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.

Do Age and Religion Have an Impact on the Attitude to Organ Transplantation?

BACKGROUND: Religious issues may be a significant reason for the lack of organs for transplantation. Younger people have a more enthusiastic attitude toward organ donation. The goal of the present study was to determine whether age and religion affect people's attitudes to organ transplantation. METHODS: This trial was a diagnostic poll study using an original survey questionnaire involving 1273 people living in Podlaskie Voivodeship. RESULTS: Treatment with the use of organs from dead donors was approved by 88.3% of the respondents aged ≤60 years and 70.5% of those aged >60 years; the highest number of those who opposed this procedure occurred in the group aged >60 years (22.3%). Baptists approved of the method more often than persons of other religions; Muslims disapproved of it more often than others (25%). Approximately 96% of the participants, regardless of religion, had a positive attitude toward organ transplantation, but only 81% aged >60 years had a positive attitude toward organ donation; there were significantly more Catholics in this group (P < .026). In the group aged >60 years, 63.8% expressed their consent; 66.7% of them were Muslims and Baptists. Approximately 86% of persons aged ≤60 years were willing to donate their own organs after death. These people were significantly more often Catholic (P < .045). CONCLUSIONS: Age and religion have a considerable influence on positive attitudes toward transplantation. The majority of younger people, as well as Catholics, approve of the removal of organs from living donors and from dead donors.

Opinions and Attitudes of University Students Concerning Organ Transplantation.

INTRODUCTION: Organ donation and transplantology are receiving more and more support and approval all over the world every year. However, there remains a considerable and growing difference between the number of patients awaiting transplantation and the number of donors. The aim of the work was to find out the opinions and attitudes of university students concerning organ donation and transplantology. MATERIAL AND METHODS: Our poll surveyed 405 students from 2 universities (Medical University of Bialystok [MU] and Bialystok University of Technology [UT]). The research tool used in the study was an original survey questionnaire. RESULTS: Treatment with the use of organs taken from living persons was approved by 55.6% of the students, from dead donors, by 73.6%, and 1.2% of the participants did not approve of that way of treatment. Of the students from the MU, 84% approved the removal of organs from close relatives after their death; 79.5% of those from the UT approved. Of the UT students, 8% were against the removal of organs from close relatives after their death; 4% of MU students were against it. Of MU students 94.5%, would agree to have their own organs removed after death; 85.3% of UT students would agree. Of MU students, 54.2% of students had informed their families about their will to have organs removed; 29.4% of UT students had informed their families. A greater number of medical students had a declaration of will (28.9% vs 13.2%; P < .001). The kind of university had a significant (P = .002) influence on the students' attitudes to transplantation. A positive attitude was displayed by 94.5% of MU students and 83.8% of UT students, whereas a negative one, by 2% of UT students and 0.5% of MU students. CONCLUSIONS: Different degrees of knowledge and acceptance of organ donation were manifested by university students. To a great extent, this depended on the kind of university. MU students understood the topic and approved of the treatment to a greater degree. A permanent educational campaign should be carried out among young people, especially those studying at universities other than medical.

Vascular adhesion protein-1, a novel molecule, in kidney and heart allograft recipients.

BACKGROUND: VAP-1 (vascular adhesion protein-1) is a copper-containing SSAO (semicarbazide-sensitive amine oxidase) secreted by vascular smooth muscle cells, adipocytes, and endothelial cells. Elevation of SSAO activity is observed in atherosclerosis, diabetes mellitus, and obesity. The aim of the study was to assess VAP-1 in prevalent heart and kidney allograft recipients. METHODS: Complete blood count, urea, serum lipids, fasting glucose, and creatinine were studied by standard laboratory methods. VAP-1, N-terminal pro brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP) were estimated using commercially available assays. RESULTS: Healthy volunteers showed higher hemoglobin and estimated glomerular filtration rate (eGFR) but lower creatinine, NT-proBNP, hsCRP and VAP-1 relative to heart and kidney transplantation (OHT) (KTx). Among heart transplant recipients, VAP-1 correlated with age, presence of diabetes, insulin therapy, ejection fraction, estimated glomerular filtration rate by MDRD (Modification of Diet in Renal Disease), eGFR by CKD-EPI (Chronic Kidney Disease-Epidemiological Collaboration), use of tacrolimus, LVIDd (left ventricular internal end-diastolic dimension), New York Heart Association class and NT-proBNP. VAP-1 was significantly lower among patients treated with tacrolimus than cyclosporine. Diabetic patients versus nondiabetic subjects as well as patients with eGFR below 60 versus ≥ 60 mL/min showed higher serum VAP-1 in OHT and KTx populations. Multiple regression analysis revealed VAP-1 to be predicted in 25% by LVIDd, and use of tacrolimus in OHT. In kidney transplant recipients, VAP-1 correlated only with time after transplantation and serum glucose. CONCLUDING: VAP-1 elevations in heart transplant recipients were predominantly dependent on left ventricular diameter and use of tacrolimus; however, the precise associations with the immunosuppressive regimen warrant further studies. VAP-1 elevations in kidney transplant recipients may relate to glucose control.

Iron metabolism, hepcidin, and anemia in orthotopic heart transplantation recipients treated with mammalian target of rapamycin.

PURPOSE: Functional iron deficiency is characterized by the presence of adequate stores as defined by conventional criteria, but with the inability to sufficiently mobilize iron for erythropoiesis. Hepcidin, produced by hepatocytes in response to anemia, hypoxia, or inflammation, is a key regulator of iron homeostasis. Anemia is relatively common among patients treated with mammalian target of rapamycin (mTOR) antagonists. We tested hypothesis that hepcidin was related to the functional iron deficiency, defined as a ferritin value above 200 ng/mL with transform saturation (TSAT) below 20% among orthotopic heart transplant recipients (OHT) treated (n = 35) versus not treated (n = 134) with mTOR. METHODS AND MATERIALS: Using standard laboratory methods we assessed iron status: serum iron, total iron binding capacity, ferritin, TSAT, complete blood count and creatinine. Soluble transferrin receptor (sTFR), high sensitivity C-reactive protein (hSCRP), interleukin-6 (IL-6) hepcidin, and cystatin C were measured using commercially available kits. RESULTS: According to the World Health Organization definition, the prevalence of anemia was 51% among mTOR treated whereas in the rest of the OHT the prevalence of anemia 30% among the other OHT patients. Functional iron deficiency was present in 80% of mTOR-treated patients. Serum hepcidin, IL-6, hsCRP, serum creatinine, cystatin C, NT-proBNP were significantly higher among mTOR treated patients; whereas sTFR, estimated glomerular filtration rate, hemoglobin, and erythrocyte count were significantly lower. CONCLUSIONS: Functional iron deficiency which is common among OHT patients treated with mTOR, was associated with high hepcidin levels and inflammatory markers. This form of anemia in mTOR-treated OHT resembles the disorder of chronic disease, suggesting that OHT patients show low-grade inflammation, which should be investigated for underlying, potentially reversible causes. Iron treatment should also be considered.

Hemojuvelin and iron metabolism in kidney and heart allograft recipients.

INTRODUCTION: Hemojuvelin plays an essential role in the regulation of hepcidin expression, specifically in the iron-sensing pathway. Dietary iron sensing and inflammatory pathways converge in the regulation of the key regulator hepcidin. Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. We studied correlations of hemojuvelin with markers of iron status and of inflammation among 61 prevalent kidney allograft recipients and 136 prevalent heart transplant recipients. METHODS: Complete blood count, urea, serum lipids, fasting glucose, and creatinine were measured using standard laboratory methods in the central laboratory of the hospital. Hepcidin, soluble transferin receptor (sTFR), interleukin-6 (IL-6) and hemojuvelin were assayed by enzyme immunosorbent assay using commercially available kits. RESULTS: Among heart transplant recipients hemojuvelin correlated strongly with kidney function, transferrin saturation and white blood cell count; moderately with red blood cell count, hepcidin, IL-6, high-sensitivity C-reactive protein (hsCRP) and weakly with sTfR. Multiple regression analysis revealed the predictors of hemojuvelin to be kidney function and TSAT, explaining 79% of the variations among hemojuvelin values in heart transplant recipients. Among kidney transplant recipients hemojuvelin correlated with kidney function, TSAT, hepcidin and hsCRP, and tended to correlate with IL-6. Predictors of hemojuvelin on multiple regression analysis were TSAT and creatinine. CONCLUSIONS: Elevated hemojuvelin as well as hepcidin levels in kidney or heart transplant recipients may be due to the impaired kidney function and disturbed iron status frequently encountered among this population.

Renalase and endothelial dysfunction in heart transplant recipients.

INTRODUCTION: Renalase, an enzyme that cetabolyzes catecholamines, such as circulating adrenaline and noradrenaline, is released by the human kidney to regulate blood pressure. In solid organ transplant recipients endothelial dysfunction is often present. The aim of our study was to assess correlations among renalase, blood pressure, endothelial injury markers, and kidney function in 130 prevalent heart allograft recipients (OHT). METHODS: Complete blood counts, urea, serum lipids, fasting glucose and creatinine were measured using standard laboratory methods in the hospital central laboratory. We assessed markers of endothelial function/injury: vWF (von Willebrand factor), inflammation: hsCRP, interleukin (IL)-6, TRAIL (tumor necrosis factor related apoptosis-inducing ligand), TWEAK (tumor necrosis factor-like weak inducer of apoptosis) and midkine renalase using commercially available kits. RESULTS: The mean serum renalase among OHT was significantly higher compared with a control group (P < .001). Among heart transplant recipients renalase correlated weakly (P < .05) with time after transplantation and TRAIL; moderately (P < .01), with ejection fraction and age; and strongly, with kidney function, IL-6, vWF, midkine, and New York Heart Association class (P < .05). Multiple regression analysis revealed renalase values to be 70% predicted by serum creatinine measurements. CONCLUSION: Impaired kidney function was strongly associated with endothelial damage and inflammation. Renalase, which was highly elevated among heart transplant recipients, was predominantly dependent on renal function, which deteriorated with time after transplantation and in correlation with age.

Is hemojuvelin a possible new player in iron metabolism in hemodialysis patients?

INTRODUCTION: Hemojuvelin (HJV) is highly expressed in the liver, skeletal muscles, and heart, seems to play a role in iron absorption and release from cells, and has anti-inflammatory properties. Moreover, HJV plays an essential role in the regulation of hepcidin expression, specifically in the iron-sensing pathway. Hepcidin has emerged as a key regulator of iron homeostasis. In this study we tested for the first time the hypothesis that HJV is related to iron metabolism in hemodialysis (HD) patients. METHODS: Iron status, complete blood count, and serum creatinine, albumin, and lipids were assessed, using standard laboratory methods. Serum levels of soluble transferrin receptor (sTFR), high-sensitivity CRP, IL-6, hepcidin, and HJV were measured using commercially available kits. RESULTS: Serum HJV, hepcidin, ferritin, IL-6, hsCRP, and serum creatinine were significantly higher (all P<0.001), whereas serum iron, sTFR, transferrin, hemoglobin, and erythrocyte count were significantly lower in HD patients, compared to healthy volunteers (all P<0.001). In univariate analysis, HJV was strongly correlated (P<0.001) with ferritin, transferrin saturation, and TIBC, as well as with hsCRP, hepcidin, Kt/V (P<0.01) and residual renal function, the presence of diabetes, APKD, and coronary heart disease. Predictors of HJV level in multiple regression analysis were ferritin (beta value was 0.50, P=0.00004) and transferrin saturation (beta value was 0.47, P=0.0002), explaining 81% of the HJV variations. CONCLUSIONS: Serum HJV is elevated in HD patients and related predominantly to kidney function and iron metabolism. However, HJV is probably not correlated to inflammation. HJV appears to be a new player in iron metabolism in these patients.

Real-time myocardial contrast echocardiography as a useful tool to select candidates for coronary revascularization among patients with end-stage renal disease - a 3-year follow-up study.

PURPOSE: To evaluate a real-time myocardial contrast echocardiography (MCE) as a tool to select candidates for coronary revascularization among patients with ESRD and to assess the rate of revascularization and mortality. MATERIAL/METHODS: 58 ESRD patients were screened for CAD using MCE. We analyzed the rate of coronary revascularization during 3-year follow-up. Patients with and without perfusion disturbances on MCE were compared. RESULTS: CAD was found in 46.2% patients out of 39 who underwent coronary angiography. 11 (39.3%) patients out of 28 from the group with perfusion defects on MCE underwent revascularization procedure (21.4% - PCI, 17.9% - CABG). No one from the group without perfusion defects had revascularization procedure. Perfusion defect (OR 1.37 CI 1.37-1.86, p=0.022) was related to revascularization in multivariant analysis (OR 12.87, CI 1.86-89.21, p=0.025). There was no difference in mortality between the group which underwent invasive procedures and treated conservatively (p=0.6643). In ROC analysis defects on MCE and CAD on angiography were equally good in anticipating combined end-point (AUC 0.716, CI 95% 0.544-0.851 and AUC 0.747, CI 95% 0.577-0.875, p=0.701) and death (AUC 0.752, CI 95% 0.582-0.878 and AUC 0.729, CI 95% 0.558-0.861, p=0.805). CONCLUSIONS: Our results indicate that MCE is a safe and uncomplicated method which may help along with other methods to select candidates for coronary revascularization among ESRD patients. In our study coronary revascularization procedures were successful but they did not improve patients' survival on 3-year follow-up.

Compliance with lifestyle recommendations in kidney allograft recipients.

BACKGROUND: Many factors affect long-term graft and patient survival. Compliance with lifestyle recommendation may be an important factor. Lifestyle modifications may play a therapeutic and protective role against graft failure and possible death. METHODS: The aim of this work was to assess compliance with lifestyle recommendations among 110 kidney allograft recipients. All patients were asked to complete a questionnaire regarding life style, frequency of outpatient visits, self-control, diet, physical activity and addictions. RESULTS: The mean age of the population was 48.79±13.18 years, and their mean time after transplantation was 69±44.5 years with a mean serum creatinine value of 1.45±0.7 mg/dL. Physicians were the major source of information (40%) for patients while in the hospital; nurses informed patients in only 5.5% of cases. The majority of patients (97.5%) attended regular outpatient clinic visits. A similar percentage of subjects regularly measured their blood pressure at home. One-fifth of the patient wrote a self-control diary. Only 55.5% of patients knew the immunosuppressive regimen, including the doses of the medications. An overweight condition was diagnosed in 39%, with obesity in 22%; 16% of the patients were smokers; one-fourth of the patients drank alcohol at least several times a month; 85.3% of patients did not change their diet after kidney transplantation; and one-half of the patients (64.2%) were not aware of dietary recommendations after kidney transplantation. CONCLUSIONS: The majority of patients regularly attended the outpatient clinic and ingested immunosuppressive medications. However, their knowledge regarding diet, cancer prophylaxis, and self-control was insufficient. Therefore, there is a need to introduce more intense organizational and educational activities to improve patient knowledge.

Iron metabolism in kidney allograft recipients: still a mystery?

INTRODUCTION: All living organisms have evolved sophisticated mechanisms to maintain appropriate iron levels in their cells and within their body. Recently our understanding of iron metabolism has dramatically increased. Overt labile plasma iron (LPI) represents a component of non-transferrin-bound iron (NTBI) that is both redox active and chelatable, capable of permeating into organs and inducing tissue iron overload. LPI measures the iron-specific capacity of a given sample to produce reactive oxygen species. We studied NTBI correlations with markers of iron status and inflammation in prevalent kidney allograft recipients. METHODS: Complete blood count, urea, creatinine, serum lipids, fasting glucose, ferritin, serum iron, and total iron-binding capacity (TIBC) were studied by standard laboratory method in the hospital central laboratory. NTBI was assessed by FeROS eLPI kit by Aferrix Ltd (Tel Aviv, Israel). A test result of 0.6 U of LPI or more indicated a potential for iron-mediated production of reactive oxygen species in the sample. RESULTS: In kidney transplant recipients NTBI was correlated with TIBC (r=.46, P<.001) and ferritin (r=.31, P<.05), with tendencies to correlate with C-reactive protein. Patients with LPI units≥0.6 showed higher serum iron (P<.05), TIBC (P<.05), ferritin (P<.001) and mean corpuscular volume. High ferritin values together with elevated NTBI content were observed among patients undergoing multiple transfusions before and/or after transplantation. CONCLUSIONS: Elevated NTBI as well as ferritin levels in kidney transplant patients may be due to disturbed iron metabolism, since the human body has no possibility to remove an iron excess. NTBI could be responsible for excessive synthesis of reactive oxygen species. Therefore, it may be linked to complications such as atherosclerosis, which is frequently encountered among this population.

Renalase, a novel regulator of blood pressure, is predicted by kidney function in renal transplant recipients.

BACKGROUND: Renalase is an enzyme that catabolizes catecholamines such as adrenaline and noradrenaline in the circulation. The human kidney releases this protein into the bloodstream to regulate blood pressure. In kidney transplant recipients, the prevalence of hypertension is 60%-80%. OBJECTIVE: The aim of our study was to assess possible correlations between renalase, blood pressure, and kidney function among 89 prevalent kidney allograft recipients. To obtain normal ranges, we also studied renalase levels in 27 healthy volunteers. METHODS: Complete blood counts, urea, serum lipids, fasting glucose, and creatinine were measured by standard laboratory methods in the hospital central laboratory. Renalase was assessed with the use of a commercially available kit. RESULTS: In kidney transplant recipients renalase was significantly higher than in healthy volunteers (P<.001). In kidney transplant recipients, renalase correlated with age (r=0.29; P<.05), time after transplantation (r=0.34; P<.01), systolic blood pressure (r=0.28; P<.05), diastolic blood pressure (r=0.27; P<.05), serum creatinine (r=0.49; P<.001), estimated glomerular filtration rate (Chronic Kidney Disease Endemiology collaboration: r=-0.44; P<.0001; Modification of Diet in Renal Disease: r=-0.43; P<.001; Cockcroft-Gault r=-0.39; P<.01), serum phosphate (r=0.34; P<.05). Upon multiple regression analysis renalase was predicted by 70% using age (beta value 0.21, P=0.043), time after transplantation (beta value, 0.22; P=.037), serum creatinine (beta value, 0.50; P=.016), and diastolic blood pressure (beta value, 0.33; P=.027). CONCLUSIONS: Renalase is highly elevated in kidney transplant recipients, predominantly dependent on kidney function, which deteriorates with time after kidney transplantation and age. Further studies are needed to establish its putative role in the pathogenesis of hypertension after transplantation and possible novel targeted therapies.

Kidney injury molecule-1 correlates with kidney function in heart allograft recipients.

Serum creatinine and estimated glomerular filtration rate (eGFR) (24 hours creatinine clearance, Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, Cockcroft-Gault formulae), and urinary kidney injury molecule-1 (KIM-1), were evaluated in 111 heart allograft recipients on therapy with a calcineurin inhibitor, mycophenolate mofetil or azathioprine plus prednisone. KIM-1 was assessed using commercially available assay. Normotensive heart allograft recipients showed significantly lower KIM-1 values than hypertensive subjects. Urinary KIM-1 was significantly higher among New York Heart Association class III versus I and II patients. Upon univariate analysis, urinary KIM-1 strongly correlated with serum creatinine (r=.54) and eGFR (r=.66) but only weakly with other parameters. It was not related to cystatin C. Upon multiple regression analysis, the best predictor of urinary KIM-1 was eGFR (beta -0.56), explaining 76% of KIM-1 concentrations. Even a successful heart transplantation is associated with kidney injury as reflected by elevated urinary KIM-1 and reduced eGFR. Therefore, KIM-1 needs to be investigated as a potential early marker for impaired kidney function/kidney injury, especially in patients with other risk factor for kidney damage, for example, hypertension or congestive heart failure.

Liver fatty-acid-binding protein in heart and kidney allograft recipients in relation to kidney function.

Mammalian intracellular fatty-acid-binding proteins (FABPs), a large multigene family, encode 14-kD proteins that are members of a superfamily of lipid-binding proteins. FABPs are tissue specific. Liver-type FABP (L-FABP) can be filtered through the glomerulus owing to its small molecular size, similar to cystatin C, but it is reabsorbed by proximal tubule epithelial cells like other small proteins. In the human kidney, L-FABP is expressed predominantly in proximal tubules. It had been suggested that the presence of L-FABP in urine reflects hypoxic conditions resulting from decreased peritubular capillary flow, serving as a marker of acute kidney injury. The aim of this study was to assess urinary L-FABP in 111 heart and 76 kidney transplant recipients in relation to kidney function. Complete blood count, urea, fasting glucose, creatinine, and the N-terminal fragment of brain natriuretic protein were studied by standard laboratory methods; L-FABP and cystatin C, by ELISA using commercially available kits. Kidney transplant recipients displayed significantly higher L-FABP than heart recipients. Upon univariate analysis, urinary L-FABP correlated, with serum creatinine, cystatin C and estimated glomerular filtration ratio (eGFR) in kidney allograft recipients. However, in heart transplant recipients it was not related to kidney function, as reflected by creatinine or eGFR; was strongly related to cystatin C (r=0.34; P<.001) and urinary creatinine (r=-0.29; P<.01), and NGAL (r=0.29; P<.01). Upon multiple regression analysis, the best predictor of urinary L-FABP in kidney allograft recipients, was eGFR whereas in heart recipients, no parameter independently predicted L-FABP. Successful heart transplantation is associated with kidney injury as reflected by a reduced eGFR; however, in this population, L-FABP did not serve as a marker of kidney function. In contrast, in kidney allograft recipients, L-FABP may be a potential early marker for impaired kidney function/injury.

Lack of non-transferrin-bound iron in heart transplant recipients.

BACKGROUND: Labile plasma iron (LPI) is a heterogeneous fraction thought to be composed of iron bound to serum albumin, citrate, and other undefined negatively charged ligands called non-transferrin-bound iron (NTBI). It is associated with formation of reactive oxygen species which are implicated in the pathogenesis of myocardial infarction and bacterial infection. Therefore, the measurement of NTBI could serve as an early marker for reactive oxygen species-induced tissue damage. In this study, we assessed the prevalence of NTBI in heart transplant recipients. METHODS: Complete blood counts, urea, serum lipids, fasting glucose, creatinine, and N-terminal pro-B-type natriuretic peptide were studied by standard laboratory methods in the central laboratory of the hospital. Soluble transferrin receptor was measured using kits from R&D (Abington, UK) and interleukin-6 with kits from Diaclone (Germany). NTBI was assessed in Israel by Aferrix Ltd; LPI≤0.4 units was considered to be negative. RESULTS: In all of the studied patients, NTBI was negative. In the 15 healthy volunteers, all the results were negative. CONCLUSIONS: In heart allograft recipients there is no evidence of reactive oxygen species-induced tissue damage due to either iron overload from oversupplementation or excessive blood transfusion. However, this particular adverse effect should be taken into account when considering treatment of anemia with iron and/or red blood cell transfusions.

Soluble tumor necrosis factor-like weak inducer of apoptosis plasma levels as a novel biomarker of endothelial function in prevalent orthotopic heart transplant recipients.

BACKGROUND: Nonrenal solid organ transplantation is now an established method of therapy with significantly improved outcome over the last years; however, an increasingly prevalent complication in this population is chronic kidney disease. Endothelial dysfunction is highly prevalent in both cardiovascular disease and chronic kidney disease. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily of cytokines. MATERIALS AND METHODS: The aim of the study was to assess TWEAK concentration in 134 prevalent heart transplant recipients in relation to kidney function. Complete blood count, urea, serum lipids, fasting glucose, creatinine, NT-proBNP were studied. Soluble TWEAK was assayed using commercially available kits from Bender MedSystems (VIenna, Austria). High-sensitivity C-reactive protein was assayed using commercially available kits from American Diagnostica (Greenwich, Conn, USA). RESULTS: Heart transplant recipients had significantly higher serum creatinine, urea, cholesterol, triglycerides, fasting glucose, white blood cell count, lower TWEAK levels and lower estimated glomerular filtration rate (eGFR) than the control group. Serum TWEAK levels fell together with New York Heart Association (NYHA) class and rise in GFR. Serum TWEAK was related to kidney function, NYHA class, NT-proBNP, and triglycerides. Kidney function and NYHA class turn out to be predictors of TWEAK in heart transplant recipients. CONCLUSION: TWEAK level is dependent on kidney and heart function. It might also represent a surrogate marker of endothelial dysfunction and atherosclerosis.

Kidney injury molecule-1 correlates with kidney function in renal allograft recipients.

INTRODUCTION: KIM-1 (kidney injury molecule-1) is responsible for the clearance of debris from damaged renal tubules. KIM-1 can be expressed and excreted in urine within 12 hours after the initial ischemic insult and before regeneration of the epithelium, persisting over time thereafter. Urinary KIM-1 has been reported to be a noninvasive, rapid, sensitive, and reproducible biomarker of experimental nephrotoxic and ischemic acute kidney injury. Renal KIM-1 expression is significantly increased in human kidney tissue among patients with a wide range of kidney diseases, including various types of glomerulonephritis, chronic allograft nephropathy, acute rejection, hypertension, and Wegener's granulomatosis. Both renal and urinary KIM-1 correlate with kidney damage and negatively with renal function, but not with proteinuria. The aim of this study was to assess whether urinary KIM-1 correlated with kidney function in kidney allograft recipients. METHODS: Serum NGAL, creatinine and estimated glomerular filtration rate (eGFR) were evaluated in 170 kidney allograft recipients on therapy with a calcineurin inhibitor plus mycophenolate mofetil or azathioprine and prednisone as well as in healthy volunteers. KIM-1 was estimated in urine using a commercially available kit. RESULTS: Kidney transplant recipients showed significantly higher KIM-1 values than the control group. Normotensive kidney allograft recipients displayed significantly lower NGAL results than hypertensive subjects. Urinary KIM-1 was significantly higher among diabetic than nondiabetic subjects, whereas creatinine did not differ significantly between them. Upon univariate analysis urinary KIM-1 strongly correlated with serum creatinine (r = .64) and eGFR (r = -.71), and only weakly with other parameters. Upon multiple regression analysis, the best predictor of urinary KIM-1 was eGFR (beta -0.61), which explained 61% of KIM-1 concentrations. CONCLUSION: Even a successful kidney transplantation is associated with kidney injury as reflected by elevated urinary KIM-1 and lower eGFR. Therefore, KIM-1 needs to be investigated as a potential early marker for impaired renal function/kidney injury, especially in patients with other risk factors for damage such as hypertension or diabetes.

Prevalence of chronic kidney disease in orthotopic heart transplant recipients and kidney allograft recipients using the new Chronic Kidney Disease Epidemiology Collaboration formula.

Chronic kidney disease (CKD) is an important long-term complication of all forms of nonrenal organ transplantation. The aim of this study was to assess the prevalence of kidney dysfunction among heart (n = 163) and kidney allograft recipients (n = 169) using the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula, which includes age, gender, and comorbidities. The mean serum creatinine values in these populations were 1.58 ± 0.75 mg/dL and 1.36 ± 0.56 mg/dL, respectively. In heart allograft recipients mean estimated glomerular filtration rate (eGFR) by (MDRD) was 57.14 ± 26.17 mL/min, and by CKD-EPI formula was 57.44 ± 26.76 mL/min whereas in kidney allograft recipients it was 63.91 ± 25.43 mL/min and 65.20 ± 25.60 mL/min, respectively. According to the MDRD formula, stage 2 CKD was noted in 35 patients; stage 3 CKD in 79 patients, and stage 4 in 23 patients. According to the CKD-EPI formula stage 2 CKD was displayed by 35 patients; stage 3 CKD in 78 patients, and stage 4 in 23 patients. Clinically significant CKD (GFR < 60 mL/min) was observed in 62% of patients. According to the MDRD normal kidney function was present in 22 and according to the CKD-EPI formula in 27 patients. According to the MDRD formula stage 2 CKD was found in 59 kidney allograft recipients; stage 3 in 58 patients; and stage 4 in 16 patients. According to the CKD-EPI formula, stage 2 CKD was noted in 63 patients; stage 3 in 58 patients; and stage 4 in 15 patients. Clinically significant CKD was observed in 44% of patients. Using MDRD or CKD-EPI normal kidney function was found in 36 and 33 patient, respectively. CKD prevalence is extremely high among heart and kidney transplant recipients. Evaluation of renal function is important to select the appropriate strategy to reduce the cardiovascular risk.