Renal potassium handling in rats with subtotal nephrectomy: modeling and analysis.

Published

Journal Article

We sought to decipher the mechanisms underlying the kidney's response to changes in K+ load and intake, under physiological and pathophysiological conditions. To accomplish that goal, we applied a published computational model of epithelial transport along rat nephrons in a sham rat, an uninephrectomized (UNX) rat, and a 5/6-nephrectomized (5/6-NX) rat that also considers adaptations in glomerular filtration rate and tubular growth. Model simulations of an acute K+ load indicate that elevated expression levels and activities of Na+/K+-ATPase, epithelial sodium channels, large-conductance Ca2+-activated K+ channels, and renal outer medullary K+ channels, together with downregulation of sodium-chloride cotransporters (NCC), increase K+ secretion along the connecting tubule, resulting in a >6-fold increase in urinary K+ excretion in sham rats, which substantially exceeds the filtered K+ load. In the UNX and 5/6-NX models, the acute K+ load is predicted to increase K+ excretion, but at significantly reduced levels compared with sham. Acute K+ load is accompanied by natriuresis in sham rats. Model simulations suggest that the lesser natriuretic effect observed in the nephrectomized groups may be explained by impaired NCC downregulation in these kidneys. At a single-nephron level, a high K+ intake raises K+ secretion along the connecting tubule and reabsorption along the collecting duct in sham, and even more in UNX and 5/6-NX. However, the increased K+ secretion per tubule fails to sufficiently compensate for the reduction in nephron number, such that nephrectomized rats have an impaired ability to excrete an acute or chronic K+ load.

Full Text

Duke Authors

Cited Authors

  • Layton, AT; Edwards, A; Vallon, V

Published Date

  • April 2018

Published In

Volume / Issue

  • 314 / 4

Start / End Page

  • F643 - F657

PubMed ID

  • 29357444

Pubmed Central ID

  • 29357444

Electronic International Standard Serial Number (EISSN)

  • 1522-1466

International Standard Serial Number (ISSN)

  • 1931-857X

Digital Object Identifier (DOI)

  • 10.1152/ajprenal.00460.2017

Language

  • eng