The authors reply
Authors: Raina D. Ramnath, Matthew J. Butler, Rebecca R. Foster, Simon C. Satchell
Journal: Kidney International (2020)

We write in response to the letter entitled “There is Little Evidence That the Endothelial Glycocalyx Has a Specific Role in Glomerular Permeability of Albumin,”1Comper W.D. There is little evidence that the endothelial glycocalyx has a specific role in glomerular permeability of albumin.Kidney Int. 2020; 97: 1057Google Scholar in reference to our original publication.2Ramnath R.D. Butler M.J. Newman G. et al.Blocking matrix metalloproteinase-mediated syndecan-4 shedding restores the endothelial glycocalyx and glomerular filtration barrier function in early diabetic kidney disease.Kidney Int. 2020; 97: 951-965Google Scholar The title of the letter is very misleading. It represents only the opinion of this author and is diametrically opposed to the data presented in our paper and an accumulating body of evidence including in vivo multiphoton measurements.3Butler M.J. Ramnath R. Kadoya H. et al.Aldosterone induces albuminuria via matrix metalloproteinase-dependent damage of the endothelial glycocalyx.Kidney Int. 2019; 95: 94-107Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar This author’s claims are not supported by experimental observations, and we and others have addressed them extensively including in a response4Desideri S. Onions K.L. Butler M.J. et al.The authors reply.Kidney Int. 2018; 94: 220Abstract Full Text Full Text PDF Scopus (2) Google Scholar to a previous similar letter. It is curious that the major focus of the letter seems to be on charge selectivity when charge is not mentioned in our article. Aldosterone induces albuminuria via matrix metalloproteinase–dependent damage of the endothelial glycocalyxKidney InternationalVol. 95Issue 1PreviewAldosterone contributes to end-organ damage in heart failure and chronic kidney disease. Mineralocorticoid-receptor inhibitors limit activation of the receptor by aldosterone and slow disease progression, but side effects, including hyperkalemia, limit their clinical use. Damage to the endothelial glycocalyx (a luminal biopolymer layer) has been implicated in the pathogenesis of endothelial dysfunction and albuminuria, but to date no one has investigated whether the glomerular endothelial glycocalyx is affected by aldosterone. Full-Text PDF Blocking matrix metalloproteinase-mediated syndecan-4 shedding restores the endothelial glycocalyx and glomerular filtration barrier function in early diabetic kidney diseaseKidney InternationalVol. 97Issue 5PreviewThe endothelial glycocalyx is a key component of the glomerular filtration barrier. We have shown that matrix metalloproteinase (MMP)-mediated syndecan 4 shedding is a mechanism of glomerular endothelial glycocalyx damage in vitro, resulting in increased albumin permeability. Here we sought to determine whether this mechanism is important in early diabetic kidney disease, by studying streptozotocin-induced type 1 diabetes in DBA2/J mice. Diabetic mice were albuminuric, had increased glomerular albumin permeability and endothelial glycocalyx damage. Full-Text PDF Open AccessThere is little evidence that the endothelial glycocalyx has a specific role in glomerular permeability of albuminKidney InternationalVol. 97Issue 5PreviewIt is not commonly appreciated that the most accurate quantitative measure of the interaction of glycosaminoglycan chains (such as in syndecans) with each other or with albumin is through the analysis of their equilibrium thermodynamic interactions.1,2 There are many ways to do this, say through osmotic pressure analysis. These studies have, for over 70 years, shown that the interaction is not charged-based but one of steric exclusion under physiological conditions. This immediately tells you that charge selectivity, which has been proposed as a major force governing transglomerular transport of albumin, is a flawed concept. Full-Text PDF The Authors ReplyKidney InternationalVol. 94Issue 1PreviewWe write in response to the letter entitled “Glomerular Permeability Changes of Albumin in Isolated Glomeruli Do Not Mimic Changes in Albumin Excretion In Vivo in Diseased States,”1 in reference to our original publication.2 We described an isolated glomerular albumin permeability (Ps’alb) assay that robustly and sensitively measures changes in Ps’alb in various situations including diseases and disease-modifying interventions. We measured changes in Ps’alb up to 3.3-fold. However, Ps’alb in isolated glomeruli should not be expected to be linearly related to the total amount of albumin being filtered across all glomeruli in disease states. Full-Text PDF