Department of Anatomy, Charité-Universitätsmedizin Berlin, Berlin , Germany.
Department of Pathology, Charité-Universitätsmedizin Berlin, Berlin , Germany.
Am J Physiol Renal Physiol. 2019 Feb 1;316(2):F292-F300. doi: 10.1152/ajprenal.00464.2018. Epub 2018 Nov 28.
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.
低血钾症会导致慢性肾脏病的进展，尽管目前尚未建立明确的病理生理学理论来解释这一现象。钾缺乏会导致肾脏上皮细胞转运发生深刻变化。其中包括通过远端卷曲小管（DCT）中的 Na-Cl 共转运体（NCC）增加盐的重吸收，这最大限度地减少了下游肾单位段中电中性钾的丢失。在饮食钾缺乏的实验条件下，在鼠类 DCT 中发现了含有关键 NCC 调节激酶的 DCT 点状结构，被称为“WNK 体”，这是它们的组成部分，没有 K（赖氨酸）激酶（WNKs）。我们假设在人类中，WNK 体也会在低血钾症中出现。通过组织学染色和免疫荧光法检查慢性低血钾性肾病患者和适当对照的肾针活检。使用分段和细胞器特异性标记蛋白来描述已建立的 WNK 体成分，即 WNK 和 Ste20 相关脯氨酸-丙氨酸丰富激酶（SPAK）在肾内和亚细胞中的分布。在低血钾症患者中，WNK 和 SPAK 均集中在 DCT 中的非膜结合细胞质区域，与先前对 WNK 体的描述一致。假定的 WNK 体位于靠近核周区域，但不在内质网内。它们与微管紧密相邻，但不在聚集体中聚集。值得注意的是，我们首次在人类患者中报告了 WNK 体，这是与钾缺乏相关的具有挑战性的功能结构。
