Pathophysiological characterization of the ApoE mouse: A model of diabetes and atherosclerosis.

The high prevalence of type 2 diabetes and atherosclerosis makes essential the availability of in vivo experimental models that accurately replicate the pathophysiological mechanisms of these diseases. Apolipoprotein E knockout mice (ApoE) have been used in atherosclerosis studies, and the db/db mice show hyperphagia and obesity. Mice harbouring both alterations (i.

Age and Hypertension Synergize With Dehydration to Cause Renal Frailty in Rats and Predispose Them to Intrinsic Acute Kidney Injury.

Acute kidney frailty (AKF) is a condition of increased susceptibility to acute kidney injury (AKI), an abrupt impairment of renal excretory function potentially leading to severe complications. Prevention of AKI relies on the recognition of risk factors contributing to AKF. At the population level, dehydration constitutes a predisposing factor for AKI.

Urinary GM2AP coincides with renal cortical damage and grades cisplatin nephrotoxicity severity in rats.

Nephrotoxicity, including electrolytic disorders and acute kidney injury (AKI), limits the clinical dosage and utility of platinated antineoplastics such as cisplatin. Cisplatin nephrotoxicity embodies a tubulopathy involving the medullary S2 and S3 segments of the proximal and the distal tubules. Higher dosage extends damage over the cortical S1 segment and intensifies overall injury.

A wide scope, pan-comparative, systematic meta-analysis of the efficacy of prophylactic strategies for cardiac surgery-associated acute kidney injury.

Acute kidney injury (AKI) is the most common complication of cardiac surgery. Cardiac surgery-associated AKI (CSA-AKI) is caused by systemic and renal hemodynamic impairment and parenchymal injury. Prophylaxis of CSA-AKI remains an unmet priority, for which preventive strategies based on drug therapies, hydration procedures, and remote ischemic preconditioning (RIPC) have been tested in pre-clinical and clinical studies, with variable success.

Reframing acute kidney injury as a pathophysiological continuum of disrupted renal excretory function.

Surrogate measures of glomerular filtration rate (GFR) continue to serve as pivotal determinants of the incidence, severity, and management of acute kidney injury (AKI), as well as the primary reference point underpinning knowledge of its pathophysiology. However, several clinically important deficits in aspects of renal excretory function during AKI other than GFR decline, including acid-base regulation, electrolyte and water balance, and urinary concentrating capacity, can evade detection when diagnostic criteria are built around purely GFR-based assessments. The use of putative markers of tubular injury to detect "sub-clinical" AKI has been proposed to expand the definition and diagnostic criteria for AKI, but their diagnostic performance is curtailed by ambiguity with respect to their biological meaning and context specificity.

Effect of uric acid reduction on chronic kidney disease. Systematic review and meta-analysis.

Accumulating evidence suggests that hyperuricemia is a pathological factor in the development and progression of chronic kidney disease. However, the potential benefit afforded by the control of uric acid (UA) is controversial. Individual studies show discrepant results, and most existing meta-analysis, especially those including the larger number of studies, lack a placebo or control group as they aim to compare efficacy between drugs.

Pathophysiology of Acute Kidney Frailty.

Acute kidney frailty is a premorbid condition of diminished renal functional reserve that predisposes to acute kidney injury; this condition results from subclinical wear or distortion of renal homeostatic responses that protect the renal excretory function. Knowledge of its pathophysiological basis is critical for the development of diagnostic and therapeutic strategies that allow for prophylactic intervention and disease prevention.

HIPEC in Ovarian Cancer Is the Future… and Always Will Be? Results from a Spanish Multicentric Survey.

Ovarian cancer is the leading cause of death due to gynecological tumors in the female population. Despite optimal first-line treatment, including cytoreduction and platinum-based systemic chemotherapy, recurrences are frequent. The use of hyperthermic intraperitoneal chemotherapy (HIPEC) has been criticized, especially because of the lack of randomized controlled trials (RCTs) with convincing results to support the use of HIPEC in patients with ovarian cancer with peritoneal dissemination.

Identification of Pre-Renal and Intrinsic Acute Kidney Injury by Anamnestic and Biochemical Criteria: Distinct Association with Urinary Injury Biomarkers.

Acute kidney injury (AKI) is a syndrome of sudden renal excretory dysfunction with severe health consequences. AKI etiology influences prognosis, with pre-renal showing a more favorable evolution than intrinsic AKI. Because the international diagnostic criteria (i.

Renal sympathetic activity: A key modulator of pressure natriuresis in hypertension.

Hypertension is a complex disorder ensuing necessarily from alterations in the pressure-natriuresis relationship, the main determinant of long-term control of blood pressure. This mechanism sets natriuresis to the level of blood pressure, so that increasing pressure translates into higher osmotically driven diuresis to reduce volemia and control blood pressure. External factors affecting the renal handling of sodium regulate the pressure-natriuresis relationship so that more or less natriuresis is attained for each level of blood pressure.

Diagnosis of Cardiac Surgery-Associated Acute Kidney Injury: State of the Art and Perspectives.

Diagnosis of cardiac surgery-associated acute kidney injury (CSA-AKI), a syndrome of sudden renal dysfunction occurring in the immediate post-operative period, is still sub-optimal. Standard CSA-AKI diagnosis is performed according to the international criteria for AKI diagnosis, afflicted with insufficient sensitivity, specificity, and prognostic capacity. In this article, we describe the limitations of current diagnostic procedures and of the so-called injury biomarkers and analyze new strategies under development for a conceptually enhanced diagnosis of CSA-AKI.

Endothelial Activin Receptor-Like Kinase 1 (ALK1) Regulates Myofibroblast Emergence and Peritubular Capillary Stability in the Early Stages of Kidney Fibrosis.

Renal tubulo-interstitial fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM) in the tubular interstitium during chronic kidney disease. The main source of ECM proteins are emerging and proliferating myofibroblasts. The sources of myofibroblasts in the renal tubular interstitium have been studied during decades, in which the epithelial contribution of the myofibroblast population through the epithelial-to-mesenchymal (EMT) process was assumed to be the major mechanism.

Urinary KIM-1 Correlates with the Subclinical Sequelae of Tubular Damage Persisting after the Apparent Functional Recovery from Intrinsic Acute Kidney Injury.

Acute kidney injury (AKI) poses an increased risk factor for new AKI episodes, progression to chronic kidney disease, and death. A worsened evolution has been linked to an incomplete renal repair beyond the apparent functional recovery based on plasma creatinine (pCr) normalization. However, structural sequelae pass largely unnoticed due to the absence of specific diagnostic tools.

The Urinary Level of Injury Biomarkers Is Not Univocally Reflective of the Extent of Toxic Renal Tubular Injury in Rats.

Nephrotoxicity is a major cause of intrinsic acute kidney injury (AKI). Because renal tissue damage may occur independently of a reduction in glomerular filtration rate and of elevations in plasma creatinine concentration, so-called injury biomarkers have been proposed to form part of diagnostic criteria as reflective of tubular damage independently of renal function status. We studied whether the urinary level of NGAL, KIM-1, GM2AP, t-gelsolin, and REGIIIb informed on the extent of tubular damage in rat models of nephrotoxicity, regardless of the etiology, moment of observation, and underlying pathophysiology.

Determining risk factors for triple whammy acute kidney injury.

Concurrent use of a diuretic, a renin-angiotensin system (RAS) inhibitor, and a non-steroidal anti-inflammatory drug (NSAID) significantly increases the risk of acute kidney injury (AKI). This phenomenon is known as "triple whammy". Diuretics and RAS inhibitors, such as an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker, are often prescribed in tandem for the treatment of hypertension, whereas some NSAIDs, such as ibuprofen, are available over the counter.

Neural Network-Based Calculator for Rat Glomerular Filtration Rate.

Glomerular filtration is a pivotal process of renal physiology, and its alterations are a central pathological event in acute kidney injury and chronic kidney disease. Creatinine clearance (ClCr), a standard method for glomerular filtration rate (GFR) measurement, requires a long and tedious procedure of timed (usually 24 h) urine collection. We have developed a neural network (NN)-based calculator of rat ClCr from plasma creatinine (pCr) and body weight.

Protective Effect of Quercetin 3--Glucuronide against Cisplatin Cytotoxicity in Renal Tubular Cells.

Quercetin, a flavonoid with promising therapeutic potential, has been shown to protect from cisplatin nephrotoxicity in rats following intraperitoneal injection, but its low bioavailability curtails its prospective clinical utility in oral therapy. We recently developed a micellar formulation (P-quercetin) with enhanced solubility and bioavailability, and identical nephroprotective properties. As a first aim, we herein evaluated the oral treatment with P-quercetin in rats, which displayed no nephroprotection.

Protocol for a preclinical systematic review and meta-analysis of pharmacological targeting of peroxisome proliferator-activated receptors in experimental renal injury.

Introduction: Impaired lipid metabolism in the renal tubule plays a prominent role in the progression of renal fibrosis following acute kidney injury (AKI) and in chronic kidney disease (CKD). Peroxisome proliferator-activated receptors (PPARs) are promising druggable targets to mitigate renal fibrosis by redirecting metabolism, including restoration of fatty acid oxidation (FAO) capacity. We aim to synthesise evidence from preclinical studies of pharmacological PPAR targeting in experimental renal injury, and inform the design of future studies evaluating PPAR-mediated restoration of FAO in AKI and CKD.

Are Antioxidants Useful in Preventing the Progression of Chronic Kidney Disease?

Chronic kidney disease (CKD) is a progressive impairment of renal function for more than three months that affects 15% of the adult population. Because oxidative stress is involved in its pathogenesis, antioxidants are under study for the prophylaxis of CKD progression. The objective of this work was to meta-analyze the efficacy of antioxidant therapy in CKD patients and to identify the most effective candidate antioxidants.

Albuminuria Pre-Emptively Identifies Cardiac Patients at Risk of Contrast-Induced Nephropathy.

Contrast-induced nephropathy (CIN) is a complication associated with the administration of contrast media (CM). The CIN diagnosis is based on creatinine, a biomarker late and insensitive. The objective proposed was to evaluate the ability of novel biomarkers to detect patients susceptible to suffering CIN before CM administration.

Biomarkers of persistent renal vulnerability after acute kidney injury recovery.

Acute kidney injury (AKI) is a risk factor for new AKI episodes, chronic kidney disease, cardiovascular events and death, as renal repair may be deficient and maladaptive, and activate proinflammatory and profibrotic signals. AKI and AKI recovery definitions are based on changes in plasma creatinine, a parameter mostly associated to glomerular filtration, but largely uncoupled from renal tissue damage. The evolution of structural and functional repair has been incompletely described.

Regression Modeling of the Antioxidant-to-Nephroprotective Relation Shows the Pivotal Role of Oxidative Stress in Cisplatin Nephrotoxicity.

The clinical utility of the chemotherapeutic drug cisplatin is significantly limited by its nephrotoxicity, which is characterized by electrolytic disorders, glomerular filtration rate decline, and azotemia. These alterations are consequences of a primary tubulopathy causing injury to proximal and distal epithelial cells, and thus tubular dysfunction. Oxidative stress plays a role in cisplatin nephrotoxicity and cytotoxicity, but its relative contribution to overall toxicity remains unknown.

Urinary Plasminogen Activator Inhibitor-1: A Biomarker of Acute Tubular Injury.

Introduction: Acute kidney injury (AKI) is a threatening, multiaetiological syndrome encompassing a variety of forms and damage patterns. AKI lacks sufficiently specific diagnostic tools to evaluate the distinct combination of pathophysiological events underlying each case, which limits personalized and optimized handling. Therefore, a pathophysiological diagnosis based on new urinary biomarkers is sought for practical (readiness and noninvasiveness) and conceptual reasons, as the urine is a direct product of the kidneys.

Genetic Susceptibility to Acute Kidney Injury.

Acute kidney injury (AKI) is a widely held concern related to a substantial burden of morbidity, mortality and expenditure in the healthcare system. AKI is not a simple illness but a complex conglomeration of syndromes that often occurs as part of other syndromes in its wide clinical spectrum of the disease. Genetic factors have been suggested as potentially responsible for its susceptibility and severity.