Development of a cyclic-inverso AHSG/Fetuin A-based peptide for inhibition of calcification in osteoarthritis.

OBJECTIVE: Ectopic calcification is an important contributor to chronic diseases, such as osteoarthritis. Currently, no effective therapies exist to counteract calcification. We developed peptides derived from the calcium binding domain of human Alpha-2-HS-Glycoprotein (AHSG/Fetuin A) to counteract calcification. METHODS: A library of seven 30 amino acid (AA) long peptides, spanning the 118 AA Cystatin 1 domain of AHSG, were synthesized and evaluated in an in vitro calcium phosphate precipitation assay. The best performing peptide was modified (cyclic, retro-inverso and combinations thereof) and evaluated in cellular calcification models and the rat Medial Collateral Ligament Transection + Medial Meniscal Tear (MCLT + MMT) osteoarthritis model. RESULTS: A cyclic peptide spanning AA 1-30 of mature AHSG showed clear inhibition of calcium phosphate precipitation in the nM-pM range that far exceeded the biological activity of the linear peptide variant or bovine Fetuin. Biochemical and electron microscopy analyses of calcium phosphate particles revealed a similar, but distinct, mode of action in comparison with bFetuin. A cyclic-inverso variant of the AHSG 1-30 peptide inhibited calcification of human articular chondrocytes, vascular smooth muscle cells and during osteogenic differentiation of bone marrow derived stromal cells. Lastly, we evaluated the effect of intra-articular injection of the cyclic-inverso AHSG 1-30 peptide in a rat osteoarthritis model. A significant improvement was found in histopathological osteoarthritis score and animal mobility. Serum levels of IFNγ were found to be lower in AHSG 1-30 peptide treated animals. CONCLUSIONS: The cyclic-inverso AHSG 1-30 peptide directly inhibits the calcification process and holds the potential for future application in osteoarthritis.

Label-free highly multimodal nonlinear endoscope.

We demonstrate a 2 mm diameter highly multimodal nonlinear micro-endoscope allowing label-free imaging of biological tissues. The endoscope performs multiphoton fluorescence (3-photon, 2-photon), harmonic generation (second-SHG and third-THG) and coherent anti-Stokes Raman scattering (CARS) imaging over a field of view of 200 µm. The micro-endoscope is based on a double-clad antiresonant hollow core fiber featuring a high transmission window (850 nm to 1800 nm) that is functionalized with a short piece of graded-index (GRIN) fiber. When combined with a GRIN micro-objective, the micro-endoscope achieves a 1.1 µm point spread function (PSF). We demonstrate 3-photon, 2-photon, THG, SHG, and CARS high resolution images of unlabelled biological tissues.

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.

High-performance Liquid Chromatography Measured Metabolites of Endogenous Catecholamines and Their Relations to Chronic Kidney Disease and High Blood Pressure in Heart Transplant Recipients.

BACKGROUND: Patients after solid organ transplantation, especially heart and kidneys, are prone to be hypertensive. Recently chronic kidney disease and renalase metabolism of endogenous catecholamines are thought to make major contribution to the pathogenesis of hypertension. MATERIALS AND METHODS: We analyzed 75 heart recipients (80% male, 20% female), medium age 54.9 years (range, 25-75) at 0.5 to 22 years after heart transplantation (median, 10.74). Diagnosis of hypertension was made on the basis of ambulatory blood pressure monitoring. Complete blood count, urea, creatinine, estimated glomerular filtration rate (eGFR), renalase in serum, and levels of metanefrine, normetanefrine, and 3-metoxytyramine in 24-hour urine collection calculated with a high-performance liquid chromatography were recorded. RESULTS: Urine endogenous catecholamine metabolites were estimated according to creatinine clearance. Normetanefrine was correlated with age (r = 0.27; P < .05), urea (r = 0.64; P < .01), creatinine (r = 0.6; P < .01), eGFR (r = -0.51; P < .01), renalase (r = 0.5; P < .01), and diastolic blood pressure (r = 0.26; P < .05). Metanefrine was correlated with urea (r = 0.43; P < .01), creatinine (0.32; P < .01), eGFR (r = -0.4; P < .01), renalase (r = 0.34; P < .05), height (r = -0.26; P < .05), weight (r = -0.23; P < .05), and time after heart transplantation (r = 0.27; P < .05). 3-Metoxytyramine was correlated with urea (r = 0.43; P < .01), creatinine (r = 0.32; P < .01), and the eGFR (r = -0.24; P < .05). Creatinine was correlated with age (r = 0.36; P < .01), diastolic blood pressure (r = 0.26; P < .05), time after heart transplantation (r = 0.24; P < .05), and renalase (r = 0.69; P < .01). Systolic blood pressure was correlated with proteinuria (r = 0.26; P < .05). CONCLUSIONS: Chronic kidney disease and concomitant hypertension are the most prevalent comorbidities in the population of heart transplant recipients. Urine catecholamine metabolites were related to kidney function but not to blood pressure level in the studied population.

Endocan Concentration and Chronic Inflammatory Process Among Heart Transplant Recipients.

BACKGROUND: 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. Its elevated level is connected with endothelial activation, neovascularization, and inflammation or carcinogenesis. METHODS: The level of serum endocan among 131 heart transplant recipients on 3-drug immunosuppression (calcineurin inhibitor, mycophenolate mofetil/mycophenolic acid, steroid) in correlation with other markers of endothelial damage was determined. In addition, 22 healthy volunteers were studied. In cross-sectional study, markers were measured with the use of commercially available assays of endothelial damage-endocan and von Willebrand factor (VWF)-inflammation-high-sensitivity C-reactive protein (hsCRP), interleukin (IL) 6-and kidney function-cystatin C. RESULTS: The endocan, VWF, IL-6, hsCRP, and cystatin C levels were significantly higher in heart transplant recipients compared with healthy volunteers. In our cohort, endocan level was correlated with renal function (estimated glomerular filtration rate: r = -0.21; P < .05), creatinine (r = 0.21; P < .05), erythrocyte count (r = -0.24; P < .01), hemoglobin (r = -0.33; P < .01), N-terminal pro-B-type natriuretic peptide (r = 0.25; P < .01), cholesterol (r = -0.22; P < .05), LDL (r = -0.21; P < .05), New York Heart Association functional class (r = 0.21; P < .05), hsCRP (r = 0.32; P < .01), IL-6 (r = 0.31; P < .01), and VWF (r = 0.27; P < .01). In multifactorial analysis, the predictors of endocan levels were cholesterol level, cystatin C, and IL-6, predicting 54% of variability. CONCLUSIONS: Endocan concentration among heart transplant recipients is potentially connected with endothelial damage caused by subclinical inflammation resulting from hyperlipidemia.

Absolute and Functional Iron Deficiency Is a Common Finding in Patients With Heart Failure and After Heart Transplantation.

BACKGROUND: Anemia is relatively common in patients with heart failure and heart transplant recipients. Both absolute and functional iron deficiency may contribute to the anemia in these populations. Functional iron deficiency (defined as ferritin greater than 200 ng/mL with TSAT (Transferrin saturation) less than 20%) is characterized by the presence of adequate iron stores as defined by conventional criteria, but with insufficient iron mobilization to adequately support. The aim of this study was to determine prevalence of absolute and functional iron deficiency in patients with heart failure (n = 269) and after heart transplantation (n = 130) and their relation to parameters of iron status and inflammation. METHODS: Iron status, complete blood count, and creatinine levels were assessed using standard laboratory methods. C-reactive protein, hepcidin and hemojuvelin were measured using commercially available kits. RESULTS: Absolute iron deficiency was present in 15% of patients with heart failure and 30% in heart transplant recipients, whereas functional iron deficiency was present in 18% of patients with heart failure and 17% in heart transplant recipients. Functional iron deficiency was associated with significantly higher C-reactive protein and hepcidin levels in heart failure patients, and higher hepcidin and lower estimate glomerular filtration rates in heart transplant recipients. Prevalence of anemia (according to the World Health Organization) was significantly higher in heart transplant recipients (40% vs 22%, P < .001), they were also younger, but with worse kidney function than patients with heart failure. CONCLUSIONS: Both absolute and functional iron deficiency were present in a considerable group of patients. This population should be carefully screened for possible reversible causes of inflammation.

Brain death versus irreversible cardiac arrest--the background and consequences of young people's opinions on stating death in Polish transplantology.

BACKGROUND: Brain death and irreversible cardiac arrest (ICA) are legally valid diagnoses obligatory for stating organ donors' death in Poland. Their misinterpretation may affect one's attitude toward organ donation. We assessed young people's knowledge and attitudes toward stating death in transplantology and their impact on attitude toward organ transplantation. METHODS: A total of 400 medical and 400 nonmedical students from public universities in Kraków, Poland, participated. Data were collected with a questionnaire examining demographic factors and transplantologic issues. RESULTS: Brain death diagnosis has a stronger association with stating death in transplantology than ICA, although the level of trust for this diagnosis remains relatively low among nonmedical respondents (38.5% vs 78.5%). Professional knowledge about stating brain death did not correlate with the level of trust for said diagnosis as strongly as it was expected, suggesting the presence of alternate contributing factors, some identified as doubts about brain death criteria (31.5%), distrust for the medical staff's education (25%), and objectivity (20%). CONCLUSIONS: The number of nonpositive attitudes toward organ transplantation was significantly higher among respondents unwilling to accept brain death as the death of a human being, a statement proven to be related to one's opinion about the reliability of said diagnosis, one's awareness of an alternative diagnosis of ICA, and one's general transplantologic knowledge. However, a low number of respondents acknowledging ICA as the only diagnosis valid for stating death of a cadaveric donor (7.6%) suggests that the majority of young Poles are willing to accept brain death as an equally valid, if not more significant, diagnosis.

Effect of immunosuppressive therapy on the serum fatty acids of phospholipids fraction in patients after heart transplantation.

BACKGROUND: The effects of tacrolimus (Tac) and cyclosporine (CsA) on lipid profile is well known; however, little is known about the changes in fatty acids (FA) of phosholipids fraction (PL) in heart transplant patients after treatment with these immunosuppressants. This study aimed to investigate the effect of Tac and CsA on serum FA of PL in heart transplant patients. METHODS: The study included 23 patients after heart transplantation on Tac (n = 14; group II) or CsA (n = 9; group I). Eleven healthy persons served as a control group. Serum FA of PL were extracted, separated on Sep-Pak NH2, methylated, and measured with the use of gas chromatography. Chemstation software was used to analyze the data. RESULTS: No differences between the studied groups and control were noted for saturated FA, monounsaturated FA, polyunsaturated FA (PUFA), total FA, and PUFA n-6. The mean value of PUFA n-3 was significantly higher in the CsA group compared with the Tac group (P < .015) and control (P < .002) as well as in the Tac group compared with control (P < .001). For individual FA, higher mean concentration, compared with control, was found for C24, C20:2, C20:4, and C22:6 (P < .001 in all cases) and lower for C18:2cis (P < .001 in both groups) and for C18:3 in the Tac group. The mean values of PUFA n-6 to PUFA n-3 ratios were lower than in control (both P < .001). CONCLUSIONS: Different pattern of FA of PL may indicate the different FA metabolism in heart transplant patients treated by different immunosuppressants. This should be taken into account when FA supplementation in these patients is considered.

Inadequate blood pressure control in orthotopic heart transplant: is there a role of kidney function and immunosuppressive regimen?

INTRODUCTION: Cardiac transplantation is the definitive therapy for eligible patients with end-stage heart failure. Hypertension is a widely accepted risk factor for its outcome. PATIENTS AND METHODS: We analyzed 169 heart transplant recipients. The diagnosis of hypertension was made on the basis of information gathered at 3 consecutive visits. Complete blood count, urea, serum lipids, fasting glucose, creatinine, and N-terminal pro-B-type natriuretic peptide were also studied. RESULTS: In the orthotopic heart transplantation (OHT) population, 11% had diabetes and 68% had chronic kidney disease. Hypertension was diagnosed and treated in 68% of the OHT patients. Hypertensive patients were significantly older, with a lower estimated glomerular filtration rate and higher serum creatinine and erythrocyte count. Thirty-three percent of patients did not achieve target blood pressure despite optimal medical treatment. Patients treated with tacrolimus had similar systolic blood pressure compared with those treated with cyclosporine (with a tendency to have lower values). Patients treated with mammalian target of rapamycin inhibitors had similar systolic and diastolic blood pressures compared with those treated without these inhibitors. In the group of patients given steroids, systolic and diastolic blood pressures were significantly lower than in the group not treated with steroids. In addition, steroid-treated patients had a significantly lower estimated glomerular filtration rate, hemoglobin, and erythrocyte count and higher serum creatinine, N-terminal pro-B-type natriuretic peptide, and New York Heart Association class. Chronic kidney disease was also more prevalent in this group. Blood pressure was not related to the kidney function. CONCLUSIONS: Despite polytherapy, optimal blood pressure control was not achieved in the majority of patients. OHT patients have a high prevalence of hypertension, which should be treated adequately. More efforts should be made to optimize blood pressure control, particularly when other comorbidities are present. Blood pressure was not related to patient kidney function.

Dopamine and noradrenaline are unrelated to renalase, heart rate, and blood pressure in heart transplant recipients.

INTRODUCTION: Renalase may degrade catecholamines and regulate sympathetic tone and blood pressure. The aim of this study was to assess dopamine, norepinephrine, and renalase in 80 heart transplant recipients and 22 healthy volunteers and their correlations with heart rate, blood pressure control, type of hypotensive therapy, and renal function. PATIENTS AND METHODS: Renalase, dopamine, and norepinephrine were studied by using commercially available assays. RESULTS: Renalase levels were higher in heart transplant recipients compared with healthy volunteers, and noradrenaline levels were lower in the studied cohort patients than in the healthy volunteers. Noradrenaline was correlated with white blood cell count (r = -0.21, P < .05), copeptin (r = 0.41, P < .01), and left ventricular diameter (r = -0.29, P < .05), whereas dopamine was correlated in univariate analysis with white blood cell count (r = -0.22, P < .05), posterior wall of left ventricular diameter (r = 0.58, P < .01), and left atrium diameter (r = -0.31, P < .05). Neither noradrenaline nor dopamine was correlated with heart rate, blood pressure, kidney function, or New York Heart Association class. Noradrenaline was significantly higher in patients with elevated diastolic blood pressure (>90 mm Hg) compared with those with normal diastolic blood pressure (P < .05). Renalase was related to kidney function but was unrelated to catecholamines. CONCLUSIONS: Elevated renalase levels in heart transplant patients were related to kidney function but not linked to the sympathetic nervous system activity in this study population. In heart transplant recipients, these findings might suggest that sympathetic denervation and the modulation of ß-receptors persist.

Fibroblast growth factor 23 and Klotho as cardiovascular risk factors in heart transplant recipients.

BACKGROUND: Fibroblast growth factor (FGF) 23 is one of the most recently discovered FGFs. This phosphaturic hormone produced in bones is a risk factor for cardiovascular diseases and thus mortality. Klotho is an essential coreceptor for FGF23 and at the same time it is known as a "longevity" hormone. There are no data considering FGF23 and Klotho roles in heart transplant (HT) recipients. The aim of this study was to assess Klotho and FGF23 serum concentration in heart transplant recipients depending on immunosuppressive therapy regimen and comorbidities. METHODS: Eighty-four stable heart transplant recipients were enrolled in the study; 22 healthy volunteers served as control subjects. FGF23 and Klotho protein concentration, markers of renal function, such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL), and heart failure markers, such as copeptine and N-termiinal pro-B-type natriuretic peptide (NT-proBNP), were evaluated. RESULTS: FGF23 concentration was significantly higher in the HT group whereas Klotho protein was significantly lower. FGF23 correlated with creatinine level (r = 0.72; P < .001), estimated glomerular filtration rate (eGFR; r = -0.32; P < .01), cystatin C (r = 0.36; P < .01), NGAL (r = 0.51; P < .001), hemoglobin (r = -0.39; P < .001), NT-proBNP (r = 0.51; P < .001), high-density lipoprotein (HDL; r = 0.27; P < .05), intraventricular septum thickness (r = 0.42; P < .01) and right ventricular systolic pressure (r = 0.34; P < .05). Klotho protein correlated only with age (r = -0.21; P < .05), creatinine (r = -0.21; P < .05), and eGFR (r = -0.31; P < .01). FGF23 concentration was significantly higher in patients with eGFR <60 mL/min whereas Klotho protein was significantly lower. FGF23 predictors were renal function (creatinine concentration; ß = 0.45; P = .0001), HDL (ß = 0.33; P = .003), intraventricular septum thickness (ß = 0.38; P = .0003), and right ventricular systolic pressure (ß = 0.34; P = .003), explaining 70% of FGF23 variability. CONCLUSIONS: FGF23/Klotho system disorders in HT recipients are related to cardiovascular system function and kidney failure and could cause increased risk of cardiovascular disease.

Growth differentiation factor 15 is related to anemia and iron metabolism in heart allograft recipients and patients with chronic heart failure.

BACKGROUND: Growth differentiation factor (GDF) 15 was recently identified as a hepcidin-suppression factor that is expressed at high levels in patients with ineffective erythropoiesis. Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. The aim of this study was to assess GDF15 levels and its correlation with iron parameters in 134 stable heart transplant recipients compared with 157 patients with chronic heart failure (CHF). METHODS: Complete blood count, urea, creatinine, lipids, fasting glucose, and iron status were studied with the use of standard laboratory methods. We assessed GDF15, hepcidin, and soluble transferrin receptor (sTfR) with commercially available assays. RESULTS: Mean levels of GDF15 and hepcidin were significantly higher in heart allograft recipients compared with patients with chronic heart failure (P < .001). GDF15 was significantly higher in patients with anemia compared with nonanemic counterparts in both groups. In univariate analysis in heart transplant recipients, GDF15 was related to kidney function, age, time after transplantation, hepcidin, sTfR, hemoglobin, transferrin saturation, ejection fraction (EF), and New York Heart Association functional class. GDF15 was not related to serum iron or ferritin in both groups. In multivariate analysis, sTfR, creatinine, and age were found to be predictors of GDF15. In univariate analysis in CHF patients, GDF15 was related to creatinine, erythrocyte count, hemoglobin, hepcidin, and total iron binding capacity and tended to correlate with EF. In multivariate analysis, hepcidin, creatinine, and EF were found to be predictors of GDF15 in CHF. CONCLUSIONS: GDF15, by affecting iron status, might be involved in the pathogenesis of anemia in patients with cardiovascular pathology.

Zonulin and iron metabolism in heart transplant recipients.

BACKGROUND: In patients after heart transplantation, anemia is relatively common and is associated with impaired kidney function, subclinical inflammatory state, and immunosuppressive treatment. Zonulin-prehaptoglibin-2 is newly discovered protein with poorly defined function. Hemoglobin binds haptoglobin, and this stable complex prevents oxidative stress caused by hemoglobin. Zonulin is necessary for integrity of intracellular tight junction in the gut. Taking into consideration iron metabolism, including its absorption in the gut, the aim of this study was to assess zonulin levels in heart transplant recipients and their possible correlations with iron status, immunosuppressive therapy, and kidney function. METHODS: The study was performed with 80 stable heart transplant recipients and 22 healthy volunteers. Zonulin, iron status, and inflammatory markers were assessed with the use of commercially available kits. RESULTS: Zonulin correlated with intraventricular diameter (r = 0.30; P < .05), right ventricle systemic pressure (r = 0.27; P < .05), and hemoglobin (r = 0.21; P < .05). There were no correlations between zonulin and iron status. Zonulin was significantly lower in heart transplant recipients than in healthy volunteers (P < .001). Kidney function, immunosuppressive regimen, New York Heart Association functional class, sex, and presence of anemia did not affect zonulin level. CONCLUSIONS: Zonulin, despite its effect on the absorption of different nutrients and other substances and hypothethic role in oxidative stress, seems not to play a role in the pathogenesis of anemia in heart transplant recipients. Its physiologic role remains obscure.

YKL-40, a novel marker of cardiovascular complications, is related to kidney function in heart transplant recipients.

BACKGROUND: YKL-40 is an inflammatory glycoprotein involved in endothelial dysfunction and expressed in macrophages in the earliest lesions of atherosclerosis. Elevated serum YKL-40 levels are independently associated with the presence and extent of coronary artery disease and cardiovascular mortality. Because there are no data on heart transplant recipients and because they are prone to cardiovascular complications, the aim of this study was to assess YKL-40 in this population with particular attention to its relationship with endothelial damage. We studied 84 patients after heart transplantation. Healthy volunteers served as control subjects. METHODS: Complete blood count, urea, creatinine, lipids, fasting glucose, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and iron status were studied with the use of standard laboratory methods. We assessed YKL-40, copeptin, markers of inflammation high sensitivity C-reactive protein (hsCRP) and interleukin (IL) 6, and markers of endothelial cell injury von Willebrand factor (vWF) and midkine with the use of commercially available assays. RESULTS: Mean levels of YKL-40, IL-6, vWF, and hsCRP were significantly higher in heart allograft recipients than in the control group (P < .001). In univariate analysis, YKL-40 was related to kidney function (creatinine, r = 0.63 [P < .001]; estimated glomerular filtration rate, r = -0.44 [P < .001]), NT-proBNP (r = 0.45; P < .001), age (r = 0.33; P < .01), time after transplantation (r = 0.23; P < .05), copeptin (r = -0.42; P < .001), soluble transferrin receptor (r = 0.24; P < .05), hemoglobin (r = -0.42; P < .001), transferrin (r = -0.31; P < .01), haptoglobin (r = 0.39; P < .001), cystatin C (r = 0.55; P < .001), ejection fraction (r = -0.28; P < .05), New York Heart Association functional class (r = -0.41; P < .01), hsCRP (r = 0.26; P < .05), IL-6 (r = 0.23; P < .05), vWF (r = -0.40; P < .001), and midkine (r = 0.33; P < .01). In multivariate analysis, only creatinine was found to be a predictor of YKL-40 (ß = 0.59; P = .02), explaining 56% of the variation in YKL-40 levels in heart allograft recipients. CONCLUSIONS: YKL-40 may contribute to the enhanced risk of cardiovascular complications mainly owing to impaired renal function in patients after heart transplantation.