Renal Graft Rejection Research Articles

Evaluating Interleukin-2 and Its Receptors As Indicators of Acute Renal Graft Rejection

Evaluating Interleukin-2 and Its Receptors As Indicators of Acute Renal Graft Rejection

Association of Senescence Markers with Age and Allograft Rejection in Renal Transplant Recipients.

Renal transplantation is the treatment of choice for patients with end-stage renal disease. In the last decade, the number of older renal transplant recipients has significantly increased. However, these patients are at a higher risk of developing post-transplant complications. Therefore, identifying the suitable biomarkers to predict which older patients are at risk of complications is crucial. Cellular senescence could provide insights into the increased vulnerability in this population and guide personalized post-transplant care. This preliminary study involved biopsies from 25 patients with renal allograft rejection and 18 patients without rejection, further divided into older (50-65 years) and younger (29-40 years) groups. Biopsies were collected at different time points after transplantation, and rejection was classified according to the histological Banff 07 criteria. Additionally, immunohistochemistry for the markers of cellular senescence, p27kip1 and p16INK4a, was performed. We observed that the number of p27kip1-positive glomeruli was higher in the older patients with rejection compared to the younger patients with rejection, and a similar pattern was found in the patients without rejection. However, the number of p27kip1-positive tubules was higher in the older patients with rejection compared to the younger patients with rejection, as well as compared to both the older and younger patients without rejection. Tubular p16INK4a expression was not significantly different in the older patients with rejection compared to the younger patients with rejection, and the same pattern was observed in the patients without rejection. However, it was increased in the older patients with rejection in comparison to the older patients without rejection. Our preliminary data suggest the strong potential of both p16INK4a and p27kip1 as biomarkers of renal graft rejection, particularly in older renal transplant recipients.

8025 Hypocalcemia Secondary To Relative Hypoparathyroidism After Parathyroidectomy For Tertiary Hyperparathyroidism

Abstract Disclosure: N.N. Solanki: None. M.A. Bahrou: None. W. Taha: None. Parathyroidectomy is one of the treatment options for patients with tertiary hyperparathyroidism. Hypocalcemia following parathyroidectomy is a well-known occurrence due to a sudden drop in parathyroid levels, commonly to normal levels. We describe a case of hypocalcemia following subtotal parathyroidectomy for tertiary hyperparathyroidism with elevated parathyroid hormone (PTH) levels but relatively low compared to baseline. A 56-year-old female with a history of end-stage renal disease status post renal graft rejection presents for elective parathyroidectomy for tertiary hyperparathyroidism. Pre-operative investigations showed serum calcium levels of 11.6 mg/dL, normal value (NV): 9-10.5 mg/dL, serum phosphorus levels of 5.6 mg/dL, NV: 2.7-4.5 mg/dL, very high levels of serum intact PTH of 1257 pg/mL, NV: 10-65pg/mL and high level of alkaline phosphatase of 376 U/L, NV: 40-150 U/L. The patient underwent right and left inferior parathyroidectomy. Postoperatively, the patient's intact PTH levels remained elevated [895 pg/mL]; however, they decreased compared to baseline, but she developed hypocalcemia requiring intravenous and oral calcium supplementation. On postoperative day seven, she was discharged on oral calcitriol and calcium carbonate. Hypocalcemia following parathyroidectomy is well-described in cases where the PTH levels drop to the normal range. This case highlights that hypocalcemia can also occur when there is a relatively lower PTH level while the absolute value remains elevated. Presentation: 6/1/2024

Clinical characteristics of 15 cases of renal transplantation with pre-exsiting donor-specific antibody.

Currently, patients with pre-exsiting donor-specific antibody (DSA) are prone to antibody-mediated rejection (AMR) after surgery and are at a relatively high risk of postoperative complications and graft failure. The risk of postoperative complications and graft failure is relatively high. This study aims to discuss the clinical outcome of DSA-positive kidney transplantation and analyze the role and safety of preoperative pretreatment in DSA-positive kidney transplantation, providing single-center treatment experience for DSA-positive kidney transplantation. We retrospectively analyzed the clinical data of 15 DSA-positive kidney transplants in the Department of Renal Transplantation of First Affiliated Hospital of Zhengzhou University from August 2017 to July 2022. Eight cases were organ donation after citizen's death (DCD) kidney transplant recipients, of which 3 cases in the early stage were not treated with preoperative desensitisation therapy (DCD untreated group, n=3), and 5 recipients were treated with preoperative rituximab desensitisation (DCD preprocessing group, n=5). The remaining 7 cases were living related donors recipients (LRD) who received preoperative desensitisation treatment with rituximab and plasma exchange (LRD preprocessing group, n=7). We observed and recorded the incidence of complications with changes in renal function and DSA levels in the recipients and the survival of the recipients and transplanted kidneys at 1, 3 and 5 years, and to compare the differences in recovery and postoperative complications between 3 groups. All 15 recipients were positive for preoperative panel reactive antibody (PRA) and DSA and were treated with methylprednisolone+rabbit anti-human thymocyte immunoglobulin induction before kidney transplantation. DCD untreated group all suffered from DSA level rebound, delayed renal graft function (DGF) and rejection reaction after surgery. After the combined treatment, DSA level was reduced and the graft renal function returned to normal. The DCD preprocessing group were all without antibody rebound, 1 recipient developed DGF and the renal function returned to normal after plasmapheresis, and the remaining 4 recipients recovered their renal function to normal within 2 weeks after the operation. In the LRD preprocessing group, 2 cases had antibody rebound and 1 case had rejection, but all of them recovered to normal after treatment, and DSA was maintained at a low level or even disappeared. The incidence of DGF and rejection in the DCD untreated group were significantly higher than that in the DCD preprocessing group and the LRD preprocessing group; and there were no significant difference in the incidence of postoperative haematuria, proteinuria, bacterial and fungal infections, and BK virus infection between the 3 groups (all P>0.05). A total of 11 of the 15 recipients were followed up for more than 1 year, 6 for more than 3 years, and 1 for more than 5 years, and the survival rates of both the recipients and the transplanted kidneys were 100%. Effective preoperative pretreatment with desensitization therapy can effectively prevent antibody rebound in DSA-positive kidney transplantation and reduce perioperative complications.

The Role of the Duffy Blood Group Antigens in Renal Transplantation and Rejection. A Mini Review.

Finding a compatible donor for kidney transplant candidates requires overcoming immunological barriers such as human leukocyte antigens (HLA) compatibility and ABO compatibility. Emerging data suggest a role for red blood cell antigens (RCA) in renal transplant outcomes. The incidence of RCA alloimmunization is high in chronically transfused individuals, such as end stage renal disease patients, but whether antibodies to RCA can mediate renal graft rejection remains debatable. The Duffy blood group antigens (Fy) has been shown to be expressed in the kidney, among other tissues. There are some data to suggest that donor-recipient Fy mismatches may increase the risk for chronic allograft damage and that anti-Fy antibodies may be involved in renal graft rejection, however, while it is routine to screen renal transplant candidates for ABO antigens, detailed RCA phenotyping of the donor kidney is not routinely tested. In this paper, we review the current data on the role of Fy in renal transplantation and discuss the potential mechanisms of its biological function.

Identification of Renal Transplantation Rejection Biomarkers in Blood Using the Systems Biology Approach.

Renal transplantation plays an essential role in the quality of life of patients with end-stage renal disease. At least 12% of the renal patients receiving transplantations show graft rejection. One of the methods used to diagnose renal transplantation rejection is renal allograft biopsy. This procedure is associated with some risks such as bleeding and arteriovenous fistula formation. In this study, we applied a bioinformatics approach to identify serum markers for graft rejection in patients receiving a renal transplantation. Transcriptomic data were first retrieved from the blood of renal transplantation rejection patients using the GEO database. The data were then used to construct the protein-protein interaction and gene regulatory networks using Cytoscape software. Next, network analysis was performed to identify hub-bottlenecks, and key blood markers involved in renal graft rejection. Lastly, the gene ontology and functional pathways related to hub-bottlenecks were detected using PANTHER and DAVID servers. In PPIN and GRN, SYNCRIP, SQSTM1, GRAMD1A, FAM104A, ND2, TPGS2, ZNF652, RORA, and MALAT1 were the identified critical genes. In GRN, miR-155, miR17, miR146b, miR-200 family, and GATA2 were the factors that regulated critical genes. The MAPK, neurotrophin, and TNF signaling pathways, IL-17, and human cytomegalovirus infection, human papillomavirus infection, and shigellosis were identified as significant pathways involved in graft rejection. The above-mentioned genes can be used as diagnostic and therapeutic serum markers of transplantation rejection in renal patients. The newly predicted biomarkers and pathways require further studies.

Biostatistical Analysis of Relation between HLA-A/B and HLA-DR Eplet Mismatches and Renal Graft Outcome

Abstract: Despite all the clinical interventions that happened during the last 2 decades, the unavailability of a potent donor for renal transplantation remains a concern in the field of transplantation immunology. Recent studies promise the establishment of an effective clinical method to find a potent renal transplant donor, in the near future. Combining the use of molecular techniques with biostatistical methods can be a great tool for clinicians in choosing a potent donor. The present study was conducted from a cohort of 1144 (n=572 pair) renal transplant recipients and their donors to analyse eplet matches and mismatches. Initial observation of increased serum creatinine level which ranged from 2.0 to 21.0 mg/dL in patients treated for end-stage renal disease implied a single event of graft rejection. The statistical correlation between eplet mismatches and graft survival was observed to be significant with P value 0.003. A value of -0.215 at 0.01 significance showed the positive linear correlation between the increased numbers of HLA DR eplet mismatches towards chronic renal graft rejection. The correlation coefficient of -0.888 observed between the number of HLA DR eplet mismatches and days of graft survival clearly implies the effect of increased HLA DR eplet mismatch delayed graft rejection. The study gives an idea on the minimization of class II HLA DR eplet mismatches to decreased frequency of graft rejection as indicated by increased survival rate.

Comparative Study of the Impact of Human Leukocyte Antigens on Renal Transplant Survival in Andalusia and the United States

Renal transplantation is the treatment of choice for patients suffering from chronic renal disease, one of the leading causes of death worldwide. Among the biological barriers that may increase the risk of acute renal graft rejection is the presence of human leukocyte antigen (HLA) incompatibilities between donor and recipient. This work presents a comparative study of the influence of HLA incompatibilities on renal transplantation survival in the Andalusian (South of Spain) and United States (US) population. The main objective is to analyse the extent to which results about the influence of different factors on renal graft survival can be generalised to different populations. The Kaplan-Meier estimator and the Cox model have been used to identify and quantify the impact on the survival probability of HLA incompatibilities, both in isolation and in conjunction with other factors associated with the donor and recipient. According to the results obtained, HLA incompatibilities considered in isolation have negligible impact on renal survival in the Andalusian population and a moderate impact in the US population. Grouping by HLA score presents some similarities for both populations, while the sum of all HLA scores (aHLA) only has an impact on the US population. Finally, the graft survival probability of the two populations differs when aHLA is considered in conjunction with blood type. The results suggest that the disparities in the renal graft survival probability between the two populations under study are due not only to biological and transplantation-associated factors, but also to social-health factors and ethnic heterogeneity between populations.

Autoamputation of Toes in a Renal Transplant Recipient: Warning Sign of an Impending Graft Rejection?

The peripheral arterial occlusive disease is responsible for a significant amount of morbidity and mortality in patients of endstage renal disease. This disease might not be as common as end-stage renal disease in vascular complications arising after renal transplant. The peripheral arterial occlusive disease is responsible for lower limb amputation in chronic kidney disease. It is important to identify the peripheral arterial occlusive disease as it may lead to septicaemia which in turn can result in multiple organ failure and thus can prove to be a potentially fatal complication of renal disease. Here the authors report a case of a 42-year-old female who had undergone a renal transplant four years back. She presented with breathlessness and bilateral pedal oedema along with autoamputation of toes and ultimately had to be taken for haemodialysis. The patient was intrervene for an arteriovenous fistula for haemodialysis in view of graft rejection. Through this brief case report, the authors highlight the importance of a neglected autoamputation which was a missed warning sign of impending renal graft rejection in the present case.

Impact of Cytomegalovirus (CMV) Infection on Renal Transplantation and Graft Rejection.

Impact of Cytomegalovirus (CMV) Infection on Renal Transplantation and Graft Rejection.

Factors Associated With Acute Renal Graft Rejection in a Series of Transplanted Patients

Factors Associated With Acute Renal Graft Rejection in a Series of Transplanted Patients

An Adjusted Process to Improve Efficiency and Efficacy of Adsorption Procedures to Resolve Warm Autoantibody Cases.

The presence of warm autoantibodies in patient plasma typically causes extended delays in patient care due to panreactive antibody identification tests. Adsorption is the primary method for resolution. A modified adsorption procedure was devised with the intent to minimize delays, and the aim of the study was to evaluate its efficacy. To evaluate the in-house developed (experimental) adsorption method, specimens were tested in parallel with the standard adsorption method described in the AABB Technical Manual, 20th edition. Specimens selected demonstrated panreactivity at the submitting facility and contained adequate volume for parallel adsorption studies. Ninety specimens were tested with both methods. Ninety specimens achieved complete adsorption with the experimental method and 88 specimens achieved complete adsorption with the standard method. Two underlying alloantibodies, which have been reported to cause hemolytic transfusion reactions and potential renal graft rejection, were detected using the experimental method that the standard method failed to detect. The experimental method demonstrated a significant reduction in rounds of adsorption required to resolve warm autoantibody reactivity, enhanced antibody detection ability with adsorbed plasma, and more cost-effective outcomes compared to the standard method. A follow-up study is planned to assess whether the incubation time can be decreased with the experimental method to further improve the efficiency of the method without sacrificing efficacy.

Adherence to Immunosuppressive Medications in Kidney Transplant Patients at Three Centers in Khartoum State, Sudan: A Cross-sectional Hospital Study

Background: Graft survival post-kidney transplantation is of paramount importance to patients and nephrologists. Nonadherence to immunosuppressive therapy can be associated with deterioration of renal function and graft rejection. This study aimed to evaluate the adherence to immunosuppressive medications in kidney transplant patients at three centers in Khartoum, Sudan.
 Methods: In this descriptive cross-sectional hospital-based survey, 277 post-kidneytransplant patients were recruited. Data were collected using a questionnaire and analyzed using the SPSS v.23. Our scoring method was calculated based on Morisky Medication Adherence Scale (MMAS-8) related to immunosuppressive medications and was expressed as questions in the questionnaire; every correct answer was given one mark, then the marks were gathered and their summation was expressed.
 Results: Overall, 33% ,45%, and 22% of the studied participants reported high, medium, and low adherence, respectively. The major factor for nonadherence was forgetfulness affecting 36.1% of those who did not adhere. The cost of the immunosuppressive medications did not negatively affect any of the participants’ adherence (100%). However, a significant association was seen between adherence and occupational status, duration of transplantation, shortage of immunosuppressants, recognizing the name of immunosuppressant, side effect, and forgetfulness (P-values = 0.002, 0.01, 0.006 , 0.000, 0.022, and 0.000, respectively). Logistic regression analysis showed a significant association with occupational status, side effects, and forgetfulness
 Conclusion: Only one-third of the participants were classed as “highly adherent” to their immunosuppressant medications. Factors that can affect adherence to immunosuppressant medications were occupational status, side effects, and forgetfulness.

Notch3 expression in capillary pericytes predicts worse graft outcome in human renal grafts with antibody-mediated rejection.

Microvasculature consisting of endothelial cells and pericytes is the main site of injury during antibody‐mediated rejection (ABMR) of renal grafts. Little is known about the mechanisms of activation of pericytes in this pathology. We have found recently that activation of Notch3, a mediator of vascular smooth muscle cell proliferation and dedifferentiation, promotes renal inflammation and fibrosis and aggravates progression of renal disease. Therefore, we studied the pericyte expression of Notch3 in 49 non‐selected renal graft biopsies (32 for clinical cause, 17 for graft surveillance). We analysed its relationship with patients’ clinical and morphological data, and compared with the expression of partial endothelial mesenchymal transition (pEndMT) markers, known to reflect endothelial activation during ABMR. Notch3 was de novo expressed in pericytes of grafts with ABMR, and was significantly correlated with the microcirculation inflammation scores of peritubular capillaritis and glomerulitis and with the expression of pEndMT markers. Notch3 expression was also associated with graft dysfunction and proteinuria at the time of biopsy and in the long term. Multivariate analysis confirmed pericyte expression of Notch3 as an independent risk factor predicting graft loss. These data suggest that Notch3 is activated in the pericytes of renal grafts with ABMR and is associated with poor graft outcome.

ИММУНОЛОГИЧЕСКИЕ ПРЕДИКТОРЫ ОТТОРЖЕНИЯ ПОЧЕЧНОГО ТРАНСПЛАНТАТА В РАННЕМ ПОСЛЕОПЕРАЦИОННОМ ПЕРИОДЕ

Objective. To determine the immunological predictors of renal graft rejection in the early postoperative period. Methods. Three groups were formed out of the 197 renal graft recipients. The group PGF (n=101) was made up of patients with satisfactory primary graft function. The group PGD (n = 82) included patients with primary graft dysfunction without episodes of rejection. The group RGR (n=14) consisted of patients with primary dysfunction and renal graft rejection. On the 7<sup>th</sup> day after transplantation the early kidney graft function was assessed on the basis ofserum creatinine levels. When the serum creatinine value was lower than 300 μmol/L the function was considered to be primary, at a creatinine concentration was equal to or higher than 300 μmol/L, as well as in the case of needfor maintenance dialysis on the first week after transplantation, the state was classified as the renal graft dysfunction. In the early postoperative period, the number of LIN-HLA-DR+ dendritic cells with the LIN-HLA-DR+CD11c+CD123- and LIN-HLA-DR+CD11c-CD123+ phenotypes in the fluid from the drainage installed to the kidney graft during surgery was determined. Predictive characteristics of the mDC and pDC levels in the drainage fluid were determined to predict renal graft rejection, and diagnostic capability of this indicator were identified. Results. It has been revealed that renal graft rejection is characterized by a significant growth of the total number of dendritic cells in the drainage fluid, mainly due to myeloid ones. Predictive characteristics were determined by the level of myeloid and plasmacytoid dendritic cells in the drainage fluid. The cut-off point of the level of myeloid dendritic cells was determined at the level of 60.32%, and for plasmacytoid dendritic cells it corresponded to 39.68%. Conclusion. With the level of myeloid dendritic cells in the drainage fluid greater or equal 60.32%, and plasmacytoid cells lower or equal 39.68%, renal graft rejection is predicted with a sensitivity of 99% and 93%, respectively, and a specificity of 89% and 91%, respectively. What this paper adds The level of dendritic cells and their subpopulations in the drainage fluid in renal graft recipients has been firstly studied. It has been established that acute renal graft rejection is associated with a high concentration of the total number of dendritic cells in the drainage fluid. More over this increase occurs mainly due to myeloid dendritic cells. The determination of the level of myeloid and plasmacytoid dendritic cells in the drainage fluid can be used as a predictor of renal graft rejection.

MO937ASSOCIATION OF RENAL ELASTOGRAPHY WITH BANFF MICROVASCULAR INFLAMMATION IN PROTOCOL BIOPSIES FOR SUBCLINICAL RENAL GRAFT REJECTION DIAGNOSIS

Abstract Background and Aims The most common cause of renal graft failure is chronic dysfunction in 24.7% and the most common etiology of this is clinical or subclinical rejection. The incidence of subclinical rejection varies from 15 to 50% (25% in protocol biopsies in the first year after transplantation and 35% after two years). Melek E et al have shown that doppler ultrasound is a non-invasive study that, through the resistance index (RI), has traditionally been used for the early diagnosis of acute graft rejection (AR); however, it is influenced by extrarenal systemic factors. Naesens et al published that in 321 kidney transplant recipients, RI wasn´t associated with histological findings of AR in protocol biopsies. Elastography is another ultrasonographic modality for the evaluation of the kidney graft, which measures the stiffness/elasticity of the tissue expressed in Kpa (kilopascals). Stock in 2011 and Kim BJ in 2018 published studies where they showed that increased stiffness was correlated with the diagnosis of kidney graft rejection. The aim of this study was to describe the association between elastography with microvascular inflammation determined by Banff for diagnosis of renal allograft subclinical rejection. Method Observational, analytical and cross-sectional study that included kidney transplant patients who underwent protocol biopsy and renal elastography at the Central Military Hospital in Mexico City between January 2018 and December 2020. The demographic and biochemical characteristics, degree elastography stiffness and Banff 2017 lesions were determined. The sample calculation, determination of correlation degree and ROC curve elaboration were performed. Results We included 146 patients. 56.8% were men; the most common causes of CKD were undetermined and chronic glomerulonephritis with 52.7% and 17.1% respectively. 47.3% were hypertensive at biopsy time and 1.4% had chronic heart failure. The most common immunosuppression schemes were FK/MPA/steroid and FK/mTOR-i/steroid with 60.3% and 13%, respectively. The mean GFR was 65.31 ml/min which shows graft good function. The mean stiffness in the elastography was 15.73 Kpa. The rest of baseline data are shown in Table 1. Had rejection 36.3% of the biopsies, the most frequent chronic AMR C4d- with 15.1% and active AMR C4d- 8.9%. When analyzing the ROC curves, the Banff 2017 lesions AUC values that correlated better with graft stiffness were: v=0.607, i=0.594, g=0.578, C4d deposit=0.519, ptc=0.498. Figure 1. Conclusion Intimal arteritis, inflammation, and glomerulitis are the Banff lesions best associated with elastography graft stiffness in protocol biopsies. Prospective studies are recommended in patients with acute graft dysfunction to find an adequate elastography cut-off value that allows another tool for fast and non-invasive diagnosis of renal graft rejection.

Multi-center phase 1 safety and efficacy study of nivolumab in renal transplant patients with metastatic malignancy.

2567 Background: Organ Transplant Recipients (OTR) are generally excluded from trials of immune checkpoint inhibitors (ICI) due to the reported risk of allograft rejection. A recent systematic review of published case series includes only 65 cases. Transplant organ rejection rates of 41% are reported with cancer response rates of 39%. The majority of OTR treated with ICI have had reduction/cessation of immunosuppression (IS) prior to ICI. Isolated IS reduction is associated with organ rejection and therefore either IS manipulation alone and/or ICI could induce organ rejection episodes. Methods: Renal OTR with incurable cancer, for whom ICI would normally be used in the general population (without an organ transplant), were eligible if creatinine < 180 umol/l, no donor specific HLA antibodies and ECOG < 2. Treatment was with nivolumab (3mg/kg q 14 days for 5 doses, then 480 mg q 28 days), without manipulation of IS and pre-ICI-exposure alloimmune risk assessment. Treatment continued till progression, patient refusal, or graft rejection. Primary endpoint was rate of irretrievable renal graft rejection. Results: 15 patients (9 male:6 female; median age 66.6 years) were enrolled and treated with a median (range) 3(1-42) infusions and with median (range) follow-up of 128 (11-784) days. Tumour types included:1 melanoma; 2 renal tract; 1 hepatocellular carcinoma; 1 Merkel cell; 1 adenocarcinoma lung; 1 MSI high colorectal, 8 squamous cell carcinoma (SCC) head and neck. 2 patients experienced rejection; one at day 28 (2 infusions); one at day 36 (3 infusions). Both had SCC and have had a CR. One is on haemodialysis and alive at 2 years the other a creatinine 450 umol/l. Both rejections treated with steroid, plasma-exchange and anti-thymocyte-globulin (ATG). 1 patient (metastatic bladder cancer) experienced graft loss (at 300 days) due to ureteric-stent bleed and BK-nephritis indirectly related to nivolumab- this patient died of progressive disease at 65 days after nivolumab cessation. Median (range) progression free disease (PD) with ≥ 2 infusions was 300 (68-784+) days. There were 5 CR (1 MSI high colorectal, 4 SCC) median duration of response 13 months and 2 PR (1 SCC 1 bladder)- 1 without PD. Conclusions: In this interim analysis, rejection rates in OTR with incurable cancers treated with ICI was 2/15 (13%) when IS is maintained and there is pre exposure alloimmune assessment. The combined CR and PR rate was 7/15 (47%). Clinical trial information: 12617000741381.

Investigating the Role of BAFF and Its Receptors in Renal Transplant Recipients with Chronic Antibody-Mediated Rejection.

Background Kidney transplantation is the best treatment option for end stage renal disease (ESRD), but graft rejection is still a big obstacle that occurs in spite of immunosuppressive therapy. B cells are considered as the major reason for renal graft rejection because of antibody production. Due to their roles in B cell function, we intended to evaluate the B cell activating factor (BAFF) and its receptors including BAFF receptor (BAFF-R), B cell maturation antigen (BCMA), and transmembrane activator and cyclophilin ligand interactor (TACI) in renal transplant patients. Method The study included 40 kidney allograft patients with cAMR, 40 stable kidney allograft patients, and 8 healthy volunteers with normal kidney function. The percentage and absolute number of CD19+ B cells were analyzed by flow cytometry, the serum level of BAFF was analyzed by ELISA, and mRNA expressions of BAFF and BAFF receptors (BAFF-R, BCMA, and TACI) were measured using quantitative real-time PCR. Results The percentage and the absolute number of B cells decreased significantly in stable and cAMR patients compared to healthy individuals. The serum level and gene expression of BAFF, as well as the mRNA level of BCMA, were increased significantly in both cAMR and stable patients compared to healthy volunteers. There was an overexpression of TACI mRNA in cAMR patients compared to stable patients. Conclusions Both soluble protein and mRNA transcript of BAFF increased in transplant recipients. However, BAFF neither at the serum level nor at the mRNA transcript level cannot be a good biomarker for the prediction of cAMR. In addition, expression of TACI, compared to other receptors of BAFF, confers a potential to be used in distinguishing cAMR and stable kidney transplant patients.

Clinical effect analysis of 146 cases of ipsilateral simultaneous pancreas and kidney transplantation

Objective: To investigate the clinical effect of ipsilateral simultaneous pancreas and kidney transplantation (SPK). Methods: A total of 146 cases of SPK surgeries completed in the Second Affiliated Hospital of Guangzhou Medical University from September 2016 to June 2020 were selected to summarize the outcome, curative effect and complications of the operation. Results: The patients were followed up for 1 to 45 months. Good clinical results were obtained in 146 patients. Renal function indicators suggest that on the 7th day after operation, the serum creatinine returned to normal level [142.4 (108.6, 213.4)μmol/L]. The index of pancreatic function decreased to the normal level as expected. The level of blood amylase was 160.5(109.3, 249.8) U/L within 7 days after operation, and then decreased. The trend of urinary amylase was similar to that of blood amylase, which was 240(121.0, 370.0) U/L 7 days after operation, and glycosylated hemoglobin decreased to the normal level (5.8%±1.4%) 1 month after operation. The main medical complications were infection including pulmonary infection (26.03%, 38/146), urinary tract infection (26.03%,38/146), and abdominal infection (4.79%,7/146), acute rejection including renal graft rejection (5.8%,8/146), pancreas/duodenum rejection (18.49%,27/146), and renal graft combined pancreatic graft rejeciton (6.85%,10/146), as well as gastrointestinal bleeding (30.82%,45/146), of which 5 cases were severe bleeding (3.42%, 5/146). The main surgical complications were poor incision healing (10.27%, 15/146), serious surgical complications including arteriovenous thrombosis of the transplanted pancreas (2.05%, 3/146) and intestinal leakage (0.68%,1/146). The 1-year and 3-year patient, renal and pancreatic survival rates were both 92.5%, 91.5% and 89.5%, respectively, and despite the death, the 1-year, 3-year transplanted kidney survival rate was both 99.3%, and 95% for the the 1-year, 3-year pancreas survival rate. Conclusion: Strict preoperative evaluation of the function of large organs, reasonable surgical methods, perioperative anticoagulation, and prompt diagnosis of complications can achieve good clinical results for patients with SPK.

Acute Rejection Following Kidney Transplantation: State-of-the-Art and Future Perspectives.

Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available metaanalyses, we performed a narrative review focused on the basic mechanisms and current and future therapies of acute rejection in kidney transplantation. According to Kidney Disease/Improving Global Outcomes (KDIGO) guidelines, both clinical and subclinical acute rejection episodes should be treated. Usually, high dose steroids and basal immunosuppression optimization are the first line of therapy in treating acute cellular rejection. Rabbit antithymocytic polyclonal globulins are used as rescue therapy for recurrent or steroid-resistant cellular rejection episodes. Current standard-of-care (SOC) therapy for acute antibody-mediated rejection (AbMR) is the combination of plasma exchange with intravenous immunoglobulin (IVIG). Since a significant rate of AbMR does not respond to SOC, different studies have analyzed the role of new drugs such as Rituximab, Bortezomib, Eculizumab and C1 inhibitors. Lack of randomized controlled trials and heterogenicity among performed studies limit obtaining definite conclusions. Data about new direct and indirect B cell and plasma cell depleting agents, proximal and terminal complement blockers, IL-6/IL-6R pathway inhibitors and antibody removal agents, among other promising drugs, are reviewed.