The Authors Reply

Abstract

Our study1Kuppe C. Gröne H.-J. Ostendorf T. et al.Common histological patterns in glomerular epithelial cells in secondary focal segmental glomerulosclerosis.Kidney Int. 2015; 88: 990-998Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar describes common histological patterns in secondary focal and segmental glomerulosclerosis lesions. The major finding was that parietal epithelial cells can be detected in virtually all sclerotic lesions (91%) independent of the primary glomerular disease that triggered secondary focal and segmental glomerulosclerosis (Figure 1). Thus, we proposed that activation of parietal epithelial cells is a common pathomechanism in focal and segmental glomerulosclerosis and a potential pharmacologic target. In his letter, Dr. Alexander J. Howie points out correctly that our analysis did not include the Columbia classification.2Howie A.J. Glomerular epithelial cells in secondary focal segmental glomerulosclerosis.Kidney Int. 2016; 89: 1403-1404Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar The Columbia classification has drawn considerable interest to specific histological patterns (e.g., the perihilar variant) that show associations with certain pathophysiological findings (e.g., hyperfiltration) and outcomes.3D'Agati V.D. Alster J.M. Jennette J.C. et al.Association of histologic variants in FSGS clinical trial with presenting features and outcomes.Clin J Am Soc Nephrol. 2013; 8: 399-406Crossref PubMed Scopus (93) Google Scholar However, such lesions are not entirely specific to any glomerular disorder. Often, a mixture of lesions can be observed and lesions may evolve into other lesions over time.4Zhong Y. Xu F. Li X. et al.The evolution of morphological variants of focal segmental glomerulosclerosis: a repeat biopsy-based observation.Nephrol Dial Transplant. 2016; 31: 87-95Crossref PubMed Scopus (9) Google Scholar Nevertheless, the histological patterns of the Columbia classification strongly suggest specific underlying pathomechanisms. So far, these are still incompletely understood. We agree that activated parietal epithelial cells may be a key to resolve how the histological patterns described in the Columbia classification evolve. In our study,1Kuppe C. Gröne H.-J. Ostendorf T. et al.Common histological patterns in glomerular epithelial cells in secondary focal segmental glomerulosclerosis.Kidney Int. 2015; 88: 990-998Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar only a few slides per human patient were available so that it was impossible to address this question. However, mechanistic studies on this subject including cell fate tracing in experimental animals are under way. Glomerular epithelial cells in secondary focal segmental glomerulosclerosisKidney InternationalVol. 89Issue 6PreviewKuppe et al.1 showed that in a variety of glomerular disorders, cellular adhesions between the glomerular tuft and Bowman’s capsule contain podocyte markers or parietal epithelial cell markers or both, and that areas of segmental sclerosis in these conditions contain parietal epithelial cell markers. The site of the adhesions and sclerosed areas within the tuft is not reported. There is known to be a range of pathogenetic mechanisms of segmental sclerosing lesions, and these can largely be differentiated by the site and appearance of the lesions within the tuft. Full-Text PDF Open Archive