Rejection In Renal Transplant Patients Research Articles

Optimizing tacrolimus dosing in Hispanic renal transplant patients: insights from real-world data.

Tacrolimus, an immunosuppressant used to prevent organ rejection in renal transplant patients, exhibits high inter-patient variability, necessitating therapeutic drug monitoring. Early post-transplant tacrolimus exposure in Hispanics is understudied. Although genotypic information is linked to pharmacokinetic differences, its clinical application remains limited. This study aimed to use a real-world data-driven, pharmacokinetic model-based approach for tacrolimus in Hispanics to determine a suitable initial dose and design an optimal dose titration strategy by simulations to achieve plasma trough concentration target levels of 10-12ng/mL at the earliest. Sparse concentration-time data of tacrolimus were obtained from electronic medical records for self-identified Hispanic subjects following renal transplant. Rich pharmacokinetic literature data was leveraged to estimate structural pharmacokinetic model parameters, which were then fixed in the current analysis. Only apparent clearance was estimated with the sparse tacrolimus data and potential covariates were identified. Simulations of various starting doses and different dose titration strategies were then evaluated. The analysis included 121 renal transplant patients with 2,215 trough tacrolimus concentrations. A two-compartment transit absorption model with allometrically scaled body weight and time-varying hematocrit on apparent clearance adequately described the data. The estimated apparent clearance was 13.7L/h for a typical patient weighing 70kg and at 30% hematocrit, demonstrating a 40% decrease in clearance compared to other patient populations. Model based simulations indicated the best initial dose for the Hispanic population is 0.1mg/kg/day. The proposed titration strategy, with three dose adjustments based on trough levels of tacrolimus, increased the proportion of patients within the target range (10-12ng/mL) more than 2.5-fold and decreased the proportion of patients outside the therapeutic window by 50% after the first week of treatment. Hispanic renal transplant population showed an estimated 40% decrease of apparent clearance in the typical patient compared to other populations with similar characteristics. The proposed dose adjustment attained the target range rapidly and safely. This study advocates for tailored tacrolimus dosing regimens based on population pharmacokinetics to optimize therapy in Hispanic renal transplant recipients.

Diagnosis and Treatment of Skin Lesions in Renal Transplant Recipients: A Retrospective Review.

Immunosuppressive therapy is essential for to prevent graft rejection in renal transplant patients; however, it is associated with elevating the risk of several pathologies in these patients particularly infectious and neoplastic conditions. In this study, we explore the diagnosis and treatment of skin lesions in renal transplant patients. A retrospective chart review of 12 renal transplant recipients referred to plastic and reconstructive surgery with skin lesions from 2000 to 2020 was performed. The mean age of the 12 patients was 49.6 years. Time to plastic surgery after renal transplantation ranged between 1 and 16 years. Nine cases of basal cell carcinoma, 2 cases of squamous cell carcinoma, and 1 case of skin and soft tissue infection of the lower extremity and cutaneous extranodal NK/T-cell lymphoma, nasal type was observed. Flaps, skin grafts, and artificial dermis grafts constitute the main reconstructive methods. There were no postoperative infections or wound dehiscence. Cutaneous infections and skin malignancy account for most of the skin lesions developing after renal transplantation. Posttransplant lymphoproliferative disorder warrants equal attention and should not be disregarded. Early diagnosis and treatment significantly improve prognosis as patients with longer duration of transplant were found to have more aggressive tumors. Plastic and reconstructive surgery offers a safe therapeutic method of treatment in these cases.

The Predictors and Risk Factors of 2-Year Rejection in Renal Transplant Patients: A Multicenter Case-Control Study

Introduction: Kidney transplantation is a definitive treatment for end-stage renal disease. It is associated with improved life expectancy and quality of life. One of the most common complications following kidney transplantation is graft rejection. To our knowledge, no previous study has identified rejection risk factors in kidney transplant recipients in Saudi Arabia. Therefore, this study aimed to determine the specific risk factors of graft rejection. Methods: A multicenter case-control study was conducted at four transplant centers in Saudi Arabia. All adult patients who underwent a renal transplant between January 1, 2015 and December 31, 2021 were screened for eligibility. Included patients were categorized into two groups (cases and control) based on the occurrence of biopsy-proven rejection within 2 years. The primary outcome was to determine the risk factors for rejection within the 2 years of transplant. Exact matching was utilized using a 1:4 ratio based on patients’ age, gender, and transplant year. Results: Out of 1,320 screened renal transplant recipients, 816 patients were included. The overall prevalence of 2-year rejection was 13.9%. In bivariate analysis, deceased donor status, the presence of donor-specific antibody (DSA), intraoperative hypotension, Pseudomonas aeruginosa, Candida, and any infection within 2 years were linked with an increased risk of 2-year rejection. However, in the logistic regression analysis, the presence of DSA was identified as a significant risk for 2-year rejection (adjusted OR: 2.68; 95% CI: 1.10, 6.49, p = 0.03). Furthermore, blood infection, infected with Pseudomonas aeruginosa or BK virus within 2 years of transplant, were associated with higher odds of 2-year rejection (adjusted OR: 3.10; 95% CI: 1.48, 6.48, p = 0.003, adjusted OR: 3.23; 95% CI: 0.87, 11.97, p = 0.08 and adjusted OR: 2.76; 95% CI: 0.89, 8.48, p = 0.07, respectively). Conclusion: Our findings emphasize the need for appropriate prevention and management of infections following kidney transplantation to avoid more serious problems, such as rejection, which could significantly raise the likelihood of allograft failure and probably death. Further studies with larger sample sizes are needed to investigate the impact of serum chloride levels prior to transplant and intraoperative hypotension on the risk of graft rejection and failure.

WCN24-868 MicroRNAs as biomarkers of acute antibody-mediated rejection in renal transplant patients

WCN24-868 MicroRNAs as biomarkers of acute antibody-mediated rejection in renal transplant patients

Prospective cohort study of Torque Teno Virus (TTV) viral load kinetics and the association with graft rejection in renal transplant patients.

Graft survival is mainly determined by rejections and infectious complications in transplant recipients. Torque Teno Virus (TTV), a nonpathogenic and ubiquitous single-stranded DNA virus, has been proposed as a biomarker of the immune status in transplant patients. This study aimed to determine the correlation between a Home-Brew TTV PCR and R-GENE®PCR; the TTV viral load kinetics in renal transplant recipients and the association with graft rejection. Prospective cohort study on 107 adult renal transplant recipients. TTV viral load was determined in 746 plasma samples collected before and after renal transplantation by a Home-Brew PCR and a commercial PCR (R-GENE®PCR). Associations of TTV viral load with graft rejections were analyzed. Agreement of both PCR assays was 93.2% and Pearson correlation coefficient was r: 0.902 (95%CI: 0.8881-0.9149, p<0.0001). TTV viral load kinetics showed an initial gradual increase reaching a peak at 3 months. This highest value was followed by a slight decrease, reaching a plateau significantly higher than the initial baseline at 6 months (p<0.0001). Between (181-270) days post-transplantation, TTV median viral load in patients with graft rejection was significantly lower, 3.59 Log10 copies/mL (by Home-Brew PCR) and 3.10 Log10 copies/mL (by R-GENE®PCR) compared to patients without graft rejection (6.14 and 5.96 Log10 copies/mL, respectively). Significantly lower TTV viral load was observed in patients with renal rejection occurring at a median of 243 days post-transplantation. Given the dynamic behavior of TTV viral load post-transplantation, cut-off values for risk stratification to predict rejection might be determined in relation to the post-transplant period.

Post-Transplant Surveillance and Management of Chronic Active Antibody-Mediated Rejection in Renal Transplant Patients in Europe.

Antibody mediated rejection (ABMR) is the leading cause of immune-related allograft failure following kidney transplantation. Chronic active ABMR (CABMR) typically occurs after one-year post-transplant and is the most common cause of late allograft failure. This study was designed to assess common practices in Europe for post-transplant surveillance 1year after kidney transplant, as well as the diagnosis and management of CABMR. A 15-minute online survey with 58 multiple choice or open-ended questions was completed by EU transplant nephrologists, transplant surgeons and nephrologists. Survey topics included patient caseloads, post-transplant routine screening and treatment of CABMR. The results indicated that observing clinical measures of graft function form the cornerstone of post-transplant surveillance. This may be suboptimal, leading to late diagnoses and untreatable disease. Indeed, less than half of patients who develop CABMR receive treatment beyond optimization of immune suppression. This is attributable to not only late diagnoses, but also a lack of proven efficacious therapies. Intravenous Immunoglobulin (IVIG), steroid pulse and apheresis are prescribed by the majority to treat CABMR. While biologics can feature as part of treatment, there is no single agent that is being used by more than half of physicians.

Targeting CD38 in Neoplasms and Non-Cancer Diseases.

Simple SummaryCD38 remains an interesting target for anticancer therapy. Its relatively high abundance in neoplasms and crucial impact on NAD+/cADPR metabolism and the activity of T cells allows for changing the immune response in autoimmune diseases, neoplasms, and finally the induction of cell death. Antibody-dependent cell cytotoxicity is responsible for cell death induced by targeting the tumor with anti-CD38 antibodies, such as daratumumab. A wide range of laboratory experiments and clinical trials show an especially promising role of anti-CD38 therapy against multiple myeloma, NK cell lymphomas, and CD19- B-cell malignancies. More studies are required to include more diseases in the therapeutic protocols involving the modulation of CD38 activity.CD38 is a myeloid antigen present both on the cell membrane and in the intracellular compartment of the cell. Its occurrence is often enhanced in cancer cells, thus making it a potential target in anticancer therapy. Daratumumab and isatuximab already received FDA approval, and novel agents such as MOR202, TAK079 and TNB-738 undergo clinical trials. Also, novel therapeutics such as SAR442085 aim to outrank the older antibodies against CD38. Multiple myeloma and immunoglobulin light-chain amyloidosis may be effectively treated with anti-CD38 immunotherapy. Its role in other hematological malignancies is also important concerning both diagnostic process and potential treatment in the future. Aside from the hematological malignancies, CD38 remains a potential target in gastrointestinal, neurological and pulmonary system disorders. Due to the strong interaction of CD38 with TCR and CD16 on T cells, it may also serve as the biomarker in transplant rejection in renal transplant patients. Besides, CD38 finds its role outside oncology in systemic lupus erythematosus and collagen-induced arthritis. CD38 plays an important role in viral infections, including AIDS and COVID-19. Most of the undergoing clinical trials focus on the use of anti-CD38 antibodies in the therapy of multiple myeloma, CD19- B-cell malignancies, and NK cell lymphomas. This review focuses on targeting CD38 in cancer and non-cancerous diseases using antibodies, cell-based therapies and CD38 inhibitors. We also provide a summary of current clinical trials targeting CD38.

W027 The importance of cytokine concentration measurement in the assessment of allograft rejection in renal transplant patients

W027 The importance of cytokine concentration measurement in the assessment of allograft rejection in renal transplant patients

Noninvasive Diagnosis of Acute Rejection in Renal Transplant Patients Using Mass Spectrometric Analysis of Urine Samples: A Multicenter Diagnostic Phase III Trial.

Background.Timely recognition and treatment of acute kidney graft rejection is important to prevent premature graft failure. A predefined urinary marker set for acute T cell–mediated rejection (TCMR) containing 14 peptides was tested for this purpose in a multicenter in-place validation study.Methods.Three hundred twenty-nine prospectively collected and 306 archived urine samples from 11 transplant centers in Germany, France, and Belgium were examined. Samples were taken immediately before a biopsy, performed for graft dysfunction within the first transplant year. Primary outcomes were sensitivity and specificity of the marker set for the diagnosis of biopsy-proven acute TCMR, with prespecified thresholds of 83% for sensitivity and 70% for specificity.Results.Eighty-two patients (13%) had acute TCMR grade I–III. In relation to the biopsy diagnosis of TCMR, the sensitivity of the urine test was 0.66 (95% confidence interval, 0.56-0.76) and the specificity 0.47 (95% confidence interval, 0.43-0.51), with an area under the curve (AUC) of 0.60. The different TCMR grades I–III were not reflected by the marker set, and borderline TCMR was not specifically detected. Secondary independent masked assessment of biopsies consented by 2 pathologists revealed an interobserver kappa value of 0.49 for diagnosing TCMR, compared with the local center’s diagnosis. Using this consensus diagnosis, the AUC of the urine test was 0.63 (sensitivity 0.73, specificity 0.45). Post hoc optimization of the marker set improved the diagnostic performance in the study cohort (AUC 0.67) and in an independent patient cohort (AUC 0.69).Conclusions.This study illustrates the difficulty of proteomics-based diagnosis of TCMR and highlights the need for rigorous independent in-place validation and optimization of diagnostic biomarkers.

Influence of TGFB1 and CTLA4 polymorphisms on calcineurin inhibitors dose and risk of acute rejection in renal transplantation

Organ transplant is often the treatment of choice as it extends and improves patient life. Immunosuppressive treatment, which prevents acute rejection of the organ, is used in transplant patients to prevent the loss of transplant. The aim of the study was to determine the impact of the CTLA4 (+49A>G, rs231775) and the TGF-β1 (−800G>A, rs1800468) polymorphisms on the therapeutic effect of immunosuppressive drugs (cyclosporine—CsA, tacrolimus—TAC) and the risk of acute rejection in renal transplant patients. The analysis of the CTLA4 +49A>G and the TGF-β1 −800G>A polymorphisms was carried out in 392 patients after kidney transplant using real-time PCR. The CTLA4 +49A>G polymorphism did not affect CsA or TAC dose, ratio of drug concentration to dose (C/D), and blood concentrations. As for the TGF-β1 -800G>A polymorphism, patients with the GA genotype required lower TAC doses compared to the GG genotype (TAC 12 h: 3.63 mg vs 5.3 mg, TAC 24 h: 2.38 mg vs 3.29 mg). Comparing the C/D ratio in both groups (TAC 12 h and TAC 24 h), higher C/D ratio was observed in patients with the GA genotype. These results indicate that patients with the A allele require slightly lower doses of TAC. The results suggest that the TGF-β1 −800 G>A polymorphism may influence the TAC dose, while the +49A>G polymorphism of the CTLA4 gene does not correlate with the dose of CsA or TAC. The analysis of the biochemical parameters of the renal profile showed no impact of the CTLA4 and the TGF-β1 polymorphisms on the risk of organ rejection.

Clinical and Analytical Validation of a Novel Urine-Based Test for the Detection of Allograft Rejection in Renal Transplant Patients.

In this clinical validation study, we developed and validated a urinary Q-Score generated from the quantitative test QSant, formerly known as QiSant, for the detection of biopsy-confirmed acute rejection in kidney transplants. Using a cohort of 223 distinct urine samples collected from three independent sites and from both adult and pediatric renal transplant patients, we examined the diagnostic utility of the urinary Q-Score for detection of acute rejection in renal allografts. Statistical models based upon the measurements of the six QSant biomarkers (cell-free DNA, methylated-cell-free DNA, clusterin, CXCL10, creatinine, and total protein) generated a renal transplant Q-Score that reliably differentiated stable allografts from acute rejections in both adult and pediatric renal transplant patients. The composite Q-Score was able to detect both T cell-mediated rejection and antibody-mediated rejection patients and differentiate them from stable non-rejecting patients with a receiver–operator characteristic curve area under the curve of 99.8% and an accuracy of 98.2%. Q-Scores < 32 indicated the absence of active rejection and Q-Scores ≥ 32 indicated an increased risk of active rejection. At the Q-Score cutoff of 32, the overall sensitivity was 95.8% and specificity was 99.3%. At a prevalence of 25%, positive and negative predictive values for active rejection were 98.0% and 98.6%, respectively. The Q-Score also detected subclinical rejection in patients without an elevated serum creatinine level but identified by a protocol biopsy. This study confirms that QSant is an accurate and quantitative measurement suitable for routine monitoring of renal allograft status.

Acute rejection in kidney transplantation and the evaluation of associated polymorphisms (SNPs): the importance of sample size.

Background Acute rejection (AR) is one of the most frequent complications after kidney transplantation (KT). Scientific evidence reports that some single-nucleotide polymorphisms (SNPs) located in genes involved in the immune response and in the pharmacokinetics and pharmacodynamics of immunosuppressive drugs are associated with rejection in renal transplant patients. The aim of this study was to evaluate some SNPs located in six genes: interleukin-10 (IL-10), tumor necrosis factor (TNF), adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1), uridine diphosphate glucuronosyltransferase family 1 member A9 (UGT1A9), inosine monophosphate dehydrogenase 1 (IMPDH1) and IMPDH2. Methods We enrolled cases with at least one AR after KT and two groups of controls: patients without any AR after KT and healthy blood donors. Genetic analysis on DNA was performed. The heterozygosity (HET) was determined and the Hardy-Weinberg equilibrium (HWE) test was performed for each SNP. The sample size was calculated using the QUANTO program and the genetic associations were calculated using the SAS program (SAS Institute Inc., Cary, NC, USA). Results In our previous preliminary study (sample size was not reached for cases), the results showed that patients with the C allele in the SNP rs1045642 and the A allele in the SNP rs2032582 of the ABCB1 gene had more frequent AR. In contrast, with the achievement of sample size, the trend of the previous data was not confirmed. Conclusions Our study highlights a fundamental aspect of scientific research that is generally presumed, i.e. the sample size of groups enrolled for a scientific study. We believe that our study will make a significant contribution to the scientific community in the discussion of the importance of the analysis and the achievement of sample size to evaluate the associations between SNPs and the studied event.

Coronary artery bypass grafting in a renal transplant patient: case report

The patients with end-stage renal disease have an increased risk of atherosclerosis and the probability of cardiovascular diseases. Due to the use of immunosuppressive agents, the patients having renal graft carry an additional risk of atherosclerosis or endocarditis. A 67-year-old male patient with a history of renal transplantation was referred to our hospital with a severe chest pain and dyspnea. After diagnosing severe ischemic coronary artery disease by coronary angiography, the patient underwent a successful operation of a single vessel coronary artery bypass grafting (CABG) in beating heart. Up to 20% of post-renal transplantation mortality is attributed to cardiovascular diseases. Graft rejection, the need of hemodialysis, perioperative infection are some of the major complications for renal transplant patients undergoing CABG surgery. Off-pump CABG (OPCABG) surgery is a less invasive technique in comparison with CABG with cardiopulmonary bypass (CPB), and protects the patient from negative effects of CPB such as complement system activation, inflammatory mediator secretion, thrombocytopenia, clotting disorders. We recommend to prefer OPCABG and have preoperative prophylaxis in order to avoid both perioperative infection and renal graft rejection in renal transplant patients undergoing CABG surgery.

Association of UGT2B7, UGT1A9, ABCG2, and IL23R polymorphisms with rejection risk in kidney transplant patients

ABSTRACTDespite advances in testing compatibility between donor and recipient, graft rejection remains a current concern. Single-nucleotide polymorphisms (SNPs) that codify altered enzymes of metabolism, drug transport, and the immune system may contribute to graft rejection in transplant patients. This study examined the association between SNPs present in genes of these processes and occurrence of graft rejection episodes in 246 kidney transplant patients, 35% of which were diagnosed with rejection. Genotype–gene expression associations were also assessed. Peripheral blood samples were used for genotyping of 24 SNPs on the following genes: CYP3A4, CYP3A5, CYP2E1, POR, UGT2B7, UGT1A9, ABCB1, ABCC2, ABCG2, SLCO1B1, TNF, IL2, IRF5, TGFB1, NFKBIA, IL10, IL23R, NFAT, and CCR5 by real-time PCR. The analysis of gene expression was performed by RT-qPCR. The association between graft rejection episodes and polymorphic variants was assessed using odds ratios. Polymorphisms rs7662029 (UGT2B7) and rs6714486 (UGT1A9) were associated with occurrence of graft rejection episodes, rs7662029 (UGT2B7) exhibited a protective effect (1.85-fold), and rs6714486 (UGT1A9) an increased 1.6-fold increased risk of graft rejection. Among drug transporter genes, only rs2231142 (ABCG2) demonstrated an association with a 1.92-fold decrease in the risk of graft rejection. The immunological SNP rs10889677 (IL23R) was associated with a 1.9-fold enhanced risk of graft rejection. Association between genotypes and gene expression was not detected. Therefore, SNPs of UGT2B7, UGT1A9, ABCG2, and IL23R genes may be useful as candidate markers for screening of risk graft rejection in renal transplant patients. These markers may improve medical decisions, avoiding adverse effects.

The association of urinary interferon-gamma inducible protein-10 (IP10/CXCL10) levels with kidney allograft rejection.

Interferon-gamma inducible protein-10 (IP-10/CXCL10) is a chemokine involved in the alloimmune response against kidney allograft. We aimed to investigate the association of urinary CXCL10 protein levels with rejection in renal transplant patients. A total of 273 urine samples from (biopsy-proven) rejection and non-rejection patients and controls were included in this study. CXCL10 levels were analyzed for association with rejection. The data showed statistically significant differences in the CXCL10 levels between rejection vs. non-rejection (p < 0.001). Among the rejection groups, statistically significant differences for CXCL10 levels were found between ACR vs. NAD (p < 0.001), ACR vs. BLR (p = 0.019) and AVR vs. NAD (p = 0.009). Receiver Operating Characteristic (ROC) curve analysis of CXCL10 showed an area under the curve (AUC) of 0.74 with 72% sensitivity and 71% specificity at 27.5pg/ml between rejection and non-rejection group. Kaplan-Meier curve analysis among different levels of CXCL10 showed a better rejection-free graft survival in patients with <100pg/ml when compared to >200pg/ml (38 ± 6 vs. 12 ± 1.0 weeks; log-rank p < 0.001) and 100-200pg/ml (38 ± 6 vs. 22 ± 9 weeks; log-rank p = 0.442) concentration. The results indicate significantly increased levels of CXCL10 protein in the urine at the time of allograft rejection. This association of urinary CXCL10 protein levels with rejection could provide an additional tool for the non-invasive monitoring of allograft rejection.

Therapy Modalities for Antibody Mediated Rejection in Renal Transplant Patients

ABSTRACTIntroduction: The aim of our study was to determine the effectiveness of immunoglobulin, rituximab and plasmapheresis in renal transplant patients with antibody mediated rejection (AMR). Patients and Methods: Fourteen renal transplant patients with AMR were included in this study. The mean age of the patients was 33.9 ± 10.3 years and 10 (71.4%) of them were male. Lymphocyte cross match was negative for all patients and 10 (71.4%) of them were living donor transplants. Six patients were administered tacrolimus, three patients cyclosporine, two patients everolimus, and three patients sirolimus for immunosuppression. The patients with AMR were administered IVIG, rituximab and plasmapheresis. Results: Patient survival rate was 100%, graft survival rate after AMR was 50% in the first year and 33% in the 2nd and third years. AMR developed 31.9 ± 25.9 months after transplantation. Seven (50%) patients lost their grafts. Delayed graft function was observed in 28.6%, chronic allograft dysfunction in 78.5%, diabetes after transplantation in 14.3%, and cytomegalovirus infection in 7.1% of the patients. At the last follow-up, the mean blood creatinine was 3.1 ± 1.4, the mean proteinuria was 2300 (1300–3300) mg/day and the mean GFR was 34.5 ± 17.6 ml/min. C4d was positive in peritubullar capillaries in all patients, while neutrophil accumulation in peritubular and glomerular capillaries was observed in 8 patients. Chronic allograft vasculopathy was observed in 12 patients. Conclusion: AMR leads to progressive loss of renal function and has low graft survival. More effective treatment alternatives are needed for this clinical issue.

Role of Immunosuppressants in Graft Rejection in Renal Transplant Patients

Background: Organ transplants save a thousands of life each year of modern medicine. The main advantage of such intrusive procedure is that the patients can live a more natural life after the surgery with the help of immunosuppressants. But these immunosuppressants are found to produce certain toxicities and complications in renal transplant patients. Hence we designed a study to determine the variety of immunosuppressive drug regimens for post renal transplant patients and analyze the drug toxicities and complications in renal transplant patients. Aim : The main aim of the study is to determine the incidence and recurrence of rate of graft rejection, toxicities due to immunosuppressive drugs, complications in renal transplant patients and the risk factors of infections in post renal transplant recipients. Methods and Materials: The study was carried out in a multispeciality hospital in for a period of six months. A total of 45 patients between 18-65 years undergoing a single organ transplant were included in the study. These patients received any of the following immunosuppressive drug regimens such as cyclosporine A (CSA), mycophenolate mofetil (MMF), Azathioprine (AZA), Tacrolimus, Predniosolone, Methotrexate, Rituximab and Plasma exchange for renal transplantation. Exclusion criteria included patient on multiorgan transplant or second transplant, patients of any anatomical abnormalities, history of multi drug resistant fungal infection, advanced cardio- or pulmonary disease and patients whose interleukin 2 and granulocyte macrophage colony stimulating factor is high before 6 months of transplantation. Results : Among the 45 renal transplant patients 75.5% were males and 24.5% were females. Patients in the age group of 40 - 50 years were at a higher risk of renal failure. Majority of the post renal transplant patients received CSA, MMF and AZA. Based on toxicities, AZA produced toxicities in 17.7 % of patients followed by CSA in 15.5% and MMF in 15.5% cases. Of the total patients, 17.7% had major infections causing graft rejections that included the UTI (48.8%), upper respiratory tract infections (20%) and lower respiratory tract infections (17%). Post transplant diabetes mellitus was seen in 13.3% patients and post renal hypertension in 17.7% cases. Hemolytic uremic syndrome was predominant with 17.7% of patients, followed by glomerulonephritis (15.5%) and pyelonephritis (11.1%). Drug Toxicity is one of the factors for causing rejection in renal transplant in which 7 (28.8%) patients were affected from acute rejection by receiving immunosuppressive therapy, followed by 13 (55.5%) patients in chronic rejection and 14 (31.1%) patients not having toxicity to cause the rejection.

Treatment of antibody-mediated rejection in renal transplant patients: a clinical practice survey.

Preferences for the testing and treatment of antibody-mediated rejection (AMR) in renal transplant patients vary among programs and individual practitioners. The description of these preferences and identification of commonalities can contribute to creating a standard of care. A survey was distributed through the Transplant Listserv of the American College of Clinical Pharmacy (ACCP) and via email to members of the American Society of Transplantation Community of Pharmacy (AST CoP), collected, and analyzed. Most clinicians (26/28) test for donor-specific antibodies (DSAs) when evaluating a patient with possible AMR. Treatments for AMR varied widely among responding clinicians and included intravenous immune globulin (IVIG, n = 25), plasmapheresis (n = 24), rituximab (n = 8), bortezomib (n = 4), rabbit antithymocyte globulin (n = 2), and eculizumab (n = 1). Weight-based dosing of IVIG averaged 1.8 g/kg total dose. Six centers use rituximab as initial therapy, while two use rituximab if other therapy fails. Four centers use bortezomib as initial therapy, while two centers use it for severe/persistent AMR. One center uses eculizumab as initial therapy and one center uses it for severe AMR. Methods for the detection of AMR are similar, yet treatment of AMR varies widely. Most centers utilize DSA for detection and a combination of IVIG and plasmapheresis for treatment.

MTOR Inhibitors in Cancer: What Can We Learn from Exceptional Responses?

mTOR Inhibitors in Cancer: What Can We Learn from Exceptional Responses?

Molecular detection and characterization of BK and JC polyomaviruses in urine samples of renal transplant patients in Southern Brazil.

The human polyomaviruses JC (JCPyV) and BK (BKPyV) are widespread in the human population. Following the primary infection, virus reactivation may lead to nephropathy and graft rejection in renal transplant patients. This study was carried out to access the presence of BKPyV and JCPyV DNA in urine samples collected from renal transplant patients (n = 92) and healthy individuals (n = 88) in Porto Alegre, Rio Grande do Sul. The samples were submitted to a nested PCR. A significantly higher frequency (P < 0.001) of BKPyV was found in renal transplant patients (65.2%) in comparison to the control group (32.9%). JCPyV was detected equally in both groups. Phylogenetic analysis of both BKPyV and JCPyV amplicons demonstrates the presence of the BKPyV subtypes I and II, whereas for JCPyV, four different groups are found (1, 2, 3, and 4).