Saudi Journal of Kidney Diseases and Transplantation

: 2013  |  Volume : 24  |  Issue : 6  |  Page : 1259--1261

Fathoming uric acid nephropathy

Dilip Gude, Sashidhar Chennamsetty, Ratan Jha 
 Department of Nephrology, Medwin Hospital, Chirag Ali Lane, Nampally, Hyderabad, AP, 500001, India

Correspondence Address:
Dilip Gude
Department of Nephrology, Medwin Hospital, Chirag Ali Lane, Nampally, Hyderabad, AP, 500001

How to cite this article:
Gude D, Chennamsetty S, Jha R. Fathoming uric acid nephropathy.Saudi J Kidney Dis Transpl 2013;24:1259-1261

How to cite this URL:
Gude D, Chennamsetty S, Jha R. Fathoming uric acid nephropathy. Saudi J Kidney Dis Transpl [serial online] 2013 [cited 2020 Jan 24 ];24:1259-1261
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Full Text

To the Editor,

Urate nephropathy has not been deciphered in entirety, and we attempt to throw light on this issue with our experience. A 45-year-old male with a history of chronic gouty arthritis from 18 years and with an underlying renal dysfunction [baseline serum creatinine (SCr) 2.5 mg/dL for the last two years] presented with multiple, tender, soft tissue nodules that have been increasing in size. His labs showed SCr 2.6 mg/dL, serum urea 55 mg/dL, urinalysis - normal, serum uric acid 9.6 mg/dL and 24-h uric acid 151 mg/day. X-ray of the right foot showed extensive erosion of the second toe with overhanging edges [Figure 1]. Ultrasonography showed borderline small kidneys [Figure 2]. Another patient, a 60-year-old male, presented with a history of gouty tophi for 20 years [Figure 3]. Labs revealed SCr 2.1 mg/ dL, urinalysis - 1+ protein and serum uric acid 9.1 mg /dL; his 24-h uric acid and protein were within normal limits. Ultrasonography showed slightly smaller kidneys. Both the patients were noted to have chronic kidney disease (CKD) secondary to urate nephropathy and were started on Febuxostat 40 mg/day (later increased to 80 mg), Colchicine 0.5 mg/day and supportive treatment for CKD.{Figure 1}{Figure 2}{Figure 3}

Uric acid has been shown to independently predict the development of new-onset kidney disease, and the risk increased linearly with increase in the uric acid level (7-8.9 mg/dL doubled and >9.0 mg/dL tripled the risk). [1] The risk of proteinuria correlates with initial kidney damage, progression of renal failure and end-stage renal disease. Uric acid has also been strongly associated with hypertension and cardiovascular disease, especially in those with metabolic syndrome, diabetes and cerebrovascular disease.

Increased platelet adhesiveness, activation of the renin - angiotensin and cyclooxygenase-2 systems in progressive renal disease (by up-regulating angiotensin-1 receptors on vascular smooth muscle cells) and action along with oxonic acid in inducing systemic hypertension, glomerular hypertrophy/hypertension, afferent arteriolar sclerosis and macrophage infiltration are some of the pathophysiologic components in uric acid-mediated injury. [1],[2] The innate arteriolopathy of preglomerular vessels caused by hyperuricemia impairs the autoregulatory response of the afferent arterioles, resulting in glomerular hypertension and lumen obliteration induced by vascular wall thickening, ultimately resulting in severe renal hypoperfusion. Local inhibition of endothelial nitric oxide levels, stimulation of vascular smooth muscle cell proliferation, stimulation of vasoactive and inflammatory mediators and "pro-oxidant"-like action seem to be the direct actions of uric acid up on entry into endothelial and vascular smooth muscle cells. [3] Neutrophil influx seems to be mediated by inflammasome (NALP3 component) and the pro-inflammatory cytokines (IL- lß , IL-8 and TNF-a) released by monocytes and macrophages upon stimulation by mono-sodium urate crystals. [4] Hence, IL-1 inhibition can remarkably ameliorate the resultant inflammation. Also, urate homoeostasis seems to be governed by URAT-1 transporter and the gene SLC 2A9, and future therapies may target these entities. [5] Asymptomatic hyperuricemia has been shown to cause abnormal indices of renal and endothelial function and elevated blood pressure states and detrimental renal microvascular, glomerular and tubulointerstitial lesions have been noted following induction of hyperuricemia.

Xanthine oxidase inhibitors (allopurinol, febuxostat), uricosuric agents, recombinant uri-case (rasburicase), combination therapy with allopurinol and benzbromarone (potent inhibitor of CYP2C9) and IL-1 blockade (anakinra) have shown benefit in lowering hyperuricemia.


The authors would like to thank their colleagues and the staff of Internal Medicine and Nephrology.


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