Myocardial fibrosis in chronic kidney disease: potential benefits of torasemide.

Interstitial and perivascular fibrosis is a constant finding in heart biopsies and necropsy studies in patients with chronic kidney disease and hypertension, namely in those with left ventricular hypertrophy. Fibrosis is the result of the unbalance between exaggerated collagen synthesis and unchanged or depressed collagen degradation. A number of factors linked to hypertension and the progressive deterioration of renal function may facilitate such an unbalance. Patients with chronic kidney disease and hypertension are prone to develop diastolic heart failure, and myocardial fibrosis has been suggested as a major determinant of disturbances in diastolic function in these patients. Thus, the therapeutic strategies aimed to reduce cardiac fibrosis may provide a particular cardioprotective benefit in patients with chronic kidney disease. In this regard, recent data suggest that the loop diuretic torasemide reduces myocardial fibrosis and ameliorates cardiac function in patients with chronic heart failure through local mechanisms beyond its effects on the renal excretion of fluid and electrolytes and systemic hemodynamics.

Blood pressure control in patients with chronic renal insufficiency in Spain: a cross-sectional study.

OBJECTIVE: Despite therapeutic advances, strict control of hypertension remains elusive in patients with chronic renal insufficiency (CRI). The present study was designed for assessment of control rates of blood pressure in patients with CRI. Secondary objectives included evaluation of the control rates of proteinuria and cardiovascular comorbidities. METHODS: A multicenter and cross-sectional survey of unselected patients with CRI attending outpatient nephrology clinics in Spain between April and September 2003 was performed. RESULTS: Fifty-two centers recruited 2501 patients with a mean age 64.8 years (65.7% men). The prevalence of previous cardiovascular disease was 55%. The two most prevalent renal diseases were vascular (38.9%) and diabetic nephropathy (20.1%). Blood pressure below 130/80 mmHg was observed in 435 patients (17.4%). A poor blood pressure control was associated with older age, greater proteinuria and higher low-density lipoprotein cholesterol levels. Proteinuria less than 0.5 g/day was observed in 1209 cases (48.3%). A total of 1899 patients (75.9%) were receiving drugs suppressing the activity of the renin-angiotensin system and 1048 patients (41.9%) were being treated with three or more antihypertensive drugs. Lipid-lowering agents and antiplatelet therapy were used in 49.3 and 38.1% of patients, respectively. CONCLUSIONS: The control rate of blood pressure in patients with CRI is inadequate despite frequent use of combination therapy that most commonly included an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Greater emphasis should be made to increase the number and dose of antihypertensive drugs and the need for using a statin as well as antiplatelet therapy in order to improve renal and cardiovascular outcomes.

The A1166C polymorphism of the AT1 receptor gene is associated with collagen type I synthesis and myocardial stiffness in hypertensives.

OBJECTIVES: We have investigated whether the A1166C polymorphism of the angiotensin II type 1 (AT1) receptor gene modulates the effects of angiotensin II on collagen type I turnover and myocardial stiffness in hypertension. METHODS: We studied 255 hypertensive patients before and after 1 year of treatment with either losartan (n = 185) or atenolol (n = 70). Serum concentrations of the carboxy-terminal propeptide of procollagen type I (PIP) and the carboxy-terminal telopeptide of collagen type I (CITP), markers of extracellular collagen type I synthesis and degradation, respectively, were measured by specific radioimmunoassays. Left ventricular chamber stiffness (KLV), was determined from the deceleration time of the early mitral filling wave, as measured by Doppler echocardiography. Hypertensives were genotyped by polymerase chain reaction and divided in two subgroups: AA (n = 126) and AC/CC (n = 129). RESULTS: Baseline PIP and KLV were increased (P < 0.01) in AA hypertensives compared with AC/CC hypertensives. No changes in baseline CITP were observed between the two subgroups of hypertensives. Confounding factors were similar between the two subgroups of hypertensives. Administration of losartan was associated with reduction (P < 0.01) in PIP and KLV in AA hypertensives but not in AC/CC hypertensives. Treatment with atenolol did not change PIP and KLV in either subgroup of hypertensives. No changes in CITP were observed with the two treatments. CONCLUSION: These findings suggest that the A1166C polymorphism of the AT1 receptor gene is associated with collagen type I synthesis and myocardial stiffness in patients with hypertensive heart disease.

Diagnóstico bioquímico de la fibrosis miocárdica hipertensiva / Biochemical diagnosis of hypertensive myocardial fibrosis

Se ha descrito que en el ventrículo izquierdo de animales y de humanos con hipertensión arterial el contenido de fibras de colágeno está aumentado. La fibrosis es el resultado de la acumulación de fibras de colágeno de tipo I y de tipo III debido a que su síntesis está estimulada y su degradación está inhibida o es normal. En el origen del desequilibrio entre la síntesis y la degradación participarían tanto factores hemodinámicos como no hemodinámicos. Clínica y experimentalmente se ha demostrado que la acumulación exagerada de colágeno fibrilar en el miocardio ventricular facilita el desarrollo de alteraciones de la función cardíaca, de la reserva coronaria y de la actividad eléctrica. Aunque el examen microscópico de biopsias endomiocárdicas es el método más fiable para evaluar la fibrosis miocárdica, en los pacientes hipertensos se impone el desarrollo de métodos no invasivos. Nuestro grupo ha desarrollado un método bioquímico consistente en la determinación de los péptidos que aparecen en la sangre cuando se sintetizan y se degradan las moléculas de colágeno fibrilar y lo ha aplicado al estudio de la fibrosis miocárdica en las ratas con hipertensión espontánea y en los pacientes con hipertensión arterial esencial (AU)

A substantial increase in fibrillar collagen has been observed in the left cardiac ventricle of animals and humans with arterial hypertension. Hypertensive myocardial fibrosis is the result of both increased collagen types I and III due to the fact that its synthesis by fibroblasts and myofibroblasts is stimulated and its extracellular collagen degradation unchanged or decreased extracellular collagen degradation. Hemodynamic and non-hemodynamic factors may be involved in the disequilibrium between collagen synthesis and degradation that occurs in hypertension. As shown experimentally and clinically, an exaggerated rise in fibrilar collagen content promotes abnormalities of cardiac function, contributes to the decrease in coronary reserve and facilitates alterations in the electrical activity of the left ventricle. Although microscopic examination of cardiac biopsies is the most reliable method for documenting and measuring myocardial fibrosis, the development of non-invasive methods to indicate the presence of myocardial fibrosis in hypertensive patients would be useful. We have therefore applied a biochemical method based on the measurement of serum peptides derived from the tissue formation when synthesized and degradation of fibrillar collagens to monitor the turnover of these molecules in rats with spontaneous hypertension and patients with essential hypertension (AU)