A single mRNA, transcribed from an alternative, erythroid-specific, promoter, codes for two non-myristylated forms of NADH-cytochrome b5 reductase.

Two forms of NADH-cytochrome b5 reductase are produced from one gene: a myristylated membrane-bound enzyme, expressed in all tissues, and a soluble, erythrocyte-specific, isoform. The two forms are identical in a large cytoplasmic domain (Mr approximately 30,000) and differ at the NH2-terminus, which, in the membrane form, is responsible for binding to the bilayer, and which contains the myristylation consensus sequence and an additional 14 uncharged amino acids. To investigate how the two differently targeted forms of the reductase are produced, we cloned a reductase transcript from reticulocytes, and studied its relationship to the previously cloned liver cDNA. The reticulocyte transcript differs from the liver transcript in the 5' non-coding portion and at the beginning of the coding portion, where the seven codons specifying the myristoylation consensus are replaced by a reticulocyte-specific sequence which codes for 13 non-charged amino acids. Analysis of genomic reductase clones indicated that the ubiquitous transcript is generated from an upstream "housekeeping" type promoter, while the reticulocyte transcript originates from a downstream, erythroid-specific, promoter. In vitro translation of the reticulocyte-specific mRNA generated two products: a minor one originating from the first AUG, and a major one starting from a downstream AUG, as indicated by mutational analysis. Both the AUGs used as initiation codons were in an unfavorable sequence context. The major, lower relative molecular mass product behaved as a soluble protein, while the NH2-terminally extended minor product interacted with microsomes in vitro. The generation of soluble reductase from a downstream AUG was confirmed in vivo, in Xenopus oocytes. Thus, differently localized products, with respect both to tissues and to subcellular compartments, are generated from the same gene by a combination of transcriptional and translational mechanisms.

Visfatin, a new adipocytokine, is predominantly related to inflammation/endothelial damage in kidney allograft recipients.

Visfatin, a ubiquitous adipokine, was first described in 2005. It was found to be selectively up-regulated in the adipose tissue and to have insulin-mimetic effects. It has been reported that visfatin is associated with endothelial damage in chronic kidney disease. We investigated plasma visfatin levels (using commercially available kits) in 100 clinically stable kidney allograft recipients. We assessed visfatin markers of coagulation: thrombin-antithrombin complexes, prothrombin fragments 1 + 2; fibrinolysis: tissue plasminogen activator, plasminogen activator inhibitor, plasmin-antiplasmin complexes; endothelial function/injury: von Willebrand factor, thrombomodulin, intracellular adhesion molecule, vascular cell adhesion molecule (VCAM); inflammation: hsCRP and interleukin-6. Visfatin was significantly higher in kidney allograft recipients than in healthy volunteers. Visfatin did not differ significantly between diabetic and nondiabetics, hypertensives and normotensives, patients with and without coronary artery disease, and between male and female subjects. Type of immunosuppressive regimen (mycophenolate mofetil vs azathioprine) did not affect visfatin levels. On univariate analysis, visfatin correlated positively with prothrombin fragments 1 + 2, VCAM, creatinine, high-sensitivity C-reactive protein, and negatively with albumin. In multivariate analysis, only VCAM was associated with visfatin in kidney allograft recipients. Visfatin, which is related to markers of inflammation, may represent a novel link between inflammation and adipocytokines among long-term kidney transplant recipients.

Neutrophil gelatinase-associated lipocalin is a new and sensitive marker of kidney function in chronic kidney disease patients and renal allograft recipients.

BACKGROUND/AIMS: Few biomarkers exist to monitor chronic kidney disease (CKD). Neutrophil gelatinase-associated lipocalin (NGAL), a member of lipocalin family, has recently been proven useful to quantitate CKD. The aim of the study was to assess whether NGAL could represent a novel, sensitive marker of kidney function in adult patients with CKD and in kidney transplant recipients. METHODS: We studied possible relations between serum NGAL, creatinine, and estimated glomerular filtration rate (eGFR) in 80 nondiabetic patients with CKD stages 2 to 4; 80 nondiabetic kidney transplant recipients on a calcineurin inhibitor mycophenolate mofetil, or azathioprine as well as prednisone and in healthy volunteers (n = 32, mean age 50 years). RESULTS: Serum NGAL and creatinine values were significantly higher and eGFR significantly lower in kidney allograft recipients and patients with CKD compared with controls. NGAL rose gradually, reaching the higher value in stage 4 CKD. In univariate analysis serum NGAL was related to serum creatinine, hemoglobin, hematocrit, leukocyte count, and eGFR. Predictors of serum NGAL were creatinine and eGFR among patients with CKD. On univariate analysis serum NGAL was related to serum creatinine, urea, hemoglobin, hematocrit, white blood cell count, calcineurin concentration, eGFR, and albumin in kidney transplant recipients. On multiple regression analysis, predictors of NGAL were creatinine, calcineurin concentration, and high-sensitivity C-reactive protein. In healthy volunteers, serum NGAL correlated with age, serum creatinine, eGFR, and leukocyte count. CONCLUSION: NGAL should be investigated as a potential early, sensitive marker of kidney impairment/injury, which might provide an additional accurate measure of kidney impairment in CKD and among transplant recipients, particularly at advanced stages.

Neutrophil gelatinase-associated lipocalin and cystatin C could predict renal outcome in patients undergoing kidney allograft transplantation: a prospective study.

Urinary neutrophil gelatinase-associated lipocalin (NGAL) may represent an early, predictive biomarker of delayed graft function due to ischemia-reperfusion injury. Unfortunately, creatinine is an unreliable indicator of acute changes in kidney function. NGAL was proposed as a novel early marker for detection of acute renal failure. Therefore, the aim of the study was to assess whether NGAL and cystatin C predicted outcomes among 41 consecutive patients undergoing kidney transplantation. Serum NGAL and cystatin C were evaluated before, as well as 1, 3, 6, and 10 days after kidney transplantation using commercially available kits. Serum creatinine was assessed at each time. We observed a significant fall in serum NGAL as early as 1 day following kidney transplantation. Serum cystatin C decreased significantly 3 days after transplantation. Before transplantation, serum NGAL was related to creatinine and cystatin C. At each time point, serum NGAL was related positively to serum creatinine, cystatin C, and negatively to urine volume. In patients with delayed graft function, there was no fall in serum NGAL or cystatin C. Our findings may have important implications for the clinical management of patients undergoing kidney transplantation. The "window of opportunity" to distinguish between acute rejection and calcineurin inhibitor nephrotoxicity is narrow in delayed graft function. Time is limited to introduce proper treatment after the initiating insult. Therefore, NGAL needs to be investigated as a potential early marker for delayed graft function, especially in the settings of early dialysis treatment or antirejection therapy.

Adipokines, linking adipocytes and vascular function in hemodialyzed patients, may also be possibly related to CD146, a novel adhesion molecule.

Possible correlations between adiponectin, leptin, CD146, a novel adhesion molecule localized at the endothelial junction, and other markers of endothelial cell injury, von Willebrand factor, thrombomodulin, vascular cell adhesion molecule, and intracellular adhesion molecule, and markers of inflammation, tumor necrosis factor-alpha, interleukin-6, and high-sensitivity C-reactive protein in nondiabetic hemodialyzed patients with and without coronary artery disease were studied. Markers of endothelial dysfunction were elevated in hemodialyzed patients, predominantly with coronary artery disease. In multivariate analysis, kinetic urea modeling and plasminogen activator inhibitor-1 remained the only positive predictors of adiponectin. In multivariate analysis, predictors of leptin were triglycerides, tissue plasminogen activator, CD146, and coronary artery disease. In multivariate analysis, predictors of CD146 were age, hemoglobin, and adiponectin. Elevated adiponectin correlated to CD146 may be the expression of a counterregulatory response aimed at mitigating the consequences in endothelial damage and increased cardiovascular risk in renal failure. The data provide further support for a link between adipocytokines, endothelial dysfunction, cardiovascular risk, and renal failure.

Endothelial function and novel adhesion molecule CD44 in kidney allograft recipients.

BACKGROUND: Disturbances in hemostasis and endothelial damage are common complications of kidney disease. Endothelial dysfunction may link these 2 processes and inflammation is closely related to endothelial dysfunction. PATIENTS AND METHODS: This cross-sectional study on serum concentrations of markers of endothelial damage and inflammation in relation to adhesion molecules was performed in 90 kidney allograft recipients and 30 healthy volunteers. We measured markers of endothelial damage-von Willebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM), vascular adhesion molecule (VCAM), CD146, CD44, and CD40L; markers of inflammation-high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNFalpha), and interleukin-6 (IL-6); and other hemostatic parameters-thrombin-antithrombin complexes (TAT), plasmin-antiplasmin complexes, and thrombin activatable fibrinolysis inhibitor (TAFI) using commercially available kits. RESULTS: Markers of endothelial dysfunction and inflammation were significantly elevated in kidney allograft recipients compared with control subjects. CD44 was independently related to hsCRP (r = .37; P < .01), ICAM (r = .23; P < .05), eGFR (r = -.37; P < .01), thrombomodulin (r = .43; P < .001), VCAM (r = -.44; P < .001), hemoglobin (r = -.26; P < .01), red blood cell count (r = -.25; P < .05), creatinine (r = .37; P < .01), CD146 (r = .34; P < .01), and CD40L (r = .23; P < .05). Upon multiple regression analysis the predictors of elevated CD44 were hsCRP concentration (beta = .25; P < .05), CD146 (beta = .39; P < .05), creatinine (beta = .55; P < .01), and thrombomodulin (beta = .39; P < .05) with an adjusted R(2) = .40 (F = 4.12; P < .00028; SE of estimate = 151.19). CONCLUSIONS: As demonstrated in multiple regression analysis, kidney function was strictly linked to the degree of inflammation and endothelial injury. Endothelial cell injury and the presence of an inflammatory state, as reflected by elevated marker concentrations, and endothelial activation/injury may play roles in the pathogenesis of atherosclerosis and cardiovascular complications among kidney allograft recipients.

Apelin, a novel adipocytokine, in relation to endothelial function and inflammation in kidney allograft recipients.

Apelin, a newly discovered adipocytokine produced by white adipose tissue, is also expressed in kidney and heart. It has been reported that apelin is related to echocardiographic features in hemodialyzed patients. Cardiovascular disease is a major contributor to the mortality and morbidity among patients with chronic renal failure as well as kidney allograft recipients. The aim of this study was to assess the association between apelin and coronary artery disease (CAD) among kidney allograft recipients. We investigated plasma apelin levels in 100 clinically stable, kidney allograft recipients with versus without CAD. We also assessed markers of endothelial cell injury-von Villebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM), and CD146; markers of inflammation-high-sensitivity-reactive protein (hsCRP); other hemostatic parameters-tissue plasminogen activator (tPA) and its inhibitor (PAI-1); as well as other adipocytokines-adiponectin and resistin-using commercially available kits. Markers of endothelial dysfunction and inflammation were significantly elevated among patients with CAD levels, as well as with CAD or diabetes, compared with those without CAD. Apelin was significantly lower among patients with CAD, but higher in diabetic patients. Apelin content was similar in hypertensive versus normotensive kidney allograft recipients. We observed significant correlations between apelin and ICAM, resistin, adiponectin, calcium, phosphate, alanine and aspartate aminotransferase levels, with CAD or diabetes. Upon multiple regression analysis as well as CAD, adiponectin, and ICAM were predictors of apelin. Apelin was significantly reduced in kidney allograft recipients with CAD; its level was predicted by the presence of CAD, endothelial damage, or inflammation. Apelin and other adipocytokines may be associated with inflammation and its clinical consequences.

Eye Problems in Patients on the Active and Inactive Kidney Transplantation Waiting List.

Renal transplant is the best form of treatment for most patients with end-stage renal disease. The aim of this study was to examine the prevalence of eye problems in patients with end-stage renal disease on the kidney transplantation waiting list in regard to their status (active vs temporarily disqualified). The cross-sectional study was conducted on 90 prevalent patients in 1 regional qualification center. There were 24 peritoneally dialyzed patients, 5 patients registered for preemptive transplantation, and 61 hemodialyzed patients. Average age of patients who had been registered on the cadaver kidney waiting list was 50 (± 14) years, with a balanced sex ratio and median dialysis duration of 38 months. The primary cause of end-stage renal failure was chronic glomerulonephritis in 42 cases, diabetic nephropathy in 10 cases, hypertensive nephropathy in 12 cases, autosomal dominant polycystic kidney disease in 7 cases, and other or unknown in the remaining patients. The major diagnosis was hypertensive angiopathy (related to the presence of long-term hypertension and history of kidney disease) in 56 patients, diabetic retinopathy in 8 patients, blindness in 4 cases (due to solvent intoxication in 1 case), and eyesight abnormalities (myopia, hyperopia, anisometropia) in 7 cases. Cataracts were described in 10 patients in addition to other findings. In 15 patients ophthalmology examination was normal, predominantly in younger patients. Abnormalities were more common in patients on the inactive list. In the vast majority of potential kidney transplant recipients, ophthalmology disturbances are primarily related to the underlying disease. The ophthalmology consult is part of the qualification, but the abnormalities are not the exclusion criteria.

Endocan Concentration in Kidney Transplant Recipients.

INTRODUCTION: Endocan is a novel soluble dermatan sulfate proteoglycan derived from endothelium. It has the capacity of binding to different biologically active molecules associated with cellular signaling, adhesion and regulating proliferation, differentiation, migration, and adhesion of different cell types in health and pathology. Elevated endocan levels are connected with endothelial activation/damage, neo-angiogenesis, and inflammation or carcinogenesis. MATERIALS AND METHODS: The level of serum endocan among 63 kidney transplant recipients on three immunosuppressives (calcineurin inhibitors, mycophenolate mofetil, steroids) in correlation with other markers of endothelial damage was estimated. Additionally, 22 healthy volunteers were studied. Using a cross-sectional study design, the markers of endothelial damage like endocan, von Willebrand factor (vWF), intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM); markers of inflammation high-sensitivity C-reactive protein (hsCRP) and IL-6; and marker of kidney function cystatin C were measured using commercially available assays. RESULTS: Endocan, vWF, IL-6, hsCRP, ICAM, and VCAM levels were significantly higher in kidney transplant recipients comparing to healthy volunteers. In kidney transplant recipients, endocan levels correlated with renal function (estimated glomerular filtration rate by Modification of Diet in Renal Disease, r = -0.24, P < .05, creatinine r = 0.26, P < .05), time after transplantation r = -0.24, P < .05, activity of aspartate aminotransferase r = -0.46, P < .001, alanine aminotransferase r = 0.34, P < .01), ICAM r = -0.53, P < .001, VCAM r = -0.34, P < .01, hsCRP r = 0.35, P < .01, IL-6 r = 0.28, P < .05, vWF r = 0.26, P < .05. In a multifactorial analysis, the predictors of endocan levels were creatinine, ICAM, and VCAM predicting 59% of variability. CONCLUSION: Endocan concentration among kidney transplant recipients is potentially connected with endothelial damage dependent upon graft function and time after transplantation.

Underrecognition and Underestimation of Disturbances in Calcium-Phosphate Balance in Kidney Transplant Recipients.

Disturbances in mineral metabolism, namely chronic kidney disease-metabolic bone disease, became more profound with impairment of renal function. The aim of the study was to assess how often calcium, phosphate, alkaline phosphatase, and parathyroid hormone (PTH) were measured in kidney transplant recipients relative to hemodialyzed patients. In addition, prevalence of hypercalcemia defined as calcium concentration over 10.5 mg/dL was assessed. PATIENTS AND METHODS: We studied 200 kidney allograft recipients and 100 hemodialyzed patients. Calcium, phosphate, alkaline phosphatase, 25-hydroxy vitamin D, and PTH were obtained from outpatient charts. RESULTS: All the studied parameters were available in 100% of the hemodialyzed patients. In kidney allograft recipients, calcium and phosphate levels were available in 80%, alkaline phosphatase activity was available in 40%, PTH was available in less than 10%, and vitamin D was available in 1%. Hypercalcemia was present in 10% of hemodialyzed patients and in 5% of kidney allograft recipients. Vitamin D analogue was administered to 98% of hemodialyzed patients, whereas vitamin D was administered to 28% of kidney allograft recipients, particularly those with impaired kidney function. In conclusion, calcium and phosphate are seldom assessed on an outpatient basis in kidney allograft recipients, making the diagnosis and treatment of secondary hyperparathyroidism in this population difficult. Care of kidney transplant recipients could be substantially improved, particularly in regard to chronic kidney disease-metabolic bone disease, when regular check-ups for calcium-phosphate balance are implemented and proper treatment could be introduced to prevent further chronic kidney disease-metabolic bone disease.

Vitamin D Concentration in Patients After Heart and Kidney Transplantation.

BACKGROUND: One of the main actions of vitamin D is bone mineralization regulation. Vitamin D is linked also to hypertension, diabetes, and cardiovascular disease. Vitamin D deficiency may result in osteomalacia, but its excess may result in bone calcium mobilization. Kidney transplant recipients are also at risk of hypovitaminosis D because of impaired graft function. The aim of the study was to assess vitamin D concentration in patients after heart and kidney transplantation. MATERIAL AND METHODS: Ninety-eight stable heart transplant recipients were enrolled in the study; 80 kidney transplant recipients and 22 healthy volunteers served as controls. The laboratory tests, including parameters of 25-hydroxyvitamin D (calcidiol), were assayed using commercially available kits. RESULTS: Calcidiol deficiency (level below 10 ng/mL) was observed in 10% of the transplant group and in 55 % of the orthotopic heart transplant recipients (OHT). There was positive correlation between calcidiol concentration, hemoglobin, kidney function, and serum glucose in kidney transplant recipients. In OHT, vitamin D correlated with age, kidney function, hemoglobin, cholesterol, low-density lipoprotein cholesterol, and glucose. Both groups had similar kidney function. In both groups of patients with estimated glomerular filtration rate above 60 mL/min/1.72 m2, vitamin D was significantly higher. In OHT, vitamin D was higher in nondiabetic patients. In OHT in multivariate analysis, vitamin D was predicted in 24% by kidney function (beta = -0.30; P = .02) and hemoglobin concentration (beta = 0.25; P = .03). CONCLUSIONS: Vitamin D deficiency is more common in patients after heart transplantation than in kidney allograft recipients despite similar kidney function. The possible associations between the cardiovascular system and vitamin D merit further studies.

Kallistatin Concentration and Hypertension in Heart Transplant Recipients.

Development of arterial hypertension is to some extent related to decreased activity of the kallikrein-kinin system. This poorly understood hormonal system consists of blood proteins playing a role in the process of inflammation, coagulation, blood pressure control, and pain conduction. The system consists of kallikreins (plasma and tissue), kallistatin, kininogens, kinins (bradykinin, kallidin-lizynobradykinin), kininases (I and II), and membrane receptors of bradykinin. The aim of the study was the assessment of kallistatin in correlation to blood pressure value in heart transplant recipients. PATIENTS AND METHODS: Kallistatin level was estimated in 131 heart transplant recipients on standard 3 drugs immunosuppressive regimens (calcineurin inhibitor, mycophenolate mofetil/mycophenolic acid, and steroids) in correlation to inflammation markers and blood pressure values. Additionally, 22 healthy volunteers served as controls. In cross-sectional study, kallistatin and catecholamine concentrations were assessed using commercially available assays. RESULTS: Kallistatin concentration did not differ significantly among heart transplant recipients in comparison with controls; serum noradrenaline concentration was lower in the study group. In the orthotopic heart transplant group, kallistatin correlated with renal function; estimated glomerular filtration rate was calculated by Modification of Diet in Renal Disease formula (r = -0.28, P < .01; hemoglobin r = -0.19, P < .05; cholesterol level r = -0.23, P < .01; low-density lipoprotein r = 0.25, P < .01; ferritin r = 0.21, P < .05; noradrenaline r = -0.28, P < .01). No correlation with blood pressure values were revealed. In multivariate analysis, cholesterol serum level and age predicted 32% of variability of kallistatin concentration. CONCLUSION: Kallistatin among heart transplant recipients does not seem to be the pathogenetic factor of arterial hypertension but may be involved in the development of hyperlipidemia often present in this group of patients.

Opinions and Attitudes of Medical Students About Organ Donation and Transplantation.

BACKGROUND: Although transplantation has gained more support and acceptance, there are still many ethical, moral, and legal barriers associated with this form of treatment. The demand for organs is higher than what can be accommodated. Current medical students are forming their views about transplantation. METHODS: The aim of this study was to investigate the perspectives of 569 students from the Faculty of Medicine, Medical University of Bialystok, Poland, with regard to their beliefs about organ donation. RESULTS: Respondents included in this study were 21.77 ± 2.03 years of age (73.6% female, 80.1% living in an urban setting). Organ procurement and transplantation from living donors was found to be acceptable by 97.54% of respondents, and 98.77% found deceased donor procurement to be acceptable. More than 90% of respondents agreed with organ donation from family members after death, and agreed to donation after their own death. However, only 54.77% indicated an agreement to donate in their lifetime for nonrelatives. It was found that 70.74% believe the final decision on cadaveric organ donation should be made by the family. A positive attitude toward organ transplantation was expressed by 96.47% of respondents, but 2% submitted an objection to placement on a central registry. Refusals for organ donation included emotions associated with death (88%), religious beliefs (42%), and lack of knowledge of medical terminology (24.78%). According to respondents, the concept of transplantation should be managed by patients and donors (65.38%), universities (49.56%), or the media (44.64%). CONCLUSION: Medical students generally agree on procurement of organs from deceased and living donors. However, their enthusiasm for organ donation after death diminished with regard to their family members. An educational campaign promoting organ transplantation should be considered.

Future Lawyers Support Organ Donation and Transplantation.

In 2016 the total number of solid organ transplantations in Poland was 1469; the number of patients on waiting lists was approximately 1600 every month, and demand for organs is increasing every year. Transplantation has achieved increasing support and acceptance among Polish people; however, there are still many ethical, moral, and legal barriers related to this form of treatment of end-stage organ failure. MATERIAL AND METHODS: The research method is a diagnostic survey of 347 law students from the Faculty of Law, University of Bialystok, Poland. The research tool was the authors' questionnaire. RESULTS: Responders were 21.172 ± 1.34 years old (67.4% female, 74.4% urban residence). Organ procurement and transplantation from living donors are accepted by 95.6% of respondents; 97.4% are accepted from deceased donors. More than 80.4% of the respondents would agree to organ donation from their family members after death and to be donors after their death. The majority of students (80.1%) believe that the final decision of deceased organ donation should be made by the family. Despite positive attitude towards transplantation (97%), about 2% have submitted their objection to the central registry. Refusal of organ donation was associated mainly with emotions related to death (89%) and religion (47.6%). According to responders, the transplantation should be managed by patients and donors (42.1%) and universities (31.7%). CONCLUSIONS: Law students generally accept procurement of organs from deceased and living donors, but in situations related to family members, their acceptance rates drop significantly. According to future lawyers, patients, donors, and universities should educate society about issues related to organ transplantation.

Could neutrophil-gelatinase-associated lipocalin and cystatin C predict the development of contrast-induced nephropathy after percutaneous coronary interventions in patients with stable angina and normal serum creatinine values?

The value of neutrophil-gelatinase-associated lipocalin (NGAL) was highlighted as a novel biomarker for the detection of acute renal failure. We tested the hypothesis whether NGAL could represent an early biomarker of contrast-induced nephropathy (CIN) in 100 patients with normal serum creatinine values undergoing percutaneous coronary interventions (PCI). In addition, we assessed serum and urinary NGAL in relation to cystatin C, estimated glomerular filtration rate, and serum and urinary creatinine in these patients. We measured urinary and serum NGAL values before and 2, 4, 8, 24, and 48 h after the PCI. We found a significant rise in serum NGAL levels 2, 4, and 8 h after the PCI and in urinary NGAL values 4, 8, and 24 h after a PCI procedure. Cystatin C rose significantly 24 h after the procedure. The prevalence of CIN was 11%. The NGAL levels were significantly higher 2 h after the PCI (serum NGAL) or 4 h after the PCI (urinary NGAL), whereas the cystatin C values were higher only 8 and 24 h after a PCI procedure in patients with CIN. In multivariate analysis, only serum creatinine was a predictor of serum NGAL before a PCI. NGAL may represent a sensitive early biomarker of renal impairment after PCI. Serum creatinine level, the presence of diabetes, and the duration of the PCI may affect serum NGAL values and kidney function following a PCI procedure.

Comparison of serology assays and polymerase chain reaction for the monitoring of active cytomegalovirus infection in renal transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) infection is a common complication of renal transplantation. It can be diagnosed serologically, mainly based on seroconversion or by the detection of viral antigen via CMV-DNA amplification (polymerase chain reaction [PCR]). AIM: We sought diagnosis of an active CMV infection in renal transplant patients comparing serologic assays of CMV-IgM antibodies with CMV-DNA amplification. METHODS: We retrospectively studied renal transplant recipients 26 (including 15 women) hospitalized with clinical suspicion of CMV disease. The diagnosis of CMV infection was suspected on the basis of nonspecific symptoms, including fever, leukopenia, hyperbilirubinemia, and alanine aminotransferase elevation, alone or in combination. At the time of admission, all patients were screened for CMV-IgM antibody (immunoassays AxSYM/IMx) and CMV-DNA (qualitative PCR). RESULTS: The confirmation of CMV infection by the two methods (immunoassay and PCR) was obtained in only three patients (11.5%), its unambiguous exclusion--in four cases (15.4%). Nineteen patients (73.1%) were positive for CMV-IgM and negative for CMV-DNA. CONCLUSION: Detection of CMV-IgM antibodies by various immunoassays is not sensitive enough for diagnosis and cannot be used for monitoring during the active period in renal transplant recipients. This observation supported the prolonged presence of IgM antibodies after recent CMV infection in this patient group.

The predictive value of arterial renal blood flow parameters in renal graft survival.

BACKGROUND: Renal allograft survival depends on a number of factors, however, no reliable simple parameter has been shown to predict long-term outcome after transplantation. Ultrasound is recognized and relatively inexpensive, providing information about renal location, contour, and size. Doppler ultrasonography shows kidney morphology and hemodynamics. The aim of this study was the evaluation of whether Doppler ultrasound of renal arteries performed in the early stage after transplantation was a valuable predictor for long-term-outcomes. MATERIAL AND METHODS: The study included 17 female and 24 male patients, aged 17-69 years with stable graft function. The Doppler ultrasound of renal flow was done on the 1st and 3rd day after transplantaion, and estimated glomerular filtration rate (eGFR) on the 20th day. The measured indices were as follows: maximum blood flow velocity (V(max)), minimum blood flow velocity (V(min)), resistive index (RI), and pulsatile index (PI). The creatinine concentration was evaluated, and eGFR calculated. RESULTS: Mean renal and intrarenal artery RI increased to day 3 after transplantation, and then reduced. The mean renal and intrarenal V(max) at day 3 correlated positively with eGFR (r = 0.38; P = .015); (r = 0.45; P = .003, respectively). Mean renal and intrarenal V(min) correlated positively with eGFR (r = 0.50; P = .001; r = 0.41; P = .008, respectively). The mean renal and intrarenal V(max) and V(min) on day 1 did not correlate with eGFR. CONCLUSIONS: Early Doppler Ultrasonography of renal graft hemodynamics may be a valuable predictor of graft survival and long-term outcomes. Blood flow velocity within renal arteries seemed to be an important factor.

Hepcidin, an acute-phase protein and a marker of inflammation in kidney transplant recipients with and without coronary artery disease.

BACKGROUND: In kidney transplant recipients, endothelial dysfunction and atherosclerosis are almost universal, as are cardiovascular complications. Inflammatory markers have been shown to play a role in the pathogenesis and progression of atherosclerosis, regarded as a chronic inflammatory condition. Iron metabolism is disturbed in chronic inflammatory diseases such as atherosclerosis. Hepcidin, the liver-expressed antimicrobial peptide, LEAP-1, is an acute-phase reactant produced in the liver that displays intrinsic antimicrobial activity. Cross-sectional study was performed to assess possible relations between hepcidin and inflammatory markers in kidney transplant recipients with versus without coronary artery disease (CAD). METHODS: Iron status, complete blood count, creatinine, albumin, and lipids were estimated using standard laboratory methods. Glomerular filtration rate (GFR) was calculated using the MDRD formula. Hepcidin, high-sensitivity C-reactive protein (CRP), IL-6, TNFalpha, and soluble receptor of transferrin were measured using commercially available kits. RESULTS: Kidney transplant recipients with CAD were older, and showed higher hepcidin, hsCRP, IL-6, TNFalpha, sTFR, ferritin, and lower cholesterol levels than did patients without CAD. Univariate analysis of values in kidney transplant recipients showed hepcidin to correlate significantly with total protein, ferritin, time after transplantation, creatinine, eGFR (simplified MDRD), cholesterol, neutrophil count, hsCRP, and IL-6. There were tendencies to correlate with TNFalpha. Multiple regression analysis showed that hepcidin was independently related to GFR, cholesterol, and hsCRP. CONCLUSIONS: Elevated hepcidin values in kidney allograft recipients may be due not only to impaired renal function, but also to a low-grade inflammatory state, as reflected by hepcidin correlations with hsCRP, IL-6, and ferritin.

Resistin, a new adipokine, is related to inflammation and renal function in kidney allograft recipients.

BACKGROUND: Among patients without chronic kidney disease, resistin, an adipocytokine, has been related to inflammatory markers, coronary artery disease, and cardiovascular disease in the metabolic syndrome. Moreover, resistin up-regulates adhesion molecules. Since inflammation and endothelial cell damage or injury are invariably associated with thrombosis, atherosclerosis, and their major clinical consequences, resistin may play a role to link inflammation and CVD. The aim of this study was to correlate resistin with markers of inflammation and endothelial cell injury in 96 kidney allograft recipients. METHODS: We measured resistin and the following markers of endothelial function/injury: vWF, thrombomodulin, VCAM, hsCRP, tumor necrosis factor alpha (TNFalpha), and interleukin-6 (IL-6). RESULTS: Triglycerides, CRP (assessed by high-sensitivity method), phosphate, creatinine, IL-6, TNFalpha, vWF, prothrombin fragments 1 + 2, and resistin were elevated among kidney transplant recipients compared with the control group. Kidney allograft recipients with coronary artery disease displayed significantly higher resistin levels than those in patients without this complication. Upon univariate analysis resistin levels in kidney allograft recipients were related to hsCRP, IL-6, thrombomodulin, red blood cell count, white blood cell count, platelet count, creatinine, urea, VCAM, CSA, dose and eGFR. Upon multiple regression analysis, resistin was independently related only to creatinine, hsCRP, and white blood cell count in kidney allograft recipients. CONCLUSIONS: The relation of elevated resistin levels to markers of inflammation may represent a novel link between these conditions and adipocytokines. Renal function was a major determinant of elevated resistin in kidney allograft recipients.

Possible relations between thyroid function, endothelium, and kidney and liver function in kidney allograft recipients.

BACKGROUND: Renal function affects the thyroid gland in many ways. Disturbances in hemostasis and endothelial damage are common complications of kidney disease. Endothelial dysfunction may link these two processes. AIM AND METHODS: This cross-sectional study examined thyroid hormones in relation to markers of endothelial damage and inflammation among 80 kidney allograft recipients and 29 healthy volunteers. Thyroid hormones, markers of endothelial damage (vWF, thrombomodulin, intracellular adhesion molecule [ICAM] vascular adhesion molecule [VCAM], CD146), markers of inflammation (hsCRP), other hemostatic parameters (thrombin-antithrombin complexes [TAT], prothrombin fragments 1 + 2 [F1 + 2], plasmin-antiplasmin complexes, tissue plasminogen activator and its inhibitor, platelet glycoprotein [V-GPV]) as well as P-selectin were measured using commercially available kits. RESULTS: Total T3 was significantly lower among kidney allograft recipients, whereas markers of endothelial dysfunction and inflammation were significantly elevated over controls. In kidney allograft recipients total T3 was independently related to PAI-1, ICAM, and eGFR, whereas free T3 was independently related to thrombomodulin, aspartate, and alanine aminotransferases, hemoglobin, urea, eGFR, dose of cyclosporine and treatment with mycophenolate mofetil/azathioprine. Total T4 was related to aspartate and alanine aminotransferases, dose of cyclosporine, PAI-1, and ICAM. In multiple regression analysis the only correlates of T3 were PAI-1 and ICAM, whereas the only correlates of free T3 were thrombomodulin, aspartate aminotransferase, eGFR, and cyclosporine dose. In healthy volunteers GPV was related only to TSH. CONCLUSIONS: We described novel relations between thyroid hormones and markers of endothelial dysfunction in kidney transplant recipients. In kidney transplant recipients thyroid function metrics were associated with endothelial damage, immunosuppressive treatment, liver and kidney function. Therefore, the relations between thyroid axis and endothelium in kidney allograft recipients merit additional studies.