics and antifungals. Patient continued to deteriorate and a repeat abdominal CT revealed an increase in liver size and rupture of liver abscess. Sample collected on pigtail catheter insertion was also sent for culture.ResultsThe pus aspirate was received for bacterial and fungal culture. Aerobic bacterial culture yielded Klebsiella species. Examination with KOH Calcofluor revealed broad aseptate fungal hyphae. However, fungal culture did not yield any growth. Pain resistant (PDR) Klebsiella species was isolated from blood culture. Pigtail catheter sample also yielded the same. Aseptate fungal hyphae were observed in the pigtail catheter sample also. The team decided on conservative management and patient was started on intravenous amphotericin B deoxycholate(50 mg/day), tigecycline, and meropenem. Immunosuppressants were withheld. The clinical course worsened and the patient succumbed to illness after 18 days of antifungal therapy. The pus sample was then sent to the referral center PGIMER for PCR and sequencing where it was identified as Lichtheimia species.ConclusionMucormycosis is an increasingly emerging invasive fungal infection especially in immune-compromised patients, including solid organ transplant recipients. Though uncommon it is frequently a fatal mycosis in transplant patients. Hepatic mucormycosis in renal transplant recipients has been reported in three patients so far. None are due to Lichtheimia species. The diagnosis of hepatic mucormycosis was confirmed as microscopy was positive in two successive samples. Our patient also had bacteremia with PDR Klebsiella.Diagnosis is challenging and often delayed, as the clinical presentation is non-specific. Although mucormycosis in a renal transplant recipient is rare, a high index of suspicion and critical microscopic examination is warranted for early initiation of specific therapy which includes liposomal amphotericin B and surgery. Often cultures yield no growth and gene sequencing proves to be efficient and time-saving. This probably is the way ahead, especially for culture-negative samples to establish the etiological diagnosis.

210.1: Immunosuppression Minimization During COVID Infection: Is It Safe?

Introduction: Managing post-transplant COVID-19 patients has proven challenging. On one hand, they are more vulnerable due to their immunocompromised status, and on the other hand, reducing immunosuppression (IS) may result in graft rejection and formation of de-novo donor specific antibodies (DSA). Here, we share our experience of balancing disease treatment and the risk of rejection in a cohort of renal post-transplant recipients. Methods: We retrospectively collected data on 136 renal transplant recipients who were diagnosed with COVID-19 between May 2020 and December 2021. Clinical information, demographics and HLA antibody data were extracted from patients’ medical records. Results: The median time from transplant to COVID-19 diagnosis in our cohort was 4.1 years (range 13 days to 30.8 years). The average age at diagnosis was 50.5 and 63% were males. 28% of the patients were hospitalized and 13.2% had died as a result of their infection. The most common therapies included Monoclonal antibodies (39.7%), Dexamethasone (22%) and Remdesivir (18.4%). IS modulation, which primarily included holding off the anti-metabolite, was done in 98/136 patients (72%), and was later resumed in 70 of the 98 patients with a median time of 8.6 days (range 2-204) from holding off to resuming IS. 25 patients had pre- and post-infection DSA data. Despite the modulation in IS, 23 out of the 25 patients did not exhibit a change in DSA status (within a median time follow up of 70 days) nor a significant change in sensitization status as determined by calculated panel reactive antibody (cPRA). Only two patients developed de-novo DSA post COVID-19 infection, however a biopsy performed on one patient did not show acute rejection. Four patients progressed to graft failure post infection - Two due to worsening chronic antibody mediated rejection, one had renal injury due to direct effects of COVID-19 infection, and one had failing graft before COVID-19, suffered a severe disease including intubation and lost his graft shortly after recovering. Conclusions: Reduction of the anti-metabolic immunosuppressive therapy for a short period of time did not seem to correlate with development of de-novo DSA or increased rates of acute rejection in our expanded cohort. Studies on larger cohorts will help further determine the impact of IS reduction on transplant outcomes following COVID-19 infection in renal transplant recipients.

Clinical utility of immune function based on IFN-γ monitoring of lymphocyte subsets for parvovirus B19 infection in renal recipients.

There should be a heightened index of suspicion for Parvovirus B19 (PVB19)-related anemia in organ transplant recipients. Thus far, there is no consensus or recommendation for clinical routine monitoring methods of PVB19 recipients to allow tailoring of immunosuppression. We conducted a retrospective study to evaluate the utility of the function (represented by the abilities to secrete IFN-γ) and numbers of lymphocyte subsets in monitoring PVB19 infections in renal recipients posttransplant. The enrolled 109 patients were split into 2 groups according to whether the recipients had an occurrence of PVB19 infection: 37 (33.94%) recipients developed PVB19 infection and 72 (66.06%) immune-stable recipients. The PVB19 infected group had significantly lower absolute counts and functions of different lymphocyte subsets compared with immune-stable recipients. We showed that the frequencies of IFN-γ+CD4+T cells, IFN-γ+CD8+T cells, and IFN-γ+NK cells increased markedly after treatment when compared to the occurrence in patients with timepoint before therapy, especially the percentages of IFN-γ+CD4+T cells were significantly higher. Receiver operating characteristic (ROC) analysis showed that the optimal infection indicator was IFN-γ+NK cells frequency, with an auROC curve of 0.925. Concomitantly, Cox regression analysis indicated that the post-therapy increasing level of IFN-γ secreting function was significantly predictive of recurrent infections (P<0.001). We recommend prospective risk stratification for the high-risk population at risk of early-onset PVB19 infection and its recurrence involves screening strategies of immune-based surveillance with the sensitive IFN-γ+secreting monitoring for antiviral prophylaxis and preemptive therapy goal. Clinical Trial Notation: clinical trial registration number: chiCTR-ROC-17010756.