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1
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Uwatoko R, Mori H, Ueda K, Iio R. Co-occurrence of exercise-induced acute kidney injury and rhabdomyolysis in a holding cell at a police station: a case report. J Nephrol 2025; 38:745-749. [PMID: 39847208 DOI: 10.1007/s40620-024-02186-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Accepted: 11/30/2024] [Indexed: 01/24/2025]
Abstract
We present a rare case of a patient with co-occurring exercise-induced acute kidney injury (AKI) and rhabdomyolysis. A 67-year-old man was referred to our department with AKI. Five days before referral, the patient had sudden-onset loin pain while banging and kicking on a door in a holding cell at a police station. Diffusion-weighted magnetic resonance imaging showed wedge-shaped areas of signal hyperintensity in both kidneys. Serum and urinary myoglobin levels were mildly elevated. Kidney biopsy showed cellular injury of the tubular epithelial cells and myoglobin casts in the tubules. The patient was diagnosed with exercise-induced AKI and mild rhabdomyolysis and was treated conservatively. His kidney function improved gradually with no need for hemodialysis. This case report exhibits a unique presentation of the co-occurrence of exercise-induced AKI and rhabdomyolysis after intense anaerobic and aerobic exercise. To the best of our knowledge, this is the first report to pathologically demonstrate co-occurring exercise-induced AKI and rhabdomyolysis.
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Affiliation(s)
- Ryuta Uwatoko
- Department of Nephrology, Osaka Habikino Medical Center, Habikino, Osaka, Japan.
| | - Hideo Mori
- Department of Pathology, Osaka Habikino Medical Center, Habikino, Osaka, Japan
| | - Kayo Ueda
- Department of Pathology, Osaka Habikino Medical Center, Habikino, Osaka, Japan
| | - Rei Iio
- Department of Nephrology, Osaka Habikino Medical Center, Habikino, Osaka, Japan
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2
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Sugihara S, Yamamoto Y, Teramoto K, Hamada T, Miyazaki S, Ogino K, Kuwabara M, Ohtahara A, Mizuta E, Ichida K, Endo Y, Minato H, Ninomiya H, Kato M, Yamamoto K, Hisatome I. Annual change in eGFR in renal hypouricemia: a retrospective pilot study. Clin Exp Nephrol 2025; 29:173-181. [PMID: 39361182 PMCID: PMC11828821 DOI: 10.1007/s10157-024-02558-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 08/29/2024] [Indexed: 02/16/2025]
Abstract
BACKGROUND Extremely low uric acid (UA) levels or increased urinary UA (Uua) excretion might be risk factors for kidney disease in renal hypouricemia (RHU) patients, but their relationship with kidney dysfunction is unclear. This study investigated time-dependent changes in eGFR in RHU patients. METHODS This multicenter retrospective study assessed UA metabolism and changes in eGFR (median 5.5 years) in 13 RHU patients. We then compared eGFR change in 7 of 13 RHU patients whose eGFR could be measured for 4 years with those in normouricemic group (n = 31). In addition, 7 RHU patients were divided into two groups based on URAT1 gene mutations: homozygote and compound heterozygote mutations (Homo/Com group, n = 3), and wild-type and heterogeneous mutations (WT/Hetero group, n = 4). RESULTS In 13 RHU patients, the median and mean serum UA (SUA) were 0.8 (0.4-2.5) and 1.1 ± 0.7 mg/dL. The median and mean Uua were 44.3 (12.7-141.1) and 49.7 ± 36.2 mg/dL. The median and mean urinary urate clearance (Cua/Ccr) were 46.8 (11.3-73.6) and 43.3 ± 19.7%. Over 4 years, eGFR did not change in the RHU group but declined in the normouricemic group. Annual mean eGFR decline and change rate in the RHU group were the same as those in the normouricemic group (- 1.09 ± 1.11 vs. - 1.09 ± 1.92 mL/min/1.73 m2/year, p = 0.996) (- 1.74 ± 1.96 vs. - 1.36 ± 2.10%, p = 0.664). And no significant difference was found in eGFR decline or change rate between Homo/Com and WT/Hetero groups (- 0.33 ± 1.03 vs. - 1.67 ± 0.85 mL/min/1.73 m2/year, p = 0.116) (- 0.61 ± 1.62 vs. - 2.59 ± 1.91%, p = 0.210). CONCLUSION RHU from URAT1 genetic mutation may not show eGFR decline over 4 consecutive years.
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Affiliation(s)
- Shinobu Sugihara
- Matsue Health Service Center, Shimane University, Matsue, Japan.
| | | | - Kei Teramoto
- The Division of Medical Informatics, Tottori University Hospital, Tottori, Japan
| | - Toshiro Hamada
- Department of Community-Based Family Medicine, Faculty of Medicine, Tottori University, Yonago, Japan
| | - Satoshi Miyazaki
- Division of Cardiology, Fujii Masao Memorial Hospital, Kurayoshi, Japan
| | - Kazuhide Ogino
- Department of Cardiology, Japanese Red Cross Tottori Hospital, Tottori, Japan
| | | | - Akira Ohtahara
- Department of Cardiology, Sanin Rosai Hospital, Yonago, Japan
| | - Einosuke Mizuta
- Department of Cardiology, Sanin Rosai Hospital, Yonago, Japan
| | - Kimiyoshi Ichida
- Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan
| | - Yusuke Endo
- Advanced Medicine, Innovation and Clinical Research Center, Tottori University Hospital, Yonago, Japan
| | - Hiroyuki Minato
- Department of Anesthesiology, Faculty of Medicine, Tottori University, Yonago, Japan
| | - Haruaki Ninomiya
- Department of Biological Regulation, Tottori University, Yonago, Japan
| | - Masahiko Kato
- Division of School of Health Science, Department of Pathobiological Science and Technology, Faculty of Medicine, Tottori University, Yonago, Japan
| | - Kazuhiro Yamamoto
- Department of Cardiovascular Medicine and Endocrinology and Metabolism, Faculty of Medicine, Tottori University, Yonago, Japan
| | - Ichiro Hisatome
- Department of Cardiology, National Hospital Organization, Yonago Medical Center, Yonago, Japan
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3
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Sakurabu Y, Uchida HA, Tahara T, Asakawa T, Yamasaki H, Katayama K, Okamoto S, Onishi Y, Matsuoka‐Uchiyama N, Tanaka K, Takeuchi H, Tsuji K, Umebayashi R, Ohashi Y, Ichida K, Wada J. A case of renal hypouricemia due to T217M mutation in SLC22A12 incidentally associated with IgA nephropathy. Clin Case Rep 2024; 12:e9368. [PMID: 39206069 PMCID: PMC11349819 DOI: 10.1002/ccr3.9368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 07/29/2024] [Accepted: 08/10/2024] [Indexed: 09/04/2024] Open
Abstract
A T217M heterozygous mutation in the SLC22A12 gene caused renal hypouricemia; this patient with IgA nephropathy had no findings other than IgA nephropathy on renal biopsy. Hypouricemia was susceptible to oxidative stress, but IgA nephropathy in the patient with hypouricemia could be treated with steroid pulse therapy without adverse events.
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Affiliation(s)
- Yoshimasa Sakurabu
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Haruhito A. Uchida
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
- Department of Chronic Kidney Disease and Cardiovascular DiseaseOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Toshihisa Tahara
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Tomohiko Asakawa
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Haruka Yamasaki
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
- Department of Internal MedicineKagawa Rosai HospitalMarugameKagawaJapan
| | - Katsuyoshi Katayama
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Shugo Okamoto
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Yasuhiro Onishi
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Natsumi Matsuoka‐Uchiyama
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Keiko Tanaka
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Hidemi Takeuchi
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Kenji Tsuji
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Ryoko Umebayashi
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
| | - Yuki Ohashi
- Department of PathophysiologyTokyo University of Pharmacy and Life SciencesTokyoJapan
- Public Health Informatics Unit, Department of Integrated Health Sciences, Graduate School of MedicineNagoya UniversityNagoyaAichiJapan
| | - Kimiyoshi Ichida
- Department of PathophysiologyTokyo University of Pharmacy and Life SciencesTokyoJapan
| | - Jun Wada
- Department of Nephrology, Rheumatology, Endocrinology and MetabolismOkayama University Faculty of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
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4
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Maruyama H, Sada KE, Ohtake T. Patchy reversible renal vasoconstriction. Eur J Intern Med 2024; 125:124-125. [PMID: 38772829 DOI: 10.1016/j.ejim.2024.05.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 05/15/2024] [Indexed: 05/23/2024]
Affiliation(s)
- Haruka Maruyama
- Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura, Kanagawa 247-8533, Japan
| | - Ken-Ei Sada
- Department of Clinical Epidemiology, Kochi Medical School, Kohasu, Oko-cho, Nankoku, Kochi 783-8505, Japan.
| | - Takayasu Ohtake
- Kidney Disease and Transplant Center, Shonan Kamakura General Hospital, 1370-1 Okamoto, Kamakura, Kanagawa 247-8533, Japan
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5
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Yazawa S, Matsuoka D, Murase T, Nakayama Y. Recurrent Abdominal Pain Due to Acute Renal Failure With Loin Pain and Patchy Renal Ischemia After Anaerobic Exercise. Cureus 2024; 16:e63220. [PMID: 39070417 PMCID: PMC11279141 DOI: 10.7759/cureus.63220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/26/2024] [Indexed: 07/30/2024] Open
Abstract
Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE) is a rare condition characterized by severe loin pain and patchy renal ischemia following vigorous exercise. Moreover, its diagnosis relies on clinical manifestations. Here, we present the case of a 16-year-old male with recurrent abdominal pain attributed to ALPE. He developed recurrent abdominal pain after he started playing handball, and no definite cause could be identified despite a thorough examination. His symptoms worsened when he resumed handball practice after a one-month interruption. This case underscores the varied presentations of ALPE and the importance of considering it in the differential diagnosis of recurrent abdominal pain, particularly following strenuous exercise. Moreover, caution should be exercised when resuming exercise after periods of detraining, as this may predispose individuals to ALPE. Healthcare providers should be vigilant in recognizing and managing this condition, especially in individuals with recent exercise initiation following detraining.
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Affiliation(s)
- Shiori Yazawa
- Department of Pediatrics, Minaminagano Medical Center, Shinonoi General Hospital, Shinonoi, JPN
- Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, JPN
| | - Daisuke Matsuoka
- Department of Pediatrics, Shinshu University Hospital, Matsumoto, JPN
| | - Tsubasa Murase
- Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, JPN
| | - Yoshiko Nakayama
- Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, JPN
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6
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Hughes KG, Miller NL. Acute Renal Failure with Severe Loin Pain and Patchy Renal Ischemia after Anaerobic Exercise in Active Duty Marines. Mil Med 2024; 189:e429-e432. [PMID: 37534888 DOI: 10.1093/milmed/usad258] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 05/02/2023] [Accepted: 06/29/2023] [Indexed: 08/04/2023] Open
Abstract
Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE) is a rare cause of exertional acute kidney injury. The proposed mechanism of injury in ALPE is renovascular spasm, in the setting of oxidative stress and muscular damage, which creates a characteristic wedge-shaped infarction pattern on delayed imaging. Patients present with nausea, vomiting, loin or abdominal pain, and fatigue within 1-2 days of anaerobic exercise, associated with an acute rise in serum creatinine, which generally plateaus within 3 days. This process is likely exacerbated by dehydration, analgesic usage, and lower baseline fitness levels. This disease process is distinct from rhabdomyolysis, in that creatine kinase levels are not significantly elevated, myoglobinuria is not seen, and aggressive fluid resuscitation is not beneficial. We present three cases of ALPE following participation in the Marine Combat Fitness Test (CFT), an anaerobic evolution. Medical workup demonstrated no additional etiology for acute renal failure. The average peak creatinine in these patients was 2.9 mg/dL, and all demonstrated return to normal renal function, without hemodialysis. One patient experienced recurrent ALPE, after short-interval CFT participation. Military medical providers should be aware of this diagnosis when evaluating service members with acute renal injury after exercise. The clinical course is benign, and affected service members are at increased risk of recurrence, with subsequent intense exercise. Service members should engage in a graduated exercise program, before intense exercise activities, and should be monitored closely for recurrent renal injury.
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Affiliation(s)
- Kathryn G Hughes
- Internal Medicine Department, Naval Medical Center San Diego, San Diego, CA 92134, USA
| | - Nancy L Miller
- Internal Medicine Department, Naval Medical Center San Diego, San Diego, CA 92134, USA
- Nephrology Division, Naval Medical Center San Diego, San Diego, CA 92134, USA
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7
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Ichida K. [Uric Acid Metabolism, Uric Acid Transporters and Dysuricemia]. YAKUGAKU ZASSHI 2024; 144:659-674. [PMID: 38825475 DOI: 10.1248/yakushi.23-00217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/04/2024]
Abstract
Serum urate levels are determined by the balance between uric acid production and uric acid excretion capacity from the kidneys and intestinal tract. Dysuricemia, including hyperuricemia and hypouricemia, develops when the balance shifts towards an increase or a decrease in the uric acid pool. Hyperuricemia is mostly a multifactorial genetic disorder involving several disease susceptibility genes and environmental factors. Hypouricemia, on the other hand, is caused by genetic abnormalities. The main genes involved in dysuricemia are xanthine oxidoreductase, an enzyme that produces uric acid, and the urate transporters urate transporter 1/solute carrier family 22 member 12 (URAT1/SLC22A12), glucose transporter 9/solute carrier family 2 member 9 (GLUT9/SLC2A9) and ATP binding cassette subfamily G member 2 (ABCG2). Deficiency of xanthine oxidoreductase results in xanthinuria, a rare disease with marked hypouricemia. Xanthinuria can be due to a single deficiency of xanthine oxidoreductase or in combination with aldehyde oxidase deficiency as well. The latter is caused by a deficiency in molybdenum cofactor sulfurase, which is responsible for adding sulphur atoms to the molybdenum cofactor required for xanthine oxidoreductase and aldehyde oxidase to exert their action. URAT1/SLC22A12 and GLUT9/SLC2A9 are involved in urate reabsorption and their deficiency leads to renal hypouricemia, a condition that is common in Japanese due to URAT1/SLC22A12 deficiency. On the other hand, ABCG2 is involved in the secretion of urate, and many Japanese have single nucleotide polymorphisms that result in its reduced function, leading to hyperuricemia. In particular, severe dysfunction of ABCG2 leads to hyperuricemia with reduced extrarenal excretion.
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MESH Headings
- Humans
- Hyperuricemia/etiology
- Hyperuricemia/metabolism
- Hyperuricemia/genetics
- Uric Acid/metabolism
- ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics
- ATP Binding Cassette Transporter, Subfamily G, Member 2/metabolism
- Organic Anion Transporters/metabolism
- Organic Anion Transporters/genetics
- Glucose Transport Proteins, Facilitative/metabolism
- Glucose Transport Proteins, Facilitative/genetics
- Neoplasm Proteins/genetics
- Neoplasm Proteins/metabolism
- Xanthine Dehydrogenase/metabolism
- Xanthine Dehydrogenase/genetics
- Xanthine Dehydrogenase/deficiency
- Animals
- Organic Cation Transport Proteins/genetics
- Organic Cation Transport Proteins/metabolism
- Renal Tubular Transport, Inborn Errors/genetics
- Renal Tubular Transport, Inborn Errors/etiology
- Renal Tubular Transport, Inborn Errors/metabolism
- Urinary Calculi/etiology
- Urinary Calculi/metabolism
- Urinary Calculi/genetics
- Metabolism, Inborn Errors
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Affiliation(s)
- Kimiyoshi Ichida
- Department of Pathophysiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
- Division of Kidney and Hypertension, The Jikei University School of Medicine
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8
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Nakayama A, Kurajoh M, Toyoda Y, Takada T, Ichida K, Matsuo H. Dysuricemia. Biomedicines 2023; 11:3169. [PMID: 38137389 PMCID: PMC10740884 DOI: 10.3390/biomedicines11123169] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 11/16/2023] [Accepted: 11/21/2023] [Indexed: 12/24/2023] Open
Abstract
Gout results from elevated serum urate (SU) levels, or hyperuricemia, and is a globally widespread and increasingly burdensome disease. Recent studies have illuminated the pathophysiology of gout/hyperuricemia and its epidemiology, diagnosis, treatment, and complications. The genetic involvement of urate transporters and enzymes is also proven. URAT1, a molecular therapeutic target for gout/hyperuricemia, was initially derived from research into hereditary renal hypouricemia (RHUC). RHUC is often accompanied by complications such as exercise-induced acute kidney injury, which indicates the key physiological role of uric acid. Several studies have also revealed its physiological role as both an anti-oxidant and a pro-oxidant, acting as both a scavenger and a generator of reactive oxygen species (ROSs). These discoveries have prompted research interest in SU and xanthine oxidoreductase (XOR), an enzyme that produces both urate and ROSs, as status or progression biomarkers of chronic kidney disease and cardiovascular disease. The notion of "the lower, the better" is therefore incorrect; a better understanding of uric acid handling and metabolism/transport comes from an awareness that excessively high and low levels both cause problems. We summarize here the current body of evidence, demonstrate that uric acid is much more than a metabolic waste product, and finally propose the novel disease concept of "dysuricemia" on the path toward "normouricemia", or optimal SU level, to take advantage of the dual roles of uric acid. Our proposal should help to interpret the spectrum from hypouricemia to hyperuricemia/gout as a single disease category.
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Affiliation(s)
- Akiyoshi Nakayama
- Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan
| | - Masafumi Kurajoh
- Department of Metabolism, Endocrinology and Molecular Medicine, Graduate School of Medicine, Osaka Metropolitan University, Osaka 545-8585, Japan
| | - Yu Toyoda
- Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan
- Department of Pharmacy, The University of Tokyo Hospital, Tokyo 113-8655, Japan
| | - Tappei Takada
- Department of Pharmacy, The University of Tokyo Hospital, Tokyo 113-8655, Japan
| | - Kimiyoshi Ichida
- Department of Pathophysiology, Tokyo University of Pharmacy and Life Science, Hachioji 192-0392, Japan
| | - Hirotaka Matsuo
- Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan
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9
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Tamura H. Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise. World J Nephrol 2023; 12:56-65. [PMID: 37476010 PMCID: PMC10354565 DOI: 10.5527/wjn.v12.i3.56] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2022] [Revised: 02/20/2023] [Accepted: 03/22/2023] [Indexed: 05/19/2023] Open
Abstract
BACKGROUND There are two known types of exercise-induced acute renal failure. One is the long-known myoglobinuria-induced acute renal failure due to severe rhabdomyolysis, and the other is the recently recognized non-myoglobinuria-induced acute renal failure with mild rhabdomyolysis. Exercise-induced acute renal failure was first reported in 1982. Non-myoglobinuria-induced acute renal failure is associated with severe low back pain and patchy renal vasoconstriction, and it is termed post-exercise acute renal failure because it usually occurs hours after exercise. It is also called acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE).
AIM To makes a significant contribution to medical literature as it presents a study that investigated a not-widely-known type of exercise-induced acute renal failure known as ALPE.
METHODS We performed a database search selecting papers published in the English or Japanese language. A database search was lastly accessed on September 1, 2022. The results of this study were compared with those reported in other case series.
RESULTS The study evaluated renal hypouricemia as a key risk factor of ALPE. The development of ALPE is due to the sum of risk factors such as exercise, hypouricemia, nonsteroidal anti-inflammatory drugs, vasopressors, and dehydration.
CONCLUSION In conclusion, hypouricemia plays a key role in the development of ALPE and is often associated with anaerobic exercise. The development of ALPE is a result of the cumulative effects of risk factors such as exercise, hypouricemia, NSAIDs, vasopressors, and dehydration.
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Affiliation(s)
- Hiroshi Tamura
- Department of Pediatrics, Kumamoto University, Kumamoto 8608556, Japan
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10
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Otani N, Ouchi M, Mizuta E, Morita A, Fujita T, Anzai N, Hisatome I. Dysuricemia-A New Concept Encompassing Hyperuricemia and Hypouricemia. Biomedicines 2023; 11:biomedicines11051255. [PMID: 37238926 DOI: 10.3390/biomedicines11051255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 04/20/2023] [Accepted: 04/21/2023] [Indexed: 05/28/2023] Open
Abstract
The importance of uric acid, the final metabolite of purines excreted by the kidneys and intestines, was not previously recognized, except for its role in forming crystals in the joints and causing gout. However, recent evidence implies that uric acid is not a biologically inactive substance and may exert a wide range of effects, including antioxidant, neurostimulatory, proinflammatory, and innate immune activities. Notably, uric acid has two contradictory properties: antioxidant and oxidative ones. In this review, we present the concept of "dysuricemia", a condition in which deviation from the appropriate range of uric acid in the living body results in disease. This concept encompasses both hyperuricemia and hypouricemia. This review draws comparisons between the biologically biphasic positive and negative effects of uric acid and discusses the impact of such effects on various diseases.
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Affiliation(s)
- Naoyuki Otani
- Department of Cardiology, Dokkyo Medical University Nikkyo Medical Center, Nikko 321-1298, Tochigi, Japan
| | - Motoshi Ouchi
- Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu 321-0293, Tochigi, Japan
| | - Einosuke Mizuta
- Department of Cardiology, Sanin Rosai Hospital, Yonago 683-8605, Tottori, Japan
| | - Asuka Morita
- Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu 321-0293, Tochigi, Japan
| | - Tomoe Fujita
- Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu 321-0293, Tochigi, Japan
| | - Naohiko Anzai
- Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu 321-0293, Tochigi, Japan
- Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba 260-8670, Chiba, Japan
| | - Ichiro Hisatome
- Yonago Medical Center, National Hospital Organization, Yonago 683-0006, Tottori, Japan
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11
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Genetic Basis of the Epidemiological Features and Clinical Significance of Renal Hypouricemia. Biomedicines 2022; 10:biomedicines10071696. [PMID: 35885001 PMCID: PMC9313227 DOI: 10.3390/biomedicines10071696] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 07/08/2022] [Accepted: 07/11/2022] [Indexed: 11/17/2022] Open
Abstract
A genetic defect in urate transporter 1 (URAT1) is the major cause of renal hypouricemia (RHUC). Although RHUC is detected using a serum uric acid (UA) concentration <2.0 mg/dL, the relationship between the genetic state of URAT1 and serum UA concentration is not clear. Homozygosity and compound heterozygosity with respect to mutant URAT1 alleles are associated with a serum UA concentration of <1.0 mg/dL and are present at a prevalence of ~0.1% in Japan. In heterozygous individuals, the prevalence of a serum UA of 1.1−2.0 mg/dL is much higher in women than in men. The frequency of mutant URAT1 alleles is as high as 3% in the general Japanese population. The expansion of a specific mutant URAT1 allele derived from a single mutant gene that occurred in ancient times is reflected in modern Japan at a high frequency. Similar findings were reported in Roma populations in Europe. These phenomena are thought to reflect the ancient migration history of each ethnic group (founder effects). Exercise-induced acute kidney injury (EI-AKI) is mostly observed in individuals with homozygous/compound heterozygous URAT1 mutation, and laboratory experiments suggested that a high UA load on the renal tubules is a plausible mechanism for EI-AKI.
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12
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Otani N, Ouchi M, Misawa K, Hisatome I, Anzai N. Hypouricemia and Urate Transporters. Biomedicines 2022; 10:biomedicines10030652. [PMID: 35327453 PMCID: PMC8945357 DOI: 10.3390/biomedicines10030652] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 03/09/2022] [Accepted: 03/10/2022] [Indexed: 02/07/2023] Open
Abstract
Hypouricemia is recognized as a rare disorder, defined as a serum uric acid level of 2.0 mg/dL or less. Hypouricemia is divided into an overexcretion type and an underproduction type. The former typical disease is xanthinuria, and the latter is renal hypouricemia (RHUC). The frequency of nephrogenic hypouricemia due to a deficiency of URAT1 is high in Japan, accounting for most asymptomatic and persistent cases of hypouricemia. RHUC results in a high risk of exercise-induced acute kidney injury and urolithiasis. It is vital to promote research on RHUC, as this will lead not only to the elucidation of its pathophysiology but also to the development of new treatments for gout and hyperuricemia.
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Affiliation(s)
- Naoyuki Otani
- Department of Clinical Pharmacology and Therapeutics, Faculty of Medicine, Oita University, Yufu 879-5593, Oita, Japan;
| | - Motoshi Ouchi
- Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Mibu 321-0293, Tochigi, Japan;
| | - Kazuharu Misawa
- Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Kanagawa, Japan;
| | - Ichiro Hisatome
- Yonago Medical Center, National Hospital Organization, Yonago 683-0006, Tottori, Japan;
- Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Sciences, Tottori University, Yonago 680-8550, Tottori, Japan
| | - Naohiko Anzai
- Department of Pharmacology, Chiba University Graduate School of Medicine, Chiba 260-8670, Chiba, Japan
- Correspondence:
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Takehara K, Mizobe M, Endo K, Miyake A, Suzuki T, Funakoshi H. Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise caused by rapid resumption after prolonged detraining. Acute Med Surg 2022; 9:e732. [PMID: 35223044 PMCID: PMC8857942 DOI: 10.1002/ams2.732] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2021] [Revised: 01/08/2022] [Accepted: 01/19/2022] [Indexed: 11/10/2022] Open
Affiliation(s)
- Kei Takehara
- Department of Emergency and Critical Care Medicine Tokyobay Urayasu Ichikawa Medical Center 3‐4‐32 Todaijima, Urayasu Chiba 279‐0001 Japan
| | - Michiko Mizobe
- Department of Emergency and Critical Care Medicine Tokyobay Urayasu Ichikawa Medical Center 3‐4‐32 Todaijima, Urayasu Chiba 279‐0001 Japan
| | - Keita Endo
- Department of Nephrology, Endocrinology and Diabetes Tokyobay Urayasu Ichikawa Medical Center 3‐4‐32 Todaijima, Urayasu Chiba 279‐0001 Japan
| | - Akihiro Miyake
- Department of Nephrology, Endocrinology and Diabetes Tokyobay Urayasu Ichikawa Medical Center 3‐4‐32 Todaijima, Urayasu Chiba 279‐0001 Japan
| | - Toshihiko Suzuki
- Department of Nephrology, Endocrinology and Diabetes Tokyobay Urayasu Ichikawa Medical Center 3‐4‐32 Todaijima, Urayasu Chiba 279‐0001 Japan
| | - Hiraku Funakoshi
- Department of Emergency and Critical Care Medicine Tokyobay Urayasu Ichikawa Medical Center 3‐4‐32 Todaijima, Urayasu Chiba 279‐0001 Japan
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Hosoya T, Uchida S, Shibata S, Tomioka NH, Matsumoto K, Hosoyamada M. Xanthine Oxidoreductase Inhibitors Suppress the Onset of Exercise-Induced AKI in High HPRT Activity Urat1- Uox Double Knockout Mice. J Am Soc Nephrol 2022; 33:326-341. [PMID: 34799437 PMCID: PMC8819989 DOI: 10.1681/asn.2021050616] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 11/09/2021] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Hereditary renal hypouricemia type 1 (RHUC1) is caused by URAT1/SLC22A12 dysfunction, resulting in urolithiasis and exercise-induced AKI (EIAKI). However, because there is no useful experimental RHUC1 animal model, the precise pathophysiologic mechanisms underlying EIAKI have yet to be elucidated. We established a high HPRT activity Urat1-Uox double knockout (DKO) mouse as a novel RHUC1 animal model for investigating the cause of EIAKI and the potential therapeutic effect of xanthine oxidoreductase inhibitors (XOIs). METHODS The novel Urat1-Uox DKO mice were used in a forced swimming test as loading exercise to explore the onset mechanism of EIAKI and evaluate related purine metabolism and renal injury parameters. RESULTS Urat1-Uox DKO mice had uricosuric effects and elevated levels of plasma creatinine and BUN as renal injury markers, and decreased creatinine clearance observed in a forced swimming test. In addition, Urat1-Uox DKO mice had increased NLRP3 inflammasome activity and downregulated levels of Na+-K+-ATPase protein in the kidney, as Western blot analysis showed. Finally, we demonstrated that topiroxostat and allopurinol, XOIs, improved renal injury and functional parameters of EIAKI. CONCLUSIONS Urat1-Uox DKO mice are a useful experimental animal model for human RHUC1. The pathogenic mechanism of EIAKI was found to be due to increased levels of IL-1β via NLRP3 inflammasome signaling and Na+-K+-ATPase dysfunction associated with excessive urinary urate excretion. In addition, XOIs appear to be a promising therapeutic agent for the treatment of EIAKI.
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Affiliation(s)
- Takuji Hosoya
- Department of Human Physiology and Pathology, Faculty of Pharma-Science, Teikyo University, Tokyo, Japan,Biological Research Department, Research Institute, Fuji Yakuhin Co., Ltd., Saitama, Japan
| | - Shunya Uchida
- Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Shigeru Shibata
- Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan
| | - Naoko H. Tomioka
- Department of Human Physiology and Pathology, Faculty of Pharma-Science, Teikyo University, Tokyo, Japan
| | - Koji Matsumoto
- Biological Research Department, Research Institute, Fuji Yakuhin Co., Ltd., Saitama, Japan
| | - Makoto Hosoyamada
- Department of Human Physiology and Pathology, Faculty of Pharma-Science, Teikyo University, Tokyo, Japan
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Affiliation(s)
- T Tadokoro
- Department of Internal Medicine, Japan Community Healthcare Organization Kyushu Hospital, 1-8-1, Kishinoura, Yahatanishi-ku, Kitakyushu, Fukuoka, 806-8501, Japan
| | - Y Tamura
- Department of Internal Medicine, Japan Community Healthcare Organization Kyushu Hospital, 1-8-1, Kishinoura, Yahatanishi-ku, Kitakyushu, Fukuoka, 806-8501, Japan
| | - M Mohri
- Department of Internal Medicine, Japan Community Healthcare Organization Kyushu Hospital, 1-8-1, Kishinoura, Yahatanishi-ku, Kitakyushu, Fukuoka, 806-8501, Japan
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Miyazaki S, Hamada T, Sugihara S, Mizuta E, Endo Y, Ohtahara A, Komatsu K, Kuwabara M, Fukuuchi T, Kaneko K, Ichida K, Ogino K, Ninomiya H, Yamamoto K, Nakamura T, Hisatome I. Xanthinuria Type 1 with a Novel Mutation in Xanthine Dehydrogenase and a Normal Endothelial Function. Intern Med 2022; 61:1383-1386. [PMID: 35491177 PMCID: PMC9152847 DOI: 10.2169/internalmedicine.7897-21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Whether or not extremely low levels of serum uric acid (SUA) in xanthinuria are associated with impairment of the endothelial function and exercise-induced acute kidney injury (EIAKI) is unclear. A 59-year-old woman without EIAKI or urolithiasis had undetectable levels of UA in serum and urine and elevated levels of hypoxanthine and xanthine in urine. A genetic analysis revealed homozygous mutations in the XDH gene [c.1585 C>T (p. Gln529*)]. Flow-mediated dilation was within the normal range. This is the first report of a case with extremely low levels of SUA, xanthinuria with novel mutations of xanthine dehydrogenase (XDH) and a normal endothelial function.
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Affiliation(s)
| | - Toshihiro Hamada
- Department of Community-Based Family Medicine, Tottori University, Faculty of Medicine, Japan
| | | | | | - Yusuke Endo
- Advanced Medicine, Innovation and Clinical Research Center, Tottori University Hospital, Japan
| | | | - Koji Komatsu
- Department of Psychiatry Disease, Tottori University, Japan
| | | | - Tomoko Fukuuchi
- Laboratory of Biomedical and Analytical Sciences, Faculty of Pharma-Science, Teikyo University, Japan
| | - Kiyoko Kaneko
- Faculty of Pharmaceutical Sciences, Teikyo Heisei University, Japan
| | - Kimiyoshi Ichida
- Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Japan
| | - Kazuhide Ogino
- Department of Cardiology, Japanese Red Cross Tottori Hospital, Japan
| | - Haruaki Ninomiya
- Department of Biological Regulation, Tottori University Faculty of Medicine, Japan
| | - Kazuhiro Yamamoto
- Division of Cardiovascular Medicine, Department of Molecular Medicine and Therapeutics, Faculty of Medicine, Tottori University, Japan
| | | | - Ichiro Hisatome
- Department of Cardiovascular Medicine, Yonago Medical Center, Japan
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Hypothetical Mechanism of Exercise-Induced Acute Kidney Injury Associated with Renal Hypouricemia. Biomedicines 2021; 9:biomedicines9121847. [PMID: 34944661 PMCID: PMC8698656 DOI: 10.3390/biomedicines9121847] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 11/29/2021] [Accepted: 12/03/2021] [Indexed: 11/17/2022] Open
Abstract
Renal hypouricemia (RHUC) is a hereditary disease that presents with increased renal urate clearance and hypouricemia due to genetic mutations in the urate transporter URAT1 or GLUT9 that reabsorbs urates in the renal proximal tubule. Exercise-induced acute kidney injury (EIAKI) is known to be a complication of renal hypouricemia. In the skeletal muscle of RHUC patients during exhaustive exercise, the decreased release of endothelial-derived hyperpolarization factor (EDHF) due to hypouricemia might cause the disturbance of exercise hyperemia, which might increase post-exercise urinary urate excretion. In the kidneys of RHUC patients after exhaustive exercise, an intraluminal high concentration of urates in the proximal straight tubule and/or thick ascending limb of Henle’s loop might stimulate the luminal Toll-like receptor 4–myeloid differentiation factor 88–phosphoinositide 3-kinase–mammalian target of rapamycin (luminal TLR4–MyD88–PI3K–mTOR) pathway to activate the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and may release interleukin-1β (IL-1β), which might cause the symptoms of EIAKI.
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Kawamura Y, Nakayama A, Shimizu S, Toyoda Y, Nishida Y, Hishida A, Katsuura-Kamano S, Shibuya K, Tamura T, Kawaguchi M, Suzuki S, Iwasawa S, Nakashima H, Ibusuki R, Uemura H, Hara M, Takeuchi K, Takada T, Tsunoda M, Arisawa K, Takezaki T, Tanaka K, Ichida K, Wakai K, Shinomiya N, Matsuo H. A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of URAT1/SLC22A12 among 30,685 Japanese Individuals. Biomedicines 2021; 9:biomedicines9081012. [PMID: 34440216 PMCID: PMC8393673 DOI: 10.3390/biomedicines9081012] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 08/06/2021] [Accepted: 08/09/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FEUA). Further studies on FEUA in hypouricemic individuals are needed for a more accurate diagnosis of RHUC. METHODS In 30,685 Japanese health-examination participants, we genotyped the two most common nonfunctional variants of URAT1 (NFV-URAT1), W258X (rs121907892) and R90H (rs121907896), in 1040 hypouricemic individuals (SUA ≤ 3.0 mg/dL) and 2240 individuals with FEUA data. The effects of NFV-URAT1 on FEUA and SUA were also investigated using linear and multiple regression analyses. RESULTS Frequency of hypouricemic individuals (SUA ≤ 3.0 mg/dL) was 0.97% (male) and 6.94% (female) among 30,685 participants. High frequencies of those having at least one allele of NFV-URAT1 were observed in 1040 hypouricemic individuals. Furthermore, NFV-URAT1 significantly increased FEUA and decreased SUA, enabling FEUA and SUA levels to be estimated. Conversely, FEUA and SUA data of hypouricemic individuals are revealed to be useful to predict the number of NFV-URAT1. CONCLUSIONS Our findings reveal that specific patterns of FEUA and SUA data assist with predicting the number of nonfunctional variants of causative genes for RHUC, and can also be useful for practical diagnosis of RHUC even before genetic tests.
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Affiliation(s)
- Yusuke Kawamura
- Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan; (Y.K.); (A.N.); (S.S.); (Y.T.); (M.K.); (N.S.)
| | - Akiyoshi Nakayama
- Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan; (Y.K.); (A.N.); (S.S.); (Y.T.); (M.K.); (N.S.)
| | - Seiko Shimizu
- Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan; (Y.K.); (A.N.); (S.S.); (Y.T.); (M.K.); (N.S.)
| | - Yu Toyoda
- Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan; (Y.K.); (A.N.); (S.S.); (Y.T.); (M.K.); (N.S.)
- Department of Pharmacy, Faculty of Medicine, The University of Tokyo Hospital, The University of Tokyo, Tokyo 113-8655, Japan;
| | - Yuichiro Nishida
- Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan; (Y.N.); (M.H.); (K.T.)
| | - Asahi Hishida
- Department of Preventive Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan; (A.H.); (T.T.); (K.T.); (K.W.)
| | - Sakurako Katsuura-Kamano
- Department of Preventive Medicine, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan; (S.K.-K.); (K.A.)
| | - Kenichi Shibuya
- Department of International Island and Community Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan; (K.S.); (R.I.); (T.T.)
- Department of Emergency and Intensive Care Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
| | - Takashi Tamura
- Department of Preventive Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan; (A.H.); (T.T.); (K.T.); (K.W.)
| | - Makoto Kawaguchi
- Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan; (Y.K.); (A.N.); (S.S.); (Y.T.); (M.K.); (N.S.)
| | - Satoko Suzuki
- Department of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa 359-8513, Japan; (S.S.); (S.I.); (H.N.); (M.T.)
| | - Satoko Iwasawa
- Department of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa 359-8513, Japan; (S.S.); (S.I.); (H.N.); (M.T.)
| | - Hiroshi Nakashima
- Department of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa 359-8513, Japan; (S.S.); (S.I.); (H.N.); (M.T.)
| | - Rie Ibusuki
- Department of International Island and Community Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan; (K.S.); (R.I.); (T.T.)
| | - Hirokazu Uemura
- Department of Health and Welfare System, College of Nursing Art and Science, University of Hyogo, Akashi 673-8588, Japan;
| | - Megumi Hara
- Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan; (Y.N.); (M.H.); (K.T.)
| | - Kenji Takeuchi
- Department of Preventive Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan; (A.H.); (T.T.); (K.T.); (K.W.)
| | - Tappei Takada
- Department of Pharmacy, Faculty of Medicine, The University of Tokyo Hospital, The University of Tokyo, Tokyo 113-8655, Japan;
| | - Masashi Tsunoda
- Department of Preventive Medicine and Public Health, National Defense Medical College, Tokorozawa 359-8513, Japan; (S.S.); (S.I.); (H.N.); (M.T.)
| | - Kokichi Arisawa
- Department of Preventive Medicine, Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8503, Japan; (S.K.-K.); (K.A.)
| | - Toshiro Takezaki
- Department of International Island and Community Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan; (K.S.); (R.I.); (T.T.)
| | - Keitaro Tanaka
- Department of Preventive Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan; (Y.N.); (M.H.); (K.T.)
| | - Kimiyoshi Ichida
- Department of Pathophysiology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan;
- Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo 105-8461, Japan
| | - Kenji Wakai
- Department of Preventive Medicine, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan; (A.H.); (T.T.); (K.T.); (K.W.)
| | - Nariyoshi Shinomiya
- Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan; (Y.K.); (A.N.); (S.S.); (Y.T.); (M.K.); (N.S.)
| | - Hirotaka Matsuo
- Department of Integrative Physiology and Bio-Nano Medicine, National Defense Medical College, Tokorozawa 359-8513, Japan; (Y.K.); (A.N.); (S.S.); (Y.T.); (M.K.); (N.S.)
- Correspondence: ; Tel.: +81-4-2995-1482
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19
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Gundlapalli S, Gaur Y, Rao MV, Bande SR, Sandhya P. Renal Hypouricemia with Exercise Induced Acute Kidney Injury-A Case Report. Indian J Nephrol 2021; 31:307-310. [PMID: 34376951 PMCID: PMC8330661 DOI: 10.4103/ijn.ijn_127_20] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 05/18/2020] [Accepted: 05/31/2020] [Indexed: 01/04/2023] Open
Abstract
Acute kidney injury after exercise is most commonly secondary to rhabdomyolysis. Non-rhabdomyolysis AKI is secondary to a limited number of disorders of which renal hypouricemia (RHUC) needs a special mention. It is relatively a rare genetic disorder and is reported in Japanese and Ashkenazi Jews. Humans have lost the ability to metabolize uric acid as the “uricase” gene is suppressed. Renal tubules handle uric acid and aid in maintaining serum concentrations in the soluble range. Uric acid excretion is increased in RHUC patients due to proximal tubular defects. This leads to the loss of antioxidant capabilities of the kidney, predisposing them to severe AKI following anaerobic exercise. We report a case of exercise-induced AKI secondary to renal hypouricemia.
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Affiliation(s)
| | - Yogesh Gaur
- Department of Nephrology, AINU, Hyderabad, Telangana, India
| | | | | | - P Sandhya
- Department of Anesthesiology, Axon Group, Hyderabad, Telangana, India
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20
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Kelly R, Semple D, Harper A. Recurrent Acute Kidney Injury with Severe Loin Pain and Patchy Renal Ischaemia after Anaerobic Exercise without Renal Hypouricaemia in a New Zealand European Male. Case Rep Nephrol Dial 2021; 11:176-182. [PMID: 34327220 PMCID: PMC8299420 DOI: 10.1159/000517114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 05/07/2021] [Indexed: 12/29/2022] Open
Abstract
Acute kidney injury with severe loin pain and patchy renal ischaemia after anaerobic exercise (ALPE) is a rare clinical syndrome. ALPE has predominantly been described in Japanese and Korean populations to date. Many cases and most recurrent examples are associated with renal hypouricaemia. We describe a 28-year-old New Zealand European male without renal hypouricaemia who developed recurrent ALPE whilst performing elite-level sport. Avoiding elite-level anaerobic exercise was successful at preventing further episodes. This report confirms the first known case of ALPE in a New Zealand European male and raises the possibility that ALPE is an under-recognized condition. Long-term outcomes of recurrent ALPE remain unclear, and preventative strategies should be implemented to preserve renal function. Avoiding intense anaerobic exercise is an effective preventative strategy.
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Affiliation(s)
- Richard Kelly
- Auckland District Health Board, Auckland, New Zealand
| | - David Semple
- Department of Renal Medicine, Auckland District Health Board, Auckland, New Zealand.,School of Medicine, University of Auckland, Auckland, New Zealand
| | - Alana Harper
- Adult Emergency Department, Auckland District Health Board, Auckland, New Zealand.,Auckland Rescue Helicopter Trust, Auckland, New Zealand
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21
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Hisatome I, Li P, Miake J, Taufiq F, Mahati E, Maharani N, Utami SB, Kuwabara M, Bahrudin U, Ninomiya H. Uric Acid as a Risk Factor for Chronic Kidney Disease and Cardiovascular Disease ― Japanese Guideline on the Management of Asymptomatic Hyperuricemia ―. Circ J 2021; 85:130-138. [DOI: 10.1253/circj.cj-20-0406] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Ichiro Hisatome
- Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science
| | - Peili Li
- Division of Regenerative Medicine and Therapeutics, Department of Genetic Medicine and Regenerative Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Science
| | - Junichiro Miake
- Department of Pharmacology, Tottori University Faculty of Medicine
| | - Fikri Taufiq
- Department of Physiology, Faculty of Medicine, Sultan Agung Islamic University
| | - Endang Mahati
- Department of Pharmacology and Therapy, Faculty of Medicine, Diponegoro University
| | - Nani Maharani
- Department of Pharmacology and Therapy, Faculty of Medicine, Diponegoro University
| | - Sulistiyati Bayu Utami
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Diponegoro University
| | - Masanari Kuwabara
- Intensive Care Unit and Department of Cardiology, Toranomon Hospital
| | - Udin Bahrudin
- Department of Cardiology and Vascular Medicine, Faculty of Medicine, Diponegoro University
| | - Haruaki Ninomiya
- Department of Biological Regulation, Tottori University Faculty of Medicine
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22
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Park JH, Jo YI, Lee JH. Renal effects of uric acid: hyperuricemia and hypouricemia. Korean J Intern Med 2020; 35:1291-1304. [PMID: 32872730 PMCID: PMC7652664 DOI: 10.3904/kjim.2020.410] [Citation(s) in RCA: 60] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 08/31/2020] [Indexed: 02/07/2023] Open
Abstract
The prevalence of chronic kidney disease (CKD) is increasing worldwide. Although hyperuricemia has been associated with CKD in many studies, it remains controversial whether this is the cause or the result of decreased renal function. Recent observational studies of healthy populations and patients with CKD have reported that uric acid (UA) has an independent role in the development or progression of CKD. Experimental studies have shown several potential mechanisms by which hyperuricemia may cause or promote CKD. However, other reports have indicated an association between hypouricemia and CKD. This opposing effect is hypothesized to occur because UA is a major antioxidant in human plasma and is associated with oxidative stress. In this article, we discuss the potential association between UA imbalance and CKD and how they can be treated.
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Affiliation(s)
- Jung Hwan Park
- Division of Nephrology, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
- Correspondence to Jung Hwan Park, M.D. Division of Nephrology, Department of Internal Medicine, Konkuk University Medical Center, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, Korea Tel: +82-2-2030-7528, Fax: +82-2-2030-7748, E-mail:
| | - Yong-Il Jo
- Division of Nephrology, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Jong-Ho Lee
- Division of Nephrology, Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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Furuhashi M. New insights into purine metabolism in metabolic diseases: role of xanthine oxidoreductase activity. Am J Physiol Endocrinol Metab 2020; 319:E827-E834. [PMID: 32893671 DOI: 10.1152/ajpendo.00378.2020] [Citation(s) in RCA: 182] [Impact Index Per Article: 36.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Xanthine oxidoreductase (XOR) consists of two different forms, xanthine dehydrogenase and xanthine oxidase (XO), and is a rate-limiting enzyme of uric acid production from hypoxanthine and xanthine. Uric acid is the end product of purine metabolism in humans and has a powerful antioxidant effect. The lack of ascorbic acid, known as vitamin C, in hominoids has been thought to cause a compensatory increase in uric acid as an antioxidant by unfunctional gene mutation of uricase to a pseudogene. Because XO is involved in an increase in reactive oxygen species (ROS) by generating superoxide and hydrogen peroxide, inadequate activation of XOR promotes oxidative stress-related tissue injury. Plasma XOR activity is associated with obesity, smoking, liver dysfunction, hyperuricemia, dyslipidemia, insulin resistance, and adipokines, indicating a novel biomarker of metabolic disorders. However, XOR activity in adipose tissue is low in humans unlike in rodents, and hypoxanthine is secreted from human adipose tissue. The concentration of hypoxanthine, but not xanthine, is independently associated with obesity in a general population, indicating differential regulation of hypoxanthine and xanthine. Treatment with an XOR inhibitor can decrease uric acid for preventing gout, reduce production of XO-related ROS, and promote reutilization of hypoxanthine and ATP production through the salvage pathway. It has recently been suggested that discontinuation of an XOR inhibitor causes adverse cardiovascular outcomes as XOR inhibitor withdrawal syndrome, possibly due to cardiac disturbance of conduction and contraction by reduced ATP production. New insights into purine metabolism, including the role of XOR activity in the past 5 yr, are mainly discussed in this review.
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Affiliation(s)
- Masato Furuhashi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan
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Shoho M, Kuriyama A. Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise. Am J Emerg Med 2020; 43:291.e1-291.e3. [PMID: 33059989 DOI: 10.1016/j.ajem.2020.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2020] [Revised: 10/02/2020] [Accepted: 10/02/2020] [Indexed: 10/23/2022] Open
Abstract
Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE) is gradually gaining recognition. In this case series, we describe the presentation of ALPE in the emergency department setting and its clinical course. In Case 1, an 18-year-old man presented with acute-onset nausea, vomiting, and right flank pain after playing basketball, with a creatinine level of 6.42 mg/dL on initial presentation. He received fluid therapy and intravenous furosemide for 2 days. His creatinine level was 1.80 mg/dL on day 8 and finally declined to 0.71 mg/dL on day 39. In Case 2, a 31-year-old man presented with acute-onset nausea and right lower abdominal pain after swimming, with a creatinine level of 4.68 mg/dL on initial presentation. He only received fluid therapy, and his creatinine level finally declined to 0.90 mg/dL on day 11. In both cases, severe loin pain began after anaerobic exercise, and acute kidney injury without myoglobinuria was observed. The findings of our case series suggest that emergency physicians should consider ALPE in the differential diagnosis of abdominal and loin pain accompanied by an elevated creatinine level in young patients because it can be treated conservatively and has a good prognosis. Moreover, watchful waiting is recommended for ALPE while also emphasizing the need to exclude potentially life threatening or treatable kidney diseases.
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Affiliation(s)
- Miyuki Shoho
- Emergency and Critical Care Center, Kurashiki Central Hospital, Japan
| | - Akira Kuriyama
- Emergency and Critical Care Center, Kurashiki Central Hospital, Japan.
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Aomura D, Sonoda K, Harada M, Hashimoto K, Kamijo Y. A Case of Acute Kidney Injury in a Patient with Renal Hypouricemia without Intense Exercise. Case Rep Nephrol Dial 2020; 10:26-34. [PMID: 32309296 PMCID: PMC7154233 DOI: 10.1159/000506673] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 02/15/2020] [Indexed: 01/18/2023] Open
Abstract
Exercise-induced acute kidney injury (EIAKI) frequently develops in patients with renal hypouricemia (RHUC). However, several cases of RHUC with acute kidney injury (AKI) but without intense exercise have been reported. We encountered a 15-year-old male with RHUC who experienced AKI. He reported no episodes of intense exercise and displayed no other representative risk factors of EIAKI, although a vasopressor had been administered for orthostatic dysregulation before AKI onset. His kidney dysfunction improved with discontinuation of the vasopressor and conservative treatment. Thus, AKI can develop in patients with RHUC in the absence of intense exercise, for which vasopressors may be a risk factor.
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Affiliation(s)
- Daiki Aomura
- Department of Nephrology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Kosuke Sonoda
- Department of Nephrology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Makoto Harada
- Department of Nephrology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Koji Hashimoto
- Department of Nephrology, Shinshu University School of Medicine, Matsumoto, Japan
| | - Yuji Kamijo
- Department of Nephrology, Shinshu University School of Medicine, Matsumoto, Japan
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Furuto Y, Kawamura M, Namikawa A, Takahashi H, Shibuya Y, Mori T, Sohara E. Non-urate transporter 1, non-glucose transporter member 9-related renal hypouricemia and acute renal failure accompanied by hyperbilirubinemia after anaerobic exercise: a case report. BMC Nephrol 2019; 20:433. [PMID: 31771519 PMCID: PMC6878684 DOI: 10.1186/s12882-019-1618-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Accepted: 11/08/2019] [Indexed: 11/11/2022] Open
Abstract
Background Renal hypouricemia (RHUC) is an inherited heterogenous disorder caused by faulty urate reabsorption transporters in the renal proximal tubular cells. Anaerobic exercise may induce acute kidney injury in individuals with RHUC that is not caused by exertional rhabdomyolysis; it is called acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE). RHUC is the most important risk factor for ALPE. However, the mechanism of onset of ALPE in patients with RHUC has not been elucidated. The currently known genes responsible for RHUC are SLC22A12 and SLC2A9. Case presentation A 37-year-old man presented with loin pain after exercising. Despite having a healthy constitution from birth, biochemical examination revealed hypouricemia, with a uric acid (UA) level of < 1 mg/dL consistently at every health check. We detected acute kidney injury, with a creatinine (Cr) level of 4.1 mg/dL, and elevated bilirubin; hence, the patient was hospitalized. Computed tomography revealed no renal calculi, but bilateral renal swelling was noted. Magnetic resonance imaging detected cuneiform lesions, indicating bilateral renal ischemia. Fractional excretion values of sodium and UA were 0.61 and 50.5%, respectively. Urinary microscopy showed lack of tubular injury. The patient’s older sister had hypouricemia. The patient was diagnosed with ALPE. Treatment with bed rest, fluid replacement, and nutrition therapy improved renal function and bilirubin levels, and the patient was discharged on day 5. Approximately 1 month after onset of ALPE, his Cr, UA, and TB levels were 0.98, 0.8, and 0.9 mg/dL, respectively. We suspected familial RHUC due to the hypouricemia and family history and performed genetic testing but did not find the typical genes responsible for RHUC. A full genetic analysis was opposed by the family. Conclusions To the best of our knowledge, this is the first report of ALPE with hyperbilirubinemia. Bilirubin levels may become elevated as a result of heme oxygenase-1 activation, occurring in exercise-induced acute kidney injury in patients with RHUC; this phenomenon suggests renal ischemia-reperfusion injury. A new causative gene coding for a urate transporter may exist, and its identification would be useful to clarify the urate transport mechanism.
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Affiliation(s)
- Yoshitaka Furuto
- Department of Hypertension and Nephrology, NTT Medical Centre, Tokyo, 5-9-22, Higasi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan.
| | - Mariko Kawamura
- Department of Hypertension and Nephrology, NTT Medical Centre, Tokyo, 5-9-22, Higasi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan
| | - Akio Namikawa
- Department of Hypertension and Nephrology, NTT Medical Centre, Tokyo, 5-9-22, Higasi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan
| | - Hiroko Takahashi
- Department of Hypertension and Nephrology, NTT Medical Centre, Tokyo, 5-9-22, Higasi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan
| | - Yuko Shibuya
- Department of Hypertension and Nephrology, NTT Medical Centre, Tokyo, 5-9-22, Higasi-Gotanda, Shinagawa-ku, Tokyo, 141-8625, Japan
| | - Takayasu Mori
- Department of Nephrology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Eisei Sohara
- Department of Nephrology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
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Jeon Y, Lis JB, Chang WG. NSAID associated bilateral renal infarctions: a case report. Int J Nephrol Renovasc Dis 2019; 12:177-181. [PMID: 31447577 PMCID: PMC6682756 DOI: 10.2147/ijnrd.s212010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 07/04/2019] [Indexed: 11/23/2022] Open
Abstract
Renal infarctions (RIs) are caused by interruptions in the renal arterial blood flow. RIs are generally considered to be rare, however we present the case of a 37 year old woman whose renal infarction was likely due to the vasoconstrictive effects of non-steroidal anti-inflammatory drugs. Although high-dose non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause a decrease in renal perfusion, they have not been accepted as causative agents in renal infarction. Theoretically, patients in prostaglandin dependent states should be more vulnerable to renovascular vasoconstriction and resulting hypoperfusion in the presence of NSAIDs. Given the high prevalence of NSAID use, we suspect that this mechanism of renal injury may be more prevalent than previously thought.
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Affiliation(s)
- Yejoo Jeon
- Yale School of Medicine, Department of Internal Medicine, Yale University, New Haven, CT, USA
| | - Jonathan B Lis
- Yale School of Medicine, Department of Internal Medicine, Yale University, New Haven, CT, USA
| | - William G Chang
- Yale School of Medicine, Department of Internal Medicine, Yale University, New Haven, CT, USA
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Shimizu Y, Wakabayashi K, Totsuka A, Hayashi Y, Nitta S, Hara K, Akira M, Tomino Y, Suzuki Y. Exercise-Induced Acute Kidney Injury in a Police Officer with Hereditary Renal Hypouricemia. Case Rep Nephrol Dial 2019; 9:92-101. [PMID: 31602378 PMCID: PMC6738254 DOI: 10.1159/000501877] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2019] [Accepted: 07/02/2019] [Indexed: 12/27/2022] Open
Abstract
Hereditary renal hypouricemia is characterized by hypouricemia with hyper-uric acid clearance due to a defect in renal tubular transport. Patients with hereditary renal hypouricemia have a higher risk of exercise-induced acute kidney injury (EAKI) and reduced kidney function. Although the best preventive measure is avoiding exercise, there are many kinds of jobs that require occupational exercise. A 27-year-old male police officer suffered from stage 3 AKI after performing a 20-m multistage shuttle run test. His mother had previously been diagnosed as having renal hypouricemia at another facility. The patient had reported having hypouricemia during a health check at a previous police station, but his serum uric acid concentration was within the normal range at our hospital. After treatment, he recovered from EAKI and exhibited low serum uric acid and hyper-uric acid clearance. Since the patient desired to continue his career requiring strenuous exercise, it was difficult to establish a preventive plan against the recurrence of EAKI. Patients with hereditary renal hypouricemia who must undergo strenuous occupational anaerobic exercise are at higher risk of developing EAKI than other workers. The risks of EAKI among patients with hypouricemia should be considered when undergoing physical occupational training.
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Affiliation(s)
- Yoshio Shimizu
- Division of Nephrology, Department of Internal Medicine, Juntendo University Shizuoka Hospital, Izunokuni, Japan.,Shizuoka Medical Research Center for Disaster, Juntendo University, Tokyo, Japan
| | - Keiichi Wakabayashi
- Division of Nephrology, Department of Internal Medicine, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Ayako Totsuka
- Division of Nephrology, Department of Internal Medicine, Juntendo University Shizuoka Hospital, Izunokuni, Japan.,Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan
| | - Yoko Hayashi
- Division of Nephrology, Department of Internal Medicine, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Shusaku Nitta
- Division of Nephrology, Department of Internal Medicine, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Kazuaki Hara
- Division of Nephrology, Department of Internal Medicine, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Maiko Akira
- Division of Nephrology, Department of Internal Medicine, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Yasuhiko Tomino
- Asian Pacific Renal Research Promotion Office, Showakai Medical Corporation, Tokyo, Japan
| | - Yusuke Suzuki
- Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan
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Furuhashi M, Mori K, Tanaka M, Maeda T, Matsumoto M, Murase T, Nakamura T, Koyama M, Moniwa N, Ohnishi H, Saitoh S, Shimamoto K, Miura T. Unexpected high plasma xanthine oxidoreductase activity in female subjects with low levels of uric acid. Endocr J 2018; 65:1083-1092. [PMID: 30068899 DOI: 10.1507/endocrj.ej18-0127] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Hypouricemia is a high-risk factor of exercise-induced acute kidney injury (EIAKI) probably through a lack of an antioxidant effect of uric acid. Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the formation of uric acid from hypoxanthine and xanthine, leading to an increase in superoxide and reactive oxygen species. Activation of XOR has been proposed to promote oxidative stress-related tissue injury. We measured plasma XOR activity by a sensitive and accurate assay using a combination of liquid chromatography and triple quadrupole mass spectrometry in subjects with relatively low levels of uric acid (≤4.0 mg/dL) who were recruited from 627 subjects (male/female: 292/335) in the Tanno-Sobetsu Study, a population-based cohort. The numbers of subjects with uric acid ≤4.0 mg/dL, ≤3.0 mg/dL and ≤2.0 mg/dL were 72 (11.5%, male/female: 5/67), 13 (2.1%, all females) and 2 (0.3%, both females), respectively. Plasma XOR activities in 5 male subjects were below the median value of the 292 male subjects. In 12 (17.9%) of the 67 female subjects with uric acid ≤4.0 mg/dL, plasma XOR activities were above the upper quartile value of the 335 female subjects. Eleven of the 12 female subjects with high plasma XOR activity and a low uric acid level had liver dysfunction and/or insulin resistance. In conclusion, unexpected high plasma XOR activities were found in some female subjects with relatively low levels of uric acid. Measurement of plasma XOR activity may help to identify hypouricemic patients with a high risk for EIAKI.
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Affiliation(s)
- Masato Furuhashi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
| | - Kazuma Mori
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
| | - Marenao Tanaka
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
| | - Takuto Maeda
- Department of Nephrology, Teine Keijinkai Hospital, Sapporo 006-8555, Japan
| | - Megumi Matsumoto
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
| | - Takayo Murase
- Sanwa Kagaku Kenkyusho Co., Ltd., Inabe 511-0406, Japan
| | | | - Masayuki Koyama
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
- Department of Public Health, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
| | - Norihito Moniwa
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
| | - Hirofumi Ohnishi
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
- Department of Public Health, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
| | - Shigeyuki Saitoh
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
- Department of Nursing, Division of Medical and Behavioral Subjects, Sapporo Medical University School of Health Sciences, Sapporo 060-8543, Japan
| | | | - Tetsuji Miura
- Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan
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Serine Protease Inhibitor Kazal Type I (SPINK1) Mutation: A Risk Factor for Early-onset Chronic Pancreatitis? J Pediatr Gastroenterol Nutr 2018; 67:e40. [PMID: 29746346 DOI: 10.1097/mpg.0000000000002024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
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Shimizu Y, Takaori K, Maeda S. Exercise-induced acute renal failure in a trainee cyclist without hypouricemia: Successful athletic career post-treatment. J Gen Fam Med 2017; 18:432-435. [PMID: 29264080 PMCID: PMC5729381 DOI: 10.1002/jgf2.108] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Accepted: 03/21/2017] [Indexed: 02/04/2023] Open
Abstract
Acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE) is exercise‐induced acute renal failure that occurs without myoglobinuria. We describe a typical case involving an 18‐year‐old man. Generally, patients with ALPE are advised to avoid anaerobic exercise due to risk of recurrence, but our patient continued and went on to become a professional cyclist without relapse. About 51% of ALPE cases involve patients with renal hypouricemia. His serum uric acid levels were rather high, at 6.4 mg/dL. He is the first patient with ALPE to succeed as a professional athlete in an anaerobic sport.
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Affiliation(s)
- Yoko Shimizu
- Department of Nephrology Otsu Red-Cross Hospital Otsu Japan
| | - Koji Takaori
- Department of Nephrology Otsu Red-Cross Hospital Otsu Japan
| | - Sayako Maeda
- Department of Nephrology Otsu Red-Cross Hospital Otsu Japan
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Maekawa M, Imaizumi T, Yamakawa T, Ito Y. Acute Renal Failure with Severe Loin Pain and Patchy Renal Vasoconstriction in a Patient without Hypouricemia, Provoked by Epileptic Seizure. Intern Med 2017; 56:2001-2005. [PMID: 28768971 PMCID: PMC5577077 DOI: 10.2169/internalmedicine.56.8328] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Accepted: 11/08/2016] [Indexed: 11/11/2022] Open
Abstract
A 26-year-old Japanese man without hypouricemia and with 3 previous episodes of seizures concurrent with acute kidney injury (AKI) was admitted due to an epileptic seizure, lower back pain and AKI. His creatinine kinase levels were slightly elevated. Patchy renal ischemia on contrast-enhanced computed tomography and persistent residual contrast medium was observed, consistent with acute renal failure with severe loin pain and patchy renal ischemia after anaerobic exercise (ALPE). Diffusion-weighted imaging (DWI) demonstrated signal changes in the corresponding area. ALPE should be considered a cause of AKI following seizures. We recommend DWI as an alternative diagnostic modality.
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Affiliation(s)
| | | | - Taishi Yamakawa
- Department of Nephrology, Toyohashi Municipal Hospital, Japan
| | - Yasuhiko Ito
- Department of Nephrology and Renal Replacement Therapy, Nagoya University Graduate School of Medicine, Japan
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Hodgson LE, Walter E, Venn RM, Galloway R, Pitsiladis Y, Sardat F, Forni LG. Acute kidney injury associated with endurance events-is it a cause for concern? A systematic review. BMJ Open Sport Exerc Med 2017; 3:e000093. [PMID: 29259804 PMCID: PMC5731225 DOI: 10.1136/bmjsem-2015-000093] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2015] [Revised: 03/23/2016] [Accepted: 03/26/2016] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION A growing body of evidence suggests even small rises in serum creatinine (SCr) are of considerable clinical relevance. Given that participants in endurance events are exposed to potential (repeated) renal insults, a systematic review was undertaken to collate current evidence for acute kidney injury (AKI), complicating such events. METHODS A systematic review of studies and case reports meeting inclusion criteria on Medline and EMBASE (inception to October 2015). Included: studies with markers of renal function before and after endurance or ultraendurance events; case reports of severe AKI. Two reviewers assessed risk of bias using the Newcastle-Ottawa scale. RESULTS Eleven case report publications (n=27 individuals) of severe AKI, were retrieved, with risk factors including systemic illness or nephrotoxic medications usually identified. From 30 studies of endurance and ultraendurance events, mean rise in SCr was 29 (±12.3) µmol/L after marathon or ultramarathon (17 studies, n=568 participants) events. Where follow-up tests were conducted, SCr returned to baseline within 48 hours. Rises in biomarkers suggest potential parenchymal insult, rather than simply muscle breakdown. However, evidence of long-term deleterious effects is lacking. CONCLUSIONS Raised levels of SCr are reported immediately after endurance events. It is not clear whether this is either clinically significant, or if repeated participation predisposes to long-term sequelae. The aetiology of severe exercise-associated AKI is usually multifactorial, with risk factors generally identified in the rare cases reported. On-site biochemistry, urine analysis and biomarkers of AKI may help identify collapsed runners who are at significant short-term risk and allow suitable follow-up.
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Affiliation(s)
- LE Hodgson
- Department of Anaesthesia, Western Sussex Hospitals NHS Foundation Trust, West Sussex, UK
| | - E Walter
- Department of Emergency Medicine, Royal Sussex County Hospital, East Sussex, UK
| | - RM Venn
- Department of Anaesthesia, Western Sussex Hospitals NHS Foundation Trust, West Sussex, UK
| | - R Galloway
- Faculty of Health and Medical Sciences, University of Surrey, Surrey, UK
| | - Y Pitsiladis
- Department of Emergency Medicine, Royal Sussex County Hospital, East Sussex, UK
| | - F Sardat
- Department of Intensive Care, Surrey Peri-operative Anaesthesia Critical care collaborative Research group (SPACeR), Royal Surrey County Hospital, Surrey, UK
| | - LG Forni
- Department of Emergency Medicine, Royal Sussex County Hospital, East Sussex, UK
- The centre for sport and exercise science and medicine (SESAME), Sport and Service Management, Eastbourne, UK
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Kuwabara M, Niwa K, Ohtahara A, Hamada T, Miyazaki S, Mizuta E, Ogino K, Hisatome I. Prevalence and complications of hypouricemia in a general population: A large-scale cross-sectional study in Japan. PLoS One 2017; 12:e0176055. [PMID: 28448596 PMCID: PMC5407834 DOI: 10.1371/journal.pone.0176055] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Accepted: 04/04/2017] [Indexed: 11/18/2022] Open
Abstract
BACKGROUNDS Hypouricemia was reported as a risk factor for exercise-induced acute renal injury (EIAKI) and urinary stones. However, the prevalence of kidney diseases among hypouricemic subjects has not been evaluated. This study was conducted to clarify the prevalence of hypouricemia and the association of hypouricemia with kidney diseases by using a large-scale Japanese population data. METHODS This study is a retrospective cross-sectional study at the Center for Preventive Medicine, St. Luke's International Hospital, Tokyo, Japan, and Sanin Rousai Hospital, Yonago, Japan. We analyzed the medical records of 90,143 Japanese subjects at the center in St. Luke's International Hospital, Tokyo, and 4,837 subjects in Sanin Rousai Hospital, Yonago, who underwent annual regular health check-up between January 2004 and June 2010. We defined hypouricemia as serum uric acid level of ≤2.0 mg/dL. We checked the medical history of all the study subjects and compared the rates of complications including urinary stones and kidney diseases among those with or without hypouricemia. RESULTS The prevalence of hypouricemia was 0.19% in St. Luke's International Hospital, Tokyo, and 0.58% in Sanin Rousai Hospital, Yonago. The prevalence of hypouricemia in women was larger than that in men both in Tokyo (0.31% vs 0.068%, p<0.001) and in Yonago (1.237% vs 0.318%, p<0.001). Among 172 hypouricemic subjects (30 men), the rates of previous urinary stones and kidney diseases (including nephritis/nephrosis) were 1.2% (3.3% men, 0.7% women) and 2.3% (10% men, 0.7% women), respectively. Hypouricemic men had a 9-fold higher rate of previously having kidney diseases compared to non-hypouricemic men (p<0.001). However, the rates of other diseases including urinary stones were not significantly different between the two groups. CONCLUSIONS Hypouricemia was associated with a history of kidney disease especially in men.
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Affiliation(s)
- Masanari Kuwabara
- Department of Cardiology, Toranomon Hospital, Tokyo, Japan
- Division of Renal Diseases and Hypertension, School of Medicine, University of Colorado Denver, Aurora, Colorado, United States of America
- Department of Cardiology, Cardiovascular Center, St. Luke's International Hospital, Tokyo, Japan
- * E-mail:
| | - Koichiro Niwa
- Department of Cardiology, Cardiovascular Center, St. Luke's International Hospital, Tokyo, Japan
| | - Akira Ohtahara
- Department of Cardiology, Sanin Rosai Hospital, Yonago, Tottori, Japan
| | - Toshihiro Hamada
- Department of Community-Based Family Medicine, Tottori University Faculty of Medicine, Yonago, Tottori, Japan
| | - Satoshi Miyazaki
- Department of Cardiovascular Medicine, Masao Fujii Memorial Hospital, Kurayoshi, Tottori, Japan
| | - Einosuke Mizuta
- Department of Cardiology, Sanin Rosai Hospital, Yonago, Tottori, Japan
| | - Kazuhide Ogino
- Department of Clinical Laboratory, Tottori University Hospital, Yonago, Tottori, Japan
| | - Ichiro Hisatome
- Division of Regenerative Medicine and Therapeutics, Institute of Regenerative Medicine and Biofunction, Tottori University Graduate School of Medical Sciences, Yonago, Tottori, Japan
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Hosoyamada M, Tsurumi Y, Hirano H, Tomioka NH, Sekine Y, Morisaki T, Uchida S. Urat1-Uox double knockout mice are experimental animal models of renal hypouricemia and exercise-induced acute kidney injury. NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS 2017; 35:543-549. [PMID: 27906636 DOI: 10.1080/15257770.2016.1143559] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
Renal hypouricemia (RHUC) is a hereditary disease characterized by a low level of plasma urate but with normal urinary urate excretion. RHUC type 1 is caused by mutations of the urate transporter URAT1 gene (SLC22A12). However, the plasma urate levels of URAT1 knockout mice are no different from those of wild-type mice. In the present study, a double knockout mouse, in which the URAT1 and uricase (Uox) genes were deleted (Urat1-Uox-DKO), were used as an experimental animal model of RHUC type 1 to investigate RHUC and excise-induced acute kidney injury (EIAKI). Mice were given a variable content of allopurinol for one week followed by HPLC measurement of urate and creatinine concentrations in spot urine and blood from the tail. The urinary excretion of urate in Urat1-Uox-DKO mice was approximately 25 times higher than those of humans. With allopurinol, the plasma urate levels of Urat1-Uox-DKO mice were lower than those of Uox-KO mice. There were no differences in the urinary urate excretions between Urat1-Uox-DKO and Uox-KO mice administered with 9 mg allopurinol /100 g feed. In the absence of allopurinol, plasma creatinine levels of some Urat1-Uox-DKO mice were higher than those of Uox-KO mice. Consequently, hypouricemia and normouricosuria may indicate that the Urat1-Uox-DKO mouse administered with allopurinol may represent a suitable animal model of RHUC type 1. Urat1-Uox-DKO mice without allopurinol exhibited acute kidney injury, thus providing additional benefit as a potential animal model for EIAKI. Finally, our data indicate that allopurinol appears to provide prophylactic effects for EIAKI.
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Affiliation(s)
- Makoto Hosoyamada
- a Department of Human Physiology & Pathology , Faculty of Pharma-Sciences, Teikyo University , Tokyo , Japan
| | - Yu Tsurumi
- b Department of Practical Pharmacology , Faculty and Graduate School of Pharmaceutical Sciences, Chiba University , Chiba , Japan
| | - Hidenori Hirano
- b Department of Practical Pharmacology , Faculty and Graduate School of Pharmaceutical Sciences, Chiba University , Chiba , Japan
| | - Naoko H Tomioka
- a Department of Human Physiology & Pathology , Faculty of Pharma-Sciences, Teikyo University , Tokyo , Japan
| | - Yuko Sekine
- b Department of Practical Pharmacology , Faculty and Graduate School of Pharmaceutical Sciences, Chiba University , Chiba , Japan
| | - Takayuki Morisaki
- c Department of Bioscience , National Cardiovascular Center Research Institute , Osaka , Japan
| | - Shunya Uchida
- d Department of Internal Medicine , Faculty of Medicine, Teikyo University , Tokyo , Japan
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Uedono H, Tsuda A, Ishimura E, Nakatani S, Kurajoh M, Mori K, Uchida J, Emoto M, Nakatani T, Inaba M. U-shaped relationship between serum uric acid levels and intrarenal hemodynamic parameters in healthy subjects. Am J Physiol Renal Physiol 2017; 312:F992-F997. [PMID: 28249837 DOI: 10.1152/ajprenal.00645.2016] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 02/17/2017] [Accepted: 02/23/2017] [Indexed: 02/04/2023] Open
Abstract
Hyperuricemia has been reported to affect renal hemodynamics. In a recent study, both low and high levels of serum uric acid (SUA) were found to be associated with loss of kidney function. The goal of this study was to evaluate the relationship between SUA levels and intrarenal hemodynamic parameters in healthy subjects, using plasma clearance of para-aminohippurate (CPAH) and inulin (Cin). Renal and glomerular hemodynamics were evaluated by simultaneous measurements of CPAH and Cin in 48 healthy subjects (54.6 ± 13.4 yr). Intrarenal hemodynamic parameters, including efferent and afferent (Ra) arteriolar resistance, were calculated using Gómez's formulas. Relationships of SUA levels with these intrarenal hemodynamic parameters were examined. In quadratic regression analysis, SUA levels had a significant inverse U-shaped relationship with Cin (P < 0.0001, R2 = 0.350) and CPAH (P = 0.0093, R2 = 0.188) and a U-shaped relationship with Ra (P = 0.0011, R2 = 0.262). In multiple regression analysis with normal (3.5-6.0 mg/dl) and mildly low or high (<3.5 or >6.0 mg/dl) SUA levels entered as dummy variables of zero and one, respectively, mildly low or high SUA levels were significantly and independently associated with Ra (β = 0.230, P = 0.0403) after adjustment for several factors (R2 = 0.597, P < 0.0001). Both mild hyperuricemia and mild hypouricemia are significantly associated with increased Ra, although weakly. The increase in Ra in subjects with mild hyperuricemia or hypouricemia may be related to renal hemodynamic abnormalities, possibly leading to a decline in renal function.
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Affiliation(s)
- Hideki Uedono
- Departments of Nephrology, and Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan; and
| | - Akihiro Tsuda
- Departments of Nephrology, and Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan; and
| | - Eiji Ishimura
- Departments of Nephrology, and Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan; and
| | - Shinya Nakatani
- Departments of Nephrology, and Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan; and
| | - Masafumi Kurajoh
- Departments of Nephrology, and Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan; and
| | - Katsuhito Mori
- Departments of Nephrology, and Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan; and
| | - Junji Uchida
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Masanori Emoto
- Departments of Nephrology, and Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan; and
| | - Tatsuya Nakatani
- Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Masaaki Inaba
- Departments of Nephrology, and Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan; and
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Fujita K, Ichida K. A novel compound heterozygous mutation in the SLC22A12 (URAT1) gene in a Japanese patient associated with renal hypouricemia. Clin Chim Acta 2016; 463:119-121. [PMID: 27780716 DOI: 10.1016/j.cca.2016.10.025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2016] [Revised: 10/19/2016] [Accepted: 10/21/2016] [Indexed: 10/20/2022]
Abstract
A novel compound heterozygous mutation, including c.935_997delinsTGG, in exons 5/6 of SLC22A12 (URAT1) was identified in a patient with renal hypouricemia. This case expands the molecular mechanisms of renal hypouricemia, and suggests a potential relationship with exercise-induced renal failure.
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Affiliation(s)
- Kyoko Fujita
- Department of Pathophysiology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji 192-0392, Tokyo, Japan
| | - Kimiyoshi Ichida
- Department of Pathophysiology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji 192-0392, Tokyo, Japan.
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Kamei K, Konta T, Hirayama A, Ichikawa K, Kubota I, Fujimoto S, Iseki K, Moriyama T, Yamagata K, Tsuruya K, Narita I, Kondo M, Shibagaki Y, Kasahara M, Asahi K, Watanabe T. Associations between serum uric acid levels and the incidence of nonfatal stroke: a nationwide community-based cohort study. Clin Exp Nephrol 2016; 21:497-503. [DOI: 10.1007/s10157-016-1311-7] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2016] [Accepted: 07/07/2016] [Indexed: 02/07/2023]
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A case of xanthinuria type I with a novel mutation in xanthine dehydrogenase. CEN Case Rep 2016; 5:158-162. [PMID: 28508967 DOI: 10.1007/s13730-016-0216-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Accepted: 02/19/2016] [Indexed: 12/13/2022] Open
Abstract
Hereditary hypouricemia is generally caused by renal hypouricemia, an autosomal recessive disorder that is characterized by impaired renal tubular uric acid transport, or by xanthinuria, a rare autosomal recessive disorder caused by a deficiency of xanthine dehydrogenase (XDH; xanthinuria type I) or by a deficiency of both XDH and aldehyde oxidase (xanthinuria type II). In contrast to renal hypouricemia, which sometimes leads to exercise-induced acute kidney injury (EIAKI), xanthinuria has not been associated with this disorder. We report here a case of xanthinuria type I due to a compound heterozygous mutation. A 46-year-old woman was found to have undetectable plasma and urinary levels of uric acid. She had no symptoms and no history of EIAKI. Xanthinuria type I was diagnosed following the allopurinol loading test. Mutation analysis revealed a compound heterozygous mutation [c.305A>G (p.Gln102Arg) and c.2567delC (p.Thr856Lysfs*73)] in the XDH gene. Of these two mutations, the former is novel. The patient did not exhibit EIAKI. However, because xanthinuria is a rare disease, the identification of additional cases is necessary to determine whether this disease is complicated with EIAKI.
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Kanda E, Muneyuki T, Kanno Y, Suwa K, Nakajima K. Uric acid level has a U-shaped association with loss of kidney function in healthy people: a prospective cohort study. PLoS One 2015; 10:e0118031. [PMID: 25658588 PMCID: PMC4320097 DOI: 10.1371/journal.pone.0118031] [Citation(s) in RCA: 74] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2014] [Accepted: 01/06/2015] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND The relationship between hyperuricemia and chronic kidney disease (CKD) has been found in various observational studies. Although hypouricemia is associated with cardiovascular events, it has not been established as a risk factor for CKD. We investigated the relationship between serum uric acid level and the loss of kidney function and incident CKD in healthy people. MATERIALS AND METHODS Healthy people were enrolled in this community-based prospective cohort study, the Saitama Cardiometabolic Disease and Organ Impairment Study, Japan. The analysis was conducted on 4188 subjects followed up for at least 3 years, 3102 for 6 years and 1052 for 9 years. Their data including glomerular filtration rate (eGFR) decline were examined every three years. The outcome event was incident CKD or the decrease in eGFR by more than 25% in three years. Multivariate statistical models were adjusted for the baseline characteristics. RESULTS The following data was obtained: mean ± SD age, male, 39.6 ± 10.4 years, female 38.4 ± 10.8 years; eGFR, male, 81.9 ± 16.4 ml/min/1.73 m2, female, 82.1 ± 17.5 ml/min/1.73 m2; serum uric acid level, male, 5.8 ± 1.2 mg/dl, female, 4.1 ± 0.9 mg/dl. Both low and high serum uric acid levels were associated with the outcome and eGFR decline in males (multivariate logistic additional additive models, linear p = 0.0001, spline p = 0.043; generalized additive models, linear p = 0.0001, spline p = 0.012). In subjects with low serum uric acid levels (male, <5 mg/dl; female, <3.6 mg/dl), multivariate linear mixed models showed that low serum uric acid levels were associated with eGFR decline in a time-dependent manner (male, p = 0.0001; female, p = 0.045). CONCLUSION This study showed that low as well as high levels of uric acid are associated with the loss of kidney function. Hypouricemia is a candidate predictor of kidney function decline in healthy people.
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Affiliation(s)
- Eiichiro Kanda
- Department of Nephrology, Tokyo Kyosai Hospital, Meguro, Tokyo, Japan
- Center for life science and bioethics, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan
| | | | - Yoshihiko Kanno
- Department of Nephrology, Tokyo Medical University, Shinjuku, Tokyo, Japan
| | - Kaname Suwa
- Saitama Health Promotion Corporation, Hikigun, Saitama, Japan
| | - Kei Nakajima
- Division of Clinical Nutrition, Department of Medical Dietetics, Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan
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Ishikawa I. [Acute kidney injury: progress in diagnosis and treatments. Topics: IV. Pathophysiology and treatments; 5. Exercise induced AKI]. NIHON NAIKA GAKKAI ZASSHI. THE JOURNAL OF THE JAPANESE SOCIETY OF INTERNAL MEDICINE 2014; 103:1101-1107. [PMID: 25026780 DOI: 10.2169/naika.103.1101] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
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A novel homozygous GLUT9 mutation cause recurrent exercise-induced acute renal failure and posterior reversible encephalopathy syndrome. J Nephrol 2014; 28:387-92. [PMID: 24643436 DOI: 10.1007/s40620-014-0073-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2013] [Accepted: 02/19/2014] [Indexed: 12/31/2022]
Abstract
Renal hypouricemia (RHU) is an autosomal recessive hereditary disease characterized by impaired renal urate reabsorption and subsequent profound hypouricemia. There are two types of RHU, type 1 and type 2, caused by the loss-of-function mutation of SLC22A12 and SLC2A9 genes, respectively. RHU predisposes affected people to exercise-induced acute renal failure (EIARF), posterior reversible encephalopathy syndrome (PRES) and nephrolithiasis. A Chinese patient had experienced three episodes of EIARF and one episode of PRES. The investigations showed profound hypouricemia and significantly increased renal excretion of UA. Cranial magnetic resonance imaging showed communicating hydrocephalus. Renal biopsy displayed interlobular artery intimal thickening with reduction of lumen and acute tubulointerstitial injury. The mutational analysis revealed a homozygous splice-site mutation in the SLC2A9 gene encoding glucose transporter 9. The patient was diagnosed as RHU type 2 caused by a loss-of-function mutation of the SLC2A9 gene. Consequently, he was strictly prohibited from strenuous exercise. During the 5-year follow-up, EIARF and PRES never recurred. Strenuous exercise may induce systemic (including renal and cerebrovascular) vasoconstriction eventually resulting in EIARF and PRES in patients with RHU. To our knowledge, this is the first report of a homozygous splice-site mutation in the SLC2A9 gene, renal arteriolar chronic lesion, concurrence of RHU and communicating hydrocephalus.
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Kaito H, Ishimori S, Nozu K, Shima Y, Nakanishi K, Yoshikawa N, Iijima K. Molecular background of urate transporter genes in patients with exercise-induced acute kidney injury. Am J Nephrol 2013; 38:316-20. [PMID: 24107611 DOI: 10.1159/000355430] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2013] [Accepted: 08/30/2013] [Indexed: 02/04/2023]
Abstract
BACKGROUND/AIMS Exercise-induced acute renal failure [exercise-induced acute kidney injury (EI-AKI)] is defined as AKI due to heavy anaerobic exercise. Although hypouricemia is known to be a risk factor for the onset of EI-AKI, a direct causal link between EI-AKI and serum uric acid has not been established. This study aimed to analyze urate transporter genes in patients with EI-AKI and its molecular mechanism. METHODS Genomic DNA and total RNA were isolated from peripheral blood leukocytes of patients with a history of EI-AKI. Mutations were analyzed by PCR and a direct sequencing method. We first analyzed the SLC22A12 gene, and then the SLC2A9 gene if no mutations were found in SLC22A12. RESULTS Seventeen patients were enrolled in this study and 16 had mutations: 15 in SLC22A12 and 1 in SLC2A9. Fourteen (82.4%) patients showed hypouricemia, and all of the patients with hypouricemia had either homozygous or compound heterozygous mutations in SLC22A12 or SLC2A9, which confirmed that all of them had renal hypouricemia. Two patients had heterozygous mutations of SLC22A12, and they were not accompanied by hypouricemia. One patient was found to have no mutations in SLC22A12 or SLC2A9. CONCLUSION We were able to determine the genetic background of urate transporter genes in patients with EI-AKI. Decreased function of urate transporters, rather than decreased serum uric acid levels, may be of great importance for the onset of EI-AKI.
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Affiliation(s)
- Hiroshi Kaito
- Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan
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Moningka NC, Cunningham MW, Sterling M, West CA, Verlander JW, Croker BP, Ahlgren J, Hayward L, Baylis C. Effects of voluntary wheel running on the kidney at baseline and after ischaemia-reperfusion-induced acute kidney injury: a strain difference comparison. J Physiol 2012; 591:1313-24. [PMID: 23266936 DOI: 10.1113/jphysiol.2012.244327] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Abstract
Exercise-induced vascular endothelial adaptations in the kidney are not well understood. Therefore, we investigated the impact of voluntary wheel running (VWR) on the abundance of endothelial nitric oxide synthase (eNOS) and extracellular superoxide dismutase (EC SOD), in kidney and lung, and other SOD isoforms and total antioxidant capacity (TAC), in kidney. We also determined whether VWR influences susceptibility to acute kidney injury (AKI). Male Sprague-Dawley and Fisher 344 rats, VWR or sedentary for 12 weeks, were subjected to AKI (uninephrectomy (UNX) and 35 min of left kidney ischaemia-24 h reperfusion, IR). We measured glomerular filtration rate (GFR) and renal plasma flow (RPF), and analysed renal structural injury. Running was comparable between strains and VWR reduced body weight. In Sprague-Dawley rats, VWR reduced eNOS and EC SOD, but increased Mn SOD in kidney. Similar changes were seen after 6 weeks of VWR in Sprague-Dawley rats. In Fisher 344 rats, VWR increased eNOS, all SOD isoforms and TAC in kidney. Both strains increased eNOS and EC SOD in lung with VWR. Compared to UNX alone, UNX-IR injury markedly reduced renal function for both strains; however, in the Sprague-Dawley rats, VWR exacerbated falls in GFR and RPF due to UNX-IR, whereas in the Fisher 344 rats, GFR was unaffected by VWR. Some indices of renal structural injury due to UNX-IR tended to be worse in SD vs. F344. Our study demonstrates that genetic background influences the effect of exercise on kidney eNOS and EC SOD, which in turn influence the susceptibility to AKI.
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Affiliation(s)
- Natasha C Moningka
- Department of Cellular & Molecular Physiology, Yale University, P.O. Box 208026, New Haven, CT 208026, USA.
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Takagi S, Omae R, Makanga JO, Kawahara T, Inazu T. Simple and rapid detection method for the mutations in SLC22A12 that cause hypouricemia by allele-specific real-time polymerase chain reaction. Clin Chim Acta 2012; 415:330-3. [PMID: 23148994 DOI: 10.1016/j.cca.2012.10.046] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2012] [Accepted: 10/26/2012] [Indexed: 01/26/2023]
Abstract
BACKGROUND Hypouricemia is a disorder that serum urate level is less than 2.0 mg/dl, and relatively common in the Japanese population, where the main genetic cause of hypouricemia is W258X and R90H mutations in human urate trasnsporter 1(SLC22A12). Small scale screening has relied on time-consuming traditional ways like polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Therefore, it is beneficial that we have an easy and rapid detection method for these mutations. METHODS In this report, we established a touchdown allele-specific real-time polymerase chain reaction (ASPCR) assay for detecting W258X and R90H mutations in SLC22A12, respectively. RESULTS Quantifiable discrimination was successfully achieved by ∆Ct value. Furthermore, we conducted W258X and R90H screening against 120 control genome sets, whereby frequency was 2.92% for W258X, and not detected for R90H, respectively. CONCLUSIONS The two mutations, W258X and R90H in SLC22A12 were successfully genotyped by an easy and rapid ASPCR assay.
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Affiliation(s)
- Shota Takagi
- Department of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan
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Lee J, Lee SW, Lee JW, Chin HJ, Joo KW, Kim YS, Ahn C, Kim S, Cho JY, Han JS. Clinical characteristics of acute renal failure with severe loin pain and patchy renal vasoconstriction. Kidney Res Clin Pract 2012; 31:170-6. [PMID: 26894023 PMCID: PMC4716092 DOI: 10.1016/j.krcp.2012.06.005] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2012] [Revised: 05/14/2012] [Accepted: 05/23/2012] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Acute renal failure (ARF) with severe loin pain and patchy renal vasoconstriction (PRV) is a syndrome presenting with sudden loin pain after anaerobic exercise. We aimed to investigate the clinical characteristics and the efficacy of diagnostic imaging studies of patients with this syndrome. METHODS We retrospectively selected 17 patients with ARF accompanied by loin or abdominal pain who showed multiple patchy wedge-shaped delayed contrast enhancements on a computerized tomography scan. Information about the clinical characteristics, including the nature of pain and combined symptoms, suspected causes, such as exercise, drug or alcohol intake, and renal hypouricemia, and the results of laboratory and imaging tests were gathered. RESULTS The mean age of patients with episodes of ARF accompanied by loin pain was 23.0±6.5 (range 16-35) years old. Pain was mainly located in the loin (70.6%) or abdominal area (76.5%) and continued for approximately 3.5±4.0 days. Exercise was suspected as a primary cause of disease in 12 (70.6%) patients. Maximal serum creatinine was 5.42±3.16 (1.4-12.1) mg/dL 3.1±1.8 (1-7) days after the onset of pain. The peak level of serum uric acid was 9.41±2.91 (6.0-15.8) mg/dL. All of the patients recovered to near-normal renal function, and one patient showed hypouricemia after recovery. CONCLUSION ARF with severe loin pain and PRV can present with loin or abdominal pain, even without a history of anaerobic exercise. Careful history taking and appropriate imaging studies are critical in the diagnosis and management of this syndrome.
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Affiliation(s)
- Jeonghwan Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Seong Woo Lee
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Jae Wook Lee
- Epithelial Systems Biology Laboratory, National Heart Lung and Blood Institute, National Institute of Health, Bethesda, Maryland, United States
| | - Ho Jun Chin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Kwon Wook Joo
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Yon Su Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Curie Ahn
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Suhnggwon Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Jeong Yeon Cho
- Department of Radiology, Seoul National University Hospital, Seoul, Korea
| | - Jin Suk Han
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
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Hirashio S, Yamada K, Naito T, Masaki T. A case of renal hypouricemia and a G774A gene mutation causing acute renal injury that was improved by hemodialysis. CEN Case Rep 2012; 1:24-28. [PMID: 28509149 DOI: 10.1007/s13730-012-0007-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2011] [Accepted: 02/08/2012] [Indexed: 11/25/2022] Open
Abstract
A 16-year-old man came to our hospital complaining of loin pain after a middle-distance race. Following admission, his renal dysfunction worsened rapidly, requiring several hemodialysis sessions. A renal biopsy showed no change in the glomeruli, although interstitial edema was observed. Following the recovery of renal function, we confirmed that his uric acid level was abnormally low and urate clearance was abnormality high. Gene analysis showed that he had a G774A mutation which dominated the SLC22A12 gene encoding the urate transporter 1.
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Affiliation(s)
- Shuma Hirashio
- Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
- Department of Nephrology, National Hospital Organization Kure Medical Center and Chugoku Cancer Center, Kure, Japan.
| | - Kyoko Yamada
- Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Takayuki Naito
- Department of Nephrology, Hiroshima Prefectural Hospital, Hiroshima, Japan
| | - Takao Masaki
- Department of Nephrology, Hiroshima University Hospital, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
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Abstract
It has been known for decades that uric acid causes acute kidney injury by intratubular crystal precipitation and obstructing the renal tubules. Uric acid crystals stimulate inflammation and elicit immune responses in many disease conditions, including gouty arthritis. More recently, soluble uric acid has been reported to stimulate proliferation of vascular smooth muscle cells, inhibit endothelial function, cause renal vasoconstriction, impair renal blood flow autoregulation, and induce inflammatory response via crystal-independent mechanisms. This article examines the changing role for uric acid in acute kidney injury.
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Affiliation(s)
- Michiko Shimada
- Division of Cardiology, Respiratory Medicine and Nephrology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
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49
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Sakurai H. Transporter-centric view of urate metabolism: From genome-wide association study to pathophysiology. JOURNAL OF PHYSICAL FITNESS AND SPORTS MEDICINE 2012. [DOI: 10.7600/jpfsm.1.413] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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Kim AJ, Park SY, Jung JY, Chang JH, Lee HH, Chung WY, Ro H. A Case of Recurrent Exercise-Induced Acute Renal Failure and Renal Hypouricemia with R90H Mutation in a SCL22A12 Gene. Yeungnam Univ J Med 2012. [DOI: 10.12701/yujm.2012.29.2.150] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Ae Jin Kim
- Department of Internal Medicine, Gachon Unniversity Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea
| | - Soo Yong Park
- Department of Internal Medicine, Gachon Unniversity Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea
| | - Ji Yong Jung
- Department of Internal Medicine, Gachon Unniversity Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea
| | - Jae Hyun Chang
- Department of Internal Medicine, Gachon Unniversity Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea
| | - Hyun Hee Lee
- Department of Internal Medicine, Gachon Unniversity Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea
| | - Wook Yung Chung
- Department of Internal Medicine, Gachon Unniversity Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea
| | - Han Ro
- Department of Internal Medicine, Gachon Unniversity Gil Medical Center, Gachon University of Medicine and Science, Incheon, Korea
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