WNK Bodies Develop in the Distal Convoluted Tubule of the Human Kidney in Chronic Hypokalemia

Abstract

Hypokalemia contributes to the progression of chronic kidney disease and is associated with the distinct histopathological entity of chronic hypokalemic nephropathy. 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 K+ wasting in downstream nephron segments. Within days to hours of dietary K+ depletion, punctate structures in the DCT containing crucial NCC-regulating kinases arise in the murine DCT. In the recent literature, these structures have been termed “WNK bodies”, referring to their essential components, with no lysine (WNK) kinases. We hypothesized that hypokalemia may stimulate WNK body formation in humans. Renal needle biopsies of patients with chronic hypokalemic nephropathy (n=2) and appropriate controls were examined by electron microscopy, histological stains and immunofluorescence. Staining of 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 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 and 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. Support or Funding Information Deutsche Forschungsgemeinschaft (MU 2924/2-1,2 und BA 700/22-1,2; INST 335/596-1 FUGG) Immunofluorescent staining of SPAK and pS-WNK SPAK and catalytically active WNK isoforms are colocalized in punctate accumulations in the DCT of hypokalemic patients (top); these are absent in controls (bottom). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.