Kidney Graft Loss Research Articles

Recurrent Membranous Nephropathy After Kidney Transplantation Associated With Phospholipase A2 Receptor and Successfully Treated With Rituximab: A Case Report

Primary membranous nephropathy (MN) is an organ-specific autoimmune disease mainly caused by autoantibodies acting against the podocyte antigen M-type phospholipase A2 receptor 1 (PLA2R). Herein we present the clinical and histologic findings, including PLA2R staining, of early recurrent MN after kidney transplantation that was successfully treated with rituximab.A 60-year-old Japanese man had end-stage renal failure due to steroid-resistant primary MN and underwent ABO-incompatible living donor kidney transplantation. At 1 month after transplantation, a protocol biopsy revealed positive granular staining of IgG, C4d, and PLA2R on glomerular capillaries (GCs) without any abnormalities on light microscopy (LM). Although the patient had low-level proteinuria, recurrent MN was suspected based on the positive PLA2R staining; he was treated with an angiotensin receptor blocker and a single dose of 200 mg rituximab. However, proteinuria gradually increased to 877 mg/d. At 21 months after transplantation, a graft biopsy revealed spikes along the outer aspects of GC on LM, with stronger staining for PLA2R than that at 1 month after transplantation. A single dose of 500 mg rituximab was added, which effectively reduced proteinuria, and clinical remission continued until 3 years after transplantation. The latest graft biopsy showed reduced staining of PLA2R. The disease activity and therapeutic effect were well-reflected in the intensity of PLA2R staining.An approach intending an early diagnosis by protocol biopsy using PLA2R immunostaining is made and early treatment with rituximab will help reduce the risk of kidney graft loss due to recurrent primary MN.

Results of Transplantation of Kidneys Procured From Donors After Brain Death Aged 60 Years and Older

ObjectiveTo analyze results of transplantation of kidneys procured from donors after brain death aged 60 years and older (hereafter denoted by “≥60”) compared to kidneys procured from donors after brain death aged 40–59 years (hereafter denoted by “40–59”) in medium-term follow-up period, and to assess factors that affect recipient and kidney graft survival. Material and methods92 transplant recipients of kidneys procured from donors after brain death ≥60 were enrolled into the study. The control group were 363 recipients of kidneys procured from donors after brain death 40–59. ResultsMean values of serum creatinine were higher in recipients of kidneys procured from donors after brain death ≥60 compared to control after 3 years: 168.2 ± 57.5 (n = 59) vs 147.9 ± 65.7 (n = 294), P < .05; and after 5 years: 196.2 ± 95.3 (n = 38) vs 157.3 ± 80.0 μmol/L (n = 211), P < .01. Restricted mean recipient survival time was 56.4 (95% confidence interval: 55.0–57.8) and 52.0 (48.0–56.1) months, P < .05; and kidney graft survival time was 51.6 (49.6–53.5) and 43.9 (39.0–48.9) months, P < .01 in recipients who received kidneys from donors after brain death 40–59 and from donors after brain death ≥60 respectively. In Cox regression, donor death due to cardiovascular disease proved to be the factor increasing risk of kidney graft loss (hazard ratio 1.553, P < .001). ConclusionsThe survival and function of kidneys procured from donors after brain death ≥60 at medium-term follow-up remain worse compared to kidneys procured from donors after brain death 40–59, and the donor dependent risk factor of kidney graft loss is cardiovascular disease, which caused donor death.

PD54 Associated Factors Renal Graft Loss Using Real-World Evidence In Brazil

Introduction:Renal transplantation is considered a cost-effective treatment compared to dialysis and represents a significant percentage of public health resources. Post-transplant treatment requires the use of three immunosuppressive drugs. The immunosuppressive regimens consists of a corticosteroid, a calcineurin inhibitor (cyclosporine or tacrolimus) and an antiproliferative agent (azathioprine or mycophenolate) and also by sirolimus or everolimus. In Brazil, the Unified Health System (as known as Sistema Único de Saúde - SUS) is responsible for 95 percent of all kidney transplants performed, as well as ensuring access to immunosuppressive drugs. Therefore, there is a huge and growing economic impact caused by the distribution of these drugs in SUS. We evaluated the factors associated with kidney graft loss in patients who received deceased donor organ and used maintenance immunosuppressive regimens in SUS, in fifteen years.Methods:We analyzed a nationwide cohort of kidney transplant recipients from January 2000 to December 2015 developed through deterministic-probabilistic linkage of SUS administrative databases: Hospital Information System (SIH/SUS); Subsystem for High Complexity Procedures (SIA/SUS) and the Mortality Information System (SIM). Graft loss was defined as death or dialysis for more than three months. All regimens included corticosteroid. We used Cox proportional hazards model to evaluate the factors associated with progression to graft loss.Results:In total, 18,333 patients were included; 58.5 percent used tracolimus+mycophenolate, 11.7 percent cyclosporine+mycophenolate, 8.9 percent tacrolimus+azathyoprine, 5.5 percent cyclosporine+azathyoprine and 15.4 percent received other immunosuppressive regimens (sirolimus+mycophenolate, everolimus+mycophenolate, tacrolimus, mycophenolate, cyclosporine, azathyoprine) . Most patients were male with a median age of 46 years. A higher risk of graft loss was associated with the use of tracolimus+mycophenolate (HR = 1.069; 95% CI, 0.999–1.146), sirolimus+mycophenolate (HR1.395;95% CI, 1 .150–1.692), tracolimus (monotherapy) (1.468;1.239–1.739); mycophenolate (monotherapy) (1.297;1.126–1.493), male gender (1.144; 1.072–1.221), an additional year of age (1.010; 1.007–1.013), a median dialysis period greater than 38 months (1.266; 1.182–1.356), a diagnosis of diabetes (1.211; 1.071–1.367) and a diagnosis of arterial hypertension (1.209; 1.134–1.288) (HR=1.468;95% CI,1.239 −1.739); mycophenolate (monotherapy) (HR = 1.297; 95% CI, 1.126–1.493), male gender (HR = 1.144; 95% CI 1.072–1.221), an additional year of age (HR = 1.010; 95% CI, 1.007–1.013), a median dialysis period greater than 38 months (HR = 1.266; 95% CI, 1.182–1.356), a diagnosis of diabetes (HR = 1.211; 95% CI, 1.071–1.367) and a diagnosis of arterial hypertension (HR = 1.209; 95% CI, 1.134–1.288)as the primary cause of chronic kidney disease.Conclusions:In Brazil, the use of regimens mycophenolate, tacrolimus, tacrolimus+mycophenolate was associated a higher risk of graft loss, among other factors. The choice of drug therapy is one of the few factors that influence survival amenable to direct action by health professionals. Therefore, the results of this study are important and should be disseminated aiming to better outcomes for kidney transplant patients.

Quantitative detection of BK virus in kidney transplant recipients: a prospective validation study.

Introduction:BK virus (BKV) infection in renal transplant patients may cause kidney allograft dysfunction and graft loss. Accurate determination of BKV viral load is critical to prevent BKV-associated nephropathy (BKVAN) but the cut-off that best predicts BKVAN remains controversial.Objective:To evaluate the performance of a commercial and an in-house qPCR test for quantitative detection of BK virus in kidney transplant recipients.Methods:This was a prospective study with kidney transplant recipients from two large university hospitals in Brazil. Patients were screened for BKV infection every 3 months in the first year post-transplant with a commercial and an in-house real time polymerase chain reaction (qPCR) test. BKVAN was confirmed based on histopathology. The area under the curve for plasma qPCR was determined from receiver operating characteristic analysis.Results:A total of 200 patients were enrolled. Fifty-eight percent were male, 19.5% had diabetes mellitus, and 82% had the kidney transplanted from a deceased donor. BKV viremia was detected in 32.5% and BKVAN was diagnosed in 8 patients (4%). BKVAN was associated with viremia of 4.1 log copies/mL, using a commercial kit. The cut-off for the in-house assay was 6.1 log copies/mL. The linearity between the commercial kit and the in-house assay was R2=0.83.Conclusion: Our study shows that marked variability occurs in BKV viral load when different qPCR methodologies are used. The in-house qPCR assay proved clinically useful, a cheaper option in comparison to commercial qPCR kits. There is an urgent need to make BKV standards available to the international community.

Pre-transplant AT1R antibodies correlate with early allograft rejection

Studies investigating the potential pathogenic effects of non-HLA antibodies (Ab) have identified Ab against the angiotensin II type 1 receptor (AT1R-Ab) as a risk factor for rejection and kidney graft loss. This study sought to validate the risk of AT1R-Ab for acute rejection and to explore the role of other non-HLA Abs in this capacity.Pre- and post-transplant sera from a cohort of 101 patients (n=453 samples total) were tested for AT1R-Ab and other non-HLA Ab using a commercially available ELISA kit and the Luminex platform, respectively.Patients positive for pre-transplant AT1R-Ab were more likely to develop de novo donor-specific Ab (dnDSA) compared to patients that were negative for AT1R-Ab (28% vs 10%, p=0.027). Pre-transplant positivity for AT1R-Ab was associated with TCMR in the first year post-transplant (p=0.034), but did not predict graft loss independent of dnDSA (p=0.063). AT1R-Ab positivity was significantly associated with positivity for Ab against the endothelin A type 1 receptor (ETAR-Ab) inclusive of all study time points (p=0.0021).Given the high prevalence of AT1R-Ab pre-transplant (20%) and its association with dnDSA and early TCMR, a prospective study to determine if more intense immunosuppression and/or AT1R blockade has an impact on outcomes in these patients is warranted.

Rabbit anti-human thymocyte immunoglobulin for the rescue treatment of chronic antibody-mediated rejection after pediatric kidney transplantation.

Chronic antibody-mediated rejection (cAMR) is the leading cause of late kidney graft loss, but current therapies are often ineffective. Rabbit anti-human thymocyte immunoglobulin (rATG) may be helpful, but its use is virtually undocumented. Data were analyzed retrospectively from nine pediatric kidney transplant patients with cAMR were treated with rATG (1.5mg/kg × 5days) at our center after non-response to pulsed prednisolone, intravenous immunoglobulin, rituximab, and increased immunosuppressive intensity (including switching to belatacept in some cases), with or without bortezomib. The median time from diagnosis to cAMR was 179days. rATG was started 5-741days after diagnosis. Median estimated glomerular filtration rate (eGFR) increased from 40mL/min/1.73m2 when rATG was started to 62mL/min/1.73m2 9months later (p=0.039). Four patients showed substantially higher eGFR after 9months and 2 patients showed a small improvement; eGFR continued to decline in 3 patients after starting rATG. No grafts were lost during follow-up. At last follow-up, donor-specific antibodies (DSAs) were no longer detectable in 4 out of 8 patients for whom data were available, median fluorescence intensity had decreased substantially in 1 out of 8 patients; anti-HLA DQ DSAs persisted in 2 out of 8 patients. No adverse events with a suspected relation to rATG, including allergic reactions, leukocytopenia or infections, were observed in any of the patients. In this small series of patients, rATG appears a promising treatment for unresponsive cAMR. Further evaluation, including earlier introduction of rATG, is warranted.

BK viremia surveillance and outcomes in simultaneous pancreas-kidney transplant recipients.

While screening for asymptomatic BK viremia (BKV) has been well studied in isolated kidney transplant recipients, there is a paucity of published outcomes in simultaneous pancreas-kidney (SPK) transplant recipients who underwent BKV screening followed by pre-emptive reduction in immunosuppression. This is a single-center, retrospective review of 31 consecutive SPK recipients who were transplanted over a 5-year period following the initiation of a serum BKV screening protocol. BK viremia developed in 11 (35.5%) patients, and all patients achieved complete viral clearance following reduction in immunosuppression. Two patients (6.5%) developed BK virus nephropathy, but both had preserved allograft function. One patient developed mild rejection of the kidney allograft following clearance of BKV, and two patients developed mild rejection of the pancreas allograft after reduction in immunosuppression, but there were no kidney or pancreas allograft losses due to rejection. The development of BK viremia did not impact overall patient survival or kidney and pancreas allograft survival. Screening asymptomatic SPK recipients for BKV followed by reduction in maintenance immunosuppression appears to be an effective strategy to prevent kidney allograft dysfunction and graft loss due to BK virus nephropathy, without compromising pancreas allograft outcomes.

Molecular and Functional Noninvasive Immune Monitoring in the ESCAPE Study for Prediction of Subclinical Renal Allograft Rejection.

Subclinical acute rejection (sc-AR) is a main cause for functional decline and kidney graft loss and may only be assessed through surveillance biopsies. The predictive capacity of 2 novel noninvasive blood biomarkers, the transcriptional kidney Solid Organ Response Test (kSORT), and the IFN-γ enzyme-linked immunosorbent spot assay (ELISPOT) assay were assessed in the Evaluation of Sub-Clinical Acute rejection PrEdiction (ESCAPE) Study in 75 consecutive kidney transplants who received 6-month protocol biopsies. Both assays were run individually and in combination to optimize the use of these techniques to predict sc-AR risk. Subclinical acute rejection was observed in 22 (29.3%) patients (17 T cell-mediated subclinical rejection [sc-TCMR], 5 antibody-mediated subclinical rejection [sc-ABMR]), whereas 53 (70.7%) showed a noninjured, preserved (stable [STA]) parenchyma. High-risk (HR), low-risk, and indeterminate-risk kSORT scores were observed in 15 (20%), 50 (66.7%), and 10 (13.3%) patients, respectively. The ELISPOT assay was positive in 31 (41%) and negative in 44 (58.7%) patients. The kSORT assay showed high accuracy predicting sc-AR (specificity, 98%; positive predictive value 93%) (all sc-ABMR and 58% sc-TCMR showed HR-kSORT), whereas the ELISPOT showed high precision ruling out sc-TCMR (specificity = 70%, negative predictive value = 92.5%), but could not predict sc-ABMR, unlike kSORT. The predictive probabilities for sc-AR, sc-TCMR, and sc-ABMR were significantly higher when combining both biomarkers (area under the curve > 0.85, P < 0.001) and independently predicted the risk of 6-month sc-AR in a multivariate regression analysis. Combining a molecular and immune cell functional assay may help to identify HR patients for sc-AR, distinguishing between different driving alloimmune effector mechanisms.

Post-Transplant Diabetes Mellitus After Kidney Transplant in Hispanics and Caucasians Treated with Tacrolimus-Based Immunosuppression

BackgroundDevelopment of post-transplant diabetes mellitus after kidney transplant (PTDM) significantly increases kidney graft loss and mortality. Several risk factors for PTDM have been reported, including Hispanic ethnicity and the use of calcineurin inhibitors and corticosteroids. The incidence and impact of PTDM in the Hispanic kidney transplant population is unknown.Material/MethodsWe retrospectively reviewed the medical records of 155 Hispanic and 124 Caucasian patients, who were not diabetics and underwent kidney transplant between January 2006 and December 2011. We analyzed their clinical outcomes at 12 months post-transplant, including the incidence of PTDM, acute rejection rates, and patient and graft survival.ResultsHispanics who developed PTDM (n=22) were more than 10 years older and had higher body mass index (BMI) than Hispanics without PTDM (p<0.001 and p=0.001, respectively). Caucasians with PTDM (n=13) were non-significantly older (2.5 years) and had higher BMI than Caucasians without PTDM (p=0.526, p=0.043, respectively). The incidence of PTDM was not significantly different between Hispanics and Caucasians treated with tacrolimus-based immunosuppression (14.2% and 10.5%, respectively).ConclusionsPTDM did not cause significant difference in short-term outcomes after kidney transplant in Hispanics or Caucasians. Larger multicenter prospective and long-term clinical trials are needed to validate these findings.

Stressors and coping resources of Australian kidney transplant recipients related to medication taking: a qualitative study.

To understand the stressors related to life post kidney transplantation, with a focus on medication adherence, and the coping resources people use to deal with these stressors. Although kidney transplantation offers enhanced quality and years of life for patients, the management of a kidney transplant post surgery is a complex process. A descriptive exploratory study. Participants were recruited from five kidney transplant units in Victoria, Australia. From March-May 2014, patients who had either maintained their kidney transplant for ≥8months or had experienced a kidney graft loss due to medication nonadherence were interviewed. All audio-recordings of interviews were transcribed verbatim and underwent Ritchie and Spencer's framework analysis. Participants consisted of 15 men and 10 women aged 26-72years old. All identified themes were categorised into: (1) Causes of distress and (2) Coping resources. Post kidney transplantation, causes of distress included the regimented routine necessary for graft maintenance, and the everlasting fear of potential graft rejection, contracting infections and developing cancer. Coping resources used to manage the stressors were first, a shift in perspective about how easy it was to manage a kidney transplant than to be dialysis-dependent and second, receiving external help from fellow patients, family members and health care professionals in addition to using electronic reminders. An individual well-equipped with coping resources is able to deal with stressors better. It is recommended that changes, such as providing regular reminders about the lifestyle benefits of kidney transplantation, creating opportunities for patients to share their experiences and promoting the usage of a reminder alarm to take medications, will reduce the stress of managing a kidney transplant. Using these findings to make informed changes to the usual care of a kidney transplant recipient is likely to result in better patient outcomes.

Infectious complications as the leading cause of death after kidney transplantation: analysis of more than 10,000 transplants from a single center

To identify specific causes of graft failure in a large sample of kidney transplant patients from a middle-income, developing country. Retrospective cohort study analyzing all consecutive single kidney transplants (KTs) performed at a single center in Brazil between January 1st 1998 and December 31st 2013. The database closing date was December 31st 2014. Out of 10,400 KTs, there were 1191 (11.45%) deaths with a functioning graft, 40 cases (0.38%) of primary non-function (PNF) and 1417 cases (13.62%) of graft loss excluding death and PNF as the cause. Infectious complications (404 cases, 34% of all deaths) were the major cause of death. Most deaths due to infection occurred within the first year after transplantation (157 deaths, 38.86%). Immunologic mechanisms, comprising acute rejection and immune-mediated interstitial fibrosis/tubular atrophy (IF/TA), were responsible for 52% of all cases of graft failure not involving recipient death. Half of the losses by acute rejection occurred late after transplantation. Contrary to what is observed in developed countries, infectious complications are the main challenge with kidney transplantation in Brazil. Non-adherence to treatment also appears to contribute significantly to long-term kidney graft loss. Strategies for improvement should focus on better compliance and a greater safety profile of immunosuppressive treatment.

Polyreactive natural antibodies in transplantation.

Antibody-mediated rejection (ABMR), especially in its chronic manifestation, is increasingly recognized as a leading cause of late graft loss following solid organ transplantation. In recent years, autoantibodies have emerged as a significant component of the humoral response to allografts alongside anti-human leukocyte antigen antibodies. These include polyreactive antibodies also known as natural antibodies (Nabs) secreted by innate B cells. A hallmark of Nabs is their capacity to bind altered self such as oxidized lipids on apoptotic cells. This review provides an overview of these overlooked antibodies and their implication in the pathophysiology of ABMR. New evidence reported in the past few years support a contribution of immunoglobulin (Ig) G Nabs to ABMR. Serum IgG Nabs levels are significantly higher in patients with ABMR compared with control kidney transplant recipients with stable graft function. Pretransplant IgG Nabs are also associated with ABMR and late graft loss. IgG Nabs are almost exclusively of the IgG1 and IgG3 subclasses and have the capacity to activate complement. In conclusion, Nabs are important elements in host immune responses to solid organ grafts. The recent description of their implication in ABMR and late kidney graft loss warrants further investigation into their pathogenic potential.

Liver-kidney simultaneous transplantation in adult patients with primary hyperoxaluria. Experience at Hospital Universitario 12 de Octubre.

Primary hyperoxaluria (PH) is a metabolic liver disease with an autosomal recessive inheritance that results in oxalate overproduction that cannot be metabolized by the liver. Urinary excretion of oxalate results in lithiasis and nephrocalcinosis leading to a progressive loss of renal function that often requires renal replacement therapy despite medical treatment. Type 1 PH is the most common form and is due to a deficiency in the alanine-glycolate aminotransferase enzyme found in hepatic peroxisomes. Therefore, a liver-kidney simultaneous transplant (LKST) is the definitive treatment for end-stage renal disease (ESRD) patients. However, some studies suggest that the morbidity and mortality rates are greater when this procedure is performed instead of only a kidney transplant (IKT). Herein, we report five patients with PH and a mean glomerular filtration rate of 20.2 ± 1.3 ml/min/1.73 m2 who received a LKST between 1999 and 2015 at the Hospital Universitario 12 de Octubre. Recurrence and liver or kidney graft loss was not observed during the postoperative period and only one case of late acute rejection without graft loss was diagnosed. The recipient survival rate was 100% with a median follow up of 84 months. As LKST is a curative and safe procedure with a low mortality and high survival rate, it must be considered as the treatment of choice in adults with HP and ESRD.

Influence of specific thoracic donor therapy on kidney donation and long-term kidney graft survival.

To analyze the impact of a specific thoracic donor-treatment protocol (including restrictive fluid balance) on kidney donation and on kidney graft survival. A cohort study. Lung Donors and kidney recipients from 2003 to 2008 were the pre-protocol cohort, and those from 2009 to 2013 were the protocol cohort. The main outcome variables were graft survival and rate of kidney donation. Kidney donation rates were similar in both periods (86.2 vs. 86.2 %; p > 0.05). Both donors and kidney recipients were older and with more comorbidities in the protocol group and this is the reason there were more cases of delayed graft function (differences not statistically significant) and with higher sequential creatinine levels of kidney recipients during the protocol period. However, graft survival was similar in both groups. The probability of graft survival 5 years after transplantation was 0.75 (95 % confidence interval 0.65-0.85) in the pre-protocol cohort and 0.81 (0.70-0.92) in the protocol cohort. Specific treatment for multi-organ donors including restrictive fluid balance does not affect kidney donation or kidney graft loss, and has no impact on long-term viability. Hemodynamics must be closely monitored by medical personnel with specific training.

Tracing clinically relevant HLA antibodies prior to kidney transplantation: Commentary on "Pre-transplant HLA antibodies detected by single antigen bead assay are a risk factor for long-term kidney graft loss even in the absence of donor specific antibodies".

Tracing clinically relevant HLA antibodies prior to kidney transplantation: Commentary on "Pre-transplant HLA antibodies detected by single antigen bead assay are a risk factor for long-term kidney graft loss even in the absence of donor specific antibodies".

Incidences of acute kidney injury, dialysis, and graft loss following intravenous administration of low-osmolality iodinated contrast in patients with kidney transplants.

To determine the incidence of acute kidney injury (AKI), need for emergent dialysis, and renal graft loss in patients with kidney transplants, who underwent CT examinations with low-osmolality iodine-based contrast material (IBCM). Our institutional review board approved this retrospective Health Insurance Portability and Accountability Act compliant study. From January 2005 to April 2015, a total of 224 CT examinations were performed using low-osmolality IBCM in patients with kidney transplants. Six patients who had septic or cardiogenic shock and 30 patients with documented, failed transplants were excluded from our analysis, yielding a total of 188 examinations. Of these, pre- and post-CT serum creatinine (SCr) values were available for 104 examinations, to allow evaluation of AKI. The mean baseline SCr and estimated glomerular filtration rate (eGFR) in this subgroup were 1.37mg/dL (median 1.18, range 0.5-6.05) and 65.8mL/min/1.73m2, respectively (median 65, range 9-114). AKI was defined as a rise in SCr of either (a)≥0.3mg/dL or (b)≥0.5mg/dL in the 24- to 72-h period following IBCM administration. For all patients undergoing the 188 examinations, need for dialysis and graft loss 30days after contrast administration were evaluated. In patients with pre- and post-CT SCr values, the incidence of AKI was 7% (7/104) based on a rise of ≥0.3mg/dL and 3% (3/104) based on a rise of ≥0.5mg/dL. All three patients with the more strict definition (≥0.5mg/dL) had a pre-CT eGFR <60mL/min/1.73m2. No patient required dialysis or had renal graft loss 30days after contrast administration. The incidence of AKI after administration of low-osmolality IBCM administration in renal transplant recipients is low, with no instances of emergent dialysis or graft loss at 30days post contrast.

Pretransplant human leukocyte antigen antibodies detected by single-antigen bead assay are a risk factor for long-term kidney graft loss even in the absence of donor-specific antibodies.

Clinical relevance of ELISA- and single-antigen bead assay (SAB)-detected pretransplant HLA antibodies (SAB-HLA-Ab) for kidney graft survival was evaluated retrospectively in 197 patients transplanted between 2002 and 2009 at the University Clinic Frankfurt. Having adjusted for retransplantation and delayed graft function, a significantly increased risk for death-censored graft loss was found in patients with pretransplant SAB-HLA-Ab [HR: 4.46; 95% confidence interval (CI): 1.47-13.48; P = 0.008]. The risk for increased graft loss was also significant in patients with pretransplant SAB-HLA-Ab but without SAB-detected donor-specific Ab (SAB-DSA) (HR: 4.91; 95% CI of 1.43-16.991; P = 0.012). ELISA was not sufficient to identify pretransplant immunized patients with an increased risk for graft loss. In immunized patients, graft loss was predominantly present in patients who received transplants with a mismatch on the HLA-DR locus. In conclusion, even if our study is limited due to small sample size, the results show an increased risk for long-term graft loss in patients with pretransplant SAB-HLA, even in the absence of DSA. SAB-HLA-Ab-positive patients, being negative in ELISA or CDC assay, might profit from a well-HLA-DR-matched graft and intensified immunosuppression.

A compilation of consumers' stories: the development of a video to enhance medication adherence in newly transplanted kidney recipients.

To describe the design, development and evaluation of a consumer-centred video, which was underpinned by the Theory of Planned Behaviour and it was created to educate newly transplanted kidney recipients about the importance of medication adherence. Kidney transplantation is a treatment whereby medication adherence is critical to ensure long-term kidney graft success. To date, many interventions aimed to improve medication adherence in kidney transplantation have been conducted but consumers remain largely uninvolved in the interventional design. Qualitative sequential design. Twenty-two participants who had maintained their kidney transplant for at least 8months and three participants who had experienced a kidney graft loss due to non-adherence were interviewed from March-May 2014 in Victoria, Australia. These interviews were independently reviewed by two researchers and were used to guide the design of the story plot and to identify storytellers for the video. The first draft of the video was evaluated by a panel of seven experts in the field, one independent educational expert and two consumers using Lynn's content validity questionnaire. The content of the video was regarded as highly relevant and comprehensive, which achieved a score of >3·7 out of a possible 4. The final 18-minute video comprised 15 sections. Topics included medication management, the factors affecting medication adherence and the absolute necessity of adherence to immunosuppressive medications for graft survival. This paper has demonstrated the feasibility of creating a consumer-driven video that supports medication adherence in an engaging way.

Association of Kidney Graft Loss With De Novo Produced Donor-Specific and Non-Donor-Specific HLA Antibodies Detected by Single Antigen Testing.

The association of donor-specific HLA antibodies (DSA) with kidney graft failure has been addressed previously; however, the majority of studies were based on small numbers of patients with graft failure. We investigated 83 patients with failed kidney transplants for a possible association of de novo development and persistence or loss of pre-existing DSA with graft failure. Single Antigen Bead assay-detected DSA and non-DSA antibodies were compared between patients with graft loss and matched controls with functioning grafts. The incidence of weak de novo DSA or non-DSA at a mean fluorescence intensity of 500 or higher was higher in the graft loss than in the nonrejector group (76% vs 40%, P < 0.001). Because of the low number of patients developing de novo DSA, the DSA results did not reach statistical significance (only 22% of patients with graft loss developed de novo DSA). However, at all cutoffs, there was a significantly higher rate of graft loss in patients with de novo non-DSA. The incidence of strong pretransplant DSA that persist after transplantation was higher in the graft loss group (10% vs 1%, P = 0.034). When C1q-binding ability in sera of rejectors and nonrejectors with posttransplant de novo or persistent DSA was compared, none of the nonrejectors demonstrated C1q positivity, whereas 43% of patients with graft loss showed C1q-positive antibodies, although not necessarily donor-specific (P < 0.001). Our data show that the posttransplant presence of persisting or de novo HLA antibodies, especially if C1q binding, is associated with graft loss, even if the antibodies are not specific for mismatched donor HLA.

Evaluation of polyreactive monoclonal antibodies using HLA solid phase assays

It is well established that HLA antibodies play an important role in antibody-mediated rejection (AMR) and there is a growing body of literature demonstrating that non-HLA antibodies may also contribute to AMR. To study the source of non-donor specific HLA antibodies and self-reactive antibodies in patients with kidney graft loss, Porcheray et al. (Am J Transplant 2012; 12: 2088–2097) expanded immortalized polyreactive B-cell clones from a patient with kidney graft rejection and showed that some of these natural antibodies are cross-reactive to HLA and self-antigens. Gao et al. (Am J Transplant 2014; 14:1581–1591) also showed that the presence of IgG natural antibodies, with activity to apoptotic cells, correlates with late kidney allograft loss even after excluding patients with high reactivity to HLA. We have further characterized the HLA reactivity of 4 polyreactive B-cell clones isolated by Porcheray, Gao et al. using solid phase assays (Immucor, Inc.). We report here that while these clones do not react with HLA on the Immucor single antigen beads, they react to other HLA products, with some variation between different solid phase assays. Their reactivity appears to be enhanced upon denaturation, as judged by the monoclonal antibody 210.4, which reacts with denatured antigen, suggesting that they primarily react to cryptic epitopes. B. Ray: Employee; Company/Organization; Immucor.