Medical researchers, including Fernando Fervenza, M.D., Ph.D., Mayo Clinic College of Medicine, recently reviewed kidney disease caused by genetic or acquired dysregulation of the complement alternative pathway (AP) in the Journal of the American Society of Nephrology.
Kidney diseases caused by genetic or acquired dysregulation of the complement AP are traditionally classified on the basis of clinical presentation (atypical hemolytic uremic syndrome as thrombotic microangiopathy), biopsy appearance (dense deposit disease and C3 GN), or clinical course (atypical postinfectious GN). Each is characterized by an inappropriate activation of the AP, eventuating in renal damage.
The clinical diversity of these disorders highlights important differences in the triggers, the sites and intensity of involvement, and the outcome of the AP dysregulation. In the review, the researchers discuss that these diseases should be grouped as disorders of the AP and classified on an etiologic basis.
The researchers also defined different pathophysiologic categories of AP dysfunction. The precise identification of the underlying abnormality is the key to predict the response to immune suppression, plasma infusion, and complement-inhibitory drugs and the outcome after transplantation. In a patient with presumed dysregulation of the AP, the collaboration of the clinician, the renal pathologist, and the biochemical and genetic laboratory is very much encouraged, because this enables the elucidation of both the underlying pathogenesis and the optimal therapeutic approach.