Automatic Assessment of Transcatheter Aortic Valve Implantation Results on Four-Dimensional Computed Tomography Images Using Artificial Intelligence.

Transcatheter aortic valve implantation (TAVI) is a procedure to treat severe aortic stenosis. There are several clinical concerns related to potential complications after the procedure, which demand the analysis of computerized tomography (CT) scans after TAVI to assess the implant's result. This work introduces a novel, fully automatic method for the analysis of post-TAVI 4D-CT scans to characterize the prosthesis and its relationship with the patient's anatomy. The method enables measurement extraction, including prosthesis volume, center of mass, cross-sectional area (CSA) along the prosthesis axis, and CSA difference between the aortic root and prosthesis, all the variables studied throughout the cardiac cycle. The method has been implemented and evaluated with a cohort of 13 patients with five different prosthesis models, successfully extracting all the measurements from each patient in an automatic way. For Allegra patients, the mean of the obtained inner volume values ranged from 10,798.20 mm3 to 18,172.35 mm3, and CSA in the maximum diameter plane varied from 396.35 mm2 to 485.34 mm2. The implantation of this new method could provide information of the important clinical value that would contribute to the improvement of TAVI, significantly reducing the time and effort invested by clinicians in the image interpretation process.

Consenso SOCHOG/SOCHUMB: utilizar en Chile la curva estándar OMS ultrasonográfica de crecimiento fetal / SOCHOG/SOCHUMB consensus: OMS fetal ultrasound curve is the standard curve for ultrasound growth assessment to use in Chile

La Sociedad Chilena de Obstetricia y Ginecología (SOCHOG) y la Sociedad Chilena de Ultrasonido en Medicina y Biología (SOCHUMB) convocaron a un comité de expertos en el tema de ultrasonido y crecimiento fetal con el fin de proponer utilizar la curva fetal que mejor se adapte a la población chilena. Luego de la discusión, al no contar con curvas chilenas de crecimiento fetal, se concluye proponer que la curva estándar de la Organización Mundial de la Salud (OMS) sería la indicada dada la calidad de su metodología y por ser multicéntrica.

The Chilean Society of Obstetrics and Gynecology (SOCHOG) and the Chilean Society of Ultrasound in Medicine and Biology (SOCHUMB) have convened a committee of experts on the subject of ultrasound and fetal growth in order to propose using the fetal curve that best adapts to the Chilean population. After the discussion, since there are no Chilean fetal growth curves, it is concluded that the World Health Organization (WHO) standard curve would be the one to use given the quality of its methodology and the fact that it is multicentric.

Two-Step Approach for Occupancy Estimation in Intensive Care Units Based on Bayesian Optimization Techniques.

Due to the high occupational pressure suffered by intensive care units (ICUs), a correct estimation of the patients' length of stay (LoS) in the ICU is of great interest to predict possible situations of collapse, to help healthcare personnel to select appropriate treatment options and to predict patients' conditions. There has been a high amount of data collected by biomedical sensors during the continuous monitoring process of patients in the ICU, so the use of artificial intelligence techniques in automatic LoS estimation would improve patients' care and facilitate the work of healthcare personnel. In this work, a novel methodology to estimate the LoS using data of the first 24 h in the ICU is presented. To achieve this, XGBoost, one of the most popular and efficient state-of-the-art algorithms, is used as an estimator model, and its performance is optimized both from computational and precision viewpoints using Bayesian techniques. For this optimization, a novel two-step approach is presented. The methodology was carefully designed to execute codes on a high-performance computing system based on graphics processing units, which considerably reduces the execution time. The algorithm scalability is analyzed. With the proposed methodology, the best set of XGBoost hyperparameters are identified, estimating LoS with a MAE of 2.529 days, improving the results reported in the current state of the art and probing the validity and utility of the proposed approach.

Data-Driven Phenotyping of Alzheimer's Disease under Epigenetic Conditions Using Partial Volume Correction of PET Studies and Manifold Learning.

Alzheimer's disease (AD) is the most common form of dementia. An increasing number of studies have confirmed epigenetic changes in AD. Consequently, a robust phenotyping mechanism must take into consideration the environmental effects on the patient in the generation of phenotypes. Positron Emission Tomography (PET) is employed for the quantification of pathological amyloid deposition in brain tissues. The objective is to develop a new methodology for the hyperparametric analysis of changes in cognitive scores and PET features to test for there being multiple AD phenotypes. We used a computational method to identify phenotypes in a retrospective cohort study (532 subjects), using PET and Magnetic Resonance Imaging (MRI) images and neuropsychological assessments, to develop a novel computational phenotyping method that uses Partial Volume Correction (PVC) and subsets of neuropsychological assessments in a non-biased fashion. Our pipeline is based on a Regional Spread Function (RSF) method for PVC and a t-distributed Stochastic Neighbor Embedding (t-SNE) manifold. The results presented demonstrate that (1) the approach to data-driven phenotyping is valid, (2) the different techniques involved in the pipelines produce different results, and (3) they permit us to identify the best phenotyping pipeline. The method identifies three phenotypes and permits us to analyze them under epigenetic conditions.

Improving Intensive Care Unit Early Readmission Prediction Using Optimized and Explainable Machine Learning.

It is of great interest to develop and introduce new techniques to automatically and efficiently analyze the enormous amount of data generated in today's hospitals, using state-of-the-art artificial intelligence methods. Patients readmitted to the ICU in the same hospital stay have a higher risk of mortality, morbidity, longer length of stay, and increased cost. The methodology proposed to predict ICU readmission could improve the patients' care. The objective of this work is to explore and evaluate the potential improvement of existing models for predicting early ICU patient readmission by using optimized artificial intelligence algorithms and explainability techniques. In this work, XGBoost is used as a predictor model, combined with Bayesian techniques to optimize it. The results obtained predicted early ICU readmission (AUROC of 0.92 ± 0.03) improves state-of-the-art consulted works (whose AUROC oscillate between 0.66 and 0.78). Moreover, we explain the internal functioning of the model by using Shapley Additive Explanation-based techniques, allowing us to understand the model internal performance and to obtain useful information, as patient-specific information, the thresholds from which a feature begins to be critical for a certain group of patients, and the feature importance ranking.

Using Bayesian Optimization and Wavelet Decomposition in GPU for Arterial Blood Pressure Estimation.

Continuous monitoring of arterial blood pressure (ABP) of patients in hospital is currently carried out in an invasive way, which could represent a risk for them. In this paper, a noninvasive methodology to optimize ABP estimators using electrocardiogram and photoplethysmography signals is proposed. For this, the XGBoost machine learning model, optimized with Bayesian techniques, is executed in a Graphics Processing Unit, which drastically reduces execution time. The methodology is evaluated using the MIMIC-III Waveform Database. Systolic and diastolic pressures are estimated with mean absolute error values of 15.85 and 11.59 mmHg, respectively, similar to those of the state of the art. The main advantage of the proposed methodology with respect to others of the current state of the art is that it allows the optimization of the estimator model to be performed automatically and more efficiently at the computational level for the data available. Clinical Relevance- This approach has the advantage of using noninvasive methods to continuously monitor patient's arterial blood pressure, reducing the risk for patients.

Functional Alterations Involved in Increased Bleeding in Hereditary Hemorrhagic Telangiectasia Mouse Models.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal-dominant genetic disorder involving defects in two predominant genes known as endoglin (ENG; HHT-1) and activin receptor-like kinase 1 (ACVRL1/ALK1; HHT-2). It is characterized by mucocutaneous telangiectases that, due to their fragility, frequently break causing recurrent epistaxis and gastrointestinal bleeding. Because of the severity of hemorrhages, the study of the hemostasis involved in these vascular ruptures is critical to find therapies for this disease. Our results demonstrate that HHT patients with high bleeding, as determined by a high Epistaxis Severity Score (ESS), do not have prolonged clotting times or alterations in clotting factors. Considering that coagulation is only one of the processes involved in hemostasis, the main objective of this study was to investigate the overall mechanisms of hemostasis in HHT-1 (Eng +/-) and HHT-2 (Alk1 +/-) mouse models, which do not show HHT vascular phenotypes in the meaning of spontaneous bleeding. In Eng +/- mice, the results of in vivo and in vitro assays suggest deficient platelet-endothelium interactions that impair a robust and stable thrombus formation. Consequently, the thrombus could be torn off and dragged by the mechanical force exerted by the bloodstream, leading to the reappearance of hemorrhages. In Alk1 +/- mice, an overactivation of the fibrinolysis system was observed. These results support the idea that endoglin and Alk1 haploinsufficiency leads to a common phenotype of impaired hemostasis, but through different mechanisms. This contribution opens new therapeutic approaches to HHT patients' epistaxis.

Automatic Identification of Bioprostheses on X-ray Angiographic Sequences of Transcatheter Aortic Valve Implantation Procedures Using Deep Learning.

Transcatheter aortic valve implantation (TAVI) has become the treatment of choice for patients with severe aortic stenosis and high surgical risk. Angiography has been established as an essential tool in TAVI, as this modality provides real-time images required to support the intervention. The automatic interpretation and parameter extraction on such images can lead to significative improvements and new applications in the procedure that, in most cases, rely on a prior identification of the transcatheter heart valve (THV). In this paper, U-Net architecture is proposed for the automatic segmentation of THV on angiographies, studying the role of its hyperparameters in the quality of the segmentations. Several experiments have been conducted, testing the methodology using multiple configurations and evaluating the results on different types of frames captured during the procedure. The evaluation has been performed in terms of conventional classification metrics, complemented with two new metrics, specifically defined for this problem. Those new metrics provide a more appropriate assessment of the quality of the results, given the class imbalance in the dataset. From an analysis of the evaluation results, it can be concluded that the method provides appropriate segmentation results for this dataset.

Using Explainable Machine Learning to Improve Intensive Care Unit Alarm Systems.

Due to the continuous monitoring process of critical patients, Intensive Care Units (ICU) generate large amounts of data, which are difficult for healthcare personnel to analyze manually, especially in overloaded situations such as those present during the COVID-19 pandemic. Therefore, the automatic analysis of these data has many practical applications in patient monitoring, including the optimization of alarm systems for alerting healthcare personnel. In this paper, explainable machine learning techniques are used for this purpose, with a methodology based on age-stratification, boosting classifiers, and Shapley Additive Explanations (SHAP) proposed. The methodology is evaluated using MIMIC-III, an ICU patient research database. The results show that the proposed model can predict mortality within the ICU with AUROC values of 0.961, 0.936, 0.898, and 0.883 for age groups 18-45, 45-65, 65-85 and 85+, respectively. By using SHAP, the features with the highest impact in predicting mortality for different age groups and the threshold from which the value of a clinical feature has a negative impact on the patient's health can be identified. This allows ICU alarms to be improved by identifying the most important variables to be sensed and the threshold values at which the health personnel must be warned.

[Current status of Therapeutic Hypothermia in Hypoxic-Ischemic Encephalopathy]. / Estado actual de la Hipotermia Terapéutica en la Encefalopatía Hipóxico-Isquémica.

Therapeutic hypothermia (TH) has been the standard treatment for neonatal Hypoxic-Ischemic En cephalopathy (HIE) for more than a decade. This therapy has been one of the best studied treatments in neonatal medicine, moving from preclinical models to patient application. Its implementation has been accompanied by the development of neuromonitoring, neonatal neurology as a specific area of expertise, and the intense search for new neuroprotective strategies. This article provides an update on the clinical scope of this therapy, with emphasis on the problems of our geographic region. In addition, some additional strategies that can improve the therapeutic efficacy of TH are reviewed, as well as controversial aspects in its application and some future perspectives in the care of neonates with HIE.

Aneurisma de arteria pulmonar: una revisión y dos casos ilustrativos / Pulmonary artery aneurysm: a review and two illustrative cases

El aneurisma de la arteria pulmonar (AAP) es una patología poco frecuente, con una prevalencia estimada en 0,06 %; si bien sus mecanismos fisiopatológicos aún se encuentran en estudio, se cree que la principal causa es el incremento de la presión y/o del flujo a través de la arteria pulmonar (AP), como sucede en la hipertensión pulmonar y el síndrome de Eisenmenger. Con frecuencia el AAP tiene un curso asintomático o desencadena síntomas inespecíficos, pero sus complicaciones pueden presentarse con independencia de los síntomas y llegar a tener un desenlace fatal. En el presente artículo se realiza una revisión de la literatura y se presentan dos casos de AAP.

Pulmonary artery aneurysm (PAA) is a rare disease with an estimated prevalence of 0.06%. Although its pathophysiological mechanisms are still under study, the main cause is believed to be an increased pressure and/or flow through the pulmonary artery (PA), as occurs in pulmonary hypertension and Eisenmenger syndrome. PAA often has an asymptomatic course or triggers nonspecific symptoms, but its complications can occur regardless of the symptoms and be fatal. In this article, a literature review is carried out and two cases of PAA are reported.

Pregnancy-Induced High Plasma Levels of Soluble Endoglin in Mice Lead to Preeclampsia Symptoms and Placental Abnormalities.

Preeclampsia is a pregnancy-specific disease of high prevalence characterized by the onset of hypertension, among other maternal or fetal signs. Its etiopathogenesis remains elusive, but it is widely accepted that abnormal placentation results in the release of soluble factors that cause the clinical manifestations of the disease. An increased level of soluble endoglin (sEng) in plasma has been proposed to be an early diagnostic and prognostic biomarker of this disease. A pathogenic function of sEng involving hypertension has also been reported in several animal models with high levels of plasma sEng not directly dependent on pregnancy. The aim of this work was to study the functional effect of high plasma levels of sEng in the pathophysiology of preeclampsia in a model of pregnant mice, in which the levels of sEng in the maternal blood during pregnancy replicate the conditions of human preeclampsia. Our results show that wild type pregnant mice carrying human sEng-expressing transgenic fetuses (fWT(hsEng+)) present high plasma levels of sEng with a timing profile similar to that of human preeclampsia. High plasma levels of human sEng (hsEng) are associated with hypertension, proteinuria, fetal growth restriction, and the release of soluble factors to maternal plasma. In addition, fWT(hsEng+) mice also present placental alterations comparable to those caused by the poor remodeling of the spiral arteries characteristic of preeclampsia. In vitro and ex vivo experiments, performed in a human trophoblast cell line and human placental explants, show that sEng interferes with trophoblast invasion and the associated pseudovasculogenesis, a process by which cytotrophoblasts switch from an epithelial to an endothelial phenotype, both events being related to remodeling of the spiral arteries. Our findings provide a novel and useful animal model for future research in preeclampsia and reveal a much more relevant role of sEng in preeclampsia than initially proposed.

Resultados de la cirugía endoscópica de la glándula tiroides por vía transaxilar en Perú / Results of transaxillary endoscopic surgery of the thyroid gland in Peru

RESUMEN Objetivo: Describir los resultados de la tiroidectomía endoscópica transaxilar sin insuflación de CO2 en Perú. Material y métodos: Estudio descriptivo, retrospectivo de una serie de casos basado en la revisión de las historias clínicas de los pacientes con tumor tiroideo sometidos a tiroidectomía endoscópica transaxilar sin insuflación de CO entre noviembre 2014 y marzo 2017, en instituciones públicas y privadas del sistema nacional de salud de la ciudad de Lima. Resultados: Se realizaron 24 tiroidectomías endoscópicas, de las cuales 15 fueron hemitiroidectomia, 8 tiroidectomía total y una tiroidectomía subtotal. El tiempo operatorio promedio fue de 193,8 minutos. Las complicaciones más frecuentes fueron el hematoma postoperatorio (12,5%) seguido de la hipocalcemia transitoria (8,3%); ningún caso presentó lesión del plexo braquial. Conclusiones: La tiroidectomía endoscópica por vía transaxilar es un procedimiento seguro, factible de realizar en instituciones de salud que cuenten con el equipamiento de cirugía video endoscópica, que podría indicarse en determinados pacientes.

SUMMARY Objective: To describe the results of transaxillary endoscopic surgery of the thyroid gland without insufflating CO2 in Peru. Methods: A retrospective case series based of chart review of patients with thyroid cancer undergoing transaxillary endoscopic surgery of the thyroid gland without insufflating CO2 from November 2014 to March 2017 in public and private institutions in Lima. Results: 24 transaxillary endoscopic procedures were performed, 15 of which were hemithyroidectomies, 8 were total thyroidectomies and one subtotal thyroidectomy. Mean operating time was 193.8 minutes. The most common complication was post operatory hematoma (12.5%) followed by transient hypocalcemia (8.3%), no lesions of the brachial plexus were observed. Conclusions: Transaxillary endoscopic surgery of the thyroid gland is a safe and feasible procedure to be performed in equipped centers.

Potential Role of Circulating Endoglin in Hypertension via the Upregulated Expression of BMP4.

Endoglin is a membrane glycoprotein primarily expressed by the vascular endothelium and involved in cardiovascular diseases. Upon the proteolytic processing of the membrane-bound protein, a circulating form of endoglin (soluble endoglin, sEng) can be released, and high levels of sEng have been observed in several endothelial-related pathological conditions, where it appears to contribute to endothelial dysfunction. Preeclampsia is a multisystem disorder of high prevalence in pregnant women characterized by the onset of high blood pressure and associated with increased levels of sEng. Although a pathogenic role for sEng involving hypertension has been reported in several animal models of preeclampsia, the exact molecular mechanisms implicated remain to be identified. To search for sEng-induced mediators of hypertension, we analyzed the protein secretome of human endothelial cells in the presence of sEng. We found that sEng induces the expression of BMP4 in endothelial cells, as evidenced by their proteomic signature, gene transcript levels, and BMP4 promoter activity. A mouse model of preeclampsia with high sEng plasma levels (sEng+) showed increased transcript levels of BMP4 in lungs, stomach, and duodenum, and increased circulating levels of BMP4, compared to those of control animals. In addition, after crossing female wild type with male sEng+ mice, hypertension appeared 18 days after mating, coinciding with the appearance of high plasma levels of BMP4. Also, serum levels of sEng and BMP4 were positively correlated in pregnant women with and without preeclampsia. Interestingly, sEng-induced arterial pressure elevation in sEng+ mice was abolished in the presence of the BMP4 inhibitor noggin, suggesting that BMP4 is a downstream mediator of sEng. These results provide a better understanding on the role of sEng in the physiopathology of preeclampsia and other cardiovascular diseases, where sEng levels are increased.

Impaired Tubular Reabsorption Is the Main Mechanism Explaining Increases in Urinary NGAL Excretion Following Acute Kidney Injury in Rats.

Neutrophil gelatinase-associated lipocalin (NGAL) is a secreted low-molecular weight iron-siderophore-binding protein. NGAL overexpression in injured tubular epithelia partly explains its utility as a sensitive and early urinary biomarker of acute kidney injury (AKI). Herein, we extend mechanistic insights into the source and kinetics of urinary NGAL excretion in experimental AKI. Three models of experimental AKI were undertaken in adult male Wistar rats; renal ischemia-reperfusion injury (IRI) and gentamicin (G) and cisplatin (Cisp) nephrotoxicity. Alongside standard histological and biochemical assessment of AKI, urinary NGAL excretion rate, plasma NGAL concentration, and renal NGAL mRNA/protein expression were assessed. In situ renal perfusion studies were undertaken to discriminate direct shedding of NGAL to the urine from addition of NGAL to the urine secondary to alterations in the tubular handling of glomerular filtrate-derived protein. Renal NGAL expression and urinary excretion increased in experimental AKI. In acute studies in both the IRI and G models, direct renal perfusion with Kreb's buffer eliminated urinary NGAL excretion. Addition of exogenous NGAL to the Kreb's buffer circuit, reestablishment of perfusion with systemic blood or reperfusion with renal vein effluent restored high levels of urinary NGAL excretion. Urinary NGAL excretion in AKI arises in large proportion from reduced reabsorption from the glomerular filtrate. Hence, subclinical cellular dysfunction could increase urinary NGAL, particularly in concert with elevations in circulating prerenal NGAL and/or pharmacological inhibition of tubular reabsorption. More granular interpretation of urinary NGAL measurements could optimize the scope of its clinical utility as a biomarker of AKI.

Continuous endoglin (CD105) overexpression disrupts angiogenesis and facilitates tumor cell metastasis.

Endoglin (CD105) is an auxiliary receptor for members of the TFG-ß superfamily. Whereas it has been demonstrated that the deficiency of endoglin leads to minor and defective angiogenesis, little is known about the effect of its increased expression, characteristic of several types of cancer. Angiogenesis is essential for tumor growth, so high levels of proangiogenic molecules, such as endoglin, are supposed to be related to greater tumor growth leading to a poor cancer prognosis. However, we demonstrate here that endoglin overexpression do not stimulate sprouting or vascularization in several in vitro and in vivo models. Instead, steady endoglin overexpression keep endothelial cells in an active phenotype that results in an impairment of the correct stabilization of the endothelium and the recruitment of mural cells. In a context of continuous enhanced angiogenesis, such as in tumors, endoglin overexpression gives rise to altered vessels with an incomplete mural coverage that permit the extravasation of blood. Moreover, these alterations allow the intravasation of tumor cells, the subsequent development of metastases and, thus, a worse cancer prognosis.

Urinary TCP1-eta: A Cortical Damage Marker for the Pathophysiological Diagnosis and Prognosis of Acute Kidney Injury.

Acute kidney injury (AKI) is a serious syndrome with increasing incidence and health consequences, and high mortality rate among critically ill patients. Acute kidney injury lacks a unified definition, has ambiguous semantic boundaries, and relies on defective diagnosis. This, in part, is due to the absence of biomarkers substratifying AKI patients into pathophysiological categories based on which prognosis can be assigned and clinical treatment differentiated. For instance, AKI involving acute tubular necrosis (ATN) is expected to have a worse prognosis than prerenal, purely hemodynamic AKI. However, no biomarker has been unambiguously associated with tubular cell death or is able to provide etiological distinction. We used a cell-based system to identify TCP1-eta in the culture medium as a noninvasive marker of damaged renal tubular cells. In rat models of AKI, TCP1-eta was increased in the urine co-relating with renal cortical tubule damage. When kidneys from ATN rats were perfused in situ with Krebs-dextran solution, a portion of the urinary TCP1-eta protein content excreted into urine disappeared, and another portion remained within the urine. These results indicated that TCP1-eta was secreted by tubule cells and was not fully reabsorbed by the damaged tubules, both effects contributing to the increased urinary excretion. Urinary TCP1-eta is found in many etiologically heterogeneous AKI patients, and is statistically higher in patients partially recovered from severe AKI. In conclusion, urinary TCP1-eta poses a potential, substratifying biomarker of renal cortical damage associated with bad prognosis.

Preventive Effect of Cardiotrophin-1 Administration before DSS-Induced Ulcerative Colitis in Mice.

Ulcerative colitis is a relatively frequent, chronic disease that impacts significantly the patient's quality of life. Although many therapeutic options are available, additional approaches are needed because many patients either do not respond to current therapies or show significant side effects. Cardiotrophin-1 (CT-1) is a cytokine with potent cytoprotective, anti-inflammatory, and antiapoptotic properties. The purpose of this study was to assess if the administration of CT-1 could reduce colon damage in mice with experimental colitis was induced with 5% dextran sulfate sodium (DSS) in the drinking water. Half of the mice received an i.v. dose of CT-1 (200 µg/kg) 2 h before and 2 and 4 days after DSS administration. Animals were followed during 7 days after DSS administration. The severity of colitis was measured by standard scores. Colon damage was assessed by histology and immunohistochemistry. Inflammatory mediators were measured by Western blot and PCR. CT-1 administration to DSS-treated mice ameliorated both the clinical course (disease activity index), histological damage, inflammation (colon expression of TNF-α, IL-17, IL-10, INF IFN-γ, and iNOS), and apoptosis. Our results suggest that CT-1 administration before induction of colitis improves the clinical course, tissue damage, and inflammation in DSS-induced colitis in mice.

Cardiotrophin-1 opposes renal fibrosis in mice: Potential prevention of chronic kidney disease.

AIM: Chronic kidney disease is characterized by tubulointerstitial fibrosis involving inflammation, tubular apoptosis, fibroblast proliferation and extracellular matrix accumulation. Cardiotrophin-1, a member of the interleukin-6 family of cytokines, protects several organs from damage by promoting survival and anti-inflammatory effects. However, whether cardiotrophin-1 participates in the response to chronic kidney injury leading to renal fibrosis is unknown. METHODS: We hypothesized and assessed the potential role of cardiotrophin-1 in a mice model of tubulointerstitial fibrosis induced by unilateral ureteral obstruction (UUO). RESULTS: Three days after UUO, obstructed kidneys from cardiotrophin-1-/- mice show higher expression of inflammatory markers IL-1ß, Cd68, ICAM-1, COX-2 and iNOs, higher activation of NF-κB, higher amount of myofibroblasts and higher severity of tubular damage and apoptosis, compared with obstructed kidneys from wild-type littermates. In a later stage, obstructed kidneys from cardiotrophin-1-/- mice show higher fibrosis than obstructed kidneys from wild-type mice. Interestingly, administration of exogenous cardiotrophin-1 prevents the increased fibrosis resulting from the genetic knockout of cardiotrophin-1 upon UUO, and supplementation of wild-type mice with exogenous cardiotrophin-1 further reduces the renal fibrosis induced by UUO. In vitro, renal myofibroblasts from cardiotrophin-1-/- mice have higher collagen I and fibronectin expression and higher NF-κB activation than wild-type cells. CONCLUSIONS: Cardiotrophin-1 participates in the endogenous response that opposes renal damage by counteracting the inflammatory, apoptotic and fibrotic processes. And exogenous cardiotrophin-1 is proposed as a candidate for the treatment and prevention of chronic renal fibrosis.