Cause Of Renal Allograft Dysfunction Research Articles

Oxidized ATP Suppresses B Lymphocyte Activity to Attenuate Antibody-mediated Rejection of Kidney Allografts in Mice

Background. Antibody-mediated rejection (AMR) is a major cause of renal allograft dysfunction and loss. Targeting B cells and/or donor-specific antibody removal using plasma exchange and anti-CD20 antibodies are increasingly used in clinical practice, but the efficacy remains limited. Recent studies suggest that targeting purinergic P2X7 receptor/ATP axis can have profound immune regulatory effects in transplant models, but the mechanisms involved remain incompletely defined. Methods. Purified B cells were isolated from the spleen of Balb/C mice and cultured with oxidized ATP at different concentrations. Proliferation and differentiation of B cells were examined. Effects of oxidized ATP were examined in a presensitized animal model where kidney allograft rejection mimics aspects of clinical AMR. Histopathology was assessed at the time of rejection or on day 5 after kidney transplantation. Infiltrating immune cells in renal allografts were detected by flow cytometry. Results. Oxidized ATP inhibited B-cell activation and proliferation in vitro, significantly attenuated histological signs of graft injury and prolonged kidney allograft survival. Mechanistically, oxidized ATP inhibited antibody secretion by activated B cells in response to lipopolysaccharide stimulation and markedly suppressed the production of donor-specific antibody in kidney allograft recipients. Oxidized ATP also reduced graft infiltration by other inflammatory cells. Conclusions. These findings provide evidence for the involvement of the purinergic P2X7 receptor pathway in AMR and suggest that targeting this pathways may have important clinical implications.

Functional MRI evaluation of blood oxygen dependent (BOLD) in renal allograft dysfunction: a prospective study.

Blood oxygen level dependent-magnetic resonance imaging (BOLD-MRI) is a non-invasive functional imaging technique that can be used to assess renal allograft dysfunction. To evaluate the diagnostic performance of BOLD-MRI using a 3-T scanner in discriminating causes of renal allograft dysfunction in the post-transplant period. This prospective study was conducted on 112 live donor-renal allograft recipients: 53 with normal graft function, as controls; 18 with biopsy-proven acute rejection (AR); and 41 with biopsy-proven acute tubular necrosis (ATN). Multiple fast-field echo sequences were performed to obtain T2*-weighted images. Cortical R2* (CR2*) level, medullary R2* (MR2*) level, and medullary over cortical R2* ratio (MCR) were measured in all participants. The mean MR2* level was significantly lower in the AR group (20.8 ± 2.8/s) compared to the normal group (24 ± 2.4/s, P <0.001) and ATN group (27.4 ± 1.7/s, P <0.001). The MCR was higher in ATN group (1.47 ± 0.18) compared to the AR group (1.18 ± 0.17) and normal functioning group (1.34 ± 0.2). Both MR2* (area under the curve [AUC] = 0.837, P <0.001) and MCR (AUC = 0.727, P = 0.003) can accurately discriminate ATN from AR, however CR2* (AUC = 0.590, P = 0.237) showed no significant difference between both groups. In early post-transplant renal dysfunction, BOLD-MRI is a valuable non-invasive diagnostic technique that can differentiate between AR and ATN by measuring changes in intra-renal tissue oxygenation.

The Use of Diffusion Tensor Imaging in the Identification of Acute Rejection and Chronic Allograft Nephropathy After Renal Transplantation.

Identifying the cause of renal allograft dysfunction is important for the clinical management of kidney transplant recipients. To evaluate the diagnostic efficiency of diffusion tensor imaging (DTI) for identifying allografts with acute rejection (AR) and chronic allograft nephropathy (CAN). Prospective. Seventy-seven renal transplant patients (aged 42.5 ± 9.5 years), including 29 patients with well-functioning stable allografts (Control group), 25 patients diagnosed with acute rejection (AR group), and 23 patients diagnosed with chronic allograft nephropathy (CAN group). 1.5 T/T2-weighted imaging and DTI. The serum creatinine, proteinuria, pathologic results, and fractional anisotropy (FA) values were obtained and compared among the three groups. One-way analysis of variance; correlation analysis; independent-sample t-test; intraclass correlation coefficients and receiver operating characteristic curves. Statistical significance was set to a P-value <0.05. The AR and CAN groups presented with significantly elevated serum creatinine as compared with the Control group (191.8 ± 181.0 and 163.1 ± 115.8 μmol/L vs. 82.3 ± 20.9 μmol/L). FA decreased in AR group (cortical/medullary: 0.13 ± 0.02/0.31 ± 0.07) and CAN group (cortical/medullary: 0.11 ± 0.02/0.27 ± 0.06), compared with the Control group (cortical/medullary: 0.15 ± 0.02/0.35 ± 0.05). Cortical FA in the AR group was higher than in the CAN group. The area under the curve (AUC) for identifying AR from normal allografts was 0.756 and 0.744 by cortical FA and medullary FA, respectively. The AUC of cortical FA and medullary FA for differentiating CAN from normal allografts was 0.907 and 0.830, respectively. The AUC of cortical FA and medullary FA for distinguishing AR and CAN from normal allografts was 0.828 and 0.785, respectively. Cortical FA was able to distinguish between AR and CAN with an AUC of 0.728. DTI was able to detect patients with dysfunctional allografts. Cortical FA can further distinguish between AR and CAN. 2 TECHNICAL EFFICACY: Stage 2.

Molecular immune monitoring in kidney transplant rejection: a state-of-the-art review.

Although current regimens of immunosuppressive drugs are effective in renal transplant recipients, long-term renal allograft outcomes remain suboptimal. For many years, the diagnosis of renal allograft rejection and of several causes of renal allograft dysfunction, such as chronic subclinical inflammation and infection, was mostly based on renal allograft biopsy, which is not only invasive but also possibly performed too late for proper management. In addition, certain allograft dysfunctions are difficult to differentiate from renal histology due to their similar pathogenesis and immune responses. As such, non-invasive assays and biomarkers may be more beneficial than conventional renal biopsy for enhancing graft survival and optimizing immunosuppressive drug regimens during long-term care. This paper discusses recent biomarker candidates, including donor-derived cell-free DNA, transcriptomics, microRNAs, exosomes (or other extracellular vesicles), urine chemokines, and nucleosomes, that show high potential for clinical use in determining the prognosis of long-term outcomes of kidney transplantation, along with their limitations.

POS-115 IMPACT OF EARLY SCREENING FOR BK VIRURIA ON ALLOGRAFT OUTCOME AT ONE YEAR IN KIDNEY TRANSPLANT RECIPIENTS: A SINGLE-CENTER EXPERIENCE

BK virus nephropathy (BKVN) is a potential cause of renal allograft dysfunction and loss in kidney transplantation recipients (KTR). BK viruria (BKVu) occurs in 30-40% of the KTR, while BK viremia (BKVb) and BKVN occur in approximately 13% and 8%, respectively. High-level BKVu can progress to BKVb, and BKVN. Early screening for BKVu and reduction in immunosuppression in BKVu positive patients may prevent the progression to BKVN and may improve long-term patient and allograft outcomes.

RtNet: a deep hybrid neural network for the identification of acute rejection and chronic allograft nephropathy after renal transplantation using multiparametric MRI.

Reliable diagnosis of the cause of renal allograft dysfunction is of clinical importance. The aim of this study is to develop a hybrid deep-learning approach for determining acute rejection (AR), chronic allograft nephropathy (CAN) and renal function in kidney-allografted patients by multimodality integration. Clinical and magnetic resonance imaging (MRI) data of 252 kidney-allografted patients who underwent post-transplantation MRI between December 2014 and November 2019 were retrospectively collected. An end-to-end convolutional neural network, namely RtNet, was designed to discriminate between AR, CAN and stable renal allograft recipient (SR), and secondarily, to predict the impaired renal graft function [estimated glomerular filtration rate (eGFR) ≤50 mL/min/1.73 m2]. Specially, clinical variables and MRI radiomics features were integrated into the RtNet, resulting in a hybrid network (RtNet+). The performance of the conventional radiomics model RtRad, RtNet and RtNet+ was compared to test the effect of multimodality interaction. Out of 252 patients, AR, CAN and SR was diagnosed in 20/252 (7.9%), 92/252 (36.5%) and 140/252 (55.6%) patients, respectively. Of all MRI sequences, T2-weighted imaging and diffusion-weighted imaging with stretched exponential analysis showed better performance than other sequences. On pairwise comparison of resulting prediction models, RtNet+ produced significantly higher macro-area-under-curve (macro-AUC) (0.733 versus 0.745; P = 0.047) than RtNet in discriminating between AR, CAN and SR. RtNet+ performed similarly to the RtNet (macro-AUC, 0.762 versus 0.756; P > 0.05) in discriminating between eGFR ≤50 mL/min/1.73 m2 and >50 mL/min/1.73 m2. With decision curve analysis, adding RtRad and RtNet to clinical variables resulted in more net benefits in diagnostic performance. Our study revealed that the proposed RtNet+ model owned a stable performance in revealing the cause of renal allograft dysfunction, and thus might offer important references for individualized diagnostics and treatment strategy.

POS-773 THE PATTERN OF INFECTION FOLLOWING ANTI-REJECTION THERAPY IN RENAL ALLOGRAFT RECIPIENTS: EXPERIENCE FROM A LOW RESOURCE COUNTRY

Graft rejection is an important cause of renal allograft dysfunction and requires antirejection therapy (ART) for its reversal. However, it is associated with risk of over-immunosuppression, which is often underestimated against improved graft outcome. In this study we aim to assess the complications attributed to ART in a cohort of renal allograft recipients (RAR) out of hospital based renal transplant registry (RTR).

Crystalline nephropathy due to adenine phosphoribosyl transferase deficiency as a cause of renal allograft dysfunction

APRT deficiency is a rare but under recognized genetic disease. Recurrent urolithiasis and DHA nephropathy are the two clinical manifestations of APRT deficiency and diagnosis can be made at any age and recurs after renal transplant. Allopurinol is the cornerstone in preventing recurrence. APRT activity assay and genetic testing are useful for confirmation of diagnosis, for family screening and in difficult cases of urolithias or crystalline nephropathy.

Noninvasive quantification of intrarenal allograft C4d deposition with targeted ultrasound imaging.

Antibody-mediated rejection (AMR) has emerged as a major cause of renal allograft dysfunction. C4d, a specific marker for AMR diagnosis, was strongly recommended for routine surveillance; however, currently, C4d detection is dependent upon tissue biopsy, which is invasive and provides only local semi-quantitative data. Targeted ultrasound imaging has been used extensively for noninvasive and real-time molecular detection with advantages of high specificity and sensitivity. In this study, we designed C4d-targeted microbubbles (MBC4d ) using a streptavidin-biotin conjugated method and detected C4d deposition in vivo in a rat model of AMR by enhanced ultrasound imaging. This noninvasive procedure allowed successful acquisition of the first qualitative image of C4d deposition in a wide renal allograft section, which reflected real-time C4d distribution in grafts. Moreover, we introduced normal intensity difference for quantitative analysis, which exhibited a nearly linear correlation with the grade of C4d deposition according to pathologic analysis. In addition, this approach showed no influence on survival rates and pathologic features in the microbubble injection groups, thereby demonstrating its safety. These findings demonstrated a simple, noninvasive, quantitative, and safe evaluation method for C4d, with the utility of this approach potentially preventing patients from having to undergo an invasive biopsy.

Efficacy of the Sonoelastography Method for Diagnosis of Fibrosis in Renal Transplant Patients.

Although biopsy is the most important method for diagnosing the cause of renal allograft dysfunction, sonoelastography, a new ultrasonography method, can be used to distinguish between the soft or hard nature of lesions. In this study, our aim was to investigate whether sonoelastography could diagnose fibrosis in renal transplant patients. In this prospective study, we included patients over 18 years old who were recommended for clinical biopsy. Sonoelastographic evaluation was made by conducting acoustic radiation force impulse measurements for each patient after they were admitted to the clinic for biopsy. Measurements were performed just before the biopsy procedure. All results were examined by 2 experienced radiologists using the Siemens S3000 Ultrasound Machine (Erlangen, Germany). Comparisons of ultrasonographic values with biopsy results were made with SPSS software (SPSS: An IBM Company, version 20, IBM Corporation, Armonk, NY, USA). Of the 65 patients included in this study, pathology showed acute T-cell-mediated rejection in 37 patients. There was a significant correlation between the pathologic Banff scores and the sonographic acoustic radiation force impulse values (P = .002), where the degree of Banff increased as the mean acoustic radiation force impulse values elevated. A rise in mean impulse values correlated with increased degree of interstitial fibrosis in renal allografts. Renal parenchymal echogenicity of patients significantly differed by sex (P = .009), with an average renal echogenicity of grade 1 in women and grade 0 in men. Also, a statistically significant difference was found between age of the renal transplant recipient and resistive index values. Our study showed a significant correlation between Banff degree and the acoustic radiation force impulse values of renal transplant patients. In addition to biopsy, sonoelastography can be beneficial for the diagnosis of fibrosis in renal transplant patients.

Renal Blood Flow Measurements by Magnetic Resonance Imaging using Arterial Spin Labelling as a Novel Non-Invasive Biomarker in Paediatric Renal Transplant Recipients

Introduction To investigate our hypothesis that non-invasive cortical renal blood flow (cRBF) measurements using functional magnetic resonance imaging (MRI) arterial spin labelling (ASL) are sensitive biomarkers of early damage of the transplanted kidney in paediatric renal transplant recipients (pRTR). Methods Prospective study of pRTR undergoing MRI imaging using 1.5T Siemens Avanto system with multi-TI pulsed ASL acquisition performed at 10-20 days, 2 and 12 months with a FAIR labelling scheme and multi-shot 3D grase imaging module with background suppression. Results 14 pRTR (50% (7) male) aged 9.2-17.1 (median 13.2) years of whom 64% (9) had ESKD due to congenital anomalies of the kidneys and urinary tract underwent MRI ASL after transplantation (86% (12) living-related) with eGFR of 41.0-92.0 (median 60.9) mls/min/1.73m2 at follow-up of 3.5-5.4 (median 4.5) years. 46% (6) were pre-emptive transplants with 7% (1) re-transplanted. Patients had 0-5 (median 1) post-transplant UTI with 50% (7) EBV viraemia and underwent 1-7 (median 2) percutaneous renal transplant biopsies with evidence of steroid-resistant acute rejection episode due to non-adherence and borderline rejection in 7% (1) and 14% (2) pRTR respectively. Baseline MRI ASL at median 10 days showed cRBF of 86-268 (median 198) mls/100g/min with changes at subsequent and latest MRI performed at median 70 and 344 days respectively of -70 to +121 (median 52) and -56 to +147 (median 36) mls/100g/min respectively.Discussion Renal blood flow maximises in the first month after renal transplantation with subsequent reduction in first year in pRTR. There are multiple causes of renal allograft dysfunction in pRTR and associated risks in performing surveillance percutaneous renal transplant biopsies. MRI ASL is a useful and novel non-invasive biomarker of renal allograft function in pRTR.

Spectrum of renal allograft biopsy: A five-year experience at a tertiary care center of Eastern India

Renal allograft dysfunction (RAD) can have myriad causes and presentations. Allograft biopsy remains the gold standard for optimum management. This is a retrospective study carried out at a tertiary care institute from August 2011 to March 2016. Details of the renal allograft biopsy requisitions were recorded and analyzed. Two hundred and two patients had undergone kidney transplantation (KT) during the study period. One hundred and twenty-six had undergone renal biopsy for RAD. The acute asymptomatic rise of serum creatinine was the most common clinical presentation (47.61%) followed by chronic RAD (CRAD) (19.84%), proteinuria (15.87%), immediate graft dysfunction (10.31%), and persistent active urinary sediments (6.34%) in that order. The incidence of delayed graft function was 1.98%. The overall incidence of biopsy-proven rejection was 8.41% within oneyear and 8.91% beyond oneyear of transplant. Acute cellular rejection (ACR) [with or without antibody-mediated rejection (AMR)] was found in 65%; AMR was found in 40% and 15% had both ACR and AMR. Borderline acute cell-mediated rejection was found in 22.5% of biopsies. CRAD was due to chronic rejection and chronic calcineurin inhibitor toxicity in only about one-fourth of the cases. Incidence of glomerulo-nephritis was 10.89% and most of these occurred two years after KT. Renal allograft biopsy was associated with minor complications in 3.17% of cases. Clinical presentations do not reliably distinguish the various causes of RAD. Allograft biopsy is a mainstay in the diagnosis of RAD and is safe. Results of live donor first transplantation using complement-dependent cytotoxi-city crossmatch are comparable to those programs using newer methods like solid-phase assays. However, the direct comparison of these results with other studies may not be completely applicable.

In Vivo Attenuation of Antibody-Mediated Acute Renal Allograft Rejection by Ex Vivo TGF-β-Induced CD4+Foxp3+ Regulatory T Cells.

Antibody-mediated rejection (AMR) has emerged as the major cause of renal allograft dysfunction, and more effective strategies need to be explored for improving transplant outcomes. Regulatory T cells (Tregs), consisting of at least natural and induced Treg subsets, suppress effector responses at multiple levels and play a key role in transplantation tolerance. In this study, we investigated the effect of induced Tregs (iTregs) on preventing antibody-mediated renal injury and rejection in a mouse model. We observed that infusion of iTregs markedly attenuated histological graft injury and rejection and significantly improved renal allograft survival. iTregs exhibited a comprehensive ability to regulate immunological disorders in AMR. First, iTreg treatment decreased the levels of circulating antidonor antibody and the antibody deposition within allografts. Second, iTregs significantly reduced cell infiltration including CD4+ T cells (including Th1, Th17, and Tfh), CD8+IFN-γ+ cells, natural killer cells, B cells, and plasma cells, which are involved in the process of AMR. Our results also highlight a predominance of M1 macrophage infiltration in grafts with acute AMR, and M1 macrophage could be reduced by iTreg treatment. Collectively, our data demonstrate, for the first time, that TGF-β-induced Tregs can attenuate antibody-mediated acute renal allograft injury through targeting multiple effectors. Thus, use of iTregs in prevention of AMR in clinical practice could be expected.

URINARY BIOMARKERS FOR FOLLOW-UP OF RENAL TRANSPLANTATION - WHERE WE ARE!

Early diagnosis of renal allograft dysfunction is crucial for the management and long-term survival of the transplanted kidney. Early after transplantation, acute tubular necrosis (ATN) manifesting as delay graft function (DGF) or slow graft function, acute rejection (AR) or drug toxicity (e.g. calcineurin inhibitor) are the leading causes of Acute kidney injury (AKI). Acute rejection, ATN, and calcineurin inhibitor toxicity continue to be major causes of renal allograft dysfunction along with other causes like infections (e.g. BK and CMV viruses, pyelonephritis), obstruction, and recurrence of the original disease. Clinicians have been searching for non-invasive tools that would allow the diagnosis of acute renal allograft dysfunction early and accurately without performing a kidney biopsy. The following comprehensive review will describe the latest findings on urinary biomarkers in acute allograft dysfunction.

Risk Factors for the Development of BK Virus Nephropathy in Renal Transplant Recipients

The BK polyoma virus has, in recent years, become a significant cause of renal allograft dysfunction and failure. Among 260 adult kidney transplant recipients, those with biopsy-proven BK virus nephropathy (BKVN) were compared with those without BKVN with regard to gender, age, race, rejection episodes, time on dialysis, number of organs transplanted, HLA match, live donor versus deceased donor, cold ischemia time, delayed graft function, cytomegalovirus (CMV) serostatus of donor and recipient, induction therapy, and maintenance immunosuppression. Episodes of rejection (35.7% of patients with BKVN vs 8.5% of patients without BKVN; P = .01), transplantation of >1 organ (35.7% of patients with BKVN vs 9.0% of patients without BKVN; P = .01), positive CMV serology in both donor and recipient (71.4% of patients with BKVN vs 41.1% of patients without BKVN; P = .03), and a greater cumulative dose of daclizumab use at the time of induction (2.24 ± 0.05 mg/kg in patients with BKVN vs 2.03 ± 0.14 mg/kg in patients without BKVN; P = .04) were statistically significant risk factors for the development of BKVN. Those who developed BKVN received a higher mean cumulative dose of rabbit antithymoglobulin for induction therapy, but that difference failed to achieve statistical significance (P = .07).

Quantitative analysis of BKV-specific CD4 + T cells before and after kidney transplantation

BackgroundBK virus (BKV) is the main infectious cause of renal allograft dysfunction. Although recent studies showed an inverse correlation between BKV-specific T-cell responses and viral load after transplantation, the importance of pre-transplant response in the process of virus reactivation has only been studied once. In this study, we aimed to determine whether pre-transplant CD4+ T-cell response can be used for prediction of BKV reactivation and BKV nephropathy (BKVN), by a method that can practically be used in routine patient monitoring. MethodsBKV-specific CD4+ T-cell responses of 31 kidney recipients (all from live donors) were measured by an IFN-γ-enzyme-linked-immunospot (ELISPOT) method using mixture of peptides, at day 0 and +1, +3, and +6months posttransplant. Additionally, seven other reactivation patients as another group were also analyzed. BKV viral loads in plasma were measured by real-time polymerase chain reaction (PCR). Responses of 10 healthy people were also included as controls in the analysis. ResultsAll but one patient and all of the controls had detectable CD4+ T-cell responses. Reactivation occurred in 8 out of 31 patients. There was no significant association between pretransplant BKV-specific CD4+ T-cell responses and BKV reactivation and between BKV DNA levels and CD4+ T-cell responses. In the additional group consisting of reactivation patients, four patients who had BKVN showed negative correlation between BKV-DNA levels and BKV-specific CD4+ T-cell responses (p<0.05). One patient who developed BKVN, however, was not able to mount a similar CD4+ T-cell response to viral reactivation despite immunosuppressive reduction. ConclusionEven though our cohort is small, our results may suggest that pre-transplant measurement of BKV specific CD4+ T-cell response may not be necessary, and that post-transplant monitoring, particularly during reactivation, may be more helpful in the management of the infection.

Utility of Iron Staining in Identifying the Cause of Renal Allograft Dysfunction in Patients with Sickle Cell Disease.

Sickle cell nephropathy (SCN) is associated with iron/heme deposition in proximal renal tubules and related acute tubular injury (ATI). Here we report the utility of iron staining in differentiating causes of renal allograft dysfunction in patients with a history of sickle cell disease. Case 1: the patient developed acute allograft dysfunction two years after renal transplant. Her renal biopsy showed ATI, supported by patchy loss of brush border and positive staining of kidney injury molecule-1 in proximal tubular epithelial cells, where diffuse increase in iron staining (2+) was present. This indicated that ATI likely resulted from iron/heme toxicity to proximal tubules. Electron microscope confirmed aggregated sickle RBCs in glomeruli, indicating a recurrent SCN. Case 2: four years after renal transplant, the patient developed acute allograft dysfunction and became positive for serum donor-specific antibody. His renal biopsy revealed thrombotic microangiopathy (TMA) and diffuse positive C4d stain in peritubular capillaries. Iron staining was negative in the renal tubules, implying that TMA was likely associated with acute antibody-mediated rejection (AAMR, type 2) rather than recurrent SCN. These case reports imply that iron staining is an inexpensive but effective method in distinguishing SCN-associated renal injury in allograft kidney from other etiologies.

Treatment of Presumptive BK Nephropathy with Ciprofloxain in Kidney Transplant Recipients: Three Case Reports

BK virus nephropathy has emerged as an important cause of renal allograft dysfunction. Reduction in immunosuppression is the mainstay of BK virus nephropathy treatment. However, decreasing immunosuppressive medications is not sufficient for treatment of BK virus nephropathy. Therefore, there is a need for other treatment strategies such as cidofovir, leflunomide, and intravenous immunoglobulin in combination with immunosuppression reduction. Ciprofloxacin has recently been reported to have antiviral activity and decrease BK viral load in kidney transplant recipients. These findings suggest that the use of ciprofloxacin represents a valuable treatment strategy in patients with BK virus nephropathy. Here, we report on our experience with three patients who developed presumptive BK virus nephropathy after kidney transplantation, who, after 2 months of ciprofloxacin treatment, showed disappearance of BK viremia and improvement in the estimated glomerular filtration rate. Ciprofloxacin may be consid- ered an effective treatment option for BK viremia in kidney transplant recipients.

P042 : PREVALENCE AND CLINICAL SIGNIFICANCE OF C1q BINDING DONOR SPECIFIC ANTIBODIES IN RENAL TRANSPLANTATION

Antibody-mediated injury is a major cause of renal allograft dysfunction and loss. In this study, we aimed to determine the prevalence and clinical significance of complement binding donor-specific antibodies (C1q + DSA) in renal transplant recipients with functioning allografts after 3–30 years post-transplantation. A total of 405 patients who received renal transplantation at our center from 1982 to 2009 were enrolled in this study. HLA-A, B, C, DR and DQ typing information was available for all patient and donor pairs. All patients were transplanted based on a negative crossmatch and had current serum samples available for DSA testing. Serum IgG- and C1q-binding HLA antibodies were tested using the Single Antigen Bead assay. Based on DSA status, 3 distinct groups were identified in our patient population: 33 patients (8%) with C1q + DSA, 44 patients (11%) with C1q- DSA and 328 patients (81%) without DSA. There were no differences between the groups in terms of gender, race, previous transplantation and induction therapy. However, age and transplant type were significantly different between the groups, with C1q + DSA + patients receiving transplantation at a younger age and more frequently from deceased donors than the other groups ( p p Conclusion Our results indicate that C1q + DSA occured at a frequency of 8% in patients with functioning renal allografts 3–30 years after transplantation. Such antibodies occured more frequently in younger patients and those who received deceased donor allografts. C1q + DSA were associated with an increased incidence of acute and chronic antibody mediated rejection. Thus, monitoring of high-strength/complement binding DSA may assist in the identification of patients at risk for graft loss late after transplantation.

Antibody-mediated rejection: analyzing the risk, proposing solutions.

Antibody-mediated rejection: analyzing the risk, proposing solutions.