Uric Acid and the Risks of Kidney Failure and Death in Individuals With CKD

Srivastava, Anand; Kazé, Arnaud D.; McMullan, Ciaran J.; Isakova, Tamara; Waikar, Sushrut S.

doi:10.1053/j.ajkd.2017.08.017

Cited by 233 publications

(189 citation statements)

References 53 publications

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“…In the present study, a J-shaped relationship was observed, but was not significant. In contrast, elevated SUA levels are associated with an increased risk of mortality in the general population [6] and in nondialyzed chronic kidney disease patients [7][8][9]. These results are in contrast to previous findings obtained in the general population and suggest that higher UA levels are protective against mortality in dialysis patients.…”

Section: Discussioncontrasting

confidence: 64%

“…Elevated levels of serum UA (SUA) are associated with an increased risk of mortality in the general population [6] and in nondialyzed chronic kidney disease patients [7][8][9]. Few studies have examined UA as a predictor of outcomes in HD patients, and controversy surrounds whether SUA is an independent risk factor for mortality in patients receiving HD [4,10,11].…”

Section: Introductionmentioning

confidence: 99%

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Pre- and Postdialysis Uric Acid Difference and Risk of Long-Term All-Cause and Cardiovascular Mortalities in Japanese Hemodialysis Patients; Miyazaki Dialysis Cohort Study

et al. 2019

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Background/Aims: Uric acid (UA) levels are affected by changes in dialysis; however, the relationship between the pre- and postdialysis UA difference (UAD) and mortality remains unclear. Methods: A total of 1,073 patients receiving maintenance hemodialysis (HD) were enrolled in this cohort study and followed up for 5 years. Patients were divided into quartile categories according to baseline UAD. Cox’s regression analyses were used to investigate the relationship between UAD categories and all-cause and cardiovascular (CV) mortalities while adjusting for potential confounders. Results: A total of 280 patients died of all causes, including 121 CV deaths, during the follow-up. In the analysis for all-cause mortality, hazard ratios were significantly higher in the lowest UAD group (< 4.7 mg/dL) than in the highest UAD group (> 6.2 mg/dL). A correlation was not observed with CV mortality. Conclusion: UAD correlated with all-cause mortality. UAD may be the most appropriate reference for controlling UA in HD patients.

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Section: Discussioncontrasting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Pre- and Postdialysis Uric Acid Difference and Risk of Long-Term All-Cause and Cardiovascular Mortalities in Japanese Hemodialysis Patients; Miyazaki Dialysis Cohort Study

et al. 2019

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“…[2][3][4] Studies have suggested a positive association between hyperuricemia and progression of disease in individuals with renal insufficiency, including chronic kidney disease (CKD) and unrecovered allograft kidney. [5][6][7][8][9][10] Elevated serum UA is associated with abnormal endothelial function, mitochondria dysfunction and glomerular arteriolopathy and also could result in the formation of urate crystals in the nephron collecting ducts with tubular obstruction and then cause the damage of kidney structure progressively. 11 Available UA-lowering agents include the xanthine oxidase inhibitors such as febuxostat, allopurinol and benzbromarone.…”

Section: What Is Ne W and Objec Tivementioning

confidence: 99%

Comparison of efficacy and safety between febuxostat and allopurinol in early post-renal transplant recipients with new onset of hyperuricemia

Shen

et al. 2018

J Clin Pharm Ther

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Summary What is known and objective Febuxostat and allopurinol are xanthine oxidase inhibitors for urate‐lowering therapy. The efficacy and safety of febuxostat and allopurinol have been mostly reported in hyperuricemia patients with normal renal function. Here, we aimed to compare the effects of these two drugs in early post‐renal transplant recipients, focusing on evaluating the urate‐lowering effect and recovery of allograft renal function. Methods A retrospective cohort study was performed in early post‐renal transplant recipients with new onset of hyperuricemia receiving febuxostat or allopurinol therapy. Serum uric acid (UA) and estimated glomerular filtration rate (eGFR) were detected on days 3, 7 and 15 and months 1, 3 and 6 after therapy initiation. Liver and blood functions were monitored and other adverse events were recorded. Results and discussion A total of 48 and 33 patients were enrolled in the febuxostat and allopurinol groups, respectively. Significant UA‐lowering effects were observed on day 3 in both groups. Febuxostat caused a more rapid UA decline, starting on day 3 and lasting for 1 month. The most apparent contrast was found in UA level (267.25 ± 93.66 vs 334.18 ± 96.56 μmol/L, P = 0.003) on day 7; 62.5% and 30.3% of patients achieved target UA level in febuxostat and allopurinol groups respectively on day 3 (P = 0.004), but there was no significant difference between two groups from days 15 to months 6. The median times to achieve target UA level were 3 and 5 days in febuxostat and allopurinol groups respectively (P = 0.002). The eGFR levels and recovering rates were gradually upregulated but no significant differences were found between two groups. No abnormities related to febuxostat or allopurinol were observed. What is new and conclusion This is the first comprehensive evaluation of UA‐lowering effects of febuxostat and allopurinol in early post‐renal transplant recipients. Febuxostat caused a marginally quicker serum UA‐lowering effect than allopurinol, but there was no advantage for long‐term use of febuxostat. The drugs had no significant differences in impacting renal allograft function recovery, and both were well tolerated.

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“…Moreover, it is also associated with major related comorbidities including, chronic kidney disease (CKD), cardiovascular disease, hypertension, diabetes, and metabolic syndrome [2,4*,7,8]. Thus, a J-shaped association between serum uric acid and all-cause mortality among patients with CKD [9], and a J-shaped association with the risk of CKD, has been shown [10]. …”

Section: Introductionmentioning

confidence: 99%

The systems biology of uric acid transporters

Nigám¹,

Bhatnagar

2018

Current Opinion in Nephrology and Hypertension

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Purpose of review Uric acid homeostasis in the body is mediated by a number of SLC and ABC transporters in the kidney and intestine, including several multispecific ‘drug’ transporters (e.g., OAT1, OAT3, and ABCG2). Optimization of uric acid levels can be viewed as a ‘systems biology’ problem. Here, we consider uric acid transporters from a systems physiology perspective using the framework of the ‘Remote Sensing and Signaling Hypothesis.’ This hypothesis explains how SLC and ABC ‘drug’ and other transporters mediate interorgan and interorganismal communication (e.g., gut microbiome and host) via small molecules (e.g., metabolites, antioxidants signaling molecules) through transporters expressed in tissues lining body fluid compartments (e.g., blood, urine, cerebrospinal fluid). Recent findings The list of uric acid transporters includes: SLC2A9, ABCG2, URAT1 (SLC22A12), OAT1 (SLC22A6), OAT3 (SLC22A8), OAT4 (SLC22A11), OAT10 (SLC22A13), NPT1 (SLC17A1), NPT4 (SLC17A3), MRP2 (ABCC2), MRP4 (ABCC4). Normally, SLC2A9, – along with URAT1, OAT1 and OAT3, – appear to be the main transporters regulating renal urate handling, while ABCG2 appears to regulate intestinal transport. In chronic kidney disease (CKD), intestinal ABCG2 becomes much more important, suggesting remote organ communication between the injured kidney and the intestine. Summary The remote sensing and signaling hypothesis provides a useful systems-level framework for understanding the complex interplay of uric acid transporters expressed in different tissues involved in optimizing uric acid levels under normal and diseased (e.g., CKD, gut microflora dysbiosis) conditions.

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Uric Acid and the Risks of Kidney Failure and Death in Individuals With CKD

Cited by 233 publications

References 53 publications

Pre- and Postdialysis Uric Acid Difference and Risk of Long-Term All-Cause and Cardiovascular Mortalities in Japanese Hemodialysis Patients; Miyazaki Dialysis Cohort Study

Pre- and Postdialysis Uric Acid Difference and Risk of Long-Term All-Cause and Cardiovascular Mortalities in Japanese Hemodialysis Patients; Miyazaki Dialysis Cohort Study

Comparison of efficacy and safety between febuxostat and allopurinol in early post-renal transplant recipients with new onset of hyperuricemia

The systems biology of uric acid transporters

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