Patients with hypokalemia develop WNK bodies in the distal convoluted tubule of the kidney

Martin N. Thomson, Wolfgang Schneider, Kerim Mutig, David Ellison, Ralph Kettritz, Sebastian Bachmann

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Hypokalemia contributes to the progression of chronic kidney disease, although a definitive pathophysiological theory to explain this remains to be established. K+ deficiency results in profound alterations in renal epithelial transport. These include an increase in salt reabsorption via the Na+-Cl- cotransporter (NCC) of the distal convoluted tubule (DCT), which minimizes electroneutral K+ loss in downstream nephron segments. In experimental conditions of dietary K+ depletion, punctate structures in the DCT containing crucial NCC-regulating kinases have been discovered in the murine DCT and termed "WNK bodies," referring to their component, with no K (lysine) kinases (WNKs). We hypothesized that in humans, WNK bodies occur in hypokalemia as well. Renal needle biopsies of patients with chronic hypokalemic nephropathy and appropriate controls were examined by histological stains and immunofluorescence. Segment- and organelle-specific marker proteins were used to characterize the intrarenal and subcellular distribution of established WNK body constituents, namely, WNKs and Ste20-related proline-alanine-rich kinase (SPAK). In both patients with hypokalemia, WNKs and SPAK concentrated in non-membrane-bound cytoplasmic regions in the DCT, consistent with prior descriptions of WNK bodies. The putative WNK bodies were located in the perinuclear region close to, but not within, the endoplasmic reticulum. They were closely adjacent to microtubules but not clustered in aggresomes. Notably, we provide the first report of WNK bodies, which are functionally challenging structures associated with K+ deficiency, in human patients.

Original languageEnglish (US)
Pages (from-to)F292-F300
JournalAmerican journal of physiology. Renal physiology
Volume316
Issue number2
DOIs
StatePublished - Feb 1 2019

Keywords

  • hypokalemic nephropathy
  • microtubules
  • NCC
  • SPAK
  • trafficking

ASJC Scopus subject areas

  • Physiology
  • Urology

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