Uric Acid and the Kidney: Urate Transport, Stone Disease and Progressive Renal Failure

Capasso, Giovambattista; Jaeger, P; Robertson, WG; Unwin, Robert J.

doi:10.2174/138161205774913219

Cited by 31 publications

(23 citation statements)

References 51 publications

(60 reference statements)

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“…So, URAT1 mediated transport is accounted for all the luminal urate influx into the PT cells. [11][12][13] In this study, in the isolated PT segments of both exercising and hyperuricemic rats, URAT1 mediated influx was found to be increased significantly in association with elevated urinary urate excretion ( Figure 1, Table 1). Although the exercise-induced enhancement in tubular urate reabsorption has been known, neither in exercisers nor in hyperuricemics, the involvement of URAT1 activity in this reabsorption was previously demonstrated.…”

Section: Discussionsupporting

confidence: 49%

“…11 Interestingly however, despite its potential harm, kidneys are not in a hurry to eliminate uric acid and its handling by PT cells. 12,13 According to four-component hypothesis, following its glomerular filtration, 98% of filtered urate is reabsorbed from the S1 segment of the PT (presecretory reabsorption). Subsequently, 50% of urate is then secreted by the S2 segment into the lumen (secretion).…”

Section: Introductionmentioning

confidence: 99%

“…Eventually, 40% of urate is reabsorbed once again (postsecretory reabsorption). 12,13 Possibly, being one of the free radical scavengers, its tubular recirculation contributes to the efficient use of urate before being fully eliminated into the urine.…”

Section: Introductionmentioning

confidence: 99%

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Exercise-induced changes in renal URAT1 activity and expression in rats

Cırrık¹,

Yavuzer²,

Öner³

2010

Renal Failure

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During exercise, the plasma urate levels and urinary excretion increase due to the enhanced purine degradation in skeletal muscle. Although urate transporter-1 (URAT1) is the main transporter responsible for the reabsorption of filtered urate, potential changes in its activity and expression during exercise have not been studied yet. Therefore, the effect of heavy muscle activity on renal URAT1 activity and expression was investigated in this study. Wistar rats were used in the study and the experimental design consisted of three groups: a control group, an exercise group where animals were exhausted once a day for 5 days, and a hyperuricemia group, which was induced by an uricase inhibitor, oxonic acid. URAT1 activity measurements were performed in isolated proximal tubule segments and expression of URAT1 mRNA and protein levels were determined by the reverse transcription polymerase chain reaction and western blot analyses, respectively. Increased citrate synthase activity in soleus muscle of exercised animals proved the efficiency of our exercise protocol. Proteinuria, glucosuria, and hypoglycemia were observed only in exercised animals; however, plasma and urinary urate levels were found to be elevated in both exercising and hyperuricemia groups. Moreover, in both of the groups URAT1 transporter activity was found to be increased despite the significant decrease in URAT1 protein levels. Considering the similar changes of urate metabolism observed in both exercising and hyperuricemic rats, our results suggest that exercise-induced changes in URAT1 expression and activity depend on the increased urate concentration in plasma.

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Section: Discussionsupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

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Exercise-induced changes in renal URAT1 activity and expression in rats

Cırrık¹,

Yavuzer²,

Öner³

2010

Renal Failure

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“…These observations showed that increased TAS values seem to be dependent mainly on increased uric acid levels, which explains the lower test results in the control group. In vitro experiments have shown uric acid to be a powerful scavenger of reactive oxygen species [38] ; however, hyperuricemia is an accepted risk factor and marker of chronic cardiovascular disease [39,40] ; therefore, the TAS test which is influenced by uric acid seems to be an unreliable method for assessing the antioxidant capacity of patients with CKD. These findings additionally emphasize that in order to avoid false conclusions, the proper choice of method for describing oxidative stress is very important.…”

Section: Discussionmentioning

confidence: 99%

Estimation of Oxidative Stress Markers in Chronic Kidney Disease

Kuchta¹,

Pacanis²,

Kortas-Stempak³

et al. 2010

Kidney Blood Press Res

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Changes mediated by oxidative stress are thought to be involved with atherosclerosis in patients with chronic kidney disease (CKD). The purpose of this study was to analyze the markers of oxidative damage and the activity of antioxidative enzymes as well as the total antioxidant capability in patients with different stages of CKD, both conventionally treated and dialyzed. We evaluated the oxidative modification of lipids (by oxidized low-density lipoprotein and malonodialdehyde levels) and proteins (by advanced oxidation protein products level). We also assessed the activity of paraoxonase-1 and glutathione peroxidases and total antioxidant status. Compared with the control group, the uremic patients, both dialyzed and nondialyzed, had higher levels of all studied plasma oxidative stress markers and decreased activity of antioxidative enzymes. Our results lead us to conclude that oxidative stress seems to be related rather to the uremic state than to the dialysis treatment. We also showed that estimating total antioxidant status in a simple test is unreliable for assessing the antioxidant ability of patients with CKD.

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“…On the positive side, urate is a potent scavenger of free radicals (Hediger et al 2005), helping to protect from oxidative damage. Unfortunately, because of its relatively low aqueous solubility, urate crystals may form -leading to renal stones, gout, and chronic renal failure (Capasso et al 2005;Hediger et al 2005). Moreover, in the human, mutational silencing leads to a lack of urate oxidase enzyme activity, resulting in plasma urate concentrations higher than in other species (240-350 μM) (Capasso et al 2005;Enomoto and Endou 2005;Hediger et al 2005), increasing potential for stone formation.…”

Section: Substrate Specificitymentioning

confidence: 99%

Physiology, structure, and regulation of the cloned organic anion transporters

2008

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Abstract1. The transport of negatively charged drugs, xenobiotics, and metabolites by epithelial tissues, particularly the kidney, plays critical roles in controlling their distribution, concentration, and retention in the body. Thus, organic anion transporters (OATs) impact both their therapeutic efficacy and potential toxicity.2. This review summarizes current knowledge of the properties and functional roles of the cloned OATs, the relationships between transporter structure and function, and those factors that determine the efficacy of transport. Such factors include plasma protein binding of substrates, genetic polymorphisms among the transporters, and regulation of transporter expression.3. Clearly, much progress has been made in the decade since the first OAT was cloned. However, unresolved questions remain. Several of these issues -drug-drug interactions, functional characterization of newly cloned OATs, tissue differences in expression and function, and details of the nature and consequences of transporter regulation at genomic and intracellular sites -are discussed in the concluding Perspectives section.

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Uric Acid and the Kidney: Urate Transport, Stone Disease and Progressive Renal Failure

Cited by 31 publications

References 51 publications

Exercise-induced changes in renal URAT1 activity and expression in rats

Exercise-induced changes in renal URAT1 activity and expression in rats

Estimation of Oxidative Stress Markers in Chronic Kidney Disease

Physiology, structure, and regulation of the cloned organic anion transporters

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