RICHARD JOSEPH JOHNSON

..This pathway unites many of the previous hypotheses on the etiology of hypertension, and offers insights into ways to prevent, ameliorate, or cure the underlying process...

..Although other mechanisms certainly contribute to the pathogenesis of hypertension, the possibility that serum uric acid level may have a major role is suggested by these studies...

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..Finally, we suggest that high intakes of fructose in African Americans may explain their greater predisposition to develop cardiorenal disease, and we provide a list of testable predictions to evaluate this hypothesis...

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..Understanding the pathogenetic pathways mediating renal progression in hypertensive subjects should help identify those subjects at highest risk and may provide insights into new therapeutic maneuvers to slow or prevent progression...

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..If diabetes might result from excessive intake of fructose, then simple public health measures could have a major impact on improving the overall health of our populace...

..These studies provide direct evidence that uric acid may be a true mediator of renal disease and progression...

..Addition of potassium supplements and allopurinol with thiazides might be helpful in the management of metabolic syndrome...

..In conclusion, hyperuricemia has a pathogenic role in the mild tubulointerstitial injury associated with diabetic nephropathy but not glomerular damage in db/db mice. Lowering uric acid may reduce tubulointerstitial injury in diabetes...

..The mechanism may relate to a proinflammatory pathway involving chemokine expression with leukocyte infiltration...

..However, its anti-angiogenic actions suggest countering effects that could partially offset its benefit in chronic kidney diseases...

..A lack of eNOS accelerates both glomerular and tubulointerstitial injury with a loss of glomerular capillaries and peritubular capillaries. Impaired endothelial function is likely a direct risk factor for renal disease...

..In conclusion, lead accelerates chronic renal disease, primarily by raising blood pressure and accelerating microvascular and tubulointerstitial injury...

..The effect is independent of total energy intake and is associated with focal tubulointerstitial injury. These studies may provide a mechanism by which metabolic syndrome causes renal disease...

..Interestingly, inhibition of NO synthesis did not lead to a loss of the preglomerular endothelium, which may relate to the effect of NO blockade to stimulate VEGF synthesis in the adjacent vascular smooth muscle cell...

..Although it provided a survival advantage to early hominoids, hyperuricemia may have a major role in the current cardiovascular disease epidemic...

..Fructose increased intracellular uric acid, and uric acid induced production of MCP-1 as well. In summary, postprandial concentrations of fructose stimulate redox- and urate-dependent inflammatory mediators in proximal tubular cells...

..The feasibility of long-term overexpression of a gene using the AAV serotype 1 vector system in a model of renal disease is also demonstrated...

..We conclude that blocking p38-dependent inflammation may have resulted in enhanced proliferation and increased ERK1/2 activation, and thereby explains the worse renal lesions observed...

..We propose the use of a fructose index to categorize foods and propose studies to determine the effect of low fructose diets as a means to prevent obesity, diabetes, and cardiovascular disease in the population...

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..This study shows a potential mechanism by which UA may deplete NO and cause endothelial dysfunction, particularly under conditions of oxidative stress in which UA is elevated and intracellular glutathione is depleted...

..Thus hyperuricemia induces a renal arteriolopathy in rats that is blood pressure independent and involves the renin-angiotensin system...

..Thus, it is time to reevaluate the role of uric acid as a risk factor for cardiovascular disease and hypertension and to design human studies to address this controversy...

..We propose that subtle acquired renal injury may underlie the etiology of some forms of salt-sensitive hypertension...

..Studies in humans should be performed to address whether lowering uric acid levels will help to prevent this condition...

..Our data indicate that chronic fructose consumption induces leptin resistance prior to body weight, adiposity, serum leptin, insulin, or glucose increases, and this fructose-induced leptin resistance accelerates high-fat induced obesity...

..We conclude that UA-induced arginase activation is a potential mechanism for reduction of NO production in PAEC...

..In conclusion, urinary soluble CD80 is elevated in idiopathic MCD, which could be relevant to both diagnosis and pathogenesis...

..The new method was used to show that smoking, which can induce oxidative stress, is associated with elevated triuret levels in urine. Thus, the method may be helpful in identifying pathways of oxidative stress in biological samples...

..These reactive intermediates could possibly explain how uric acid contributes to the pathogenesis of diseases such as the metabolic syndrome and hypertension...

..CONCLUSION: OPN partially mediates arteriolopathy, early macrophage recruitment and fibrosis in murine CsA nephropathy. OPN also may be involved in CsA associated neurotoxicity...

..10 to 103.59% and 98.74 to 106.12% for in vivo and in vitro analyses, respectively. This study demonstrates that intracellular levels of UA can be measured using LC-MS/MS with isotope labeled UA as an internal standard...

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..Uric acid has been reported to be a risk factor for the development of chronic kidney disease; however, no study has examined whether uric acid may confer a risk for acute kidney injury...

..We propose studies to investigate the role of uric acid in pulmonary hypertension and to determine if lowering serum uric acid may have clinical benefit in this condition...

..The ions of m/z 352 were characterized as the PBN-triuretcarbonyl radical adduct and the m/z 223 ion was identified as the PBN-aminocarbonyl radical adduct. Their mechanism of formation is discussed...

..This study was undertaken to determine the role of eNOS in the development of diabetic retinopathy (DR), by investigating the functional consequences of its deficiency in the diabetic state...

..Because TSP-1 is a major antiangiogenic molecule and an activator of TGF-beta1, this provides an important insight to the mechanism by which TGF-beta1 may mediate interstitial fibrosis and progressive renal disease...

..These data suggest that fructose induces inflammatory changes in vascular cells at physiologic concentrations...

..It is proposed that fructose- and purine-rich foods that have in common the raising of uric acid may have a role in the epidemic of metabolic syndrome and renal disease that is occurring throughout the world...

..Furthermore, we suggest that the recent increased intake in the American diet of fructose, which is a known cause of hyperuricemia, may be contributing to the current epidemic of obesity and diabetes...

..Thus, an attractive hypothesis could be that THP would bind to uric acid in the distal tubule, and decrease its subsequent reabsorption in the distal nephron...

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..Natriuretic peptides have been shown to have favorable renal effects. However, recent evidence suggests potential renal side effects in patients with congestive heart failure...

..In conclusion, consumption of a high-fructose diet greatly accelerates progression of chronic kidney disease in the rat remnant kidney model...

..It is suggested that studies are needed to investigate the role of chronic hyperuricemia on renal outcomes after acute tubular injury...

..These results may provide new insights into the understanding of the mechanism of diabetic vascular disease...

..In progressive renal disease, such as cyclosporine nephropathy and remnant kidney in rat, uric acid accelerated the progression of renal disease. Thus, we concluded that uric acid is not a simple marker, but a cause of renal disease...

..CONCLUSION: Both afferent arteriolar disease and subtle tubulointerstitial inflammation and injury occur early in hypoxic rats. These changes may predispose these animals to persistent hypertension...

..In this review, we discuss the clinical and experimental evidence for a causal role of hyperuricemia in renal diseases and potential relationships of hyperuricemia with metabolic syndrome...

..Previously, we showed that soluble uric acid directly stimulated the redox-dependent proinflammatory signaling in adipocytes. In this study we demonstrate the role of hyperuricemia in the production of key adipokines...

..In conclusion, the absence of the AT(1) receptor is associated with marked renal alterations in vasoactive, profibrotic, and immune mediators with an inflammatory pattern favoring a Th1 phenotype...

..Therefore, we hypothesized that aging attenuates vasodilatory responses in the kidney. These changes may be mediated by a loss of nitric oxide and endothelial-derived hyperpolarizing factor (EDHF)...

..Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid...

..It was postulated that endothelial dysfunction should predict nephropathy and that correction of the dysfunction may prevent these important complications...

..Thus TGF-beta and hypoxia act via additive/synergistic but distinct pathways to stimulate VEGF in proximal tubular cells, a finding that may be important in understanding how VEGF is stimulated in renal disease...

..Recent studies have shown that VEGF-A as well as TSP-1 is regulated by transforming growth factor-beta1 (TGF-beta1), but the mechanism remains unclear...

..Thus, our study supports the hypothesis that MCD and FSGS represent two different diseases rather than a continuum of one disease. Urinary CD80 excretion may be a useful marker to differentiate between MCD and FSGS...

..This training grant will support a focused program for training promising candidates in basic, translational, and clinical research which should help them prepare for an academic career in nephrology. ..

..This training grant will support a focused program for training promising candidates in basic, translational, and clinical research which should help them prepare for an academic career in nephrology. ..