Impact of Hyper- and Hypo-Uricemia on Kidney Function
Uric acid (UA) forms monosodium urate (MSU) crystals to exert proinflammatory actions, thus causing gout arthritis, urolithiasis, kidney disease, and cardiovascular disease. UA is also one of the most potent antioxidants that suppresses oxidative stress. Hyper andhypouricemia are caused by genetic m...
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MDPI AG
2023-04-01
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| author | Junichiro Miake Ichiro Hisatome Katsuyuki Tomita Tadahiro Isoyama Shinobu Sugihara Masanari Kuwabara Kazuhide Ogino Haruaki Ninomiya |
| author_facet | Junichiro Miake Ichiro Hisatome Katsuyuki Tomita Tadahiro Isoyama Shinobu Sugihara Masanari Kuwabara Kazuhide Ogino Haruaki Ninomiya |
| author_sort | Junichiro Miake |
| collection | DOAJ |
| description | Uric acid (UA) forms monosodium urate (MSU) crystals to exert proinflammatory actions, thus causing gout arthritis, urolithiasis, kidney disease, and cardiovascular disease. UA is also one of the most potent antioxidants that suppresses oxidative stress. Hyper andhypouricemia are caused by genetic mutations or polymorphism. Hyperuricemia increases urinary UA concentration and is frequently associated with urolithiasis, which is augmented by low urinary pH. Renal hypouricemia (RHU) is associated with renal stones by increased level of urinary UA, which correlates with the impaired tubular reabsorption of UA. Hyperuricemia causes gout nephropathy, characterized by renal interstitium and tubular damage because MSU precipitates in the tubules. RHU is also frequently associated with tubular damage with elevated urinary beta2-microglobulin due to increased urinary UA concentration, which is related to impaired tubular UA reabsorption through URAT1. Hyperuricemia could induce renal arteriopathy and reduce renal blood flow, while increasing urinary albumin excretion, which is correlated with plasma xanthine oxidoreductase (XOR) activity. RHU is associated with exercise-induced kidney injury, since low levels of SUA could induce the vasoconstriction of the kidney and the enhanced urinary UA excretion could form intratubular precipitation. A U-shaped association of SUA with organ damage is observed in patients with kidney diseases related to impaired endothelial function. Under hyperuricemia, intracellular UA, MSU crystals, and XOR could reduce NO and activate several proinflammatory signals, impairing endothelial functions. Under hypouricemia, the genetic and pharmacological depletion of UA could impair the NO-dependent and independent endothelial functions, suggesting that RHU and secondary hypouricemia might be a risk factor for the loss of kidney functions. In order to protect kidney functions in hyperuricemic patients, the use of urate lowering agents could be recommended to target SUA below 6 mg/dL. In order to protect the kidney functions in RHU patients, hydration and urinary alkalization may be recommended, and in some cases an XOR inhibitor might be recommended in order to reduce oxidative stress. |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T03:55:40Z |
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| spelling | doaj.art-5eb4902fbe4d405dba5217948810d2cb2023-11-18T00:34:21ZengMDPI AGBiomedicines2227-90592023-04-01115125810.3390/biomedicines11051258Impact of Hyper- and Hypo-Uricemia on Kidney FunctionJunichiro Miake0Ichiro Hisatome1Katsuyuki Tomita2Tadahiro Isoyama3Shinobu Sugihara4Masanari Kuwabara5Kazuhide Ogino6Haruaki Ninomiya7Division of Pharmacology, Department of Pathophysiological and Therapeutic Science, Tottori University Faculty of Medicine, Tottori 683-8503, JapanDepartment of Cardiology, Yonago Medical Center, Tottori 683-0006, JapanDepartment of Respiratory Disease, Yonago Medical Center, Tottori 683-0006, JapanDepartment of Urology, Yonago Medical Center, Tottori 683-0006, JapanHealth Service Center, Shimane University, Matsue 690-0823, JapanIntensive Care Unit and Department of Cardiology, Toranomon Hospital, Tokyo 105-8470, JapanDepartment of Cardiology, Tottori Red Cross Hospital, Tottori 680-0017, JapanDepartment of Biological Regulation, Tottori University Faculty of Medicine, Tottori 683-8503, JapanUric acid (UA) forms monosodium urate (MSU) crystals to exert proinflammatory actions, thus causing gout arthritis, urolithiasis, kidney disease, and cardiovascular disease. UA is also one of the most potent antioxidants that suppresses oxidative stress. Hyper andhypouricemia are caused by genetic mutations or polymorphism. Hyperuricemia increases urinary UA concentration and is frequently associated with urolithiasis, which is augmented by low urinary pH. Renal hypouricemia (RHU) is associated with renal stones by increased level of urinary UA, which correlates with the impaired tubular reabsorption of UA. Hyperuricemia causes gout nephropathy, characterized by renal interstitium and tubular damage because MSU precipitates in the tubules. RHU is also frequently associated with tubular damage with elevated urinary beta2-microglobulin due to increased urinary UA concentration, which is related to impaired tubular UA reabsorption through URAT1. Hyperuricemia could induce renal arteriopathy and reduce renal blood flow, while increasing urinary albumin excretion, which is correlated with plasma xanthine oxidoreductase (XOR) activity. RHU is associated with exercise-induced kidney injury, since low levels of SUA could induce the vasoconstriction of the kidney and the enhanced urinary UA excretion could form intratubular precipitation. A U-shaped association of SUA with organ damage is observed in patients with kidney diseases related to impaired endothelial function. Under hyperuricemia, intracellular UA, MSU crystals, and XOR could reduce NO and activate several proinflammatory signals, impairing endothelial functions. Under hypouricemia, the genetic and pharmacological depletion of UA could impair the NO-dependent and independent endothelial functions, suggesting that RHU and secondary hypouricemia might be a risk factor for the loss of kidney functions. In order to protect kidney functions in hyperuricemic patients, the use of urate lowering agents could be recommended to target SUA below 6 mg/dL. In order to protect the kidney functions in RHU patients, hydration and urinary alkalization may be recommended, and in some cases an XOR inhibitor might be recommended in order to reduce oxidative stress.https://www.mdpi.com/2227-9059/11/5/1258hyperuricemiahypouricemiaurolithiasistubular diseasekidney diseaseU-shaped association |
| spellingShingle | Junichiro Miake Ichiro Hisatome Katsuyuki Tomita Tadahiro Isoyama Shinobu Sugihara Masanari Kuwabara Kazuhide Ogino Haruaki Ninomiya Impact of Hyper- and Hypo-Uricemia on Kidney Function Biomedicines hyperuricemia hypouricemia urolithiasis tubular disease kidney disease U-shaped association |
| title | Impact of Hyper- and Hypo-Uricemia on Kidney Function |
| title_full | Impact of Hyper- and Hypo-Uricemia on Kidney Function |
| title_fullStr | Impact of Hyper- and Hypo-Uricemia on Kidney Function |
| title_full_unstemmed | Impact of Hyper- and Hypo-Uricemia on Kidney Function |
| title_short | Impact of Hyper- and Hypo-Uricemia on Kidney Function |
| title_sort | impact of hyper and hypo uricemia on kidney function |
| topic | hyperuricemia hypouricemia urolithiasis tubular disease kidney disease U-shaped association |
| url | https://www.mdpi.com/2227-9059/11/5/1258 |
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