Dysfunction In Renal Transplant Recipients Research Articles

Arteriovenous fistula, pulmonary hypertension, and tricuspid dysfunction in renal transplant recipients. A possible solution

Introduction: Cardiovascular dysfunction is the first cause of death in patients with chronic kidney disease. Methods: Observational, longitudinal and prospective study, which included 58 patients with functioning renal transplant who were studied different echocardiographic variables, before and six months after the closure of the arteriovenous fistula. Results: The average age was 46.62 years and the most frequent was male 30 (51.72%). The flow of angioaccesses at the wrist level was demonstrated in 28 patients (45.9%) with evidence of regression of mean pulmonary artery pressure from 25.56 to 19.58 mmHg (p=0.002), more connoted for those of intermediate flow; 14. Also, the area of tricuspid insufficiency was greater for that group; from 3.15 to 1.96 cm2 (p=0.001). The pattern of mild dysfunction was observed in 38 patients (62.3%) prior to closure. Subsequent to this 27; (51.9%), exhibited minimal valvular insufficiency and 9 individuals (14.9%) did not show any degree of valvular dysfunction. Conclusions: Closure of the arteriovenous fistula in patients with functioning renal transplantation contributed to decrease the risk of pulmonary hypertension and progression of tricuspid valve dysfunction.

Association between Circulating MicroRNAs (miR-21-5p, miR-20a-5p, miR-29b-3p, miR-126-3p and miR-101-3p) and Chronic Allograft Dysfunction in Renal Transplant Recipients.

Chronic allograft dysfunction (CAD) is a major condition affecting long-term kidney graft survival. Serum microRNA (miRNA) has been reported as a biomarker for various conditions of allograft injuries. The upregulation of miR-21 is the best-known miRNA change in graft tissue, urine and plasma. However, the correlation of plasma miR-21 with the severity of CAD remains unclear. In our study, 40 kidney transplantation recipients with late graft survival for more than 10 years were enrolled. The CAD group (n = 20) had either an eGFR between 15 to 60 mL/min or a biopsy-proved chronic allograft nephropathy or rejection. The control group (n = 20) had an eGFR ≥ 60 mL/min without proteinuria and hematuria for a consecutive 3 months before the study. We performed RNA sequencing to profile the miRNAs expression. There were six differentially expressed miRNAs in the CAD group. Among them, miR-21-5p and miR-101-3p were decreased, and miR-20a-5p was increased. We found that miR-21-5p, miR-20a-5p and miR-101-3p all participated in the TGF-beta pathway. We demonstrated that decreased miR-21-5p and miR-101-3p, and increased miR-20a-5p were the novel CAD-associated miRNAs in the TGF-beta pathway. These findings may pave the way for developing early prediction miRNAs biomarkers for CAD, and possibly developing therapeutic tools in the field of kidney transplantation.

Clinical significance of copeptin as an early predictor of renal graft dysfunction in renal transplant recipients

Background: Copeptin is the carboxyl-terminal part of the vasopressin precursor protein, and its concentration is an independent predictor of the onset of chronic kidney disease and a rapid decline in the glomerular filtration rate. The glomerular filtration rate is regarded as the best indicator of kidney transplant function and is a predictor of graft and patient survival. We investigated the clinical significance of copeptin as an early predictor of renal graft dysfunction in renal transplant recipients.Methods: We measured serum creatinine, cystatin C, and copeptin concentrations in renal transplant recipients on the day of their operation, as well as on postoperative days 3, 7, 30, and 365. Acute rejection was defined as a sudden decrease in renal function accompanied by histological changes.Results: Eight renal transplant recipients were enrolled in the study from July 2018 to December 2019. Four patients experienced histologically confirmed transplant rejection. All four cases involved acute T-cell rejection. No significant correlation was found between the copeptin level and the presence or absence of rejection at any time point. In subgroup analyses, changes in creatinine, the estimated glomerular filtration rate, cystatin, and copeptin did not show statistical significance.Conclusions: We anticipated that copeptin would be useful to identify individuals at high risk of transplant rejection; however, our study failed to show an association. Further research will be needed to overcome the limitations of this study.

P8.016: Gram Negative Blood Stream Infection in Renal Transplant Recipients: Risk Factors and Outcome From a Transplant Center in Pakistan

Background: Gram-negative bacteremia (GNB) is a common cause of bloodstream infection in renal transplant recipients (RTR). The risk factors are cytomegalovirus infection (CMV), pre-transplant dialysis, acute rejection, urological abnormalities, and ureteral stent. The mortality rate is 2.5 to 11%. Considering the huge impact on morbidity and mortality, our aim is to analyze the characteristics and outcomes of GNB in RTRs. Methods: A case-control study at Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan. The files of all renal transplant recipients who had documented GNB from January 2015 to December 2017 were reviewed till December 2020. The controls were matched with age, sex, and date of transplant. The first episode of GNB was taken. Clinical features, received anti-thymocyte globulin (ATG) or solumederol and cytomegalovirus infection (CMV) 90 days pre or post bacteremia, recurrent urinary tract infections (UTI), source of bacteremia and microbiology, all-cause mortality at day 28 and graft function at the last follow up were noted. Results: Out of 1009 RTR, 33 (3.3%) episodes of GNB occurred. The mean age was 30±11.85years, 61% males. Around 48% developed bacteremia within 6 months post-transplant. The most common source was UTI (75.8%). Fever in 48% and only 39% had leukocytosis. Around 9% were admitted in the intensive care unit. E-coli was the most common organism (70%) (Table 1). Stone disease at the time of transplant was significantly associated with bacteremia (p=0.029). There was no difference in receiving ATG or solumeredol and CMV before bacteremia. A significant number of patients received solumeredol for rejection (p=0.035) and had CMV (p=0.044) within 90 days after bacteremia. Recurrent UTI is significantly associated with bacteremia (p<0.001). The graft function at the last follow-up (2 years) was significantly deranged in patients with bacteremia (p=0.0001). Conclusion: Gram-negative bacteremia was found in 3% of RTR and half of them developed within 6 months post-transplant. UTI was the most common source and recurrent UTI was significantly associated with bacteremia. The stone disease was the most significant risk factor. Patients develop rejection and CMV infection within 3 months post bacteremia. There was a significant graft dysfunction among patients with bacteremia at a mean follow-up of 2 years. We need to focus on the management of recurrent UTIs to prevent bacteremia and graft dysfunction in renal transplant recipients.

Underlying Causes and Risk Factors of Chronic Renal Allograft Dysfunction Among Renal Transplant Recipients

Objective: Dialysis or renal transplantation are the two treatment options for end-stage renal disease patients. Renal transplantation from an appropriate donor increases survival and quality of life compared to treatment with dialysis. Recent advances in immunosuppressive therapy have significantly improved the success in 1-year graft survival. However, the long-term graft survival remains the same. Therefore, we aimed to determine the underlying causes and risk factors of chronic allograft dysfunction in renal transplant recipients.&#x0D; Materials and Methods: From 2000 to 2012, all consecutive renal transplant recipients followed in our tertiary referral center who underwent renal biopsy due to an increase in serum creatinine level were enrolled. Etiologies of chronic allograft dysfunction were assessed according to pathologic results of renal biopsy specimens and laboratory findings. The immunological and non-immunological risk factors of chronic allograft dysfunction were screened and recorded retrospectively.&#x0D; Results: Eighty (80) renal transplant recipients with a mean age of 38±10 years were included in the study. Delayed graft function (p=0.007), history of acute rejection (p&lt;0.001), positive panel reactive antibody (p=0.033) (Class I (p=0.013), Class II (p=0.006)), positive donor specific antibodies (p=0.001), number of recurrent acute rejections (p&lt;0.001), number of human leukocyte antigens mismatches (p=0.051), cold ischemia time (p=0.001) were found to be risk factors for chronic allograft dysfunction. The donor specific antibodies positivity (p&lt;0.001) and the panel reactive antibody positivity (Class I (p=0.003), Class II (p=0.001)) were significantly higher in patients with antibody mediated rejection than patients without antibody mediated rejection (p=0.002).&#x0D; Conclusion: Delayed graft function, presence and the number of acute rejections, increased cold ischemia time, panel reactive antibody positivity, donor specific antibodies positivity, and the number of human leukocyte antigens mismatches were risk factors for chronic allograft dysfunction.

A novel biomarker of chronic allograft dysfunction in renal transplant recipients (serum calreticulin and CD47)

BackgroundChronic allograft dysfunction (CAD) is considered the leading cause of late allograft loss. The cluster of differentiation 47 (CD47) and calreticulin (CRT) are involved in many and diverse cellular processes. The present study was designed to study the role of the pro-phagocytic CRT and anti-phagocytic CD47 signals in patients with renal transplantation in relation to graft function.Thirty renal transplantation recipients (RTR) for more than 6 months [15 with stable renal function and 15 with chronic allograft dysfunction (CAD)] and 15 healthy controls were enrolled in the study. Quantification of CRT, CD47, and high-sensitivity C-reactive protein (hsCRP) levels in serum was done using standardized enzyme-linked immunosorbent assay (ELISA) kits. Measurement of renal function and urinary alkaline phosphatase (U.ALP) was done. Renal interstitial fibrosis (IF) was graded in renal biopsies of CAD.ResultsSerum CRT and urinary ALP levels were statistically significant higher (P < 0.001) while serum CD47 level was statistically significant lower (P < 0.001) in patients with CAD than patients with stable graft function and controls. There was statistically insignificant difference between controls and patients with stable graft function. Serum CRT and serum CD47 levels were positively correlated with each other and with worsening renal and tubular function, serum hsCRP in RTR and with degree of renal IF in patients with CAD (P < 0.05).ConclusionsThe activation and dysregulation of CRT and CD47 could play a role in the development of CAD and could be a potential biomarker for renal allograft dysfunction.

BK Virus Associated Nephropathy, a Cause of Early Renal Allograft Dysfunction: A Single Centre Study.

BK virus associated nephropathy (BKVN) is an important cause of early graft dysfunction in renal transplant recipients. The present study was carried out to determine the burden of BKVN in a single renal transplant centre in Australia. A retrospective analysis of de novo renal transplant recipients from 2010 to 2013 was performed to identify biopsy proven BKVN. Estimated glomerular filtration rate (eGFR) was compared at baseline, at BKVN diagnosis and 3 and 12 months postdiagnosis. Of the 317 de novo renal transplants recipients in the study period, 20 (6.3%) developed BKVN. The mean age was 54.8 ± 13.1 years and 13 (65%) were male. The mean time from transplant to BKVN was 8.7 ± 6.7 months with 17 (85%) diagnosed within 12 months. Four recipients each were diagnosed BKVN on 3 and 12 month surveillance biopsy. Six (30%) had normal eGFR at diagnosis. Mean eGFR at diagnosis was 38.8 ± 19.2 ml/min/1.73 m2, which was significantly lower (p < 0.01) than that at baseline (50.3 ± 16.4 ml/min/1.73 m2). eGFR improved numerically at 3 and 12 months post-diagnosis, however the difference was not significant. One patient had graft failure, 19 months after diagnosis. BKVN generally occurs in first post-transplant year and is an important cause of early graft dysfunction. Surveillance biopsy helps in detecting subclinical BKVN.

BK nephropathy in the native kidneys of patients with organ transplants: Clinical spectrum of BK infection.

Nephropathy secondary to BK virus, a member of the Papoviridae family of viruses, has been recognized for some time as an important cause of allograft dysfunction in renal transplant recipients. In recent times, BK nephropathy (BKN) of the native kidneys has being increasingly recognized as a cause of chronic kidney disease in patients with solid organ transplants, bone marrow transplants and in patients with other clinical entities associated with immunosuppression. In such patients renal dysfunction is often attributed to other factors including nephrotoxicity of medications used to prevent rejection of the transplanted organs. Renal biopsy is required for the diagnosis of BKN. Quantitation of the BK viral load in blood and urine are surrogate diagnostic methods. The treatment of BKN is based on reduction of the immunosuppressive medications. Several compounds have shown antiviral activity, but have not consistently shown to have beneficial effects in BKN. In addition to BKN, BK viral infection can cause severe urinary bladder cystitis, ureteritis and urinary tract obstruction as well as manifestations in other organ systems including the central nervous system, the respiratory system, the gastrointestinal system and the hematopoietic system. BK viral infection has also been implicated in tumorigenesis. The spectrum of clinical manifestations from BK infection and infection from other members of the Papoviridae family is widening. Prevention and treatment of BK infection and infections from other Papovaviruses are subjects of intense research.

Functional and histological improvement after everolimus rescue of chronic allograft dysfunction in renal transplant recipients.

BackgroundWe tested the strategy of mTOR inhibitors with calcineurin inhibitor minimization in renal transplant recipients with known chronic allograft dysfunction.MethodsIn this open-label, single-arm study, renal transplant patients were recruited after biopsy-confirmed chronic allograft dysfunction in the absence of acute rejection episode within 2 months, with proteinuria <0.8 g/day, and serum creatinine <220 μmol/L or estimated glomerular filtration rate >40 mL/min/1.73 m2. They were converted to everolimus (aiming for trough everolimus level 3–8 ng/mL) with cyclosporine minimization, to assess the effect on renal function, rate of glomerular filtration rate decline, and longitudinal transplant biopsy at 12 months.ResultsSeventeen Chinese patients (median transplant duration, 4.2 years) were recruited; no patients discontinued study medication. The mean slope of the glomerular filtration rate over time was −4.31±6.65 mL/min/1.73 m2 per year in the year before everolimus, as compared with 1.29±5.84 mL/min/1.73 m2 per year in the 12 months of everolimus therapy, a difference of 5.61 mL/min/1.73 m2 per year (95% confidence interval [CI], 0.40–10.8) favoring everolimus therapy (P=0.036). Serial renal biopsy histology showed significant decrease of tubular atrophy (15.7%±11.3% versus 7.1%±7.3%, P=0.005) and interstitial fibrosis (14.8%±11.5% versus 7.2%±8.2%, P=0.013). Intrarenal expression of TGF-β1 mRNA showed a nonsignificant decrease after everolimus treatment.ConclusionIn renal transplant recipients with biopsy-confirmed chronic allograft dysfunction, we found a significant beneficial effect of everolimus rescue therapy and calcineurin inhibitor minimization strategy on the improvement of glomerular filtration rate decline rate. In secondary analysis, everolimus was shown to slow down the disease progression by reducing the tubular atrophy and interstitial fibrosis scoring.

Endothelial Dysfunction in Renal Transplant Recipients: Role of Vitamin D and Fibroblast Growth Factor-23

BackgroundEndothelial dysfunction can be detected at early stages of chronic kidney disease. Although endothelial functions improve after successful renal transplantation, renal transplant recipients have still worse endothelial functions compared to healthy subjects. Vitamin D deficiency and high fibroblast growth factor−23 (FGF-23) levels may have a role on endothelial dysfunction in chronic kidney disease patients. The aim of this study is to investigate the association between endothelial functions, vitamin D, and FGF-23 levels in renal transplant recipients. MethodsOne hundred nine renal transplant recipients (71 male, 38 female) underwent brachial flow-mediated dilatation (FMD), serum 25-OH vitamin D, and FGF-23 level measurements. Vitamin D and FGF-23 levels were compared between patients with normal and abnormal endothelial functions. Correlations between FMD, vitamin D, and FGF-23 were also investigated. ResultsEndothelial functions were abnormal in 72.5% of the patients. Prevalence of vitamin D deficiency was 80.7%. Vitamin D levels were significantly lower in patients with endothelial dysfunction compared to patients with normal endothelial functions (12.6 ± 6.6 μg/L vs 17.3 ± 10.0 μg/L respectively, P = .02). FGF-23 levels were not different between the two groups. 25-OH vitamin D levels had a significant positive correlation with amount of FMD (r = 0.218 and P = .02) and were an independent predictor of FMD after adjusting for potential confounding factors including age, transplantation duration, body mass index, mean blood pressure, glomerular filtration rate, proteinuria, hemoglobin, and FGF-23 in multivariate regression analysis (beta = 0.194, P = .04). FGF-23 levels were not predictive of FMD in this model (beta: −0.125, P = .197) ConclusionVitamin D deficiency is associated with endothelial dysfunction in renal transplant recipients. Further clinical and experimental studies are necessary to define a causal relationship between the parameters, discover the potential mechanisms, and observe the effect of vitamin D replacement on endothelial functions in renal transplant recipients.

Are Levels of NT-proBNP and SDMA Useful to Determine Diastolic Dysfunction in Chronic Kidney Disease and Renal Transplant Patients?

The aim of the study was to determine the clinical usefulness of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and symmetric dimethylarginine (SDMA) for detection of renal and left ventricular (LV) diastolic dysfunction in chronic kidney disease (CKD) patients and renal transplant (RT) recipients. We included 98 CKD and 44 RT patients. We assessed LV function using pulsed-wave Doppler ultrasound. Diastolic dysfunction was defined when the E:A ratio was <1. Independent predictors of NT-proBNP levels were age, creatinine, and albumin in CKD patients and age and urea in RT patients. Determinants of SDMA in CKD patients were glomerular filtration rate (GFR) and NT-proBNP and creatinine in RT patients. In RT patients with diastolic dysfunction, NT-proBNP and SDMA were significantly higher than in patients without diastolic dysfunction (F = 7.478, P < 0.011; F = 2.631, P < 0.017). After adjustment for GFR, the differences were not seen. In CKD patients adjusted NT-proBNP and SDMA values for GFR were not significantly higher in patients with diastolic dysfunction than in patients without diastolic dysfunction. NT-proBNP is useful for detection of LV diastolic dysfunction in RT recipients. When evaluating both NT-proBNP and SDMA it is necessary to consider GFR as a confounding factor.

Association Between Calcineurin Inhibitor Treatment and Peripheral Nerve Dysfunction in Renal Transplant Recipients

Neurotoxicity is a significant clinical side effect of immunosuppressive treatment used in prophylaxis for rejection in solid organ transplants. This study aimed to provide insights into the mechanisms underlying neurotoxicity in patients receiving immunosuppressive treatment following renal transplantation. Clinical and neurophysiological assessments were undertaken in 38 patients receiving immunosuppression following renal transplantation, 19 receiving calcineurin inhibitor (CNI) therapy and 19 receiving a calcineurin-free (CNI-free) regimen. Groups were matched for age, gender, time since transplant and renal function and compared to normal controls (n = 20). The CNI group demonstrated marked differences in nerve excitability parameters, suggestive of nerve membrane depolarization (p < 0.05). Importantly, there were no differences between the two CNIs (cyclosporine A or tacrolimus). In contrast, CNI-free patients showed no differences to normal controls. The CNI-treated patients had a higher prevalence of clinical neuropathy and higher neuropathy severity scores. Longitudinal studies were undertaken in a cohort of subjects within 12 months of transplantation (n = 10). These studies demonstrated persistence of abnormalities in patients maintained on CNI-treatment and improvement noted in those who were switched to a CNI-free regimen. The results of this study have significant implications for selection, or continuation, of immunosuppressive therapy in renal transplant recipients, especially those with pre-existing neurological disability.

Late Calcineurin Inhibitor Withdrawal Prevents Progressive Left Ventricular Diastolic Dysfunction in Renal Transplant Recipients

Late Calcineurin Inhibitor Withdrawal Prevents Progressive Left Ventricular Diastolic Dysfunction in Renal Transplant Recipients

CYP2C8*3 Polymorphism and Donor Age are Associated With Allograft Dysfunction in Kidney Transplant Recipients Treated With Calcineurin Inhibitors

Epoxieicosatrienoic acids (EETs) play a protective role against damaging processes in the kidney. We have assessed the effect of polymorphisms in EETs-producing enzymes (CYP2C8 and CYP2J2) and other proteins involved in calcineurin inhibitors (CNIs) disposition (CYP3A4, CYP3A5, and ABCB1) on graft function and clinical outcome in 166 renal transplant recipients treated with CNIs. Both CYP2C8*3 and donor age greater than 48 years were associated to a higher incidence of delayed graft function (DGF) [OR = 2.01 (1.1-4.1), P = .04 and 5.14 (2.4-10.9), P < .0001; respectively] and worse creatinine clearance 1 year after grafting (P < .05 and P < .001, respectively). In addition, carrying 4-6 variants in the 3 ABCB1 loci and older donor age were individually associated to higher incidence of calcineurin-inhibitor-induced nephrotoxicity [OR = 2.38 (1.1-5.4), P = .03 and OR = 1.03 (1.01-1.06), P = .038]. Regression analyses confirmed the relevant effect of both CYP2C8*3 and donor age on graft dysfunction. Carrying the 2C8*3 allele and having a donor older than 48 years was defined as a high-risk status and observed to be highly related to DGF [OR = 3.91 (1.46-10.48), P < .01] and worse creatinine clearance (P = .033). Our results show that genetic and clinical parameters can be combined to identify risk factors for allograft dysfunction in renal transplant recipients.

Prevalence and prognostic factors for erectile dysfunction in renal transplant recipients

The purpose of this study was to determine the prevalence of erectile dysfunction (ED) at our institution in the postrenal transplant population and to compare those patients who had ED with those who did not have ED, with respect to several patient characteristics. We conducted a cross-sectional study of male renal transplant recipients who were in attendance at the transplant clinic from April 1, 2004, to March 31, 2006. Erectile function was evaluated using the International Index of Erectile Function short form questionnaire. Patients were also screened for depression using the Beck Depression Inventory. We performed a chart review to obtain various patient characteristics. This study involved 55 patients. Their average age was 50 years old and the mean duration of the current transplant was 7.9 years. ED was identified in 28 of the patients (51%). More patients with ED were over age 50 years (64% v. 26%, p = 0.004). There was a higher prevalence of diabetes mellitus (39% v. 11%, p = 0.02) in patients with ED compared with those patients without ED. More patients with ED were depressed compared with those patients who did not have ED (29% v. 7%, p = 0.04). These 3 factors were significantly associated with ED and this relationship was confirmed on multivariate analysis. ED remains a common problem in the renal transplant population. The cause of ED is multifactorial, with increasing age and the presence of diabetes mellitus and depression increasing the risk of ED.

Relationship between hemorheology and endothelial dysfunction in renal transplant patients receiving calcineurin inhibitors

Calcineurin inhibitors, mainly cyclosporin A (CsA), are associated with endothelial dysfunction in renal transplant recipients (RTRs). Hemorheological disturbances including decreased erythrocyte deformability (ED), increased plasma viscosity and erythrocyte aggregation (EA) have also been reported in CsA-treated RTRs. The aim of this study was to investigate the relationship between hemorheological factors and endothelial dysfunction in CsA- and tacrolimus (Tc)-treated RTRs. Thirty-one RTRs and 16 healthy subjects were recruited. The RTR group received either CsA (n = 16) or Tc (n = 15). Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. ED and EA were measured with laser-assisted optical rotational cell analyzer, and plasma viscosity by a cone-plate viscometer. FMD of the CsA group was significantly lower than that of controls (6.3% ± 5.1% vs. 11.9% ± 5.6%, p = 0.024), whereas, there was no significant difference between the Tc group (8.8% ± 5.4%) and controls. At shear stresses ranging between 0.95 and 30 Pa, EDs of the CsA group were significantly lower compared with controls. In the Tc group, the decrease in ED was significant at shear stresses ranging between 0.53 and 5.33 Pa. ED indices did not correlate with FMD in any of the groups. The degree of endothelial dysfunction and reduction in ED were more remarkable in patients on CsA therapy. Hemorheological factors were not likely to be associated with endothelial dysfunction in RTRs.

Late Calcineurin Inhibitor Withdrawal Prevents Progressive Left Ventricular Diastolic Dysfunction in Renal Transplant Recipients

Calcineurin inhibitor (CNI)-based therapy is associated with adverse cardiovascular effects. We examined the effects of late CNI or mycophenolate mofetil (MMF) withdrawal on echocardiographic parameters. This study was conducted as a substudy of a randomized trial in stable renal transplant recipients who were on a triple CNI-based regimen with prednisone and MMF that evaluated late concentration-controlled withdrawal of CNI or MMF on renal function. A total of 108 patients (age, 52.3±11.5 years; 67% male; at a median of 2.0 years post-transplantation, (interquartile range 1.3-3.3 years); estimated glomerular filtration rate, 57±16 mL/min/1.73 m; 66% on cyclosporine and 34% on tacrolimus) entered the cardiovascular substudy examining echocardiographic parameters at baseline and 2 years after randomization. In all patients, traditional cardiovascular risk factors were treated according to predefined targets. Late CNI withdrawal prevented progressive development of left ventricular (LV) diastolic dysfunction, as assessed by markers of LV diastolic function (mitral deceleration time and mitral annular e' velocity). Conversely, in the MMF-withdrawal group, the left atrial volume index (an indicator of chronic LV diastolic dysfunction) was significantly increased at 2 years (from 24.1±6.7 to 27.0±7.0 mL/m, P<0.05). In addition, CNI withdrawal resulted in a higher proportion of patients achieving the predefined blood pressure targets (<130/85 mm Hg: 41.5% vs. 12.7%, P=0.001) at 2 years while requiring less antihypertensive drugs. Changes in the left atrial volume index were significantly associated with treatment arm (P=0.03) and changes in systolic (P=0.005) and diastolic (P=0.005) blood pressure. Late CNI withdrawal, from a triple-drug regimen in stable renal transplant recipients, prevented progressive deterioration of LV diastolic function and facilitated better blood pressure control.

53-P

Aim The presence of antibodies against human leukocyte antigen (HLA) is a major challenge for successful kidney transplantation and results in prolonged waiting times. The aim of the study is to investigate the efficacy of high dose intravenous immune globulin (IVIG) on HLA antibody reduction and graft dysfunction in renal transplant recipients transplanted against DSA. Methods Between 07/2005 and 04/2012, 53 sensitized patients whose T and B flow crossmatches were under 200 median channel shift were transplanted with single or multiple dose of IVIG (2 g/kg). Levels of HLA antibodies were measured using single antigen Luminex assay, T/B cell crossmatches were performed by cytotoxicity and flow cytometry. Results All 53 patients displayed DSA to their donors pretransplant. Among them, 25/53 (47%) patients had a calculated PRA (cPRA) >90%. 26 patients had pretransplant DSA to HLA class I, 17 had DSA to class II and 10 had DSA to both class I and class II. 10 (18.8%) patients experienced antibody mediated rejection (AMR) posttransplant, and 5 (9.4%) patients were diagnosed with acute cellular rejection (ACR). 65% (17/26) of patients transplanted with pretransplant DSA to only class I antigens lost their DSA after transplant. However, for patients with pretransplant DSA to class II, only 5/17 (29%) patients showed no detectable DSA posttransplant (p = 0.02). For the 10 patients who had pretransplant DSA to both class I and class II, 4 patients no longer had detectable DSA posttransplant. Four patients had persistent class II DSA and 2 patients had persistent DSA to both class I and class II posttransplant. Conclusions IVIG seems to be more efficient in removing HLA class I antibodies than class II. Patients who had pretransplant DSA to HLA class II had higher risk of AMR compared to patients who had DSA to class I, with the highest risk in patients with DSA to both. Additional study should be performed to understand the differential mechanisms of IVIG on HLA class I and class II antibodies.

Renalase, kidney function, and markers of endothelial dysfunction in renal transplant recipients

Renalase is an enzyme released by the kidneys, which breaks down catecholamines in the blood and thus may regulate blood pressure. In kidney transplant recipients, endothelial dysfunction is often present. The aim of the study was to assess associations between renalase, blood pressure, and kidney function in kidney allograft recipients. We studied 62 kidney allograft recipients. Complete blood count, urea and creatinine levels, serum lipids, and fasting glucose were measured by standard laboratory methods. We also assessed markers of coagulation: prothrombin fragments 1+2; fibrinolysis: tissue plasminogen activator (tPA), plasminogen activator inhibitor, plasmin-antiplasmin complexes; endothelial function/injury: von Willebrand factor (vWF), thrombomodulin, intercellular adhesion molecule, vascular cell adhesion molecule (VCAM); and inflammation: high‑sensitivity C‑reactive protein and interleukin 6. Renalase levels were assessed using a commercially available kit. Mean serum renalase levels in kidney allograft recipients correlated with age, time after transplantation, soluble CD44 (sCD44), VCAM, serum creatinine, estimated glomerular filtration rate (eGFR; measured by CKD-EPI, MDRD, and Cockcroft‑Gault formulas), serum phosphate, urea, sCD146, vWF, and thrombomodulin and tended to correlate with tPA. In patients with eGFR above 60 ml/min, renalase was lower than in those with lower eGFR. In hypertensive allograft recipients, renalase was significantly higher than in normotensives. A multiple regression analysis showed that renalase was predicted in 58% by serum creatinine. Renalase, which is highly elevated in kidney transplant recipients, is dependent primarily on kidney function, which deteriorates with age and time after transplantation. Further studies are needed to establish the putative role of renalase in the pathogenesis of hypertension after transplantation and its possible use in novel targeted therapies.

44-OR: Donor-specific MICA antibodies correlate with cellular rejection and chronic graft dysfunction in renal transplant recipients

44-OR: Donor-specific MICA antibodies correlate with cellular rejection and chronic graft dysfunction in renal transplant recipients