A case of lipoprotein glomerulopathy with thrombotic microangiopathy due to malignant hypertension

BMC Nephrology

Zhangxue Hu³  Ping Fu³  Ye Tao³  Xiaoxia Liu³  Baohe Wang¹  Yuan Yang²  Xiaohan Chen³  Yu Wu⁴ 

[1] Department of Nephrology, Nuclear industry 416 Hospital, Chengdu, Sichuan Province, China;Department of Medical Genetics, West China Hospital, National Key Laboratory of Biotherapy of Human Diseases, Sichuan University, Chengdu, Sichuan Province, China;Department of Nephrology, West China Hospital, National Key Laboratory of Biotherapy of Human Diseases, Sichuan University, Chengdu, Sichuan Province, China;Department of Hematology, West China Hospital, National Key Laboratory of Biotherapy of Human Diseases, Sichuan University, Chengdu, Sichuan Province, China

关键词: APOE Kyoto;    Malignant hypertension;    Thrombotic microangiopathy;    Lipoprotein glomerulopathy;   

Others  :  1082985
DOI  :  10.1186/1471-2369-14-53

 received in 2012-09-08, accepted in 2013-02-13,  发布年份 2013

【 摘 要 】

Background

Lipoprotein glomerulopathy (LPG) is a rare inherited renal disease characterized by intraglomerular lipoprotein within the lumina of severely dilated glomerular capillaries. The common clinical presentation of LPG includes proteinuria or nephrotic syndrome. Hypertension and anemia were thought to be mild in LPG. Thrombotic microangiopathy (TMA) in LPG has not been previously reported. In this report, we present a patient with LPG that developed TMA. To the best of our knowledge, this is the first report of TMA in LPG.

Case presentation

Four years ago (2005), a 19-year-old Chinese woman was diagnosed with nephrotic syndrome and provided prednisone treatment. A combination of prednisone and cyclophosphamide did not have any effect and was discontinued after six months. Although she was steroid-resistant, over the next subsequent three years, she maintained normal renal function without anemia and thrombocytopenia. In February 2009, she had a severe headache and blurry vision and presented at a local hospital with severe hypertension. Blood pressure was 220/160 mmHg. Laboratory data showed hemoglobin 3.8 g/dL; platelet counts 29×10⁹/L; urinary protein 7.90 g/d; total bilirubin 29.9 umol/L; indirect bilirubin 28.2 umol/L; LDH 1172 U/L; ALB 2.66 g/dL; urea nitrogen 52 mg/dL; serum creatinine 3.2 mg/dL; triglyceride 253 mg/dL; total cholesterol 273 mg/dL. ANA, ds-DNA, ANCA, anti-GBM antibody and anticardiolipin were all negative. A renal biopsy revealed LPG with TMA. Genetic evaluation showed the patient carried the APOE Kyoto mutation. Adequate control of blood pressure improved microangiopathic anemia and thrombocytopenia, however, renal function did not improve and she eventually developed uremia and became hemodialysis dependent.

Conclusion

We report on a rare case of TMA probably due to malignant hypertension in LPG. Early lipid-lowering and antihypertensive treatment may improve outcome. The pathophysiologic relationship between LPG and TMA should be investigated further.

【 授权许可】

   
2013 Wu et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Liberopoulos E, Siamopoulos K, Elisaf M: Apolipoprotein E and renal disease. Am J Kidney Dis 2004, 43(2):223-233.
• [2]Saito T, Ishigaki Y, Oikawa S, Yamamoto TT: Etiological significance of apolipoprotein E mutations in lipoprotein glomerulopathy. Trends Cardiovasc Med 2002, 12(2):67-70.
• [3]Hixson JE, Vernier DT: Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 1990, 31(3):545-548.
• [4]Saito T, Sato H, Kudo K, Oikawa S, Shibata T, Hara Y, Yoshinaga K, Sakaguchi H: Lipoprotein glomerulopathy: glomerular lipoprotein thrombi in a patient with hyperlipoproteinemia. Am J Kidney Dis 1989, 13(2):148-153.
• [5]Saito T, Matsunaga A, Oikawa S: Impact of lipoprotein glomerulopathy on the relationship between lipids and renal diseases. Am J Kidney Dis 2006, 47(2):199-211.
• [6]Sam R, Wu H, Yue L, Mazzone T, Schwartz MM, Arruda JA, Dunea G, Singh AK: Lipoprotein glomerulopathy: a new apolipoprotein E mutation with enhanced glomerular binding. Am J Kidney Dis 2006, 47(3):539-548.
• [7]Ruggenenti P, Cravedi P, Remuzzi G: Thrombotic microangiopathies, including hemolytic uremic syndrome. In Comprehensive clinical nephrology. 4th edition. Edited by Floege J, Johnson RJ, Feehally J. Missouri: Elsevier Saunders; 2010:344-355.
• [8]Yokomine T, Hirakawa H, Ozawa E, Shibata K, Nakayama T: Pulmonary thrombotic microangiopathy caused by gastric carcinoma. J Clin Pathol 2010, 63(4):367-369.
• [9]Mii A, Shimizu A, Masuda Y, Fujino T, Kaneko T, Utsumi K, Arai T, Ishikawa A, Wakamatsu K, Tajika K, et al.: Renal thrombotic microangiopathy associated with chronic humoral graft versus host disease after hematopoietic stem cell transplantation. Path Int 2011, 61(1):34-41.
• [10]Hu WX, Liu ZZ, Chen HP, Zhang HT, Li LS, Liu ZH: Clinical characteristics and prognosis of diffuse proliferative lupus nephritis with thrombotic microangiopathy. Lupus 2010, 19(14):1591-1598.
• [11]Dlott JS, Danielson CFM, Blue-Hnidy DE, McCarthy LJ: Drug-induced thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: a concise review. Ther Apher Dial 2004, 8(2):102-111.
• [12]George JN, Raskob GE, Shah SR, Rizvi M, Hamilton S, Osborne S, Vondracek T: Drug-induced thrombocytopenia: a systematic review of published case reports. Ann Intern Med 1998, 129(11):886-890.
• [13]Jackson AM, Rose BD, Graff LG, Jacobs JB, Schwartz JH, Strauss GM, Yang JP, Rudnick MR, Elfenbein IB, Narins RG: Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy. Ann Intern Med 1984, 101(1):41-44.
• [14]Akimoto T, Muto S, Ito C, Takahashi H, Takeda S, Ando Y, Kusano E: Clinical features of malignant hypertension with thrombotic microangiopathy. Clin Exp Hypertens 2011, 33(2):77-83.
• [15]Pardo V, Aburano A: Thrombotic microangiopathy and malignant hypertension. Am J Clin Pathol 1966, 45(5):605-613.
• [16]van den Born BJ, Honnebier UP, Koopmans RP, van Montfrans GA: Microangiopathic hemolysis and renal failure in malignant hypertension. Hypertension 2005, 45(2):246-251.
• [17]van den Born BJ, van der Hoeven NV, Groot E, Lenting PJ, Meijers JC, Levi M, van Montfrans GA: Association between thrombotic microangiopathy and reduced ADAMTS13 activity in malignant hypertension. Hypertension 2008, 51(4):862-866.
• [18]Shibagaki Y, Fujita T: Thrombotic microangiopathy in malignant hypertension and hemolytic uremic syndrome (HUS)/ thrombotic thrombocytopenic purpura (TTP): can we differentiate one from the other? Hypertens Res 2005, 28(1):89-95.
• [19]Lip GY, Beevers M, Beevers DG: Complications and survival of 315 patients with malignant-phase hypertension. J Hypertens 1995, 13(8):915-924.
• [20]Xin Z, Zhihong L, Shijun L, Jinfeng Z, Huiping C, Caihong Z, Daxi J, Leishi L: Successful treatment of patients with lipoprotein glomerulopathy by protein A immunoadsorption: a pilot study. Nephrol Dial Transplant 2009, 24(3):864-869.
• [21]Russi G, Furci L, Leonelli M, Magistroni R, Romano N, Rivasi P, Albertazzi A: Lipoprotein glomerulopathy treated with LDL-apheresis (heparin-induced extracorporeal lipoprotein precipitation system): a case report. J Med Case Reports 2009, 3:9311. BioMed Central Full Text
• [22]Hamatani H, Hiromura K, Kobatake K, Yoshida H, Kobayashi S, Yoneda N, Kayakabe K, Matsumoto T, Kuroiwa T, Ueki K, et al.: Successful treatment of lipoprotein glomerulopathy in a daughter and a mother using niceritrol. Clin Exp Nephrol 2010, 14(6):619-624.
• [23]Matsunaga A, Furuyama M, Hashimoto T, Toyoda K, Ogino D, Hayasaka K: Improvement of nephrotic syndrome by intensive lipid-lowering therapy in a patient with lipoprotein glomerulopathy. Clin Exp Nephrol 2009, 13(6):659-662.
• [24]Ieiri N, Hotta O, Taguma Y: Resolution of typical lipoprotein glomerulopathy by intensive lipid-lowering therapy. Am J Kidney Dis 2003, 41(1):244-249.
• [25]Arai T, Yamashita S, Yamane M, Manabe N, Matsuzaki T, Kiriyama K, Kanayama Y, Himeno S, Matsuzawa Y: Disappearance of intraglomerular lipoprotein thrombi and marked improvement of nephrotic syndrome by bezafibrate treatment in a patient with lipoprotein glomerulopathy. Atherosclerosis 2003, 169(2):293-299.
• [26]Fisher DC, Sherrill GB, Hussein A, Rubin P, Vredenburgh JJ, Elkordy M, Ross M, Petros W, Peters WP: Thrombotic microangiopathy as a complication of high-dose chemotherapy for breast cancer. Bone Marrow Transplant 1996, 18(1):193-198.
• [27]Porta C, Danova M, Riccardi A, Bobbio-Pallavicini E, Ascari E: Cancer chemotherapy-related thrombotic thrombocytopenic purpura: biological evidence of increased nitric oxide production. Mayo Clin Proc 1999, 74(6):570-574.