Hurdles to the introduction of new therapies for immune-mediated kidney diseases.

Innovative immunotherapies continue to markedly benefit many disciplines in clinical medicine but disappointingly, these benefits have not translated to the treatment of kidney diseases despite encouraging findings from preclinical models of kidney dysfunction. This lack of progress in nephrology might relate to the unique biology of the kidney. More likely, this lack of progress relates to conceptual hurdles in the application of newer therapies to renal disease. In this Review we discuss seven hurdles that must be addressed in order to appropriately assess and introduce immunologic therapies for immune-mediated kidney disease: the use of appropriate criteria to define disease categories; issues relating to the heterogeneity of kidney diseases and how this heterogeneity affects approaches to treatment; issues related to the rarity of most kidney diseases; the paucity of good animal models of human kidney disease; issues relating to trial design; problems with current approaches to the identification and use of appropriate and feasible study end points; and a lack of adequate biomarkers of intrarenal inflammation and parenchymal injury. We suggest that overcoming these hurdles, in addition to searching for better therapeutic targets, will be necessary to progress the treatment of immune-mediated kidney disease into a new age of drug therapy.