Implication for health policy/practice/research/medical:
Diabetic nephropathy is the most common cause of end-stage renal disease worldwide. Recently, some prospective randomized controlled trials suggested that lowering of uric acid with allopurinol could decrease the severity of proteinuria and probably slow the progression of renal failure in diabetic patients. Mechanism of beneficial effect of xanthine oxidase inhibitor may related to preventing uric acid-induced renal inflammation.
Diabetic nephropathy is the most common cause of end stage renal disease worldwide. The pathogenesis of diabetic nephropathy is incompletely understood but may be include glycosylation of circulating and intrarenal proteins and abnormal intrarenal hemodynamics. Hyperglycemia may cause increase mesangial cell glucose concentration and glycation of matrix proteins that lead to increased matrix production and mesangial cell apoptosis (1). Cytokines activation, inflammation, and vascular growth factors may be responsible in the matrix accumulation in diabetic nephropathy (2).Glomerular hypertension and hyperfiltration are also responsible for development and progression of in diabetic nephropathy, hence, blockade of the renin-angiotensin system is beneficial in the treatment of disease. Detection of microalbuminuria is the screening method of choice for identifying of early stage of diabetic nephropathy (3). Correlation of serum uric acid (UA) with diabetic nephropathy was shown in several studies. For example level of serum UA was shown significantly higher in type 1 diabetic patients with persistent macroalbuminuria, compared to patients with normoalbuminuria (4). Elevated UA is associated with endothelial dysfunction, insulin resistance, development of hypertension, and cardiovascular disease (5). Elevated serum uric acid may be also associated with progression of non-diabetic renal disease (6). Currently renin-angiotensin system blockade is the gold standard in diabetic nephropathy treatment that lead to slowing the renal impairment but not arrest or reverse of the disease. Thus we require adjunctive therapeutic strategies, especially in patients with complications of treatment or lack of appropriate response. Recently, some prospective randomized controlled trials suggested that lowering of uric acid with allopurinol could decrease the severity of proteinuria and probably slow the progression of renal failure in diabetic patients (7) and also in the patients with hyperuricemia and non-diabetic chronic kidney disease (8). Mechanism of beneficial effect of xanthine oxidase inhibitor may related to preventing uric acid-induced renal inflammation (9). Indeed, allopurinol decrease serum uric acid level and reduce oxidative stress, it is not exactly obvious the main beneficial mechanism of allopurinol in the diabetic nephropathy. In conclusion, it seems that further studies are needed to clarify the effect of uric acid in initiation and progression of diabetic nephropathy and effect of uric acid lowering drugs on preventing or slowing of disease progression.
Authors’ contributions
AM is the single author of the manuscript.
Conflict of interests
The author declared no competing interests.
Ethical considerations
Ethical issues (including plagiarism, informed consent, misconduct, double publication and redundancy) have been completely observed by the authors.
Funding/Support
None declared
Please cite this paper as: Momeni A. Serum uric acid and diabetic nephropathy. J Renal Inj Prev 2012; 1(1): 37-38. DOI: 10.12861/jrip.2012.13
References
- 1.Mishra R, Emancipator SN, Kern T, Simonson MS. High glucose evokes an intrinsic proapoptotic signaling pathway in mesangial cells. Kidney Int. 2005;67:82–93. doi: 10.1111/j.1523-1755.2005.00058.x. [DOI] [PubMed] [Google Scholar]
- 2.Hohenstein B, Hausknecht B, Boehmer K, Riess R, Brekken RA, Hugo CP. Local VEGF activity but not VEGF expression is tightly regulated during diabetic nephropathy in man. Kidney Int. 2006;69:1654–61. doi: 10.1038/sj.ki.5000294. [DOI] [PubMed] [Google Scholar]
- 3.Nagai Y, Yao L, Kobori H, Miyata K, Ozawa Y, Miyatake A. et al. Temporary angiotensin II blockade at the prediabetic stage attenuates the development of renal injury in type 2 diabetic rats. J Am Soc Nephrol. 2005;16:703–11. doi: 10.1681/ASN.2004080649. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Jalal DI, Rivard CJ, Johnson RJ, Maahs DM, McFann K, Rewers M. et al. Serum uric acid levels predict the development of albuminuria over 6 years in patients with type 1 diabetes: findings from the Coronary Artery Calcification in Type 1 Diabetes study. Nephrol Dial Transplant. 2010;25:1865–9. doi: 10.1093/ndt/gfp740. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Modan M, Halkin H, Karasik A, Lusky A. Elevated serum uric acid--a facet of hyperinsulinaemia. Diabetologia. 1987;30:713–8. doi: 10.1007/BF00296994. [DOI] [PubMed] [Google Scholar]
- 6.Obermayr RP, Temml C, Gutjahr G, Knechtelsdorfer M, Oberbauer R, Klauser-Braun R. Elevated uric acid increases the risk for kidney disease. J Am Soc Nephrol. 2008;19:2407–13. doi: 10.1681/ASN.2008010080. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Momeni A, Shahidi S, Seirafian S, Taheri S, Kheiri S. Effect of allopurinol in decreasing proteinuria in type 2 diabetic patients. Iran J Kidney Dis. 2010;4:128–32. [PubMed] [Google Scholar]
- 8.Siu YP, Leung KT, Tong MK, Kwan TH. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis. 2006;47:51–9. doi: 10.1053/j.ajkd.2005.10.006. [DOI] [PubMed] [Google Scholar]
- 9.Kosugi T, Nakayama T, Heinig M, Zhang L, Yuzawa Y, Sanchez-Lozada LG. et al. Effect of lowering uric acid on renal disease in the type 2 diabetic db/db mice. Am J Physiol Renal Physiol. 2009;297:F481–8. doi: 10.1152/ajprenal.00092.2009. [DOI] [PMC free article] [PubMed] [Google Scholar]