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

Item Type:Article
Title:Patients with hypokalemia develop WNK bodies in the distal convoluted tubule of the kidney
Creators Name:Thomson, M.N., Schneider, W., Mutig, K., Ellison, D.H., Kettritz, R. and Bachmann, S.
Abstract:Hypokalemia contributes to the progression of chronic kidney disease, while a definitive pathophysiogical theory to explain this remains to be established. K(+) deficiency results in profound alterations of renal epithelial transport. These include an increase of 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 lysine (WNK) kinases. We hypothesized that in humans, WNK bodies occur as well in hypokalemia. 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 WNK and Ste20-related proline-alanine-rich (SPAK) kinases. In both hypokalemic patients, 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.
Keywords:Hypokalemic Nephropathy, Microtubules, NCC, SPAK, Trafficking
Source:American Journal of Physiology Renal Physiology
Publisher:American Physiological Society
Page Range:F292-F300
Date:February 2019
Official Publication:https://doi.org/10.1152/ajprenal.00464.2018
External Fulltext:View full text on PubMed Central
PubMed:View item in PubMed

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