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Experimental and clinical aspect of calcineurin inhibitors-induced nephrotoxicity.
Hošková, Lenka ; Málek, Ivan (advisor) ; Tesař, Vladimír (referee) ; Špinarová, Lenka (referee)
The introduction of calcineurin inhibitors (CNI) into immunosuppressive regimens significantly improved patients prognosis after heart transplantation. Some of the most significant complications have been recognized, such as the development of arterial hypertension and renal impairment due to calcineurin inhibitor toxicity. The aim of the study was to compare the effect of the dual blockade of the renin-angiotensin system (dual RAS combination) with standard antihypertensive medication on blood pressure control. The second aim was to evaluate whether effective antihypertensive combination therapy (dual RAS or a standard antihypertensive drugs combination) would reduce the progression of chronic kidney disease in patients with chronic immunosuppressive prophylaxis. Treatment of arterial hypertension involving the combination of angiotensin-converting enzyme inhibitor (ACEi) and angiotensin II receptor blocker (ARB) was similarly effective compared to the standard combination of antihypertensives. Blood pressure treatment targets were achieved in both studies. Administration of antihypertensive combination therapy including dual blockade of RAS alleviated the progression of chronic renal disease in the experimental and clinical part, where the nephroprotective effect of dual RAS blockade...
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The value of neurohormonal activation assessment for treatment monitoring in congestive heart failure
Kubánek, Miloš ; Málek, Ivan (advisor) ; Špinarová, Lenka (referee) ; Pudil, Radek (referee)
Summary: Congestive heart failure (CHF) is associated with neurohormonal activation (NHA) which contributes to further progression of disease. Measurement of NHA has been used for diagnosis and prognostic stratification in CHF. Aims: The aim of this academic disertation was to analyze the value of NHA for treatment monitoring in CHF. We studied the relationship between NHA and pulmonary hypertension in compensated CHF using B-type natriuretic peptide (BNP) and big endothelin-1 (big ET-1). The rationale was to minimize repeated right heart catheterizations in candidates for orthotopic heart transplantation. A similar design had the second clinical study which used N-terminal pro-B- type natriuretic peptide (NT-proBNP) as a marker of NHA. In the third clinical study, we evaluated whether basal levels and/or change in NHA during treatment predict clinical efficacy of cardiac resynchronization therapy (CRT). We supposed that BNP and big ET-1 might be better predictors of outcome than standard methods of follow-up. Results: 1. Natriuretic peptides correlated with hemodynamic parameters better than big ET-1. An isolated measurement of BNP or NT-proBNP did not allow a reliable assessment of pulmonary hypertension or left ventricular filling pressure, respectively. On the other hand, serial evaluation of...
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