Renal Recipients Research Articles

Optimizing Immunosuppressive Regimens Among Living-Donor Renal Transplant Recipients.

We review different immunosuppressant protocols used for living-donor kidney transplant recipients at our center. Many prospective randomized studies from our center have been reported between March 1976 and 2016, with more than 2700 renal transplant procedures conducted. The first study was a prospective randomized trial of azathioprine versus cyclosporine. The second study compared triple therapy (prednisolone + azathioprine + cyclosporine) versus conventional therapy (prednisolone + azathioprine). The third study was a cost-saving study, in which 100 patients received ketoconazole along with the triple regimen. Another trial demonstrated the advantages of a microemulsion form of cyclosporine. A subsequent trial compared calcineurin inhibitor minimization versus avoidance protocols. Rescue therapies were carried out to intensify immunosuppressive regimens after repeated rejection. In addition, steroid-free regimens were evaluated during both short- and long-term treatment. A recent trial reported a step-forward avoidance protocol with a calcineurin inhibitor and a steroid-free regimen, whereas another current study is the TRANSFORM one. The rationale behind antibody therapy was tho roughly evaluated among living-donor renal trans plant recipients with different agents, including basiliximab, daclizumab, antithymocyte globulin, and alemtuzumab. Earlier studies have demonstrated the efficacy of conventional regimens without induction therapy, especially in longer follow-up. The standard triple therapy has emerged with intensified immunosuppressive and lowered dose of each drug, especially cyclosporine. In minimization studies, no significant differences were encountered regarding patient and graft survival, even in the long-term. Steroid avoidance was safe and effective. Calcineurin inhibitors and steroid-free regimens have shown comparable patient and graft survival. Induction therapy has lowered the incidence and severity of acute rejection. A better 5-year graft survival and less posttransplant complications have been achieved with steroid avoidance after induction with basiliximab. Induction therapy did not affect graft and patient survival rates despite lowered incidence and severity of acute rejections.

Evaluation of the area under the curve of enteric-coated mycophenolate sodium using a limited sampling strategy in Chinese kidney transplant recipients .

To investigate the area under the curve (AUC) of mycophenolic acid (MPA) in adult Chinese renal allograft recipients receiving concomitant enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine (CsA) during the early post-transplant phase and to develop optimal model equations for estimation of the MPA area under the plasma concentration-time curve from 0 to 12 hours (AUC0-12h) using a limited-sampling strategy (LSS). The present study enrolled 24 Chinese renal recipients treated with EC-MPS, CsA, and corticosteroid, from whom 24 serial blood samples were collected over 12 hours. MPA concentration was evaluated with enzyme multiplied immunoassay technique (EMIT). LSS was developed by multiple stepwise regression analysis using a two-group method (test group, n=12; and validation group, n=12). The MPA predose concentration had a poor correlation with MPA AUC0-12h, and the best equations obtained from the test group were the following: 25.73+0.59 × C1.5 + 0.79 × C2 + 2.03 × C4 (for three time points, r2 = 0.761) and 22.13 + 1.7 × C0.5 + 0.61 × C1.5 + 0.78 × C2 + 1.83 × C4 (for four time points, r2 = 0.853). When these equations were tested in the validation group, there were no significant differences in prediction errors. An LSS using time points at 1.5, 2, and 4 hours or 0.5, 1.5, 2, and 4 hours provides the most accurate and reliable estimation of the MPA AUC0-12h in Chinese adult renal recipients treated concomitantly with EC-MPS and CsA during the early post-transplant phase. .

Severe intellectual disability is not a contraindication to kidney transplantation in children

Renal transplantation in children with ID is controversial. Acceptability of these children as candidates varies between programs. Limited outcome data in pediatric renal TXP recipients with cognitive impairment diminish their access to TXP. A retrospective chart review was performed of all children who underwent renal transplantation between January 1, 2002 and June 30, 2012 (N=72). Patients were divided into two groups, those with ID prior to transplantation (n=10) and those without (non-ID; n=62). Graft survival and BPAR episodes were compared between the two groups using Kaplan-Meier estimates. Graft survival rates at 3years post-TXP were 100% in the ID group and 80% in the non-ID group (P=.13). Rates of BPAR at 3years post-TXP were 10% in the ID group and 27% in the non-ID group (P=.29). Graft survival and acute rejection-free survival rates are similar between children with ID and those without. Based on midterm outcomes, there is no apparent contraindication to renal transplantation in pediatric patients with ID. Children with ID should be considered as TXP candidates provided that they have an adequate social support network.

Classification of abdominal vascular anomalies and use of 3D printing to support complex renal transplantation in children

BackgroundTransplantation is the treatment of choice for paediatric renal recipients. However, there are increased challenges in small (<20 kg) children who have complex abnormalities of the abdominal vascular system (aorta and inferior vena cava [IVC]). In this context surgical feasibility and planning is informed by review of medical images. Conventional presentation on a computer screen demands expertise in image interpretation if the spatial associations of complex anatomy are to be fully appreciated. We assessed the feasibility and potential utility of 3D printed models of patient-specific anatomy, as a means to facilitate transplantation. MethodsWe describe our management in five paediatric renal recipients with vascular anomalies (median age 7 years [IQR 4·5–13·0], median weight 18 kg [IQR 14·5–29·0]). We assessed the utility of 3D printing as a planning tool in four children with complex abnormalities (one retrospective case, three prospective cases) for whom implantation was uncertain as judged by conventional imaging. Surgically relevant donor and recipient anatomy was segmented from MRI or CT data (Mimics Medical v18.0, Materialise, Leuven, Belgium). The segmentation geometry derived from the extracted anatomical data was then exported in STL file format and physically fabricated with multimaterial, polyjet 3D printing technology (Objet500 Connex1, Objet-Stratasys). We assessed the value of models using questionnaires and geometric validation studies. FindingsFour (80%) of five children survived after one death from sepsis (with a functioning graft). At the latest median follow-up of 19 months (IQR 10·5–83·0) renal allograft survival was 100% (death censored) with a median estimated glomerular filtration rate of 55 mL/min per 1·73 m2 (IQR 45–66). We have previously classified these vascular anomolies on the basis of aortic and IVC patency (I=aorta patent, II=infrarenal segment occluded, III=suprarenal segment occluded, IV=all aorta occluded) and similarly for IVC patency (A–D). By independent questionnaire, all prospective 3D printed models were considered useful for preoperative planning, and thereby facilitated transplantation. In our retrospective proof of concept, Bland–Altman analysis found that the mean difference in vascular diameter between the printed model and segmentation geometry was −0·1 mm (95% CI −0·7 to 0·5), which was insignificant when compared with the measurement uncertainty (±0·4 mm) and the limits of surgical precision. All models showed geometrical consistency with preprinting designs and intraoperative anatomical correlation within surgical acceptance for crucial decision making. InterpretationVascular anomalies do not necessarily preclude transplantation, and a classification system could guide management. Our feasibility study of patient-specific 3D printing suggests that cases classified as sufficiently complex can benefit from this technology. Patient-specific models provide the surgical team with the full, 3D, accessible, haptic, and spatial appreciation of anatomy that is crucial in surgical decision making and planning. This technology can inform the selection of suitable anastamosis sites in the presence of anomalies and the best surgical approach for implantation of an adult-sized kidney into a small child. FundingNone.

A comparison of the effects of oral vs. intravenous hydration on subclinical acute kidney injury in living kidney donors: a protocol of a randomised controlled trial

BackgroundOptimal treatment for established renal failure is living donor kidney transplantation. However this pathway exposes healthy individuals to significant reduction in nephron mass via major surgical procedure. Laparoscopic donor nephrectomy is now the most common method for live donor transplantation, reducing both donor post-operative pain and recovery time. However this procedure exposes kidneys to additional haemodynamic stresses. It has been suggested that donor hydration—particularly the use of preoperative intravenous fluids—may counteract these stresses, reducing subclinical acute kidney injury and ultimately improving long-term renal function. This may be important in both preservation of donor renal function and recipient graft longevity.Methods/DesignA prospective single-centre single-blinded randomized controlled trial will be carried out to determine the effects of donor preoperative intravenous fluids. The primary outcome is donor subclinical acute kidney injury (defined as plasma NGAL, >153 ng/ml) on day 1 postoperatively. Secondary outcomes include intraoperative haemodynamics, recipient subclinical acute kidney injury, perioperative complications and donor sleep quality.Donors will be randomised into two groups: the intervention group will receive active pre-hydration consisting of three litres of intravenous Hartmann’s solution between midnight and 8 am before morning kidney donation, while the control group will not receive this. Both groups will receive unlimited oral fluids until midnight, as is routine. Plasma NGAL will be measured at pre-specified perioperative time points, intraoperative haemodynamic data will be collected using non-invasive cardiac output monitoring and clinical notes will be used to obtain demographic and clinical data. The researcher will be blinded to the donor fluid hydration status. Blinded statistical analysis will be performed on an intention-to-treat basis. A prospective power calculation estimates a required sample size of 86 patients.DiscussionThis study will provide important data, as there is currently little evidence about the use of donor preoperative fluids in laparoscopic nephrectomy. It is hoped that the results obtained will guide future clinical practice.Trial registrationThis study has been approved by the West of Scotland Research Ethics Committee 3 (reference no. 14/WS/1160, 27 January 2015) and is registered with the International Standard Randomised Controlled Trial Number Register (reference no. ISRCTN10199225, 20 April 2015).

Potential applications of lipid peroxidation products – F4-neuroprostanes, F3-neuroprostanesn-6 DPA, F2-dihomo-isoprostanes and F2-isoprostanes ‐ in the evaluation of the allograft function in renal transplantation

F4-neuroprostanes, F3-neuroprostanesn-6 DPA, and F2-dihomo-isoprostanes, metabolites of non-enzymatic lipid peroxidation of polyunsaturated fatty acids [docosahexaenoic acid, n-6 docosapentanoic acid, and adrenic acid respectively], have become important biomarkers for oxidative stress in several diseases like epilepsy and alzheimer. These biomarkers and the 15-F2t-isoprostane (also known as 8-iso-PGF2α), a F2-isoprostane isomer measured as reference oxidative marker at systemic level, were analyzed by UHPLC-QqQ-MS/MS in the urine of 60 renal recipients from cadaveric donors of the Nephrology Unit of the University Hospital Virgen de la Arrixaca, at six different times during the first six months after renal transplantation, and were compared with a control group of 60 healthy subjects from the same hospital. A total of 11 metabolites were analyzed and different patterns were observed. A tendency to decrease was observed in three metabolites (4-epi−4-F3t- NeuroPn-6 DPA, ent−7(RS)−7-F2t-dihomo-IsoP, and ent−7(S)−7-F2t-dihomo-IsoP) and in our reference oxidative marker (15-F2t-IsoP) when kidney function improved and the excretion of urine proteins decreased. These results suggest that these three biomarkers of oxidative stress could be useful to assess renal function in the postransplant phase. Unfortunately, little is known about this kind of biomarker in this cohort of patients, so further investigation would be required in the clinical field to clarify the relationship between oxidative stress and the graft function, as well as the usefulness of these biomarkers as rejection markers.

Effect of discontinuing morning dose of antihypertensive for renal transplant surgery on haemodynamic and early graft functioning: A prospective, double-blind, randomised study

Background and Aims:Antihypertensive drugs are continued until the day of renal transplant surgery. These are associated with increased incidence of hypotension and bradycardia. Hence, this study was designed to evaluate perioperative haemodynamic and early graft functioning in renal recipients with discontinuation of antihypertensive drugs on the morning of surgery.Methods:This prospective, randomised, double-blind study recruited 120 patients. Group 1 patients received placebo tablet while Group 2 patients received usual antihypertensive drugs on the day of surgery. Perioperative haemodynamics and time for reinstitution of antihypertensives were the primary outcome measures. The secondary outcome measures were need for inotropic support and graft function. Perioperative haemodynamics were analysed using ANOVA and Student's t-tests with Bonferroni correction. Fischer's exact test was used for analysis.Results:Systolic blood pressure (SBP) declined, which was more in Group 2. Forty-one patients developed significant hypotension; a correlation was found between the maximum observed hypotension and number of antihypertensive medications (P = 0.003). Four cases had slow graft function (one in Group 1 and three in Group 2). Twenty-eight patients in Group 2 required mephentermine boluses to maintain their SBP compared to 13 patients in Group 1 (P < 0.001). Two patients in Group 2 required dopamine to maintain SBP above 90 mmHg after the establishment of reperfusion as compared to none in Group 1.Conclusion:Single dose of long-acting antihypertensive drugs can be omitted on the morning of surgery without any haemodynamic fluctuations and graft function in controlled hypertensive end-stage renal disease renal transplant patients receiving a combined epidural and general anaesthesia.

Laparoscopic vs open donor nephrectomy: Lessons learnt from single academic center experience.

AIMTo compare laparoscopic and open living donor nephrectomy, based on the results from a single center during a decade.METHODSThis is a retrospective review of all living donor nephrectomies performed at the Massachusetts General Hospital, Harvard Medical School, Boston, between 1/1998 - 12/2009. Overall there were 490 living donors, with 279 undergoing laparoscopic living donor nephrectomy (LLDN) and 211 undergoing open donor nephrectomy (OLDN). Demographic data, operating room time, the effect of the learning curve, the number of conversions from laparoscopic to open surgery, donor preoperative glomerular filtration rate and creatinine (Cr), donor and recipient postoperative Cr, delayed graft function and donor complications were analyzed. Statistical analysis was performed.RESULTSOverall there was no statistically significant difference between the LLDN and the OLDN groups regarding operating time, donor preoperative renal function, donor and recipient postoperative kidney function, delayed graft function or the incidence of major complications. When the last 100 laparoscopic cases were analyzed, there was a statistically significant difference regarding operating time in favor of the LLDN, pointing out the importance of the learning curve. Furthermore, another significant difference between the two groups was the decreased length of stay for the LLDN (2.87 d for LLDN vs 3.6 d for OLDN).CONCLUSIONRecognizing the importance of the learning curve, this paper provides evidence that LLDN has a safety profile comparable to OLDN and decreased length of stay for the donor.

Pneumonia and in-hospital mortality after renal transplantation

Introduction/Objective. Pneumonias remain one of the most frequent reasons for morbidity and mortality in the group of kidney recipients. The objective of the study was to define the factors associated with a higher risk for in-hospital mortality from pneumonia after renal transplantations. Methods. A total of 124 patients with kidney transplants hospitalized with pneumonia for the period of nine years were studied. Different noninvasive and invasive diagnostic tests were used. Results. Forty-one of the patients died as a result of pneumonia or related complications during their hospital stay. The factors associated with the increased risk for in-hospital mortality were as follows: the development of pneumonia during the early postoperative period (during the first month after surgery) (HR = 2.027; p = 0.025) or between the first and sixth month after surgery (HR = 2.303; p = 0.026), dyspnoea (HR = 2.184; p = 0.007) and hypoxemia (HR = 2.261; p = 0.003). The presence of bilateral infiltrates (HR = 2.482; p = 0.001), failure of initial antibiotic therapy (HR = 3.548; p &lt; 0.001), intubation and mechanical ventilation (HR = 4.635; p &lt; 0.001) also increased the risk for the fatal outcome. Conclusion. Knowing the prognostic factors associated with the increased risk for in-hospital fatal outcome from pneumonia after renal transplantation makes it possible to differentiate the high-risk group of renal recipients who require early etiological diagnosis and strict control of the condition, in order to reduce the mortality from pulmonary infections in the group.

Stenosis of internal jugular vein detected by ultrasound imaging in renal recipient patient

Central Venous Stenosis (CVS) has been reported as a later complication of recurrent and long-term Central Venous Cannulation (CVC). Using ultrasonography (USG) before or during CVC greatly increases first-pass success and decreases the complications such as arterial puncture or hemotoma. Anatomical abnormalities of Internal Jugular Vein (IJV) often leads to increase the complication rate and the failed attempt. In this presentation; we aimed to report that the use of USG during CVC in renal recipient patient with CVS.

Analysis of Sera of Recipients with Allograft Rejection Indicates That Keratin 1 Is the Target of Anti-Endothelial Antibodies.

Anti-endothelial cell antibodies (AECAs) are usually directed against the surface antigens on the vascular endothelial cells. Clinical studies suggest a pathogenic role for nonhuman leukocyte antigen in antibody-mediated rejection; however, the antigens on the donor vascular endothelium that serve as the first-line targets for an immune response during allograft rejection have not been fully identified. Here, we used immunoprecipitation and mass spectrometry to identify antigens from the sera of kidney transplant recipients who were experiencing antibody-mediated rejection. Keratin 1 (KRT1) was identified as a novel antigenic target expressed on endothelial cells. To validate our finding, we produced recombinant proteins representing the three most common alleles of KRT1. The serum used for immunoprecipitation showed a strong reaction to KRT1 recombinants in western blot and ELISA. In the kidney transplant cohort, more AECA-positive recipients than AECA-negative recipients had KRT1 antibodies (32.2% versus 11.9%, p = 0.002). Sera from 255 renal recipients were tested by ELISA. Of the 77 recipients with deteriorating graft function (serum creatinine > 120 μmol/L), 23 had anti-KRT1 antibodies. KRT1-IgG positivity was, therefore, associated with a higher risk of kidney transplant rejection (29.9% (23/77) versus 16.9% (30/178), p = 0.0187). A better understanding of this antigenic target will improve long-term allograft survival.

Occurrence of malignancies after kidney transplantation in adults: Slovak multicenter experience.

Malignancies are one of the three major causes of renal recipient´s death with afunctioning graft after cardiovascular diseases and infections. Among the variety of risk factors, including conventional and specific to transplant recipients, the duration of immunosuppressive therapy, the intensity of therapy, and the type of immunosuppressive agent all have an impact on development of post-transplant malignancy. The aim of our retrospective study was to document the incidence, the type of malignancies, the patient/graft survival in the group of kidney transplant recipients in Slovak Republic, and to identify the factors which influenced the outcome. We analyzed the data of 1421 patients who underwent renal transplantation from deceased or living donors in the period from 2007 to 2015 in the Slovak transplant centers. The incidence of malignant tumors was 6%, the malignancy was diagnosed in 85 patients at the age of 54.1 ± 9.8 years, more frequently in men (68.2 %; P< 0.0001). The mean time of malignancy occurrence was 45 months after transplantation. The most frequent malignancies were skin cancers- basal cell carcinoma (BCC) in 17.6%, squamous cell carcinoma (SCC) in 8.2%, and malignant melanoma (MM) in 2.4% of patients, followed by non-skin tumors such as renal cell carcinoma (RCC) in 16.5%, cancer of colon in 12.9%, prostatic cancer in 9.4%, breast cancer in 9.4%, cancer of lung in 7.1%, post-transplant lymphoproliferative disease (PTLD) in 2.4%, cancer of urine bladder in 2.4%, and cancer of sublingual gland in 1.17% of patients. Surgical treatment was used in 40% of patients, chemotherapy in 7.1%, radiotherapy in 2.4%, treatment with biological agents in 15.3%, combined therapy in 29.4% and palliative treatment in 5.9% of patients. 55.3% of patients underwent conversion from other immunosuppressive agents into mTORi at the time of malignancy occurrence. The remission was achieved in 48.2% of patients, 28.2% of patients were in the oncology treatment in the end of the year 2015, and 23.5% of patients died. There was no difference in the kidney function at the time of malignancy occurrence (s-creat 133.7 ± 59.8 µmol/l) and one year later (s-creat 131.1 ± 47.9 µmol/l) (P = 0.7768). The patients after successful treatment more frequently suffered from BCC (P = 0.0140), did not undergo palliative treatment (P = 0.0033), but were more frequently treated surgically (P < 0.0001).

Pretransplantation Risk Factors Associated With New-onset Diabetes After Living-donor Kidney Transplantation

Mid-term date of kidney recipients with new-onset diabetes mellitus after transplantation (NODAT) was poor. We made a retrospective study of 397 patients who had living-donor kidney transplantation between January 2007 and May 2010 in our center. Pretransplantation risk factors for NODAT were identified by univariate and multivariate analyses. The mean follow-up was 53.5 ± 10.4 months. The prevalence of NODAT was 9.3%. Univariate analyses found the mean recipient age ≥40 years, body mass index (BMI) ≥24 kg/m2, family history of diabetes, fasting blood glucose (FBG) ≥5.6 mmol/L, 2-hour plasma glucose ≥7.8 mmol/L, and tacrolimus were risk factors for NODAT. In logistic regression, BMI ≥24 kg/m2 (odds ratio [OR]: 4.14, confidence interval [CI]: 2.02 ∼ 8.49, P < .001), family history of diabetes (OR: 2.62, CI: 1.09 ∼ 6.34, P = .032), and FBG ≥5.6 mmol/L (OR: 3.21, CI: 1.52 ∼ 6.79, P = .002) were independent risk factors. In conclusion, the mid-term prevalence of NODAT in Chinese renal recipients was low (9.3%). Pretransplantation independent risk factors were BMI ≥24 kg/m2, family history of diabetes, and FBG ≥5.6 mmol/L; thus identifying which factors might help to prevent NODAT.

Zika Virus Infection and Solid Organ Transplantation: A New Challenge.

Public health concerns exist surrounding the epidemic of the Zika virus (ZIKV) and the rapid growth of transplantation in developing countries, including endemic zones of active arbovirus transmission, as well as travel to such regions by potential organ donors and recipients. Few data exist regarding the clinical characteristics of ZIKV infection in immunocompromised hosts. Laboratory screening protocols for transplantation to differentiate ZIKV infections from other endemic viral diseases and for the detection of possible donor-derived infection have not been stated. The diagnosis of ZIKV infection remains a challenge, fueled by the lack of standardized commercially available diagnostic tests and validated reference diagnostic laboratories, as well as the limited duration of ZIKV viremia. In this small series, ZIKV infection in renal and liver recipients presented without rash, conjunctivitis, or neurological symptoms, and with abnormal graft function, thrombocytopenia, and bacterial superinfection. We report the first case series of ZIKV infection in solid organ recipients, with a description of clinical and laboratory features and therapeutic management.

Molecular Analysis of Ganciclovir-Resistant Cytomegalovirus in Renal Transplant Recipients with High Viral Load.

Gancyclovir-resistant (GanR) cytomegalovirus (CMV) remains an issue, especially in solid organ transplant (SOT) recipients. Some mutations in UL54 and UL97 confer this resistance. Long-lasting high-dose drug exposure, high viral load, together with lack of sufficient compliance with treatment may account for these mutations. The aim of this study was to detect UL97 and UL54 putative mutations conferring ganciclovir-resistance in renal organ transplant recipients with high CMV load. In this cross-sectional study, 58 serum samples were collected from renal transplant recipients who had referred to three hospitals in Tehran from January 2014 to June 2015. Specific criteria such as CMV syndrome, presence of CMV in blood and organ dysfunction were considered. Then, they were tested for viral load in their early fourth month of intravenous ganciclovir treatment. Fifty cases revealing more than 200 copies/mL were analyzed for mutations. Two fragments of UL54 and Ul97 genes were amplified and sequenced bidirectionally. Sequence alignment and statistical analysis were performed by Mutation Surveyor software and t-test respectively. A significant difference was observed in viral load between seronegative and seropositive recipients (P = 0.036). The most frequent mutation was related to D605E in UL97 gene with the rate of 25%. Regardless of viral load, neither putative mutation nor simultaneous mutation was detected in either UL97 and UL54 regions. In spite of high viral load and persistence of symptoms, our population study did not reveal putative mutations. Hence, the direct relationship between the presence of high quantity of CMV and the occurrence of putative mutation cannot be considered. Non-putative gancyclovir resistant mutations and prolonged drug exposure may have a role in these manifestations.

Prolongation of kidney allograft survival regulated by indoleamine 2, 3-dioxygenase in immature dendritic cells generated from recipient type bone marrow progenitors.

Immature dendritic cells (iDCs) are bone marrow-derived professional antigen-presenting cells, exhibit very low levels of the co-stimulatory molecules CD80 (B7-1), CD86 (B7-2), and CD40 and major histocompatibility complex (MHC) class II and play a critical role in triggering antigen-specific immunotolerance. The enzyme indoleamine 2, 3-dioxygenase (IDO) is a cytosolic tryptophan catabolism rate-limiting step enzyme. IDO secreted by DCs shows an association with the suppression of T-cell responses and promotion of tolerance. In this study, BN rat recipients were pre-injected with donor renal alloantigen-treated recipient iDCs before kidney transplantation. The renal allograft exhibited a lighter renal rejection response, prolonged graft survival time, and an increasing content of CD4+CD25+Foxp3+ regulatory T cells (Tregs). Additionally, up-regulated secretion of Th2 cytokines were found in recipient sera post-transplantation. Transfection of si-IDO1 RNA into renal-antigen-treated recipient iDCs reversed these changes, which suggested that IDO channel signaling may be involved in iDC-induced allograft immunotolerance. These results suggested that iDC-induced and IDO-mediated allograft immunotolerance might be a potentially feasible tactic to prolong allograft survival, in addition to immunosuppressive drugs.

P125 How can we develop the best test algorithm to monitor hla antibodies for renal recipients? – An evaluation of solid phase antibody assays

Aim Solid-phase HLA antibody assays have diverse sensitivity and specificity. Our goal was to determine which One Lambda (OL) and Immucor (I/LC) assays to include in a test algorithm to provide the “best” information, improve workflow and reduce cost and the need for serum pre-treatment. Methods Sera from 20 problematic and 21 routine patients were selected to examine several issues: reaction strength, specificity and background; unexplained crossmatch results; and reactivity to denatured proteins. Testing followed assay instructions; sera were frozen and thawed before testing, with no pre-treatment or dilution. Positive and negative results were identified, MFI values compared and agreement between assay combinations was determined. Control values were used to identify the need for serum pre-treatment. Results Since a single-antigen bead (SAB) assay is part of our algorithm, results from each manufacturer’s assay were compared with SAB assays. Class I and/or II positive samples had better agreement between assay types than negative samples. Several comparisons including I/LC assays saw less disparity, with better agreement for negative test samples. When disparity was seen with Class I or II SAB assays, more samples were OL positive but I/LC negative. With less reactivity due to interfering substances, I/LC assays need less serum pre-treatment. Download : Download high-res image (186KB) Download : Download full-size image Conclusions An algorithm using OL screen, ID and SAB assays could provide better correlation with decreased serum pre-treatment. Including I/LC SAB assays could provide similar sensitivity and specificity, with additional allele specificities and even less serum pre-treatment. I/LC screen and ID assays provide similar results, a simple kit, lower cost and less pre-treatment, making them attractive to include in the algorithm. While limited by small sample numbers, the study information allowed us to identify how both manufacturers’ assays work in our laboratory.

Antibody-mediated rejection and aHUS in renal graft recipient

AbstractA 46-year-old female who lost her native kidney function due a biopsy proven collapsing type of FSGS, had a living kidney transplant after which, she developed acute renal allograft dysfunction, thrombocytopenia and microangiopathichemolytic anemia five days post-transplant. Renal biopsy revealed acute antibody-mediated rejection (AMR). Genetic studies showed that this patient has a homozygous mutation of complement factor B (CFB) gene and heterozygous variant of C 3 gene consistent with atypical hemolytic uremic syndrome type 4. Intravenous immunoglobulin (IV IG) and plasma exchange did not resolve these abnormalities. Eculizumab and bortezomib, on other hand, were very effective.

Anuria since birth: does it impact outcome of kidney transplant in infants?

Kidney transplantation (txp) in infants has recently made much progress but provides a unique challenge in infants anuric since birth. Little data exists on outcome of renal txp recipients with anuria since birth. Retrospective chart review was done for outcome of 27 children with wt ≤15kg and they were divided into two groups: Group A (N=21) with urine output and Group B (N=6) anuric since birth had their urological complications and long-term outcome compared. Median age at the time of txp 18 vs 23months, mean wt 10.8 vs 11.8kg, and mean ht 77cm in both, mean follow-up post-txp: 9.4 vs 5.6years, and neurological problems were noted in 48% and 33% in Group A and Group B. There was no graft thrombosis or post-transplant lymphoproliferative disease and only two rejections. Anuric Group B were older, had more post-txp urological surgeries (66% vs 19%) and UTIs (66% vs 38%) compared to Group A. The overall graft survival at 1, 5, and 10years was 96%, 86%, and 70%; patient survival at 1, 5, and 10years was 96%, 85%, and 85%. Long-term graft outcomes in small children, anuric prior to txp, were excellent despite higher rates for UTIs and urological complications.

High-Risk Human Papillomavirus Infection in Latvian Male Kidney Transplant Recipients / Augsta Riska Cilvēka Papilomas Vīrusa Infekcija Vīriešu Dzimuma Nieru Transplantāta Saņēmējiem Latvijā

Abstract Kidney transplant recipients have higher incidence of human papillomavirus (HPV)-related malignancies, but studies on the natural history of HPV infection are insufficient, especially regarding in male recipients. The aim of this study was to evaluate the course of high-risk HPV (HR-HPV) infection after kidney allograft transplantation in male recipients: to estimate frequency and activity of HR-HPV infection under immune system suppression. Twenty male renal recipients (age 20 - 68) were enrolled in this investigation and examined in dynamics. Peripheral EDTA-blood samples and urine samples were collected from each patient 2 weeks, 6 months and 12 months after transplantation. Polymerase chain reaction (PCR) with consensus primers was used for initial detection of high range HPV types, a commercial qPCR kit for detection of HR-HPV load in urine samples and ELISA for detection of serum IgG class antibodies to HR-HPV L1-capsid protein. Overall, combining molecular (HR-HPV genomic sequences detected by real-time PCR) and serological studies (IgG class antibodies to HR-HPV L1-capsids’ protein), high frequency of HRHPV infection among male kidney transplant recipients (9/20; 45%) was showed. However, the majority of HR-HPV positive recipients (7/9; 78%) showed signs of infection clearance. It means that, despite the applied immune suppressive therapy, the host’s immune system is capable of dealing with HR-HPV infection up to the 12th month after transplantation. However, the sample size should be increased to enable through statistical analysis before final conclusions are made.