2021年 · 第101卷第42期

Potassium plays a vital role in the normal cell membrane potential. Both hyperkalemia and hypokalemia will affect the electrophysiological conduction of the heart, causing abnormalities in the resting membrane potential of cardiomyocytes, cardiac depolarization and myocardial excitability, causing serious arrhythmia and threatening patients' lives. Potassium balance regulation is mainly dependent on the kidneys, and hyperkalemia and hypokalemia tend to occur when kidney disease is present. Although arrhythmias due to hyperkalemia and hypokalemia have been associated with higher short-term all-cause mortality in previous observational studies, few studies have reported the long-term effects of abnormal blood kalemia on cardiovascular disease-related mortality, and there is a lack of exploration of long-term outcomes of renal disease.

Acute kidney injury and chronic renal failure are very common in hospitalized patients. Therefore, in order to better judge the prognosis of disease, more accurate predictive indicators are needed to guide clinical practice. The study enrolled a total of 1,538 inpatients in a multicenter prospective cohort study. During the 3-month outpatient follow-up, patients' urine was collected for monocyte chemotactic protein (MCP-1/CCL2), uromodulin (UMOD) and human chitinase 3-like protein 1 (CHI3L1). The median follow-up time was 4.3 years to assess the relationship between biomarker levels and glomerular filtration rate and renal outcome combined events (incidence, progression, and end-stage renal disease of chronic renal failure). At the same time, the results of these clinical studies were validated in the mouse model of renal atrophy and renal repair to further clarify the role of these molecular markers in the progression of renal disease.

Several studies have confirmed the existence of autophagy dysregulation in diabetic nephropathy, but its underlying pathological mechanism is not clear. Through the analysis of kidney tissues of diabetic mice and diabetic patients, the study found that autophagy was significantly inhibited in the kidneys. Specific knockout of the autophagy-related gene Atg6 in the proximal tubules of mice kidney can inhibit autophagy, lead to kidney hypertrophy in diabetic mice, aggravate tubular damage, inflammatory reaction and fibrosis, and finally lead to increased proteinuria, indicating that autophagy plays a protective role in diabetic nephropathy. At the same time, it was found that small RNA214 (miR-214) expression was upregulated in diabetic tissues, thereby inhibiting the expression of downstream UNC-51-like autophagy-related activating enzyme (ULK1), ultimately leading to a decrease in autophagy expression. Specific silencing of the expression of miR-214 in the proximal tubules of the kidney reduced the inhibition of ULK1, prevented the increase of kidney size in diabetic nephropathy, and reduced the level of proteinuria. Furthermore, p53 and miR-214 were highly expressed in kidney tissues of diabetic patients compared to non-diabetic samples. Blocking the expression of p53 can increase ULK1 and autophagy levels, thereby favoring the improvement of diabetic nephropathy. The study also found that p53/miR-214 was positively associated with renal fibrosis, while ULK1/LC3 was inversely associated with renal fibrosis in diabetic patients. Therefore, the final results of this study confirmed the role of p53/miR-214/ULK1 axis-regulated autophagy in kidney tissue of diabetic patients, providing a new target for clinical treatment of diabetic nephropathy.