Graft Rejection Episodes Research Articles

Factors influencing renal graft survival: 7-Year experience of a single center

Background and objectiveThe demand for kidney transplants exceeds the existing supply. This leads to a recently growing interest of research in the area of factors that could prolong graft long-term outcomes and survival. In Lithuania, approximately 90% of kidney transplantations are from deceased donors. Donor organs are received and shared only inside the country territory in Lithuania; therefore, donor data is accurate and precise. This study was performed to present particularities of kidney transplantation data in Lithuania and to identify the effect of donor and recipient factors and histologic findings on renal graft outcomes. The aim of this study was to identify the effect of donor and recipient factors and histologic findings on renal graft outcomes. Materials and methodsWe analyzed the influence of deceased donor and recipient factors and histological findings on the graft function in 186 renal transplant patients. Graft survival was estimated within the first year after transplantation. ResultsThe donors and recipients were older in worse eGFR group 1 year after transplantation. Dissimilarity of degree of glomerulosclerosis (GS), interstitial fibrosis (IF) and arteriolar hyalinosis (AH) were significant in inferior and superior renal function groups (GS >20% 11.4 vs. 0%, P=0.017; IF 9.3 vs. 0%, P=0.034; AH 69 vs. 26.2%, P<0.001). Nine independent variables were significantly associated with a worse renal transplant function 1 year posttransplantation: AH (OR=6.287, P<0.001), an episode of urinary tract infection (OR=2.769, P=0.020), acute graft rejection (OR=3.605, P=0.037), expanded criteria (OR=4.987, P=0.001), female gender donors (OR=3.00, P=0.014), cerebrovascular disease caused donor brain death (OR=5.00, P=0.001), donor's age (OR=1.07, P<0.001), and recipient's age (OR=1.047, P=0.022). Worse renal graft survival 1 year posttransplantation was associated with a delayed graft function and a higher level of glomerulosclerosis in time-zero biopsy. ConclusionsDonor factors, such as age, female gender, brain death of cerebrovascular cause and expanded criteria donor status had a significant negative impact on the renal graft function 1 year after transplantation. Recipients’ age, urinary tract infection and acute graft rejection episodes after transplantation were associated with a worse kidney function 1 year after transplantation. Lower 1-year graft survival was related to a delayed graft function (DGF) and a higher degree of glomerulosclerosis.

Efficacy and tolerability of interferon-free antiviral therapy in kidney transplant recipients with chronic hepatitis C

The development of direct-acting antiviral agents (DAAs) is a major step forward in the treatment of hepatitis C (HCV). The aims of the study were to evaluate the efficacy and tolerability of DAAs in kidney transplant (KT) recipients. Hepa-C is a Spanish registry of patients treated with DAAs in which clinical, virological and analytical data were prospectively included. We report on the data from 103 KT recipients who received DAAs. The most commonly used DAAs combinations were sofosbuvir/ledipasvir (n=59, 57%) and sofosbuvir+daclatasvir (n=18, 17%). Ribavirin was used in 41% of patients. Sustained viral response after 12weeks (SVR12) rate was 98%. Grade 2 or 3 anemia appeared in 14 (33%) of patients receiving ribavirin and in 9 (15%) without (p=0.03). There were three episodes of acute humoral graft rejection. No patient discontinued therapy due to adverse events. Importantly, 57 (55%) patients required immunosuppression dose adjustment. Overall, there were no statistically significant differences in the mean level of serum creatinine, eGFR and proteinuria before and after treatment. Nonetheless, seventeen (16%) patients experienced renal dysfunction (increase in serum creatinine >25%) during antiviral therapy, of whom 65% were cirrhotic in comparison with only 29% cirrhotic patients who did not develop significant renal dysfunction (p=0.004). Antiviral therapy with DAAs was highly efficacious and safe in KT recipients. Nevertheless, a non-negligible number of patients, most of them cirrhotic, developed mild allograft dysfunction and a significant proportion of patients required immunosuppression dose adjustment, warranting a close follow-up during therapy. Infection by hepatitis C virus is often found in kidney transplant patients and its presence increases mortality and graft failure. We investigated the efficacy and safety of the new direct-acting hepatitis C antivirals in this population, in which previous information is scarce. Our data shows that, as occurs in the non-transplant setting, new anti-HCV antivirals are highly efficacious kidney transplant patients. Overall, this therapy is also quite safe, although worsening of renal function is observed in 16% of patients warranting a close follow-up observation of graft function during antiviral therapy.

Monocyte Chemoattractant Protein-1 (MCP-1/CCL2) Levels and Its Association with Renal Allograft Rejection

ABSTRACTBackground: CCL2 is a chemoattractant for monocytes/macrophages, T cells, and natural killer cells. It is shown to be involved in the immunological responses against renal allograft. This study was conducted to access the role of urinary CCL2 expression in predicting the rejection episodes in renal transplant patients.Method: A total of 409 urine samples included in this study. The samples were consisted of (a) biopsy-proven graft rejection (n = 165); (b) non-rejection (n = 93); (c) non-biopsy stable-graft (n = 42), and (d) healthy renal donors (n = 109). The samples were quantified for the CCL2 using the MCP-1/CCL2 ELISA kit. The data were analyzed using the Statistical Package for Social Sciences (SPSS®) and MedCalc® statistical software.Results: Results showed that the CCL2 levels were significantly increased in rejection group when compared with the non-rejection, stable-graft, and control, P < 0.05. The receiver operating curve’s characteristics illustrated that the urinary CCL2 level is a good predictor for graft rejection, with an area under the curve of 0.81 ± 0.03 with optimum sensitivity and specificity of 87% and 62%, respectively, at a cut-off value of 198 pg/mL. Kaplan–Meier curve also showed better cumulative rejection-free graft survival time in group with less than 198 pg/mL of CCL2 as compared to those with expression levels of more than 198 pg/mL (30 weeks vs. 3 weeks; log-rank test, P < 0.001).Conclusion: In our study, noninvasive investigation of CCL2 levels in urine has showed potential to predict rejection episodes. It is suggested that the CCL2, with others markers, may help in early detection and monitoring of graft rejection episodes.

Safety outcomes and long-term effectiveness of ex vivo autologous cultured limbal epithelial transplantation for limbal stem cell deficiency

PurposeTo evaluate the safety and effectiveness of ex vivo autologous cultured limbal stem cell transplantation (CLET).MethodsWe reviewed the clinical records of 59 consecutive patients treated with 65 CLETs. Efficacy was...

Matched-pair analysis: identification of factors with independent influence on the development of PTLD after kidney or liver transplantation.

BackgroundPost-transplant lymphoproliferative disorder (PTLD) adversely affects patients’ long-term outcome.MethodsThe paired t test and McNemar’s test were applied in a retrospective 1:1 matched-pair analysis including 36 patients with PTLD and 36 patients without PTLD after kidney or liver transplantation. Matching criteria were age, gender, indication, type of transplantation, and duration of follow-up. All investigated PTLD specimen were histologically positive for EBV. Risk-adjusted multivariable regression analysis was used to identify independence of risk factors for PTLD detected in matched-pair analysis. The resultant prognostic model was assessed with ROC-curve analysis.ResultsPatients suffering with PTLD had shorter mean survival (p = 0.004), more episodes of CMV infections or reactivations (p = 0.042), and fewer recipient HLA A2 haplotypes (p = 0.007), a tacrolimus-based immunosuppressive regimen (p = 0.052) and higher dosages of tacrolimus at hospital discharge (Tac dosage) (p = 0.052). Significant independent risk factors for PTLD were recipient HLA A2 (OR = 0.07, 95 % CI = 0.01–0.55, p = 0.011), higher Tac dosages (OR = 1.29, 95 % CI = 1.01–1.64, p = 0.040), and higher numbers of graft rejection episodes (OR = 0.38, 95 % CI = 0.17–0.87, p = 0.023). The following prognostic model for the prediction of PTLD demonstrated good model fit and a large area under the ROC curve (0.823): PTLD probability in % = Exp(y)/(1 + Exp(y)) with y = 0.671 − 1.096 × HLA A2-positive recipient + 0.151 × Tac dosage − 0.805 × number of graft rejection episodes.ConclusionsThis study suggests prognostic relevance for recipient HLA A2, CMV, and EBV infections or reactivations and strong initial tacrolimus-based immunosuppression. Patients with risk factors may benefit from intensified screening for PTLD.

Impact of De Novo and Preexisting Inflammatory Bowel Disease on the Outcome of Orthotopic Liver Transplantation

Diarrhea is a common problem in the setting of solid-organ transplantation, especially orthotopic liver transplant (OLT). De novo or preexisting inflammatory bowel disease (IBD) is one of the differential diagnoses. The aims of our study were to evaluate the frequency of de novo IBD in patients with OLT and to assess the impact of de novo IBD and preexisting IBD on the outcome of OLT. This case-control study included all eligible patients who had OLT from January 2001 to December 2009. The study group included all patients who had a biopsy-proven diagnosis of IBD after their OLT (the de novo IBD group). The control groups included patients with existing IBD before OLT and those without IBD before and after OLT. The groups were matched based on their underlying diagnoses of end-stage liver disease. Univariate and multivariate analyses were performed. A total of 66 subjects were included in the study. The mean age was 45.4 ± 13.4 years, with 44 (66.7%) being male. Fifteen patients (23%) had de novo IBD, 21 (32%) had existing IBD before OLT, and 30 (45%) had no underlying IBD before or after OLT. There were no significant differences between the 2 IBD groups in any of the IBD characteristics, including IBD medications. Subjects without IBD were more likely to receive mycophenolate mofetil within 1 week of OLT than those in the de novo or preexisting IBD (70% versus 23% P = 0.018). Episodes of graft rejection were more commonly observed in subjects with preexisting IBD (52%) than de novo IBD (27%) or no IBD (20%) (P = 0.045). The rate of retransplantation was highest in the de novo IBD group followed by the preexisting IBD group and non-IBD group (20% versus 14% versus 0%; P = 0.029). Combined together, patients with IBD in the setting of OLT were more likely to be retransplanted than those without IBD (16.7% versus 0%, P = 0.045). In multivariate analysis, we found that patients with IBD were 6.7 (95% confidence interval, 1.9-23.9) times more likely to have an adverse outcome after liver transplant (P = 0.004), after adjusting for primary sclerosing cholangitis. De novo IBD can occur in patients after OLT. De novo IBD and preexisting IBD were found to be associated with a higher risk for graft failure, suggesting that early diagnosis and closer monitoring of the patients at risk are critical.

Should Asymptomatic Bacteriuria Be Systematically Treated in Kidney Transplant Recipients? Results From a Randomized Controlled Trial.

The indication for antimicrobial treatment of asymptomatic bacteriuria (AB) after kidney transplantation (KT) remains controversial. Between January 2011 and December 2013, 112 KT recipients that developed one episode or more of AB beyond the second month after transplantation were included in this open-label trial. Participants were randomized (1:1 ratio) to the treatment group (systematic antimicrobial therapy for all episodes of AB occurring ≤24 mo after transplantation [53 patients]) or control group (no antimicrobial therapy [59 patients]). Systematic screening for AB was performed similarly in both groups. The primary outcome was the occurrence of acute pyelonephritis at 24-mo follow-up. Secondary outcomes included lower urinary tract infection, acute rejection, Clostridium difficile infection, colonization or infection by multidrug-resistant bacteria, graft function and all-cause mortality. There were no differences in the primary outcome in the intention-to-treat population (7.5% [4 of 53] in the treatment group vs. 8.4% [5 of 59] in the control group; odds ratio [OR] 0.88, 95% confidence interval [CI] 0.22-3.47) or the per-protocol population (3.8% [1 of 26] in the treatment group vs. 8.0% [4 of 50] in the control group; OR 0.46, 95% CI 0.05-4.34). Moreover, we found no differences in any of the secondary outcomes. In conclusion, systematic screening and treatment of AB beyond the second month after transplantation provided no apparent benefit among KT recipients (NCT02373085).

Immunosuppressive drug therapy for preventing rejection following lung transplantation in cystic fibrosis.

For people with cystic fibrosis and advanced pulmonary damage, lung transplantation is an available and viable option. However, graft rejection is an important potential consequence after lung transplantation. Immunosuppressive therapy is needed to prevent episodes of graft rejection and thus subsequently reduce morbidity and mortality in this population. There are a number of classes of immunosuppressive drugs which act on different components of the immune system. There is considerable variability in the use of immunosuppressive agents after lung transplantation in cystic fibrosis. While much of the research in immunosuppressive drug therapy has focused on the general population of lung transplant recipients, little is known about the comparative effectiveness and safety of these agents in people with cystic fibrosis. This is an update of a previously published review. To assess the effects of individual drugs or combinations of drugs compared to placebo or other individual drugs or combinations of drugs in preventing rejection following lung transplantation in people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register and scanned references of the potentially eligible study. We also searched the www.clinicaltrials.gov registry to obtain information on unpublished and ongoing studies.Date of latest search: 19 May 2015. Randomised and quasi-randomised studies. We independently assessed the studies identified from our searches for inclusion in the review. Should eligible studies be identified and included in future updates of the review, we will independently extract data and assess the risk of bias. While two studies met our inclusion criteria, we did not include them in the review because the investigators of the studies did not report any information specific to people with cystic fibrosis. Our attempts to obtain this information have not yet been successful. We will include any provided data in future updates of the review. The lack of currently available evidence makes it impossible to draw conclusions about the comparative efficacy and safety of the various immunosuppressive drugs among people with cystic fibrosis after lung transplantation. A recent Cochrane review comparing tacrolimus with cyclosporine in all lung transplant recipients (not restricted to those with cystic fibrosis) reported no significant difference in mortality and risk of acute rejection. However, tacrolimus use was associated with lower risk of broncholitis obliterans syndrome and arterial hypertension and higher risk of diabetes mellitus. It should be noted that this wider review contained only a small number of included studies (n = 3) with a high risk of bias. Additional randomised studies are required to provide evidence for the benefit and safety of the use of immunosuppressive therapy among people with cystic fibrosis after lung transplantation.

Chronic Renal Transplant Rejection and Possible Anti-Proliferative Drug Targets.

The global prevalence of renal transplants is increasing with time, and renal transplantation is the only definite treatment for end-stage renal disease. We have limited the acute and late acute rejection of kidney allografts, but the long-term survival of renal tissues still remains a difficult and unanswered question as most of the renal transplants undergo failure within a decade of their transplantation.Among various histopathological changes that signify chronic allograft nephropathy (CAN), tubular atrophy, fibrous thickening of the arteries, fibrosis of the kidney interstitium, and glomerulosclerosis are the most important. Moreover, these structural changes are followed by a decline in the kidney function as well. The underlying mechanism that triggers the long-term rejection of renal transplants involves both humoral and cell-mediated immunity. T cells, with their related cytokines, cause tissue damage. In addition, CD 20+ B cells and their antibodies play an important role in the long-term graft rejection. Other risk factors that predispose a recipient to long-term graft rejection include HLA-mismatching, acute episodes of graft rejection, mismatch in donor-recipient age, and smoking.The purpose of this review article is the analyze current literature and find different anti-proliferative agents that can suppress the immune system and can thus contribute to the long-term survival of renal transplants. The findings of this review paper can be helpful in understanding the long-term survival of renal transplants and various ways to improve it.

Immunosuppressants for the prophylaxis of corneal graft rejection after penetrating keratoplasty.

Immunosuppressants for the prophylaxis of corneal graft rejection after penetrating keratoplasty.

Delta Neutrophil Index as a Marker for Differential Diagnosis between Acute Graft Pyelonephritis and Acute Graft Rejection.

IntroductionThe delta neutrophil index (DNI) is the fraction of circulating immature granulocytes, which reflect infectious and/or septic condition. Acute graft pyelonephritis (AGPN) versus acute graft rejection is a frequently encountered diagnostic and therapeutic dilemma in kidney transplant recipients, but little is known about the clinical usefulness of DNI value in the differentiation of the two conditions.Material & MethodsA total of 90 episodes of AGPN or acute graft rejection were evaluated at the Kangdong Sacred Heart Hospital between 2008 and 2014. We performed retrospective analysis of demographic, clinical, and laboratory parameters data. Receiver operating curves (ROC) and multivariate logistic regression were conducted to ascertain the utility of DNI in discriminating between AGPN and acute graft rejection.ResultsAGPN group had significantly higher DNI values than acute graft rejection group (2.9% vs. 1.9%, P < 0.001). The area under the ROC curve for DNI value to discriminate between AGPN and acute graft rejection was 0.85 (95% confidence interval [CI]; 0.76–0.92, P < 0.001). A DNI value of 2.7% was selected as the cut-off value for AGPN, and kidney transplant recipients with a DNI value ≥ 2.7% were found to be at a higher risk of infection than those with a DNI < 2.7% (odd ratio [OR] 40.50; 95% CI 8.68–189.08; P < 0.001). In a multivariate logistic regression analysis, DNI was a significant independent factor for predicting AGPN after adjusting age, sex, log WBC count, log neutorphil count, log lymphocyte count, CRP concentration, and procalcitonin concentration (OR 4.32; 95% CI 1.81–10.34, P < 0.001).ConclusionsThis study showed that DNI was an effective marker to differentiate between AGPN and acute graft rejection. Thus, these finding suggest that DNI may be a useful marker in the management of these patients.

Loteprednol Etabonate 0.5% Gel Vs. Prednisolone Acetate 1% Solution After Descemet Membrane Endothelial Keratoplasty: Prospective Randomized Trial.

To compare intraocular pressure (IOP) elevation and graft rejection with loteprednol etabonate 0.5% gel and prednisolone acetate 1% solution after Descemet membrane endothelial keratoplasty (DMEK). In this prospective, evaluator-masked trial, 167 patients were randomized to loteprednol or prednisolone in a 1:1 ratio 1 month after DMEK; 66 fellow eyes were enrolled and assigned to the opposite treatment. Dosing was 4 times daily for 2 months, thrice daily for 1 month, twice daily for 1 month, and once daily for 7 months. The main outcomes were IOP elevation (defined as IOP ≥ 24 mm Hg or an increase of ≥10 mm Hg over the baseline preoperative level) and immunologic rejection episodes, assessed by Kaplan-Meier survival analysis and proportional hazards modeling. A total of 233 eyes were assigned to treatment. Loteprednol etabonate 0.5% gel and prednisolone acetate 1% solution were equally effective in preventing immunologic rejection episodes; none (0%) occurred with either treatment (P = 1). IOP elevation was twice as likely in the prednisolone-treated eyes (relative risk = 2.3, 95% confidence interval: 1.2-4.5, P = 0.016). The proportion with IOP elevation was 25% in prednisolone-treated eyes versus 11% in loteprednol-treated eyes (P = 0.013). In 66 subjects with fellow eyes assigned to opposite treatments, an IOP increase of ≥10 mm Hg was significantly more likely in the prednisolone-treated eye (P = 0.031). Loteprednol etabonate 0.5% gel was as effective as prednisolone acetate 1% solution in preventing immunologic graft rejection episodes after DMEK and was significantly less likely to cause IOP elevation.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01853696.

Comparison of Sulfur Hexafluoride 20% versus Air Tamponade in Descemet Membrane Endothelial Keratoplasty

To compare clinical outcomes using 20% sulfur hexafluoride (SF6) versus 100% air as a tamponade for graft attachment in Descemet membrane endothelial keratoplasty (DMEK). Retrospective, comparative, interventional case series. Pseudophakic patients with Fuchs' endothelial dystrophy or pseudophakic bullous keratopathy that underwent DMEK using either 20% SF6 (group 1; 42 eyes) or 100% air (group 2; 39 eyes) tamponade between April 2010 and August 2011. A bimanual infusion technique was used to introduce and position the donor endothelium-Descemet membrane graft tissue. Outcome measures were analyzed at the following time points: before surgery, 3 and 6 months after surgery, and at yearly intervals up to at least 3 years. Corrected distance visual acuity (CDVA), manifest refraction, pachymetry, central endothelial cell count (cECC), complications, and rebubbling rates. Three years after surgery, mean CDVA improved from 0.48±0.45 logarithm of the minimum angle of resolution (logMAR) to 0.04±0.23 in group 1 (P < 0.001) and from 0.67±0.45 logMAR to 0.09±0.13 logMAR in group 2 (P < 0.001). The percentage of eyes with CDVA of 20/25 or more was 85.71% (36/42 eyes) in group 1 and 82.05% (32/39 eyes) in group 2 (P = 0.43). Mean preoperative cECCs and at last follow-up were: group 1, 2525±338 cells/mm(2) and 1758 ± 398 cells/mm(2) (mean cell loss, 30±11%; P = 0.008); and group 2, 2492±204 cells/mm(2) and 1678±373 cells/mm(2) (mean cell loss, 32±13%; P = 0.008). Endothelial cell loss was similar in both groups (P = 0.65). Intracameral air reinjection was needed in 1 patient in group 1 (2.38%) and in 5 patients in group 2 (12.8%). The rebubbling rate was significantly higher in group 2 (P = 0.004). No episodes of immunologic graft rejection were documented. Although clinical outcomes and corneal endothelial cell loss were similar in both groups, tamponade with 20% SF6 yielded a significantly lower incidence of graft detachments that may warrant its routine use in DMEK. Longer-term, randomized studies are needed to recommend this approach fully.

Safety and efficacy of femtosecond laser–assisted arcuate keratotomy to treat irregular astigmatism after penetrating keratoplasty

To determine the refractive efficacy, predictability, stability, and complication rate of Intralase femtosecond laser-assisted astigmatic keratotomy (AK) for irregular astigmatism after penetrating keratoplasty (PKP). Ophthalmology Department, Hôtel-Dieu, Paris, France. Retrospective case series. Femtosecond laser-assisted AK was performed to treat high irregular astigmatism (>5.0 diopters [D]) after PKP. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities, manifest refraction, vector analysis, and complications were evaluated. The study evaluated 62 eyes of 57 patients over a mean follow-up of 28 months ± 3.5 (SD). Preoperatively, the mean CDVA was 0.51 ± 0.26 logMAR and the mean UDVA was 0.98 ± 0.24 logMAR; 6 months postoperatively, the mean CDVA and UDVA improved to 0.40 ± 0.22logMAR and 0.60 ± 0.2 logMAR, respectively (both P < .01). The mean preoperative absolute astigmatism was 7.1 ± 1.72 D; 6 months postoperatively, the mean refractive astigmatism was2.6 ± 2.4 D (P < .001). The UDVA, CDVA, and astigmatism remained stable up to the end of follow-up. The efficacy index was 0.81 at 6 months and 0.67 at 2 years. There were 2 cases of microperforation, 3 cases of infectious keratitis, 3 graft rejection episodes, and 1 case of endophthalmitis. Overcorrection occurred in 12 eyes. Femtosecond laser-assisted AK was effective in reducing irregular astigmatism after PKP. Predictability of astigmatism correction is variable over time with a decrease in the efficacy index 2 years postoperatively. Refinement of the treatment nomogram for femtosecond laser-assisted AK for high astigmatism after PKP remains a major issue. No author has a financial or proprietary interest in any material or method mentioned.

(333) - Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Heart Transplant Recipients After Conversion to Everolimus Therapy

Background: Due to the lack of nephrotoxic activity, proliferation signal inhibitors (PSI) such as everolimus are recommended for immunosuppression after heart transplantation, but the assessment of renal function in patients receiving PSI has led to conflicting results. We examined renal integrity and function using neutrophil gelatinase-associated lipocalin (NGAL) and conventional markers [plasma creatinine, cystatin C, urine albumin, a1-microglobulin (a1M)] in heart transplant patients, who underwent conversion to everolimus due to allograft vasculopathy, graft rejection episodes, or renal function deterioration, and in patients maintained on calcineurin inhibitors (CNI). Methods: This cross-sectional study included 121 consecutive heart transplant recipients: 44 patients received CNI-free immunosuppressive therapy with everolimus and 77 patients received CNI. Renal parameters were determined in plasma and urine samples using standard enzymatic or immunochemical methods. Results: Heart transplant recipients receiving everolimus therapy had significantly lower NGAL concentrations in plasma [median (95% CI): 128 (97–176) ng/mL vs. 252 (224–283) ng/mL, p < 0.001] and urine [median (95% CI): 6.4 (4.5–7.6) ng/g vs. 15.7 (10.2–25.9) ng/g creatinine, p < 0.001]. In contrast, no significant differences were observed between everolimusand CNI-treated groups with regard to creatinine and cystatin C, as well as urine albumin and a1M levels. Significant correlations were noted between plasma NGAL and creatinine (r = 0.42, p < 0.001), cystatin C (r = 0.44, p < 0.001), N-terminal brain natriuretic propeptide (r = 0.31, p < 0.01) and indicators of chronic inflammation [lipoprotein-associated phospholipase A2 (Lp-PLA2), r = 0.31, p < 0.01] and soluble CD40 ligand (sCD40L, r = 0.22, p < 0.05), and between urinary NGAL and a1M (r = 0.21, p < 0.05). Multiple regression analysis indicated that cystatin C and Lp-PLA2 were the best predictors of plasma NGAL. Conclusion: The present study documents reduced plasma and urinary NGAL levels in the absence of differences in conventional renal parameters in patients on CNI-free immunosuppressive therapy with everolimus. These results support favorable effects of everolimus on renal integrity in heart transplant recipients. 2015 Published by Elsevier Ltd on behalf of Japanese College of Cardiology.

Neutrophil gelatinase-associated lipocalin (NGAL) in heart transplant recipients after conversion to everolimus therapy

BackgroundDue to the lack of nephrotoxic activity, proliferation signal inhibitors (PSI) such as everolimus are recommended for immunosuppression after heart transplantation, but the assessment of renal function in patients receiving PSI has led to conflicting results. We examined renal integrity and function using neutrophil gelatinase-associated lipocalin (NGAL) and conventional markers [plasma creatinine, cystatin C, urine albumin, α1-microglobulin (α1M)] in heart transplant patients, who underwent conversion to everolimus due to allograft vasculopathy, graft rejection episodes, or renal function deterioration, and in patients maintained on calcineurin inhibitors (CNI). MethodsThis cross-sectional study included 121 consecutive heart transplant recipients: 44 patients received CNI-free immunosuppressive therapy with everolimus and 77 patients received CNI. Renal parameters were determined in plasma and urine samples using standard enzymatic or immunochemical methods. ResultsHeart transplant recipients receiving everolimus therapy had significantly lower NGAL concentrations in plasma [median (95% CI): 128 (97–176)ng/mL vs. 252 (224–283)ng/mL, p<0.001] and urine [median (95% CI): 6.4 (4.5–7.6)ng/g vs. 15.7 (10.2–25.9)ng/g creatinine, p<0.001]. In contrast, no significant differences were observed between everolimus- and CNI-treated groups with regard to creatinine and cystatin C, as well as urine albumin and α1M levels. Significant correlations were noted between plasma NGAL and creatinine (r=0.42, p<0.001), cystatin C (r=0.44, p<0.001), N-terminal brain natriuretic propeptide (r=0.31, p<0.01) and indicators of chronic inflammation [lipoprotein-associated phospholipase A2 (Lp-PLA2), r=0.31, p<0.01] and soluble CD40 ligand (sCD40L, r=0.22, p<0.05), and between urinary NGAL and α1M (r=0.21, p<0.05). Multiple regression analysis indicated that cystatin C and Lp-PLA2 were the best predictors of plasma NGAL. ConclusionThe present study documents reduced plasma and urinary NGAL levels in the absence of differences in conventional renal parameters in patients on CNI-free immunosuppressive therapy with everolimus. These results support favorable effects of everolimus on renal integrity in heart transplant recipients.

Long-term efficacy of atorvastatin in allograft rejection following renal transplantation: A randomized clinical trial.

Statins are a class of drug that can efficiently reduce the level of low-density lipoprotein (LDL) as well as increase the LDL receptors. Several non-lipid-lowering effects of this type of drug have been described. It is reported that they have an influence in preventing graft rejection, especially of the acute type. In this study, patients with end-stage renal disease and candidates for kidney transplantation were divided into two groups. Group A (intervention group) received atorvastatin for two weeks prior to their transplant surgery while group B (control group) received placebo. The lipid profile was tested (triglycerides, cholesterol, LDL) in all patients two weeks before the transplantation. After transplantation, drug use was stopped. We also checked the LDL serum levels in patients with raised lipid levels (LDL >100) every two weeks. After this period, the serum lipid levels were checked monthly up to six months. Hyperlipidemia, when present, was controlled by fibrates. Concerning the rejection episodes, there was no significant difference between the two groups. In group A (13 men and nine women), three (14.3%) cases of rejection were observed whereas four (21.3%) cases of rejection were seen in group B (11 men and 10 women) (P = 0.5). Within group A, five (22.7%) cases of delayed graft function were found while four (19%) similar cases were observed in group B (P = 0.7). There was no statistically significant difference concerning delayed graft function between the two groups. Despite all the mechanisms attributed to the probable anti-rejection properties of statins, we found no significant correlation with the administration of these drugs before transplantation and the protection against graft rejection episodes.

Clinical Characteristics and Long-Term Outcomes of Patients Undergoing Combined Heart-Kidney Transplantation: A Single-Center Experience

BackgroundThe purpose of the study was to describe clinical characteristics and long-term survival of patients undergoing combined heart-kidney transplant in a single center. MethodsWe conducted a retrospective analysis of 22 consecutive patients who underwent combined heart-kidney transplant at our institution between 1995 and 2013. Long-term outcomes were analyzed by means of the Kaplan-Meier method. ResultsFour patients underwent re-do transplant (2 cardiac re-transplants, 1 kidney re-transplant, and 1 combined heart-kidney re-transplant). Most frequent underlying cardiac conditions were coronary artery disease (54%), dilated cardiomyopathy (23%), and chronic rejection of a previous heart graft (18%). Known causes of chronic renal dysfunction were nephroangioesclerosis (23%), drug-related toxicity (14%), and Wegener granulomatosis (5%). Non-specified chronic renal dysfunction was present in 50% patients. In-hospital postoperative mortality rate was 5 of 22 (23%). Causes of early death were directly related to kidney transplant surgery in 4 of 5 (80%) patients. Among the remaining 17 patients who surmounted the postoperative period, long-term survival rates 1 year, 5 years, and 10 years after HKT were 88%, 82%, and 65%, respectively. Over a mean follow-up of 6.7 ± 6.4 years, cumulative incidences of cytomegalovirus infection, coronary allograft vasculopathy, malignancy, and acute cardiac graft rejection were 41%, 6%, 24%, and 41%, respectively. There was no episode of acute renal graft rejection. At the end of follow-up, all survivors (n = 11) were in functional New York Heart Association class I. Mean creatinine serum level was 1.68 mg/dL. ConclusionsIn our experience, combined heart-kidney transplant is a feasible therapeutic option that yielded favorable long-term outcomes, with a low cumulative incidence of cardiac graft dysfunction. These results were obtained at the expense of a significant risk of early postoperative mortality, which was mainly related to complications of kidney transplant surgery.

An Interferon-free Antiviral Regimen for HCV after Liver Transplantation

BackgroundHepatitis C virus (HCV) infection is the leading indication for liver transplantation worldwide, and interferon-containing regimens are associated with low response rates owing to treatment-limiting toxic effects in immunosuppressed liver-transplant recipients. We evaluated the interferon-free regimen of the NS5A inhibitor ombitasvir coformulated with the ritonavir-boosted protease inhibitor ABT-450 (ABT-450/r), the nonnucleoside NS5B polymerase inhibitor dasabuvir, and ribavirin in liver-transplant recipients with recurrent HCV genotype 1 infection.MethodsWe enrolled 34 liver-transplant recipients with no fibrosis or mild fibrosis, who received ombitasvir–ABT-450/r (at a once-daily dose of 25 mg of ombitasvir, 150 mg of ABT-450, and 100 mg of ritonavir), dasabuvir (250 mg twice daily), and ribavirin for 24 weeks. Selection of the initial ribavirin dose and subsequent dose modifications for anemia were at the investigator's discretion. The primary efficacy end point was a sustained virologic response 12 weeks after the end of treatment.ResultsOf the 34 study participants, 33 had a sustained virologic response at post-treatment weeks 12 and 24, for a rate of 97% (95% confidence interval, 85 to 100). The most common adverse events were fatigue, headache, and cough. Five patients (15%) required erythropoietin; no patient required blood transfusion. One patient discontinued the study drugs owing to adverse events after week 18 but had a sustained virologic response. Blood levels of calcineurin inhibitors were monitored, and dosages were modified to maintain therapeutic levels; no episode of graft rejection was observed during the study.ConclusionsTreatment with the multitargeted regimen of ombitasvir–ABT-450/r and dasabuvir with ribavirin was associated with a low rate of serious adverse events and a high rate of sustained virologic response among liver-transplant recipients with recurrent HCV genotype 1 infection, a historically difficult-to-treat population. (Funded by AbbVie; CORAL-I ClinicalTrials.gov number, NCT01782495.)

Dermoscopy in near-full facial transplantation

From an O th Th In Publ Fund Conf CLINICAL PRESENTATION We report the case of a 32-year-old male recipient of a life-saving near-full facial transplant performed in May 2013 (Fig 1, A). Induction immunosuppression consisted of anti-thymocyte globulin, tacrolimus, mofetil mycophenolate, and high-dose methylprednisolone. On day 36 posttransplant, confluent erythema with edema of transplanted skin developed (Fig 1, B) and was diagnosed as acute graft rejection, which was successfully treated with methylprednisolone 2 mg/kg body weight tapered after 3 days. No further episodes of graft rejection have been observed (Fig 1, C ).