Where is uric acid filtered

Additionally, SUA concentrations may also be different according to the type of diabetes [ 35 ]. Levels of SUA are often lower in patients with type 1 diabetes compared with their nondiabetic peers [ 36 ], which may be induced by glycosuria. But whether GLUT9 is involved in this phenomenon has not been confirmed. In contrast, type 2 diabetes is often correlated to higher SUA concentrations [ 37 , 38 ], although some studies have reported the presence of hypouricemia in type 2 diabetes [ 39 , 40 ].

It is likely that the presence of insulin resistance and hyperinsulinemia stimulate the renal tubular cells to reabsorb sodium coupling with uric acid [ 35 ]. The failure to detect a change in urate excretion in diabetes in our study may be explained by the fact that increase in FEur in all the studies was related to glycosuria, not diabetes per se, which may not be prominent in a well-treated population.

Currently, the association of albuminuria with urinary uric acid excretion has not been extensively studied. Many studies focused on the association between albuminuria and SUA, and documented that SUA is positively associated with albuminuria and predicts the development of albuminuria, including general population [ 15 ], diabetes mellitus [ 41 ], and hypertension [ 18 ].

Moreover, in another study conducted in general population, Scheven [ 43 ] found a positive association of albuminuria with tubular uric acid reabsorption, independent of potential confounders such as. As to the negative association between h Uur, Cur and UACR, it may well be that albumin or concomitant non-albumine compounds, such as plasmin, found in urinary of albuminuric subjects, can specifically upregulate or downregulate the expression of genes encoding for tubular uric acid transporters.

This phenomenon has been shown for other, non-uric acid membrane transporters in tubular proximal epithelial cells [ 20 , 21 , 22 , 23 ].

Since the patients with CKD are in steady state in these studies, this must reflect either a change in uric acid production or an increase in non-renal excretory pathways induced by metabolic changes, such as protein-energy wasting, accumulated uremic toxins, dyslipidemia and insulin resistance, in severe CKD [ 9 , 12 ]. In genetic analyses of CKD cohorts, Bhatnagar et al. Their data supported the notion that uric acid transporters in remote organs intestine versus kidney may regulate serum uric acid levels, especially after acute or chronic organ damage, as suggested in the Remote Sensing and Signaling Hypothesis [ 45 ].

As far as we know, it is possible that actually uric acid changes proteinuria or that proteinuria and uric acid are dependent on the same variable. A well-designed study is needed to verify a causal relation between albuminuria and uric acid.

As has been previously described, with increasing severity of CKD, FEur of residual nephrons increased in order to maintain homeostasis of uric acid. This finding may actually reflect the compensation of residual nephrons or may arise from a presently undefined influence of uremia per se. Recently, researcher Andrew Rule and colleagues have developed a method to determine GFR at the level of the single nephron, and found that CKD risk factors were associated with increased single-nephron GFR, but they thought uric acid levels were associated with lower nephron number rather than single-nephron GFR, leading to a lower total GFR [ 46 ].

Indeed, our study demonstrated that UACR was negatively associated with h Uur and Cur, but not with FEur, after adjusting for confounders, suggesting that albuminuria may be associated with total uric acid excretion but was not strong enough to be correlated with the residual tubular excretion of uric acid in CKD patients.

Accordingly, our findings indicate that in clinical practice, it is better to use h Uur and Cur to estimate the capacity of renal uric acid excretion in CKD patients, while FEur reflects more on the compensatory residual renal tubular function and should be valued with caution in patients with reduced kidney function.

Our study has some limitations that need to be mentioned. First, the cross-sectional nature of the present study makes it hard to determine any causal relationship. Second, the effect of specific etiology of CKD was not explored, since the extent of specific renal tubular damage was different. Finally, UACR was measured once, which is known to be subject to more variability.

Influencing factors of renal uric acid excretion is complicated, and albuminuria, evaluated as UACR, was negatively correlated with h Uur and Cur after adjusting for multiple confounders in Chinese CKD patients. This phenomenon may explain in part the association between albuminuria and serum uric acid.

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Clin Kidney J. Nigam SK. What do drug transporters really do? Nat Rev Drug Discov. Carney EF. Nat Rev Nephrol. Download references. It supported the analysis, interpretation of data and writing of the manuscript. You can also search for this author in PubMed Google Scholar. All authors read and approved the final manuscript. Correspondence to Jing Xiao or Zhibin Ye. Our study was approved by the ethics committee of Huadong hospital affiliated to Fudan University, and conformed to the ethics guidelines, including safety, fairness, informed consent, rights protection of the subject, and secrecy in our research.

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