Modeling the Effects of Functional Adaptation to Reduction in Renal Mass

Abstract

When kidney tissue is removed or damaged, the remaining nephrons undergo compensatory growth and adaptive functional changes. The objective of this study is to assess the impact of such structural and functional adaptation. To do so, we developed computational models of solute transport along different nephron populations of a uninephrectomized and a 5/6‐nephrectomized rat kidney. The model represents detailed epithelial and paracellular transport processes along both the superficial and juxtamedullary nephrons. The loop of Henle of each model nephron extends to differing depths of the inner medulla. Each nephron segment is represented as a rigid tubule lined by a layer of epithelial cells, with apical and basolateral transporters that vary according to cell type. To simulate a uninephrectomized or 5/6‐nephrectomized kidney, we reduced the nephron population, increased single‐nephron glomerular filtration rate, and increased nephron size based on data in the literature. Model simulations were conducted to determine what tubular transport changes are necessary to preserve baseline salt excretion. Model results also revealed the differing degrees to which salt transport and oxygen consumption are changed along the different nephron segments.Support or Funding InformationThis research was supported in part by NIH grant DK‐106102.