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.
Similar content being viewed by others
References
Scolari F, Ravani P. Atheroembolic renal disease. Lancet. 2010;375:1650–60.
Modi KS, Rao VK. Atheroembolic renal disease. J Am Soc Nephrol. 2001;12:1781–7.
Kronzon I, Saric M. Cholesterol embolization syndrome. Circulation. 2010;122:631–41.
Fine MJ, Kapoor W, Falanga V. Cholesterol crystal embolization: a review of 221 cases in the English literature. Angiology. 1987;38:769–84.
Belenfant X, Meyrier A, Jacquot C. Supportive treatment improves survival in multivisceral cholesterol crystal embolism. Am J Kidney Dis. 1999;33:840–50.
Lye WC, Cheah JS, Sinniah R. Renal cholesterol embolic disease. Case report and review of the literature. Am J Nephrol. 1993;13:489–93.
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.
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.
Woolfson RG, Lachmann H. Improvement in renal cholesterol emboli syndrome after simvastatin. Lancet. 1998;351:1331–2.
Muso E. Beneficial effect of LDL-apheresis in refractory nephrotic syndrome. Clin Exp Nephrol. 2014;18:286–90.
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.
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.
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.
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.
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.
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.
Ishiyama K, Sato T, Taguma Y. Low-density lipoprotein apheresis ameliorates renal prognosis of cholesterol crystal embolism. Ther Apher Dial. 2015;19:355–60.
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.
Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.
Jones DB, Iannaccone PM. Atheromatous emboli in renal biopsies. An ultrastructural study. Am J Pathol. 1975;78:261–76.
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.
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.
Mann SJ, Sos TA. Treatment of atheroembolization with corticosteroids. Am J Hypertens. 2001;14:831–4.
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.
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.
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.
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.
Hovland A, Lappegard KT, Mollnes TE. LDL apheresis and inflammation—implications for atherosclerosis. Scand J Immunol. 2012;76:229–36.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Acknowledgments
This study was funded by grants from the Miyagi Kidney Foundation. These results were presented in part at the 27th Annual Meeting of the Japanese Society of Kidney and Lipids. The authors have declared that they have no conflicts of interest.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Ishiyama, K., Sato, T., Yamaguchi, T. et al. Efficacy of low-density lipoprotein apheresis combined with corticosteroids for cholesterol crystal embolism. Clin Exp Nephrol 21, 228–235 (2017). https://doi.org/10.1007/s10157-016-1272-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10157-016-1272-x