Dendrin Ablation Prolongs Life Span by Delaying Kidney Failure

Astrid Weins, Jenny S. Wong, John M. Basgen, Ritu Gupta, Ilse Daehn, Lisette Casagrande, David Lessman, Monica Schwartzman, Kristin Meliambro, Jaakko Patrakka, Andrey Shaw, Karl Tryggvason, John Cijiang He, Susanne B. Nicholas, Peter Mundel, Kirk N. Campbell

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Podocyte loss is central to the progression of proteinuric kidney diseases leading to end-stage kidney disease (ESKD), requiring renal replacement therapy, such as dialysis. Despite modern tools and techniques, the 5-year mortality of some patients requiring dialysis remains at about 70% to 80%. Thus, there is a great unmet need for podocyte-specific treatments aimed at preventing podocyte loss and the ensuing development of ESKD. Here, we show that ablation of the podocyte death-promoting protein dendrin delays the onset of ESKD, thereby expanding the life span of mice lacking the adapter protein CD2AP. Ablation of dendrin delays onset and severity of proteinuria and podocyte loss. In addition, dendrin ablation ameliorates mesangial volume expansion and up-regulation of mesangial fibronectin expression, which is mediated by a podocyte-secreted factor. In conclusion, onset of ESKD and death can be markedly delayed by blocking the function of dendrin.

Original languageEnglish
Pages (from-to)2143-2157
Number of pages15
JournalAmerican Journal of Pathology
Issue number8
StatePublished - 1 Aug 2015


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