Skip to main content
Erschienen in: Heart and Vessels 10/2016

23.12.2015 | Original Article

Long-term effects of AST-120 on the progression and prognosis of pre-dialysis chronic kidney disease: a 5-year retrospective study

verfasst von: Eiichi Sato, Atsushi Tanaka, Jun-ichi Oyama, Ayumu Yamasaki, Mitsuhiro Shimomura, Atsushi Hiwatashi, Yoshihiko Ueda, Mayuko Amaha, Mayumi Nomura, Daisuke Matsumura, Tsukasa Nakamura, Koichi Node

Erschienen in: Heart and Vessels | Ausgabe 10/2016

Einloggen, um Zugang zu erhalten

Abstract

AST-120 has been used widely in Japan to slow the deterioration of renal function in patients with chronic kidney disease (CKD) by decreasing uremic toxins. The heart and the kidney are closely related, with cardiorenal interaction being very important. This retrospective study examined whether AST-120 influences the prevalence of dialysis induction, mortality, and cardiac and stroke events in CKD patients. The study included 278 patients diagnosed with chronic renal failure (CKD stage: III–V) in 2006. Of these patients, 128 received AST-120 (6 g/day), while the remaining 150 patients did not. A log-rank test was performed to compare dialysis induction, mortality, and cardiac and stroke events in the two groups. Univariate and multivariate Cox proportional hazard regression analyses were used to identify the potential factors that contributed to dialysis induction, mortality, and cardiac and stroke events over the next 5 years. Patient profiles before the study were almost the same other than age, primary disease (DM or non-DM) and urine volume. The prevalence of dialysis induction, mortality, and cardiac and stroke events in patients treated with AST-120 was significantly lower after 3 and 5 years (p < 0.0001) compared with the prevalence observed in the untreated patients. The absence of AST-120 treatment was associated independently with a high risk of dialysis induction (hazard ratio 4.979, 95 % CI 3.502–7.079, p < 0.0001), mortality (4.536, 2.666–7.720, p < 0.0001), cardiac event (3.590, 2.572–5.011, p < 0.001) and stroke (1.949, 1.342–2.829, p = 0.0005). The results of this retrospective analysis suggest that long-term treatment with AST-120 may improve the prognosis of CKD patients in the pre-dialysis stage. Long-term (i.e., >5 years) prospective randomized studies are needed to confirm the findings of the current study.
Literatur
1.
Zurück zum Zitat Izumi Y, Hayashi M, Morimoto R, Cheng XW, Wu H, Ishii H, Yasuda Y, Yoshikawa D, Izawa H, Matsuo S, Osio Y, Murohara T (2014) Impact of circulating cathepsin K on the coronary calcification and the clinical outcome in chronic kidney disease patients. Heart Vessels. doi:10.1007/s00380-014-0570-z Izumi Y, Hayashi M, Morimoto R, Cheng XW, Wu H, Ishii H, Yasuda Y, Yoshikawa D, Izawa H, Matsuo S, Osio Y, Murohara T (2014) Impact of circulating cathepsin K on the coronary calcification and the clinical outcome in chronic kidney disease patients. Heart Vessels. doi:10.​1007/​s00380-014-0570-z
2.
Zurück zum Zitat Kosuga T, Komukai K, Miyanaga S, Kubota T, Nakata K, Suzuki K, Yamada T, Yoshida J, Kimura H, Yoshimura M (2015) Diabetes is a predictor of coronary artery stenosis in patients hospitalized with heart failure. Heart Vessels. doi:10.1007/s00380-015-0669-x PubMed Kosuga T, Komukai K, Miyanaga S, Kubota T, Nakata K, Suzuki K, Yamada T, Yoshida J, Kimura H, Yoshimura M (2015) Diabetes is a predictor of coronary artery stenosis in patients hospitalized with heart failure. Heart Vessels. doi:10.​1007/​s00380-015-0669-x PubMed
3.
Zurück zum Zitat Niwa T, Nomura T, Sugiyama S, Miyazaki T, Tsukushi S, Tsutsui S (1997) The protein metabolite hypothesis, a model for the progression of renal failure: an oral adsorbent lowers indoxyl sulfate level in undialysis uremic patient. Kidney Int Suppl 62:S23–S28PubMed Niwa T, Nomura T, Sugiyama S, Miyazaki T, Tsukushi S, Tsutsui S (1997) The protein metabolite hypothesis, a model for the progression of renal failure: an oral adsorbent lowers indoxyl sulfate level in undialysis uremic patient. Kidney Int Suppl 62:S23–S28PubMed
4.
Zurück zum Zitat Fujii H, Nishijima F, Goto S, Sugano M, Yamato H, Kitazawa S, Fukagawa M (2009) Oral damage in chronic kidney disease through suppression of oxidative stress. Nephrol Dial Transplant 24:2089–2095CrossRefPubMed Fujii H, Nishijima F, Goto S, Sugano M, Yamato H, Kitazawa S, Fukagawa M (2009) Oral damage in chronic kidney disease through suppression of oxidative stress. Nephrol Dial Transplant 24:2089–2095CrossRefPubMed
5.
Zurück zum Zitat Namikoshi T, Tomita N, Satoh M, Sakuta T, Kuwabara A, Kobayashi S, Higuchi Y, Nishijima F, Kashihara N (2009) Oral adsorbent AST-120 ameliorates endothelial dysfunction independent of renal function in rats with subtotal nephrectomy. Hypertens Res 32:194–200CrossRefPubMed Namikoshi T, Tomita N, Satoh M, Sakuta T, Kuwabara A, Kobayashi S, Higuchi Y, Nishijima F, Kashihara N (2009) Oral adsorbent AST-120 ameliorates endothelial dysfunction independent of renal function in rats with subtotal nephrectomy. Hypertens Res 32:194–200CrossRefPubMed
6.
Zurück zum Zitat Lee CT, Hsu CY, Tain YL, Ng HY, Cheng BC, Yng CC, Wu CH, Chiou TT, Lee YT, Liao SC (2014) Effects of AST-120 on blood concentration of protein-bound uremic toxins and biomarkers of cardiovascular risk in chronic dialysis patients. Blood Purif 37:76–83CrossRefPubMed Lee CT, Hsu CY, Tain YL, Ng HY, Cheng BC, Yng CC, Wu CH, Chiou TT, Lee YT, Liao SC (2014) Effects of AST-120 on blood concentration of protein-bound uremic toxins and biomarkers of cardiovascular risk in chronic dialysis patients. Blood Purif 37:76–83CrossRefPubMed
7.
Zurück zum Zitat Rena I, Kompa AR, Skommer J, Wang BH, Lekawanvijit S, Kelly DJ, Krum H, Charchar FJ (2015) Contribution of microRNA to pathological fibrosis in cardio-renal syndrome: impact of uremic toxins. Physiol Rep 3(4):e12371CrossRef Rena I, Kompa AR, Skommer J, Wang BH, Lekawanvijit S, Kelly DJ, Krum H, Charchar FJ (2015) Contribution of microRNA to pathological fibrosis in cardio-renal syndrome: impact of uremic toxins. Physiol Rep 3(4):e12371CrossRef
8.
Zurück zum Zitat Nakamura T, Kawagoe Y, Matsuda T, Ueda Y, Shimada N, Ebihara I, Koide H (2004) Oral ADSORBENT AST-120 decreases carotid intima-media thickness and arterial stiffness in patients with chronic renal failure. Kidney Blood Press Res 27:121–126CrossRefPubMed Nakamura T, Kawagoe Y, Matsuda T, Ueda Y, Shimada N, Ebihara I, Koide H (2004) Oral ADSORBENT AST-120 decreases carotid intima-media thickness and arterial stiffness in patients with chronic renal failure. Kidney Blood Press Res 27:121–126CrossRefPubMed
9.
Zurück zum Zitat Ebihara I, Nakamura T, Ushiyama C, Suzuki S, Shimada N, Koide H (1999) Effect of oral adsorbent AST-120 on plasma metalloproteinase-9 and serum tissue inhibitor of metalloproteinase-1 concentrations in chronic renal failure. Nephron 83:169CrossRefPubMed Ebihara I, Nakamura T, Ushiyama C, Suzuki S, Shimada N, Koide H (1999) Effect of oral adsorbent AST-120 on plasma metalloproteinase-9 and serum tissue inhibitor of metalloproteinase-1 concentrations in chronic renal failure. Nephron 83:169CrossRefPubMed
10.
Zurück zum Zitat Nakamura T, Sato E, Fujiwara N, Kawagoe Y, Suzuki T, Ueda Y, Yamagishi S (2011) Oral adsorbent AST-120 ameliorates tubular injury in chronic renal failure patients by reducing proteinuria and oxidative stress generation. Metabolism 60:260–264CrossRefPubMed Nakamura T, Sato E, Fujiwara N, Kawagoe Y, Suzuki T, Ueda Y, Yamagishi S (2011) Oral adsorbent AST-120 ameliorates tubular injury in chronic renal failure patients by reducing proteinuria and oxidative stress generation. Metabolism 60:260–264CrossRefPubMed
11.
Zurück zum Zitat Ueda H, Shibahara N, Takagi S, Inoue T, Katsuoka Y (2008) AST-120 treatment in pre-dialysis period affects the prognosis in patients on hemodialysis. Ren Fail 30:856–860CrossRefPubMed Ueda H, Shibahara N, Takagi S, Inoue T, Katsuoka Y (2008) AST-120 treatment in pre-dialysis period affects the prognosis in patients on hemodialysis. Ren Fail 30:856–860CrossRefPubMed
12.
Zurück zum Zitat Maeda K, Hamada C, Hayashi T, Shou I, Wakabayashi M, Fukui M, Horikoshi S, Tomino Y (2009) Long-term effects of the oral adsorbent, AST-120, in patients with chronic renal failure. J Int Med Res 37:205–213CrossRefPubMed Maeda K, Hamada C, Hayashi T, Shou I, Wakabayashi M, Fukui M, Horikoshi S, Tomino Y (2009) Long-term effects of the oral adsorbent, AST-120, in patients with chronic renal failure. J Int Med Res 37:205–213CrossRefPubMed
13.
Zurück zum Zitat Akizawa T, Asano Y, Morita S, Wakita T, Onishi Y, Fukuhara S, Gejyo F, Matsuno S, Yorioka N, Kurokawa K (2009) Effect of a carbonaceous oral adsorbent on the progression of CKD: a multicenter, randomized, controlled trial. Am J Kidney Dis 54:459–467CrossRefPubMed Akizawa T, Asano Y, Morita S, Wakita T, Onishi Y, Fukuhara S, Gejyo F, Matsuno S, Yorioka N, Kurokawa K (2009) Effect of a carbonaceous oral adsorbent on the progression of CKD: a multicenter, randomized, controlled trial. Am J Kidney Dis 54:459–467CrossRefPubMed
14.
Zurück zum Zitat Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A, Collaborators developing the Japanese equation for estimated GFR (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53:982–992CrossRefPubMed Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A, Collaborators developing the Japanese equation for estimated GFR (2009) Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53:982–992CrossRefPubMed
15.
Zurück zum Zitat Jennete C, Olson JL, Schwartz MM, Silva FG (2007) Diabetic nephropathy. Heptinstall’s Pathology of the Kidney, 6th edn. Lippincott Williams & Wilkins, Philadelohia, pp 803–852 Jennete C, Olson JL, Schwartz MM, Silva FG (2007) Diabetic nephropathy. Heptinstall’s Pathology of the Kidney, 6th edn. Lippincott Williams & Wilkins, Philadelohia, pp 803–852
16.
Zurück zum Zitat Sato E, Amaha M, Nomura M, Matsumura D, Ueda Y, Nakamura T (2014) LDL-apheresis contributes to survival extension and renal function maintenance of severe diabetic nephropathy patients: a retrospective analysis. Diabetes Res Clin Prac 106:241–246CrossRef Sato E, Amaha M, Nomura M, Matsumura D, Ueda Y, Nakamura T (2014) LDL-apheresis contributes to survival extension and renal function maintenance of severe diabetic nephropathy patients: a retrospective analysis. Diabetes Res Clin Prac 106:241–246CrossRef
17.
Zurück zum Zitat Kamijo A, Sugaya T, Hikawa A, Okada M, Okumura F, Yamanouchi M, Honda A, Okabe M, Fujino T, Hirata Y, Omata M, Kaneko R, Fujii H, Fukamizu A, Kimura K (2004) Urinary excretion of fatty acid binding protein reflects stress overload on the proximal tubules. Am J Pathol 165:1243–1255CrossRefPubMedPubMedCentral Kamijo A, Sugaya T, Hikawa A, Okada M, Okumura F, Yamanouchi M, Honda A, Okabe M, Fujino T, Hirata Y, Omata M, Kaneko R, Fujii H, Fukamizu A, Kimura K (2004) Urinary excretion of fatty acid binding protein reflects stress overload on the proximal tubules. Am J Pathol 165:1243–1255CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Gelasco AK, Raymond JR (2006) Indoxyl sulfate induces complex redox alterations in mesangial cells. Am J Physiol Renal Physiol 290:F1551–F1558CrossRefPubMed Gelasco AK, Raymond JR (2006) Indoxyl sulfate induces complex redox alterations in mesangial cells. Am J Physiol Renal Physiol 290:F1551–F1558CrossRefPubMed
19.
Zurück zum Zitat Owada S, Goto S, Bannai K, Hayashi H, Nishijima F, Niwa T (2008) Indoxyl sulfate reduces superoxide scavenging activity in the kidneys of normal and uremic rats. Am J Nephrol 28:446–454CrossRefPubMed Owada S, Goto S, Bannai K, Hayashi H, Nishijima F, Niwa T (2008) Indoxyl sulfate reduces superoxide scavenging activity in the kidneys of normal and uremic rats. Am J Nephrol 28:446–454CrossRefPubMed
20.
Zurück zum Zitat Crouse JR III, Tang R, Espeland MA, Terry JG, Morgan T, Mereuri M (2002) Association of extracranial carotid atherosclerosis progression with coronary status and risk factors in patients with and without coronary artery disease. Circulation 106:2061–2066CrossRefPubMed Crouse JR III, Tang R, Espeland MA, Terry JG, Morgan T, Mereuri M (2002) Association of extracranial carotid atherosclerosis progression with coronary status and risk factors in patients with and without coronary artery disease. Circulation 106:2061–2066CrossRefPubMed
21.
Zurück zum Zitat Ueda S, Yamagishi SI, Takeuchi M, Kohno K, Shibata R, Matsumoto Y, Kaneyuki U, Fujimura T, Hayashida A, Okuda S (2006) Oral adsorbent AST-120 decreases serum levels of AGEs in patients with chronic renal failure. Mol Med 12:180–184CrossRefPubMedPubMedCentral Ueda S, Yamagishi SI, Takeuchi M, Kohno K, Shibata R, Matsumoto Y, Kaneyuki U, Fujimura T, Hayashida A, Okuda S (2006) Oral adsorbent AST-120 decreases serum levels of AGEs in patients with chronic renal failure. Mol Med 12:180–184CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Nakamura T, Kawagoe Y, Ueda Y, Ebihara I, Koide H (2004) Effect of oral adsorbent AST-120 in patients with chronic renal failure with or without diabetes. Ren Fail 26:99–101CrossRefPubMed Nakamura T, Kawagoe Y, Ueda Y, Ebihara I, Koide H (2004) Effect of oral adsorbent AST-120 in patients with chronic renal failure with or without diabetes. Ren Fail 26:99–101CrossRefPubMed
23.
Zurück zum Zitat Mann JF, Geestein HC, Pogue J, Bosch J, Yusuf S (2001) Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med 134:629–636CrossRefPubMed Mann JF, Geestein HC, Pogue J, Bosch J, Yusuf S (2001) Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med 134:629–636CrossRefPubMed
24.
Zurück zum Zitat Kubo M, Hata J, Doi Y, Tanizaki Y, Iida M, Kiyohara Y (2008) Secular trends in the incidence of and risk factors for ischemic stroke and its subtypes in Japanese population. Circulation 118:2672–2678CrossRefPubMed Kubo M, Hata J, Doi Y, Tanizaki Y, Iida M, Kiyohara Y (2008) Secular trends in the incidence of and risk factors for ischemic stroke and its subtypes in Japanese population. Circulation 118:2672–2678CrossRefPubMed
25.
Zurück zum Zitat Shibahara H, Shibahara N (2010) Cardiorenal protective effect of the oral uremic toxin absorbent AST-120 in chronic heart disease patients with moderate CKD. J Nephrol 23:535–540PubMed Shibahara H, Shibahara N (2010) Cardiorenal protective effect of the oral uremic toxin absorbent AST-120 in chronic heart disease patients with moderate CKD. J Nephrol 23:535–540PubMed
26.
Zurück zum Zitat Ito S, Higuchi Y, Yagi Y, Nishijima F, Yamato H, Ishii H, Osaka M, Yoshida M (2013) Reduction of indoxyl sulfate by AST-120 attenuates monocyte inflammation related to chronic kidney disease. J Leukoc Biol 93:837–845CrossRefPubMed Ito S, Higuchi Y, Yagi Y, Nishijima F, Yamato H, Ishii H, Osaka M, Yoshida M (2013) Reduction of indoxyl sulfate by AST-120 attenuates monocyte inflammation related to chronic kidney disease. J Leukoc Biol 93:837–845CrossRefPubMed
27.
Zurück zum Zitat Hatakeyama S, Yamamoto H, Okamoto A, Imanishi K, Tokui N, Okamoto T, Suzuki Y, Sugiyama N, Imai A, Kubo S, Yoneyama T, Hashimoto Y, Koie T, Kamimura N, Saitoh H, Funyu T, Ohyama C (2012) Effect of an oral adsorbent, AST-120, on dialysis initiation and survival in patients with chronic kidney disease. Int J Nephrol 2012:376128PubMedPubMedCentral Hatakeyama S, Yamamoto H, Okamoto A, Imanishi K, Tokui N, Okamoto T, Suzuki Y, Sugiyama N, Imai A, Kubo S, Yoneyama T, Hashimoto Y, Koie T, Kamimura N, Saitoh H, Funyu T, Ohyama C (2012) Effect of an oral adsorbent, AST-120, on dialysis initiation and survival in patients with chronic kidney disease. Int J Nephrol 2012:376128PubMedPubMedCentral
28.
Zurück zum Zitat Tan X, He J, Cao X, Zou J, Liu H, Ding X (2015) Effects of oral carbonic adsorbent (AST-120) on kidney of early-stage chronic kidney disease rats. Ren Fail 37:337–342CrossRefPubMed Tan X, He J, Cao X, Zou J, Liu H, Ding X (2015) Effects of oral carbonic adsorbent (AST-120) on kidney of early-stage chronic kidney disease rats. Ren Fail 37:337–342CrossRefPubMed
Metadaten
Titel
Long-term effects of AST-120 on the progression and prognosis of pre-dialysis chronic kidney disease: a 5-year retrospective study
verfasst von
Eiichi Sato
Atsushi Tanaka
Jun-ichi Oyama
Ayumu Yamasaki
Mitsuhiro Shimomura
Atsushi Hiwatashi
Yoshihiko Ueda
Mayuko Amaha
Mayumi Nomura
Daisuke Matsumura
Tsukasa Nakamura
Koichi Node
Publikationsdatum
23.12.2015
Verlag
Springer Japan
Erschienen in
Heart and Vessels / Ausgabe 10/2016
Print ISSN: 0910-8327
Elektronische ISSN: 1615-2573
DOI
https://doi.org/10.1007/s00380-015-0785-7

Weitere Artikel der Ausgabe 10/2016

Heart and Vessels 10/2016 Zur Ausgabe

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.