The complement system comprises a complex network of plasma proteins that cooperate in the defence against pathogens and the maintenance of tissue homeostasis. Although a role for complement in renal disease has long been recognized, increasing understanding of the mechanisms by which complement mediates renal injury has led to the development of strategies by which complement may be targeted to prevent renal disease and its associated complications. This focus issue on targeting complement in renal disease contains five Reviews written by experts in the field, describing the mechanisms by which complement deregulation causes kidney disease, how improved understanding of complement has resulted in the reclassification of renal disease, and potential treatment strategies to target complement in renal disease.


STEC-HUS, atypical HUS and TTP are all diseases of complement activation

Marina Noris, Federica Mescia & Giuseppe Remuzzi


Nature Reviews Nephrology 8, 622-633 (2012)

Atypical haemolytic uraemic syndrome (HUS), Shiga toxin-producing Escherichia coli-associated HUS and thrombotic thrombocytopaenic purpura are diseases characterized by microvascular thrombosis, with subsequent dysfunction of affected organs. In this Review, the authors discuss data indicating that complement dysregulation is a common pathogenetic effector of all three diseases, and describe the emerging evidence indicating that targeting complement may effectively treat these disease entities.

Pathogenesis of the C3 glomerulopathies and reclassification of MPGN

Andrew S. Bomback & Gerald B. Appel


Nature Reviews Nephrology 8, 634-642 (2012)

Improved understanding of the role of complement in the pathogenesis of a number of glomerular diseases has led to progress in disease classification and treatment. In this Review, Bomback and Appel re-examine the previous classification schemes for membranoproliferative glomerulonephritis (MPGN) and discuss the role of complement in the various MPGN lesions including the C3 glomerulopathies. In addition, they discuss the pathogenesis, diagnosis, treatment, and prognosis of the C3 glomerulopathies.

Use of eculizumab for atypical haemolytic uraemic syndrome and C3 glomerulopathies

Julien Zuber, Fadi Fakhouri, Lubka T. Roumenina, Chantal Loirat & Véronique Frémeaux-Bacchi on behalf of the French Study Group for aHUS/C3G


Nature Reviews Nephrology 8, 643-657 (2012)

Here, Zuber et al., on behalf of the French Study Group for aHUS/C3G, discuss the role of eculizumab in the treatment of atypical haemolytic uraemic syndrome (aHUS). They review data from case reports and preliminary data from prospective trials, present their opinions, and describe issues that require further study. In addition, they discuss the potential use of eculizumab in C3 glomerulopathies.

Renal and neurological involvement in typical Shiga toxin-associated HUS

Howard Trachtman, Catherine Austin, Maria Lewinski & Rolf A. K. Stahl


Nature Reviews Nephrology 8, 658-669 (2012)

Shiga toxin-producing Escherichia coli-associated haemolytic uraemic syndrome (STEC-HUS) is associated with renal and neurological injury. This Review summarizes the pathophysiology and clinical presentation of STEC-HUS and its acute and long-term effects on the kidney and central nervous system. The authors also describe the experience of a single centre that was affected by the STEC-HUS outbreak in Germany in 2011.

The role of complement in antibody-mediated rejection in kidney transplantation

Mark D. Stegall, Marcio F. Chedid & Lynn D. Cornell


Nature Reviews Nephrology 8, 670-678 (2012)

Much progress has been made in understanding the processes underlying antibody-mediated rejection (AMR) of transplanted organs. In this Review, the authors discuss the role of the complement system in acute and chronic AMR, with specific emphasis on renal transplantation, and describe studies demonstrating that blockade of terminal complement activation can prevent AMR in sensitized renal transplant recipients.


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