Peripheral Blood Absolute Lymphocyte Count as a Predictor of Cytomegalovirus Infection in Kidney Transplant Recipients

BackgroundCytomegalovirus viremia and infection have been reported to increase the risks for acute graft rejection and mortality in kidney transplant recipients. Previous studies demonstrated that a lower absolute lymphocyte count in peripheral blood is associated with cytomegalovirus infection. The aim of this study was to investigate whether absolute lymphocyte count could predict cytomegalovirus infection in kidney transplant recipients.MethodsFrom January 2010 to October 2021, 48 living kidney transplant recipients in whom both donor and recipient were positive for immunoglobulin G of cytomegalovirus were included in this retrospective study. The primary outcome was defined as cytomegalovirus infection occurring ≥28 days after kidney transplantation. All recipients were followed for 1 year after kidney transplantation. The diagnostic accuracy of absolute lymphocyte count on day 28 post-transplantation for cytomegalovirus infection was analyzed using receiver operating characteristic curves. A Cox proportional hazards model was used to calculate hazard ratios for the incidence of cytomegalovirus infection.ResultsThere were 13 patients (27%) with cytomegalovirus infection. The sensitivity and specificity for cytomegalovirus infection were 62% and 71%, respectively; the negative predictive value was 83% when an absolute lymphocyte count of 1100 cells/μL on day 28 post-transplantation was used as the cutoff. The incidence of cytomegalovirus infection was significantly higher when the absolute lymphocyte count was <1100 cells/μL on day 28 post-transplantation (hazard ratio, 3.32; 95% CI, 1.08-10.2).ConclusionAbsolute lymphocyte count is an inexpensive and easy test that can effectively predict cytomegalovirus infection. Further validation is needed to confirm its utility.     

Macrochimerism in Intestinal Transplantation: Association With Lower Rejection Rates and Multivisceral Transplants,Without GVHD

Blood chimerism has been reported sporadically among visceral transplant recipients, mostly in association with graft‐vs‐host disease (GVHD). We hypothesized that a higher degree of mixed chimerism would be observed in multivisceral (MVTx) than in isolated intestinal (iITx) and isolated liver transplant (iLTx) recipients, regardless of GVHD. We performed a longitudinal prospective study investigating multilineage blood chimerism with flow cytometry in 5 iITx and 4 MVTx recipients up to one year posttransplant. Although only one iITx patient experienced GVHD, T cell mixed chimerism was detected in 8 out of 9 iITx/MVTx recipients. Chimerism was significantly lower in the four subjects who displayed early moderate to severe rejection. Pre‐formed high‐titer donor‐specific antibodies, bound in vivo to the circulating donor cells, were associated with an accelerated decline in chimerism. Blood chimerism was also studied in 10 iLTx controls. Among nonsensitized patients, MVTx recipients exhibited greater T and B cell chimerism than either iITx or iLTx recipients. Myeloid lineage chimerism was present exclusively among iLTx and MVTx (6/13) recipients, suggesting that its presence required the hepatic allograft. Our study demonstrates, for the first time, frequent T cell chimerism without GVHD following visceral transplantation and a possible relationship with reduced rejection rate in MVTx recipients.     

Differential cytokine and chemokine expression during rejection and infection following intestinal transplantation

Background/objectivesRejection and infectious enteritis in intestinal transplant (ITx) patients present with virtually identical symptoms. Currently, the gold standard for differentiating between these two conditions is endoscopy, which is invasive and costly. Our primary aim was to identify differences in peripheral blood cytokines during episodes of acute cellular rejection (ACR) and infectious enteritis in patients with intestinal transplants.MethodsThis was a prospective, cross-sectional study involving ITx patients transplanted between 2000 and 2016. We studied 63 blood samples collected from 29 ITx patients during periods of normal (n = 24) and abnormal (n = 17) allograft function. PBMCs from whole blood samples were cultured under unstimulated or stimulated conditions with phytohemagglutinin (PHA). The supernatant from these cultures were collected to measure cytokine and chemokine levels using a 38-plex luminex panel.ResultsOur study found that cytokines and chemokines are differentially expressed in normal, ACR, and infectious enteritis samples under unstimulated conditions based on heatmap analysis. Although each cohort displayed distinctive signatures, only MDC (p = 0.037) was found to be significantly different between ACR and infectious enteritis. Upon stimulation of PBMCs, patients with ACR demonstrated increased immune reactivity compared to infectious enteritis; though this did not reach statistical significance.ConclusionsTo our knowledge, this is the first comprehensive study comparing cytokine expression during acute rejection and infectious enteritis in intestinal transplant recipients. Our results suggest that cytokines have the potential to be used as clinical markers for risk stratification and/or diagnosis of ACR and infectious enteritis.     

Pulmonary Infections in Intestinal Transplant Recipients With Preexisting Pulmonary Nodules

BackgroundPulmonary nodules in asymptomatic patients could represent latent pulmonary infections. Intestinal transplant (ITx) recipients with preexisting lung nodules might be at higher risk for pulmonary infections. However, data is scarce.MethodsThis retrospective study included adult patients who underwent ITx from May 2016 to May 2020. Chest computed tomography scans performed within 12 months before ITx were obtained to evaluate for preexisting pulmonary nodules. Screening for endemic mycoses, Aspergillus, Cryptococcus, and latent tuberculosis infection performed within 12 months before ITx was obtained. We assessed for worsening pulmonary nodules, and fungal and mycobacterial infections during the first year post-transplant. Survival and graft loss at 1-year post-transplant was also assessed.ResultsForty-four patients underwent ITx. Thirty-one had preexisting lung nodules. No invasive fungi were recorded in the pretransplant period and one individual had latent tuberculosis infection. In the post-transplant period, one individual developed probable invasive aspergillosis and had worsening nodular opacities, whereas one had disseminated histoplasmosis with stable lung nodules in chest computed tomography. No mycobacterial infections were documented. The cohort survival was 84% at 12 months after transplant.ConclusionPreexisting pulmonary nodules were common in the cohort (71%), yet latent and active pulmonary infections were rare. Appearance of new or worsening pulmonary nodules does not appear to directly correlate with pulmonary infections in the post-transplant period. Routine chest computed tomography is not recommended in the pretransplant period, but follow-up is favored in patients with confirmed nodular opacities. Clinical monitoring is essential.     

Focal Segmental Glomerulosclerosis (FSGS) Progressing to Collapsing Glomerulopathy in Renal Transplant Recipients With and Without COVID-19 Infection.

BackgroundCollapsing glomerulopathy (CGN) secondary to HIV or COVID-19 infection mainly occurs in patients of African American descent due to APOL-1 gene mutations, but CGN is occasionally reported in white patients. CGNs are rarely reported in renal transplant biopsies and their association with idiopathic focal segmental glomerulosclerosis (FSGS) is unclear.Methods and ResultsPatient #1 was a 48-year-old Caucasian white man who had a renal transplant 8 years ago and was recently diagnosed with COVID-19 infection. Two weeks post infection, his serum creatinine (SCr) increased to 2.01 mg/dL from a baseline of 1.40 mg/dL, and he developed concomitant nephrotic range proteinuria. The first renal transplant biopsy showed FSGS. Four weeks later, his sCr level increased to 2.65 mg/dL with worsening proteinuria, and a second renal transplant biopsy revealed CGN. Patient #2 was a 32-year-old African American man whose native renal biopsy revealed primary FSGS. He received a renal transplant with initial post-transplant sCr level at 1.17 mg/dL. Four months later, his sCr and protein-to-creatinine ratio began to rise. Sequential biopsies revealed that the patient had developed recurrent FSGS, which progressed to show features of CGN. The CGN was further confirmed in his transplant kidney graft at autopsy later.ConclusionsThis is the first case report of CGN in a white renal recipient with COVID-19 infection. The pathologic presentations of FSGS progressing to collapsing FSGS in our 2 renal transplant recipients suggest that FSGS and GGN may share a common pathophysiologic mechanism of podocytopathy.     

Prophylactic fluconazole in liver transplant recipients: A randomized,double-blind,placebo-controlled trial

Background:Among persons who receive solid organ 0842 transplants, liver transplant recipients have the highest incidence of invasive fungal infection; however, no antifungal prophylaxis has been proven to be effective.Objective:To evaluate the efficacy and safety of prophylactic0842 fluconazole in liver transplant recipients.Design:Randomized, double-blind, placebo-controlled trial. 0842Setting:University-affiliated transplantation center.0842Patients:212 liver transplant recipients who received fluconazole0842 (400 mg/d) or placebo until 10 weeks after transplantation.Measurements:Fungal colonization, proven superficial 0842 or invasive fungal infection, drug-related side effects, and death.Results:Fungal colonization increased in 0842 patients who received placebo (from 60% to 90%) but decreased in patients who received fluconazole (from 70% to 28%). Proven fungal infection occurred in 45 of 104 placebo recipients (43%) but in only 10 of 108 fluconazole recipients (9%) (P < 0.001). Fluconazole prevented both superficial infection (29 of 104 placebo recipients became infected [28%] compared with 4 of 108 fluconazole recipients [4%]; P < 0.001) and invasive infection (24 of 104 placebo recipients became infected [23%] compared with 6 of 108 fluconazole recipients [6%]; P < 0.001). Fluconazole prevented infection by most Candida species, except C. glabrata. However, infection and colonization by organisms intrinsically resistant to fluconazole did not seem to increase. Fluconazole was not associated with any hepatotoxicity. Patients receiving fluconazole had higher serum cyclosporine levels and more adverse neurologic events (headaches, tremors, or seizures in 13 fluconazole recipients compared with 3 placebo recipients; P = 0.01). Although the overall mortality rate was similar in both groups (12 of 108 [11%] in the fluconazole group compared with 15 of 104 [14%] in the placebo group; P > 0.2), fewer deaths related to invasive fungal infection were seen in the fluconazole group (2 of 108 patients [2%]) than in the placebo group (13 of 104 patients [13%]) (P = 0.003).Conclusions:Prophylactic 0842 fluconazole after liver transplantation decreases fungal colonization, prevents superficial and invasive fungal infections, and has no appreciable hepatotoxicity. Although fluconazole prophylaxis is associated with fewer deaths from fungal infection, it does not improve overall survival. Patients receiving prophylactic fluconazole require close monitoring of serum cyclosporine levels to avoid neurologic toxicity.     

Management of leukopenia in kidney and pancreas transplant recipients

Abstract: Leukopenia is frequently observed in the setting of solid organ transplantation. The risk factors, natural history, and outcomes associated with leukopenia post‐transplantation have not been well defined. We retrospectively studied 102 adult kidney and/or pancreas transplant recipients over a one‐yr period of time. By defining leukopenia as a white blood cell count ≤3000 cells/mm³ and neutropenia as an absolute neutrophil count ≤2000/mm³, the combined incidence of either leukopenia or neutropenia was 58% (59/102); the first episode occurred at a mean of 91 d post‐transplant. A significant increase in the incidence of leukopenia was found in patients who either received alemtuzumab induction (42% with alemtuzumab vs. 9% with rabbit anti‐thymocyte globulin induction, p < 0.05) and/or had rapid steroid withdrawal in the early post‐transplant period (44% with vs. 16% without steroid withdrawal, p < 0.05). The most common intervention performed for leukopenia was reducing the dose of mycophenolate mofetil and/or valganciclovir. When granulocyte stimulating factors were used, a mean of 3.1 doses were needed to successfully manage the leukopenia. Although leukopenia was a common finding in our study of kidney and/or pancreas transplant recipients, there was no difference in the rates of infection or acute rejection in patients with and without leukopenia.     

Risk Factors for Refractory Ascites After Living Donor Liver Transplant

ObjectivesRefractory ascites after liver transplant commonly occurs in living donor liver transplant (LDLT). Refractory ascites is associated with postoperative complications and poor prognosis. This study sought to determine the risk factors of refractory ascites and discuss their perioperative management.MethodsA retrospective study of 122 living donor liver transplant recipients between 2008 and 2017 was performed to analyze the risk factors, incidence, and characteristics of refractory ascites. Refractory ascites post LDLT was defined as the production of ascites fluid >1000 mL/d on postoperative day 14 or required repeated drainage.ResultsA total of 24 patients (19.6%) developed refractory ascites. The 1-year survival rate was significantly worse in the refractory ascites group compared with the nonrefractory ascites group (P < .001). In a univariate analysis, patients with refractory ascites had a higher Model for End-Stage Liver Disease (MELD) score, donor age, presence of left lobe graft, ascites at laparotomy, portal venous pressure just after surgery, cold ischemia time, and absence of hepatocellular carcinoma compared with patients without refractory ascites. Multivariate proportional regression analyses revealed that MELD score ≥20, left lobe graft, donor age 50 years or older, and ascites at laparotomy ≥350 mL were independently associated with refractory ascites. Postoperative complications, such as bleeding (P < .001), sepsis (P < .001), and bloodstream infection within 30 days after LDLT (P < .00), were significantly higher in the refractory ascites group.ConclusionRefractory ascites is associated with reduced 1-year survival and increased postoperative complications. Four factors including MELD score ≥20, donor age 50 years or older, presence of left graft, and ascites at laparotomy ≥350 mL were independent predictors for refractory ascites.     

Multidrug-resistant organisms: A significant cause of severe sepsis in pediatric intestinal and multi-visceral transplantation

Severe sepsis in immunocompromised children is associated with increased mortality. This paper describes the epidemiology landscape, clinical acuity, and outcomes for severe sepsis in pediatric intestinal (ITx) and multi-visceral (MVTx) transplant recipients requiring admission to the pediatric intensive care unit (PICU). Severe sepsis episodes were retrospectively reviewed in 51 ITx and MVTx patients receiving organs between 2009 and 2015. Twenty-nine (56.8%) patients had at least one sepsis episode (total of 63 episodes) through December 2016. Bacterial etiologies accounted for 66.7% of all episodes (n = 42), occurring a median of 122.5 days following transplant (IQR 59–211.8 days). Multidrug-resistant organisms (MDROs) accounted for 73.8% of bacterial infections; extended spectrum beta-lactamase producers, vancomycin-resistant enterococcus, and highly-resistant Pseudomonas aeruginosa were the most commonly identified. Increased mechanical ventilation and vasoactive requirements were noted in MDRO episodes (OR 3.03, 95% CI 1.09–8.46 and OR 3.07, 95% CI 1.09–8.61, respectively; p < .05) compared to non-MDRO episodes. PICU length of stay was significantly increased for MDRO episodes (7 vs. 3 days, p = .02). Graft loss was 24.1% (n = 7) and mortality was 24.1% (n = 7) in patients who experienced severe sepsis. Further attention is needed for MDRO risk mitigation and modification of sepsis treatment guidelines to ensure MDRO coverage for this population.     

Predictive Value of Red Blood Cell Distribution Width,Platelet Count to Lymphocyte Count Ratio,and Neutrophil Count to Lymphocyte Count Ratio Values for the Detection of Postoperative Infection in Patients Undergoing Liver Transplantation

BackgroundThe red blood cell distribution width (RDW) value is a simple and fast parameter that shows an elevation in the presence of infectious disease. It is thought that proinflammatory signals cause changes in the cell wall of the erythrocytes. In our study, we aimed to investigate the prognostic value of RDW and other parameters in patients undergoing liver transplantation.MethodsWe retrospectively investigated 200 patients who underwent liver transplantation (LT) in our center. The study group was 100 patients who underwent LT and developed a postoperative abdominal or catheter-related infection in the early period between the first and second weeks of hospitalization. The control group comprises 100 patients who underwent LT and were discharged without complications. In 4 different periods, inflammatory markers and RDW, platelet count to lymphocyte count ratio, and neutrophil count to lymphocyte count ratio (NLR) values were compared in the 2 groups.ResultsIn our study, we found RDW and NLR parameters to be elevated in correlation with infection in patients who underwent LT (P < .05). Other markers were elevated but not significantly correlated with infection.ConclusionsThese parameters can be simple and effective additional tools to implement in patients suspected of infection. Further prospective studies with larger patient groups and varying infection states are required for validating RDW and NLR as additional diagnostic markers.     

Thrombotic and hemorrhagic complications during visceral transplantation: risk factors,and association with intraoperative disseminated intravascular coagulation‐like thromboelastographic qualities: a single‐center retrospective study

This study describes the risk of thrombotic and hemorrhagic complications, both intraoperatively, and up to 1 month following visceral transplantation. Data from 48 adult visceral transplants performed between 2010 and 2017 were retrospectively studied [32 multivisceral (MVTx); 10 isolated intestine; six modified‐MVTx]. Intraoperatively, intracardiac thrombosis (ICT)/pulmonary embolism (PE) occurred in 25%, 0% and 0% of MVTx, isolated intestine and modified MVTx, respectively, and was associated with 50% (4/8) mortality. Preoperative portal vein thrombosis (PVT) was a significant risk factor for ICT/PE (P = 0.0073). Thromboelastography resembling disseminated intravascular coagulation (DIC) (r time <4 mm combined with fibrinolysis or flat‐line) was statistically associated with occurrence of ICT/PE (P < 0.0001). Compared to subgroup without ICT/PE, occurrence of ICT/PE was associated with an increased demand for all blood product components both overall, and each surgical stage. Hyperfibrinolysis (56%) was identified as cause of bleeding in MVTx. Incidence of postoperative thrombotic event at 1 month was 25%, 30% and 17% for MVTx, isolated intestine and modified MVTx, respectively. Incidence of postoperative bleeding complications at 1 month was 11%, 20% and 17% for MVTx, isolated intestine and modified MVTx. In conclusion, MVTx recipients with preoperative PVT are at an increased risk of developing intraoperative life‐threatening ICT/PE events associated with DIC‐like coagulopathy.     

Risk Factors for Mortality in Liver Transplant Recipients With ESKAPE Infection

BackgroundAlthough infections caused by the pathogens Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp (ESKAPE) have recently been identified as serious emerging problems in solid organ transplant, no information in liver transplant (LT) recipients is available. We sought to investigate the risk factors for associated mortality in LT recipients with ESKAPE infections.MethodsA retrospective analysis of infection after LT was reviewed. Risk factors for mortality caused by ESKAPE infection were identified.ResultsFifty-three episodes of infections caused by ESKAPE were documented in 51 LT recipients. The main sites of infection were the bloodstream (49.0%), the lungs (33.3%), and the intra-abdominal/biliary tract (17.6%). The risk factors for mortality independently associated with ESKAPE infection were female sex (odds ratio [OR] = 6.6, 95% confidence interval [CI] = 1.1–40.8, P = .042), septic shock (OR = 30.1, 95% CI = 3.7–244.8, P = .001), and lymphocyte counts <300/mm³ (OR = 20.2, 95% CI = 2.9–142.2, P = .003).ConclusionsTo improve the results of LT, more effective therapeutic treatments are of paramount importance when female LT recipients with ESKAPE infection present with septic shock and decreased lymphocyte counts.     

Use of sodium-glucose co-transporter 2 inhibitors in solid organ transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus: A systematic review

IntroductionSodium-Glucose Co-Transporter 2 (SGLT2) inhibitors have demonstrated kidney, cardiovascular and mortality benefits in the general population; however, the evidence is limited in solid organ transplant recipients. The aim of this systematic review was to evaluate the current efficacy and safety data of SGLT2 inhibitors in adult kidney, heart, lung, and liver transplant recipients with pre-existing type 2 or post-transplantation diabetes mellitus.MethodWe searched MEDLINE, MEDLINE Epub, CENTRAL, CDSR, EMBASE, CINAHL, and sources of unpublished literature. All primary interventional and observational studies on SGLT2 inhibitors in transplant recipients were included. Clinical outcomes included mortality, cardiovascular and kidney events, and adverse events such as graft rejection. Surrogate markers including hemoglobin A1c (HbA1c) and weight reduction were also evaluated.ResultsOf the 17 studies that were included in this systematic review, there were 15 studies on kidney transplant recipients (n = 2417 patients) and two studies on heart transplant recipients (n = 122 patients). There was only one randomized controlled trial which evaluated 49 kidney transplant patients over 24 weeks. Overall, studies were heterogeneous in study design, sample size, duration of diabetes, time to SGLT2 inhibitor initiation post-transplantation (ranging from 0.88 to 11 years post kidney transplant; five to 5.7 years post heart transplant) and follow-up (ranging from 0.4 to 5.25 years in kidney transplant patients; 0.75 to one year in heart transplant patients). Only one retrospective study evaluated mortality as a part of a composite outcome in kidney transplant patients; however, study limitations restrict generalizability of results. Overall, studies could not confirm clinical cardiovascular and kidney benefits in the transplant population. Findings suggested that SGLT2 inhibitors may improve glycemic control; however, they are associated with urinary tract infection. Diabetic ketoacidosis and acute kidney injury also occurred in these studies, with precipitating factors such as infection and acute heart failure exacerbation.ConclusionsWhile SGLT2 inhibitors are promising agents with expanding indications in the non-transplant population, these agents may not be suitable for all solid organ transplant recipients, and close monitoring (e.g. for urinary tract infections) and patient education (e.g. sick day management) are essential if these agents are initiated. Evidence is based on short-term findings and suggests an association with hemoglobin A1c reduction and increased adverse events. Further long-term randomized controlled trials are needed to evaluate the effect of SGLT2 inhibitors on clinically important outcomes, including mortality reduction, in solid organ transplant recipients.     

Clinical outcomes of intestinal transplant recipients colonized with multidrug‐resistant organisms: a retrospective study

Rates of multidrug‐resistant organisms (MDRO) colonization among intestinal transplant (ITx) recipients have not been reported. Colonization rates with vancomycin‐resistant Enterococcus (VRE), carbapenem‐resistant Gram‐negative bacteria (CR‐GNB), and methicillin‐resistant Staphylococcus aureus (MRSA) were obtained retrospectively in adults undergoing ITx (isolated or multivisceral) from 1/2009 to 12/2015. We assessed for VRE, CR‐GNB, and MRSA bacteremia during the first year post‐transplant for patients colonized with VRE, CR‐GNB, and MRSA, respectively, and for those who were not colonized. We evaluated whether the number of hospitalization days and one year post‐transplant survival were different in MDRO‐colonized patients. Forty‐five ITx recipients were identified. Twenty‐eight (62%) were colonized with MDRO [VRE in 22 (50%) patients, MRSA in seven (16%), and CR‐GNB in six (15%)]. VRE and CR‐GNB‐colonized patients were more likely to develop VRE and CR‐GNB bacteremia, respectively, than noncolonized patients [8/22 (36%) vs. 1/23 (4%), and 4/6 (67%) vs. 2/39 (5%), P < 0.05 for both]. There was no difference in one‐year survival between MDRO‐colonized and noncolonized patients. However, survival was lower among MDRO‐colonized patients who developed VRE, CR‐GNB, or MRSA bacteremia (P < 0.001). MDRO colonization was common among our ITx recipients. VRE and CR‐GNB bacteremia was more common among colonized patients, and survival was lower among MDRO‐colonized patients who developed bacteremia.     

Cause of End-Stage Renal Disease Is Not a Risk Factor for Cytomegalovirus Infection After Kidney Transplant

BackgroundCytomegalovirus infection (CMV) after kidney transplantation leads to increased morbidity and mortality. Whether the cause of end-stage renal disease (ESRD) influences the risk of CMV infection post-transplant is not known.MethodsWe analyzed data from 2741 adult kidney transplant recipients from January 1993 through December 2014. The causes of ESRD included diabetes mellitus (n = 947), hypertension (n = 442), polycystic kidney disease (n = 549), and glomerulonephritis (GN) (n = 803). The primary outcome was incidence of CMV infection, defined as the first episode of detectable CMV DNA in the blood following transplant.ResultsThree hundred and thirty patients developed a CMV infection over a median follow-up of 4.5 years. Patients with diabetes mellitus (DM) as the cause of ESRD had a higher incidence of CMV infection post-transplant compared to patients with GN (2.37 vs 1.58/100 person-years, P < .005) whereas hypertension (HTN) and autosomal dominant polycystic kidney disease (PKD) were similar (2.17 and 2.07/100 person-years). DM was associated with a 35% higher risk of CMV infection compared to GN in unadjusted analyses [hazard ratio=1.35 [95% confidence interval 1.02–1.78], P = .04). However, after adjustment for age, the risk of CMV infection was similar in all groups (DM: age-adjusted hazard ratio 1.02 [0.78–1.39]; HTN: 0.96 (0.67–1.36); PKD: 1.08 [0.78–1.48]; compared to GN). The risk of CMV infection increased with age (adjusted hazard ratio=1.32 [1.18–1.47] for every decade of life, P < .001).ConclusionsOur study demonstrates that the cause of ESRD is not a significant risk factor for CMV infection in kidney transplant recipients once adjusted for age. Future studies are needed to identify risk factors for CMV infection to define patient-centered monitoring and prevention.     

Blood Stream Infections in Renal Transplant Recipients: A Single-Center Study

IntroductionBacteremias among renal transplant recipients are more frequent as a result of immunosuppression. They are considered extremely high-risk because they are correlated with decreased allograft and recipient survival.Patients and MethodsAll episodes of bacteremia among renal transplant recipients were documented following review of medical records, from January 2010 to May 2013.ResultsIn total 26 episodes of bacteremia were observed in 22 patients. Gram negative bacteremia was identified in 73% (19/26) cases. Pathogens according to their frequency were the following Escherichia coli (6/26, 23%), Klebsiella pneumonia (5/26, 19%), Pseudomonas aeruginosa (3/26, 11%), Staphylococcus epidermidis (3/26, 11%), Acinetobacter baumanni (2/26, 7.7%), Enterococcus faecalis (2/26, 7.7%). The first trimester post renal transplantation 18 episodes (69%) of bacteremia were presented that were not correlated to indwelling urinary catheter or stent. Positive urinary culture with the same pathogen was recognized in 13 patients. All recipients manifested fever, eight recipients had leucocytosis and three cases were complicated by septic shock. Immediate resuscitation with intravenous fluids and non-nephrotoxic antibiotic regimen was initiated. Acute renal allograft dysfunction (defined as an increase in serum creatinine more than 0.5 mg/dL from baseline) was observed in five patients and was restored following infection resolution.ConclusionIncreased prevalence of bacteremia in renal transplant recipients is attributed to immunosuppression and usually bacteremic episodes follow urinary tract infection. The commonest pathogens are Gram negative bacteria with E. coli the most frequent. Early detection and proper management are important as bacteremia affects renal allograft and recipient survival.     

Serum Levels of S100β, Neuron-Specific Enolase,Glial Fibrillary Acidic Protein in Kidney Transplant Recipients and Donors: A Prospective Cohort Study

BackgroundThe aim of this study was to evaluate changes in serum levels of S100β, neuron-specific enolase, glial fibrillary acidic protein in living donors and recipients after kidney transplantation.MethodsWe enrolled 56 patients into the study. Of these, 27 underwent donor nephrectomy (group D), and the remaining 29 underwent kidney transplantation (recipient, group R). Neuromarkers were measured in samples obtained before the procedure, on postoperative day 7, and at 1 month postoperatively.ResultsPostoperative kidney functions were impaired in patients who underwent living donor nephrectomy compared with their preoperative levels (P < .001), although no significant difference was observed in their neuromarkers. The postoperative delirium rating scale was also impaired after living donor nephrectomy compared with preoperative levels (P < .05). Postoperative kidney functions were improved (P < .001), and a progressive decrease in neuromarker levels (P < .05) was observed in kidney transplant recipients compared with their preoperative levels. Linear regression analysis showed a significant correlation between neuron-specific enolase, glial fibrillary acidic protein levels and kidney functions in recipients.ConclusionThe present study demonstrated that neuron-specific enolase and glial fibrillary acidic protein levels decrease in kidney transplant recipients and do not change in donors. This result indicated that there is no evidence of neurotoxicity in either recipients and donors in kidney transplantation.     

Characterization of T cell immunophenotypes in intestinal transplantation: A pilot study

Immunophenotyping of peripheral blood mononuclear cells has been shown to be a useful, non-invasive method of predicting acute cellular rejection (ACR) following intestinal transplantation (ITx). Our objectives were to characterize differences in the T cell immunophenotype of ITx recipients in peripheral blood samples (1) collected late versus early after ITx and (1) associated with episodes of ACR and infectious enteritis. An IRB-approved, cross-sectional study of ITx recipients was performed. Peripheral blood samples were collected during normal visits and episodes of allograft dysfunction. A total of 38 patients were included in the analysis: 31 ITx recipients (87% liver-inclusive allografts) and 7 intestinal failure control patients. Of the ITx patients, 26 patients were pediatric patients (<21 years). A total of 70 samples were analyzed from ITx recipients, including 51 during normal visits and 19 during episodes of allograft dysfunction (median of 2 samples per patient; range of 1–6 samples per patient). In the late (n = 32) versus early post-ITx (n = 19) normal samples, there was a significantly higher percentage of central memory CD4 T cells (p = .001). In the ACR (n = 5) versus infectious enteritis (n = 14) samples, there was a higher percentage of CD8 T cells expressing HLA-DR (p = .002), CD57 (p < .001), and KLRG1 (p < .001) and a higher percentage of CD4 T cells expressing CD57 (p = .03). Additional studies are needed with larger cohorts to validate these changes in the T cell immunophenotype. Further elucidating T cell immunophenotypes in ITx will lead to a better understanding of immune mechanisms of allograft dysfunction, identification of potential biomarkers in ITx, and optimized selection of immunosuppressive therapies.     

Conversion From Immediate-Release Tacrolimus to Prolonged-Release Tacrolimus in Stable Heart Transplant Patients: A Retrospective Study

BackgroundLifelong adherence with post-transplant immunosuppression is challenging, with nonadherence associated with greater acute rejection (AR) risk.MethodsThis retrospective study evaluated conversion from immediate-release tacrolimus (IRT) to prolonged-release tacrolimus (PRT), between January 2008 and December 2012 in stable adult heart transplant recipients. Cumulative incidence rate (IR) of AR and infection pre- and postconversion, safety, tacrolimus dose and trough levels, concomitant immunosuppression, and PRT discontinuation were analyzed (intention-to-treat population).ResultsOverall, 467 patients (mean age, 59.3 [SD, 13.3] years) converted to PRT at 5.1 (SD, 4.9) years post transplant and were followed for 3.4 (SD, 1.5) years. During the 6 months post conversion, 5 patients (1.1%; 95% CI, 0.35%–2.48%) had an AR episode and IR was 2.2/100 patient-years (95% CI, 0.91–5.26). Incidence of rejection preconversion varied by time from transplant to conversion. Infection IR was similar post- and preconversion (9.2/100 patient-years [95% CI, 7.4–11.3] vs 10.6/100 patient-years [95% CI, 8.8–12.3], respectively; P = .20). Safety variables remained similar post conversion. The IR of mortality/graft loss was 2.3/100 patient-years (95% CI, 1.7–3.1).ConclusionsConversion from IRT to PRT in heart transplant recipients in Spain was associated with no new safety concerns and appropriate immunosuppressive effectiveness.