Atypical hemolytic-uremic syndrome and glomerulopathies. Clinical observation and a brief literature review

According to modern concepts, for the development of atypical hemolytic uremic syndrome (aHUS) in predisposed individuals, additional factors are necessary, which today are considered as complement-activating states. The most common of them are infections, pregnancy and childbirth, autoimmune diseases, transplantation of bone marrow and solid organs, some medications. Less commonly, aHUS is preceded by malignant arterial hypertension and glomerular kidney disease. Clinical observation of a patient suffering from a steroid-sensitive relapsing nephrotic syndrome (NS) for 10 years, in which after a viral infection first increased blood pressure, developed impaired renal function and hematological manifestations of thrombotic microangiopathy (ТМА), is given. In the presented observation, aHUS developed as a “second disease” in a patient with previously diagnosed glomerular kidney disease, which led to the rapid progression of chronic kidney disease with the development of terminal renal failure. This is evidenced by the nature of the course of the disease – NS recurring after acute respiratory viral infections, not accompanied by changes in urine sediment, arterial hypertension, impaired renal function and easily stopped by corticosteroids with rapid disappearance of proteinuria and normalization of protein blood counts. The change in the clinical picture of nephritis after a herpes zoster infection made us think about the development of a second renal disease of a different nature, other than glomerulonephritis. Undoubted AKI, combined with severe anemia and thrombocytopenia, was the basis for the exclusion of primarily TMA. The exclusion of TTP, STEC-HUS and the most common causes of secondary TMA made it possible to diagnose atypical HUS. The role of NS in the development of TMA is discussed. Blood coagulation disorders and VEGF-dependent mechanisms are considered as possible mechanisms.

atypical hemolytic uremic syndrome, nephrotic syndrome, glomerulopathy

1. Smirnov AV, Karunnaya AV, Dobronravov VA. Nephrological aspects of complement-mediated thrombotic microangiopathy. Ter arh 2017;89(6):34–40. doi: 10.17116/terarkh201789634-40 (In Russ.)

2. Siegler RL, Brewer ED, Pysher TJ. Hemolytic uremic syndrome associated with glomerular disease. Am Journ Kidney Diseases 1989; XIII(2):144–147. doi: 10.2169/internalmedicine.38.495

3. Morita S, Sakai T, Okamoto N et al. Hemolytic uremic syndrome associated with Immunoglobulin A nephropathy: a case report and review of cases of hemolytic uremic syndrome with glomerular disease. Internal Med 1999;38(6):495–499. doi: 10.2169/internalmedicine.38.495

4. Sürmeli-Döven S, Delibaş A, Gürses İ et al. Hemolytic uremic syndrome and IgA nephropathy in a child: Coincidence or not? The Turkish Journal of Pediatrics 2018;60:81–85. doi: 10.24953/turkjped.2018.01.012.

5. Benz K, Amann K, Dittrich K. Thrombotic microangiopathy as a complication in a patient with focal segmental glomerulosclerosis. Pediatr Nephrol 2007;22:2125–2128. doi: 10.1007/s00467-007-0563-6

6. Manenti L, Gnappi E, Vaglio A et al. Atypical hemolytic uremic syndrome with underlying glomerulopathies. A case series and a review of the literature. Nephrol Dial Transplant 2013;28:22462259. doi: 10.1093/ndt/gft220.

7. Izumi T, Hyodo T, Kikuchi Y et al. An adult with Acute poststreptococcal glomerulonephritis complicated by hemolytic uremic syndrome and nephrotic syndrome. Am Journ Kidney Diseases 2005;46(4):E59–E63. doi: 10.1053/j.ajkd.2005.06.010

8. Kakajiwala A, Bhatti T, Kaplan BS et al. Post-streptococcal glomerulonephritis associated with atypical hemolytic uremic syndrome: to treat or not to treat with eculizumab? Clinical Kidney Journal 2016;9(1):90–96. doi: 10.1093/ckj/sfv119.

9. Parekh M, Konnur A, Gang S. Poststreptococcal Glomerulonephritis with Atypical Hemolytic Uremic Syndrome: An Unusual Presentation. Saudi J Kidney Dis Transpl 2018;29(3):728–731. doi: 10.4103/1319-2442.235201.

10. Bulanov NM, Kozlovskaya NL, Moiseev SV. ANCA-associated vasculitis and atypical hemolytic uremic syndrome in a patient with DGKE mutation (Сlinical discussion). Nefrologiya i dializ 2018;20(2):212–224. doi: 10.28996/2618-9801-2018-2-212-224 (In Russ.)

11. Sathe KP, Mehta KP. Coexistence of Atypical Hemolytic Uremic Syndrome with Membranoproliferative Glomerulonephritis and Antineutrophil Cytoplasmic Antibodies-associated Vasculitis. Saudi J Kidney Dis Transpl 2016;27(4):800–804. doi: 10.4103/1319-2442.185267

12. Song D, Wu L, Wang F et al. The spectrum of renal thrombotic microangiopathy in Lupus nephritis. Arthritis Research&Therapy 2013;15:R12–R23. doi: 10.1186/ar4142.

13. Blum D, Blake G. Lupus-associated thrombotic thrombocytopenic purpura-like microangiopathy. World J Nephrol 2015;4(5):528–531. doi: 10.5527/wjn.v4.i5.528.

14. Ono M, Ohashi N, Namikawa A et al. A Rare Case of Lupus Nephritis Presenting as Thrombotic Microangiopathy with Diffuse Pseudotubulization Possibly Caused by Atypical Hemolytic Uremic Syndrome. Intern Med 2018;57:1617–1623. doi: 10.2169/internalmedicine.0228-17

15. Tao J, Lieberman J, Lafayette RA, Kambham N. A rare case of Alport syndrome, atypical hemolytic uremic syndrome and Pauci-immune crescentic glomerulonephritis. BMC Nephrology 2018;19:355–361. doi: 10.1186/s12882-018-1170-4.

16. Noris M, Remuzzi G. Glomerular Diseases Dependent on Complement Activation, Including Atypical Hemolytic Uremic Syndrome, Membranoproliferative Glomerulonephritis, and C3 Glomerulopathy. Am J Kidney Dis 2015;66:359–375. doi: 10.1053/j.ajkd.2015.03.040.

17. Ankawi GA, Clark WF. Atypical haemolytic uremic syndrome (aHUS) and membranoproliferative glomerulonephritis (MPGN), different diseases or a spectrum of complement mediated glomerular diseases? BMJ Case Rep 2017.doi:10.1136/bcr-2017-220974

18. Chen G, Liu H, Liu F. A glimpse of the glomerular milieu: from endothelial cells to thrombotic disease in nephrotic syndrome. Microvascular research 2013;89:1–6. doi: 10.1016/j.mvr.2013.06.011

19. Noris M, Mele C, Remuzzi G. Podocyte dysfunction in atypical haemolytic uraemic syndrome. Nature Reviews Nephrology 2015. doi:10.1038/nrneph.2014.250

20. Tkaczyk M, Czupryniak A, Owczarek D et al. Markers of endothelial dysfunction in children with idiopathic nephrotic syndrome. Am J Nephrol 2008;28:197–202. doi: 10.1159/000110088

21. Gao C, Xie R, Yu C et al. Procoagulant activity of erythrocytes and platelets through phosphatidylserine exposure and microparticles release in patients with nephrotic syndrome. Thromb Haemost 2012;107:681–689. doi: 10.1160/TH11-09-0673

22. Burger D, Schok S, Thompson CS et al. Microparticles: biomarkers and beyond. Clin Sci (London) 2013;124:423–441. doi: 10.1042/CS20120309

23. Khan F, Yamakami K, Machmood J et al. Alteration of cell adhesion molecules in human glomerular endothelial cells in response to nephritis-associated plasminogen receptor. Nephron Exp Nephrol 2007;105:e53–e64. doi: 10.1159/000097840

24. Eremina V, Jefferson J, Kowalewska J et al. VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008;358:1129–1136. doi: 10.1056/NEJMoa0707330

25. Keir LS, Firth R, Aponic L et al. VEGF regulates local inhibitory complement proteins in the eye and kidney. J Clin Invest 2017;127(1):199–214. doi: 10.1172/JCI86418

26. Allison SJ. VEGF-complement interactions. Nature Reviews Nephrology 2016. doi:10.1038/nrneph.2016.184

27. Amore A, Conti G, Cirina P et al. Aberrantly glycosylated IgA molecules downregulate the synthesis and secretion of vascular endothelial growth factor in human mesangial cells. Am J Kidney Disease 2000;36:1242–1252. doi: 10.1053/ajkd.2000.19840