Efecto de los antagonistas de aldosterona en nefropatía diabética: revisión sistemática de la literatura / Systematic review of the effect of aldosterone antagonists on urinary albumin excretion in diabetic nephropathy

The beneficial effect angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARA) for diabetic nephropathy can be hampered by the phenomenon of aldosterone escape. Aldosterone antagonists such as espironolactone or epleronone could potentiate the effects of ACEI and ARA and avoid the later problem. We performed a systematic search of the literature on the effects of aldosterone antagonists on diabetic nephropathy. We searched for clinical trials and follow up studies measuring the effects of aldosterone antagonists on urinary albumin excretion among patients with diabetic nephropathy. We retrieved 1345 papers on the subject and 10 were selected for analysis. Among these, spironolactone was more effective than comparing drugs to achieve a reduction in urinary albumin excretion of approximately 30 to 40 percent. On the other hand epleronone was not superior to comparing drugs. All studies reported a modest reduction in glomerular filtration rate and an increase in serum potassium levels. In conclusion, spironolactone in doses of 25 to 100 mg/day reduces urinary albumin excretion but reduces also glomerular filtration rate and increases serum potassium levels.

Progestógenos: farmacologia e uso clínico / Progestagens: pharmacology and clinical use

Os progestógenos são esteroides que podem ser sintéticos ou naturais. A progesterona é o único progestágeno natural. Os progestógenos sintéticos tentam mimetizar o efeito da progesterona, e são chamados de progestinas. Cada progestina apresenta diferentes propriedades farmacológicas, dependendo da molécula da qual foi originada, usualmente testosterona e progesterona. Pequenas mudanças estruturais nas moléculas originais levam a diferenças consideráveis na atividade de cada uma das progestinas. O objetivo deste trabalho é revisar a origem dos progestógenos, as peculiaridades de cada grupo e seu uso clínico mais comum. As informações já levantadas sobre o efeito das progestinas em patologias importantes e prevalentes, como o câncer de mama e eventos tromboembólicos, também será abordado.

Progestagens are natural or synthetic steroids, and progesterone is the only natural one. Synthetic progestagens, called progestins, were created to mimic the effects of natural progesterone. The progestins have different pharmacological properties depending on the parent molecule, usually testosterone or progesterone, from which they are derived. Very small structural changes in the original molecule may induce considerable differences in the activity of the derivative. The aim of this paper is to review the origin of each progestin, the peculiarities of each group and its most common clinical use. The current knowledge about the effect of progestins on important and prevalent diseases, such as breast cancer and thromboembolic events, will also be addressed.

Potential antioxidant and antiapoptotic effects of eplerenone versus omeprazole on water immersion restraint stress induced gastric injury in rats

Use of proton pump inhibitors as omeprazole in prophylaxis against gastric stress ulcers complicating acute myocardial infarction leads to serious cardiovascular events. Eplerenone is one of the drugs used in treatment of acute myocardial infarction. We have investigated in the current study the possible protective effects of eplerenone versus omeprazole against water immersion restraint stress-induced gastric injury in rats. Twenty four male white albino wistar rats were divided into four groups having six rats in each. These groups were normal control, stress non treated control and two stress groups pretreated with either eplerenone [100 mg/kg i.p] or omeprazole [8 mg/kg i.p]. The injury index of gastric mucosa and structural change of parietal cells was observed under scanned electron microscope. Malondialdehyde and protein carbonyl were quantified in gastric tissues as biomarkers of lipid peroxidation and protein damage respectively. Apoptosis was assessed by measuring DNA fragmentation%. The injury index, Malondialdehyde level, protein carbonyl content and DNA fragmentation% parameters were significantly decreased in water immersion restraint stress groups pretreated with either eplerenone or omeprazole [p<0.05]. The scanned electron microscope of eplerenone pretreated group showed significant reduction in the degree of damage while the omeprazole pretreated group showed nearly complete healing. Our results demonstrated that gastric lesions attenuation by eplerenone are through its antioxidant and antiapoptotic effects and therefore it can be regarded as a useful option for therapy of patients with acute myocardial infarction at risk of developing gastric stress ulcers and threatened gastrointestinal bleeding risk

Acción novedosa de la aldosterona en la nefrotoxicidad por ciclosporina / Novel action of aldosterone in CsA nephrotoxicity

Calcineurin inhibitors are helpful ímmunosuppressíve agents in clinical practice. Thanks to their lower cost respect with new ímmunosuppressíve therapy, calcineurin inhibitors in our country continue being the most used treatment in solid organ transplant recipients or patients with autoimmune disease. In the 80's decade cyclosporine A (CsA) was introduced as the first calcineurin inhibitor transforming the immunosuppression therapy. Up to date, many articles evaluating beneficial and adverse effects of CsA have been published. In this review, basic aspects and actions of CsA are analyzed together with studies from our laboratory that pointed out the pathophysiological role of aldosterone as a mediator of functional and structural changes that are observed in CsA nephrotoxicity. Based in our findings, we proposed that in CsA nephrotoxicity, the aldosterone mediates renal vasoconstriction and enhances TGFJ3 expression promoting the development of nefrotoxicity. Finally, results from our laboratory and others allow us to suggest that aldosterone receptors blockade with spironolactone or eplerone could be a pharmacological therapy to reduce or prevent acute and chronic CsA nephrotoxicity in transplant recipients.

Los inhibidores de calcineurina son los agentes inmunosupresores más potentes con los que se cuenta en la práctica clínica, y gracias a su bajo costo respecto a las nuevas terapias inmunosupresoras, en nuestro país continúan siendo los agentes terapéuticos más utilizados para el manejo de pacientes con enfermedades autoinmunes o que reciben trasplantes. En la década de los 80's se introdujo la ciclosporina A (CsA) como primer inhibidor de calcineurina, lo cual revolucionó la terapia inmunosupresora. Desde entonces se han publicado muy variados artículos donde se han evaluado los efectos benéficos y deletéreos de estos inhibidores; específicamente nos enfocaremos a revisar las acciones de CsA y, en particular, los resultados de nuestro laboratorio que muestran el papel fisiopatológico que juega la aldosterona como mediador de los cambios funcionales y estructurales que se observan en la nefrotoxicidad por ciclosporina. Específicamente su participación en promover la vasoconstricción renal asociada a CsA y en el desarrollo de fibrosis al inducir la expresión de TGFβ. Por lo tanto, nuestros resultados y los de otros autores nos permiten proponer el bloqueo de los receptores de aldosterona con espironolactona o eplerone como un tratamiento farmacológico útil para reducir la incidencia de nefrotoxicidad aguda y crónica, inducida por CsA en pacientes con enfermedades autoinmunes o que reciben trasplante de órganos.