1,721,091 research outputs found
ERA-EDTA fellowship, a 'bonne opportunité': the scientific and human experience of a fellow
No full textAs a fellow of the ERA-EDTA long-term fellowship programme, I spent two fantastic years as a post-doc in Prof. D. Eladari's laboratory at Inserm U970, Paris-Cardiovascular Research Centre. It was a highly formative and productive scientific experience. On a personal level, immersion into the French society and the international environment of the laboratory were added bonuses that enriched my experience. I am honoured to report my experience here from the ERA-EDTA fellowship programme. I hope this will inspire young fellows to apply for such a programme and pursue their career in science. Good mentorship, a passion for scientific investigation and determination are required
Hyperuricemia and cardiovascular diseases: from phylogenesys to patogenetic mechanisms
No full textDuring human evolution, the accumulation of loss of function mutations of the uricase gene led progressively to the lack of the ability to metabolize uric acid into further end-products. Consequently, serum uric acid levels progressively increased over time along with the dietary availability of purine-rich foods. At first, the increase in uricemia contributed positively to primate development by increasing the antioxidant power of the organism, favouring an increase in blood pressure and lipid metabolism. However, later, these positive effects have been overcome by more dangerous consequences. In fact, in the recent period of human being history, the impact of dietary changes on uricemia was so significant that pathological consequences such as gout or renal stones appeared. Furthermore, it has been proved that abnormal uric acid level induces endothelial dysfunction and renal fibrosis. The shift between positive and negative consequences secondary to uric acid is clearly in accordance with the J curve shaped relation that describes the correlation between mortality and serum uric acid level
Relative Roles of Principal and Intercalated Cells in the Regulation of Sodium Balance and Blood Pressure
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Lithium-induced nephrogenic diabetes insipidus: New clinical and experimental findings
No full textLithium (Li+) salts are widely used to treat bipolar mood disorders. Recent trials suggest a potential efficacy also in the treatment of amyotrophic lateral sclerosis and Alzheimer's disease. Li+ is freely filtered by the glomerulus and mainly reabsorbed in the proximal convoluted tubule. Reabsorption in the distal nephron becomes significant under sodium-restricted conditions. Nevertheless, the distal nephron is greatly affected by Li+ even under normal sodium intake. Polyuria, renal tubular acidosis and finally chronic renal failure are the most frequent adverse effects. The occurrence of an overt nephrogenic diabetes insipidus (NDI) limits Li+ usage and imposes suspension. The molecular mechanisms of Li+-related urinary concentration defect involve a dysregulation of the aquaporin system in principal cells of the collecting duct. ENaC is crucial as the entry route for intracellular Li+ accumulation. The basolateral exit route is not clearly identified, but some evidence suggests Na+/H+ exchanger 1 (NHE1) as a potential candidate. Li+ promotes polyuria mainly counteracting the intracellular vasopressin signaling. An additional role of the inner medullary interstitial cells and PGE-2 pathway has to be considered. The GSK3β cascade is also regulated by Li+. GSK3β inhibition could lead not only to the polyuria, but also to the Li+-dependent proliferative effect on principal cells. Cellular reorganization of the collecting duct and microcysts are the main pathological findings during Li+ treatment. Their relationship with the urinary concentration defect and an eventual Li+-induced ciliopathy has to been investigated. Li+-induced NDI has been a matter of investigation since the early 1970s. This manuscript reports the latest clinical and experimental findings in combination with the older fundamental results
Up-Regulation of apical Sodium Chloride Cotransporter (NCC) and basolateral Chloride Channels (CLlC-K) are responsible for the maintenance of sodium sensitive hypertension
No full textSGK3: a novel regulator of renal phosphate transport?
No full textPhosphate is a key constituent of several important molecules, and hyperphospatemia has been associated with increased cardiovascular mortality. The kidney plays a crucial role in phosphate metabolism, as it is able to modulate phosphate excretion. Serum- and glucocorticoid-inducible kinase 3 (SGK3) has been shown to regulate a wide variety of transport systems. Bhandaru et al. suggest that SGK3 may have a significant role in the regulation of renal tubular phosphate transport
Serum and urine osmolality: clinical and laboratory features
No full textClinical practice is frequently challenged by limited funding and resources, which finally limit both clinical effectiveness and safety of some therapies. Electrolyte disorders represent serious problems in the clinical management. Nonetheless the osmometer, that is the reference instrument for routine assessment of osmolality, it is only available in a limited number of healthcare facilities. The diagnosis of the leading electrolyte disorders relies therefore on indirect criteria, frequently inaccurate, especially when inappropriately used. According to recent evidences emerged on prevalence, severity and therapeutic approach of patients with electrolyte disturbances such as hyponatremia, the diagnostic appropriateness is now regarded as an essential aspect of the clinical decision making. Recent multidisciplinary guidelines indicate that urinary osmolality is a mainstay in the differential diagnosis of hyponatremic states. Since hyponatremia is commonplace across a broad range of clinical conditions, it is noteworthy that accurate knowledge of the different equations that may be used for its calculation in serum or urine is not widespread among general and hospital physicians. To couple with these clinical issues, this article is aimed to briefly describe the epidemiology and clinics of osmolality disturbances and to suggest some equations that may be useful for its routine assessment in serum or urine, and which can be applied to different categories of patients. The usefulness and reliability of additional indirect methods used in the diagnostic approach of electrolyte disturbances, such as the assessment of urine specific gravity, will also be briefly discussed. The equations that will be proposed have been validated in small sample population studies, but are commonly used as a surrogate or replacement of direct osmolality assessment. A larger multicentric study is hence necessary to validate the clinical use of the equations used for the calculation of serum and urine osmolality
Role of microRNAs in aquaporin 2 regulation
No full textPurpose of review The current review aims to present the most recent achievements on the role of microRNAs (miRNAs) on the kidney function to stimulate research in the field and to expand new emerging concepts. Recent findings The focus is on the role of miRNAs in intercellular communication along the segments of the nephron and on the epi-miRNAs, namely the possibility of some miRNAs to modulate the epigenetic machinery and so gene expression. Indeed, recent evidence showed that miRNAs included in exosomes and released by proximal tubule cells can modulate ENaC activity on cells of collecting duct. These data, although, from in-vitro models open to a novel role for miRNAs to participate in paracrine signaling pathways. In addition, the role of miRNAs as epigenetic modulators is expanding not only in the cancer field, but also in the other kidney diseases. Recent evidence identified three miRNAs able to modulate the AQP2 promoter metilation and showing an additional level of regulation for the AQP2. These evidence can inspire novel area of research both for renal physiology and drug discovery. The diseases involving the collecting duct are still missing disease modifying agents and the expanding miRNAs field could represent an opportunity
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