Pathological aspects of membranoproliferative glomerulonephritis (MPGN) and haemolytic uraemic syndrome (HUS) / thrombocytic thrombopenic purpura (TTP)

Summary

In this paper, epidemiology, pathogenesis and typical morphological aspects of all three types of membranoproliferative glomerulonephritis (MPGN), of the haemolytic uraemic syndrome (HUS) as well as of thrombotic thrombopenic purpura (TTP) will be reviewed on the light microscopical, immunohistological or immunofluorescence and electron microscopical level. In particular, differences in the pathogenesis of these diseases are discussed. Important recent molecular and genetic insights into the pathogenesis of the three types of MPGN, of typical and atypical HUS and of TTP, i.e. dysregulation of the complement system, distinct molecular defects in C3 and factor H, the major regulatory protein of the alternative pathway of complement activation, and deficiency of a von Willebrand factor (VWF) -cleaving protease, i.e. ADAMTS13, are highlighted. Finally, particular emphasis will be put on differences in glomerular and vascular morphology in the three types of MPGN and in thrombotic microangiopathy (TMA), which is the characteristic morphological alteration of the kidney in HUS and TTP, respectively.

Keywords

Membranoproliferative GN (MPGN) - dense deposit disease (DDD) - thrombotic microangiopathy (TMA) - haemolytic uremic syndrome (HUS) - thrombocytic thrombopenic purpura (TTP) - pathology

• References

• 1 Schena FP, Alpers CE. Membranoproliferative Glomerulonephritis and Cryoglobulinemic glomerulonephritis. In: Comprehensive Clinical Nephrology. Mosby; Edinburgh: 2007. pp. 243-252.
• 2 Smith KD, Alpers CE. Pathogenic mechanisms in membranoproliferative glomerulonephritis. Curr Opin Nephrol Hypertens 2005; 14: 396-403.
• 3 Pickering MC, Cook HT. Translational mini-review series on complement factor H: Renal diseases associated with complement factor H: novel insights from humans and animals. Clin Exp Immunol 2008; 151: 210-230.
• 4 Andresdottir MB, Wetzels J. Differences between type I and II membranoproliferative glomerulonephritis. Kidney Int 2006; 69: 504-511.
• 5 Razukeviciene L. et al. Membranoproliferative glomerulonephritis is still the most frequent glomerulonephritis in Lithuania. Clin Nephrol 2006; 65: 87-90.
• 6 Rychlík I. et al. The Czech registry of renal biopsies. Occurrence of renal diseases in the years 1994–2000. Nephrol Dial Transplant 2004; 19: 3040-3049.
• 7 Covic A. et al. Epidemiology of renal disease in Romania: a 10 year review of two regional renal biopsy databases. Nephrol Dial Transplant 2006; 21: 419-424.
• 8 Gesualdo L. et al. Italian Immunopathology Group, Italian Society of Nephrology. The Italian experience of the national registry of renal biopsies. Kidney Int 2004; 66: 890-894.
• 9 Nair R, Walker PD. Is IgA nephropathy the commonest primary glomerulopathy among young adults in the USA?. Kidney Int 2006; 69: 1455-1458.
• 10 Swaminathan S. et al. Changing incidence of glomerular disease in Olmsted County, Minnesota: a 30-year renal biopsy study. Clin J Am Soc Nephrol 2006; 1: 483-487.
• 11 Zipfel PF. et al. Complement and diseases: Defective alternative pathway control results in kidney and eye disease. Mol Immunol 2006; 43: 97-106.
• 12 Pickering MC. et al. Uncontrolled C3 activation causes membranoproliferative glomerulonephritis in mice deficient in complement factor H. Nat Genet 2002; 31: 333-334.
• 13 Linshaw MA. et al. Hypocomplementemic glomerulonephritis in an infant and mother. Evidence for an abnormal form of C3. Am J Nephrol 1987; 7: 470-477.
• 14 Little MA. et al. Severity of primary MPGN, rather than MPGN type, determines renal survival and post-transplantation recurrence risk. Kidney Int 2006; 69: 504-511.
• 15 Appel GB. et al. Membranoproliferative glomerulonephritis type II (dense deposit disease): an update. J Am Soc Nephrol 2005; 16: 1392-1403.
• 16 Smith RJ. et al. Dense Deposit Disease Focus Group: New approaches to the treatment of dense deposit disease. J Am Soc Nephrol 2007; 18: 2447-2456.
• 17 West CD, McAdams AJ. Paramesangial glomerular deposits in membranoproliferative glomerulonephritis type II correlate with hypocomplementemia. Am J Kidney Dis 1995; 25: 853-861.
• 18 Walker PD. et al. Dense deposit disease is not a membranoproliferative glomerulonephritis. Mod Pathol 2007; 20: 605-616.
• 19 Walker PD. Dense deposit disease: new insights. Curr Opin Nephrol Hypertens 2007; 16: 204-212.
• 20 West CD. et al. Composition of nephritic factor-generated glomerular deposits in membranoproliferative glomerulonephritis type 2. Am J Kidney Dis 2001; 37: 1120-1130.
• 21 de Córdoba SR, de Jorge EG. Translational mini-review series on complement factor H: genetics and disease associations of human complement factor H. Clin Exp Immunol 2008; 151: 1-13.
• 22 Hogasen K. et al. Hereditary procine membranoproliferative glomerulonpehritis type II is caused by factor H deficiency. J Clin Invest 1995; 95: 1054-1061.
• 23 Licht C. et al. MPGN II--genetically determined by defective complement regulation?. Pediatr Nephrol 2007; 22: 2-9.
• 24 Joshi K. et al. Recurrent glomerulopathy in the renal allograft. Transplant Proc 2007; 39: 734-736.
• 25 Aita K. et al. Early recurrence of dense deposit disease with marked endocapillary proliferation after renal transplantation. Pathol Int 2006; 56: 101-109.
• 26 West CD, McAdams AJ. Membranoproliferative glomerulonephritis type III: association of glomerular deposits with circulating nephritic factor-stabilized convertase. Am J Kidney Dis 1998; 32: 56-63.
• 27 Neary J. et al. Familial membranoproliferative glomerulonephritis type III. Am J Kidney Dis 2002; 40: E1.
• 28 Neary JJ. et al. Linkage of a gene causing familial membranoproliferative glomerulonephritis type III to chromosome 1. J Am Soc Nephrol 2002; 13: 2052-2057.
• 29 Strife CF. et al. Membranoproliferative glomerulonephritis with disruption of the glomerular basement membrane. Clin Nephrol 1977; 7: 65-72.
• 30 Ruggenenti P. et al. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int 2001; 60: 831-846.
• 31 Tsai HM. The kidney in thrombotic thrombocytopenic purpura. Minerva Med 2007; 98: 731-747.
• 32 Fakhouri F, Frémeaux-Bacchi V. Does hemolytic uremic syndrome differ from thrombotic thrombocytopenic purpura?. Nat Clin Pract Nephrol 2007; 3: 679-687.
• 33 Desch K, Motto D. Is there a shared pathophysiology for thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome?. J Am Soc Nephrol 2007; 18: 2457-2460.
• 34 Martinez-Barricarte R. et al. European Working Party on the Genetics of HUS. The complement factor H R1210C mutation is associated with atypical haemolytic uremic syndrome. J Am Soc Nephrol 2008; 12: 639-646.
• 35 Jokiranta TS. et al. Where next with atypical haemolytic syndrome?. Mol Immunol 2007; 44: 3889-3900.
• 36 Servais A. et al. Primary glomerulonephritis with isolated C3 deposits: a new entity which shares common genetic factors with haemolytic uraemic syndrome. J Med Genet 2007; 44: 193-199.
• 37 Pickering MC. et al. Spontaneous haemolytic uremic syndrome triggered by complement factor H lacking surface recognition domains. J Exp Med 2007; 204: 1249-1256.
• 38 Jha V. et al. Secondary membranoproliferative glomerulonephritis due to hemolytic uremic syndrome: an unusual presentation. Ren Failure 1998; 20: 845-850.
• 39 Benz K. et al. Thrombotic microangiopathy as a complication in a patient with focal segmental glomerulosclerosis. Pediatr Nephrol 2007; 22: 2125-2128.