Seminars in nephrology
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Water reabsorption in the renal collecting duct is regulated by the antidiuretic hormone vasopressin (AVP). When the vasopressin V2 receptor, present on the basolateral site of the renal principal cell, becomes activated by AVP, aquaporin-2 (AQP2) water channels will be inserted in the apical membrane, and in this fashion, water can be reabsorbed from the pro-urine into the interstitium. The essential role of the vasopressin V2 receptor and AQP2 in the maintenance of body water homeostasis became clear when it was shown that mutations in their genes cause nephrogenic diabetes insipidus, a disorder in which the kidney is unable to concentrate urine in response to AVP. This review describes the current knowledge on AQP2 mutations in nephrogenic diabetes insipidus.
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Acute kidney injury (AKI), previously referred to as acute renal failure, represents a common and devastating problem in clinical medicine. Despite significant improvements in therapeutics, the mortality and morbidity associated with AKI remain high. A major reason for this is the lack of early markers for AKI, and hence an unacceptable delay in initiating therapy. ⋯ It is also probable that the AKI panels will distinguish between the various etiologies of AKI and predict clinical outcomes. It will be important in future studies to validate the sensitivity and specificity of these biomarker panels in clinical samples from large cohorts and from multiple clinical situations. Such studies will be facilitated markedly by the development of commercial tools for the reproducible measurement of biomarkers across different laboratories.
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Hyponatremia is a frequent and symptomatic electrolyte disorder for which specific treatments have been lacking. Hyponatremia is attributable to nonosmotic vasopressin stimulation and continued increased fluid intake. In the past, peptidic derivatives of arginine vasopressin proved that blockade of vasopressin V-2 receptors served to improve hyponatremia, however, these antagonists had intrinsic agonistic activity, too. ⋯ In animal and clinical studies all of the agents were able to correct water retention and hyponatremia in a dose-dependent manner. There was no tachyphylaxis, even when the agents were given over many weeks. It is expected that the clinical use of the agents will lead to a major improvement in the treatment of hyponatremia.
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Seminars in nephrology · Nov 2005
Review Comparative StudyTreatment of hypertension in chronic kidney disease.
Chronic kidney disease (CKD) is a major public health problem in the United States. It is estimated that nearly 20 million Americans have some degree of chronic kidney disease defined as an estimated glomerular filtration rate of less than sixty milliliters per minute or evidence of kidney damage by imaging study, biopsy, biochemical testing or urine tests with an estimated glomerular filtration rate more than sixty milliliters per minute. Hypertension is present in more than 80% of patients with CKD and contributes to progression of kidney disease toward end stage (ESRD) as well as to cardiovascular events such as heart attack and stroke. ⋯ Thereafter, beta-blockers, calcium channel blockers, apha blockers and alpha 2 agonists (e.g. clonidine) and finally vasodilators (e.g. minoxidil) should be added to achieve blood pressure goal. Combinations of ACEi and ARB are helpful in reducing proteinuria and may also lower blood pressure further in some some cases. Blood pressure should be monitored closely in hypertensive patients with CKD and both clinic and home blood pressure measurements may help the clinician adjust treatment.
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Seminars in nephrology · Nov 2005
Review Comparative StudyPredictors of cardiovascular death in ESRD.
End stage renal disease (ESRD) is a situation with a cardiovascular risk profile of almost unique severity. While traditional risk factors dominate the scene in the general population, non traditional risk factors like inflammation (high C Reactive Protein, CRP), high brain natriuretic peptide, as an expression of left ventricular hypertrophy and left ventricular dysfunction, and accumulation of the endogenous inhibitor of the NO synthase, asymmetric dimethyl arginine are all markers of high CV risk of ESRD patients. To obtain a quantitative insight on the predictive power of traditional and emerging risk factors in ESRD, we performed a detailed multivariate survival analysis in the cardiovascular risk extended evaluation (CREED) cohort database. ⋯ In conclusion, traditional risk factors explain about half of all-cause and cardiovascular mortality variation in the ESRD population. The combined use of 2 biomarkers reflecting inflammation and left ventricular mass and function increases by about one fifth the explained mortality variation in this population. Biomarkers give information beyond that provided by traditional risk factors and therefore represent an useful adjunct for the definition of the risk profile of ESRD patients.