2021年 · 第101卷第38期

Primary hyperaldosteronism (PA) is considered a rare condition and is almost always associated with hypokalemia. Extensive screening of hypertensive patients has shown an increased prevalence of normokalemic hypertension. Many studies have reported the prevalence of hypokalemia in patients with PA; In contrast, the prevalence of PA in patients with hypokalemia remains unknown. The aim of this study was to investigate the prevalence of hypokalemia in patients in a tertiary hypertension medical center and to determine the prevalence of PA in patients with hypokalemia. At the same time, independently of the diagnosis of PA, the authors also considered the correlation between blood potassium imbalance and cardiovascular disease, and also evaluated the cardiovascular risk of patients with normopotassium and patients with hypokalemia. In this retrospective observational study, the authors defined the prevalence of hypokalemia in patients referred to a tertiary hypertension medical center and the prevalence of PA in patients with hypokalemia and hypertension in 5 100 hypertensive patients included in the study. The results showed that 15.8% of the 5 100 cases of hypertension were hypokalemia, 76.9% were normopotassium and 7.3% were hyperkalemia. The prevalence of PA was 28.1% in patients with hypokalemia, which increased with decreasing blood potassium concentrations, up to 88.5% in patients with spontaneous hypokalemia, with potassium concentrations of<2.5 mmol/L. Multivariate regression analysis showed that hypokalemia was associated with the occurrence of cardiovascular events and not with PA diagnosis. PA was associated with the occurrence of cardiovascular events and target organ damage, not with hypokalemia. The results of this study confirm that PA is a common cause of secondary hypertension in patients with hypokalemia, and the presence of hypertension and spontaneous hypokalemia is a strong indication for the diagnosis of PA. Clinicians and general practitioners should focus on the risk of hypokalemia in patients diagnosed with essential hypertension and PA. The reported prevalence of PA in patients with hypokalemia should also be confirmed in large prospective multicenter cohort studies. Future research by the team may further clarify the relationship between hypokalemia and PA and increased cardiovascular risk and target organ damage.

Advances in computer software and three-dimensional (3D) printing have reduced the complexity and cost of model manufacturing, and increased the accessibility of its application in the medical field. In the field of urology, 3D printing and modeling technology has now been commonly used in the improvement of surgical protocols, surgical operation training and the development of patient-specific rehearsal (PSR) for complex urological procedures. In order to evaluate the anatomical accuracy of 3D printing and modeling techniques, 10 cases of PSR hydrogel 3D printing models of robot-assisted partial nephrectomy (RAPN) and percutaneous nephrolithotomy (PCNL) were selected in this study. First, 20 cases of 3D printing models were reconstructed by computer-aided design (CAD), and then the above 20 newly acquired CAD models were compared with their corresponding original CAD models in geometric similarity, volumetric overlap and spatial alignment, and finally compared by means of mean. In the comparison of geometric similarity, all structures of the RAPN 3D printed model (including renal parenchyma, tumor, renal arteriovenous, and collective system) had more than 80% point deviation<3 mm, while the PCNL 3D-printed model of calculus and ensemble system bias<94% and 59% for 3 mm points, respectively; In the comparison of volume overlap degree, except for the poor anastomosis degree of arterial structure in RAPN 3D printed model, the rest of the structures are ideal, while the anastomosis degree of stone in PCNL 3D printed model is ideal; In the comparison of the degree of spatial alignment, the tumor structure of the RAPN 3D printed model was most ideal aligned with the renal parenchyma, with 75% point deviation<3 mm, while the most ideal alignment reference for the PCNL 3D printed model is the rib tip with a deviation of 0.1%.

The incidence of kidney stones is high, which is closely related to lifestyle. However, in addition to surgical intervention, the development of pharmacological treatment of kidney stones is slow. Studies have confirmed that inflammation and oxidative stress can increase the adhesion of calcium oxalate (CaOx) crystals to renal tubular cells (RTCs) and promote the formation of kidney stones. Therefore, alleviation of cellular damage and inflammatory response can be used as a strategy to inhibit kidney stone formation. Among the protective mechanisms against cell injury, autophagy and ubiquitin proteasome system are the main pathways of cell degradation. Autophagy is upregulated when cells are ready for structural remodeling. It can be seen that autophagy not only plays a major role in the supply of nutrients for cell survival, but also plays an important role in cellular homeostasis. First, this study detected significant downregulation of autophagy activity in RTCs exposed to calcium oxalate crystals monohydrate (COM), GFP-MAP1LC3B (microtubule-associated protein 1 light chain 3 β) transgenic mouse models of glyoxylic acid (GOX) -induced CaOx nephrocalcification, and in the mucosa to which crystal plaques attached in patients with CaOx kidney stones. Due to decreased autophagy, the damaged organelles were not completely removed, exacerbating the inflammatory response and oxidative stress. Moreover, damaged organelles that have not been cleared can form cellular vacuoles, which accumulate in the lumen and may become nuclei for crystal formation. This study further explored the relevant mechanism and found that the reduction of autophagy was mainly caused by the upregulation of the rapamycinase mechanism target (mTOR) signal and the inhibition of the upstream autophagy regulator TFEB (transcription factor EB). Based on the above results, in vitro and in vivo experiments of mTOR signaling inhibition were conducted in this study. In vitro experiments, treating cells with the mTOR inhibitor Torin1 could reverse the decrease in autophagy activity caused by COM exposure, alleviate mitochondrial damage, impaired lysosomal pH homeostasis, and accumulation of LGALS3, while alleviating the inflammatory response and crystal adhesion caused by COM exposure. In vivo experiments, the number of autophagy lysosomes in GOX mice injected with rapamycin (inhibiting mTOR) daily was stable after 1~2 d, which inhibited the rise of GOX-induced SQSTM1. However, the number of autophagic lysosomes decreased after 1~2 d in mice without rapamycin injection. These results suggest that rapamycin can antagonize the decrease of autophagic activity. In summary, the upregulation of mTOR signal caused by calcium oxalate stone stimulation will lead to the reduction of autophagy function, which in turn promotes stone formation. mTOR inhibitors may be a promising treatment for kidney stones.

Patients with primary aldosteronism (PA) account for 3% to 10% of all hypertensive patients, which exceeds previous general perception. Adrenal vein sampling (AVS) is the standard procedure for determining excessive lateralization of aldosterone. Based on studies showing that adrenalectomy (AdX) has potential advantages over mineralocorticoid receptor antagonist (MRAs) drug therapy, the current clinical treatment guidelines recommend adrenalectomy as a treatment for unilateral PA. However, the majority of PA cases are composed of PA with bilateral adrenal hyperplasia as the etiology, so the efficacy of AdX will vary with different subtypes of PA. The aim of the study was to compare the clinical (improved blood pressure) and biochemical outcomes (improved hypokalemia) of AdX and MRAs in patients with unilateral PA with confirmed AVS subtype. The study included 339 patients with unilateral PA in the Japanese PA study database, of which 276 patients (AdX group) and 63 patients (MRAs group) received unilateral AdX and MRAs treatment, respectively. Baseline clinical features before treatment suggest that potassium replacement, plasma aldosterone concentration, aldosterone-to-renin ratio, glomerular filtration rate, and imaging prevalence of adrenal masses were significantly higher in the AdX group than in the MRAs group. After 6 months of PA-specific therapy, patients with unilateral PA who underwent adrenalectomy and medical therapy showed improvement in blood pressure. The increase of serum potassium in AdX group was greater than that in MRAs group, and the difference of serum potassium normalization rate between the two groups was statistically significant. The clinical and biochemical outcomes in the AdX group were better than those in the MRAs group.