Assessment of CTLA-4 Gene Expression Levels on CD8+ T Cells in Renal Transplant Patients and Relation with Serum sCTLA-4 Levels.

CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) is an immune regulator molecule that is expressed on a variety of immune cells, including CD4+ and CD8+ T cells. After realizing the significance of this regulator molecule, researchers began to concentrate on its activation or inhibition in cancer. Even though there have been some studies on organ transplantation and autoimmunity, the role of the CTLA-4 molecule in renal transplantation has not been demonstrated. The goal of this study was to see how CTLA-4 gene expression and serum sCTLA-4 levels affected renal transplant patients. Peripheral blood samples were collected before and 1-3 months after renal transplantation from 29 recipients. CD8+ T lymphocytes were separated using magnetic beads and purity of the cells controlled by Flow cytometry. CTLA-4 mRNA levels were determined by Real-Time PCR while serum sCTLA-4 levels were assessed by ELISA. 55% of the patient had decreased level of CTLA-4 mRNA after transplantation when compared to pre-transplantation levels. Moreover 61% of the patient had lower serum sCTLA-4 levels after transplantation. sCTLA-4 levels were decreased 11% of the patients with rejection episode after transplantation when compared to stabile patients (5%). Kidney rejection is a complicated process influenced by numerous unknown factors. Several parameters should be evaluated together to precise rejection episodes or graft dysfunctions. Further research focused on the other immune checkpoint regulator molecules could give an opportunity to have an idea about the effect of these molecules on renal transplantation.

Relationship between disease awareness and severity of kidney disease in autosomal dominant polycystic kidney disease patients.

INTRODUCTION: Polycystic kidney disease (PKD) is responsible for 5%-10% of end-stage renal disease. We examined the relationship between renal and extrarenal findings, disease severity, and the level of consciousness of PKD patients. METHODS: Patients were asked to answer the questionnaire about PKD. Disease severity was determined according to estimated glomerular filtration rate, and disease awareness was assessed by adapting the Disease Perception Scale to PKD. Awareness of patients was evaluated comparatively with chronic kidney disease stage, age, region, and symptoms. RESULTS: One out of five patients does not know that this disease is inherited. Mean awareness scores of the patients decreased significantly with increasing age. Awareness scores were significantly higher in patients with flank pain, hematuria, and urinary tract stones. CONCLUSION: Although PKD is the most common hereditary kidney disease, the rate of patients' knowledge on this subject is low. Increased awareness might lead to better treatment in those patients.

Middle-term outcomes in renal transplant recipients with COVID-19: a national, multicenter, controlled study.

Background: In this study, we evaluated 3-month clinical outcomes of kidney transplant recipients (KTR) recovering from COVID-19 and compared them with a control group. Method: The primary endpoint was death in the third month. Secondary endpoints were ongoing respiratory symptoms, need for home oxygen therapy, rehospitalization for any reason, lower respiratory tract infection, urinary tract infection, biopsy-proven acute rejection, venous/arterial thromboembolic event, cytomegalovirus (CMV) infection/disease and BK viruria/viremia at 3 months. Results: A total of 944 KTR from 29 different centers were included in this study (523 patients in the COVID-19 group; 421 patients in the control group). The mean age was 46 ± 12 years (interquartile range 37-55) and 532 (56.4%) of them were male. Total number of deaths was 8 [7 (1.3%) in COVID-19 group, 1 (0.2%) in control group; P = 0.082]. The proportion of patients with ongoing respiratory symptoms [43 (8.2%) versus 4 (1.0%); P < 0.001] was statistically significantly higher in the COVID-19 group compared with the control group. There was no significant difference between the two groups in terms of other secondary endpoints. Conclusion: The prevalence of ongoing respiratory symptoms increased in the first 3 months post-COVID in KTRs who have recovered from COVID-19, but mortality was not significantly different.

Evaluation of renal transplantation recipients those who do not use steroid with panel reactive antibody and donor specific antibody / Evaluación de receptores de trasplante renal que no usan esteroides con panel de anticuerpos reactivos y anticuerpos específicos del donante

ABSTRACT Background: Steroids are the mainstream drugs of immu- nosuppressive regimen in renal transplantation. They are successfully used on induction, maintenance and rejection treatment. Due to complications caused by steroids, treatments are switched to immunosuppressive agents. Graft dysfunction risk caused by reduced total immunosuppression disturbs clinicians very often. We documented the differences among patients by means of clinical presentation and PRA/DSA levels between patients who are using steroids and patients that were prescribed for steroid-free regimen. Methods: 82 individuals who did not use steroid and 52 patients on steroid treatment were included with similar rates of age, sex, primary renal disease, dialysis type, posttransplant follow-up duration and donor type. Pre and posttransplant PRA, DSA levels, posttransplant and current graft function and comorbidities were evaluated. Results: Individuals who do not use steroids were found to have a lower posttransplant creatinine level and glomerular filtration rate (GFR) compared to steroid users. Posttransplant and current spot urinary protein/creatinine rates were also lower in the steroid-free group. However DM, BKVN and induction therapy rates were higher in the steroid-free group. PRA and DSA levels were similar in both groups. On the other hand, posttransplant PRA-I levels were significantly higher in those with less steroid use time. Conclusions: Although steroid free regimens usually worry the clinicians, they can be preferred in patients with low immunological risk for rejection to avoid its side effects such as uncontrolled diabetes, obesity, musculoskeletal problems and cataracts.

RESUMEN Antecedentes: Los esteroides son los principales fármacos del régimen inmunosupresor en el trasplante renal. Se utilizan con éxito en tratamientos de inducción, mantenimiento y rechazo. Debido a las complicaciones causadas por los esteroides, los tratamientos se cambian a agentes inmunosupresores. El riesgo de disfunción del injerto causado por la reducción de la inmunosupresión total perturba a los médicos con mucha frecuencia. Documentamos la diferencia entre los pacientes por medio de la presentación clínica y los niveles de PRA/DSA en aquellos que utilizan esteroides y a los que se les prescribió un regimen sin esteroides. Material y métodos: Se incluyeron 82 individuos que no usaban esteroides y 52 pacientes en tratamiento con esteroides con tasas similares de edad, sexo, enfermedad renal primaria, tipo de diálisis, duración del seguimiento postrasplante y tipo de donante. Se evaluaron la ARP pre y postrasplante, los niveles de DSA, la función y comorbilidades postrasplante y actual del injerto. Resultados: Se encontró que las personas que no usan esteroides tienen un nivel de creatinina postrasplante y una tasa de filtración glomerular (TFG) más bajas en comparación con los usuarios de esteroides. Las tasas de proteína/creatinina urinarias postrasplante y puntuales actuales también fueron más bajas en el grupo sin esteroides. Sin embargo, las tasas de DM, BKVN y terapia de inducción fueron más altas en el grupo sin esteroides. Los niveles de PRA y DSA fueron similares en ambos grupos. Por otro lado, los niveles de PRA-I postrasplante fueron significativamente más altos en aquellos con menos tiempo de uso de esteroides. Conclusiones: Aunque los regimenes libres de esteroides suelen preocupar a los clínicos, pueden ser preferidos en pacientes con bajo riesgo inmunológico de rechazo para evitar sus efectos secundarios, como diabetes no controlada, obesidad, problemas musculoesqueléticos y cataratas.

Immunological Results of Long-Term Use of Mammalian Target of Rapamycin (mTOR) Inhibitors and Its Effects on Renal Graft Functions.

BACKGROUND Calcineurin inhibitor drugs (CNI), which are the basis of immunosuppression in kidney transplantation, contribute to renal graft loss, with increased morbidity and mortality due to their potentially harmful effects on the renal graft, cardiovascular system, and tumor pathology. For this reason, the mammalian target of rapamycin inhibitors (mTORi) such as sirolimus (SRL) and everolimus (EVE) has been preferred more frequently, as they are associated with fewer complications and longer graft function. MATERIAL AND METHODS We enrolled 89 adult renal transplant patients (37 patients on mTORi and 52 on CNI) who had similar age, sex, primary renal disease, dialysis type, post-transplant follow-up period, and donor type. We analyzed and compared the data between patients using mTORi for longer than 5 years and those using CNI regarding pre- and post-transplant panel reactive antibody (PRA), and donor-specific antibody (DSA), as well as post-transplantation and current graft functions. RESULTS Although those using mTORi for more than 5 years had significantly higher mismatch rates (P=0.024) than those using CNI, there was no significant change in PRA and DSA levels. Transplant time was longer in mTORi users (P=0.025). The switch time to mTORi in patients ranged from 0 to 19 years, but the average was 4 years. As expected, actual spot urine protein/creatinine was significantly higher in those using mTORi (P=0.009). Diabetes mellitus (DM) and BK virus nephropathy (BKVN) rates were significantly higher due to switching the regimen from CNI to mTORi. CONCLUSIONS Long-term use of mTORi does not appear to be an immunological problem.

Relationship between plasminogen activator inhibitor-1 gene alterations and fibrosis in peritoneal dialysis patients.

Peritoneal fibrosis (PF) is a pathological change that occurs mostly long-term peritoneal dialysis (PD) patients, as a result of triggering the inflammatory response. Plasminogen activator inhibitor-1 (PAI-1) is an important molecule featured in the development of fibrosis. It has been shown in literature that PAI-1 gene alterations are associated with fibrosis in many tissues and organs. However, PAI-1 gene alterations in long-term PD patients have not yet been investigated. In this study, PAI-1 4G/5G polymorphism was examined by reverse hybridization, and all coding exons of the PAI-1 gene were examined by sequence analysis to provide treatment modification in patients with predisposition before fibrosis develops. The patients were divided into two groups according to ultrafiltration failure test and duration of PD treatment: those with suspected PF or a high probability of developing PF (36%) and those with a low probability of developing PF (64%). There was no significant difference between the two groups in findings such as peritoneal equilibration test (PET), Kt/V, the content of the PD solution used, peritonitis, and PAI-1 4G/5G polymorphism (P > .05). A total of eight gene alterations (rs2227660, rs2227668, rs2854233, rs41281004, rs61553169, rs368413856, rs2227684) were detected by sequence analysis, one of which was exonic (rs6092). When the genotype distributions of these variants were examined, no significant difference was found between the two groups. PAI-1 gene changes were not detected in patients with the probability of developing PF. There is a need for further studies involving other molecules responsible for predisposing to PF with larger patient populations in patients undergoing long-term PD treatment.

Impact of Subclinical Rejection on Kidney Graft Function.

BACKGROUND: In kidney transplant recipients with borderline infiltration, protocol biopsy results demonstrated the relationship with chronic injury. The purpose of this study was to evaluate the effect of subclinical rejection (SCR) on 6-month protocol biopsy results in long-term renal function in renal transplant recipients with stable graft function. MATERIAL AND METHODS: Transplant protocol biopsies performed in 45 patients with stable renal function were included in this study at 6 months. Biopsy specimens were evaluated for SCR. Study groups were divided into patients with and without SCR. Renal functions were compared with pathologic evaluation. The effect of immunosuppressive regimens on renal function were evaluated in patients with SCR RESULT: The median age of patients was 32 years (range, 18-64 years). The median follow-up was 56 months (range, 24-84 months). According to the 6-month protocol biopsy results, 20 of 45 patients (44.4%) met SCR criteria based on Banff 07 parameters. There was not a statistically significant difference in renal function with SCR. CONCLUSION: The presence of SCR on the 6-month protocol biopsy results in renal transplant recipients with a stable graft function does not cause deterioration in the long-term graft function.

Factors affecting TST level in patients undergoing dialysis: a multicenter study.

INTRODUCTION: The risk of TB is increased in patients with chronic kidney disease (CKD) when compared with individuals with normal renal function. We aimed to determine tuberculin skin test (TST) response and the factors which might affect the response in patients with CKD undergoing dialysis in this study. METHODS: The purified protein derivative solution was administered to the patients and the diameter of induration was measured. Additionally, the age, gender and smoking status of the patients were interrogated. Comorbidities were recorded both by patients' self-reports and data from the hospital files. The number of Bacille Calmette-Guerin (BCG) scars was recorded by checking both shoulders. FINDINGS: The study was conducted with a total of 371 patients (194 men and 177 women). The mean age was 60.09 ± 15.88, TST was 6.99 ± 6.9, duration of dialysis was 4.44 ± 4.5 (3.8-0.1,24). A total of 229 patients have comorbodities (61.7%, the most frequent was hypertension). Logistic regression model was performed. Gender, vitamin D treatment and high parathormone (PTH) levels remained in the final stage of the analysis and vitamin D intake and PTH levels were detected to be statistically significant (P = 0.002, 0.007, respectively). DISCUSSION: This study is the first study which showed a correlation between TST negativity and increased PTH levels and receiving vitamin D treatment. Starting from this point, it was concluded that PTH may suppress the immune system and especially cellular immunity.

Acute renal infarction in Turkey: a review of 121 cases.

PURPOSE: Renal infarction is a clinical condition which is caused by renal artery occlusion and leads to permanent renal parenchymal damage. In the literature, there are generally case reports on this subject, and few studies that include a large group of patients. Therefore, we aimed to present the data of a large group of patients who were diagnosed with acute renal infarction in our country in this retrospective study. METHODS: The data of patients who were diagnosed with acute renal infarction according to clinical and radiological findings in Turkey in the last 3 years were examined. For this purpose, we contacted with more than 40 centers in 7 regions and obtained support from clinically responsible persons. Demographic data of patients, laboratory data at the time of diagnosis, tests performed for etiologic evaluation, given medications, and patients' clinical status during follow-up were obtained from databases and statistical analysis was performed. RESULTS: One-hundred and twenty-one patients were included in the study. The mean age was 53 ± 1.4 (19-91) years. Seventy-one (58.7%) patients were male, 18 (14.9%) had diabetes, 53 (43.8%) had hypertension, 36 (30%) had atrial fibrillation (AF), and 6 had a history of lupus + antiphospholipid syndrome (APS). Forty-five patients had right renal infarction, 50 patients had left renal infarction, and 26 (21.5%) patients had bilateral renal infarction. The examinations for the ethiologies revealed that, 36 patients had thromboemboli due to atrial fibrillation, 10 patients had genetic anomalies leading to thrombosis, 9 patients had trauma, 6 patients had lupus + APS, 2 patients had hematologic diseases, and 1 patient had a substance abuse problem. Fifty-seven (57%) patients had unknown. The mean follow-up period was 14 ± 2 months. The mean creatinine and glomerular filtration rate (GFR) values at 3 months were found to be 1.65 ± 0.16 mg/dl and 62 ± 3 ml/min, respectively. The final mean creatinine and GFR values were found to be 1.69 ± 0.16 mg/dl and 62 ± 3 ml/min, respectively. CONCLUSIONS: Our study is the second largest series published on renal infarction in the literature. More detailed studies are needed to determine the etiological causes of acute renal infarction occurring in patients.

Pretreatment with paricalcitol attenuates level and expression of matrix metalloproteinases in a rat model of renal ischemia-reperfusion injury
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BACKGROUND: Ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI). The inflammatory response that drives IRI involves upregulation of matrix metalloproteinases (MMPs), which results in proteolytic degradation of renal microvascular matrix. Evidence suggests a potential protective role of active vitamin D on ischemic injury by downregulating MMPs. In the present study, we aimed to determine the expression and level of MMP-2 and MMP-9 in renal IRI model and the potential beneficial effect of paricalcitol on both level and expression of MMPs and tubular injury caused by IRI. MATERIALS AND METHODS: 20 Wistar albino rats were divided into three groups: sham-operated, ischemia-reperfusion, and paricalcitol-pretreated. IRI model was induced by bilateral clamping of renal arteries for 45 minutes followed by 24 hours of reperfusion. The analysis of serum creatinine and levels of MMPs were performed after 24 hours of IRI. The effects of paricalcitol on the quantity and expression of MMP-2 and MMP-9 in renal tubular epithelial cells were investigated by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The pathological examinations were performed to score tubular damage by light microscopy. RESULTS: Creatinine levels decreased in the paricalcitol group, although this was not proven to be significant. Rats in the paricalcitol group showed significant decrease in both level and expression of MMPs and in tubular injury scores as compared to the IRI group. CONCLUSION: Paricalcitol may attenuate renal tubular injury caused by IRI by decreasing both level and expression of MMPs. Further studies are required to investigate the interplay between activated vitamin D and MMPs in AKI.
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Pretreatment with nebivolol attenuates level and expression of matrix metalloproteinases in a rat model of renal ischaemia-reperfusion injury.

AIM: Matrix metalloproteinases (MMPs) are zinc-containing proteinases that are involved in the degradation of extracellular matrix (ECM) and a number of cell surface proteins in order to maintain tissue homeostasis. They are involved in pathogenesis of several ischaemic organ injuries. In the present study, we aimed to determine the expression and level of MMP-2 and MMP-9 in renal ischaemia-reperfusion injury (IRI) model and the potential beneficial effect of nebivolol, a ß1 -adrenergic receptor blocker, on both MMP-2 and -9 level and expression and tubular injury caused by IRI. METHODS: Twenty Wistar albino rats were divided into three groups: sham-operated , ischaemia-reperfusion, and nebivolol-pretreated. IRI model was induced by bilateral clamping of renal arteries for 45 min followed by 24 h of reperfusion. The analysis of serum creatinine levels, quantity and expression of MMP-2 and MMP-9 were performed after 24 h of IRI. The effects of nebivolol on level and expression of MMP-2 and MMP-9 levels were investigated by enzyme-linked immunosorbent assay and immunohistochemistry, respectively. The pathological examinations were performed to score tubular damage by light microscopy. RESULTS: Creatinine levels increased significantly in the ischaemia-reperfusion group compared to the sham-operated group. Rats in the nebivolol-pretreated group showed significant decrease in expression and quantity of MMP-2 and MMP-9 during IRI. The pathological examinations demonstrated significantly low level of tubular injury score in nebivolol-pretreated group. CONCLUSION: Nebivolol attenuated IRI by decreasing the expression and level of MMP-2 and MMP-9.

Screening Fabry's disease in chronic kidney disease patients not on dialysis: a multicenter study.

OBJECTIVES: Fabry's disease is an X-linked inherited, rare, progressive, lysosomal storage disorder, affecting multiple organs due to the deficient activity of α-galactosidase A (α-Gal A) enzyme. The prevalence has been reported to be 0.15-1% in hemodialysis patients; however, the information on the prevalence in chronic kidney disease not on dialysis is lacking. This study aimed to determine the prevalence of Fabry's disease in chronic kidney disease. METHODS: The patients older than 18 years, enclosing KDIGO 2012 chronic kidney disease definitions, not on dialysis, were enrolled. Dried blood spots on Guthrie papers were used to analyze α-Gal A enzyme and genetic analysis was performed in individuals with enzyme activity ≤1.2 µmol/L/h. RESULTS: A total of 1453 chronic kidney disease patients not on dialysis from seven clinics in Turkey were screened. The mean age of the study population was 59.3 ± 15.9 years. 45.6% of patients were female. The creatinine clearance of 77.3% of patients was below 60 mL/min/1.73 m2, 8.4% had proteinuria, and 2.5% had isolated microscopic hematuria. The mean value of patients' α-Gal A enzyme was detected as 2.93 ± 1.92 µmol/L/h. 152 patients had low levels of α-Gal A enzyme activity (≤1.2 µmol/L/h). In mutation analysis, A143T and D313Y variants were disclosed in three male patients. The prevalence of Fabry's disease in chronic kidney disease not on dialysis was found to be 0.2% (0.4% in male, 0.0% in female). CONCLUSION: Fabry's disease should be considered in the differential diagnosis of chronic kidney disease with unknown etiology even in the absence of symptoms and signs suggestive of Fabry's disease.

Delayed Graft Function in Kidney Transplantation: Risk Factors and Impact on Early Graft Function.

CONTEXT: Although kidney transplantations are routinely performed at many centers in Turkey, the incidence and risk factors associated with delayed graft function (DGF) here have not yet been well defined. OBJECTIVE: The aim of this study is to evaluate the incidence and risk factors of DGF and its impact on early graft function. DESIGN: The medical charts of 154 adult patients who underwent deceased donor kidney transplantation between 2000 and 2014 in a single center were reviewed retrospectively. SETTING: Delayed graft function-related risk factors for donors, recipients, and the transplant surgery itself were analyzed, and their relation with graft function was evaluated. MAIN OUTCOMES MEASURES: The median recipient age was 39 years. The median cold ischemia time (CIT) was 840 minutes (14 hours). The incidence of DGF and acute rejection were 57.8% and 8.4%, respectively. Higher serum creatinine levels at 3, 6, and 12 months were observed in patients with DGF compared to other patients without DGF (P < .05). Patients with DGF had poor graft function (glomerular filtration rate ≤ 50) at 3 and 6 months (P < .05), but these correlations were not seen at 12 months (P = not significant). RESULTS: This study showed that DGF was a common and serious problem associated with poor graft functions at 3, 6, and 12 months after transplantation. Extra effort to shorten CIT as an independent risk factor for DGF could have protective effect on graft functions.

Renal tubular acidosis in renal transplant patients: the effect of immunosuppressive drugs.

BACKGROUND: Renal tubular acidosis (RTA) is a non-anion gap metabolic acidosis and is generally mild and asymptomatic in kidney recipients. Calcineurine inhibitors (CNIs) increase the frequency of RTA but the frequency of RTA development in kidney transplant recipients receiving mammalian target of rapamycin inhibitors (mTORi) treatment remains unclear. In this study, we aimed to investigate the frequency of RTA in kidney transplant recipients on mTORi and CNI treatment and to compare both groups. MATERIAL AND METHODS: We enrolled 137 adult renal transplant patients - 82 patients on mTORi and 55 patients on CNI who had similar age, sex, posttransplant follow-up period, and graft functions. We recorded the parameters of venous blood gas analysis, including serum pH value, serum bicarbonate (HCO3) concentration, presence of metabolic acidosis defined as low HCO3 (<22 mEq/L), and serum pH value (<7.35), as well as base excess and urine pH at last follow-up. RTA was defined to be metabolic acidosis with normal serum anion gap and positive urine anion gap. RESULTS: The mean age of our study population was 41.2±11.3 years. RTA frequency was 35% in the mTORi group and 41% in the CNI group. mTORi and CNI groups did not differ significantly in terms of the development of metabolic and renal tubular acidosis. Type I RTA was common in both groups. RTA was affected by duration of time since transplantation and graft functions in both groups. CONCLUSIONS: The rates of RTA development in patients on long-term CNI and mTORi treatment were similar.

Relationship between epicardial adipose tissue, inflammation and volume markers in hemodialysis and transplant patients.

Cardiovascular (CV) diseases are still the most important cause of morbidity and mortality in both patients receiving hemodialysis (HD) treatment and individuals with renal transplantation (Rtx). Measurement of epicardial adipose tissue (EAT) thickness is an easily applied, cheap, and useful recent method predicting increased CV risk. We aimed to compare EAT changes in HD and Rtx patients and the association between EAT and inflammatory and CV volume markers in both groups. A total of 124 patients: 45 Rtx, 43 HD patients and 36 healthy controls were enrolled in the study. Laboratory parameters and inflammatory markers (interleukin-6 [IL-6] and high sensitive C-reactive protein [Hs-CRP]) were evaluated from venous blood samples after an overnight fast. EAT thickness was measured with transthoracic echocardiography. The levels of Hs-CRP, IL-6, systolic and diastolic blood pressures, left atrial (LA) diameter, left atrial index (LAI), left ventricular mass (LVM) and LVM index (LVMI) were significantly higher in the HD patients than in the other groups. EAT was positively correlated with age, body mass index (BMI), time on dialysis, serum creatinine, total cholesterol, Low density lipoprotein-cholesterol, and LVM in Rtx group and positively correlated with age, BMI, duration of dialysis, Hs-CRP, IL-6, LAI and LVMI and inversely correlated with inferior vena cava collapse index (IVC-CI) in HD group. EAT thickness of RTx patients (whose previous HD duration was similar to those in HD group) are similar to the healthy population and significantly thinner than patients on HD.

Long-term outcome of kidney transplantation from elderly living and expanded criteria deceased donors.

The imbalance between organ demand and supply causes the increasing use of suboptimal donors. The aim of this study is to investigate the survival and allograft function of kidney transplantation from standard (SLD) and elderly living (ELD), standard criteria (SCDD) and expanded criteria deceased (ECDD) donors. All patients transplanted from 1997 to 2005 were investigated according to the donor characteristics. Data were collected retrospectively during the 83.4±43.1 months of follow-up period. ELD was defined as donor age≥60 years. ECDD was defined as UNOS criteria. A total of 458 patients were divided into four groups: SLD (n:191), ELD (n:67), SCDD (n:154), and ECDD (n:46). Seven-year death-censored graft survival in SLD, ELD, SCDD, and ECDD were 81.6%, 64.8%, 84.7%, and 68.3%, respectively (p=0.003). The death-censored graft survival in ELD group was lower than in SLD (p=0.007) and SCDD (p=0.007) groups, while in ECDD group it was lower than in SCDD group (p=0.026). Patient survival was similar. In ECDD group, 83% of total deaths occurred within the first 3 years, mainly due to infections (66.6%) (p<0.05). Estimated glomerular filtration rate (eGFR) was lower in ELD (compared with SLD and SCDD); and ECDD (compared with SCDD) at last visit. In multivariate analysis, ELD, experience of an acute rejection episode and presence of delayed graft function were the independent predictors for death censored graft loss. Transplantation of a suboptimal kidney provides inferior graft survival and function. A higher number of deaths due to infection in the early post-transplant period in the ECDD group are noteworthy.

The evaluation of red cell distribution width in chronic hemodialysis patients.

Background. Red cell distribution width (RDW) has been used as a marker of iron deficiency; however, it is accepted as a marker of cardiovascular survival. We aimed to study RDW levels in hemodialysis (HD) patients and the association between RDW and inflammatory, nutritional, and volume markers. Methods. We included 296 HD patients with sufficient iron storage and without anemia or hypervolemia. We grouped patients into four groups according to clinical parameters, albumin, and C-reactive protein (CRP). Results. The lowest RDW levels were found in group 1 (13.2%). Although RDW of group 2 was higher than that of group 1, it was still in normal range (14.7% versus 13.2%, P = 0.028). RDW levels of groups 3 (17.8%) and 4 (18.5%) were significantly higher than those of groups 1 and 2 and above normal range. A positive correlation was detected between RDW and HD duration, interdialytic weight gain (IDWG), serum phosphate, and CRP levels and a negative correlation was detected with serum albumin. HD duration, CRP, IDWG, and serum albumin have been found as independent predictors of RDW elevation. Conclusions. Results of the present study reflect adverse effects of inflammation, malnutrition, and excess IDWG on RDW elevation in an HD study cohort with sufficient iron storage and without anemia and hypervolemia.

Relation between serum estradiol levels and mortality in postmenopausal female hemodialysis patients.

BACKGROUND: Recently, low serum estradiol levels have been associated with increased cardiovascular risk and mortality in non-uremic patient populations. We investigated the predictive value of serum estradiol levels for mortality in female hemodialysis patients. METHODS: One hundred and forty-seven prevalent female hemodialysis patients were included in March 2005 and followed up for 32 ± 16 months. Serum estradiol levels were determined by ELISA at baseline and studied in relation to cardiovascular and overall mortality. RESULTS: Mean serum estradiol level was 28.6 ± 15.4 pg/ml (5.7-81.3). Patients in the higher estradiol tertile were likely to be more often diabetic and to have more cardiovascular diseases and higher body mass index (BMI). Serum estradiol was inversely correlated with age and urea reduction rate and positively correlated with postdialysis body weight, BMI and hs-CRP levels. During the follow-up period, 52 (35.6 %) patients died. Patients who died were older, had shorter dialysis vintage, were more likely to have a history of diabetes and cardiovascular disease, and lower serum creatinine, albumin, hemoglobin, and higher hs-CRP levels than those who survived. In Cox regression analysis, estradiol levels, in a bimodal (U-shaped) distribution, along with diabetes, low serum albumin and high hs-CRP levels, were predictors for overall mortality. CONCLUSIONS: A U-shaped association between serum estradiol levels and cardiovascular and overall mortality was found in postmenopausal hemodialysis patients.

The effects of mammalian target of rapamycin inhibitors on serum uric acid levels in renal transplant patients.

BACKGROUNDS/AIMS: Elevated uric acid (UA) levels are frequently observed after renal transplantation. We investigated the consequences of shifting from calcineurin inhibitors (CNI) to mammalian target of rapamycin inhibitors (mTORi) on UA levels and graft functions. METHODS: Ninety-six patients were enrolled. Main points of interest were changes in UA and glomerular filtration rate (GFR). RESULTS: Mean age of the whole population was 39 ± 11 years (18-73), and 64.2 % were male. Patients were stratified into two groups according to their CNI type prior to the switch as cyclosporin A (CsA) or tacrolimus (Tac). Patients that were switched from CsA had a mean GFR of 49 ± 18 ml/min and serum UA level of 7.4 ± 1.8 mg/dl at the pre-switch period. Mean GFR increased to 53 ± 22 ml/min (p = 0.03), and UA levels decreased to 6.2 ± 1.6 mg/dl at the final visit (p < 0.001). In the Tac group, pre-switch mean GFR was 59 ± 28 ml/min and serum UA level 6.6 ± 2.6 mg/dl. In this group, mean GFR increased to 63 ± 28 ml/min (p = 0.03) and UA levels decreased to 6.2 ± 2.1 at the last visit (p < 0.001). CONCLUSION: Switch from CNI to mTORi-based regimen provides better control of UA levels and improves renal functions.

Preventive effect of nebivolol on contrast-induced nephropathy in rats.

BACKGROUND: Altered renal vasodilatation and oxidative stress are important mechanisms of contrast-induced nephropathy (CIN). The aim of the present study was to assess the effect of nebivolol, a beta blocker, on prevention of CIN. We hypothesized that nebivolol may prevent CIN due to its renal vasodilatation and antioxidant effects. METHODS: Thirty-two Wistar-albino rats were divided into four groups (n = 8 each): control (C), contrast media (CM), nebivolol (N), and nebivolol + contrast media (NCM). CIN was induced by administration of intravenous high-osmolar contrast media diatrizoate (6 ml/kg) after 72 h of dehydration. Nebivolol (2 mg/kg) was given internally once daily for 5 days. Kidney function parameters, nitric oxide metabolites and oxidative stress markers were measured. Kidneys were excised for pathological evaluation. RESULTS: The decrease of creatinine clearance was 0.180 +/- 0.11 mg/dl in CM, and 0.030 +/- 0.10 mg/dl in NCM (P = 0.01). Microproteinuria was ameliorated using nebivolol (P = 0.001). Serum protein carbonyl content, malonyldialdehyde and kidney thiobarbituric acid-reacting substances levels were higher in CM than in C (P = 0.003, P < 0.001 and P = 0.034, respectively) and serum thiol was lower in CM than in C (P = 0.001). However, oxidative stress markers were similar in NCM and C. Diatrizoate decreased kidney nitrite levels, but nebivolol increased them (P = 0.027). Nebivolol attenuated the tubular necrosis, proteinaceous casts and medullary congestion, although significant protective effects, were observed in tubular necrosis (P = 0.001) and proteinaceous cast (P < 0.001). CONCLUSION: This study demonstrated the protective role of nebivolol against CIN.