Outcomes In Renal Transplant Recipients Research Articles

Impact of cinacalcet pre-transplantation on mineral metabolism in renal transplant recipients.

Cinacalcet is effective in reducing parathyroid hormone (PTH) in patients on dialysis. Reports of biochemical profiles and other clinical outcomes in patients discontinuing cinacalcet at time of renal transplantation are limited. A retrospective study assessing markers of mineral metabolism, graft and patient outcomes in renal transplant recipients to determine differences in patients discontinuing cinacalcet (C+) compared with patients not treated with cinacalcet (C-) at time of transplantation. To allow for differences between groups in pre-transplant biochemical parameters, we also analysed a matched cohort of C- with C+ recipients (2:1), matched for age, calcium and PTH levels at transplantation. Five hundred thirty-two recipients (460 C-, 72 C+), transplanted January 2006-December 2012, were analysed, mean age 48.0 ± 12.7 years and 64.3% were men. At a median 42.9 months follow up, there were 10 deaths (1.9%), 56 allograft loss (10.6%) and 5 parathyroidectomies post-transplant (0.8%). Median PTH immediately pre-transplant was higher in C+ versus C- (50.7(25.4-75.2) versus 28.3(13.9-49.7) pmol/L, P < 0.001). Twelve-month post-transplant PTH was reduced but higher in C+ (11.7(6.9-21.2) vs 7.2(4.6-11.2) pmol/L, P < 0.001). Mean calcium was higher for C+ versus C- at 12 months (2.50 ± 0.19 vs 2.43 ± 0.17 mmol/L, P < 0.001), with differences to 4 years post-transplant. No difference was seen in renal function, graft loss, post-transplant parathyroidectomy rate and mortality. In the matched cohort (144 C- vs 72 C+), similar findings were also seen. Differences in mineral metabolism post-transplant are seen with cinacalcet pre-transplant compared with no cinacalcet. Transplant recipients discontinuing cinacalcet had higher post-transplant PTH and calcium although the clinical significance is unclear.

Survival Outcomes in Renal Transplant Recipients With Renal Cell Carcinoma or Transitional Cell Carcinoma From the ANZDATA Database.

Our objective was to determine the incidence and outcomes of renal cell carcinoma and transitional cell carcinoma in recipients of renal allografts. We analyzed data from 2000 to 2012 in the Australia and New Zealand Dialysis and Transplant Registry, a binational population-based database, to identify the incidence and survival outcomes of renal transplant recipients with renal cell and transitional cell carcinoma. Of the 8850 renal transplants, there were 60 new diagnoses of renal cancers posttransplant, with an overall cumulative incidence of 56 per 100,000 per year. Nine tumors were detected in the allograft, and 51 tumors (85%) were detected in the native kidney of the recipient. The median time of diagnosis from transplant was 6.6 years (range, 0.1-8.9 y). There were no cancer-specific deaths from allograft tumors; however, 17 cancer-specific deaths (14 from renal cell carcinoma and 3 from transitional cell carcinoma) occurred in patients with cancer in the native kidney. The 5-year and 10-year cancer-specific survival rates for renal cell carcinoma were 71.2% (95% confidence interval (CI): 57.0-84.0) and 58.5% (95% CI: 40.5-77.9), with 5-year and 10-year rates for transitional cell carcinoma of 50% (95% CI: 15.5-94.2) and 0%. Renal cell carcinoma occurring in the native kidney comprised most of the tumors detected after renal transplant; however, transitional cell carcinoma occurred sooner after transplant and resulted in a lower cancer-specific survival rate. While it is important to screen those at risk of TCC prior and after renal transplant, the low incidence of TCC maybe too small to justify a benefit with routine screening, compared to RCCs.

Characteristics and Outcomes of Renal Transplant Recipients with Hemolytic Uremic Syndrome in the United States.

Hemolytic uremic syndrome (HUS) accounts for <1% of renal transplants in the US. There are limited data on the characteristics and outcomes of HUS in pediatric and adult kidney transplant recipients in the US. This study included all renal transplant recipients identified with HUS (N=1,233) as a cause of end-stage renal disease between 1987 and 2013 using the UNOS/OPTN database. The cohort was divided into two age groups: pediatric (N=447) and adult (N=786). Main outcomes were acute rejection rate at one-year, allograft and patient survival, and recurrence of HUS post-transplant. Both age groups were then compared with a propensity score (1:2 ratio) matched control group with an alternative primary kidney disease (non-HUS cohort: pediatric [N= 829] and adult [N=1,547]). In pediatric cohort, when compared to the PS matched controls, acute rejection, death censored allograft and patient survival was similar in the HUS group. However, in the adult cohort, the graft and patient survivals were significantly worse in the HUS group. HUS was associated with allograft loss (HR=1.40, 95%CI 1.14-1.71) in adult recipients. Patients with HUS recurrence had significantly lower allograft and patient survival rates compared to the non-recurrent group in both age groups. Acute rejection was one of the major predictor of HUS recurrence in adults (OR=2.64, 95%CI 1.25-5.60). Calcineurin inhibitors (CNI) were not associated HUS recurrence in both age groups. Pediatric HUS-patients, unlike adult recipients, have similar outcomes compared to the PS matched controls. Recurrence of HUS is associated with poor allograft and patient survival in pediatric and adult patients. Use of CNIs seem to be safe as a part of maintenance immunosuppression post-transplantation. A comprehensive national registry is urgently needed.

Regression of asymptomatic cardiomyopathy and clinical outcome of renal transplant recipients: a long-term prospective cohort study.

Asymptomatic left ventricular hypertrophy (LVH) is highly prevalent and associated with an adverse outcome in renal transplant recipients (RTRs). Nonetheless, there are currently no available studies analyzing the effect of LVH regression on solid clinical endpoints in these patients. This study is the prospective observational extension of two randomized controlled trials aimed at assessing the effect of active intervention on post-transplant LVH in RTRs. We evaluated the incidence of a composite of death and any cardiovascular (CV) or renal event in 60 RTRs in whom LVH regression was observed and in 40 whose LVH remained unchanged or worsened. During an 8.4 ± 3.5-year follow-up, 8 deaths, 18 CV events and 6 renal events occurred in the entire cohort. Multivariable analysis showed that age [hazard ratio (HR) 1.07, 95% confidence interval (CI) 1.03-1.12 each 1 year, P = 0.002] and LVH regression (HR 0.42, 95% CI 0.22-0.87, P = 0.019) were significant predictors of the composite endpoint. Kaplan-Meier estimates showed better survival rates in patients in whom actual LVH regression was achieved (P < 0.001, log-rank test). Age (HR 1.09, 95% CI 1.03-1.15 each 1 year, P = 0.004), better graft function (HR 0.95, 95% CI 0.91-0.99 each 1 mL/min/1.73 m(2) increase in estimated glomerular filtration rate, P = 0.03) and LVH regression (HR 0.41, 95% CI 0.22-0.79, P = 0.01) were significant predictors of the CV endpoint. Patients with a left ventricular mass index decrease also showed better cardiac event-free survival (P = 0.0022, log-rank test). This is the first study to demonstrate that LVH regression, regardless of the therapeutic strategy adopted to achieve it, portends better long-term clinical outcome in RTRs.

The Synergistic Effect of Class II HLA Epitope-Mismatch and Nonadherence on Acute Rejection and Graft Survival

Predicting long-term outcomes in renal transplant recipients is essential to optimize medical therapy and determine the frequency of posttransplant histologic and serologic monitoring. Nonadherence and human leukocyte antigen (HLA) mismatch are risk factors that have been associated with poor long-term outcomes and may help individualize care. In the present study, class II HLA mismatches were determined at the HLA epitope level in 195 renal transplant recipients in whom medication adherence was prospectively measured using electronic monitors in medication vial caps. Recipients were grouped by medication adherence and high (≥10 HLA-DR, ≥17 HLA-DQ) or low epitope-mismatch load. We found that the combination of higher epitope mismatch and poor adherence acted synergistically to determine the risk of rejection or graft loss. Nonadherent recipients with HLA-DR epitope mismatch ≥10 had increased graft loss (35% vs. 8%, p < 0.01) compared to adherent recipients with low epitope mismatch. At the HLA-DQ locus nonadherent recipients with HLA-DQ epitope mismatch ≥17 had increased graft loss (33% vs. 10%, p < 0.01) compared to adherent recipients with low epitope mismatch. Subclinical nonadherence early posttransplant combined with HLA class II epitope mismatch may help identify recipients that could benefit from increased clinical, histologic, and serologic monitoring.

Anemia and the outcomes in renal transplant recipients: a meta-analysis

// Huang Gang 1 , Li Jun 1 , Chen Guodong 1 , Chen Lizhong 1 and Qiu Jiang 1 1 Division of Organ Transplantation, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China Correspondence to: Qiu Jiang, email: qiujiangdoc@163.com Keywords: anemia, kidney transplantation, creatinine, graft loss rate, all-cause death rate Received: April 23, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: August 17, 2017&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: December 06, 2017 ABSTRACT Background: The impact of anemia on graft loss rate and all-cause death rate remains controversial in renal transplant recipients. We performed a meta-analysis to explore the influence of anemia correction on the outcomes in renal transplant recipients. Materials and Methods: We searched PubMed and EMBASE databases from January 1st 1981 to December 31st, 2016 to identify potential studies assessing the impact of anemia on kidney transplantation. Fixed or random effect model was used according to the heterogeneity. Potential heterogeneity was checked by sensitivity analysis and meta-regression analysis. Results: A total of 9 randomized controlled trials with 1387 participants (mean age ranged from 39 to 53years) were included. Our results showed that anemia correction significantly decreased the creatinine level (WMD 0.52 mg/dl; 95% CI: 0.12, 0.92; P = 0.011), graft loss rate (0.07, 95% CI:0.05, 0.08; P &lt; 0.0001) and all-cause death rate (0.01, 95% CI:0.00,0.01; P = 0.023). Furthermore, comparing with control group, erythropoietin (EPO) treatment greatly decreased creatinine level in renal transplant recipients (WMD 1.15 mg/dl; 95% CI: 0.27, 2.03 vs. WMD 0.05 mg/dl; 95% CI: &minus;0.13, 0.23; P &lt; 0.0001). Conclusions: Our findings showed that anemia correction reduced creatinine level, graft loss rate and all-cause death rate in renal transplant recipients. And EPO treatment is a good choice for anemia correction in renal transplant recipients.

Association of Serum Fetuin-A Levels with Allograft Outcome in Renal Transplant Recipients.

To determine serum fetuin-A pattern after renal transplantation and its association with graft outcome. In 41 renal transplant recipients, serum pretransplant fetuin-A levels and serum fetuin-A concentrations on days 7 and 30 after transplantation were measured using the enzyme-linked immunosorbent as­say (ELISA) method. Also, the association between serum fetuin-A levels with clinical and laboratory parameters was evaluated. A significant decrease in serum fetuin-A levels was noted in the first week after transplantation (P < .001). Subsequently, it started to increase and surpass pretransplant values during the first month (P < .001). Pretransplant fetuin-A levels did not differ among patients with different diethylenetriamine pentaacetic acid (DTPA) results. In addition, serum fetuin-A levels did not significantly correlate with metabolic parameters. In this prospective study there was no increase in serum fetuin-A levels during the first month and pretransplant fetuin-A levels are not predictive for allograft outcome in renal transplant recipients.

Body mass index and outcome in renal transplant recipients: a systematic review and meta-analysis.

BackgroundWhether overweight or obese end stage renal disease (ESRD) patients are suitable for renal transplantation (RT) is often debated. The objective of this review and meta-analysis was to systematically investigate the outcome of low versus high BMI recipients after RT.MethodsComprehensive searches were conducted in MEDLINE OvidSP, Web of Science, Google Scholar, Embase, and CENTRAL (the Cochrane Library 2014, issue 8). We reviewed four major guidelines that are available regarding (potential) RT recipients. The methodology was in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and written based on the PRISMA statement. The quality assessment of studies was performed by using the GRADE tool. A meta-analysis was performed using Review Manager 5.3. Random-effects models were used.ResultsAfter identifying 5,526 studies addressing this topic, 56 studies were included. We extracted data for 37 outcome measures (including data of more than 209,000 RT recipients), of which 26 could be meta-analysed. The following outcome measures demonstrated significant differences in favour of low BMI (<30) recipients: mortality (RR = 1.52), delayed graft function (RR = 1.52), acute rejection (RR = 1.17), 1-, 2-, and 3-year graft survival (RR = 0.97, 0.95, and 0.97), 1-, 2-, and 3-year patient survival (RR = 0.99, 0.99, and 0.99), wound infection and dehiscence (RR = 3.13 and 4.85), NODAT (RR = 2.24), length of hospital stay (2.31 days), operation duration (0.77 hours), hypertension (RR = 1.35), and incisional hernia (RR = 2.72). However, patient survival expressed in hazard ratios was in significant favour of high BMI recipients. Differences in other outcome parameters were not significant.ConclusionsSeveral of the pooled outcome measurements show significant benefits for ‘low’ BMI (<30) recipients. Therefore, we postulate that ESRD patients with a BMI >30 preferably should lose weight prior to RT. If this cannot be achieved with common measures, in morbidly obese RT candidates, bariatric surgery could be considered.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0340-5) contains supplementary material, which is available to authorized users.

A Single Center, Open-label, Randomized Pilot Study to Evaluate the Safety and Efficacy of Tacrolimus Modified Release, ADVAGRAF, Versus Tacrolimus Twice Daily, PROGRAF, in Stable Renal Recipients (SINGLE)

BackgroundCompliance with immunosuppressive regimens may affect clinical outcomes in renal transplant recipients. The aim of this study was to assess the safety and efficacy of standard-dose tacrolimus modified-release (TAC-MR) once daily versus tacrolimus (TAC) twice daily in stable renal transplant recipients. MethodsNinety-nine stable renal transplant recipients were randomized to receive standard-dose tacrolimus twice daily or standard-dose modified-release tacrolimus once daily on a 1:1 (mg:mg) basis. The primary end point was the incidence of adverse events (AEs) in both groups. Secondary end points included biopsy-proven acute rejection, graft survival, patient survival, clinical indicators, and change in score of questionnaire. ResultsThe incidence of AEs was not different between the TAC and TAC-MR groups (56.0% vs 53.1%, P > .05). There were no significant differences in mean calculated glomerular filtration rate, blood pressure, glycosylated hemoglobulin (HbA1c), blood concentration of tacrolimus, and drug compliance. The scores of all items in the 36-item short form health survey (SF-36) were not different between groups, except for vitality. With respect to the subject questionnaire, there was no difference in question scores between the two treatment groups. ConclusionA regimen of TAC-MR once daily can be considered as an effective and safe alternative formulation of tacrolimus in stable renal transplant patients.

Outcome of renal transplant recipients with CMV and BKV co-infection nephropathy

Outcome of renal transplant recipients with CMV and BKV co-infection nephropathy

One year survival analysis and factors predicting graft outcome in renal transplant recipients: A single centre experience

One year survival analysis and factors predicting graft outcome in renal transplant recipients: A single centre experience

Blood disorders typically associated with renal transplantation.

Renal transplantation has become one of the most common surgical procedures performed to replace a diseased kidney with a healthy kidney from a donor. It can help patients with kidney failure live decades longer. However, renal transplantation also faces a risk of developing various blood disorders. The blood disorders typically associated with renal transplantation can be divided into two main categories: (1) Common disorders including post-transplant anemia (PTA), post-transplant lymphoproliferative disorder (PTLD), post-transplant erythrocytosis (PTE), and post-transplant cytopenias (PTC, leukopenia/neutropenia, thrombocytopenia, and pancytopenia); and (2) Uncommon but serious disorders including hemophagocytic syndrome (HPS), thrombotic microangiopathy (TMA), therapy-related myelodysplasia (t-MDS), and therapy-related acute myeloid leukemia (t-AML). Although many etiological factors involve the development of post-transplant blood disorders, immunosuppressive agents, and viral infections could be the two major contributors to most blood disorders and cause hematological abnormalities and immunodeficiency by suppressing hematopoietic function of bone marrow. Hematological abnormalities and immunodeficiency will result in severe clinical outcomes in renal transplant recipients. Understanding how blood disorders develop will help cure these life-threatening complications. A potential therapeutic strategy against post-transplant blood disorders should focus on tapering immunosuppression or replacing myelotoxic immunosuppressive drugs with lower toxic alternatives, recognizing and treating promptly the etiological virus, bacteria, or protozoan, restoring both hematopoietic function of bone marrow and normal blood counts, and improving kidney graft survival.

Pre-transplant low level HLA antibody shows a composite poor outcome in long-term outcome of renal transplant recipients

To determine the significance of low-level DSA (donor specific antibody) in patients transplanted with negative cytotoxicity AHG (antihuman immunoglobulin) crossmatch, data from 279 patients who received a kidney transplant between July 1999 and March 2006 were collected. All kidney recipients received ABO-compatible donors. A poor outcome was defined as any one of the following: death, Cr > 2.0 mmol/L, occurrence of a rejection episode. Luminex Screening and Single Antigen assays from Tepnel Life Codes were used to detect human leukocyte antigen antibodies on pre-transplant sera retrospectively. Twenty-four out of 279 recipients demonstrated the presence of solid-phase DSA (MFI > 1000) present pre-transplant. In DSA+ group, the accumulated good versus poor outcome rate was 0.30 versus 0.70, respectively. These rates were 0.49 and 0.51, respectively, in the DSA− group. The difference in composite poor outcome between DSA+ versus DSA− group was significant (p = 0.030). The DSA− group had no difference in patient survival as compared to the DSA+ group (p = 0.061). There is no statistically significant difference for either mortality or outcome results between high MFI (>2000) and low MFI (≤2000) groups. Our data suggest that solid-phase antibodies which are not strong enough to elicit a positive T-AHG crossmatch may influence long-term graft outcome.

Increased risk of all-cause mortality and renal graft loss in stable renal transplant recipients with hyperparathyroidism.

Hyperparathyroidism is reported in 10% to 66% of renal transplant recipients (RTR). The influence of persisting hyperparathyroidism on long-term clinical outcomes in RTR has not been examined in a large prospective study. We investigated the association between baseline parathyroid hormone (PTH) levels and major cardiovascular events, renal graft loss, and all-cause mortality by Cox Proportional Hazard survival analyses in 1840 stable RTR derived from the Assessment of LEscol in Renal Transplantation trial. Patients were recruited in a mean of 5.1 years after transplantation, and follow-up time was 6 to 7 years. Significant associations between PTH and all 3 outcomes were found in univariate analyses. When adjusting for a range of plausible confounders, including measures of renal function and serum mineral levels, PTH remained significantly associated with all-cause mortality (4% increased risk per 10 units; P=0.004), and with graft loss (6% increased risk per 10 units; P<0.001), but not with major cardiovascular events. Parathyroid hormone above the upper limit of normal (65 pg/mL) indicated a 46% (P=0.006) higher risk of death and an 85% higher risk of graft loss (P<0.001) compared with low/normal values. Hyperparathyroidism is an independent, potentially remediable, risk factor for renal graft loss and all-cause mortality in RTR.

Influence of hemodynamics and intra-operative hydration on biochemical outcome of renal transplant recipients.

Background and Aims:Early graft function is crucial for successful kidney transplantation. The aim of our study was to evaluate the effect of intra-operative central venous pressure (CVP) and mean arterial pressure (MAP) on early graft function and biochemical outcome.Material and Methods:This was a retrospective study carried out on patients undergoing renal transplant only from live-related donors between March 2011 and May 2013. We mainly divided the patients into two groups based on CVP and mean MAP. One group had CVP more than 12 and other with CVP <12 mmHg at the time of declamping. Further one group was with mean MAP >100 mmHg and other with mean MAP of <100 mmHg. The graft outcome of genetically related and genetically unrelated donors was also evaluated in early postoperative period. The trend in fall of serum creatinine was studied during the first five post-operative days. The effect of age, dry weight, sex, relation with donor and intraoperative factors like MAP and CVP on early graft function were analysed. Correlation analysis, analysis of variance test (ANOVA) and multivariate analysis technique were used in this study for statistical computation.Results:The mean CVP at the time of declamping was 13.91 mmHg. The minimum CVP was 6 mmHg in one patient who had ischemic heart disease with low ejection fraction. All 5 days mean serum creatinine values were comparable in two groups on 1st, 2nd, 3rd and 4th postoperative days. The mean MAP at the time of declamping was 111.22 mmHg. Mean MAP varied from a minimum of 95 mmHg to maximum of 131 mmHg. There was no significant difference in two groups on 1st, 2nd, 3rd, 4th and 5th postoperative days.Conclusion:A CVP around 12 mmHg and mean MAP >95 mmHg with good perioperative fluid hydration is associated with good early graft function.

Homoarginine and Clinical Outcomes in Renal Transplant Recipients: Results From the Assessment of Lescol in Renal Transplantation Study.

Despite improvements in kidney transplantation, complications, including cardiovascular morbidity and graft loss, contribute to reduced graft and patient survival. The amino acid homoarginine exerts a variety of beneficial effects that may be relevant for cardiovascular and graft outcomes, which is investigated in the present study. Homoarginine was measured in 829 renal transplant recipients participating in the placebo group of the Assessment of Lescol in Renal Transplantation study. Mean follow-up was 6.7 years. By Cox regression analyses, we determined hazard ratios (HRs) to reach prespecified, adjudicated endpoints according to baseline homoarginine levels: major adverse cardiovascular events (n = 103), cerebrovascular events (n = 53), graft failure or doubling of serum creatinine (n = 140), noncardiovascular mortality (n = 51), and all-cause mortality (n = 107). Patients mean age was 50 ± 11 years, homoarginine concentration was 1.96 ± 0.76 μmol/L, and 65% were men. Patients in the lowest homoarginine quartile (<1.40 μmol/L) had an adjusted 2.6-fold higher risk of cerebrovascular events compared to those in the highest quartile (>2.34 μmol/L) (HR, 2.56; 95% confidence interval [95% CI], 1.13-5.82). Similarly, the renal endpoint occurred at a significantly increased rate in the lowest homoarginine quartile (HR, 2.34; 95% CI, 1.36-4.02). For noncardiovascular and all-cause mortality, there was also increased risk associated with the lowest levels of homoarginine, with HRs of 4.34 (95% CI, 1.63-10.69) and 2.50 (95% CI, 1.38-4.55), respectively. Low homoarginine is strongly associated with cerebrovascular events, graft loss and progression of kidney failure and mortality in renal transplant recipients. Whether interventions with homoarginine supplementation improve clinical outcomes requires further evaluation.

Predictive factors for increased aortic pulse wave velocity in renal transplant recipients and its relation to graft outcome.

To evaluate aortic stiffness in renal transplant patients and to determine the correlation of renal insufficiency and estimated glomerular filtration rate (eGFR) with aortic pulse wave velocity (APWV), we studied 96 renal transplant patients followed-up at our center. We measured the APWV using transcutaneous Doppler flow recordings and the foot-to-foot method, and calculated the eGFR using the Modification of Diet in Renal Disease equation. The study included 81 (84.4%) males and 15 (15.6%) females. The mean age of the patients was 37.84 ± 10.10 years. The mean duration of transplant was 47.90 ± 34.40 months. The eGFR of the patients ranged from 1 to 120 mL/min, with a mean GFR of 72.6 ± 23.2 mL/min. Sixty-seven (69.8%) patients had eGFR > 60 mL/min and hence had stages 1 and 2 chronic kidney disease (CKD), 27 (28.1%) patients had eGFR 30-60 mL/min and hence had stage 3 CKD and two (2.1%) patients had eGFR <30 mL/min and hence had stages 4 and 5 CKD. The APWV of the patients ranged from 4 to 14.2 m/s, with a mean of 7.49 ± 2.47 m/s. A significant inverse correlation was found between the APWV and eGFR (Pearson correlation coefficient, -0.427, P = 0.00). The mean APWV was significantly higher among patients with higher CKD stage, P = 0.004. We conclude that the APWV is related to the renal graft dysfunction as measured by eGFR. The poorer the renal function, the higher was the APWV. Determination of the APWV may be helpful in predicting the outcome in renal transplant recipients.

Effects of Parvovirus B19 Infection in Renal Transplant Recipients: A Retrospective Review of Three Cases.

Parvovirus B19 (PVB19) is a DNA virus which causes clinically relevant infection in renal transplant recipients (RTR) leading to significant morbidity. Manifestations include erythropoietin resistant anemia, proteinuria, and glomerulosclerosis in the allograft. Severe infection may require administration of intravenous immunoglobulin, reduction in immunosuppression and transfusions. The major challenge in managing and preventing the infection in RTR involves the act of balancing the decreased level of immunosuppression and the risk of rejection. The objective of this article is to understand the importance of PVB19 infection and its outcome in RTR. We reviewed the medical records of three RTR with confirmed PVB19 infection and recorded patient information including demographics, clinical and laboratory data, management, and outcome. The average time of occurrence of PVB19 infection as transplant was 8.6 weeks and they presented with symptomatic anemia. Elevated creatinine values were noted in two of them. Following treatment, anemia improved and creatinine values returned to baseline. One of them developed an early relapse and had to be treated once again similarly. We emphasize the importance of maintaining a high index of suspicion for PVB19 infection in patients with anemia in the posttransplant phase, especially in patients on higher doses of immunosuppressants. Early and proper treatment can prevent worsening clinical condition and possible effects on the allograft.

A systematic review and meta-analysis of the relation between Body Mass Index and outcome in renal transplant recipients

A systematic review and meta-analysis of the relation between Body Mass Index and outcome in renal transplant recipients

182: The leukocyte immunoglobulin-like receptor B4 differentially regulates FcγRI-dependent TNF production via its three intracellular immunoreceptor tyrosine-based inhibitory signalling motifs (ITIMs)

The leukocyte immunoglobulin-like receptor (LILR) B4 belongs to a family of activating and inhibitory cell surface receptors that have been increasingly recognised as key regulators of the threshold and amplitude of leukocyte activation. LILRB4 which is highly expressed on monocytes and macrophages transduces inhibitory signals through its three intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Clinically, increased expression is associated with better clinical outcome in renal transplant recipients contrasted with impaired immune effector cell functions in HIV infection. However, mechanisms of how LILRB4 regulates monocyte activation and the exact contribution of the three ITIMs for its immune-regulatory functions are poorly characterised. In this study we show that co-ligation of LILRB4 with FcγRI on THP-1 cells and primary monocytes markedly inhibited the production of TNF, a key pro-inflammatory cytokine. Cross-linking of FcγRI on THP-1 cells increased phosphorylation key protein tyrosine kinase signaling molecules and an adaptor protein that targets protein tyrosine kinases for degradation (c-Cbl). Co-ligation of LILRB4 and FcγRI considerably reduced FcγRI-mediated phosphorylation of these signaling molecules and terminated cellular activation by recruiting Src homology region 2 domain-containing phosphatase-1 (SHP-1)-like molecule. Importantly, using site-targeted mutagenesis we found for the first time that the middle (Y412) and distal (Y442) tyrosine residues in its ITIM motifs were critical for the inhibitory functions of LILRB4 and Y412 alone was sufficient for maximal inhibition. By contrast, the proximal tyrosine residue at Y360 showed unexpectedly enhanced Fc γ RI-mediated TNF production. Collectively, our results suggest that LILRB4 is a potent immune regulatory receptor in which combined contribution of its multiple ITIMs may fine tune innate immune responses.