Late Post-transplant Period Research Articles

Medical management of metabolic and cardiovascular complications after liver transplantation.

Liver transplantation represents the only curative option for patients with end-stage liver disease, fulminant hepatitis and advanced hepatocellular carcinoma. Even though major advances in transplantation in the last decades have achieved excellent survival rates in the early post-transplantation period, long-term survival is hampered by the lack of improvement in survival in the late post transplantation period (over 5 years after transplantation). The main etiologies for late mortality are malignancies and cardiovascular complications. The latter are increasingly prevalent in liver transplant recipients due to the development or worsening of metabolic syndrome and all its components (arterial hypertension, dyslipidemia, obesity, renal injury, etc.). These comorbidities result from a combination of pre-liver transplant features, immunosuppressive agent side-effects, changes in metabolism and hemodynamics after liver transplantation and the adoption of a sedentary lifestyle. In this review we describe the most prevalent metabolic and cardiovascular complications present after liver transplantation, as well as proposing management strategies.

Risk factors for development and mortality of invasive pulmonary Aspergillosis in kidney transplantation recipients.

Invasive pulmonary aspergillosis (IPA) is a high mortality opportunistic infection among kidney transplant recipients. This study assessed the risk factors and outcomes of IPA after KT. A retrospective study was conducted at a tertiary-care referral hospital in Korea. Electronic medical records of patients diagnosed with IPA after KT between February 1995 and March 2015 were reviewed. The control patients comprised two patients who received KT before and after each IPA case. Twenty-six cases were diagnosed with IPA among 1963 recipients at a median of 58years old. The most common cause of end-stage renal disease was diabetic nephropathy. The median time to diagnosis was 161days. Delayed graft function was associated with the development of IPA. The overall 12-week mortality rate of IPA was 57.5%. Serum GM level ≥ 2 and BAL GM level ≥ 5 were associated with 12-week mortality in the Kaplan-Meier survival analyses. Approximately half of IPA in KT recipients developed during the late posttransplant period (> 6months), especially after treatment for acute rejection. Careful monitoring for IPA is required in patients with delayed graft function, DM, and who received rejection therapy. Higher serum and BAL GM were associated with 12-week mortality.

Lack of Relationship Between Renal Function and Genetic Variants of CYP3A4, CYP3A5, MDR1, MRP2, UGT1A9, UGT1A8, and UGT2B7 in Patients After Liver Transplantation in a 2-Year Follow-up

BackgroundThe prolonged survival time after liver transplantation (LTX) creates the possibility of the occurrence and development of complications in the late post-transplantation period. Deterioration of renal function is 1 of these complications. The nephrotoxicity of calcineurin inhibitors (CNIs) and their metabolites produced during pharmacokinetic processes in the body is also postulated. The study was aimed at assessment of the relationship between selected single gene polymorphisms (SNPs) for enzymes and transport proteins and change of estimated glomerular filtration rate (ΔeGFR) during 2-year follow-up in LTX patients. MethodsThe study involved 244 patients after LTX (105 women [43.0%] and 139 men [57.0%]) receiving tacrolimus (191; 78.3%) or cyclosporine A (53; 21.7%). The study protocol conforms with the Declaration of Helsinki. ResultsWe have not observed significant differences of ΔeGFR between groups distinguished based on analyzed genotypes in patients treated with cyclosporine or tacrolimus. ConclusionGenetic variations of CYP3A4, CYP3A5, MDR1, MRP2, UGT1A9, UGT2B7, and UGT2B7 tested in LTX recipients are not associated with kidney function during the 24-month follow-up.

Hyperbaric oxygenation in transplantology

The ability to eliminate any form of oxygen debt by transporting oxygen to organs and tissues, by dissolving it in body fluids, brings hyperbaric oxygenation to a new level of application in transplantology. The review discusses the pathophysiological aspects of hyperbaric oxygenation during ischemia and reinfusion, especially when used in transplantology, and also investigations on the use of hyperbaric oxygenation in model experiments and in clinical practice. Analysis of the efficacy of hyperbaric oxygenation therapy at various stages of the transplantation process (preconditioning, donation, organ storage, in the early and late post-transplant periods) allows us to conclude that this method should be more widely involved in transplantation practice.Authors declare no conflict of interest.

Research of subpopulation CD3+ CD4- CD8- double-negative T lymphocytes in kidney transplant recipients

Introduction. CD3+CD4- CD8- cells represent one of the subpopulations of T-regulatory lymphocytes. According to literature reports, an increase in the content of graft-infiltrating CD3+CD4- CD8- T cells was detected in the heart xenograft tissues of an experimental model with a long-term graft survival. The efficacy of CD3+CD4- CD8- infusion to induce skin graft tolerance was described. Some studies have shown that a decrease in CD3+CD4- CD8- content in peripheral blood of patients undergoing to hematopoietic stem cell transplantation was associated with the development of a graft-versus-host reaction.Objectives. To study changes in the values of CD3+CD4- CD8- double-negative T lymphocytes in peripheral blood in kidney transplant recipients.Material and methods. The study included 165 recipients who underwent kidney transplantation. The creatinine and urea concentrations in blood were determined before surgery, on day 7, and day 360 after transplantation. The content of CD3+CD4- CD8- lymphocytes was studied before surgery, on the 3rd, 7th, 30th, 90th, 180th and 360th days after surgery. Early graft function was assessed on day 7 after transplantation. The function was defined as a primary one at creatinine levels below 300 μmol/L. The graft dysfunction was defined as creatinine values equal to or greater than 300 μmol/L and the need for dialysis in the first week after surgery. The satisfactory graft function after a year was characterized by the blood creatinine level below 150 μmol/L, absent episodes of graft rejection, and no need for dialysis in the first year of follow-up. There were 4 groups of recipients formed. The first group included patients with the primary graft function and satisfactory late graft function. The second group included patients with the primary function and late graft dysfunction. The third group included patients with the primary dysfunction and late satisfactory function. The fourth group included patients with the primary and late graft dysfunction.Results. In the first and second groups, there were no significant differences in the blood level of CD3+CD4- CD8- during the year. After a year, a significant CD3+CD4- CD8- decrease was noted in the group with late graft dysfunction. A similar tendency was revealed in the third and fourth groups. In the fourth group (with late graft dysfunction), the level of CD3+CD4- CD8- was significantly lower only after a year of observation compared with the levels in the third group. A negative correlation was noted between the CD3+CD4- CD8- values and the creatinine and urea levels. Thus, high CD3+CD4- CD8- values in kidney transplant recipients after a year were associated with a satisfactory graft function.Conclusions. 1. A stable 1-year satisfactory kidney graft function is characterized by an increase in the blood level of CD3+CD4- CD8- T lymphocytes. 2. A kidney graft dysfunction in the late post-transplant period is characterized by a decrease in the blood level of CD3+CD4- CD8- T lymphocytes.Authors declare no conflict of interest.

Динамика CD3+ CD4+ CD8+ Т-лимфоцитов у реципиентов почечного трансплантата в раннем и позднем посттрансплантационном периоде

Динамика CD3+ CD4+ CD8+ Т-лимфоцитов у реципиентов почечного трансплантата в раннем и позднем посттрансплантационном периоде

ВОЗМОЖНОСТИ НЕИНВАЗИВНОЙ ДИАГНОСТИКИ ОТТОРЖЕНИЯ ТРАНСПЛАНТАТА ПЕЧЕНИ С ИСПОЛЬЗОВАНИЕМ ТЕРМИНАЛЬНОДИФФЕРЕНЦИРОВАННЫХ ЭФФЕКТОРНЫХ CD8+ Т-ЛИМФОЦИТОВ

Background. Immune-mediated graft dysfunction with the prevalence of 40% is one of the main problems of modern transplantology. Although percutaneous liver graft biopsy is associated with the development of different complications occurring in 2,2% of cases and can also lead to fatal outcome. Objective – to develop a noninvasive method of graft dysfunction diagnostics in the late post-transplant period using terminally differentiated effector CD8+ T-lymphocytes. Material and methods. There was carried out a single center observational retrospective case-control pilot study, including 45 recipients after orthotopic liver transplantation. According to the postoperative clinical course the patients were stratifed into 2 groups depending on the presence of graft rejection episodes. All patients got immunosuppressive therapy after liver transplantation. Immunophenotypes of the recipients were determined by flow cytometry method. Percutaneous liver graft biopsy was performed in all patients, the results of histological examination were evaluated according to the international Banff schema for grading liver allograft rejection. Results. The results of liver biopsies showed that 14 (31%) out of 45 patients had morphological signs of rejection. The patients with rejection had a reliably higher level of CD8+ Temra cells absolute number (0,23 (0,14;0,38) x 109/l) in comparison to those without rejection (0,09) (0,034;0,16) x 109/l (p=0,034)). The results of ROC-analysis have shown that the most optimal cut-off threshold of CD8+ T-lymphocytes level in immune-mediated graft dysfunction diagnostics in the late post-transplant period is 0,1882x109/l; sensitivity and specifcity in this case being 73,33 (95%; 44,9-92,0) and 96,55 (95%; 82,2-99,4) respectively. Conclusions. The increase of terminally differentiated effector CD8+ T-lymphocytes absolute number has diagnostic importance in patients with immune-mediated graft dysfunction in the late post-transplant period. High sensitivity and specifcity of cut-off threshold of CD8+ Temra lymphocytes absolute number in patients after liver transplantation as well as reliable difference between cell number in patients with normal postoperative period and in patients with immune-mediated graft dysfunction allow considering T-lymphocyte subpopulation as a rejection predictor in the late post-transplant period. The correlation between CD8+ T-lymphocyte absolute number and the results of histological examination makes the former an alternative and, what is more, safe noninvasive method in early diagnostics of liver graft rejection.

P6318Survival rate in patients with the identification of predictors for antibody mediated rejection

Abstract Introduction Antibody mediated rejection (AMR) is still an important issue in heart transplantation (HT). The standard methods of diagnosis and treatment remain controversial, whereas immunosuppressive therapy is mainly used to prevent cellular rejection. Purpose To determine predictors of AMR using the routine investigations in clinical practice. Methods During 7 years we conducted a single center study of 181 HT recipients. Patients were divided into 5 groups based on AMR and detected anti-HLA, such as DSA and non-DSA antibodies. Recipients underwent immunology screening and HLA antibodies tests, DSA; 2D-speckle-tracking echocardiography using the Kruskal-Wallis and Wilcoxon signed-rank tests; Spearman correlation, the table of critical values for the Pearson correlation. Kaplan-Meier curves were used to estimate the survival rate. Roc-analysis was used to measure the diagnostic accuracy. Statistical analysis was performed with the STATISTICA 10 (Tibco, USA). Results The study demonstrated the lowest survival in patients with anti-HLA antibodies, such as anti-HLA and non-DSA antibodies versus recipients without anti-HLA de novo. Survival in patients with DSA is 40%, and in patients without DSA is 68%. It should be noted that comparing of survival in patients with HLA identified in different post-transplant period showed that patients with HLA-antibodies identified in late post-transplant period had worse survival (50%) than recipients who developed antibodies in the early post-transplant period (75%). On the second stage of the study we conducted 2D-speckle-tracking echocardiography. At first we estimated 2D-STE parameters for the selected groups of patients in the first period of our study, and then during AMR and the late period of the study. AMR effectively reduces the parameters of deformation and mechanics, GLPS LV,%i = −9,94±1,37, RadS LV,% 19,36±3,66, Cir SLV,% −17,83±4,89, ROT APEX°,4,51±1,46, ROT BASE°, −4,75±2,12, ROT MID° 1,94±1,41, TWIST,% 8,90±1,85, RV-FWS,% −15,89±0,89. The possible criteria for diagnosis of AMR include global peak systolic strain, sensitivity (S) 86,2%, specificity (Sp) 90,4%, radial systolic strain, S 75,8%, Sp 84,5% circular systolic strain, S 78,6%, Sp 84,4%; left ventricular twist S 66,7%, Sp 94,2% (p<0,001). Conclusions There is a correlation between changes and parameters of 2D-speckle-tracking echocardiography. DSA limits the survival and increases the risk for AMR.

Lower limb pain following allogeneic hematopoietic stem cell transplantation in Japanese children

BackgroundPatients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) can experience musculoskeletal pains in their lower limbs in the early and late post-transplantation period. This study investigated demographics and clinical characteristics of the lower limb pain (LLP) among Japanese survivors of pediatric allo-HSCT. MethodsA total of 143 consecutive Japanese patients who had undergone allo-HSCT less than 18 years of age in a single institute between 2005 and 2015 were reviewed. Patients referred for in-house orthopedic evaluation of their sustained LLPs that impaired ambulation were defined as LLP group. Illness/transplantation-related parameters were compared between LLP group and non-LLP group. ResultsNinety children with a mean age of 8.5 years at transplantation were enrolled. Their median follow-up period following transplantation was 6.3 years (range, 2.1–12.5). There were four patients in LLP group, whose etiologies were AVN of the femoral head and insufficiency fracture (ISF) of the tibia or the medial cuneiform bone. Cumulative dose of steroids that administered from six months before transplantation to six months after discharge from hospitalization for transplantation was significantly higher in LLP group than non-LLP group. Additionally, the two groups differed significantly in terms of hospitalization period after transplantation. LLP caused by AVN of the femoral head manifested between six months and two years, whereas that caused by ISF within the first six months after transplantation. ConclusionsThe incidence of sustained LLP that impairs ambulation following contemporary allo-HSCT is not common in Japanese pediatric survivors. The risk of developing musculoskeletal LLP may increase with a higher steroid dosage in the peri-transplant period. LLP caused by AVN of the femoral head is likely to manifest later than that caused by ISF.

P3.26: Complications of the aortic conduit after intestinal transplantation with liver containing grafts - A single center experience

Introduction: Complications originating from the aortic conduit after intestinal transplantation (ITx) are currently not well described in the literature. The aim of this study was therefore to report a single center experience with diagnosis and management of complications affecting the donor aortic conduit after ITx with liver containing grafts. Methods: From 1998 to 2018, 35 ITx were performed in Gothenburg, Sweden. 29 of 35 grafts were liver containing intestinal allografts supplied by an aortic conduit (figure 1). The recipients were 24 adults (median age 38 years, range 16 – 66 years) and 5 children (median age 8 years, range 3– 10 years). The aortic conduit was anastomosed to either the aorta (n=20) or the iliac artery (n=9). The most common underlying conditions were intestinal failure (n=18) and non-resectable neuroendocrine pancreatic malignancies with liver metastases (n=6). Immunosuppression consisted primarily of ATG induction, tacrolimus and steroid bolus and tapering. Median donor age was 23 years (range 2–56 years) and median cold ischemic time was 443 min (range 90 - 873 min). Results: Four patients (4/29, 14%) presented with some type of complication originating from the aortic conduit requiring intervention (figure 2). The complications were: stenosis at the origin of the superior mesenteric artery (SMA) branch (n=1), acute bleeding caused by bacterial and fungal arteritis of the conduit (n=1), stenosis of the conduit caused by kinking of the conduit close to the aortic anastomosis (n=1), inflammatory aneurysm of the donor conduit, affecting the origins of the coeliac trunk and the SMA (n=1). The complications were diagnosed from months up to several years after ITx. Discussion In our experience, complications affecting the donor aortic conduit after ITx may present in the early or late post-transplantation period. The insidious clinical presentation and the relatively high prevalence (14%) may warrant specific post-transplantation surveillance of the donor aortic conduit. A timely multidisciplinary therapeutic approach involving interventional radiology was crucial. Figure 1. Donor aortic conduit anastomosed to the recipient aorta Figure 2. Complications affecting the donor conduit of 29 ITx with liver containing grafts

Neurological adverse events post allogeneic hematopoietic cell transplantation: major determinants of morbidity and mortality.

Despite advances in the field, diagnosis and management of the wide spectrum of neurological events post allogeneic hematopoietic cell transplantation (alloHCT) remain challenging. Therefore, we investigated their incidence, diagnosis, management and long-term prognosis in alloHCT recipients. We retrospectively recorded data from consecutive alloHCT recipients with or without neurological complications in our center. Among 758 alloHCT recipients, 127 (16.8%) presented with neurological complications. Complications developed in central nervous system (89.7%) during the late post-transplant period. Neurological adverse events included a wide spectrum of infectious and non-infectious etiologies. With a median follow-up of 11.4months, incidence of chronic graft-versus-host disease (GVHD) was 52.8%, relapse mortality 48.6%, transplant-related mortality 39.1% and 5-year overall survival (OS) 25.8% in patients with neurological complications. Timing of appearance of neurological complications, early or late, was associated only with acute and chronic graft-versus-host-disease/GVHD. Independent pre-transplant risk factors of neurological complications in the multivariate model were unrelated or alternative donors, ALL diagnosis and non-myeloablative conditioning. In multivariate analysis of post-alloHCT events, favorable OS was independently associated with resolution of neurological syndromes, absence of chronic GVHD and sibling transplantation. In our cohort, 10-year OS was significantly lower in patients with neurological complications and independently associated with acute and chronic GVHD, relapse, fungal and bacterial infections and neurological complications. Our large study with long-term follow-up highlights the wide spectrum of neurological complications in alloHCT. Accurate recognition is required for adequate management, a major determinant of survival. Thus, long-term increased awareness and collaboration between expert physicians is warranted.

Costs of Long-Term Post-Transplantation Care in Kidney Transplant Recipients

BackgroundSolid organ transplantations lead to improvements in patient survival and patient quality of life, as well as health care system economic benefits. However, over time, health problems can accumulate post-transplantation. Therefore, we hypothesized that in the late post-transplantation period, the costs of patient care increase.Material/MethodsWe retrospectively calculated costs of patient care in 306 randomly selected kidney transplant recipients who had different follow-up time periods after kidney transplantation (between 1 year and 25 years). Direct costs of inpatient care as well as outpatient care, from the perspective of a transplant center, were considered.ResultsThe mean costs, as well as median costs of post-transplantation care were the highest in the first post-transplantation year. Afterwards, the mean costs and median costs decreased, without an increase in costs of care in the late post-transplantation periods.ConclusionsFrom the perspective of a transplant center, costs of long-term post-kidney transplantation care did not increase in the late period, even as long as 25 years after transplantation. Our results confirmed that kidney transplantation is a modality of renal replacement therapy that can be associated with economic benefits even when considering long-term post-transplantation care.

Infectious complications after heart transplantation in patients screened with gene expression profiling.

The risk of infection after heart transplantation is highest within the first year and represents the leading cause of early mortality. In this cohort of patients enrolled in the Outcomes AlloMap Registry (OAR), we sought to describe infection episodes (IEp) resulting in hospitalization, in the early (<1 year) and late (≥1 year) post-transplant period and determine the impact of immunosuppression on incidence of infection. The primary aim was to assess the incidence and nature of IEp. The secondary aim was to evaluate the effect of potential risk factors, such as recipient age; sex; body mass index; panel-reactive antibodies; cytomegalovirus (CMV) primary mismatch; prednisone, tacrolimus, and sirolimus levels; and gene expression profile (GEP) score, in the development of IEp. The OAR comprises 1,504 patients, of whom 220 patients (14.6%) had an IEp during a median follow-up period of 382 days (interquartile range [IQR] 230 to 579 days). The cause-specific 5-year hazard ratio for any infection was 2.029 (p = 0.12). The pattern of early infection was consistent with nosocomial and opportunistic causes, whereas later infection was consistent with late-onset opportunistic and community-acquired etiologies. Sixty-two percent of the infections occurred early. In the time-dependent analysis, higher prednisone dose (log prednisone, hazard ratio [HR] 1.30, p = 0.022) was the most significant risk factor for all IEp. In the OAR cohort, the majority of infections occurred within 1 year after transplantation. Clinicians may consider more aggressive prednisone withdrawal in low-risk patients to reduce IEp.

1590. A Hybrid CMV Prevention Strategy Is Effective in Preventing CMV Disease Outcomes in Pediatric Solid Organ Transplant Patients

BackgroundOptimal CMV prevention strategies for pediatric solid-organ transplant (SOT) patients have not been clearly defined for early and late post-transplant periods.MethodsWe analyzed CMV prevention strategies in liver, kidney, heart, lung and intestinal SOT patients from 2005 to 2015 in our institution. A hybrid strategy was defined as prophylaxis for ≤6 months post-transplant and then transition to a pre-emptive strategy.ResultsOf 833 patients, 769 were prophylaxis and 62 were hybrid strategies. Compared with prophylaxis, hybrid patients were more likely to have a D−/R− CMV serology status, be ≤1 year old and have a heart transplant (P < 0.001). We found no significant differences in CMV disease frequency, rejection or mortality between hybrid and prophylaxis groups. In total, we found 13 cases of CMV disease, of which 1 was a hybrid and the rest a prophylaxis strategy. The median time to CMV disease was 1.5 years from transplant. We found more allograft rejection (n = 9) in patients with CMV disease compared with patients with CMV infection or no Infection. For the same comparisons, no significant difference was found for age or type of organ transplant. Late rejection was frequent (n = 6/13, 67%) in patients with CMV disease, and the majority were not started on empiric anti-virals with the rejection episode. In contrast, no CMV disease was found in patients who had late rejection and received empiric anti-viral with the rejection episode, even though these patients had increasing CMV DNAemia (P = 0.04).ConclusionIn the early post-transplant period, a hybrid CMV prevention strategy is effective with similar clinical outcomes compared with a prophylaxis strategy, even in younger CMV naïve patients and relatively more immune suppressed heart transplant patients. A hybrid strategy may provide effective long-term control of intermittent CMV replication as suggested by the low frequency of CMV disease in this group compared with prophylaxis. In the late post-transplant period, administering episodic empiric anti-virals with a rejection diagnosis may be necessary to prevent CMV disease associated with late rejection episodes.Disclosures All authors: No reported disclosures.

Natural history of mineral metabolism, bone turnover and bone mineral density in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol.

The skeletal effects of renal transplantation are not completely understood, especially in patients managed with a steroid minimization immunosuppressive protocol and long term. We enrolled 69 adult transplant recipients (39 males; ages 51.1 ± 12.2 years), free of antiresorptive therapy and managed with a steroid minimization immunosuppressive protocol, into a 5-year prospective observational study to evaluate changes in areal bone mineral density (aBMD), mineral metabolism and bone remodelling. Dual energy X-ray absorptiometry, laboratory parameters of mineral metabolism (including parathyroid hormone, sclerostin and fibroblast growth factor 23) and non-renal cleared bone turnover markers (BTMs) (bone-specific alkaline phosphatase, trimeric N-terminal propeptide and tartrate-resistant acid phosphatase 5b) were assessed at baseline and 1 and 5 years post-transplantation. The mean cumulative methylprednisolone exposure at 1 and 5 years amounted to 2.5 ± 0.8 and 5.8 ± 3.3 g, respectively. Overall, bone remodelling activity decreased after transplantation. Post-transplant aBMD changes were minimal and were significant only in the ultradistal radius during the first post-operative year {median -2.2% [interquartile range (IQR) -5.9-1.2] decline, P = 0.01} and in the lumbar spine between Years 1 and 5 [median 1.6% (IQR -3.2-7.0) increase, P = 0.009]. BTMs, as opposed to mineral metabolism parameters and cumulative corticosteroid exposure, associated with aBMD changes, both in the early and late post-transplant period. Most notably, aBMD changes inversely associated with bone remodelling changes. In summary, in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol, BMD changes are limited, highly variable and related to remodelling activity rather than corticosteroid exposure.

Vaccines in pediatric transplant recipients—Past, present, and future

Infections significantly impact outcomes for solid organ and hematopoietic stem cell transplantation in children. Vaccine-preventable diseases contribute to morbidity and mortality in both early and late posttransplant time periods. Several infectious diseases and transplantation societies have published recommendations and guidelines that address immunization in adult and pediatric transplant recipients. In many cases, pediatric-specific studies are limited in size or quality, leading to recommendations being based on adult data or mixed adult-pediatric studies. We therefore review the current state of evidence for selected immunizations in pediatric transplant recipients and highlight areas for future investigation. Specific attention is given to studies that enrolled only children.

Evaluation of Cell-mediated Immune Response by QuantiFERON Monitor® Assay in Kidney Transplant Recipients

Introduction All kidney transplant recipients (KTRs) require immunosuppression, the net level of which is difficult to assess. Current practice in assessing immune reactivity is to monitor levels of some immunosuppressive drugs. QuantiFERON Monitor® (QFM) is an in vitro diagnostic test that detects interferon-γ (IFN-γ) release in peripheral blood. Its clinical utility in assessment of the net state of immunosuppression in KTRs has not been well studied. The aim of our study was to evaluate the discriminating value of QFM testing results for infection and rejection in a single-centre cohort of KTRs. Methods Ninety adult KTRs from a tertiary transplant centre were recruited for this observational cohort pilot study. They were divided into three groups by indication for undertaking the QFM test: control (n=59), rejection (n=11) and infection (n=20). The inclusion criteria into the infection group were clinical signs, or symptoms of an infection with elevated CRP (>20mg/L). Recipients in the rejection group had biopsy-proven kidney rejection. The control group consisted of stable KTRs at various times post-transplant. QFM (Qiagen, Hilden, Germany) was performed according to the manufacturer instructions. Results Fifty-nine patients were male and 31 female. The mean age was 52.5±1.4 years and mean time after transplantation was 2.6±0.4 years. In the entire cohort age, gender, time after transplantation, serum creatinine concentration, tacrolimus concentration, mycophenolate dose and steroid dose showed no statistically significant association with QFM results. Mean QFM results were 136.24±27.85 IU/mL, 24.84±5.71 IU/mL and 69.44±25.19 IU/mL in the control, infection and rejection group (p=0.04, by analysis of variance), respectively (Figure 1). Post-hoc LSD test revealed a significant difference in QFM results between the control and infection groups (p=0.01, Figure 1), with area under the curve in ROC analysis of 0.72±0.06 (p=0.004, Figure 2). There was no statistically significant difference in QFM results between viral and bacterial infections.Discussion A recent study involving pre-transplant liver cirrhosis patients showed lowered QFM values in patients with infective complications, which corroborates our results[1]. However, unlike another study in liver transplant patients, our study did not demonstrate an increase in QFM values in late post-transplant period[2]. Conclusion QFM results are lower in KTRs presenting with infections. QFM may be used to detect patients at risk for infective complications, but further prospective studies are required.

Frequency of acute antibody mediated rejection in renal allograft biopsies as detected by morphological findings and C4d immunostaining

Introduction: Acute antibody-mediated rejection (AMR) detection using C4d immunofluorescence in combination with histopathological examination in renal allograft biopsy is a gold standard for AMR. This study will be the first one in this context in Pakistan and will generate local data. Objectives: To determine the frequency of AMR in renal allograft biopsies as detected by morphological findings and C4d immunostaining. Patients and Methods: We performed a prospective cross-sectional study at histopathology department, Shifa international hospital, Islamabad. Allograft biopsies which were performed for diagnosis of graft dysfunction were included. Interpretation was performed, according to Banff 2013. All statistical analysis of the data was performed using statistical software SPSS 20. Results: A total of 60 biopsies, including 59 (98.3%) males and 1 (1.7%) female were evaluated. Age range was 15-65 years (mean 34.6 ± 11.8). Out of 60 biopsies, in the early post-transplant period, 14 (23.3%) out of 60 cases were diagnosed as AMR on morphology. One (1.6%) case had strong C4d positive in absence of morphological features. Out of these cases, 8 (57.1%) showed C4d positivity, 2 (14.3%) showed focal C4d positivity while 4 (28.6%) were C4d negative. In the late post-transplant period, chronic allograft nephropathy (CAN) cases were 19 (31.7%). Out of these cases, 13 (68.4%) showed morphological features of AMR. C4d was positive 11 (57.9%) and C4d was negative in 2 cases (10.5%). Conclusion: C4d positivity favors AMR; however, it can be seen in absence of morphological features.

High urinary interleukin-2 in late post-transplant period portends a risk of decline in kidney allograft function: a preliminary study

BackgroundPredictive factors for the rate of decline in kidney allograft function beyond the first post-transplant year have not been thoroughly studied. We aimed to determine whether a single measurement of serum and urinary interleukin 2, interleukin 8 and interleukin 10 at 1–15 years after kidney transplantation could predict a decline in estimated glomerular filtration rate (eGFR) over a 2-year period.ResultsGreater serum concentrations of interleukin 8 and interleukin 10 in 30 recipients of kidney allograft at enrollment were associated with lower eGFR after 1 year (beta = − 0.616, p = 0.002 and beta = − 0.393, p = 0.035, respectively), whereas serum concentrations of interleukin 8 also demonstrated significant association with eGFR after 2 years of follow-up (beta = − 0.594, p = 0.003). Higher urinary interleukin 2 concentrations were associated with lower eGFR at baseline (rho = − 0.368, p = 0.049) and after the first (beta = − 0.481, p = 0.008) and the second year (beta = − 0.502, p = 0.006) of follow-up. Higher urinary interleukin 2 concentrations predicted certain decline in eGFR of ≥ 25% from baseline after 1 year of follow-up in logistic regression: odds ratio = 2.94, confidence interval 1.06–8.18, p = 0.038. When combined with time after transplantation, urinary interleukin 2 demonstrated good accuracy in predicting rapid decline in eGFR by > −5 mL/min/1.73 m2/year (area under the receiver-operator characteristic curve: 0.855, confidence interval 0.687–1.000, and p = 0.008).ConclusionsOur findings suggest that urinary interleukin 2 in the late period after kidney transplantation has promise in identifying patients who are at risk for progressive loss of graft function in a short-time perspective and need closer monitoring.

Liver Transplantation in Patients With Cardiac Disease.

Liver transplantation (LT) is a unique surgical procedure that has major hemodynamic and cardiovascular implications. Recently, there has been significant interest focused on cardiovascular issues that affect LT patients in all phases of the perioperative period. The preoperative cardiac evaluation is a major step in the selection of LT candidates. LT candidates are aging in concordance with the general population; cardiovascular disease and their risk factors are highly associated with older age. Underlying cardiovascular disease has the potential to affect outcomes in LT patients and has a major impact on candidate selection. The prolonged hemodynamic and metabolic instability during LT may contribute to adverse outcomes, especially in patients with underlying cardiovascular disease. Cardiovascular events are not unusual during LT; transplant anesthesiologists must be prepared for these events. Advanced cardiovascular monitoring techniques and treatment modalities are now routinely used during LT. Postoperative cardiovascular complications are common in both the early and late posttransplant periods. The impact of cardiac complications on posttransplant mortality is well recognized. Emerging knowledge regarding cardiovascular disease in LT patients and its impact on posttransplant outcomes will have an important role in guiding the future perioperative management of LT patients.