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Published in: Clinical and Experimental Nephrology 2/2017

01-04-2017 | Original Article

Efficacy of low-density lipoprotein apheresis combined with corticosteroids for cholesterol crystal embolism

Authors: Katsuya Ishiyama, Toshinobu Sato, Takuhiro Yamaguchi, Yoshio Taguma

Published in: Clinical and Experimental Nephrology | Issue 2/2017

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Abstract

Background

Corticosteroids have been widely used in patients with cholesterol crystal embolism (CCE) and low-density lipoprotein apheresis (LDL-A) was reported to reduce the risk of end-stage renal disease in patients with CCE. This study was designed to evaluate the renoprotective effects of LDL-A in combination with corticosteroids in patients with CCE.

Methods

Thirty-five patients with CCE who, between 2008 and 2013, had shown renal deterioration after vascular interventions were retrospectively evaluated. All patients received corticosteroids; of these, 24 also received LDL-A and 11 did not, designated LDL-A and control groups, respectively. Differences in eGFR (ΔeGFR), 3 months and 1 year after CCE diagnosis, were compared in the two groups.

Results

The median estimated glomerular filtration rate (eGFR) in all patients was 38.9 [interquartile range (IQR) 31.9–49.4] ml/min/1.73 m2 at baseline (before vascular intervention). At diagnosis, it was 14.4 (IQR 11.3–21.8) ml/min/1.73 m2. The initial corticosteroid dose was 0.34 ± 0.10 mg/kg/day. The mean number of LDL-A treatment sessions in the LDL-A group was 4.3 ± 1.8. eGFR was increased significantly after LDL-A treatments, from 15.0 (IQR 12.3–20.1) to 19.6 (IQR 14.3–23.6) ml/min/1.73 m2 (P < 0.05). ΔeGFR tended to be higher in the LDL-A than in the control group at 3 months [median 6.5 (IQR 5.1–9.3) vs. 2.6 (IQR −0.6 to 6.3) ml/min/1.73 m2, P = 0.095] and was significantly higher at 1 year [median 7.5 (IQR 5.4–8.7) vs. 2.2 (IQR −3.8 to 5.1) ml/min/1.73 m2, P = 0.019].

Conclusions

LDL-A plus corticosteroids may restore deteriorated renal function better than corticosteroids alone in patients with CCE.
Literature
2.
go back to reference Modi KS, Rao VK. Atheroembolic renal disease. J Am Soc Nephrol. 2001;12:1781–7.PubMed Modi KS, Rao VK. Atheroembolic renal disease. J Am Soc Nephrol. 2001;12:1781–7.PubMed
4.
go back to reference Fine MJ, Kapoor W, Falanga V. Cholesterol crystal embolization: a review of 221 cases in the English literature. Angiology. 1987;38:769–84.CrossRefPubMed Fine MJ, Kapoor W, Falanga V. Cholesterol crystal embolization: a review of 221 cases in the English literature. Angiology. 1987;38:769–84.CrossRefPubMed
5.
go back to reference Belenfant X, Meyrier A, Jacquot C. Supportive treatment improves survival in multivisceral cholesterol crystal embolism. Am J Kidney Dis. 1999;33:840–50.CrossRefPubMed Belenfant X, Meyrier A, Jacquot C. Supportive treatment improves survival in multivisceral cholesterol crystal embolism. Am J Kidney Dis. 1999;33:840–50.CrossRefPubMed
6.
go back to reference Lye WC, Cheah JS, Sinniah R. Renal cholesterol embolic disease. Case report and review of the literature. Am J Nephrol. 1993;13:489–93.CrossRefPubMed Lye WC, Cheah JS, Sinniah R. Renal cholesterol embolic disease. Case report and review of the literature. Am J Nephrol. 1993;13:489–93.CrossRefPubMed
7.
go back to reference Scolari F, Ravani P, Gaggi R, Santostefano M, Rollino C, Stabellini N, Colla L, Viola BF, Maiorca P, Venturelli C, Bonardelli S, Faggiano P, Barrett BJ. The challenge of diagnosing atheroembolic renal disease: clinical features and prognostic factors. Circulation. 2007;116:298–304.CrossRefPubMed Scolari F, Ravani P, Gaggi R, Santostefano M, Rollino C, Stabellini N, Colla L, Viola BF, Maiorca P, Venturelli C, Bonardelli S, Faggiano P, Barrett BJ. The challenge of diagnosing atheroembolic renal disease: clinical features and prognostic factors. Circulation. 2007;116:298–304.CrossRefPubMed
8.
go back to reference Nakayama M, Nagata M, Hirano T, Sugai K, Katafuchi R, Imayama S, Uesugi N, Tsuchihashi T, Kumagai H. Low-dose prednisolone ameliorates acute renal failure caused by cholesterol crystal embolism. Clin Nephrol. 2006;66:232–9.CrossRefPubMed Nakayama M, Nagata M, Hirano T, Sugai K, Katafuchi R, Imayama S, Uesugi N, Tsuchihashi T, Kumagai H. Low-dose prednisolone ameliorates acute renal failure caused by cholesterol crystal embolism. Clin Nephrol. 2006;66:232–9.CrossRefPubMed
9.
go back to reference Woolfson RG, Lachmann H. Improvement in renal cholesterol emboli syndrome after simvastatin. Lancet. 1998;351:1331–2.CrossRefPubMed Woolfson RG, Lachmann H. Improvement in renal cholesterol emboli syndrome after simvastatin. Lancet. 1998;351:1331–2.CrossRefPubMed
11.
go back to reference Tamura K, Tsurumi-Ikeya Y, Wakui H, Maeda A, Ohsawa M, Azushima K, Kanaoka T, Uneda K, Haku S, Azuma K, Mitsuhashi H, Tamura N, Toya Y, Tokita Y, Kokuho T, Umemura S. Therapeutic potential of low-density lipoprotein apheresis in the management of peripheral artery disease in patients with chronic kidney disease. Ther Apher Dial. 2013;17:185–92.CrossRefPubMed Tamura K, Tsurumi-Ikeya Y, Wakui H, Maeda A, Ohsawa M, Azushima K, Kanaoka T, Uneda K, Haku S, Azuma K, Mitsuhashi H, Tamura N, Toya Y, Tokita Y, Kokuho T, Umemura S. Therapeutic potential of low-density lipoprotein apheresis in the management of peripheral artery disease in patients with chronic kidney disease. Ther Apher Dial. 2013;17:185–92.CrossRefPubMed
12.
go back to reference Tsunoda S, Daimon S, Miyazaki R, Fujii H, Inazu A, Mabuchi H. LDL apheresis as intensive lipid-lowering therapy for cholesterol embolism. Nephrol Dial Transplant. 1999;14:1041–2.CrossRefPubMed Tsunoda S, Daimon S, Miyazaki R, Fujii H, Inazu A, Mabuchi H. LDL apheresis as intensive lipid-lowering therapy for cholesterol embolism. Nephrol Dial Transplant. 1999;14:1041–2.CrossRefPubMed
13.
go back to reference Kobayashi H, Abe M, Murata Y, Maruyama T, Furukawa T, Oikawa O, Okada K. Low-density lipoprotein apheresis for corticosteroid-resistant skin lesions caused by cholesterol crystal embolism: a case report and review of the literature. J Artif Organs. 2015;18:285–9.CrossRefPubMed Kobayashi H, Abe M, Murata Y, Maruyama T, Furukawa T, Oikawa O, Okada K. Low-density lipoprotein apheresis for corticosteroid-resistant skin lesions caused by cholesterol crystal embolism: a case report and review of the literature. J Artif Organs. 2015;18:285–9.CrossRefPubMed
14.
go back to reference Hirai K, Ookawara S, Miyazawa H, Ito K, Ueda Y, Kaku Y, Hoshino T, Yoshida I, Tabei K. Low-density lipoprotein apheresis ameliorates monthly estimated glomerular filtration rate declines in patients with renal cholesterol crystal embolism. J Artif Organs. 2015;18:72–8.CrossRefPubMed Hirai K, Ookawara S, Miyazawa H, Ito K, Ueda Y, Kaku Y, Hoshino T, Yoshida I, Tabei K. Low-density lipoprotein apheresis ameliorates monthly estimated glomerular filtration rate declines in patients with renal cholesterol crystal embolism. J Artif Organs. 2015;18:72–8.CrossRefPubMed
15.
go back to reference Sanai T, Matsui R, Hirano T. LDL apheresis for cholesterol embolism following coronary artery bypass graft surgery—a case report. Angiology. 2006;57:379–82.CrossRefPubMed Sanai T, Matsui R, Hirano T. LDL apheresis for cholesterol embolism following coronary artery bypass graft surgery—a case report. Angiology. 2006;57:379–82.CrossRefPubMed
16.
go back to reference Tamura K, Umemura M, Yano H, Sakai M, Sakurai Y, Tsurumi Y, Tsurumi Y, Koide Y, Usui T, Yabana M, Toya Y, Tokita Y, Umemura S. Acute renal failure due to cholesterol crystal embolism treated with LDL apheresis followed by corticosteroid and candesartan. Clin Exp Nephrol. 2003;7:67–71.CrossRefPubMed Tamura K, Umemura M, Yano H, Sakai M, Sakurai Y, Tsurumi Y, Tsurumi Y, Koide Y, Usui T, Yabana M, Toya Y, Tokita Y, Umemura S. Acute renal failure due to cholesterol crystal embolism treated with LDL apheresis followed by corticosteroid and candesartan. Clin Exp Nephrol. 2003;7:67–71.CrossRefPubMed
17.
go back to reference Ishiyama K, Sato T, Taguma Y. Low-density lipoprotein apheresis ameliorates renal prognosis of cholesterol crystal embolism. Ther Apher Dial. 2015;19:355–60.CrossRefPubMed Ishiyama K, Sato T, Taguma Y. Low-density lipoprotein apheresis ameliorates renal prognosis of cholesterol crystal embolism. Ther Apher Dial. 2015;19:355–60.CrossRefPubMed
18.
go back to reference Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Hara S, Ura N, Kiyohara Y, Hirakata H, Watanabe T, Moriyama T, Ando Y, Inaguma D, Narita I, Iso H, Wakai K, Yasuda Y, Tsukamoto Y, Ito S, Makino H, Hishida A, Matsuo S. Estimation of glomerular filtration rate by the MDRD study equation modified for Japanese patients with chronic kidney disease. Clin Exp Nephrol. 2007;11:41–50.CrossRefPubMed Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Hara S, Ura N, Kiyohara Y, Hirakata H, Watanabe T, Moriyama T, Ando Y, Inaguma D, Narita I, Iso H, Wakai K, Yasuda Y, Tsukamoto Y, Ito S, Makino H, Hishida A, Matsuo S. Estimation of glomerular filtration rate by the MDRD study equation modified for Japanese patients with chronic kidney disease. Clin Exp Nephrol. 2007;11:41–50.CrossRefPubMed
19.
go back to reference Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.CrossRef Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.CrossRef
20.
go back to reference Jones DB, Iannaccone PM. Atheromatous emboli in renal biopsies. An ultrastructural study. Am J Pathol. 1975;78:261–76.PubMedPubMedCentral Jones DB, Iannaccone PM. Atheromatous emboli in renal biopsies. An ultrastructural study. Am J Pathol. 1975;78:261–76.PubMedPubMedCentral
21.
go back to reference Mannesse CK, Blankestijn PJ, Man in ‘t Veld AJ, Schalekamp MA. Renal failure and cholesterol crystal embolization: a report of 4 surviving cases and a review of the literature. Clin Nephrol. 1991;36:240–5.PubMed Mannesse CK, Blankestijn PJ, Man in ‘t Veld AJ, Schalekamp MA. Renal failure and cholesterol crystal embolization: a report of 4 surviving cases and a review of the literature. Clin Nephrol. 1991;36:240–5.PubMed
22.
go back to reference Nakayama M, Izumaru K, Nagata M, Ikeda H, Nishida K, Hasegawa E, Ohta Y, Tsuchihashi T, Urabe K. The effect of low-dose corticosteroids on short- and long-term renal outcome in patients with cholesterol crystal embolism. Ren Fail. 2011;33:298–306.CrossRefPubMed Nakayama M, Izumaru K, Nagata M, Ikeda H, Nishida K, Hasegawa E, Ohta Y, Tsuchihashi T, Urabe K. The effect of low-dose corticosteroids on short- and long-term renal outcome in patients with cholesterol crystal embolism. Ren Fail. 2011;33:298–306.CrossRefPubMed
23.
go back to reference Mann SJ, Sos TA. Treatment of atheroembolization with corticosteroids. Am J Hypertens. 2001;14:831–4.CrossRefPubMed Mann SJ, Sos TA. Treatment of atheroembolization with corticosteroids. Am J Hypertens. 2001;14:831–4.CrossRefPubMed
24.
go back to reference Kanesaki Y, Suzuki D, Uehara G, Toyoda M, Katoh T, Sakai H, Watanabe T. Vascular endothelial growth factor gene expression is correlated with glomerular neovascularization in human diabetic nephropathy. Am J Kidney Dis. 2005;45:288–94.CrossRefPubMed Kanesaki Y, Suzuki D, Uehara G, Toyoda M, Katoh T, Sakai H, Watanabe T. Vascular endothelial growth factor gene expression is correlated with glomerular neovascularization in human diabetic nephropathy. Am J Kidney Dis. 2005;45:288–94.CrossRefPubMed
25.
go back to reference Yuasa Y, Osaki T, Makino H, Iwamoto N, Kishimoto I, Usami M, Minamino N, Harada-Shiba M. Proteomic analysis of proteins eliminated by low-density lipoprotein apheresis. Ther Apher Dial. 2014;18:93–102.CrossRefPubMed Yuasa Y, Osaki T, Makino H, Iwamoto N, Kishimoto I, Usami M, Minamino N, Harada-Shiba M. Proteomic analysis of proteins eliminated by low-density lipoprotein apheresis. Ther Apher Dial. 2014;18:93–102.CrossRefPubMed
26.
go back to reference Empen K, Otto C, Brodl UC, Parhofer KG. The effects of three different LDL-apheresis methods on the plasma concentrations of E-selectin, VCAM-1, and ICAM-1. J Clin Apher. 2002;17:38–43.CrossRefPubMed Empen K, Otto C, Brodl UC, Parhofer KG. The effects of three different LDL-apheresis methods on the plasma concentrations of E-selectin, VCAM-1, and ICAM-1. J Clin Apher. 2002;17:38–43.CrossRefPubMed
27.
go back to reference Nenseter MS, Narverud I, Graesdal A, Bogsrud MP, Halvorsen B, Ose L, Aukrust P, Holven KB. Elevated serum MMP-9/TIMP-1 ratio in patients with homozygous familial hypercholesterolemia: effects of LDL-apheresis. Cytokine. 2013;61:194–8.CrossRefPubMed Nenseter MS, Narverud I, Graesdal A, Bogsrud MP, Halvorsen B, Ose L, Aukrust P, Holven KB. Elevated serum MMP-9/TIMP-1 ratio in patients with homozygous familial hypercholesterolemia: effects of LDL-apheresis. Cytokine. 2013;61:194–8.CrossRefPubMed
28.
go back to reference Hovland A, Lappegard KT, Mollnes TE. LDL apheresis and inflammation—implications for atherosclerosis. Scand J Immunol. 2012;76:229–36.CrossRefPubMed Hovland A, Lappegard KT, Mollnes TE. LDL apheresis and inflammation—implications for atherosclerosis. Scand J Immunol. 2012;76:229–36.CrossRefPubMed
29.
go back to reference Koenig W, Ditschuneit HH, Hehr R, Grunewald RW, Ernst E, Hombach V. Blood rheology after LDL apheresis using dextran sulfate cellulose absorption—a case report. Angiology. 1992;43:606–9.CrossRefPubMed Koenig W, Ditschuneit HH, Hehr R, Grunewald RW, Ernst E, Hombach V. Blood rheology after LDL apheresis using dextran sulfate cellulose absorption—a case report. Angiology. 1992;43:606–9.CrossRefPubMed
30.
go back to reference Otto C, Geiss HC, Laubach E, Schwandt P. Effects of direct adsorption of lipoproteins apheresis on lipoproteins, low-density lipoprotein subtypes, and hemorheology in hypercholesterolemic patients with coronary artery disease. Ther Apher. 2002;6:130–5.CrossRefPubMed Otto C, Geiss HC, Laubach E, Schwandt P. Effects of direct adsorption of lipoproteins apheresis on lipoproteins, low-density lipoprotein subtypes, and hemorheology in hypercholesterolemic patients with coronary artery disease. Ther Apher. 2002;6:130–5.CrossRefPubMed
31.
go back to reference Kizaki Y, Ueki Y, Yoshida K, Yano M, Matsumoto K, Miyake S, Tominaga Y, Eguchi K, Yano K. Does the production of nitric oxide contribute to the early improvement after a single low-density lipoprotein apheresis in patients with peripheral arterial obstructive disease? Blood Coagul Fibrinolysis. 1999;10:341–9.CrossRefPubMed Kizaki Y, Ueki Y, Yoshida K, Yano M, Matsumoto K, Miyake S, Tominaga Y, Eguchi K, Yano K. Does the production of nitric oxide contribute to the early improvement after a single low-density lipoprotein apheresis in patients with peripheral arterial obstructive disease? Blood Coagul Fibrinolysis. 1999;10:341–9.CrossRefPubMed
32.
go back to reference Tamai O, Matsuoka H, Itabe H, Wada Y, Kohno K, Imaizumi T. Single LDL apheresis improves endothelium-dependent vasodilatation in hypercholesterolemic humans. Circulation. 1997;95:76–82.CrossRefPubMed Tamai O, Matsuoka H, Itabe H, Wada Y, Kohno K, Imaizumi T. Single LDL apheresis improves endothelium-dependent vasodilatation in hypercholesterolemic humans. Circulation. 1997;95:76–82.CrossRefPubMed
33.
go back to reference Mii S, Mori A, Sakata H, Nakayama M, Tsuruta H. LDL apheresis for arteriosclerosis obliterans with occluded bypass graft: change in prostacyclin and effect on ischemic symptoms. Angiology. 1998;49:175–80.CrossRefPubMed Mii S, Mori A, Sakata H, Nakayama M, Tsuruta H. LDL apheresis for arteriosclerosis obliterans with occluded bypass graft: change in prostacyclin and effect on ischemic symptoms. Angiology. 1998;49:175–80.CrossRefPubMed
34.
go back to reference Kojima S, Ogi M, Yoshitomi Y, Kuramochi M, Ikeda J, Naganawa M, Hatakeyama H. Changes in bradykinin and prostaglandins plasma levels during dextran-sulfate low-density-lipoprotein apheresis. Int J Artif Organs. 1997;20:178–83.PubMed Kojima S, Ogi M, Yoshitomi Y, Kuramochi M, Ikeda J, Naganawa M, Hatakeyama H. Changes in bradykinin and prostaglandins plasma levels during dextran-sulfate low-density-lipoprotein apheresis. Int J Artif Organs. 1997;20:178–83.PubMed
35.
go back to reference Kobayashi S, Moriya H, Negishi K, Maesato K, Ohtake T. LDL-apheresis up-regulates VEGF and IGF-I in patients with ischemic limb. J Clin Apher. 2003;18:115–9.CrossRefPubMed Kobayashi S, Moriya H, Negishi K, Maesato K, Ohtake T. LDL-apheresis up-regulates VEGF and IGF-I in patients with ischemic limb. J Clin Apher. 2003;18:115–9.CrossRefPubMed
36.
go back to reference Kojima S, Shida M, Tanaka K, Takano H, Yokoyama H, Kuramochi M. Acute changes in plasma levels of hepatocyte growth factor during low-density lipoprotein apheresis. Ther Apher. 2001;5:2–6.CrossRefPubMed Kojima S, Shida M, Tanaka K, Takano H, Yokoyama H, Kuramochi M. Acute changes in plasma levels of hepatocyte growth factor during low-density lipoprotein apheresis. Ther Apher. 2001;5:2–6.CrossRefPubMed
37.
go back to reference Nakamura T, Sugaya T, Kawagoe Y, Ueda Y, Osada S, Koide H. Urinary liver-type fatty acid-binding protein levels for differential diagnosis of idiopathic focal glomerulosclerosis and minor glomerular abnormalities and effect of low-density lipoprotein apheresis. Clin Nephrol. 2006;65:1–6.CrossRefPubMed Nakamura T, Sugaya T, Kawagoe Y, Ueda Y, Osada S, Koide H. Urinary liver-type fatty acid-binding protein levels for differential diagnosis of idiopathic focal glomerulosclerosis and minor glomerular abnormalities and effect of low-density lipoprotein apheresis. Clin Nephrol. 2006;65:1–6.CrossRefPubMed
Metadata
Title
Efficacy of low-density lipoprotein apheresis combined with corticosteroids for cholesterol crystal embolism
Authors
Katsuya Ishiyama
Toshinobu Sato
Takuhiro Yamaguchi
Yoshio Taguma
Publication date
01-04-2017
Publisher
Springer Japan
Published in
Clinical and Experimental Nephrology / Issue 2/2017
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-016-1272-x

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