Review
Behavioral Sciences
Claire L. Pince, Kimberly E. Whiting, Tammy Wang, Andras H. Leko, Lisa A. Farinelli, Diane Cooper, Mehdi Farokhnia, Leandro F. Vendruscolo, Lorenzo Leggio
Summary: This scoping review summarizes the role of aldosterone and mineralocorticoid receptor (MR) in addiction and the potential effects of pharmacological manipulations of MR on addiction-related outcomes. The findings suggest that dysregulations of aldosterone and MR occur in both peripheral and central systems and are influenced by drug exposure patterns and genetic factors. Antagonism of MR holds promise as a potential target for the treatment of addiction, but further research is needed.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2023)
Article
Biochemistry & Molecular Biology
Chiara Sabbadin, Carlo Saccardi, Alessandra Andrisani, Amerigo Vitagliano, Loris Marin, Eugenio Ragazzi, Luciana Bordin, Guido Ambrosini, Decio Armanini
Summary: Endometriosis is a chronic inflammatory disease that is associated with pelvic pain, infertility, and increased cardiovascular risk. This study aimed to evaluate the levels of aldosterone and cortisol, as well as blood pressure values, in women with endometriosis. The results showed that there was increased biological aldosterone activity and dysregulation of the hypothalamic-pituitary-adrenal axis in early stages of endometriosis. These findings suggest new therapeutic targets for aldosterone receptor blockers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Peripheral Vascular Disease
Lara Matilla, Eva Jover, Mattie Garaikoetxea, Ernesto Martin-Nunez, Vanessa Arrieta, Amaia Garcia-Pena, Adela Navarro, Amaya Fernandez-Celis, Alicia Gainza, Virginia Alvarez, Diego Alvarez de la Rosa, Rafael Sadaba, Frederic Jaisser, Natalia Lopez-Andres
Summary: There are sex differences in the pathophysiology of aortic valve (AV) calcification in patients with aortic stenosis. Aldosterone (Aldo) promotes proteoglycan synthesis in valve interstitial cells (VICs) via the mineralocorticoid receptor (MR). The MR/Aldo pathway plays a role in fibrosis in women and in early AV calcification in men.
Article
Biochemistry & Molecular Biology
Xiaomeng Gao, Jingyue Chang, Yi Chang, Lili Fan, Ziqian Liu, Cuijuan Zhang, Tatsuo Shimosawa, Fan Yang, Qingyou Xu
Summary: Renal fibrosis, a common process in chronic kidney disease (CKD), is influenced by angiogenesis. Vascular endothelial cells contribute to renal fibrosis through phenotypic transformation and extracellular matrix secretion. Aldosterone, an inflammatory mediator, stimulates angiogenesis via mineralocorticoid receptor (MR) activation. Clinical evidence suggests that MR blockers (MRBs) protect damaged kidneys possibly by inhibiting angiogenesis. In this study, aldosterone infusion in mice induced angiogenesis and endothelial-mesenchymal transition (EndMT), highlighting their involvement in renal fibrosis. Aldosterone induced inflammation and macrophages secreted vascular endothelial growth factor (VEGF)-A to regulate angiogenesis through MR activation, while EndMT occurred in response to transforming growth factor (TGF)-β1 induction, contributing to renal fibrosis. These effects were counteracted by the MRB esaxerenone. These findings suggest that reducing angiogenesis may be an effective strategy for treating renal fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Zachary M. Howard, Chetan K. Gomatam, Arden B. Piepho, Jill A. Rafael-Fortney
Summary: Duchenne muscular dystrophy (DMD) is a muscle degenerative disease caused by the loss of dystrophin protein. Current standard-of-care treatment for DMD has limited efficacy and serious side effects. Mineralocorticoid receptor antagonists (MRAs) have shown promise as a therapeutic target for DMD, as they can improve muscle function and reduce inflammation and fibrosis.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Endocrinology & Metabolism
Gianluigi Savarese, Felix Lindberg, Gerasimos Filippatos, Javed Butler, Stefan D. Anker
Summary: The overactivation of mineralocorticoid receptors affects multiple physiological systems, and the use of classical MR antagonists has shown improvements in heart failure. However, concerns about side effects and limited tolerability have hindered their implementation in other settings. Non-steroidal MR antagonists have shown potential benefits and better safety profiles. This review provides an overview of the impact of MR overactivation and discusses the potential of non-steroidal MR antagonists.
Review
Endocrinology & Metabolism
Morag J. Young, Monica Kanki, Nikshay Karthigan, Penny Konstandopoulos
Summary: Mineralocorticoid receptor (MR) antagonists, also known as aldosterone blockers, have shown clinical benefits in treating patients with heart failure, including those with reduced ejection fraction and preserved ejection fraction with reduced left ventricular filling. The MR has various physiological and pathophysiological roles in the heart, vasculature, and other tissues, which underpin the use of MR antagonists in cardiovascular disease, particularly heart failure. The development of MR antagonists has progressed from potassium-sparing diuretics to more receptor-selective options, demonstrating the evolution of treatment options for cardiovascular diseases.
Review
Endocrinology & Metabolism
Morag J. Young, Monica Kanki, Nikshay Karthigan, Penny Konstandopoulos
Summary: Mineralocorticoid receptor antagonists, also known as aldosterone blockers, have been widely recognized for their clinical benefits in treating heart failure, improving outcomes for both HFrEF and HFpEF patients. As research continues to evolve, new nonsteroidal receptor antagonists like esaxerenone and finerenone have emerged, showcasing the constantly evolving landscape of cardiovascular disease treatment.
Article
Multidisciplinary Sciences
Daniel Ackermann, Bruno Vogt, Murielle Bochud, Michel Burnier, Pierre-Yves Martin, Fred Paccaud, Georg Ehret, Idris Guessous, Belen Ponte, Menno Pruijm, Antoinette Pechere-Bertschi, Heidi Jamin, Rahel Klossner, Bernhard Dick, Markus G. Mohaupt, Carine Gennari-Moser
Summary: This study aimed to investigate alternative MR activation in proteinuric diabetic nephropathy by analyzing urinary steroid hormone profiles and assessing MR and GR expression and activity. The results showed that both aldosterone and cortisol stimulation led to increased expression of pro-fibrotic genes in primary human renal mesangial cells, and this effect was more pronounced in high glucose conditions. These findings provide insights into the potential benefits of MRAs in diabetic nephropathy.
Article
Biochemistry & Molecular Biology
Manuel Morales, Pablo Martin-Vasallo, Julio Avila
Summary: Enzalutamide treatment may increase the risk of cardiovascular-related hospitalization in patients, potentially due to MR gene polymorphism, suggesting the importance of evaluating MR rs5522 polymorphism before starting AR inhibitor therapy.
Article
Biochemistry & Molecular Biology
Paula Aldaz, Amaya Fernandez-Celis, Natalia Lopez-Andres, Imanol Arozarena
Summary: Dexamethasone (DEXA) is commonly used in glioblastoma (GBM) patients to reduce brain inflammation, activating the glucocorticoid receptor (GR) which can influence the mineralocorticoid receptor (MR) signaling. MR signaling in GBM has been shown to have anti-proliferative effects and inhibit the self-renewal of GSCs, while spironolactone (SPI) may not have significant anti-neoplastic potential in GBM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Michael Crompton, Laura J. Skinner, Simon C. Satchell, Matthew J. Butler
Summary: The renin angiotensin aldosterone system plays a crucial role in blood pressure regulation. Excessive stimulation of mineralocorticoid receptors by aldosterone can lead to various pathological effects in the heart, kidney, and endothelial cells. In this article, we discussed the association between hyperaldosteronism and fibrosis, cardiac dysfunction, maladaptive hypertrophy, proteinuria, and fibrosis. We also reviewed how aldosterone exposure damages the endothelial glycocalyx and suggested that preventing glycocalyx remodeling may offer a novel strategy for limiting endothelial damage.
Article
Physiology
Kristina S. LyngsO, Boye L. Jensen, Pernille B. L. Hansen, Henrik Dimke
Summary: The study found that aldosterone impairs endothelial function in a murine model of experimental diabetes through activation of endothelial cell mineralocorticoid receptors. This may explain the cardiovascular protection by mineralocorticoid receptor antagonists in diabetes.
Review
Endocrinology & Metabolism
Christopher Edwards
Summary: This paper explores how the SARS-CoV-2 virus causes severe complications in COVID-19 patients. It suggests that cortisol-associated MR activation leads to the release of ATP, affecting disease progression. Factors such as gender, age, race, diabetes, BMI, and blood type are also found to influence the disease outcomes.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Sofia S. Pereira, Liliana Carvalho, Madalena M. Costa, Armindo Melo, Isabel M. P. L. V. O. Ferreira, Celso E. Gomez-Sanchez, Mariana P. Monteiro, Gavin Vinson, Duarte Pignatelli
Summary: The study evaluated the effects of MRAs on adrenal cortical physiology and morphology, showing that MRA treatment may lead to aldosterone-secreting cell proliferation and higher circulating aldosterone levels, resulting in alterations in adrenal gland function and morphology.
Article
Transplantation
Fernando Caravaca-Fontan, Montserrat Diaz-Encarnacion, Virginia Cabello, Gema Ariceta, Luis F. Quintana, Helena Marco, Xoana Barros, Natalia Ramos, Nuria Rodriguez-Mendiola, Sonia Cruz, Gema Fernandez-Juarez, Adela Rodriguez, Ana Perez de Jose, Cristina Rabasco, Raquel Rodado, Loreto Fernandez, Vanessa Perez Gomez, Ana avila, Luis Bravo, Natalia Espinosa, Natalia Allende, Maria Dolores Sanchez de la Nieta, Eva Rodriguez, Teresa Olea, Marta Melgosa, Ana Huerta, Rosa Miquel, Carmen Mon, Gloria Fraga, Alberto de Lorenzo, Juliana Draibe, Marta Cano-Megias, Fayna Gonzalez, Amir Shabaka, Maria Esperanza Lopez-Rubio, Maria Angeles Fenollosa, Luis Martin-Penagos, Iara Da Silva, Juana Alonso Titos, Santiago Rodriguez de Cordoba, Elena Goicoechea de Jorge, Manuel Praga
Summary: The longitudinal change in proteinuria is strongly associated with the risk of kidney failure in patients with C3 glomerulopathy, with a doubling of proteinuria levels resulting in a 2.5-fold increase in risk. A ≥50% reduction in proteinuria over time is significantly associated with a lower risk of kidney failure.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2022)
Review
Pharmacology & Pharmacy
Jorge Rojas-Rivera, Fernando C. Fervenza, Alberto Ortiz
Summary: Immunosuppressive therapy is essential for primary membranous nephropathy patients, especially those with persistent proteinuria, anti-phospholipase A2 receptor antibodies, reduced kidney function, or other risk factors. Recent studies have shown that glucocorticoid-cyclophosphamide and rituximab are effective treatments, but may come with the risk of adverse events.
Article
Transplantation
Fernando Caravaca-Fontan, Laura Lucientes, Nuria Serra, Teresa Cavero, Raquel Rodado, Natalia Ramos, Fayna Gonzalez, Amir Shabaka, Virginia Cabello, Ana Huerta, Saul Pampa-Saico, Eduardo Gutierrez, Luis F. Quintana, Maria Esperanza Lopez-Rubio, Juliana Draibe, Juana Alonso Titos, Gema Fernandez-Juarez, Elena Goicoechea de Jorge, Manuel Praga
Summary: This study analyzed the clinical and histological features of C3G-MIg patients and found that higher chronicity scores were associated with worse kidney prognosis. Clone-targeted therapies and the development of a haematological response were associated with better kidney prognosis. Kidney transplant recipients had a poor outcome.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2022)
Article
Urology & Nephrology
Ana Huerta, Eva Merida, Laura Medina, Maria Fernandez, Eduardo Gutierrez, Eduardo Hernandez, Paula Lopez-Sanchez, Angel Sevillano, Jose Portoles, Hernan Trimarchi, Manuel Praga
Summary: Treatment with corticosteroids and mycophenolic acid analogues is effective in IgA nephropathy patients with progressive decline in kidney function accompanied by persistent proteinuria and hematuria.
CLINICAL KIDNEY JOURNAL
(2022)
Article
Urology & Nephrology
Fernando Caravaca-Fontan, Marta Rivero, Teresa Cavero, Montserrat Diaz-Encarnacion, Virginia Cabello, Gema Ariceta, Luis F. Quintana, Helena Marco, Xoana Barros, Natalia Ramos, Nuria Rodriguez-Mendiola, Sonia Cruz, Gema Fernandez-Juarez, Adela Rodriguez, Ana Perez de Jose, Cristina Rabasco, Raquel Rodado, Loreto Fernandez, Vanessa Perez-Gomez, Ana Avila, Luis Bravo, Natalia Espinosa, Natalia Allende, Maria Dolores Sanchez de la Nieta, Eva Rodriguez, Teresa Olea, Marta Melgosa, Ana Huerta, Rosa Miquel, Carmen Mon, Gloria Fraga, Alberto de Lorenzo, Juliana Draibe, Fayna Gonzalez, Amir Shabaka, Maria Esperanza Lopez-Rubio, Maria Angeles Fenollosa, Luis Martin-Penagos, Iara Da Silva, Juana Alonso Titos, Santiago Rodriguez de Cordoba, Elena Goicoechea de Jorge, Manuel Praga
Summary: This study developed and validated a practical nomogram with good discrimination and calibration to predict the risk of kidney failure in C3 glomerulopathy patients at 1, 2, 5 and 10 years.
CLINICAL KIDNEY JOURNAL
(2022)
Article
Medicine, General & Internal
Marina Sanchez-Agesta, Cristina Rabasco, Maria J. Soler, Amir Shabaka, Elisabeth Canllavi, Saulo J. Fernandez, Juan M. Cazorla, Esperanza Lopez-Rubio, Ana Romera, Sergio Barroso, Ana Huerta, Leonardo Calle, Milagros Sierra, Patricia Dominguez-Torres, Manuela Moreno-Ramirez, Sara Afonso, Victoria Mascaros, Armando Coca, Mario Espinosa
Summary: In this study, the clinical and pathological features predicting the progression of end-stage kidney disease (ESKD) and kidney survival in patients with anti-glomerular basement membrane (anti-GBM) disease were evaluated. The results showed that patients with severe disease, defined as creatinine levels > 4.7 mg/dL and > 50% crescents, had poor renal prognosis despite plasma exchange and immunosuppressive treatment. New therapies are urgently needed for the treatment of this rare renal disease.
FRONTIERS IN MEDICINE
(2022)
Article
Transplantation
Teresa Cavero, Pilar Aunon, Fernando Caravaca-Fontan, Hernando Trujillo, Emi Arjona, Enrique Morales, Elena Guillen, Miquel Blasco, Cristina Rabasco, Mario Espinosa, Marta Blanco, Catuxa Rodriguez-Magarinos, Mercedes Cao, Ana Avila, Ana Huerta, Esther Rubio, Virginia Cabello, Xoana Barros, Elena Goicoechea de Jorge, Santiago Rodriguez de Cordoba, Manuel Praga
Summary: This study investigated the presence of TMA in patients with mHTN of different aetiologies and found that TMA is associated with specific causes of mHTN. The results showed a higher proportion of TMA in primary aHUS, drug-related mHTN, some systemic diseases, and IgAN, while it is exceptional in other causes of mHTN.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Critical Care Medicine
Ester Zamarron, Ana Jaureguizar, Aldara Garcia-Sanchez, Trinidad Diaz-Cambriles, Alberto Alonso-Fernandez, Vanesa Lores, Olga Mediano, Fernanda Troncoso-Acevedo, Sheila Cabello-Pelegrin, Enrique Morales-Ruiz, Maria T. Ramirez-Prieto, Maria Isabel Valiente-Diaz, Teresa Gomez-Garcia, Raquel Casitas, Elisabet Martinez-Ceron, Raul Galera, Carolina Cubillos-Zapata, Francisco Garcia-Rio
Summary: This study investigated the effect of continuous positive airway pressure (CPAP) on the urinary albumin-to-creatinine ratio (UACR) in patients with obstructive sleep apnea (OSA) and diabetic kidney disease (DKD). The results showed that CPAP treatment, in addition to usual care, significantly reduced UACR in patients who adhered to treatment. Furthermore, CPAP treatment also improved glycemic control, insulin resistance, sleepiness, and health-related quality of life.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Cecilia Gonzalez-Cuadrado, Paula Jara Caro-Espada, Marta Chivite-Lacaba, Alberto Utrero-Rico, Claudia Lozano-Yuste, Elena Gutierrez-Solis, Enrique Morales, Justo Sandino-Perez, Francisco Javier Gil-Etayo, Luis Allende-Martinez, Rocio Laguna-Goya, Estela Paz-Artal
Summary: Patients on hemodialysis with COVID-19 exhibit dysregulated immunity, increased levels of pro-inflammatory cytokines, and altered subsets of lymphocytes. The hemodialysis session in COVID-19 patients is associated with a further increase in inflammatory cytokines and monocyte activation. These findings suggest potential biomarkers and therapeutic targets to prevent or mitigate the deterioration during hemodialysis in patients with SARS-CoV-2 infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Urology & Nephrology
Jorge E. Rojas-Rivera, Clara Garcia-Carro, Ana Avila, Mar Espino, Mario Espinosa, Gema Fernandez-Juarez, Xavier Fulladosa, Marian Goicoechea, Manuel Macia, Enrique Morales, Luis F. Quintana, Manuel Praga
Summary: The abridged version of the 2023 GLOSEN Consensus Document on Lupus Nephritis provides practical recommendations for the diagnosis, monitoring, and treatment of patients with LN, including special situations. LN is a serious manifestation of SLE and can greatly impact quality of life and prognosis. Recent advances have improved the diagnostic approach and new drugs have been developed to block specific pathways and prevent kidney damage progression. The combination of different therapies allows for reduced use of corticosteroids and other potentially toxic treatments and increases the number of patients achieving complete remission.
CLINICAL KIDNEY JOURNAL
(2023)
Article
Transplantation
Jorge E. Rojas-Rivera, Sevcan A. Bakkaloglu, Davide Bolignano, Ionut Nistor, Pantelis A. Sarafidis, Sokratis Stoumpos, Mario Gennaro Cozzolino, Alberto Ortiz, ERA ERBP
Summary: Chronic kidney disease (CKD) is diagnosed based on glomerular filtration rate (GFR) and urinary albumin:creatinine ratio (UACR). High cardiovascular risk is associated with moderate or severe CKD. The management recommendations for lupus nephritis (LN) and cardiovascular risk in rheumatic and musculoskeletal diseases do not consider albuminuria or CKD. The authors propose a change in the conceptual framework to treat LN as a cause of CKD and apply evidence from large CKD trials.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Medicine, Research & Experimental
E. Rodriguez-Almaraz, E. Gutierrez-Solis, E. Rabadan, P. Rodriguez, M. Alonso, L. Carmona, M. J. Garcia de Yebenes, E. Morales, M. Galindo-Izquierdo
Summary: This study aimed to evaluate the development of a prognostic index for lupus nephritis (LN), using clinical, analytical, and histological factors to determine which patients would have a worse disease progression and require more aggressive treatment and closer follow-up within 6 months after diagnosis of LN.
EUROPEAN JOURNAL OF MEDICAL RESEARCH
(2023)
Review
Urology & Nephrology
Justo Sandino, Lucia Cordero Garcia-Galan, Lucia Aubert Girbal, Manuel Praga, Julio Pascual, Enrique Morales
Summary: Treatment for obesity in patients with CKD includes various options, from lifestyle modification to surgery. Weight loss can improve metabolic parameters and renal function, leading to improvement in glomerular hyperfiltration. Multitarget therapies, dietary education, new drugs, and surgery may play a crucial role in achieving nephroprotection in this population. New therapeutic agents and biomarkers are needed to monitor and mitigate progression to end-stage renal disease.
Article
Urology & Nephrology
Meryl Waldman, Maria Jose Soler, Clara Garcia-Carro, Liz Lightstone, Tabitha Turner-Stokes, Megan Griffith, Joan Torras, Laura Martinez Valenzuela, Oriol Bestard, Colin Geddes, Oliver Flossmann, Kelly L. Budge, Chiara Cantarelli, Enrico Fiaccadori, Marco Delsante, Enrique Morales, Eduardo Gutierrez, Jose A. Nino-Cruz, Armando J. Martinez-Rueda, Giorgia Comai, Claudia Bini, Gaetano La Manna, Maria F. Slon, Joaquin Manrique, Alejandro Avello, Raul Fernandez-Prado, Alberto Ortiz, Smaragdi Marinaki, Carmen Rita Martin Varas, Cristina Rabasco Ruiz, Milagros Sierra-Carpio, Rebeca Garcia-Agudo, Gema Fernandez Juarez, Alexander J. Hamilton, Annette Bruchfeld, Constantina Chrysochou, Lilian Howard, Smeeta Sinha, Tim Leach, Irene Agraz Pamplona, Umberto Maggiore, Paolo Cravedi
Summary: This study investigated the acute and long-term effects of COVID-19 infection on individuals with GN, and found that GN patients are at a higher risk of impaired eGFR recovery after developing AKI.