• Users Online: 87
  • Print this page
  • Email this page


 
 
Table of Contents
REVIEW ARTICLE
Year : 2018  |  Volume : 4  |  Issue : 3  |  Page : 76-77

Hyperuricemia – Metabolic Impact on the Kidney


Co-Chair Dialysis and Director, Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, India

Date of Web Publication23-Apr-2019

Correspondence Address:
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrnm.jrnm_12_19

Get Permissions


How to cite this article:
Bhalla AK. Hyperuricemia – Metabolic Impact on the Kidney. J Renal Nutr Metab 2018;4:76-7

How to cite this URL:
Bhalla AK. Hyperuricemia – Metabolic Impact on the Kidney. J Renal Nutr Metab [serial online] 2018 [cited 2019 May 19];4:76-7. Available from: http://www.jrnm.in/text.asp?2018/4/3/76/256814




  Introduction Top


Uric acid has been implicated in the pathophysiology of renal disease; however, renal clearance makes a causal relationship difficult to prove. Uric acid is definitively linked to the development of chronic kidney disease and can be a poor prognostic factor for the development of acute renal failure, as well. However, further human research is needed before predictive models utilizing uric acid can be developed and used in the clinical setting.

Uric acid is the final oxidation product of purine metabolism and is renally excreted.[1] Therefore, elevated serum uric acid levels are seen in patients with reduced glomerular filtration rate (GFR). However, in recent years, it has been proposed that uric acid itself plays a causal role in the pathophysiology of chronic kidney disease and possibly in acute kidney injury. Review of the literature demonstrates uric acid-related cellular changes that contribute to renal disease.


  Pathophysiology of Uric Acid in the Development and Progression of Renal Disease Top


Studies performed on rats have demonstrated that, in the presence of hyperuricemia, there are fundamental changes in the renal vasculature. Ryu et al. found that uric acid decreased the expression of E-cadherin in epithelial cells, resulting in a loss of cell-to-cell contact in the renal tubular cells of rats. Without cell-to-cell contact, epithelial cells are unable to coordinate efforts to secrete substances needed to increase renal blood flow such as nitric oxide.[2]

In addition, a recent study utilizing immortalized proximal tubular epithelial cells from normal adult human male kidney has demonstrated that increasing levels of uric acid cause NAPDH-dependent oxidative changes which promote apoptosis.[3] This finding sheds light on the connection between hyperuricemia and tubulointerstitial renal damage.

Similarly, a later study by Turak et al. examined 112 patients with essential hypertension. Patients without baseline renal dysfunction had statistically higher baseline serum uric acid levels compared to those in the control group, suggesting a causal relationship between serum uric acid level and the development of essential hypertension, regardless of baseline renal function and therefore unrelated to renal clearance.[4]


  Hyperuricemia and Risk of Development of Renal Disease Top


While hyperuricemia may or may not predispose a patient to developing de novo renal disease, studies have indicated that the development of hyperuricemia leads to progression of existing renal disease and an increase in mortality. Odden et al. divided 10,956 patients into three groups based on sex-specific outcomes: lowest, middle, and highest percentiles of uric acid levels (<25th, 25th–75th, and >75th percentile) with an outcome of cardiovascular death and all-cause mortality. The lowest risk of cardiovascular and all-cause mortality occurred in women with the lowest uric acid levels, while the highest risk for cardiovascular and all-cause mortality occurred in both men and women with the highest uric acid levels. However, once renal function was accounted for, this no longer held true and there was no statistical difference for the risk for cardiovascular and all-cause mortality between those with high, intermediate, and low uric acid levels. This may suggest that estimated GFR (eGFR) and uric acid are inherently linked and may be in the same causal pathway affecting cardiovascular mortality.[5]

Weiner et al. examined approximately 1600 participants who had an eGFR between 15 and 60 mL/min/1.73 m2 and had a mean follow-up of approximately 9 years with approximately half of participants reaching one of the primary endpoints of myocardial infarction, stroke, and all-cause mortality.


  Uric Acid Levels and Acute Kidney Injury Top


Uric acid association with acute kidney injury was first demonstrated in tumor lysis syndrome. However, it is now known that even when uric acid levels are not high enough to induce intrarenal crystal deposition, it may still result in acute kidney injury.[6]

Lapsia et al. performed a retrospective study on 190 postoperative patients comparing the incidence of acute kidney injury at different levels of serum uric acid. They found that serum uric acid levels ≥5.5 mg/dL, ≥6 mg/dL, and ≥7 mg/dL were associated with odds ratios of developing acute kidney injury of 4.4 (95% confidence interval [CI]: 2.4–8.2), 5.9 (95% CI: 3.2–11.3), and 39.1 (95% CI: 11.6–131.8), respectively. However, very low uric acid levels (<2.5 mg/dL) were also associated with increased odds of the development of acute kidney injury, demonstrating a J-shaped curve for AKI incidence for hypo- and hyperuricemia.

Finally, Ejaz et al. performed a double-blind, placebo-controlled randomized trial to assess whether preoperative treatment of hyperuricemia with rasburicase would result in a decreased incidence of acute kidney injury. Indeed, treatment with rasburicase resulted in an overall trend toward a decrease in the incidence of acute kidney injury (7.7% vs. 30.8%). However, because this was a pilot study, the value was not statistically significant in the overall population. Despite this, in a subset of patients with an eGFR of 45 mL/min/1.73 m2 or less, treatment with rasburicase resulted in a statistically significant decrease in postoperative acute kidney injury incidence (0% vs. 75%).[7]


  Conclusion Top


Overall, the challenge remains that the significance of elevations in uric acid is difficult to assess in those with chronic kidney disease because, as clearance decreases, the levels of serum uric acid naturally increase. While evidence for treating asymptomatic hyperuricemia may be lacking, hyperuricemia may be used as a disease marker for the potential to develop renal disease in the future as well as predict risk for a patient with renal disease to develop worsening renal function.



 
  References Top

1.
Johnson RJ, Lanaspa MA, Gaucher EA. Uric acid: A danger signal from the RNA world that may have a role in the epidemic of obesity, metabolic syndrome, and cardiorenal disease: Evolutionary considerations. Semin Nephrol 2011;31:394-9.  Back to cited text no. 1
    
2.
Ryu ES, Kim MJ, Shin HS, Jang YH, Choi HS, Jo I, et al. Uric acid-induced phenotypic transition of renal tubular cells as a novel mechanism of chronic kidney disease. Am J Physiol Renal Physiol 2013;304:F471-80.  Back to cited text no. 2
    
3.
Verzola D, Ratto E, Villaggio B, Parodi EL, Pontremoli R, Garibotto G, et al. Uric acid promotes apoptosis in human proximal tubule cells by oxidative stress and the activation of NADPH oxidase NOX 4. PLoS One 2014;9:e115210.  Back to cited text no. 3
    
4.
Turak O, Ozcan F, Tok D, Işleyen A, Sökmen E, Taşoǧlu I, et al. Serum uric acid, inflammation, and nondipping circadian pattern in essential hypertension. J Clin Hypertens (Greenwich) 2013;15:7-13.  Back to cited text no. 4
    
5.
Odden MC, Amadu AR, Smit E, Lo L, Peralta CA. Uric acid levels, kidney function, and cardiovascular mortality in US adults: National health and nutrition examination survey (NHANES) 1988-1994 and 1999-2002. Am J Kidney Dis 2014;64:550-7.  Back to cited text no. 5
    
6.
Gores PF, Fryd DS, Sutherland DE, Najarian JS, Simmons RL. Hyperuricemia after renal transplantation. Am J Surg 1988;156:397-400.  Back to cited text no. 6
    
7.
Ejaz AA, Dass B, Lingegowda V, Shimada M, Beaver TM, Ejaz NI, et al. Effect of uric acid lowering therapy on the prevention of acute kidney injury in cardiovascular surgery. Int Urol Nephrol 2013;45:449-58.  Back to cited text no. 7
    




 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Introduction
Pathophysiology ...
Hyperuricemia an...
Uric Acid Levels...
Conclusion
References

 Article Access Statistics
    Viewed23    
    Printed1    
    Emailed0    
    PDF Downloaded4    
    Comments [Add]    

Recommend this journal