Prague, Czech Republic
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Mareckova O.,Klinika Nefrologie TC IKEM | Teplan V.,Klinika Nefrologie TC IKEM | Pitha J.,Klinika Nefrologie TC IKEM | Kalousova M.,Ustav Klinicke Chemie A Laboratorni Diagnostiky | And 3 more authors.
Aktuality v Nefrologii | Year: 2011

Introduction: A role in cardiovascular (CV) disease is played by soluble receptor for advanced glycation end products (sRAGE) and matrix metalloproteinases (MMPs). They belong to a group of non-traditional CV risk markers, and are also determined renal transplantation (RT). Matrix metalloproteinase PAPP-A (pregnancy associated plasma protein-A) and s-RAGE levels are elevated prior to RL to start declining after RT. Literary data about the serum levels of matrix metalloproteinases 2 and 9 (MMP-2and MMP-9) after RT are scanty. Aim: To determine the temporal sequence of changes in serum sRAGE and MMP levels over a one-year period post-RT, and to determine whether they correlate with preclinical atherosclerosis. Methods: Preclinical atherosclerosis was defined as a Belcaro score measured by carotid ultrasound. Serum MMP-2, MMP-9, PAPP-A, and sRAGE levels were determined before RT and at 3, 6, and 12 months post-RT in 142 patients (98 males, 44 females, age 48.7 [range, 22-76] years). A control group included 22 healthy individuals (10 males, 12 females, age 51.0 [range, 22-76] years). Serum MMP and sRAGE levels were determined using ELISA. Results: The serum levels of MMP-2 were lower compared with controls before RT (p < 0.05) and continued to decline after RT. By contrast. MMP-9 in patients awaiting RT was comparable to controls, rising after RT to be significantly increased at one year post-RT: median 602 vs 355ng/ml; p < 0.01. The increased levels of MMP-9 in the late post-RT period correlated significantly with preclinical atherosclerosis (p < 0.01). Serum sRAGE levels were elevated prior to RT to start decreasing after RT as graft function developed. When comparing subgroups with severe (Belcaro score > 2) and mild preclinical atherosclerosis (Belcaro score < 2), sRAGE levels were significantly decreased with severe-clinical atherosclerosis. Conclusion: Decreased sRAGE levels affording inadequate protection to patients exposed to the toxic action of advanced glycation end products can be regarded as a biomarker of CV risk in patients with advanced preclinical atherosclerosis. A novel finding is the increase in MMP-9 in the late post-RT period, correlating significantly with preclinical atherosclerosis and potentially serving as a marker of acute CV risk.


Mareckova O.,Klinika Nefrologie TC IKEM | Teplan V.,Klinika Nefrologie TC IKEM | Kalousova M.,Ustav Klinicke Chemie a Laboratorni Diagnostiky | Zima T.,Ustav Klinicke Chemie a Laboratorni Diagnostiky | And 2 more authors.
Aktuality v Nefrologii | Year: 2010

Introduction: Soluble Receptor for Advances Glycation End Products (s-RAGE) and Matrix-metalloproteinases (MMPs) including Pregnancy Associated Plasma Protein-A (PAPP-A). Matrix-metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9) are involved in the pathogenesis of atherosclerosis, acceleration of its progression and destabilization of plague. While serum PAPP-A has been proposed as a predictor of cardiovascular risk after renal transplantation (RTx), there is only little known about MMP-2 and MMP-9 levels after RTx. Aim: Our study was designed to determine serum AGEs, s-RAGE, PAPP-A, MMP-2 and MMP-9 after RTx and to correlate them with renal function. Methods: Serum AGEs, PAPP-A, MMP-2 and MMP-9 were determined before and at 1, 3, 6 and 12 months post-RTx in 142 pts - 98/44 M/F, age 48.7 (22-76) years and in 22 healthy controls - 10/12 M/F, age 51.0 (22-76) years. Renal function was determined as inulin clearance (Cin) ml/sec/1.73m, serum AGEs using fluorimetry Fl (AU) and serum s-RAGE, PAPP-A, MMP-2 and MMP-9 by ELISA tests. Results: Sérové AGEs, s-RAGE and PAPP-A levels decrease with the development of graft function after RTx. There was a significant negative correlation Cin with/ serum AGEs /(r = 0.30; p < 0.01) and PAPP-A (r = 0.569; p < 0.01). PAPP-A was significantly increased before RTx compared with controls (p < 0.01). Serum MMP-9 was significantly increased at time 12 months after RTx compared with control. There is a significant increase of serum MMP-9 between 6 and 12 months after RTx. Serum MMP-2 compared with controls was decreased before RTx and this decrease continued after RTx. The correlation between MMPs and renal function was not significant. Conclusion: The serum levels of AGEs, s-RAGE and PAPP-A are the highest prior to RTx, and their decline after RTx correlates with developing graft function. In contrast, significant changes in serum MMP-2 and MMP-9 were in the late post-RTx period and further research is needed to explain these changes, not due to a change in renal function. MMP-2 and MMP-9 can be considered as novel markers of cardiovascular risk after RTx.


Teplan V.,Klinika Nefrologie TC IKEM | Schuck O.,Evropska Pracovni Skupina CEKAD | Maly J.,Klinika Nefrologie TC IKEM | Horackova M.,Evropska Pracovni Skupina CEKAD | And 12 more authors.
Aktuality v Nefrologii | Year: 2010

In last decades, number of very old chronic renal failure patients dramatically increased. General organ demage does not allow kidney transplantation and very frequently also long-term dialysis treatment. Recently, there were published studies with successful long-term conservative management on modified low - protein diet supplemented with keto amino acids. Athough, up to now, there are not randomized prospective studies, our results from the CEKAD study allow to continue on conservative management in metabolically stabilized seniors up to 6-12 ml/min of glomerular filtration rate.


Sympathnetc nervous system plays significant role in pathophysiology of hypertension. New method in its management is cathether- based radiofrequency ablation of the sympathnetc nerves located around renal arteries. Comparing to dilatation of renal artery stenosis renal, renal denervation (RDN) shows promising long lasting decrease of blood pressure. RDN is indicated in resistent hypertension (three different antihypertensive drugs icl. diurnetc are not effective in correction of serious hypertension) with a risk of organ damage following heart and kidney failure. It is supposed, RDN could be effectively used also in patients with decreased renal function and refractory hypertension. In our pilots studies we confirmed no signifficant adverse effect on renal function in 12 months follow-up. On the other hand, it should be focus on sufficient correction of blood pressure in indivualized combination of antihypertensive drugs mainly central symphaticolytics.


ADVANCE ON trial is recently published observation study following ADVANCE trial analysing blood pressure lowering and glucose control in type2 of diabetes on the risk of death from any cause and cardiovascular causes as well as renal function during 6 years of follow- up with an enrollment of 8494 patients. The reductions in the risk of death from any cause and of death from cardiovascular cause that had been observed in the group receiving active blood-pressure-lowering treatment during the trial were attenuated but significant at the end of the post - trial follow-up; the hazard rations were 0,91 (95 % CI, 0,84-0,99,p = 0,03) and 0,88 (95 % CI, 0,77-0,99, p = 0,04). In ADVANCE ON trial was confirmed prolonged after 6 years signifficant effect of fixed combination of perindopril-indapamid combination in type 2 diabetes patiens who started 10 years ago.No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control and the standard-glucose control group; the hazard ratios were 1,00 (95 % CI, 0,92-1,08) and 1,00 (95 % CI 0,92-1,08).There was a significant cumulative benefit with respect to end-stage renal disease; hazard ratio 0,54 (95 % CI, 0,34-0,85, p = 0,007).

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