Potential Effects of Immunosuppression on Oxidative Stress and Atherosclerosis in Kidney Transplant Recipients

Chronic kidney disease is a public health problem that, depending on the country, affects approximately 8–13% of the population, involving both males and females of all ages. Renal replacement therapy remains one of the most costly procedures. It is assumed that one of the factors influencing the course of chronic kidney disease might be oxidative stress. It is believed that the main mediators of oxidative stress are reactive oxygen species (ROS). Transiently increased concentrations of ROS play a significant role in maintaining an organism’s homeostasis, as they are part of the redox-related signaling, and in the immune defense system, as they are produced in high amounts in inflammation. Systemic oxidative stress can significantly contribute to endothelial dysfunction along with exaggeration of atherosclerosis and development of cardiovascular disease, the leading cause of mortality in patients with kidney disease. Moreover, the progression of chronic kidney disease is strictly associated with the atherosclerotic process. Transplantation is the optimal method for renal replacement therapy. It improves better quality of life and prolongs survival compared with hemodialysis and peritoneal dialysis; however, even a successful transplantation does not correct the abnormalities found in chronic kidney disease. As transplantation reduces the concentration of uremic toxins, which are a factor of inflammation per se, both the procedure itself and the subsequent immunosuppressive treatment may be a factor that increases oxidative stress and hence vascular sclerosis and atherosclerotic cardiovascular disease. In the current work, we review the effect of several risk factors in kidney transplant recipients as well as immunosuppressive therapy on oxidative stress

Uremic Toxins, Oxidative Stress, Atherosclerosis in Chronic Kidney Disease, and Kidney Transplantation

Patients with chronic kidney disease (CKD) are at a high risk for cardiovascular disease (CVD), and approximately half of all deaths among patients with CKD are a direct result of CVD. The premature cardiovascular disease extends from mild to moderate CKD stages, and the severity of CVD and the risk of death increase with a decline in kidney function. Successful kidney transplantation significantly decreases the risk of death relative to long-term dialysis treatment; nevertheless, the prevalence of CVD remains high and is responsible for approximately 20-35% of mortality in renal transplant recipients. The prevalence of traditional and nontraditional risk factors for CVD is higher in patients with CKD and transplant recipients compared with the general population; however, it can only partly explain the highly increased cardiovascular burden in CKD patients. Nontraditional risk factors, unique to CKD patients, include proteinuria, disturbed calcium, and phosphate metabolism, anemia, fluid overload, and accumulation of uremic toxins. This accumulation of uremic toxins is associated with systemic alterations including inflammation and oxidative stress which are considered crucial in CKD progression and CKD-related CVD. Kidney transplantation can mitigate the impact of some of these nontraditional factors, but they typically persist to some degree following transplantation. Taking into consideration the scarcity of data on uremic waste products, oxidative stress, and their relation to atherosclerosis in renal transplantation, in the review, we discussed the impact of uremic toxins on vascular dysfunction in CKD patients and kidney transplant recipients. Special attention was paid to the role of native and transplanted kidney function

Netrin-1 and semaphorin 3A predict the development of acute kidney injury in liver transplant patients.

Acute kidney injury (AKI) is a serious complication after liver transplantation. Currently there are no validated biomarkers available for early diagnosis of AKI. The current study was carried out to determine the usefulness of the recently identified biomarkers netrin-1 and semaphorin 3A in predicting AKI in liver transplant patients. A total of 63 patients' samples were collected and analyzed. AKI was detected at 48 hours after liver transplantation using serum creatinine as a marker. In contrast, urine netrin-1 (897.8 ± 112.4 pg/mg creatinine), semaphorin 3A (847.9 ± 93.3 pg/mg creatinine) and NGAL (2172.2 ± 378.1 ng/mg creatinine) levels were increased significantly and peaked at 2 hours after liver transplantation but were no longer significantly elevated at 6 hours after transplantation. The predictive power of netrin-1, as demonstrated by the area under the receiver-operating characteristic curve for diagnosis of AKI at 2, 6, and 24 hours after liver transplantation was 0.66, 0.57 and 0.59, respectively. The area under the curve for diagnosis of AKI was 0.63 and 0.65 for semaphorin 3A and NGAL at 2 hr respectively. Combined analysis of two or more biomarkers for simultaneous occurrence in urine did not improve the AUC for the prediction of AKI whereas the AUC was improved significantly (0.732) only when at least 1 of the 3 biomarkers in urine was positive for predicting AKI. Adjusting for BMI, all three biomarkers at 2 hours remained independent predictors of AKI with an odds ratio of 1.003 (95% confidence interval: 1.000 to 1.006; P = 0.0364). These studies demonstrate that semaphorin 3A and netrin-1 can be useful early diagnostic biomarkers of AKI after liver transplantation

Human Papillomavirus (HPV) DNA Detection Using Self-Sampling Devices in Women Undergoing Long Term Immunosuppressive Therapy

Immunosuppression is a risk factor of persistent human papillomavirus (HPV) infections, which might lead to development of (pre)malignant lesions of the cervix and lower anogenital tract. Results of HPV DNA testing using cervicovaginal self-samples are comparable to those that are clinician-obtained and therefore might be used in cervical screening. The aim of this study was to assess the prevalence of high-risk HPV (hrHPV) infections, their risk factors and the genotypes distribution among women undergoing immunosuppressive therapy. Women undergoing immunosuppressive therapy for at least three months due to solid organ transplantation or autoimmune disorders were asked to self-collect samples for HPV testing using cervicovaginal brushes and complete questionnaires regarding cervical cancer risk factors. HPV DNA detection and genotyping were performed using Genotyping kit HPV GP version 2. hrHPV was detected in 26/90 (28.9%) specimens. Genotyping revealed a broad range of hrHPV, with type 16 being the most common genotype (11/26). The components of bivalent/quadrivalent or nonavalent vaccines cover all genotypes present in 4.4% and 17.8% women, respectively, and occur as a co-infection with other types in 12.2% and 23.3% of women, respectively. The only feature significantly associated with being hrHPV-positive was having at least two lifetime sexual partners. The high prevalence of hrHPV infections among immunosuppressed women emphasizes the need for regular cervical cancer screening with HPV DNA testing, which might be performed on self-collected specimen

Evaluation of chronic HCV infection in transplanted livers using a modified histological activity index

The majority of histopathological classifications of primary chronic viral hepatitis and recurrence of HCV infection in liver transplants is based on the histological activity index (HAI) introduced by Knodell et al in 1981; however, correlation between HAI and clinical/laboratory data is poor. Therefore, the aim of this study was to present a modification of HAI (mHAI) adapted to distinct features of graft infection, and to evaluate its usefulness in the description of disease activity

Test characteristics for various combinations of biomarkers at 2 hr post-surgery.

<p>Test characteristics for various combinations of biomarkers at 2 hr post-surgery.</p

Changes in serum creatinine (LS mean ± SE) at various time points after liver transplantation in the non-AKI and AKI group.

<p>*<i>p</i>≤0.0001 for differences between groups by repeated measures ANOVA.</p

Changes in urinary netrin-1 (A) and sema3A (B) concentrations at various time points after liver transplant surgery in non-AKI and AKI patients.

<p>Error bars are LS mean ± SEM. *<i>P</i> = <0.001 for differences between groups (non-AKI and AKI) by repeated-measures ANOVA.</p

ROC curve analysis for urinary semaphorin 3A, Netrin-1, and NGAL at 2 hours after liver transplantation.

<p>The values are urinary concentrations at 2 hours after liver transplant, which correspond to 95% sensitivity, optimal sensitivity and specificity, and 95% specificity, respectively, for each biomarker.</p

Descriptive statistics of patient characteristics.

<p>Means ± standard deviation (SD) are reported for continuous measures, percentages are reported for categorical variables.</p>a<p>Welch modified two-sample <i>t</i> test.</p>b<p>Fisher exact test.</p><p>Descriptive statistics of patient characteristics.</p