Status In Renal Transplant Recipients Research Articles

Estimation of Sensitization Status in Renal Transplant Recipients by Assessing Indirect Pathway CD4 + T Cell Response to Donor Cell-pulsed Dendritic Cell.

Generation of donor-specific human leukocyte antigen antibody (DSA) via indirect allorecognition is detrimental to long-term survival of transplant organs. The detection of such immune responses would make it possible to define patients with high risk of sensitization. In this study, we established a novel method for evaluating indirect allorecognition to assess sensitization in kidney transplant recipients. Recipient CD14 + monocytes were mixed with donor peripheral blood mononuclear cells; cultured in the presence of IL-4, GM-CSF, IL-1β, and TNFα; and used as pulsed dendritic cells (DCs). Cell proliferation and cytokine production were evaluated by carboxyfluorescein diacetate succinimidyl ester-based T cell proliferation assay and Enzyme-Linked ImmunoSpot assay, respectively. CD4 + T cell proliferation was strongly observed in following coculture with allogeneic antigen-pulsed DC leading to interferon-γ and IL-21 production. About 1% of CD4 + T cells exhibited Tfh-like phenotype (PD-1 high CXCR5 + ICOS + CD40L + ). Recipient DC pulsed with donor peripheral blood mononuclear cells was cocultured with recipient CD45RA+CD4+ and CD45RA-CD4+ (generally defined as naive and memory in humans, respectively) T cells. Irrespective of preformed or de novo DSA status, CD45RA + CD4 + T cells constantly produced IL-21. In contrast, IL-21-produced CD45RA - CD4 + T cells were significantly higher in preformed DSA-positive patients than those in negative patients (80.8 ± 51.2 versus 14.8 ± 20.4, P < 0.001). In de novo DSA-positive patients, IL-21-produced CD45RA - CD4 + T cells were significantly increased after transplantation compared with before transplantation (9.23 ± 9.08 versus 43.9 ± 29.1, P < 0.001). Assessment of indirect pathway CD4 + T cell response could provide new insights into the underlying mechanism of de novo DSA production, leading to the development of effective strategies against antibody-mediated rejection.

The Effect of Enalapril, Losartan, or Not Antihypertensive on the Oxidative Status in Renal Transplant Recipients.

The clinical and biochemical improvement observed in kidney transplant (RT) recipients is remarkable. The correct functioning of the allograft depends on various factors such as the donor's age, the alloimmune response, the ischemia-reperfusion injury, arterial hypertension, and the interstitial fibrosis of the allograft, among others. Antihypertensive drugs are necessary for arterial hypertension patients to avoid or reduce the probability of affecting graft function in RT recipients. Oxidative stress (OS) is another complex pathophysiological process with the ability to alter posttransplant kidney function. The study's objective was to determine the effect of the administration of Enalapril, Losartan, or not antihypertensive medication on the oxidative state in RT recipients at the beginning of the study and one year of follow-up. All patients included in the study found significant overexpression of the oxidative damage marker to DNA and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). In contrast, it was found that the determination of the total antioxidant capacity decreased significantly in the final determination at one year of follow-up in all the patients who ingested Enalapril and Losartan. We found dysregulation of the oxidative state characterized mainly by oxidative damage to DNA and a significant increase in antioxidant enzymes, which could suggest a compensatory effect against the imbalance of the oxidative state.

Lymphocyte function based on IFN-γ secretion assay may be a promising indicator for assessing different immune status in renal transplant recipients

BackgroundImmunological monitoring plays a crucial role in organ recipients for allowing tailoring of immunosuppression. However, there is still a paucity of promising indicators for detecting immune status in recipients. MethodsWe conducted a prospective study to characterize the immune status by detecting dynamically lymphocyte subsets and function (represented by the abilities to secrete IFN-γ) in the first 6 months posttransplant in renal recipients. Participants were classified into an immune stable group, infected group, and rejected group. ResultsIn the stable group, our study suggested that the counts and function of CD4+ T, CD8+ T, and NK lymphocytes decreased to their nadir at week 2, and thereafter these indicators were gradually restored. The counts exceeded pre-operative levels, whereas function did not reach the pre-transplant levels by 6 months. We demonstrated that function of lymphocytes was considerably decreased in infected recipients compared with the stable group when infection occurred. By contrast, the function of lymphocytes was obviously increased at the point of rejection. Receiver operating characteristic (ROC) analysis in the combination of subsets and function of lymphocytes presented a superior clinical value with an area under the curve (AUC) of 0.903 in the diagnosis of infected receivers, and IFN-γ+CD8+ T cells% is the highest indicator with the auROC curve of 0.862. Another ROC analysis confirmed that IFN-γ+CD4 T cells% presented a preferable diagnostic value with an area of 0.887 for rejected recipients. ConclusionsIn conclusion, the ability of lymphocyte subsets secreting IFN-γ may provide a promising assessment of immune status in recipients and allow timely modifying immunosuppression.

Relationship between renal function and blood pressure dipping status in renal transplant recipients: a longitudinal study

BackgroundHypertension (HT) is associated with adverse outcomes in kidney transplant (KTX) recipients. Blunting of physiological decrease in nighttime compared to daytime blood pressure (non-dipping status) is frequent in this setting. However, weather non-dipping is independently associated with renal function decline in KTX patients is unknown.MethodsWe retrospectively screened KTX outpatients attending for a routine ambulatory blood pressure monitoring (ABPM) (T1) at a single tertiary hospital. Patients had two successive follow-up visits, 1 (T2) and 2 (T3) years later respectively. Routine clinical and laboratory data were collected at each visit. Mixed linear regression models were used with estimated glomerular filtration rate (eGFR) as the dependent variable.ResultsA total of 123 patients were included with a mean follow-up of 2.12 ± 0.45 years after ABPM. Mean age and eGFR at T1 were 56.0 ± 15.1 and 54.9 ± 20.0 mL/min/1.73m2 respectively. 61 patients (50.4%) had sustained HT and 81 (65.8%) were non-dippers. In multivariate analysis, systolic dipping status was positively associated with eGFR (p = 0.009) and compared to non-dippers, dippers had a 10.4 mL/min/1.73m2 higher eGFR. HT was negatively associated with eGFR (p = 0.003).ConclusionsWe confirm a high prevalence of non-dippers in KTX recipients. We suggest that preserved systolic dipping is associated with improved renal function in this setting independently of potential confounders, including HT and proteinuria. Whether modification of dipping status by chronotherapy would preserve renal function remains to be tested in clinical trials.

Bioinformatics analyses on the immune status of renal transplant patients, a systemic research of renal transplantation

BackgroundKidney transplantation is the most effective treatment for end-stage renal disease. Allograft rejections severely affect survivals of allograft kidneys and recipients.MethodsUsing bioinformatics approaches, the present study was designed to investigate immune status in renal transplant recipients. Fifteen datasets from Gene Expression Omnibus (GEO) were collected and analysed. Analysis of gene enrichment and protein-protein interactions were also used.ResultsThere were 40 differentially expressed genes (DEGs) identified in chronic rejection group when compared with stable recipients, which were enriched in allograft rejection module. There were 135 DEGs identified in acute rejection patients, compared with stable recipients, in which most genes were enriched in allograft rejection and immune deficiency. There were 288 DEGs identified in stable recipients when compared to healthy subjects. Most genes were related to chemokine signalling pathway. In integrated comparisons, expressions of MHC molecules and immunoglobulins were increased in both acute and chronic rejection; expressions of LILRB and MAP 4 K1 were increased in acute rejection patients, but not in stable recipients. There were no overlapping DEGs in blood samples of transplant recipients.ConclusionBy performing bioinformatics analysis on the immune status of kidney transplant patients, the present study reports several DEGs in the renal biopsy of transplant recipients, which are requested to be validated in clinical practice.

Urinary Excretion of N1-Methylnicotinamide, as a Biomarker of Niacin Status, and Mortality in Renal Transplant Recipients.

Renal transplant recipients (RTR) commonly suffer from vitamin B6 deficiency and its functional consequences add to an association with poor long-term outcome. It is unknown whether niacin status is affected in RTR and, if so, whether this affects clinical outcomes, as vitamin B6 is a cofactor in nicotinamide biosynthesis. We compared 24-h urinary excretion of N1-methylnicotinamide (N1-MN) as a biomarker of niacin status in RTR with that in healthy controls, in relation to dietary intake of tryptophan and niacin as well as vitamin B6 status, and investigated whether niacin status is associated with the risk of premature all-cause mortality in RTR. In a prospective cohort of 660 stable RTR with a median follow-up of 5.4 (4.7–6.1) years and 275 healthy kidney donors, 24-h urinary excretion of N1-MN was measured with liquid chromatography-tandem mass spectrometry LC-MS/MS. Dietary intake was assessed by food frequency questionnaires. Prospective associations of N1-MN excretion with mortality were investigated by Cox regression analyses. Median N1-MN excretion was 22.0 (15.8–31.8) μmol/day in RTR, compared to 41.1 (31.6–57.2) μmol/day in healthy kidney donors (p < 0.001). This difference was independent of dietary intake of tryptophan (1059 ± 271 and 1089 ± 308 mg/day; p = 0.19), niacin (17.9 ± 5.2 and 19.2 ± 6.2 mg/day; p < 0.001), plasma vitamin B6 (29.0 (17.5–49.5), and 42.0 (29.8–60.3) nmol/L; p < 0.001), respectively. N1-MN excretion was inversely associated with the risk of all-cause mortality in RTR (HR 0.57; 95% CI 0.45–0.71; p < 0.001), independent of potential confounders. RTR excrete less N1-MN in 24-h urine than healthy controls, and our data suggest that this difference cannot be attributed to lower dietary intake of tryptophan and niacin, nor vitamin B6 status. Importantly, lower 24-h urinary excretion of N1-MN is independently associated with a higher risk of premature all-cause mortality in RTR.

Chronic Use of Proton-Pump Inhibitors and Iron Status in Renal Transplant Recipients.

Proton-pump inhibitor (PPI) use may influence intestinal iron absorption. Low iron status and iron deficiency (ID) are frequent medical problems in renal transplant recipients (RTR). We hypothesized that chronic PPI use is associated with lower iron status and ID in RTR. Serum iron, ferritin, transferrin saturation (TSAT), and hemoglobin were measured in 646 stable outpatient RTR with a functioning allograft for ≥ 1 year from the “TransplantLines Food and Nutrition Biobank and Cohort Study” (NCT02811835). Median time since transplantation was 5.3 (1.8–12.0) years, mean age was 53 ± 13 years, and 56.2% used PPI. In multivariable linear regression analyses, PPI use was inversely associated with serum iron (β = −1.61, p = 0.001), natural log transformed serum ferritin (β = −0.31, p < 0.001), TSAT (β = −2.85, p = 0.001), and hemoglobin levels (β = −0.35, p = 0.007), independent of potential confounders. Moreover, PPI use was independently associated with increased risk of ID (Odds Ratio (OR): 1.57; 95% Confidence Interval (CI) 1.07–2.31, p = 0.02). Additionally, the odds ratio in RTR taking a high PPI dose as compared to RTR taking no PPIs (OR 2.30; 95% CI 1.46–3.62, p < 0.001) was higher than in RTR taking a low PPI dose (OR:1.78; 95% CI 1.21–2.62, p = 0.004). We demonstrated that PPI use is associated with lower iron status and ID, suggesting impaired intestinal absorption of iron. Moreover, we found a stronger association with ID in RTR taking high PPI dosages. Use of PPIs should, therefore, be considered as a modifiable cause of ID in RTR.

Functional vitamin B-6 status and long-term mortality in renal transplant recipients

Background: Low plasma concentrations of pyridoxal 5'-phosphate (PLP) are common in renal transplant recipients (RTRs) and confer increased risk of long-term mortality. To our knowledge, it is not known whether low plasma PLP concentrations have functional (i.e., intracellular) consequences and, if so, whether such consequences are associated with increased risk of mortality.Objectives: We assessed the association of plasma PLP with functional vitamin B-6 status and explored the potential association of functional vitamin B-6 status with long-term mortality in RTRs.Design: In a longitudinal cohort of 678 stable RTRs with a median follow-up of 5.3 y (IQR: 4.8-6.1 y) and 297 healthy controls, PLP, plasma 3-hydroxykynurenine (3-HK), and xanthurenic acid (XA) were analyzed via validated assays. PLP was used as direct biomarker for vitamin B-6 status, and the 3-HK:XA ratio was used as functional biomarker of vitamin B-6 status with a higher ratio reflecting worse functional vitamin B-6 status.Results: Median PLP, 3-HK, and XA concentrations were 41 nmol/L (IQR: 29-60 nmol/L), 40.1 nmol/L (IQR: 33.0-48.0 nmol/L), and 19.1 nmol/L (IQR: 14.5-24.9 nmol/L), respectively, in healthy controls compared with 29 nmol/L (IQR: 17-50 nmol/L), 61.5 nmol/L (IQR: 45.6-86.5 nmol/L), and 25.5 nmol/L (IQR: 17.2-40.0 nmol/L), respectively, in RTRs (all P < 0.001). RTRs had a higher median 3-HK:XA ratio (2.38; IQR: 1.68-3.49) than did healthy controls (2.13; IQR: 1.63-2.71) (P < 0.05). In RTRs, the 3-HK:XA ratio was inversely associated with plasma PLP (β = -0.21, P < 0.001). Moreover, a higher 3-HK:XA ratio was independently associated with increased risk of all-cause mortality (HR per SD increment: 1.30; 95% CI: 1.13, 1.49), cancer mortality (HR per SD increment: 1.47; 95% CI: 1.12, 1.95), and infectious disease mortality (HR per SD increment: 1.50; 95% CI: 1.21, 1.86) in RTRs.Conclusions: Vitamin B-6-deficient RTRs have a worse functional vitamin B-6 status than do healthy controls and vitamin B-6-sufficient RTRs. Worse functional vitamin B-6 status in RTRs is independently associated with an increased risk of mortality particularly because of cancer and infectious disease. This trial was registered at clinicaltrials.gov as NCT02811835.

Vitamin D status in renal transplant recipients living in a low-latitude city: association with body fat, cardiovascular risk factors, estimated glomerular filtration rate and proteinuria.

Recent evidence suggests that vitamin D deficiency is associated with CVD, impaired kidney function and proteinuria. To date, no study has evaluated these associations in renal transplant recipients (RTR) adjusting for body adiposity assessed by a 'gold standard' method. This study aimed to evaluate the vitamin D status and its association with body adiposity, CVD risk factors, estimated glomerular filtration rate (eGFR) and proteinuria in RTR, living in Rio de Janeiro, Brazil (a low-latitude city (22°54'10"S)), taking into account body adiposity evaluated by dual-energy X-ray absorptiometry (DXA). This cross-sectional study included 195 RTR (114 men) aged 47·6 (sd 11·2) years. Nutritional evaluation included anthropometry and DXA. Risk factors for CVD were hypertension, diabetes mellitus, dyslipidaemia and the metabolic syndrome. eGFR was evaluated using the Chronic Kidney Disease Epidemiology Collaboration equation. Serum 25-hydroxyvitamin D (25(OH)D) concentration was used to define vitamin D status as follows: 10 % (n 19) had vitamin D deficiency (30 ng/ml). Percentage of body fat (DXA) was significantly associated with vitamin D deficiency independently of age, sex and eGFR. Lower 25(OH)D was associated with higher odds of the metabolic syndrome and dyslipidaemia after adjustment for age, sex and eGFR, but not after additional adjustment for body fat. Hypertension and diabetes were not related to 25(OH)D. Lower serum 25(OH)D was associated with increasing proteinuria and decreasing eGFR even after adjustments for age, sex and percentage of body fat. This study suggests that in RTR of a low-latitude city hypovitaminosis D is common, and is associated with excessive body fat, decreased eGFR and increased proteinuria.

Vitamin D Status in Renal Transplant recipients is not Associated with Erectile Dysfunction.

Erectile dysfunction (ED) is a highly prevalent disorder among renal transplant recipients. Vitamin D deficiency (VDD) has been associated with several ED risk factors but only recently directly linked to ED. We conducted a study to investigate whether vitamin D serum levels were associated with the presence and severity of ED in 40 male patients that underwent deceased donor kidney transplantation (TX) from 2001 to 2013. Blood samples were collected on two seasonally distinct occasions and 25(OH)D concentration was assessed by radioimmunoassay. A 5-item version of the International Index of Erectile Function (IIEF-5) was used for ED evaluation and group stratification. We found comparable rates of ED (75%) and VDD (42.5%-62.5%) as in previously published studies. Serum levels of 25(OH)D did not differ between patients with and those without ED on both measurements (p=0.656 and p=0.914, respectively), or when comparing different ED severity groups. Duration of renal replacement therapy before TX and graft duration until analysis were longer in patients with ED (p=0.022 and p=0.05, respectively), but with the results being nonsignificant on logistic regression. In conclusion, we found no association of 25(OH)D concentration with the presence and severity of ED in renal transplant recipients. So far, there are no similar published data.

The Current Status of Renal Transplant Recipients with Hepatitis C: A Single Center Experience

Renal transplantation (RTx) may result in the development of liver disorder/hepatic cancer or hepatitis C virus (HCV)- related membranoproliferative glomerulonephritis, which may lead to graft loss, in renal failure patients with previously untreated HCV infection. Long-term survival is longer in HCV antibody-positive renal transplant recipients than in HCV antibody-negative/-positive dialysis patients, whereas renal graft survival and patient survival are lower in HCV antibody-positive renal transplant recipients than in HCV antibody-negative patients; thus, HCV treatment should be administered to HCV antibodypositive renal transplant recipients. Interferon/ribavirin (IFN/Rib) therapy is one of the current HCV treatments in Japan. In renal failure patients including those undergoing hemodialysis, Rib is contraindicated because of possible kidney function problems; IFN monotherapy is indicated for these patients. However, in clinical practice, IFN monotherapy is not performed adequately because of efficacy problems or adverse reactions to IFN, leading to the presence of many HCV carriers and patients with previous HCV infection among hemodialysis patients in the RTx waiting list. The sustained virological response in patients receiving IFN therapy after RTx is low. Many patients discontinue the therapy and some develop graft loss because of IFN-related acute rejection. Therefore, dialysis patients with HCV infection who are scheduled for RTx should first receive IFN therapy. In Japan, daclatasvir/ asunaprevir combination therapy was introduced as an IFN-free antiviral therapy in September 2015. However, its safety in dialysis patients has not been established, and these patients still require IFN therapy. We report the current state of renal transplant recipients with HCV at our hospital.

Evaluation of Nutritional Status in Renal Transplant Recipients in Accordance with Changes in Graft Function

Introduction and AimsRenal transplantation (RT) is the ultimate treatment modality for end-stage renal disease (ESRD) patients. Malnutrition is a strong predictor of cardiovascular disease among ESRD patients. Body composition analysis using bioimpedance devices (BIA) is a useful noninvasive tool to detect malnutrition in this population. We investigated the impact of graft function on nutritional status and reliability of BIA to detect malnutrition in RT recipients. MethodsWe evaluated retrospectively 189 RT recipients including 59 females, and of overall mean age of 38.3 ± 10.6 years who had a minimum posttransplant follow-up of 12 months. Body Composition Analyzer (Tanita BC-420MA) determinations were complemented with monthly assessments of biochemical parameters. Patients were divided into 3 groups according to glomerular filtration rate (GFR) levels: normal graft function/high GFR group (group 1, normal creatinine levels, no proteinuria and GFR ≥ 90 mL/min; n = 59); low renal function/low GFR group (normal or high creatinine levels with low GFR levels; group 2; GFR 89–60 mL/min; n = 87) and group 3, (GFR < 60 mL/min; n = 43). ResultsGroup 3 patients displayed significantly lower as well as hemoglobin albumin and calcium concentrations, with higher phosphorus and parathyroid hormone levels (P = .0001). They also showed significantly lower body weight (P = .0001), body mass index (P = .002), fat (P = .002) and muscle (P = .0001) contents as well as fat-free mass (P = .0001). Group 2 patients had significantly lower values compared with group 1 and higher values than group 3. GFR values positively correlated with albumin, fat, muscle, and fat-free mass (r = 0.337, 0.299, 0.281, 0.278, respectively; P = .0001). GFR values positively correlated with visceral fat ratio (r = 0.170; P = 0.02), body mass index (r = 0.253; P = .0001), and waist-hip ratio (r = 0.218; P = .006). ConclusionLoss of muscle and fat mass is an early sign of malnutrition among RT recipients. It is closely associated with loss of GFR. BIA is a noninvasive and reliable diagnostic tool that should be included in the follow-up of these patients for an early diagnosis of malnutrition-related complications.

Evaluation of Nutritional Status in Renal Transplant Recipients in Accordance to Changes in Graft Function

Introduction and aims: Renal transplantation is the ultimate treatment modality for end stage renal disease and was reported to improve many complications associated with renal failure. Malnutrition is also a reversible process which usually resolves after transplantation. However there is insufficient data about body composition analyzes and nutritional status of renal transplantation recipients. In this study, we investigated the effect of graft function on nutritional status and body composition analysis in a group of renal transplant recipients. Methods: 189 renal transplant recipients (59 female, aged; 38.3 ± 10.6 years)who had a minimum posttransplantation follow-up duration of 12 months were included. All patients had an anthropometric and body composition analysis. Body compositions were analyzed by using the Body Composition Analyzer (Tanita BC-420MA). Monthly assessed biochemical parameters including anemia parameters, hemoglobin albumin, CRP, calcium, phosphorus, parathyroid hormone level, lipid profile of the last 6 months were retrospectively collected. Patients were divided into 2 groups according to GFR levels as normal function (group 1, GFR ≥ 90 mL/min, n: 59) and low renal function (group 2, GFR < 90 mL/min, n: 130) groups. Results: Study groups were in means of demographic characteristics. Group 2 patients had significantly lower waist-hip ratios and sagittal abdominal diameter (p:0.01 and 0.007 respectively) than group 1 patients. Group 2 patients had lower body weight (68.1±12.9 vs 77.7±4.4 kg) and lower BMI (24.9±5.3 vs 27±4.4) than group 1 patients (p:0,01). According to body composition analysis group 2 patients had significantly lower fat, muscle and bone mass values (p: 0.009, 0.0001, 0.0001 respectively). A correlation analysis revealed that GFR values were positively correlated with fat, muscle and bone mass values (r: 0.289, 0.283, 0.260 respectively, p:0.0001). GFR vales were also positively correlated with visceral fat ratio (r: 0.169, p:0.02), body mass index (r:0.253, p: 0.0001) and waist-hip ratio (r:0.218, p: 0.006). Group 2 had significantly lower albumin (p: 0.02), higher P (p: 0.05), lower calcium (0.001), higher iPTH (p: 0.029), lower hemoglobin (0.0001) levels compared to group 1. Conclusions: Our results indicate that mean predictor of nutrition after renal transplantation is graft function. As the graft function declines a significant decrease in body weight and body fat followed by a decreased in muscle mass is observed that triggers the development of malnutrition. Therefore nutritonal assessment should be mandatory in patients with failing grafts.

Relationship Among Endothelial Response to Hyperemia, Bone Marrow-Derived Progenitor Cells, and Parathyroid Hormone in Renal Transplantation

Endothelial dysfunction may contribute to modulate cardiovascular complications in renal transplant recipients (RTRs), and a relationship between endothelial dysfunction and parathyroid hormone (PTH) levels in RTRs has been demonstrated. We evaluated the relationship between endothelial response to hyperemia and circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) PTH, and genetic parameters in RTRs. In 120 RTRs and in healthy subjects without (n=107, group A) and with cardiovascular risk factors (n=109, group B), we evaluated endothelial response to hyperemia through digital tonometry (peripheral arterial tonometry) detected by reactive hyperemia index (RHI) and EPCs and CPCs by flow cytometry. In RTRs, RHI median value was lower than in group A (P=0.05). EPC number was significantly lower in RTRs than in groups A and B (P<0.0001), whereas PTH median value was significantly higher (P<0.0001). In RTRs, RHI values were significantly lower according to the presence of three or more risk factors (P=0.04) and positively correlated with EPCs (P=0.04) but not with PTH (P=0.2). In patients who underwent dialysis for more than 5 years, lower RHI values (P=0.08), EPC number (P=0.5), and higher PTH concentrations (P=0.09) than in patients with less than 1 year dialysis time were observed. No relationship between eNOS gene -786T>C, 894G>T, and 4a/4b polymorphisms and RHI, EPC, and CPC number was found. This study shows an altered endothelial response, associated with reduced EPCs, and increased PTH in RTRs; the evaluation of endothelial status in RTRs may contribute to better assess the risk profile of these patients.

Health‐related quality of life and employment among renal transplant recipients

To examine the relationship between health-related quality of life (HQoL) and employment status in renal transplant recipients (RTRs). Eighty-two RTRs met inclusion criteria: 21-65 yr of age; greater than one yr post-transplant; and received calcineurin inhibitors. A cross-sectional survey was conducted using a demographics questionnaire and the following HQoL instruments: SF-12 Health Survey version 2 (Physical Component Summary [PCS-12] and Mental Component Summary [MCS-12]) and Kidney Transplant Questionnaire (KTQ). Two multivariate logistic regression analyses (SF-12 model and KTQ model) were conducted to determine whether HQoL and demographic variables were independently associated with employment status. Seventy-five RTRs were included in the analysis. Compared with employed RTRs, a greater number of unemployed RTRs were non-white, had lower education levels, and had deceased donor transplants (p < 0.05). Employed RTRs had significantly higher SF-12 scores (p < 0.05). In the SF-12 logistic regression model, PCS-12 and education level were significant predictors of employment status (p < 0.05). In the KTQ model, the Fatigue subscale and education level were significant predictors of employment status (p < 0.05). Findings suggest higher PCS-12, higher KTQ-Fatigue, and education level are independently associated with employment status. Interventions targeted to improve HQoL, decrease fatigue, and increase education level are discussed.

Feasibility of diagnosing renal allograft dysfunction by oligonucleotide array: Gene expression profile correlates with histopathology

Background Effective non-invasive monitoring method to tell histopathology is a big challenge in renal transplantation. Methods We used 70-mer long oligonucleotide array with 449 immune related genes to determine gene expression profiles of peripheral blood mononuclear cells (PBMCs) under different immune status including stable renal function (TX), acute tubular necrosis (ATN), biopsy conformed acute rejection (AR), clinical rejection with pathology of borderline changes (BL), clinical rejection without biopsy proven/presumed rejection (PR) and renal dysfunction without rejection (NR). Results Distinct molecular expression signatures in each group were found to correlate with histopathology. And we concluded that B cell chemokine CXCL13 and mast cell may play a role in renal allograft rejection through significant difference analysis and functional pathway analysis. Conclusions It provides a potential non-invasive method for monitoring renal allograft function and immune status of renal transplant recipients.

Gingival Status of Brazilian Renal Transplant Recipients Under Sirolimus‐Based Regimens

Although the prevalence of gingival overgrowth (GO) in calcineurin-inhibitor (CNI) immunosuppressive regimens has been well documented, to the best of our knowledge data from sirolimus (SIR) regimens have not been described. We sought to investigate the gingival status of renal transplant recipients under SIR-based regimens with regard to the prevalence and potential risk variables associated with GO. A cross-sectional study was conducted at a public hospital in Belo Horizonte, MG, Brazil. Of 886 transplant recipients, an eligible sample of 144 subjects was selected. Medical, pharmacologic, and periodontal variables were recorded for each subject. GO was assessed through visual inspection and was evaluated in relation to variables of interest by univariate and multivariate analyses. Although not clinically significant, 20.8% of the samples had GO, with a mean GO score of 5.0% +/- 3.98% (range, 0% to 19%) and mean GO score per papilla of 0.378 +/- 0.361 (range, 0.1 to 1.9); the percentage of papilla affected by GO was 14.35% +/- 9.86% (range, 5% to 45%). The multivariate final model, excluding periodontal variables, showed that the concomitant use of calcium channel blockers (P = 0.033) and the interaction between time since transplant and previous CNI use (P <0.001) were associated with GO. Adding periodontal variables to the model improved its accuracy and retained papillary bleeding index as being strongly associated with GO (P <0.001). GO was observed in a considerable number of subjects under SIR-based immunosuppressive regimens, although the relationship was not clinically significant. Findings point to the importance of cooperation between medical and dental health care personnel in the maintenance of renal transplant recipients under SIR-based immunosuppressive regimens.

Gingival health status in renal transplant recipients: relationship between systemic inflammation and atherosclerosis

Cardiovascular disease (CVD) is the leading cause of mortality in renal transplant recipients (RTR). Systemic and periodontal inflammation has been suggested to have a possible role in the development of atherosclerosis. In the present study, we aimed to investigate the relationship between gingival health status, inflammation and atherosclerosis in RTRs. Eighty-three RTR (50 male, 33 female) were enrolled in the study. Routine biochemical analyses, serum lipoproteins, C-reactive protein, fibrinogen, homocystein, parathyroid hormone (PTH) and cyclosporin A (CsA) trough levels were studied. All patients had 24-h ambulatory blood pressure monitoring and B-mode ultrasound of the common carotid arteries. Gingival status was evaluated by the Löe and Silness gingival index (GI). Mean GI value was 2.3 +/- 0.5. Fifty patients (60.3%) had GI value >or= 2.1 (severe gingivitis; group A). Thirty-three patients (39.7%) had GI value < 2.1 (no or moderate gingivitis; group B). Age, carotid intima-media thickness (CIMT) and mean time on dialysis before transplantation were significantly higher in group A than in B. Systemic inflammation markers were not different between group A and group B. Mean CIMT was positively correlated with GI (r = 0.425; p = 0.001) and negatively correlated with high-density lipoprotein cholesterol (r = -0.256; p = 0.023). After the correction for confounding variables, mean CIMT was still significantly correlated with GI (r = 0.376, p = 0.02). In RTR, gingival inflammation seems to be associated with CIMT in the absence of systemic inflammation. Thus, gingivitis may, in part, play a role in the development of systemic atherosclerosis without causing any aggravation in systemic inflammatory response.

Oral health in renal transplant recipients administered cyclosporin A or tacrolimus

The aim of this study was to determine the oral status of renal transplant recipients receiving cyclosporin A (CsA) or tacrolimus (FK-506) as immunosuppressant. A total of 88 renal transplant recipients receiving CsA (63 men and 25 women, mean age 51.4 years) and 67 receiving FK-506 (57 men and 10 women, mean age 33.5 years) were included in the study. Donor type, histocompatibility, cold ischemia time and prior delayed graft function were similar between the two groups. Demographics and pharmacological data were recorded for all subjects. The results demonstrated that CsA caused a greater number of oral diseases. A greater number of gingival overgrowth was present in patients treated with CsA. However, the combined use with calcium channel blockers increased the gingival overgrowth number. The occurrence of candida in saliva was observed in 80 renal recipients treated with CsA and 20 treated with FK-506. The presence of squamous oral carcinoma (n = 3) and herpes simplex (n = 10) was observed in patients treated with CsA. These alterations were not observed in renal recipients treated with FK-506. Renal recipients constitute a high-risk group for oral diseases, as they are immunocompromised. However, the FK-506 regime appears to ameliorate this effect, compared with CsA. Adequate pre- and post-transplant oral health care is recommended for these subjects, irrespective of the time interval for which the drug is administered.

Pulmonary Function in Renal Transplant Recipients and End-Stage Renal Disease Patients Undergoing Maintenance Dialysis

The aim of this study was to reveal the pulmonary function status of renal transplant recipients and chronic renal failure patients on hemodialysis or continuous ambulatory peritoneal dialysis. The study involved 73 subjects, including 49 patients who were either on peritoneal dialysis ( n = 22) or hemodialyis ( n = 27), and 24 renal transplant recipients. The spirometry results revealed significantly higher residual volume and total lung capacity in the hemodialysis and peritoneal dialysis groups than in the transplantation group. Forced expiratory flow between 25% and 75% of vital capacity was slightly below normal in the dialysis patients. Preservation of diffusion capacity of the lung for carbon monoxide was noted in the hemodialysis group (112.4%). Inspiratory and expiratory muscle strength was reduced in all groups. Only type of dialysis was correlated with this reduction. Inspiratory muscle strength in the peritoneal dialysis group (49.9%) was significantly lower than in the transplantation and hemodialysis groups (54.7% and 66.5%, respectively). The spirometry findings suggest that small-airway disease causes increased residual volume and total lung capacity (hyperinflation) in hemodialysis and peritoneal dialysis patients and that this airway obstruction subsides after renal transplantation. Preserved diffusion capacity in the hemodialysis group was attributed to the use of biocompatible dialyzer membranes. Renal failure complications may be the main explanation for global respiratory muscle weakness in dialysis patients, whereas corticosteroid therapy might be the primary cause in kidney graft recipients. Significantly lower inspiratory muscle strength in the peritoneal dialysis group suggests that presence of intra-abdominal dialysate might interfere with diaphragmatic contraction.