Kazama Itsuro
School of Nursing, Miyagi University, Miyagi, Japan.
Kidney Res Clin Pract. 2024 Nov;43(6):703-708. doi: 10.23876/j.krcp.24.012. Epub 2024 Aug 7.
Elderly patients are prone to develop hyper- or hypokalemia, since they are susceptible to drugs or diets that affect the urinary or fecal potassium (K+) excretion. In aging mouse kidneys, in addition to glomerulosclerosis, proximal tubular atrophy, and atherosclerosis in renal arterioles, there was diffuse tubulointerstitial fibrosis with a number of inflammatory leukocytes infiltrating into the cortical interstitium. Since these pathological features greatly influence renal K+ handling, slowing the progression of kidney aging would fundamentally reduce the risk of developing hyper- or hypokalemia. Immunohistochemistry demonstrated the overexpression of K+ channels (Kv1.3) in leukocytes within the cortical interstitium, which was strongly associated with "chronic inflammation" in aging kidneys and the subsequent progression of renal fibrosis. In our basic studies, antihypertensive drugs (benidipine, nifedipine, verapamil, diltiazem) and anticholesterol drugs (lovastatin, simvastatin, pravastatin) strongly suppressed the leukocyte Kv1.3 channels and thus exerted anti-inflammatory effects. Given such pharmacological properties of these drugs, they may also be useful in slowing the progression of tubulointerstitial fibrosis in aging kidneys and reducing the risk of hyper- or hypokalemia in elderly patients.
老年患者容易发生高钾血症或低钾血症，因为他们易受影响尿钾或粪钾（K+）排泄的药物或饮食的影响。在衰老小鼠的肾脏中，除了肾小球硬化、近端肾小管萎缩和肾小动脉粥样硬化外，还存在弥漫性肾小管间质纤维化，有许多炎性白细胞浸润到皮质间质中。由于这些病理特征极大地影响肾脏对K+的处理，减缓肾脏衰老的进程将从根本上降低发生高钾血症或低钾血症的风险。免疫组织化学显示皮质间质内白细胞中K+通道（Kv1.3）过度表达，这与衰老肾脏中的“慢性炎症”及随后的肾纤维化进展密切相关。在我们的基础研究中，降压药（贝尼地平、硝苯地平、维拉帕米、地尔硫䓬）和抗胆固醇药物（洛伐他汀、辛伐他汀、普伐他汀）强烈抑制白细胞Kv1.3通道，从而发挥抗炎作用。鉴于这些药物的药理特性，它们可能也有助于减缓衰老肾脏中肾小管间质纤维化的进展，并降低老年患者发生高钾血症或低钾血症的风险。
