Abstract
A major obstacle in kidney transplantation for primary focal segmental glomerulosclerosis (FSGS) is the risk of disease recurrence. Recurrent FSGS affects up to 60% of first kidney grafts and exceeds 80% in patients who have lost their first graft due to recurrent FSGS. Clinical and experimental evidence support the hypothesis that a circulating permeability factor is the mediator in the pathogenesis of primary and recurrent disease. Despite all efforts, the causing agent has not yet been identified. Several treatment options for the management of recurrent FSGS have been proposed. In addition to plasma exchange, B-cell depleting antibodies are effective in recurrent FSGS. This indicates, that the secretion and/or activity of the postulated circulating permeability factor(s) may be B-cell related. This review summarizes the current knowledge on permeability factor(s) possibly related to the disease and discusses strategies for the management of recurrent FSGS. These include profound B-cell depletion prior to transplantation, as well as the salvage of an allograft affected by recurrent FSGS by transfer into a second recipient.
Highlights
Focal segmental glomerulosclerosis (FSGS) is an important cause of end-stage renal disease worldwide
Genetic FSGS is linked to specific mutations in key podocyte molecules, whereas secondary FSGS is caused by a variety of injuries such as drugs, infections (HIV, parvovirus B19, CMV, Epstein Barr Virus (EBV), Simian Virus 40 (SV40)), or the mal-adaptive alterations that occur after any loss of kidney parenchyma (Figure 1) [1,2,3,4,5]
In contrast to familial and secondary FSGS, primary FSGS is presumably caused by a circulating factor, possibly a cytokine elaborated from extrarenal sources, which causes generalized injury to podocytes
Summary
1. Correct assigning of FSGS to its subclasses primary, genetic, and secondary is pivotal for therapeutic decisions and assessment of recurrence risk after renal transplantation. 2. It is obvious that one or possibly more circulating permeability factors are causative in the pathogenesis of primary FSGS and its recurrence. 4. B cells may play a central role in the pathogenesis of FSGS and its recurrence. B cells may play a central role in the pathogenesis of FSGS and its recurrence This hypothesis is supported by the success of plasma exchange and B-cell depleting antibodies (rituximab, ofatumumab) in the treatment and pretreatment of FSGS recurrence. 5. Allograft transfer of a kidney transplant that failed in the first recipient due to fulminant FSGS recurrence into a second recipient is an option to rescue the allograft and to avoid futility of organs
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