"NS10043"
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BACKGROUND/AIMS: Pregnancy-associated plasma protein A (PAPP-A) is a biomarker related to vascular damage. The aim of the study was to focus on PAPP-A and related parameters and their relationship to the prognosis of long-term hemodialysis (HD) patients. METHODS: This is a prospective observational cohort study which included 261 long-term HD patients followed up for 5 years and 66 healthy subjects. PAPP-A, placental growth factor (PlGF), matrix metalloproteinase 2 and 9 (MMP-2, MMP-9), insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-4 (IGFBP-4), and cardiac, nutritional and inflammatory parameters were measured at the beginning of the study and tested as predictors of mortality. RESULTS: PAPP-A, PlGF, IGF-1, IGFBP-4 and MMP-2 were significantly increased in HD patients compared to controls (PAPP-A 27.6 ± 15.5 mIU/l in HD vs. 9.4 ± 2.5 mIU/l in controls, p < 0.001). Increased PAPP-A was a significant independent predictor of overall mortality and mortality due to infection in the multivariate Cox analysis [HR (95% CI): 1.237 (1.060-1.444), p = 0.007, and 1.416 (1.115-1.798), p = 0.004, per standard deviation, respectively]. PAPP-A was not related to cardiovascular mortality. CONCLUSION: Increased PAPP-A is a significant independent predictor of overall mortality and mortality due to infection but it was not related to cardiovascular mortality in this study.
- MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- dialýza ledvin mortalita trendy MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- míra přežití trendy MeSH
- následné studie MeSH
- prediktivní hodnota testů MeSH
- prospektivní studie MeSH
- senioři MeSH
- těhotenský plazmatický protein A metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
BACKGROUND: Dialysis patients are at high risk of cardiovascular complications. Pregnancy-associated plasma protein A (PAPP-A) as well as sRAGE (soluble receptor for advanced glycation end products) are new biomarkers related to cardiovascular disease. The aim of our study was to describe their intra- and inter-individual variability. METHODS: The studied group consisted of 21 chronic hemodialysis patients. PAPP-A, sRAGE and selected routine parameters were measured monthly during a 1-year prospective study. RESULTS: Our results show high intra-individual variability of both PAPP-A and sRAGE. Both PAPP-A and sRAGE were closely linked to serum transferrin levels. Additionally, sRAGE was significantly associated with leukocyte count and haemoglobin. CONCLUSION: Our study demonstrates high intra-individual variability of PAPP-A and sRAGE in stable clinical status. This finding could be helpful for further evaluation of the significance of PAPP-A and sRAGE in chronic kidney disease.
- MeSH
- analýza rozptylu MeSH
- biologické markery krev MeSH
- chronické selhání ledvin krev komplikace terapie MeSH
- dialýza ledvin MeSH
- kardiovaskulární nemoci krev etiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- longitudinální studie MeSH
- počet leukocytů MeSH
- prospektivní studie MeSH
- receptory imunologické krev MeSH
- regresní analýza MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- těhotenský plazmatický protein A metabolismus MeSH
- transferin metabolismus MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Patients with decreased renal function are characterized by high cardiovascular morbidity and mortality due to complications of premature atherosclerosis. Placental growth factor (PlGF) is a proatherogenic cytokine and new biomarker of cardiovascular events. The aim of this study was to determine PlGF levels and describe their relationship to renal function and risk factors of atherogenesis in patients with decreased renal function. METHODS: The study group consisted of 114 subjects: 45 patients with various degrees of decreased renal function (CHRI), 31 long-term hemodialysis (HD) patients, and 38 age-matched healthy control subjects. PlGF was assessed immunochemically (enzyme-linked immunosorbent assay) and routine biochemical parameters were measured using standard laboratory methods. RESULTS: PlGF levels were significantly increased in CHRI and HD patients compared to controls (10.5 ± 3.3 pg/mL in CHRI patients and 11.5 ± 3.4 pg/mL HD patients vs. 8.1 ± 1.8 pg/mL in controls, both p < 0.0001). In CHRI patients, PlGF was detectable in the urine, and its urine concentration correlated with its serum levels. In HD patients, PlGF correlated with low-density lipoproteins (r = 0.36, p < 0.05), but was not related to C-reactive protein levels. Higher levels of PlGF were found in CHRI patients with cardiovascular disease, compared with those free of such complication. CONCLUSIONS: PlGF levels are increased in patients with decreased kidney function. PlGF is detectable in the urine, and serum and urine levels of PlGF are significantly interrelated. It is higher in CHRI patients with cardiovascular disease. Further studies are required to demonstrate the usefulness and significance of PlGF in patients with chronic kidney disease.
- MeSH
- biologické markery krev moč MeSH
- C-reaktivní protein metabolismus MeSH
- chronická renální insuficience krev MeSH
- dospělí MeSH
- dyslipidemie krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipidy krev MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- těhotenské proteiny krev moč MeSH
- zánět krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: EN-RAGE is extracellular newly identified receptor for advanced glycation end-products binding protein playing a role in inflammation. The aim was to test the relationship of EN-RAGE to prognosis of long-term hemodialysis patients (HD). DESIGN AND METHODS: This is a prospective observational cohort study in 261 HD patients followed up for five years. Laboratory parameters were measured at the beginning of the study. RESULTS: EN-RAGE was slightly but unsignificantly increased in HD patients compared with healthy controls and correlated significantly with inflammatory markers. Univariate Cox analysis demonstrated EN-RAGE as a significant predictor for mortality due to infection (HR (95%CI): 1.305 (1.063-1.602), per standard deviation, p=0.01), but this significance disappeared in multivariate Cox analysis when CRP was included into the model. CONCLUSIONS: Our study demonstrates EN-RAGE as an inflammatory biomarker. It is related to mortality of HD patients due to infection, but in our study, it did not provide additional information to CRP.
- MeSH
- biologické markery krev MeSH
- C-reaktivní protein analýza MeSH
- časové faktory MeSH
- dialýza ledvin mortalita MeSH
- infekce metabolismus mortalita MeSH
- kardiovaskulární nemoci metabolismus mortalita MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- multivariační analýza MeSH
- prognóza MeSH
- proporcionální rizikové modely MeSH
- prospektivní studie MeSH
- proteiny S100 krev MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Pregnancy-associated plasma protein A (PAPP-A) is a biomarker routinely used in screening for Down syndrome in the first trimester of pregnancy. It is also present in very small amounts in men and non-pregnant women. PAPP-A is a key regulator of local insulin-like growth factor (IGF) bioavailability - IGFs are essential for normal body size during fetal development, but they are associated with aging and age-related diseases. Measurement of circulating PAPP-A can provide valuable information not only in pregnant women (chromosomal anomalies and adverse pregnancy outcomes) but also in patients with coronary artery disease (contribution to diagnosis, prognostic value) and in patients with kidney diseases. PAPP-A is associated with renal function and proteinuria, is increased mainly in dialysis patients and decreases after kidney transplantation. It is an independent mortality predictor of hemodialysis patients and indicator of adverse outcome of transplanted patients. PAPP-A levels can be influenced by various chemicals and drugs, among them mainly heparin. Various assays for PAPP-A exist and the type of assay used in a study should be considered. This article reviews the data summarizing basic information about PAPP-A with a particular focus on the significance of PAPP-A in renal diseases.
- MeSH
- biologické markery krev metabolismus MeSH
- lidé MeSH
- nemoci ledvin krev MeSH
- těhotenský plazmatický protein A metabolismus MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
238 l. : il., tab. ; 30 cm
Cílem projektu je studovat genetickou predispozici a nové biochemické markery kardiovaskulárního rizika u pacientů s onemocněním ledvin. Studium bude zaměřeno na vybrané polymorfismy genu pro PAPP-A (s těhotenstvím asociovaný protein) a nové biochemickémarkery - PlGF (placentární růstový fakotr) a EN-RAGE (kalgranulin) a jejich souvislost s klinickým stavem a význam v prognóze nemocných.; The aim of the project is to study genetic predisposition and new biochemical markers of cardiovascular risk in patients with kidney diseases. Studies will be aimed at selected polymorphisms of the gene for PAPP-A and new biochemical markers - PlGF (placental growth factor) and EN-RAGE (calgranulin) and their relationship to the clinical state and significance in the prognosis of patients.
- MeSH
- chronická renální insuficience patofyziologie MeSH
- dialýza ledvin MeSH
- echokardiografie MeSH
- genetická predispozice k nemoci MeSH
- insulinu podobný růstový faktor II analýza MeSH
- kardiovaskulární nemoci MeSH
- leukocytární L1-antigenní komplex analýza MeSH
- polymorfismus genetický MeSH
- rizikové faktory MeSH
- těhotenský plazmatický protein A analýza MeSH
- Konspekt
- Biochemie. Molekulární biologie. Biofyzika
- NLK Obory
- nefrologie
- kardiologie
- angiologie
- biologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
BACKGROUND: The calcium-binding protein S100A12 (EN-RAGE) causes inflammation through interaction with the multiligand receptor for advanced glycation end products (RAGE). The aim of the study was to determine S100A12 levels and describe their relationship to inflammatory markers in patients with decreased renal function. METHODS: The studied group consisted of 46 patients with various degrees of chronic renal insufficiency (CHRI), 31 long-term hemodialysis (HD) patients and 24 healthy controls. S100A12 and soluble RAGE were assessed immunochemically (ELISA), and routine biochemical parameters were measured. RESULTS: S100A12 levels were not different in CHRI (166 ± 140 ng/ml) and HD patients (127 ± 101 ng/ml) compared to controls (126 ± 106 ng/ml; p = 0.20, n.s.). In CHRI patients, S100A12 correlated with C-reactive protein (CRP) levels, orosomucoid, and inversely with α(2)-macroglobulin. In HD patients, S100A12 correlated with age, CRP, orosomucoid, fibrinogen and leukocyte levels. In multivariate regression analysis after adjustment for age, S100A12 levels remained correlated with: orosomucoid in CHRI patients; CRP, leukocytes, fibrinogen and negatively with sRAGE in HD patients; and leukocytes in controls. CONCLUSIONS: Although S100A12 levels were not elevated in patients with decreased kidney function, a relation to markers of inflammation was found. Further studies are required to demonstrate the significance of S100A12 in patients with decreased renal function.
- MeSH
- biologické markery krev MeSH
- chronická renální insuficience krev patologie patofyziologie MeSH
- chronické selhání ledvin krev patologie patofyziologie MeSH
- dospělí MeSH
- ledviny metabolismus patofyziologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mediátory zánětu krev MeSH
- proteiny S100 krev MeSH
- senioři MeSH
- vyšetření funkce ledvin metody MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH