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Published in: Clinical and Experimental Nephrology 2/2018

01-04-2018 | Original article

Effects of topiroxostat in hyperuricemic patients with chronic kidney disease

Authors: Taro Horino, Yutaka Hatakeyama, Osamu Ichii, Tatsuki Matsumoto, Yoshiko Shimamura, Kosuke Inoue, Yoshio Terada, Yoshiyasu Okuhara

Published in: Clinical and Experimental Nephrology | Issue 2/2018

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Abstract

Background

Hyperuricemia is associated with chronic kidney disease (CKD). Although topiroxostat, a novel, non-purine, selective xanthine oxidase inhibitor, has a strong effect against hyperuricemia, limited data are available on its renoprotective effect against CKD.

Methods

This study was conducted between October 2014 and May 2016. Thirty patients (20 male, 10 female) were administered 40 mg/day of topiroxostat twice daily. All patients were followed for a year. To elucidate the effects of topiroxostat, we evaluated the clinically documented primary indication of progression, viz. laboratory evidence of kidney function decline (reference indicator), uric acid, and hypertension in different patient groups, separated according to their baseline uProt levels and baseline eGFR.

Results

Topiroxostat treatment resulted in significant reduction in SUA (−1.53 mg/dL), systolic blood pressure (−8.9 mmHg), diastolic blood pressure (−5.0 mmHg), and urinary protein excretion (−795.5 mg/gCr) compared with baseline values. However, serum creatinine and urinary NAG levels, and estimated glomerular filtration rate did not change significantly.

Conclusions

Topiroxostat reduced SUA levels effectively and may exhibit renoprotective effect in hyperuricemic patients with CKD. Further studies are required to clarify whether topiroxostat prevents the progression of renal disease and improves the prognosis of CKD patients.
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Literature
1.
go back to reference Otomo K, Horino T, Miki T, Kataoka H, Hatakeyama Y, Matsumoto T, et al. Serum uric acid level as a risk factor for acute kidney injury in hospitalized patients: a retrospective database analysis using the integrated medical information system at Kochi Medical School hospital. Clin Exp Nephrol. 2016;20:235–43.CrossRefPubMed Otomo K, Horino T, Miki T, Kataoka H, Hatakeyama Y, Matsumoto T, et al. Serum uric acid level as a risk factor for acute kidney injury in hospitalized patients: a retrospective database analysis using the integrated medical information system at Kochi Medical School hospital. Clin Exp Nephrol. 2016;20:235–43.CrossRefPubMed
2.
go back to reference Iseki K, Ikemiya Y, Inoue T, Iseki C, Kinjo K, Takishita S. Significance of hyperuricemia as risk factor for developing ESRD in a screened cohort. Am J Kidney Dis. 2004;44:642–50.CrossRefPubMed Iseki K, Ikemiya Y, Inoue T, Iseki C, Kinjo K, Takishita S. Significance of hyperuricemia as risk factor for developing ESRD in a screened cohort. Am J Kidney Dis. 2004;44:642–50.CrossRefPubMed
3.
go back to reference Hatakeyama Y, Horino T, Kataoka H, Matsumoto T, Ode K, Shimamura Y, et al. Incidence of acute kidney injury among patients with chronic kidney disease: a single-center retrospective database analysis. Clin Exp Nephrol. 2017;21:43–8.CrossRefPubMed Hatakeyama Y, Horino T, Kataoka H, Matsumoto T, Ode K, Shimamura Y, et al. Incidence of acute kidney injury among patients with chronic kidney disease: a single-center retrospective database analysis. Clin Exp Nephrol. 2017;21:43–8.CrossRefPubMed
4.
go back to reference Chonchol M, Shlipak MG, Katz R, Sarnak MJ, Newman AB, Siscovick DS, et al. Relationship of uric acid with progression of kidney disease. Am J Kidney Dis. 2007;50:239–47.CrossRefPubMed Chonchol M, Shlipak MG, Katz R, Sarnak MJ, Newman AB, Siscovick DS, et al. Relationship of uric acid with progression of kidney disease. Am J Kidney Dis. 2007;50:239–47.CrossRefPubMed
5.
go back to reference Weiner DE, Tighiouart H, Elsayed EF, Griffith JL, Salem DN, Levey AS. Uric acid and incident kidney disease in the community. J Am Soc Nephrol. 2008;19:1204–11.CrossRefPubMedPubMedCentral Weiner DE, Tighiouart H, Elsayed EF, Griffith JL, Salem DN, Levey AS. Uric acid and incident kidney disease in the community. J Am Soc Nephrol. 2008;19:1204–11.CrossRefPubMedPubMedCentral
6.
go back to reference Kamei K, Konta T, Hirayama A, Suzuki K, Ichikawa K, Fujimoto S, et al. A slight increase within the normal range of serum uric acid and the decline in renal function: associations in a community-based population. Nephrol Dial Transplant. 2014;29:2286–92.CrossRefPubMed Kamei K, Konta T, Hirayama A, Suzuki K, Ichikawa K, Fujimoto S, et al. A slight increase within the normal range of serum uric acid and the decline in renal function: associations in a community-based population. Nephrol Dial Transplant. 2014;29:2286–92.CrossRefPubMed
8.
go back to reference Suliman ME, Johnson RJ, García-López E, Qureshi AR, Molinaei H, Carrero JJ, et al. J-shaped mortality relationship for uric acid in CKD. Am J Kidney Dis. 2006;48:761–71.CrossRefPubMed Suliman ME, Johnson RJ, García-López E, Qureshi AR, Molinaei H, Carrero JJ, et al. J-shaped mortality relationship for uric acid in CKD. Am J Kidney Dis. 2006;48:761–71.CrossRefPubMed
9.
go back to reference Chaudhary K, Malhotra K, Sowers J, Aroor A. Uric acid-key ingredient in the recipe for cardiorenal metabolic syndrome. Cardiorenal Med. 2013;3:208–20.CrossRefPubMedPubMedCentral Chaudhary K, Malhotra K, Sowers J, Aroor A. Uric acid-key ingredient in the recipe for cardiorenal metabolic syndrome. Cardiorenal Med. 2013;3:208–20.CrossRefPubMedPubMedCentral
10.
go back to reference Fang P, Li X, Luo JJ, Wang H, Yang XF. A double-edged sword: uric acid and neurological disorders. Brain Disord Ther. 2013;2:109.PubMedPubMedCentral Fang P, Li X, Luo JJ, Wang H, Yang XF. A double-edged sword: uric acid and neurological disorders. Brain Disord Ther. 2013;2:109.PubMedPubMedCentral
12.
go back to reference Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S, et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension. 2003;41:1183–90.CrossRefPubMed Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J, Watanabe S, et al. Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease? Hypertension. 2003;41:1183–90.CrossRefPubMed
13.
go back to reference Goicoechea M, de Vinuesa SG, Verdalles U, Ruiz-Caro C, Ampuero J, Rincón A, et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol. 2010;5:1388–93.CrossRefPubMedPubMedCentral Goicoechea M, de Vinuesa SG, Verdalles U, Ruiz-Caro C, Ampuero J, Rincón A, et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol. 2010;5:1388–93.CrossRefPubMedPubMedCentral
14.
go back to reference Elion GB, Yü TF, Gutman AB, Hitchings GH. Renal clearance of oxipurinol, the chief metabolite of allopurinol. Am J Med. 1968;45:69–77.CrossRefPubMed Elion GB, Yü TF, Gutman AB, Hitchings GH. Renal clearance of oxipurinol, the chief metabolite of allopurinol. Am J Med. 1968;45:69–77.CrossRefPubMed
15.
go back to reference Simmonds HA. Urinary excretion of purines, pyrimidines and pyrazolopyrimidines in patients treated with allopurinol or oxipurinol. Clin Chim Acta. 1969;23:353–64.CrossRefPubMed Simmonds HA. Urinary excretion of purines, pyrimidines and pyrazolopyrimidines in patients treated with allopurinol or oxipurinol. Clin Chim Acta. 1969;23:353–64.CrossRefPubMed
16.
go back to reference Hande KR, Noone RM, Stone WJ. Severe allopurinol toxicity. Description and guidelines for prevention in patients with renal insufficiency. Am J Med. 1984;76:47–56.CrossRefPubMed Hande KR, Noone RM, Stone WJ. Severe allopurinol toxicity. Description and guidelines for prevention in patients with renal insufficiency. Am J Med. 1984;76:47–56.CrossRefPubMed
17.
go back to reference Hosoya T, Ohno I, Nomura S, Hisatome I, Uchida S, Fujimori S, et al. Effects of topiroxostat on the serum urate levels and urinary albumin excretion in hyperuricemic stage 3 chronic kidney disease patients with or without gout. Clin Exp Nephrol. 2014;18:876–84.CrossRefPubMedPubMedCentral Hosoya T, Ohno I, Nomura S, Hisatome I, Uchida S, Fujimori S, et al. Effects of topiroxostat on the serum urate levels and urinary albumin excretion in hyperuricemic stage 3 chronic kidney disease patients with or without gout. Clin Exp Nephrol. 2014;18:876–84.CrossRefPubMedPubMedCentral
18.
go back to reference Hosoya T, Sasaki T, Ohashi T. Clinical efficacy and safety of topiroxostat in Japanese hyperuricemic patients with or without gout: a randomized, double-blinded, controlled phase 2b study. Clin Rheumatol. 2017;36:649–56.CrossRefPubMed Hosoya T, Sasaki T, Ohashi T. Clinical efficacy and safety of topiroxostat in Japanese hyperuricemic patients with or without gout: a randomized, double-blinded, controlled phase 2b study. Clin Rheumatol. 2017;36:649–56.CrossRefPubMed
19.
go back to reference Hosoya T, Ogawa Y, Hashimoto H, Ohashi T, Sakamoto R. Comparison of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout: a phase 3, multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study. J Clin Pharm Ther. 2016;41:290–7.CrossRefPubMed Hosoya T, Ogawa Y, Hashimoto H, Ohashi T, Sakamoto R. Comparison of topiroxostat and allopurinol in Japanese hyperuricemic patients with or without gout: a phase 3, multicentre, randomized, double-blind, double-dummy, active-controlled, parallel-group study. J Clin Pharm Ther. 2016;41:290–7.CrossRefPubMed
20.
go back to reference Nakamura T, Murase T, Nampei M, Morimoto N, Ashizawa N, Iwanaga T, et al. Effects of topiroxostat and febuxostat on urinary albumin excretion and plasma xanthine oxidoreductase activity in db/db mice. Eur J Pharmacol. 2016;780:224–31.CrossRefPubMed Nakamura T, Murase T, Nampei M, Morimoto N, Ashizawa N, Iwanaga T, et al. Effects of topiroxostat and febuxostat on urinary albumin excretion and plasma xanthine oxidoreductase activity in db/db mice. Eur J Pharmacol. 2016;780:224–31.CrossRefPubMed
21.
go back to reference Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.CrossRefPubMed Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53:982–92.CrossRefPubMed
22.
go back to reference Heerspink HJ, Kröpelin TF, Hoekman J, de Zeeuw D, Reducing Albuminuria as Surrogate Endpoint (REASSURE) Consortium. Drug-induced reduction in albuminuria is associated with subsequent renoprotection: a meta-analysis. J Am Soc Nephrol. 2015;26:2055–64.CrossRefPubMed Heerspink HJ, Kröpelin TF, Hoekman J, de Zeeuw D, Reducing Albuminuria as Surrogate Endpoint (REASSURE) Consortium. Drug-induced reduction in albuminuria is associated with subsequent renoprotection: a meta-analysis. J Am Soc Nephrol. 2015;26:2055–64.CrossRefPubMed
23.
go back to reference Bellomo G, Venanzi S, Verdura C, Saronio P, Esposito A, Timio M. Association of uric acid with change in kidney function in healthy normotensive individuals. Am J Kidney Dis. 2010;56:264–72.CrossRefPubMed Bellomo G, Venanzi S, Verdura C, Saronio P, Esposito A, Timio M. Association of uric acid with change in kidney function in healthy normotensive individuals. Am J Kidney Dis. 2010;56:264–72.CrossRefPubMed
24.
go back to reference Siu YP, Leung KT, Tong MK, Kwan TH. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis. 2006;47:51–9.CrossRefPubMed Siu YP, Leung KT, Tong MK, Kwan TH. Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level. Am J Kidney Dis. 2006;47:51–9.CrossRefPubMed
25.
go back to reference Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA. 2008;300:924–32.CrossRefPubMedPubMedCentral Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA. 2008;300:924–32.CrossRefPubMedPubMedCentral
26.
go back to reference Kanji T, Gandhi M, Clase CM, Yang R. Urate lowering therapy to improve renal outcomes in patients with chronic kidney disease: systematic review and meta-analysis. BMC Nephrol. 2015;16:58.CrossRefPubMedPubMedCentral Kanji T, Gandhi M, Clase CM, Yang R. Urate lowering therapy to improve renal outcomes in patients with chronic kidney disease: systematic review and meta-analysis. BMC Nephrol. 2015;16:58.CrossRefPubMedPubMedCentral
27.
go back to reference Barr WG. Uric acid. In: Walker HK, Hall WD, Hurst JW, editors. Clinical methods: the history, physical, and laboratory examinations, Chapter 165. 3rd ed. Boston: Butterworths; 1990. Barr WG. Uric acid. In: Walker HK, Hall WD, Hurst JW, editors. Clinical methods: the history, physical, and laboratory examinations, Chapter 165. 3rd ed. Boston: Butterworths; 1990.
Metadata
Title
Effects of topiroxostat in hyperuricemic patients with chronic kidney disease
Authors
Taro Horino
Yutaka Hatakeyama
Osamu Ichii
Tatsuki Matsumoto
Yoshiko Shimamura
Kosuke Inoue
Yoshio Terada
Yoshiyasu Okuhara
Publication date
01-04-2018
Publisher
Springer Singapore
Published in
Clinical and Experimental Nephrology / Issue 2/2018
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-017-1452-3

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