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We appreciate the letter from Silver, ‘Role of Mast Cells in Renal Fibrosis,’1.Silver R. Role of mast cells in renal fibrosis.Kidney Int. 2013; 84: 214Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar in response to our recently published article.2.Summers S.A. Gan P.Y. Dewage L. et al.Mast cell activation and degranulation promotes renal fibrosis in experimental unilateral ureteric obstruction.Kidney Int. 2012; 82: 676-685Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar These reports show causality for mast cells in experimental renal fibrosis and support the previous observations from clinical studies where mast cell numbers correlate with renal injury and fibrosis in several forms of renal injury reviewed.3.Holdsworth S.R. Summers S.A. Role of mast cells in progressive renal diseases.J Am Soc Nephrol. 2008; 19: 2254-2261Crossref PubMed Scopus (101) Google Scholar The mechanism proposed by Silver that mast cell degranulation results in the release of pro-fibrotic mediators, including rennin and histamine, is interesting and worth further investigation.1.Silver R. Role of mast cells in renal fibrosis.Kidney Int. 2013; 84: 214Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Mast cells contain a diverse array of vasoactive mediators and degranulation results in the release of these mediators, which can direct a spectrum of physiological responses.3.Holdsworth S.R. Summers S.A. Role of mast cells in progressive renal diseases.J Am Soc Nephrol. 2008; 19: 2254-2261Crossref PubMed Scopus (101) Google Scholar To best define the role of individual mast cell molecules in disease pathogenesis, we would advocate the use of mast cell reconstitutions in mast cell–deficient mice. Using this technique, injury can be compared in mast cell–deficient mice, reconstituted with mast cells from wild-type mice, or after reconstitution with mast cells with a specific deletion. Differences in the pattern or intensity of injury are a direct consequence of the specified mast cell defect.4.Summers S.A. Chan J. Gan P.Y. et al.Mast cells mediate acute kidney injury through the production of TNF.J Am Soc Nephrol. 2011; 22: 2226-2236Crossref PubMed Scopus (46) Google Scholar We endorse the concept that mast cells are a potential target for the treatment of renal fibrosis, supported by our finding that sodium chromoglycate, a mast cell stabilizer, attenuated renal fibrosis.2.Summers S.A. Gan P.Y. Dewage L. et al.Mast cell activation and degranulation promotes renal fibrosis in experimental unilateral ureteric obstruction.Kidney Int. 2012; 82: 676-685Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar