Renal Recipients Research Articles

Suspicious of Acute Kidney Graft Rejection: Tacrolimus Pharmacokinetics Under Methylprednisolone Therapy.

Acute rejection remains one of the main complications in the first months after transplantation and may influence long-term outcomes. Tacrolimus has proven its usefulness in solid organ transplants and its monitoring through the application of pharmacokinetic concepts to optimize individual drug therapy. This research proposes to evaluate the tacrolimus pharmacokinetic parameters in patients suspected of acute kidney graft rejection under methylprednisolone pulse therapy. Eleven adult tacrolimus-treated renal recipients were selected from a prospective, single-arm, single-center cohort study, with suspicion of acute rejection although in use of methylprednisolone pulses therapy. They were followed up for three months posttransplantation, being tacrolimus trough serum concentrations determined using a chemiluminescent magnetic immunoassay, and pharmacokinetic parameters were estimated by using a nonlinear mixed-effects model implemented by Monolix 2020R1. A tacrolimus trough serum concentration range of 8 to 12 ng.mL-1 was considered therapeutic. Six patients showed acute cellular rejection, and two of them in addition had an antibody- mediated rejection. Tacrolimus trough serum concentration was below the reference range in eight patients. Most patients showed a high tacrolimus concentration intrapatient and pharmacokinetic parameters variability. The obtained pharmacokinetics parameters helped in understanding the kidney recipient patients' tacrolimus behavior, assisting in the improvement of individual drug therapy and reducing the risk of acute rejection episodes.

410.9: Borderline (BL) rejection on renal recipients. Is steroid treatment enough to resolve it?.

410.9: Borderline (BL) rejection on renal recipients. Is steroid treatment enough to resolve it?.

Predictors of post-kidney transplantation complications among Egyptian recipients—1-year follow-up

BackgroundKidney transplantation is the optimal treatment modality for patients with end-stage kidney disease. We aimed to identify predictors for post-transplantation complications.MethodsA prospective cohort study with 1-year follow-up on 40 recipients (with their donors) were recruited and followed up for 1 year after transplantation. The patients were classified into two groups according to development of complications or not.ResultsIt was found that renal recipient had significantly lower mean age compared to donors (30.55 ± 10.24 vs. 41.28 ± 9.83 (years); p < 0.001). The reported complications were hypertension (42.5%), proteinuria (17.5%), surgical difficulty (17.5%), chronic rejection (12.5%), DM (7.5%), and other less common complications. Death occurred in six recipients. Significant predictors for complications were history of DM (OR = 3.429; 95% CI = 1.148–5.058; p = 0.044), BUN (OR = 2.501; 95% CI = 1.094–4.007; p = 0.038), creatinine (OR = 1.90; 95% CI = 1.025–2.806; p = 0.015), older age (OR = 1.854; 95% CI = 1.090–3.195; p = 0.033), pre-transplantation leucocytic count (OR = 1.775; 95% CI = 1.057–3.901; p = 0.039), and LDL (OR = 1.051; 95% CI = 1.009–2.441; p = 0.047). Elevated PTH in pre-transplantation showed significantly slight protective effect against development of complications (OR = 0.915; 95% CI = 0.624–0.957; p = 0.031).ConclusionComplications are common after kidney transplant in our population and are associated with history of DM, pre-transplantation BUN, creatinine, and older age, while elevated pretransplant PTH showed slightly protective effect.

Can the pan-immune-inflammation value predict gram negative bloodstream infection-related 30-day mortality in solid organ transplant patients?

BackgroundThe recently used pan-immune-inflammation value (PIV) has not been adequately studied as a predictive marker for mortality in immunosuppressed patients. The aim of this study was to evaluate the usefulness of baseline PIV level as a predictor of 30-day mortality in solid organ transplant (SOT) recipients with gram negative bloodstream infections (GN-BSI).MethodsThis retrospective, cross-sectional study was conducted between January 1, 2019, and December 31, 2022, in 1104 SOT recipients. During the study period, 118 GN-BSI were recorded in 113 patients. Clinical, epidemiological, and laboratory data were collected, and mortality rates (30-day and all-cause) were recorded.ResultsThe 113 recipients had a median age of 50 years [interquartile range (IQR) 37.5–61.5 years] with a male predominance (n = 72, 63.7%). The three most common microorganisms were as follows: 46 isolates (38.9%) of Escherichia coli, 41 (34.7%) of Klebsiella pneumoniae, and 12 (10.2%) of Acinetobacter baumannii. In 44.9% and 35.6% of the isolates, production of extended-spectrum beta-lactamases and carbapenem resistance were detected, respectively. The incidence of carbapenem-resistant GN-BSI was higher in liver recipients than in renal recipients (n = 27, 69.2% vs n = 13, 17.6%, p < 0.001). All-cause and 30-day mortality rates after GN-BSI were 26.5% (n = 30), and 16.8% (n = 19), respectively. In the group with GN-BSI-related 30-day mortality, the median PIV level was significantly lower (327.3, IQR 64.8–795.4 vs. 1049.6, IQR 338.6–2177.1; p = 0.002). The binary logistic regression analysis identified low PIV level [hazard ratio (HR) = 0.93, 95% confidence interval (CI) 0.86–0.99; p = 0.04], and increased age (HR = 1.05, 95% CI 1.01–1.09; p = 0.002) as factors associated with 30-day mortality. The receiver operating characteristic analysis revealed that PIV could determine the GN-BSI-related 30-day mortality with area under curve (AUC): 0.723, 95% CI 0.597–0.848, p = 0.0005.ConclusionsPIV is a simple and inexpensive biomarker that can be used to estimate mortality in immunosuppressed patients, but the results need to be interpreted carefully.

#1167 Examination of subsets of CD4+ lymphocyte subpopulations in long-surviving renal transplant patients

Abstract Background and Aims Subpopulations of CD4+ cells, play a major role in mediation of rejection and tolerance to a renal transplant. This study examined subsets of CD4+ T cells and CD4+CD25+CD127lo Treg in blood of renal graft recipients with grafts surviving &amp;gt;10 years for changes in lymphocyte subpopulations that may indicate transplant tolerance and potentially identify patients who could reduce immunosuppression. Based on CD45RA and CD25/Foxp3 expression, Miyara et al identified five populations (Pop) within CD4+ cells. Pop I, II and III are T regulatory cells (Treg); Pop I as naïve (CD45RA+Foxp3+) Treg, Pop II as activated (CD45RA-Foxp3hi) Treg, and Pop III as cytokine secreting (CD45RA-Foxp3+) cells which also includes activated effector cells. Pop IV are activated T cells (CD45RA-Foxp3−), and Pop V are naïve T cells (CD45RA+Foxp3−). Here, we examined three Treg populations (Pop I-III) within CD4+CD25+CD127lo Treg, and Pop IV and V within CD4+ T cells. To further characterise these subpopulations, we examined chemokine receptor expression (CXCR3, CCR4, CCR6, and CCR7) to identify T helper phenotype (Th-like) of Treg populations. Th1-like Treg were identified as CCR4+CXCR3+CCR6−, Th2-like as CCR4+CXCR3-CCR6−, Th17-like as CCR4+CXCR3-CCR6+, and Th1/Th17-like as CCR4+CXCR3+CCR6+. We also examined expression of activated Treg effector molecules CD39, Class II MHC, and PD-1. Method Peripheral blood mononuclear cells (PBMC) were isolated from fresh blood collected from healthy volunteers (HV) (n = 44) and long-term stable renal transplant patients with grafts surviving &amp;gt;10 yrs (RT) (n = 25). Panels of monoclonal antibodies for Treg (CD4/CD25/CD127/CD45RA/Foxp3), chemokine receptors (CXCR3, CCR4, CCR6, CCR7), and Treg activation and suppression-related molecules (CD39/HLA-DR/PD-1) were also used. Data was acquired on BD FACSCanto II using BD FACSDiva software (v8.0) and analysed using FlowJo. Lymphocyte populations were examined after FSC vs SSC gating and doublets exclusion. T cell and Treg populations were analysed within CD4+ and CD4+CD25+CD127lo T cells. Results RT had lower lymphocyte counts than HV (p = 0.0156) but had a similar percentage of CD4+ T cells. Treg were significantly lower in RT compared to HV (p = 0.0012). RT patients had less naïve Treg (Pop I, p = 0.0083) and naïve effector T cells (Pop V, p = 0.0003), but had higher activated effector T cells (Pop IV, p = 0.0002) than HV. There were no differences in activated Treg Pop II or III between the two groups. There were significantly less cells expressing CXCR3 in RT than HV in Pop I (p = 0.0120), Pop II (p &amp;lt; 0.0001), Pop III (p &amp;lt; 0.0001) and Pop IV (p = 0.0047). Similarly, RT had fewer cells expressing CCR6 compared to HV in Pop II (p = 0.0019), Pop III (p = 0.0015), and Pop V (p = 0.0017). RT had lower proportions of CCR7 expressing cells in Pop I (p = 0.0035), Pop IV (p = 0.0097), and Pop V (p = 0.0002), but higher in Pop II (p = 0.0041) compared to HV. There were similar percentages of cells with Th1 and Th17-like phenotypes in both groups. However, RT had significantly more Th2-like Treg in Pop II (p = 0.0033) and Pop III (p = 0.0100), and significantly less Th1/Th17-like Treg in Pop II (p = 0.0005) and Pop III (p = 0.0017) compared to HV. There were little to no differences in the Treg activation and suppression-related molecules within subpopulations of Treg. Conclusion Long-surviving RT patients had less naïve Treg and naïve effector cells, but increased proportions of activated effector cells. There were little to no differences in the expression of Treg activation or suppression-related molecules in Treg subpopulations. Unexpectedly, activated Treg in RT had significantly higher proportions with a Th2 phenotype and significantly less Treg with a Th1/Th17 phenotype. Whether this is a consequence of immunosuppression, or a biological shift associated with tolerance, remains to be resolved. Further studies are required to investigate the relevance of these changes in identifying induction of transplant tolerance.

Tacrolimus Intrapatient Variability on Graft Outcomes inAdherent Renal Transplantation Patients: A Cross-SectionalStudy.

Tacrolimus is the mainstem of immunosuppressive therapy in kidney transplant patients. It has high intrapatient variability (Tac-IPV), which has been reported to affect graft function by predisposing patients to rejection or nephrotoxicity. We conducted this study with the aim of assessing the influence of Tac-IPV on 2-year graft function, biopsy-proven rejection, and infections in compliant renal recipients. In this single-center retrospective analytic cross-sectional study, 250 patients who underwent transplantation from March 21, 2018, to March 20, 2020 and had at least three outpatient tacrolimus trough levels on the same daily dose 6 to 12 months after transplantation were recruited. Tac-IPV was defined as a coefficient variation of > 15%. Graft function, biopsy-proven rejection, cytomegalovirus (CMV) and BK virus viremia, and calcineurin inhibitor (CNI) toxicity were evaluated. Of 202 transplant recipients, 128 were included with a mean age of 45.48 ± 13.14 years. The median Tac-IPV was 13.28% with 43.75% of patients with Tac-IPV > 15%. There were no significant differences in graft function, rejection, CNI toxicity, and CMV viremia among the groups during the 24-month study (P > .05). However, BK viremia was significantly higher among patients with Tac-IPV > 15% (13 vs. 2.9%, P = .042). The risk of antibody mediated rejection alone (22.7 vs. 2.9%) or any kind of rejection (22.7 vs. 11.8%) was significantly higher in patients with higher Tac-IPV, and in those who had mean trough levels below 7 ng/mL (P = .015, .032; respectively). Tac-IPV is low in adherent patients (with the median of 13.28%) and maintaining tacrolimus trough level above 7 ng/mL can overcome the adverse graft outcome of Tac-IPV in compliant kidney transplant recipients. DOI: 10.52547/ijkd.7815.

Renal transplant recipient and deceased-donor risk profiles at Wits Donald Gordon Medical Centre, Johannesburg, South Africa: A 9-year review.

Renal transplantation is the gold-standard therapy for end-stage renal disease. Decision-making around the acceptance of deceased-donor organs is complex and time sensitive. Risk scoring systems for both donors and recipients attempt to simplify the allocation of renal grafts to the most appropriate recipient. To investigate the role of these transplant risk scores in the South African (SA) setting. A total of 188 adult deceased-donor organ referrals over the 9-year period 1 January 2013 - 31 December 2021 were included. The Kidney Donor Risk Index (KDRI) and the UK KDRI were calculated for each donor. Recipients who were allocated these grafts were characterised, and the Hennepin Transplant Risk Score and the Kidney Transplant Morbidity Index (KTMI) were calculated. The median (interquartile range) KDRI was 1.2 (0.9 - 1.6), confirming that low- to average-risk donors were being utilised. Similarly, the median UK KDRI was 0.9 (0.8 - 1.2). Both these scores performed poorly in predicting graft and patient survival, with a C-statistic of 0.5. Renal recipient risk scores also demonstrated low- to average-risk patients being transplanted, with a median Hennepin score of 2 - 4 points and a KTMI of 2 points. These recipient scores predict increased recipient mortality at high scores, albeit with low sensitivity, and were not significantly associated with graft survival. Deceased-donor and renal recipient risk scores commonly used internationally performed poorly in predicting graft survival in our cohort, and should be used with caution in the SA setting. A conservative approach to organ donor referral and utilisation as well as renal transplant recipient listing was noted.

Seroprevalencia de virus BK en donadores y receptores de trasplante renal.

Introduction: BK virus (BKV) is highly prevalent in the general population, in renal transplant (RT) patients it is the main cause of infectious tubulointerstitial nephritis, leading to graft dysfunction or loss. The seroprevalence in the Mexican population is unknown. The present study seeks to establish the seroprevalence of VBK in renal donors and recipients in the Mexican adult population. Methods: This is a cross-sectional study conducted at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City in the period June 2017, April 2018. Seroprevalence prior to renal transplantation was evaluated through qualitative BK-IgG ELISA (MyBioSource Inc, San Diego, CA), in donors and recipients of RT. Results: Qualitative measurement of IgG for BK virus by ELISA method was performed in 80 donors and 88 renal recipients. The seroprevalence in donors was 56.3% (95%CI, 45%-67%), while in recipients it was 45.5% (95%CI, 35%-56%). None of the variables analyzed showed an association with increased risk of seropositivity for BKV in either recipients or donors. Conclusion: The seroprevalence of BKV in our center was lower than expected for a developing country, having a sufficient sample size to extrapolate it to the Mexican population.

Sonographic Assessment of Renal Transplantation in Adult Saudi Patients: A Cross-Sectional Retrospective Study

Kidney transplantation stands as a practical and cost-effective treatment option for end-stage renal disease patients, offering an improved quality of life with reduced morbidity when compared to hemodialysis. To evaluate the status of transplanted kidneys in Saudi patients, we conducted a retrospective single-center study at Jazan, Saudi Arabia, involving 46 adult renal recipients enrolled randomly from 2015 to December 2022. Utilizing high-frequency ultrasound, we performed Duplex ultrasound examinations to assess renal allografts. The study revealed that the renal grafts exhibited normal length, with preserved cortical medullary differentiation (CMD) in 84.8% of cases and poor CMD in 15.2%. The echogenicity of the grafts remained normal in 69.6% of instances. Interestingly, we observed a significant rise in resistance index (RI) values as the graft duration increased (p-value = 0.04), while patients with abnormal creatinine levels displayed decreased peak systolic velocity (PSV) and end diastolic velocity (EDV). Notably, sonographic graft assessments unveiled complications, including perinephric fluid accumulation (8.7%), simple renal cysts (10.86%), hydronephrosis (8.7%), and one case of graft rejection. ROC analysis for serum blood creatinine levels and abnormal parenchymal findings yielded fair to poor predictive accuracy, with varying sensitivity and specificity measures that lacked statistical significance. In conclusion, our study revealed that most Saudi renal transplant recipients exhibited grafts with normal echogenicity, preserved CMD, and limited perinephric fluid. This investigation provides valuable insights into sonographic changes and Doppler parameters of renal grafts, potentially aiding in the early detection of graft rejection and facilitating diagnostic and therapeutic planning.

Outcomes of Kidney Transplants From Toxoplasma-Positive Donors: An Organ Procurement and Transplant Network Database Analysis.

There is a need to reconsider the acceptance of organs from donors considered suboptimal, in the absence of data. Toxoplasma antibody-positive donors (TPD) constitute one such group. The objective of our study was to compare graft survival in deceased donor renal transplant (Tx) recipients, stratified by Toxoplasma IgG status, using the Organ Procurement and Transplantation Network (OPTN) database. A log-linear event history regression model for graft failure categorized by Toxoplasma IgG status, adjusting for confounders was applied to first kidney-only Tx recipients from 2018 to 2022. Of the 51,422 Tx, 4,317 (8.4%) were from TPD. Acute rejection and graft failure (5% each) were similar between groups. Crude graft failure was 7.3 failures per 100 person-years for TPD recipients compared to 6.5 failures per 100 person-years for the Toxoplasma-negative group (p 0.008). The crude failure rate ratio was 1.14 with an adjusted hazard rate ratio of 1.04 (95% CI: 0.94, 1.15, p 0.39). In renal Tx recipients, TPD graft recipients have comparable survival to Tx from Toxoplasma-negative recipients. While caution and close monitoring of recipients post-Tx for surveillance of disseminated toxoplasmosis are still warranted, our study suggests that patients can be successfully managed using TPD organs.

Assessment of renal quality with quantitative contrast-enhanced ultrasound (CEUS) for differentiating kidney histopathology before procurement.

Purpose: This study aimed to investigate the use of contrast-enhanced ultrasonography (CEUS) to assess the kidneys' quality before procurement. Methods: This prospective study included 74 donors and 148 recipients of kidneys. 119 kidneys underwent quantitative analysis. Before organ procurement, potential kidney donors underwent CEUS, though organ procurement involved a zero-point puncture biopsy. CEUS parameters of the renal cortex and medulla were evaluated, including rise time (RT), time to peak (TTP), the area under the curve (AUC), wash-in slope (WIS), peak intensity (PI), and mean transit time (MTT). Donors' kidneys were classified based on their pathological. Additionally, short-term clinical indicators of renal recipients were collected and analyzed to determine whether the patients had delayed recovery of renal allograft function. Results: This experiment included 148 cases of kidney information, divided into two groups based on the Remuzzi score of the kidneys. However, 29 kidneys were excluded from the quantitative analysis due to loss or low quality of CEUS images. Comparing the time-intensity curve (TIC) of renal cortical region of interest (ROI), we found that the group with lower pathological scores exhibited higher PI (P=0.002), AUC(P=0.003), and WIS (P=0.009). TIC comparison results for renal medulla ROI revealed that the group with lower pathological scores had higher PI (P=0.010), AUC (P=0.023), and WIS (P=0.024). Conclusions: This study highlighted the potential of CEUS as a non-invasive, safe, and real-time examination method that correlates with the Remuzzi score and renal pathology. Therefore, it can be used as a prospective preoperative non-invasive evaluation method for the donor's kidney.

The Impact of Quadriceps Muscle Layer Thickness on Length of Stay of Patients Listed for Renal Transplant

Background: Quadriceps muscle layer thickness (QMLT), which is measured using ultrasound, is an emerging strategy to identify sarcopenia. Purpose: The purpose of the study was to assess whether pre-operative QMLT values are associated with a prolonged length of stay (LOS; defined as &gt;14 days) following a renal transplant. Methods: Between March 2019 and January 2020, we performed a prospective study among patients undergoing renal transplantation. Physical Frailty scores and QMLT measurements were performed pre-operatively. The primary outcome was a greater LOS following transplant. Secondary outcomes included complications and renal function. Statistical analysis: Percentiles divided patients into two categories of QMLT (low and high). Continuous outcomes were compared using a two-sided t-test or Mann–Whitney U test, and Chi-square analysis and Fisher exact testing were used for nominal variables. Results: Of 79 patients, the frailty prevalence was 16%. Among patients with low and higher QMLTs, LOS of &gt;14 days were 21% vs. 3% [p = 0.04], respectively. Demographically, there was a higher percentage of patients with living donors in the high- vs. low-QMLT groups (40 vs. 7%). However, in a subgroup analysis excluding living-donor recipients, the difference between groups was preserved (23% vs. 0%, p = 0.01). No differences in secondary outcomes were seen between groups. Conclusions: Low quadriceps muscle layer thickness may be associated with a prolonged length of stay for renal recipients. Further research is needed to confirm our findings.

The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living-donor Egyptian kidney transplanted patients.

Tacrolimus (TAC) is the mainstay of immunosuppressive regimen for kidney transplantations. Its clinical use is complex due to high inter-individual variations which can be partially attributed to genetic variations at the metabolizing enzymes CYP3A4 and CYP3A5. Two single nucleotide polymorphisms (SNPs), CYP3A4*22 and CYP3A5*3, have been reported as important causes of differences in pharmacokinetics that can affect efficacy and/or toxicity of TAC. Investigating the effect of CYP3A4*22 and CYP3A5*3 SNPs individually and in combination on the TAC concentration in Egyptian renal recipients. Overall, 72 Egyptian kidney transplant recipients were genotyped for CYP3A4*22 G>A and CYP3A5*3 T>C. According to the functional defect associated with CYP3A variants, patients were clustered into: poor (PM) and non-poor metabolizers (Non-PM). The impact on dose adjusted through TAC concentrations (C0) and daily doses at different time points after transplantation was evaluated. Cyp3A4*1/*22 and PM groups require significantly lower dose of TAC (mg/kg) at different time points with significantly higher concentration/dose (C0/D) ratio at day 10 in comparison to Cyp3A4*1/*1 and Non-PM groups respectively. However, CyP3A5*3 heterozygous individuals did not show any significant difference in comparison to CyP3A5*1/*3 individuals. By comparing between PM and Non-PM, the PM group had a significantly lower rate of recipients not reaching target C0 at day 14. This is the first study on Egyptian population to investigate the impact of CYP3A4*22 and CYP3A5*3 SNPs individually and in combination on the TAC concentration. This study and future multicenter studies can contribute to the individualization of TAC dosing in Egyptian patients.

Prospective assessment of pre-existing and de novo anti-HLA IgE in kidney, liver, lung and heart transplantation.

Antibody mediated rejection (ABMR) is a major factor limiting outcome after organ transplantation. Anti-HLA donor-specific antibodies (DSA) of the IgG isotype are mainly responsible for ABMR. Recently DSA of the IgE isotype were demonstrated in murine models as well as in a small cohort of sensitized transplant recipients. In the present study, we aimed to determine the frequency of pre-existing and de novo anti-HLA IgE antibodies in a cohort of 105 solid organ transplant recipients. We prospectively measured anti-HLA IgE antibodies in a cohort of kidney (n=60), liver, heart and lung (n=15 each) transplant recipients before and within one-year after transplantation, employing a single-antigen bead assay for HLA class I and class II antigens. Functional activity of anti-HLA IgE antibodies was assessed by an in vitro mediator release assay. Antibodies of the IgG1-4 subclasses and Th1 and Th2 cytokines were measured in anti-HLA IgE positive patients. Pre-existing anti-HLA IgE antibodies were detected in 10% of renal recipients (including 3.3% IgE-DSA) and in 4.4% of non-renal solid organ transplant recipients (heart, liver and lung cohort). Anti-HLA IgE occurred only in patients that were positive for anti-HLA IgG, and most IgE positive patients had had a previous transplant. Only a small fraction of patients developed de novo anti-HLA IgE antibodies (1.7% of kidney recipients and 4.4% of non-renal recipients), whereas no de novo IgE-DSA was detected. IgG subclass antibodies showed a distinct pattern in patients who were positive for anti-HLA IgE. Moreover, patients with anti-HLA IgE showed elevated Th2 and also Th1 cytokine levels. Serum from IgE positive recipients led to degranulation of basophils in vitro, demonstrating functionality of anti-HLA IgE. These data demonstrate that anti-HLA IgE antibodies occur at low frequency in kidney, liver, heart and lung transplant recipients. Anti-HLA IgE development is associated with sensitization at the IgG level, in particular through previous transplants and distinct IgG subclasses. Taken together, HLA specific IgE sensitization is a new phenomenon in solid organ transplant recipients whose potential relevance for allograft injury requires further investigation.

Telehelath Monitoring in Renal Transplantat Recipients with Diagnosis COVID-19: Retrospective Study

Amaç: COVID-19 pozitif saptanan ve tele sağlık hizmetleri aracılığıyla takip edilen böbrek nakli alıcılarının özelliklerini, hospitalizasyon ihtiyacını, klinik seyrini, durumun ciddiyetini, tedavi yönetimi hakkında bilgileri anket yolu ile retrospektif olarak incelemektir.&#x0D; Gereç Yöntem: Tanımlayıcı ve retrospektif türde olan bu çalışmanın evrenini bir üniversite hastanesinin Organ Nakli Merkezinde Mart 2020 – Mart 2021 tarihleri arasında COVID-19 pozitif olan, telesağlık hizmetleri aracılığıyla takip edilen 18 yaş üstü böbrek nakli alıcıları oluşturdu. Araştırmada örneklem seçim yöntemi kullanılmadan veri toplama tarihleri arasında telesağlık hizmeti aracılığıyla takip edilen tüm hastalar araştırma kapsamına alındı. Araştırmanın örneklemini 18 yaşını doldurmuş, COVID-19 pozitif saptanan 63 böbrek nakli alıcısı oluşturdu. Veriler, araştırmacılar tarafından hazırlanan anket formu ile tıbbi kayıtların retrospektif olarak incelenmesiyle ve hastalar ile gerçekleştirilen telefon görüşmeleri ile elde edildi. Araştırmadan elde edilen veriler tanımlayıcı istatistiksel yöntemlerle değerlendirildi. Araştırma için araştırmanın yapıldığı kurumun Klinik Araştırmalar Etik Kurulundan onay alındı.&#x0D; Bulgular: COVID-19 pozitif saptanan böbrek nakli alıcılarının yaş ortalamasının 50,70±10,89 olduğu, beden kitle indeksi ortalamasının 27,71±6,20 olduğu ve hastaların %23,8’inin obes olduğu, %52,4’ünün erkek olduğu, %60,3’ünün ilköğretim mezunu olduğu, %81’inin ek hastalığının olduğu (%84,1’inde hipertansiyon, %22,2’sinde diyabet), %52,4’ünün canlıdan nakil olduğu belirlendi. Böbrek nakli alıcılarının %52,4’ünün sonbaharda hastalığa yakalandığı, %49,2’sinde öksürük, %42,9’unda pnömoni, %42,9’unda genel vücut ağrısı/yorgunluk, %22,2’sinde dispne, %22,2’sinde tat ve koku kaybı, %11,1’inde baş ağrısı, %15,9’unda ishal, %9,5’inde bulantı kusma belirtileri olduğu saptandı. %42,9’unda torax CT tutulumu vardı, hastaların %44,4’ü hastaneye yatarak tedavi olduğu, %17,5’i yoğun bakımda tedavi aldığı, %6,3’ünün entübe edildiği, %15,9’u rejeksiyon riski yaşadığı, %7,9’unun ex olduğu, %1,6’sının hemodiyalize başladığı belirlendi.&#x0D; Sonuç: Organ nakli hastalarında COVID-19 teşhisi genel popülasyona benzer olmasına rağmen, semptomların hafif seyredip hastalığın hızlı ilerleyebildiği ve sağlıklı popülasyona göre mortalitenin yüksek seyrettiği görüldü.

Incidence of serum antibodies to xenoantigens on triple-knockout pig cells in different human groups.

Xenoantigens other than Gal, Neu5Gc, and Sda may be playing a role in pig graft rejection. We investigated the incidence of antibodies to unknown pig xenoantigen in different human groups. We collected blood from TKO/hCD55 pigs (n = 3), and isolated PBMCs and RBCs. Serum samples were collected from (i) healthy human volunteers (n = 43), (ii) patients with end-stage renal disease (ESRD) (n = 87), (iii) the same patients after kidney allotransplantation (n = 50), and (iv) renal allotransplant recipients experiencing T cell-mediated rejection (allo-TCMR, n = 10). The sera were initially incubated with TKO/hCD55 pRBCs (1×108 cells) for 1h to absorb anti-pig antibodies (except against SLA and possibly other antigens not expressed on pRBCs) and then the serum (absorbed or unabsorbed) was tested for antibody binding and complement-dependent cytotoxicity (CDC) to TKO/hCD55 pig PBMCs. A significant reduction in IgM/IgG binding and CDC was observed in the absorbed sera. Serum obtained before and after renal allotransplantation showed no significant difference in IgM or IgG binding to, or in CDC of, TKO/hCD55 pig cells. IgM antibodies (but rarely IgG) against unknown xenoantigens expressed on TKO/hCD55 PBMCs, possibly against swine leukocyte antigens, were documented in healthy humans, patients with ESRD, and those with renal allografts undergoing acute T cell rejection. IgM (but not CDC) was higher in patients experiencing allo-TCMR. Human sera contain IgM antibodies against unknown pig xenoantigens expressed on TKO/hCD55 pPBMCs. Although not confirmed in the present study, the targets for these antibodies may include swine leukocyte antigens.

When you need to dive in the deep end-Transplanting SARS-CoV-2 PCR+ recipients.

There is an ongoing need to understand whether transplantation during acute Coronavirus disease 2019 (COVID-19) can be performed safely, especially when urgent transplant is required. We collected retrospective data of all consecutive non-lung transplant recipients who had a positive SARS-CoV-2 polymerase chain reaction (PCR) on the day of planned deceased donor organ implantation. Data were collected from two large transplant centers from 01/01/2022 to 02/01/2023. Demographics, details regarding COVID-19 infection, waitlist priority, and details regarding transplantation were obtained. A descriptive analysis was performed. A total of 12 patients were identified: 7 renal, 4 liver, and 1 heart transplant recipient. All 12 patients were vaccinated for COVID-19. Ten were asymptomatic outpatients found positive on admission and transplanted immediately. Two were in-patients with mild COVID-19 symptoms and were reactivated on the waitlist following 3 days of remdesivir when no progression to severe COVID-19 occurred. Most patients (10/12) received remdesivir posttransplant. No complications attributed to COVID-19 were noted nor were any secondary family or healthcare worker infections observed. All recipients were managed with special isolation precautions befitting their potentially infectious state. Standard induction therapy was used in all recipients. After a median follow up period of 143 days (interquartile range: 96-201 days), 3 episodes of rejection were documented, 2/7 renal recipients experienced delayed graft function, and 2/4 liver recipients required renal replacement therapy. Graft and patient survival were 100%. Transplantation can safely proceed in select, minimally symptomatic, non-lung recipients with a positive SARS-CoV-2 PCR at the time of transplant.

Effects of Induction Therapy on Graft Functions in Terms of Immunologic Risk

Advances in immunosuppressive therapies and surgical techniques have led to a significant reduction in the incidence of rejection within 1 year after kidney transplantation. Immunologic risk is an important factor affecting graft functions and guiding the clinician in the selection of induction therapy. The aim of this study was to investigate graft functions based on serum creatinine levels, Chronic Kidney Disease Epidemiology Collaboration (CKD- EPI) and proteinuria levels, frequency of leukopenia, cytomegalovirus (CMV) and BK virus polymerase chain reaction (PCR) positivity in patients with low and high immunologic risk. This retrospective study included 80 renal recipients. Recipients were divided into 2 groups: patients at low immunologic risk who received basiliximab only and those with high immunologic risk who received low-dose (1.5 mg/kg for 3 days) antithymocyte globulin and basiliximab. No significant differences were observed between the 2 risk groups in terms of first, third, sixth, and 12th-month creatinine levels, CKD-EPI, proteinuria levels, leukopenia frequency, and CMV and BK virus PCR positivity. One-year graft survivals did not differ significantly between these 2 treatment modalities. The combined use of low-dose antithymocyte globulin and basiliximab in the induction treatment of patients with high immunologic risk seems promising in terms of graft survival, leukopenia frequency, and CMV and BK virus PCR positivity.

Hemophagocytic lymphohistiocytosis secondary to virus infection and followed by lupus nephritis recurrence in a renal transplantation pediatric recipient: a case report

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening disorder characterized by systemic inflammation and organ failure as a result of dysregulated immune cell activation. HLH can be induced by a variety of factors including infection, tumours and autoimmune disease and can also occur in patients following solid organ transplantation. Occurrence of HLH and lupus nephritis (LN) successively within a short period of time after renal transplantation is uncommon.Case presentationWe described an 11-year-old female post-transplant patient who presented with hemocytopenia, fever, elevated serum ferritin, splenomegaly, hyperlipidemia, and hypofibrinemia, and was clinically diagnosed with HLH. After comprehensive treatment with corticosteroids, intravenous immunoglobulin (IVIG), and reducing immunosuppressants, her condition improved, but then hematuria ensued. The transplant kidney biopsy showed LN. She was treated with hydroxychloroquine and methylprednisolone while intensive immunosuppressive agents were given. She has remained in remission for two years until now.ConclusionsThe main inducing factors of HLH should be identified as early as possible, and accurate treatment plans should be taken. The long-course IVIG regimen may be one of the effective treatments for virus-induced HLH. After remission of HLH, we need to be alert to the recurrence of autoimmune diseases in patients with underlying diseases, and timely increase immunosuppressants.

Norepinephrine infusion in brain dead organ donor: A retrospective study on its effects on graft function after renal transplant

Objective: To investigate the effect of vasoactive drugs use in brain-dead organ donors in renal recipient graft function. Material and Methods: Clinical data from 30 brain-dead organ donors, and 30 recipients in our center were analyzed retrospectively between July 2017 and November 2021. Results: Norepinephrine infusion was used in all 30 cadaveric donors, where 11 donors had inotropic combinations. Norepinephrine was infused at a median dose of 0.2mcg/kg/min. There was no relationship between duration and doses of norepinephrine in donors and graft rejection, graft loss, and dialysis requirement in renal recipients. Conclusion: Intravenous norepinephrine infusion below 0.2mcg/kg/min had no effect on graft function in the renal recipient, where fluid restitution was sufficient in the cadaveric donor. Keywords: brain dead, organ donors, vasoactive drugs, graft survival