Research Article: Serum Uric Acid and Progression of Kidney Disease: A Longitudinal Analysis and Mini-Review

Date Published: January 20, 2017

Publisher: Public Library of Science

Author(s): Ching-Wei Tsai, Shih-Yi Lin, Chin-Chi Kuo, Chiu-Ching Huang, Tatsuo Shimosawa.

http://doi.org/10.1371/journal.pone.0170393

Abstract

Increasing evidence supports the association between hyperuricemia and incident chronic kidney disease (CKD); however, there are conflicting data regarding the role of hyperuricemia in the progression of CKD. This study retrospectively assessed the longitudinal association between uric acid (UA) level and CKD progression in a Chinese population lived in Taiwan.

Patients with physician diagnosis of hyperuricemia or receiving urate-lowering therapy between 2003 and 2005 were identified in the electronic medical records (EMR) of a tertiary medical center and were followed up until December 31, 2011. Patients were divided into four UA categories at the cut-off 6, 8, and 10 mg/dL. CKD progression was estimated by the change of estimated glomerular filtration rate (eGFR) in the linear mixed models. Kidney failure was defined as an eGFR less than 15 mL/min/1.73 m2 or requiring renal replacement therapy.

A total of 739 patients were analyzed. In the full-adjusted model, patients with a baseline UA level ≥6 mg/dL had greater decline in eGFR ((β = -9.6, 95% CI -16.1, -3.1), comparing to those with a UA level less than 6 mg/dL. When stratifying patients into four UA categories, all three hyperuricemia categories (UA6-8, 8–10, ≥10 mg/dL) associated with a greater decline in eGFR over the follow-up period with an increasing dose-response, comparing to the lowest UA category. The risk of progression to renal failure increased 7% (hazard ratio 1.07, 95% CI 1.00, 1.14) for each 1mg/dL increase in baseline UA level. The influences of hyperuricemia on eGFR decline and the risk of kidney failure were more prominent in patients without proteinuria than those with proteinuria.

Our study showed a higher uric acid level is associated with a significant rapid decline in eGFR and a higher risk of kidney failure, particularly in patients without proteinuria. Our findings suggest hyperuricemia is a potential modifiable factor of CKD progression.

Partial Text

Chronic kidney disease (CKD) is a global health care burden [1]. Identification of modifiable risk factors, such as hyperglycemia and hypertension, and implantation efforts to control these factors are imperative for CKD prevention. An elevated uric acid (UA) level is commonly observed in CKD patients; however, whether it is simply a biomarker of impaired kidney function or has a true pathogenic role in kidney function remains inconclusive [2, 3]. In experimental rat models, hyperuricemia-induced kidney injury including afferent arteriolopathy, glomerulosclerosis, and tubulointerstitial fibrosis [4–6] could be reversed by urate-lowering agents [7, 8].

Our study supports that hyperuricemia is associated with a greater decline in renal function and a higher risk of progressing to kidney failure. The influences of hyperuricemia on renal function decline and the risk of kidney failure are greater in patients without proteinuria than those with proteinuria. We also found that patients treated with allopurinol had a greater eGFR decline, though the risk of progression to kidney failure did not significantly increase, comparing to those who did not use urate-lowering agents.

Our study showed a higher UA level was significantly associated with a greater decline in renal function and a higher risk of progressing to kidney failure in a Chinese population. The influence of hyperuricemia on renal function decline and risk of renal failure was greater in subjects without proteinuria than in those with proteinuria. In addition, allopurinol did not have a benefit in mitigating CKD progression. Our findings support that hyperuricemia as a potential modifiable risk factor for CKD progression, particularly in patients without proteinuria.

 

Source:

http://doi.org/10.1371/journal.pone.0170393

 

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