Regulation of renal urate excretion: A critical review

Maesaka, John K.; Fishbane, Steven

doi:10.1016/s0272-6386(98)70067-8

Cited by 229 publications

(171 citation statements)

References 0 publications

Supporting

Mentioning

157

Contrasting

Unclassified

Order By: Relevance

“…It does, however, strengthen our contention that RSW not only exists but occurs in the absence of clinical cerebral disease (1,6,11,12). It is ironic that patient 1 had RSW without cerebral disease and patient 2 had SIADH with cerebral disease, a diagnosis that would customarily be reversed when applying standard clinical practices.…”

Section: Discussionsupporting

confidence: 64%

“…We demonstrated the value of determining serum urate levels in hyponatremia and fortified our contention that the persistence of hypouricemia and elevated fractional excretion (FE) of urate after correction of hyponatremia differentiate RSW from SIADH, since the hypouricemia and elevated FEurate in SIADH normalize after correction of the hyponatremia (1,5,(11)(12)(13)(14)(15)(16)(17)(18). Differences in urate metabolism, however, are evident only after correction of the hyponatremia and would not contribute to differentiating SIADH from RSW on first encounter.…”

mentioning

confidence: 67%

“…The hypervolemia in SIADH is an unlikely cause as intense volume expansion with saline failed to attain the high FEurates seen in SIADH and RSW (32)(33)(34). This has been reviewed in our in-depth review of renal urate transport (11). The V1 receptor activity of ADH is untenable because ADH levels are still elevated when FEurate normalizes with the correction of hyponatremia (16,17,18,35) and induction of SIADH by dDAVP increased FEurate without V1 activity (36).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

More on Renal Salt Wasting Without Cerebral Disease

Bitew

Imbriano

Miyawaki

et al. 2009

Clinical Journal of the American Society of Nephrology

116

View full text Add to dashboard Cite

Background and objectives: The existence and prevalence of cerebral salt wasting (CSW) or the preferred term, renal salt wasting (RSW), and its differentiation from syndrome of inappropriate antidiuretic hormone (SIADH) have been controversial. This controversy stems from overlapping clinical and laboratory findings and an inability to assess the volume status of these patients. The authors report another case of RSW without clinical cerebral disease and contrast it to SIADH. Design, setting, participants, & measurements: Three patients with hyponatremia, hypouricemia, increased fractional excretion (FE) of urate, urine sodium >20 mmol/L, and concentrated urines were infused with isotonic saline after collection of baseline data.Results: One patient with RSW had pneumonia without cerebral disease and showed increased plasma aldosterone and FEphosphate, and two patients with SIADH had increased blood volume, low plasma renin and aldosterone, and normal FEphosphate. The patient with RSW responded to isotonic saline by excretion of dilute urines, prompt correction of hyponatremia, and normal water loading test after volume repletion. Hypouricemia and increased FEurate persisted after correction of hyponatremia. Two patients with SIADH failed to dilute their urines and remained hyponatremic during 48 and 110 h of saline infusion.Conclusions: The authors demonstrate appropriate stimulation of ADH in RSW. Differences in plasma renin and aldosterone levels and FEphosphate can differentiate RSW from SIADH, as will persistent hypouricemia and increased FEurate after correction of hyponatremia in RSW. FEphosphate was the only contrasting variable at baseline. The authors suggest an approach to treat the hyponatremic patient meeting criteria for SIADH and RSW and changing CSW to the more appropriate term, RSW.

show abstract

Section: Discussionsupporting

confidence: 64%

mentioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

More on Renal Salt Wasting Without Cerebral Disease

Bitew

Imbriano

Miyawaki

et al. 2009

Clinical Journal of the American Society of Nephrology

116

View full text Add to dashboard Cite

show abstract

“…The absence of uricase and the presence of an effective renal urate reabsorption system contribute to higher blood urate levels in humans. Therefore, it was postulated that defects in tubular urate transport cause hypouricemia and decreased renal urate clearance leads to hyperuricemia in most hyperuricemic patients (3).…”

mentioning

confidence: 99%

The Multivalent PDZ Domain-containing Protein PDZK1 Regulates Transport Activity of Renal Urate-Anion Exchanger URAT1 via Its C Terminus

Anzai

Miyazaki

Noshiro

et al. 2004

Journal of Biological Chemistry

172

163

View full text Add to dashboard Cite

The urate-anion exchanger URAT1 is a member of the organic anion transporter (OAT) family that regulates blood urate level in humans and is targeted by uricosuric and antiuricosuric agents (Enomoto, A., Kimura, H., Chairoungdua, A., Shigeta, Y., Jutabha, P., Cha, S. H., Hosoyamada, M., Takeda, M., Sekine, T., Igarashi, T., Matsuo, H., Kikuchi, Y., Oda, T., Ichida, K., Hosoya, T., Shimotaka, K., Niwa, T., Kanai, Y., and Endou, H. (2002) Nature 417, 447-452). URAT1 is expressed only in the kidney, where it is thought to participate in tubular urate reabsorption. We found that the multivalent PDZ (PSD-95, Drosophila discs-large protein, Zonula occludens protein 1) domain-containing protein, PDZK1 interacts with URAT1 in a yeast two-hybrid screen. Such an interaction requires the PDZ motif of URAT1 in its extreme intracellular C-terminal region and the first, second, and fourth PDZ domains of PDZK1 as identified by yeast two-hybrid assay, in vitro binding assay and surface plasmon resonance analysis (K D ‫؍‬ 1.97-514 nM). Coimmunoprecipitation studies revealed that the wildtype URAT1, but not its mutant lacking the PDZ-motif, directly interacts with PDZK1. Colocalization of URAT1 and PDZK1 was observed at the apical membrane of renal proximal tubular cells. The association of URAT1 with PDZK1 enhanced urate transport activities in HEK293 cells (1.4-fold), and the deletion of the URAT1 C-terminal PDZ motif abolished this effect. The augmentation of the transport activity was accompanied by a significant increase in the V max of urate transport via URAT1 and was associated with the increased surface expression level of URAT1 protein from HEK293 cells stably expressing URAT1 transfected with PDZK1. Taken together, the present study indicates the novel role of PDZK1 in regulating the functional activity of URAT1-mediated urate transport in the apical membrane of renal proximal tubules.Urate is the major inert end product of purine degradation in humans and higher primates in contrast to most other mammals because of the genetic silencing of hepatic oxidative enzyme uricase (1, 2). The kidney plays a dominant role in urate elimination; it excretes ϳ70% of the daily urate production. Urate exists primarily as a weak acid at physiological pH (pK a 5.75), and most of it is dissociated in blood and is freely filtered through the glomerulus. Thus, urate enters the proximal tubule in its anionic form, but it hardly permeates the tubular cells in the absence of facilitated mechanisms owing to its hydrophilicity. The transport mechanisms for urate are localized in the proximal tubule. In humans, urate is almost completely reabsorbed, which results in the excretion of ϳ10% of its filtered load. The absence of uricase and the presence of an effective renal urate reabsorption system contribute to higher blood urate levels in humans. Therefore, it was postulated that defects in tubular urate transport cause hypouricemia and decreased renal urate clearance leads to hyperuricemia in most hyperuricemic patients (3).Recently, we have id...

show abstract

“…Urate reabsorption is indirectly coupled to sodium transport by an electroneutral anion exchanger. Anions, such as chloride and organic acid anions, first enter the proximal tubule cell through a sodium-dependent cotransport and move back into the tubule lumen in exchange for uric acid via urate transporter 1 (URAT1) [18]. It is possible that the natriuretic factor might indirectly decrease urate reabsorption through the anion exchanger by decreasing sodium reabsorption, competing with urate for the anion exchanger.…”

Section: Discussionmentioning

confidence: 99%

Hyponatremia associated with demyelinating disease of the nervous system

et al. 2013

View full text Add to dashboard Cite

A 63-year-old man was diagnosed with periodontitis and underwent tooth extraction. Several days later, he suffered a high fever, ischuria, a change in personality, and disorientation. A urologist examined him and found severe hyponatremia (117 mEq/L), and he was then transferred to our hospital. On admission, physical findings revealed dysfunction of the bladder and bowel, altered mental status, and hypovolemia. Blood chemistry showed serum sodium of 120 mEq/L, a serum urate of 1.4 mg/dL, urinary Na of 61 mEq/L, and fractional urate excretion of 16 %. Examination of the cerebrospinal fluid (CSF) showed monocytosis. Magnetic resonance imaging (MRI) of the brain and spinal cord showed multiple lesions characterized by hyperintensity on T2-weighted sequences, suggesting demyelinating disease. His sodium concentration normalized 3 days after volume replacement therapy, and his altered mental status along with the dysfunction of the bladder and bowel were promptly improved after the initiation of high-dose glucocorticoids. Additionally, the abnormal lesions on MRI markedly

show abstract

Regulation of renal urate excretion: A critical review

Cited by 229 publications

References 0 publications

More on Renal Salt Wasting Without Cerebral Disease

More on Renal Salt Wasting Without Cerebral Disease

The Multivalent PDZ Domain-containing Protein PDZK1 Regulates Transport Activity of Renal Urate-Anion Exchanger URAT1 via Its C Terminus

Hyponatremia associated with demyelinating disease of the nervous system

Contact Info

Product

Resources

About