Skip to main content

Advertisement

Log in

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

  • Original Article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Scolari F, Ravani P. Atheroembolic renal disease. Lancet. 2010;375:1650–60.

    Article  PubMed  Google Scholar 

  2. Modi KS, Rao VK. Atheroembolic renal disease. J Am Soc Nephrol. 2001;12:1781–7.

    CAS  PubMed  Google Scholar 

  3. Kronzon I, Saric M. Cholesterol embolization syndrome. Circulation. 2010;122:631–41.

    Article  PubMed  Google Scholar 

  4. Fine MJ, Kapoor W, Falanga V. Cholesterol crystal embolization: a review of 221 cases in the English literature. Angiology. 1987;38:769–84.

    Article  CAS  PubMed  Google Scholar 

  5. Belenfant X, Meyrier A, Jacquot C. Supportive treatment improves survival in multivisceral cholesterol crystal embolism. Am J Kidney Dis. 1999;33:840–50.

    Article  CAS  PubMed  Google Scholar 

  6. Lye WC, Cheah JS, Sinniah R. Renal cholesterol embolic disease. Case report and review of the literature. Am J Nephrol. 1993;13:489–93.

    Article  CAS  PubMed  Google Scholar 

  7. 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.

    Article  PubMed  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. Woolfson RG, Lachmann H. Improvement in renal cholesterol emboli syndrome after simvastatin. Lancet. 1998;351:1331–2.

    Article  CAS  PubMed  Google Scholar 

  10. Muso E. Beneficial effect of LDL-apheresis in refractory nephrotic syndrome. Clin Exp Nephrol. 2014;18:286–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 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.

    Article  CAS  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. 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.

    Article  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  Google Scholar 

  15. 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.

    Article  PubMed  Google Scholar 

  16. 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.

    Article  PubMed  Google Scholar 

  17. Ishiyama K, Sato T, Taguma Y. Low-density lipoprotein apheresis ameliorates renal prognosis of cholesterol crystal embolism. Ther Apher Dial. 2015;19:355–60.

    Article  CAS  PubMed  Google Scholar 

  18. 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.

    Article  PubMed  Google Scholar 

  19. Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transpl. 2013;48:452–8.

    Article  CAS  Google Scholar 

  20. Jones DB, Iannaccone PM. Atheromatous emboli in renal biopsies. An ultrastructural study. Am J Pathol. 1975;78:261–76.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 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.

    CAS  PubMed  Google Scholar 

  22. 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.

    Article  CAS  PubMed  Google Scholar 

  23. Mann SJ, Sos TA. Treatment of atheroembolization with corticosteroids. Am J Hypertens. 2001;14:831–4.

    Article  CAS  PubMed  Google Scholar 

  24. 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.

    Article  CAS  PubMed  Google Scholar 

  25. 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.

    Article  CAS  PubMed  Google Scholar 

  26. 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.

    Article  PubMed  Google Scholar 

  27. 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.

    Article  CAS  PubMed  Google Scholar 

  28. Hovland A, Lappegard KT, Mollnes TE. LDL apheresis and inflammation—implications for atherosclerosis. Scand J Immunol. 2012;76:229–36.

    Article  CAS  PubMed  Google Scholar 

  29. 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.

    Article  CAS  PubMed  Google Scholar 

  30. 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.

    Article  CAS  PubMed  Google Scholar 

  31. 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.

    Article  CAS  PubMed  Google Scholar 

  32. 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.

    Article  CAS  PubMed  Google Scholar 

  33. 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.

    Article  CAS  PubMed  Google Scholar 

  34. 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.

    CAS  PubMed  Google Scholar 

  35. 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.

    Article  PubMed  Google Scholar 

  36. 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.

    Article  CAS  PubMed  Google Scholar 

  37. 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.

    Article  CAS  PubMed  Google Scholar 

Download references

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

Authors

Corresponding author

Correspondence to Katsuya Ishiyama.

About this article

Check for updates. Verify currency and authenticity via CrossMark

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-016-1272-x

Keywords

Navigation