J Huazhong Univ Sci Technol [Med Sci] 34(4):476-481,2014 DOI 10.1007/s11596-014-1302-4 J Huazhong Univ Sci Technol［Med Sci］ 34(4):2014
476
Effect of Uric-acid-lowering Therapy on Progression of Chronic Kidney Disease: A Meta-analysis Ye-fang ZHANG (张叶芳)1, 2, Fan HE (何 凡)1, Hong-hui DING (丁红晖)3, Wei DAI (代 维)1, Qian ZHANG (张 茜)1, Hong LUAN (栾 宏)1, Yong-man LV (吕永曼)1#, Hong-bing ZENG (曾红兵)1# 1 Department of Nephrology, 2Department of Ultrasonography, 3Division of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China © Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2014
Summary: The efficacy and safety of uric-acid-lowering therapy (UALT) on slowing the progression of chronic kidney disease (CKD) accompanied by hyperuricemia were assessed. We searched Cochrane Library, PubMed, EMbase, CNKI, Wanfang and Vip databases up to November 15, 2012 for randomized controlled trials (RCTs) which compared the effect of UALT to control therapy in hyperuricemic patients secondary to CKD, and then performed quality evaluation and meta-analysis on the included studies. Seven RCTs involving 451 cases were included. UALT delayed the increase of serum creatinine (MD=–62.55 μmol/L, 95% CI: –98.10 to –26.99) and blood urea nitrogen (MD= –6.15 mmol/L, 95% CI: –8.17 to –4.13) as well as the decrease of glomerular filtration rate [MD=5.65 mL/(min·1.73 m2), 95% CI: 1.88 to 9.41], decreased systolic blood pressure (SBP) (MD= –6.08 mmHg, 95% CI: –11.67 to –0.49), and reduced the risk of the renal disease progression (RR=0.30, 95% CI: 0.19 to 0.46). However, there was no statistically significant difference in 24-h urinary protein quantity and diastolic blood pressure (P>0.05). We identified that UALT could delay the progression of CKD with secondary hyperuricemia. And this also indirectly proved that hyperuricemia was a risk factor for the CKD progression. Key words: hyperuricemia; chronic kidney disease; uric-acid-lowering; meta-analysis
Hyperuricemia is a consequence of impaired kidney function and associated with increased risks of hypertension, chronic kidney disease (CKD), end-stage renal disease (ESRD), and mortality. A US survey in 2006 revealed that only 4% of rheumatologists initiated uric-acid lowering therapy (UALT) for patients with asymptomatic hyperuricemia (AHU)[1]. However, an investigation completed in 2011 showed that more than 80% of Japanese nephrologists considered that UALT was recommended to AHU when it was secondary to CKD[2]. Why did they attach so great importance to UALT in patients with CKD? There is growing evidence proving that hyperuricemia is not only an independent risk factor for renal damage, but also a promoting factor for the progression of renal disease[3–6]. A study including 5546 participants showed that groups with serum uric acid (SUA) 321–381, 387–452 and ≥458 μmol/L were 2.38, 4.17 and 10.94 times respectively more likely to develop into CKD than group with SUA ≤315 μmol/L[7]. And another study of 49 413 Japanese men with an average follow-up of 5.4 years revealed that, even when adjusted for covariate effects, the risks of ESRD in the patients with SUA ≥506 μmol/L was 8 times more than that with SUA 297–381 μmol/L[8]. CKD predisposes patients to hyperuricemia, which may aggravate the renal disease progression in turn. So it’s meaningful to disclose whether UALT can benefit for Ye-fang ZHANG, E-mail: [email protected] # Corresponding authors, Hong-bing ZENG, E-mail: [email protected]; Yong-man LV, E-mail: [email protected]
CKD. In recent years, numbers of small, short-term, single-center studies have shown slowing of CKD progression following SUA lowering with allopurinol. In this research we took meta-analysis for the RCTs offered domestically and abroad. With a larger sample size, we aimed at assessing the efficacy and safety of UALT on slowing CKD progression and providing objective evidence for clinical treatment. 1 MATERIALS AND METHODS 1.1 Search Strategy All eligible articles in English or Chinese published up to November 15, 2012 were searched from Cochrane Library, PubMed, EMbase, CNKI, Wanfang and Vip databases. Articles were also identified by use of the related-articles function in PubMed. References of articles identified were also searched manually. Furthermore, we contracted authors to acquire any possible additional published or unpublished data and searched the proceedings of the annual meeting in the Cochrane Renal Group Specialized Register. The search terms were “chronic kidney disease”, “hyperuricemia”, and “uric-acid-lowering”. All retrieval and data were obtained by two researchers independently. When their views were abhorrent, they would consult to achieve coherence. 1.2 Criteria for Inclusion and Exclusion Included studies should fulfill all the following criteria: (1) Subjects were diagnosed as having CKD with serum creatinine (SCr) exceeding the normal range or glomerular filtration rate (GFR)
476
Effect of Uric-acid-lowering Therapy on Progression of Chronic Kidney Disease: A Meta-analysis Ye-fang ZHANG (张叶芳)1, 2, Fan HE (何 凡)1, Hong-hui DING (丁红晖)3, Wei DAI (代 维)1, Qian ZHANG (张 茜)1, Hong LUAN (栾 宏)1, Yong-man LV (吕永曼)1#, Hong-bing ZENG (曾红兵)1# 1 Department of Nephrology, 2Department of Ultrasonography, 3Division of Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China © Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2014
Summary: The efficacy and safety of uric-acid-lowering therapy (UALT) on slowing the progression of chronic kidney disease (CKD) accompanied by hyperuricemia were assessed. We searched Cochrane Library, PubMed, EMbase, CNKI, Wanfang and Vip databases up to November 15, 2012 for randomized controlled trials (RCTs) which compared the effect of UALT to control therapy in hyperuricemic patients secondary to CKD, and then performed quality evaluation and meta-analysis on the included studies. Seven RCTs involving 451 cases were included. UALT delayed the increase of serum creatinine (MD=–62.55 μmol/L, 95% CI: –98.10 to –26.99) and blood urea nitrogen (MD= –6.15 mmol/L, 95% CI: –8.17 to –4.13) as well as the decrease of glomerular filtration rate [MD=5.65 mL/(min·1.73 m2), 95% CI: 1.88 to 9.41], decreased systolic blood pressure (SBP) (MD= –6.08 mmHg, 95% CI: –11.67 to –0.49), and reduced the risk of the renal disease progression (RR=0.30, 95% CI: 0.19 to 0.46). However, there was no statistically significant difference in 24-h urinary protein quantity and diastolic blood pressure (P>0.05). We identified that UALT could delay the progression of CKD with secondary hyperuricemia. And this also indirectly proved that hyperuricemia was a risk factor for the CKD progression. Key words: hyperuricemia; chronic kidney disease; uric-acid-lowering; meta-analysis
Hyperuricemia is a consequence of impaired kidney function and associated with increased risks of hypertension, chronic kidney disease (CKD), end-stage renal disease (ESRD), and mortality. A US survey in 2006 revealed that only 4% of rheumatologists initiated uric-acid lowering therapy (UALT) for patients with asymptomatic hyperuricemia (AHU)[1]. However, an investigation completed in 2011 showed that more than 80% of Japanese nephrologists considered that UALT was recommended to AHU when it was secondary to CKD[2]. Why did they attach so great importance to UALT in patients with CKD? There is growing evidence proving that hyperuricemia is not only an independent risk factor for renal damage, but also a promoting factor for the progression of renal disease[3–6]. A study including 5546 participants showed that groups with serum uric acid (SUA) 321–381, 387–452 and ≥458 μmol/L were 2.38, 4.17 and 10.94 times respectively more likely to develop into CKD than group with SUA ≤315 μmol/L[7]. And another study of 49 413 Japanese men with an average follow-up of 5.4 years revealed that, even when adjusted for covariate effects, the risks of ESRD in the patients with SUA ≥506 μmol/L was 8 times more than that with SUA 297–381 μmol/L[8]. CKD predisposes patients to hyperuricemia, which may aggravate the renal disease progression in turn. So it’s meaningful to disclose whether UALT can benefit for Ye-fang ZHANG, E-mail: [email protected] # Corresponding authors, Hong-bing ZENG, E-mail: [email protected]; Yong-man LV, E-mail: [email protected]
CKD. In recent years, numbers of small, short-term, single-center studies have shown slowing of CKD progression following SUA lowering with allopurinol. In this research we took meta-analysis for the RCTs offered domestically and abroad. With a larger sample size, we aimed at assessing the efficacy and safety of UALT on slowing CKD progression and providing objective evidence for clinical treatment. 1 MATERIALS AND METHODS 1.1 Search Strategy All eligible articles in English or Chinese published up to November 15, 2012 were searched from Cochrane Library, PubMed, EMbase, CNKI, Wanfang and Vip databases. Articles were also identified by use of the related-articles function in PubMed. References of articles identified were also searched manually. Furthermore, we contracted authors to acquire any possible additional published or unpublished data and searched the proceedings of the annual meeting in the Cochrane Renal Group Specialized Register. The search terms were “chronic kidney disease”, “hyperuricemia”, and “uric-acid-lowering”. All retrieval and data were obtained by two researchers independently. When their views were abhorrent, they would consult to achieve coherence. 1.2 Criteria for Inclusion and Exclusion Included studies should fulfill all the following criteria: (1) Subjects were diagnosed as having CKD with serum creatinine (SCr) exceeding the normal range or glomerular filtration rate (GFR)
