Uric Acid Transport in Renal Failure A Review

Gm, Danovitch

doi:10.1159/000180160

Cited by 12 publications

(11 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast, if hyperuricemia was due to renal insufficiency, the fractional excretion of uric acid would have been elevated. 21 Hyperuricemia resulting from increased proximal tubular reabsorption of uric acid has been seen in other genetic syndromes associated with salt wasting and mild volume depletion such as uromodulin-associated kidney disease. 22 (I and J) Electron microscopy of stably transfected HEK293 cell lines showing (I) overview of the WT REN -expressing cell with numerous electron-dense granules (arrows) and (J) considerable distensions of ER cisternae (asterisk) observed frequently in DL16 REN cells.…”

Section: Discussionmentioning

confidence: 99%

Dominant Renin Gene Mutations Associated with Early-Onset Hyperuricemia, Anemia, and Chronic Kidney Failure

Živná

Hůlková

Matignon

et al. 2009

The American Journal of Human Genetics

149

View full text Add to dashboard Cite

Through linkage analysis and candidate gene sequencing, we identified three unrelated families with the autosomal-dominant inheritance of early onset anemia, hypouricosuric hyperuricemia, progressive kidney failure, and mutations resulting either in the deletion (p.Leu16del) or the amino acid exchange (p.Leu16Arg) of a single leucine residue in the signal sequence of renin. Both mutations decrease signal sequence hydrophobicity and are predicted by bioinformatic analyses to damage targeting and cotranslational translocation of preprorenin into the endoplasmic reticulum (ER). Transfection and in vitro studies confirmed that both mutations affect ER translocation and processing of nascent preprorenin, resulting either in reduced (p.Leu16del) or abolished (p.Leu16Arg) prorenin and renin biosynthesis and secretion. Expression of renin and other components of the renin-angiotensin system was decreased accordingly in kidney biopsy specimens from affected individuals. Cells stably expressing the p.Leu16del protein showed activated ER stress, unfolded protein response, and reduced growth rate. It is likely that expression of the mutant proteins has a dominant toxic effect gradually reducing the viability of renin-expressing cells. This alters the intrarenal renin-angiotensin system and the juxtaglomerular apparatus functionality and leads to nephron dropout and progressive kidney failure. Our findings provide insight into the functionality of renin-angiotensin system and stress the importance of renin analysis in families and individuals with early onset hyperuricemia, anemia, and progressive kidney failure.

show abstract

Section: Discussionmentioning

confidence: 99%

Dominant Renin Gene Mutations Associated with Early-Onset Hyperuricemia, Anemia, and Chronic Kidney Failure

Živná

Hůlková

Matignon

et al. 2009

The American Journal of Human Genetics

149

View full text Add to dashboard Cite

show abstract

“…Given the fact that hyperuricemia in CKD is attributable to the decline in UA clearance [80,81], a uricosuric agent can be effective in lowering SUA. A potential drug of benzbromarone has not been widely used probably because of a fear to increase risk of urolithiasis and prejudice of thereby causing the kidney damage in addition to the liver damage.…”

Section: Benzbromaronementioning

confidence: 99%

Time to target uric acid to retard CKD progression

et al. 2016

View full text Add to dashboard Cite

Uric acid (UA) remains a possible risk factor of chronic kidney disease (CKD) but its potential role should be elucidated given a fact that multidisciplinary treatments assure a sole strategy to inhibit the progression to end-stage renal disease (ESRD). In clinical setting, most observational studies showed that elevation of serum uric acid (SUA) independently predicts the incidence and the development of CKD. The meta-analysis showed that SUA-lowering therapy with allopurinol may retard the progression of CKD but did not reach conclusive results due to small-sized studies. Larger scale, randomized placebo-controlled trials to assess SUA-lowering therapy are needed. Our recent analysis by propensity score methods has shown that the threshold of SUA should be less than 6.5 mg/dL to abrogate ESRD. In animal models an increase in SUA by the administration of oxonic acid, uricase inhibitor, or nephrectomy can induce glomerular hypertension, arteriolosclerosis including afferent arteriolopathy and tubulointerstitial fibrosis. The ever-growing discoveries of urate transporters prompt us to learn UA metabolism in the kidney and intestine. One example is that the intestinal ABCG2 may play a compensatory role at face of decreased renal clearance of UA in nephrectomized rats, the trigger of which is not a uremic toxin but SUA itself. This review will summarize the recent knowledge on the relationship between SUA and the kidney and try to draw a conclusion when and how to treat asymptomatic hyperuricemia accompanied by CKD. Finally we will address a future perspective on UA study including a Mendelian randomization approach.

show abstract

“…We speculate that this family suffers from a primary interstitial nephropathy which is accompanied by a subtle defect in tubular excretion of urate. A few similar observations have been reported in literature which suggests that dominantly inherited interstitial nephropathy with hyperuricemia and gout represents a distinct entity.Serum urate is usually maintained close to normal levels in chronic renal disease, and especially in chronic inter stitial nephropathy [7], since reduction of the glomerular filtration and hence of the filtered load is largely com pensated by increased fractional tubular excretion of urate [2], Severe hyperuricemia and gout, therefore, rarely occur in chronic renal insufficiency [20], In 1972, we reported on a family with 3 affected members, a mother and 2 daughters, who suffered from an interstitial nephropathy with dis proportionate hyperuricemia, which had led to repeated attacks of gout in the mother since the age of 20 years [9]. A few similar observations have been published [3,10,15,18,20,21,[24][25][26][27] which suggest that familial interstitial nephropathy with hyperuricemia represents a distinct en tity [11], The family mentioned above has now been fol lowed for 11 years, and the clinical data and renal biopsy findings will be described.…”

mentioning

confidence: 99%

Familial Nephropathy with Hyperuricemia and Gout

Leumann¹,

Wegmann²

1983

Nephron

View full text Add to dashboard Cite

Chronic interstitial nephropathy with disproportionate hyperuricemia (serum uric acid 10.5–14.8 mg/dl [625–880 µmol/l] at a GFR of 40 ml/min/1.73 m²) was observed in 2 girls and their mother who suffered from gout since the age of 20 years. Urinary excretion of uric acid was normal. Renal biopsies in the 3 patients showed focal tubulointerstitial nephropathy. Absolute values of GFR remained stable in the 2 pediatric patients over a period of 10 years, whereas the older patient required dialysis at the age of 34 years. We speculate that this family suffers from a primary interstitial nephropathy which is accompanied by a subtle defect in tubular excretion of urate. A few similar observations have been reported in literature which suggests that dominantly inherited interstitial nephropathy with hyperuricemia and gout represents a distinct entity.

show abstract

Uric Acid Transport in Renal Failure A Review

Cited by 12 publications

References 21 publications

Dominant Renin Gene Mutations Associated with Early-Onset Hyperuricemia, Anemia, and Chronic Kidney Failure

Dominant Renin Gene Mutations Associated with Early-Onset Hyperuricemia, Anemia, and Chronic Kidney Failure

Time to target uric acid to retard CKD progression

Familial Nephropathy with Hyperuricemia and Gout

Contact Info

Product

Resources

About