BACKGROUND: Matrix metalloproteinase-2 (MMP-2) and pregnancy-associated plasma protein-A (PAPP-A) have been implicated in chronic kidney disease (CKD) and cardiovascular disease (CVD). However, the serum determinants of MMP-2 and PAPP-A in CKD are unknown. The aim of the present study is to evaluate the clinical significance of MMP-2 and PAPP-A and their determinants in patients with CKD. METHODS: The studied group consisted of 203 subjects: 159 patients with chronic kidney disease stages 1 - 5 (CKD 1 - 5), and 44 healthy control subjects. MMP-2 levels were assessed immunochemically using ELISA (enzyme linked immunosorbent assay), PAPP-A levels were determined immunochemically with TRACE (time-resolved amplified cryptate emission), and routine biochemical parameters were measured using standard methods. RESULTS: Compared with healthy controls, CKD patients (3 - 5) had no significant changes in MMP-2 levels. MMP-2 levels (195 +/- 76 vs. 255 +/- 77 ng/mL, p < 0.0001) were significantly lower in CKD patients (1 - 2) and PAPP-A levels (12.1 +/- 8.5 vs. 9.3 +/- 2.2 mIU/L, p = 0.001) were significantly higher in CKD 4 compared to control subjects. Multivariate analysis revealed that PAPP-A (p < 0.0001), proteinuria (p = 0.002), alpha-2-macroglobulin (p = 0.01), and negatively albumin (p = 0.02) and haemoglobin (p = 0.0002), were independent correlates of MMP-2 after adjustment for age and glomerular filtration rate. Proteinuria (p = 0.02), creatinine (p < 0.0001), and negatively albumin (p = 0.01), were independent correlates of PAPP-A adjusted for age and glomerular filtration rate. CONCLUSIONS: The present study demonstrated that serum MMP-2 and PAPP-A were independent correlates of proteinuria, albumin, and other examined parameters. Our results suggest the possibility that circulating MMP-2 and PAPP-A be used as indicators for renal damage in CKD patients on conservative treatment.
- MeSH
- biologické markery metabolismus MeSH
- chronické selhání ledvin diagnóza enzymologie MeSH
- dospělí MeSH
- ELISA MeSH
- imunohistochemie MeSH
- lidé středního věku MeSH
- lidé MeSH
- matrixová metaloproteinasa 2 krev MeSH
- proteinurie diagnóza MeSH
- průřezové studie MeSH
- sérový albumin analýza MeSH
- těhotenský plazmatický protein A metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: The aim of the study was to investigate genetic and biochemical background of PAPP-A (pregnancy-associated plasma protein A) in patients with risk pregnancies. DESIGN AND METHODS: Five PAPP-A gene polymorphisms and PAPP-A maternal serum levels were studied together in 165 women in third trimester pregnancies complicated with threatening preterm labor (n=98), preeclampsia (n=35), intrauterine growth restriction (n=34) and ICP (intrahepatic cholestasis of pregnancy) (n=15). 114 healthy pregnant women served as controls. RESULTS: Preeclamptic patients had significantly higher frequency of TT genotype of Cys327Cys polymorphism compared to controls (p<0.01). Patients with ICP had increased serum levels of PAPP-A compared to controls and correlation analysis showed significant relationship between PAPP-A and CRP (C-reactive protein) in the patients with intrauterine growth restriction (r=0.49, p=0.007). CONCLUSION: Our study indicates the association of TT genotype of Cys327Cys polymorphism of the PAPP-A gene with preeclampsia. However, further study with larger groups of preeclamptic patients is needed to confirm our results.
- MeSH
- analýza rozptylu MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetické asociační studie MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus MeSH
- lidé MeSH
- pilotní projekty MeSH
- preeklampsie genetika MeSH
- rizikové faktory MeSH
- sekvenční analýza DNA MeSH
- studie případů a kontrol MeSH
- těhotenský plazmatický protein A genetika metabolismus MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Advanced glycation end product (AGE) levels are elevated in patients with decreased renal function and may contribute to the excessive cardiovascular disease in this population. However, their relation to nutrition, anemia, and micro inflammation is not well characterized. The aim of this study is to determine their relationship in patients with chronic kidney disease (CKD). METHODS: The studied group consisted of 203 subjects: 159 patients with CKD 1-5 and 44 healthy control subjects. AGE levels were assessed by spectrofluorimetry, and routine biochemical parameters were measured using standard methods. RESULTS: AGE levels were significantly increased in CKD patients compared with controls (3.9 ± 1.7 × 105 AU in CKD 1-5 patients vs. 3.2 ± 0.48 × 105 AU in controls, p < 0.0001). AGE levels increased from CKD 3. AGE levels were positively associated with age, albumin, prealbumin, and orosomucoid, and were negatively associated with hemoglobin and estimated glomerular filtration rate. In multiple regression analysis, after adjustment to age and glomerular filtration rate, AGE levels remained independently correlated with albumin and prealbumin and negatively correlated with hemoglobin. CONCLUSIONS: This study is the demonstration that nutrition markers, albumin and prealbumin, are the positive determinants and hemoglobin is the negative determinant of serum AGE levels in patients with CKD.
- MeSH
- biologické markery krev MeSH
- chronická renální insuficience krev MeSH
- dospělí MeSH
- hemoglobiny metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- prealbumin metabolismus MeSH
- produkty pokročilé glykace krev MeSH
- senioři MeSH
- studie případů a kontrol 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
BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked genetic disorder with deficient α-galactosidase A activity. The main aim of this work was to investigate possible differences in urine proteins between healthy controls and AFD patients and to identify abnormal proteins as potential biomarkers of disease. MATERIAL AND METHODS: We studied 2D electrophoresis images of urine samples collected from AFD patients and healthy subjects. The proteins were separated using isoelectric focusing method followed by SDS-PAGE. The proteins were then visualized by silver staining and characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). RESULTS: We found out that the urinary spectra of all the Fabry disease samples included identical proteins with molecular weight around 20-40 kDa. The concentration of some proteins was more than three times higher in the AFD samples, compared to the controls. The abundant proteins were identified by MALDI-TOF MS and included the following: alpha-1-antitrypsin, alpha-1-microglobulin, prostaglandin H2 d-isomerase, complement-c1q tumor necrosis factor-related protein, and Ig kappa chain V-III. Possible glycosylation at Asn51 and Asn78 sites of the prostaglandin H2 d-isomerase was detected. CONCLUSIONS: AFD urinary proteomics revealed increased secretion of several proteins. We postulate that the observed difference in the amount of prostaglandin H2 d-isomerase and its position on two-dimensional gels might be related to different glycosylation in AFD subjects.
- MeSH
- 2D gelová elektroforéza MeSH
- biologické markery moč MeSH
- dospělí MeSH
- Fabryho nemoc moč MeSH
- glykosylace MeSH
- intramolekulární oxidoreduktasy moč MeSH
- isoelektrická fokusace MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipokaliny moč MeSH
- mladiství MeSH
- mladý dospělý MeSH
- molekulová hmotnost MeSH
- proteiny izolace a purifikace MeSH
- proteom analýza MeSH
- senioři MeSH
- spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Advanced glycation end products (AGEs) belong to uremic toxins and some pathological effects of AGEs are linked to RAGE (receptor for AGEs). Their precursors are detoxified by the glyoxalase (GLO) system. The A419C (E111A) polymorphism of the GLO I gene is associated with vascular disease in hemodialysis (HD) patients and some RAGE gene polymorphisms are implicated in various pathological states. AIM: To study the relationship of A419C GLO I and four RAGE polymorphisms (-429T/C, -374T/A, 2184A/G and Gly82Ser) in the prognosis of HD patients. METHODS: The group studied consisted of 214 chronic HD patients prospectively followed up for 43 months. 100 patients died, 48 due to cardiovascular causes. RESULTS: The Kaplan-Meier analysis showed a higher mortality rate in patient-mutated homozygotes for RAGE -429CC, RAGE 2184GG and GLO I 419CC. A higher hazard risk was confirmed by the Cox proportional hazards model when wild-type homozygotes were taken as reference: RAGE -429CC 2.28 (95% CI 1.04-4.99), RAGE 2184GG 3.16 (95% CI 1.44-6.93), and GLO I 419CC 1.75 (95% CI 1.08-2.86). Both RAGE polymorphisms were also associated with cardiovascular mortality: RAGE -429CC 3.54 (95% CI 1.37-9.14) and RAGE 2184GG 5.04 (95% CI 1.93-13.11). CONCLUSION: In summary, our study shows for the first time a link between RAGE and GLO polymorphisms in the prognosis of HD patients.
- MeSH
- chronické selhání ledvin genetika mortalita terapie MeSH
- dialýza ledvin MeSH
- genetická predispozice k nemoci epidemiologie MeSH
- Kaplanův-Meierův odhad MeSH
- laktoylglutathionlyasa genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- polymorfismus genetický MeSH
- produkty pokročilé glykace genetika metabolismus MeSH
- prognóza MeSH
- prospektivní studie MeSH
- receptory imunologické genetika metabolismus MeSH
- senioři MeSH
- uremie genetika metabolismus terapie 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