摘要:

Experiments in animal models suggest that correcting abnormalities in lipid metabolism could help slow the rate of functional decline in patients with chronic progressive renal disease. Circumstantial evidence in humans also suggests that lipids may play a role in the pathogenesis of glomerulosclerosis. Nevertheless, large controlled clinical trials examining the effect of lipid-lowering strategies on renal disease progression have not been carried out. However, the recent development of antilipemic agents that appear to be safe and effective in patients with renal disease should make it possible to determine whether treating hyperlipidemia will reduce the rate of renal disease progression.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Recent studies using animal models of glomerulonephritis indicate that steady-state levels of mRNAs encoding basement membrane proteins are frequently, but not universally, increased in parallel and that mRNAs encoding interstitial matrix proteins represent a separate set of genes that may also display coordinate regulation. A variety of maneuvers that ameliorate progressive glomerulosclerosis may act, at least in part, by suppressing glomerular cell matrix protein gene expression. The observed coordinate regulation of matrix genes may be a consequence of shared genetic regulatory sequences. Future therapies designed to retard glomerulosclerosis may take advantage of similarities among the extracellular mediators and regulatory sequences that influence matrix gene expression.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Experimental data suggest that the recovery of renal function after ischemic or nephrotoxic acute renal failure is due to a replicative repair process dependent on predominantly paracrine release of growth factors. These growth factors promote renal proximal tubule cell proliferation and a differentiation phase dependent on the interaction between tubule cells and basement membrane. These insights identify the molecular basis of renal repair in ischemic and nephrotoxic acute renal failure and may lead to potential therapeutic modalities that accelerate renal repair and lessen the morbidity and mortality associated with these renal disease processes.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Ischemia-reperfusion injury occurs in many organs and is the underlying cause of many disease processes, including myocardial infarction, stroke, and acute renal failure, which in total are responsible for the majority of deaths seen in developed countries. Most of the injury seen with this process is associated with the reperfusion phase in which the blood flow to the ischemic tissues is reinstituted. This reperfusion phase is associated with the formation of reactive oxygen species (ROS) in the tissues, and the sources of these oxidants are both the neutrophil as well as parenchymal cells such as endothelium. In the kidney as well as other organs, antioxidant therapy is protective, suggesting an important role for these agents. However, there is emerging evidence that ROS are not solely responsible for the reperfusion injury. In many of the kidney models of ischemia-reperfusion, antioxidants are only partially effective in ameliorating the functional and morphologic alterations. Furthermore, in vitro, ROS do not appear to be primarily involved in the killing of renal tubular epithelial cells, which is the morphologic hallmark of acute renal failure. Thus, reperfusion injury, like other types of tissue injury, appears to be mediated by more than one class of inflammatory mediator.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Despite several decades of research interest and productivity, many aspects of hyponatremia and hypo-osmolar disorders remain incompletely understood. Among these aspects are questions relating to the morbidity and mortality actually attributable to hyponatremia, possible hormonal and gender-associated risk factors underlying susceptibility to neurologic complications from hyponatremic encephalopathy, the stimuli to arginine vasopressin secretion in some atypical subsets of patients with the syndrome of inappropriate antidiuretic hormone secretion and other hyponatremic disorders, the contributions of natriuresis and natriuretic peptides to hyponatremic states, the pathologic determinants of brain demyelination that sometimes follow rapid correction of hyponatremia, and appropriate treatment guidelines for patients with acute and chronic hyponatremia. The recent literature confirms that acceptable answers to these questions and others are still not available, and a better understanding of basic issues regarding the pathophysiology of hyponatremia is needed. Several recent advances stand out as being likely to enhance our future understanding of hyponatremia and hypo-osmolar states. First are studies of cellular mechanisms of volume regulation in kidney and brain tissue in response to changes in osmolality. Many, though clearly not all, clinical observations can be better understood by considering them in the conceptual framework provided by knowledge of cell and body fluid compartment volume regulation. Second is the elucidation of several important protein structures via complementary DNA cloning, including the arginine vasopressin V^ and V2 receptors, several organic osmolyte transporters, and the CHIP28 water channel. Future application of these new tools to carefully designed and executed physiologic studies will likely add considerable new knowledge to our understanding of hyponatremia. Third is the development and increasing application of nuclear magnetic resonance spectroscopy and imaging methods that will allow more detailed analyses of acute changes in brain metabolism during hyponatremia and following correction. Finally, the recent development of nonpeptide antagonists to arginine vasopressin V^ and V2 receptors should enable clinical studies to assess more accurately the contribution of arginine vasopressin-induced antidiuresis to hyponatremia and more importantly holds the promise of more effective therapies for hyponatremic patients.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The natriuretic peptide system, which comprises at least four related proteins: atrial natriuretic peptide; brain natriuretic peptide; C-type natriuretic peptide; and urodilatin, exerts important influences on central and renal hemodynamics and renal sodium excretion. Recent studies have examined the role of these peptides in the pathophysiology of edema formation in congestive heart failure, cirrhosis, and nephrotic syndrome and have explored the therapeutic value of manipulating their metabolic pathways. One striking feature appears common to all three states ie, a blunted response to the natriuretic effect of atrial natriuretic peptide, which becomes particularly severe in the late stages of each disease. However, whereas in congestive heart failure and cirrhosis the main mechanism responsible is enhanced proximal tubular reabsorption of sodium resulting in reduced distal sodium delivery to the major site of atrial natriuretic peptide action, in nephrotic syndrome a biochemical defect in the cellular response to atrial natriuretic peptide within the kidney is a more likely explanation. Most information regarding the efficacy of therapies that alter the metabolism or the local action of atrial natriuretic peptide pertain to congestive heart failure. However, continued investigation in this area may ultimately lead to interventions that play a valuable role in the future management of all three edematous states.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

FK506, a new macrolide immunosuppressant agent, is approximately 100 times more potent than cyclosporine. Early clinical trials demonstrated FK506 to be effective in reversing refractory rejection in liver, kidney, and heart transplantation. Like cyclosporine, FK506 has significant nephrotoxicity. The clinical presentation and morphology of FK506 nephrotoxicity are identical to those of cyclosporine. Many animal and in vitro studies suggest that FK506 may be less nephrotoxic than cyclosporine. Studies in humans after transplantation have not confirmed this advantage. FK506 has pursued the same pattern in drug development as cyclosporine, with progressive dose reductions over the years. Studies from this early developmental period suggest that the nephrotoxicity of FK506 and cyclosporine in clinical use are approximately equivalent. Further refinement in the clinical use of FK506 will likely reduce its toxicity further. Appropriate studies conducted at that stage will determine which drug possesses less nephrotoxicity.

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID

ISSN:1062-4821    

出版商:OVID    

年代:1993

数据来源: OVID