Diabetic kidney disease (DKD) is a devastating microvascular complication associated with diabetes mellitus. Recently, the major focus of glomerular lesions of DKD has partly shifted to diabetic tubulopathy because of renal insufficiency and prognosis of patients is closely related to tubular atrophy and interstitial fibrosis. Indeed, the proximal tubule enriching in mitochondria for its high energy demand and dependence on aerobic metabolism has given us pause to focus primarily on the mitochondria-centric view of early diabetic tubulopathy. Multiple studies suggest that diabetes condition directly damages renal tubules, resulting in mitochondria dysfunction, including decreased bioenergetics, overproduction of mitochondrial reactive oxygen species (mtROSs), defective mitophagy and dynamics disturbances, which in turn trigger a series of metabolic abnormalities. However, the precise mechanism underlying mitochondrial dysfunction of renal tubules is still in its infancy. Understanding tubulointerstitial's pathobiology would facilitate the search for new biomarkers of DKD. In this Review, we summarize the current literature and postulate that the potential effects of mitochondrial dysfunction may accelerate initiation of early-stage diabetic tubulopathy, as well as their potential therapeutic strategies.

Diabetic tubulopathy (DT) is a recently recognized key pathology of diabetic kidney disease (DKD). The mitochondria-centric view of DT is emerging as a vital pathological factor in different types of metabolic diseases, such as DKD. Finerenone (FIN), a novel non-steroidal mineralocorticoid receptor antagonist, attenuates kidney inflammation and fibrosis in DKD, but the precise pathomechanisms remain unclear. The role of mineralocorticoid receptor (MR) in perturbing mitochondrial function via the PI3K/Akt/eNOS signaling pathway, including mitochondrial dynamics and mitophagy, was investigated under a diabetic state and high glucose (HG) ambiance. To elucidate how the activation of MR provokes mitochondrial dysfunction in DT, human kidney proximal tubular epithelial (HK-2) cells were exposed to HG, and then mitochondrial dynamics, mitophagy, mitochondrial ROS (mitoROS), signaling molecules PI3K, Akt, Akt phosphorylation and eNOS were probed. The above molecules or proteins were also explored in the kidneys of diabetic and FIN-treated mice. FIN treatment reduced oxidative stress, mitochondrial fragmentation, and apoptosis while restoring the mitophagy via PI3K/Akt/eNOS signaling pathway in HK-2 cells exposed to HG ambiance and tubular cells of DM mice. These findings linked MR activation to mitochondrial dysfunction via PI3K/Akt/eNOS signaling pathway in DT and highlight a pivotal but previously undiscovered role of FIN in alleviating renal tubule injury for the treatment of DKD.

Introduction: Chronic kidney disease (CKD), which affects about 10% of global population, has become a global public health crisis in recent decades. It is well recognized that health information dissemination could change health behaviors, thereby greatly improving the early diagnosis and prevention of diseases. Due to fast dissemination, wide audience, intuitive and vivid, popularization through short videos has rapidly developed into the new main battlefield of health information. The objective of this study was to describe the properties of the CKD-related health information on short video apps. Methods: Searching on short video apps with high-frequency words in kidney disease as keywords, the basic information of the uploaders was retrieved and extracted short video. Five quality dimensions, awareness, popularity, utility, validity and quality, of each video were assessed with numeric rating scale (NRS) by five volunteers with CKD and three nephrologists. Results: From the platform of douyin, 65 uploaders and their 3973 short videos of CKD-related health information were investigated in this study. Most information of short videos had relatively high level in awareness, popularity and utility assessment, but some information had relatively low level in validity and quality assessment; 24 (36.9%) uploaders were from governmental hospital (tertiary hospital); 19 uploaders (29.2%) uploaded more than 100 short videos and 49 uploaders (75.4%) updated their videos weekly, and 16 uploaders (24.6%) didn’t update short videos more than one month. There were 4 uploaders (6.2%) have more than 1 million follows, and 39 uploaders (60%) had follows less than 10,000. “Lifestyles”, “Common symptoms of kidney disease” and “Nephritis or kidney disease” were the three main contents of these short videos. The comprehensive data of uploaders with millions of follows in nephrology specialty were much lower than that of orthopedics and other specialty. Conclusion: The validity and quality of short video is still unsatisfactory, and CKD-related health information also need to be led and improved, although the awareness, popularity, and utility of health information about CKD is acceptable. The public should be selective and cautious in seeking CKD information on social media.

Renal interstitial fibrosis (RIF) is the main pathological feature of end-stage renal disease (ESRD) caused by various chronic kidney diseases (CKD), and is closely related to renal dysfunction and patient prognosis. Salvianolic acid A (Sal A) and salvianolic acid B (Sal B), isolated from traditional Chinese medicine Salviae miltiorrhizae, have been confirmed to have anti-fibrotic effects on liver, cardiac and kidney. However, the precise molecular mechanism underlying the nephroprotective effects of Sal A and Sal B, and whether there is a difference between the two in RIF are still unclear. This study investigated the pharmacological effects of Sal A and Sal B in RIF and explore the underlying mechanisms by in vivo and in vitro experiments. The nephroprotective effects of Sal A, Sal B and Sal A+B were evaluated by assessing the parameters related to kidney function such as renal histology, renal function, urinary protein NAG, urinary β2 microglobulin. In addition, RIF-related markers such as CTCF and Par3 were also detected. Thereafter, the related protein or gene levels of PDGF-C/PDGFR-α signaling pathways, apoptosis and endoplasmic reticulum stress (ERS) were determined by western blot, real-time PCR, flow cytometry or immunofluorescence staining. In vivo, the results showed that Sal A, Sal B and Sal A+B partially improved kidney dysfunction, increased the expression of Par-3 and reduced the expression of CTGF, PDGF-C and PDGFR-α. In vitro, the results also showed that Sal A, Sal B and Sal A+B reversed apoptosis and ERS in HSA-induced HK-2 cells via regulating PDGF-C/PDGFR-α signaling pathway. This article revealed a novel mechanism linking PDGF-C/PDGFR-α signaling pathway to RIF and suggested that Sal A, Sal B and Sal A+B were considered as potential therapeutic agents for the amelioration of RIF.

Background: The aim of this study was to evaluate the efficacy and safety of paclitaxel-coated balloons (AcoArt Orchid) in treating dysfunctional arteriovenous fistulae. Methods: The drug-eluting balloon for arteriovenous (AV) fistula in China trial was a prospective, multicenter, randomized controlled study. Patients who had ≥50% venous stenosis of the AV fistula and symptoms indicating significant hemodynamic changes were included. After successful predilation with a high-pressure balloon (residual stenosis ≤30%), patients were randomized 1:1 to either a paclitaxel-coated balloon or an uncoated control balloon. The primary efficacy outcome was assessed at 6 months, and safety assessment was conducted within 30 days of the procedure. The 12-month results were also analyzed. Results: The study included 244 patients, equally distributed between the two groups. The primary target lesion patency was 91% (106/116) for the drug-coated balloon (DCB) group and 67% (79/118) for the plain balloon catheter group, representing a difference of 24.63% (95% confidence interval, 14.68 to 34.58; P < 0.001). The secondary efficacy end point was primary target lesion patency at 12 months, which was 66% (74/112) for the DCB group and 46% (52/112) for the plain balloon catheter group (95% confidence interval, 6.57 to 32.08; P = 0.004). The mean number of reinterventions per patient to maintain target lesion patency during the 12 months after the index procedure was 0.39 (48/122) in the DCB group and 0.77 (94/122) in the plain balloon catheter group (P = 0.001). The primary safety end point did not differ between groups (P = 0.25). Conclusions: AcoArt Orchid DCB showed better primary patency rates compared with plain balloon angioplasty for treating stenotic lesions in dysfunctional hemodialysis AV fistulae at 6 and 12 months. It required fewer repeated interventions and had comparable safety in 1 year. Clinical Trial registry name and registration number: AcoArt III/Arterio-venous Fistula in China, NCT03366727.

Right internal jugular vein (IJV) is a preferred access route for tunneled (cuffed) dialysis catheters (TDCs), and both right external jugular vein (EJV) and left IJV are alternative routes for patients in case the right IJV isn’t available for TDC placement. This retrospective study aimed to determine if a disparity exists between the two alternative routes in hemodialysis patients in terms of outcomes of TDCs. 49 hemodialysis patients who required TDCs through right EJV (n = 21) or left IJV (n = 28) as long-term vascular access were included in this study. The primary end point was cumulative catheter patency. Secondary end points include primary catheter patency, proportion of patients that never required urokinase and incidence of catheter-related bloodstream infections (CRBSI). A total of 20,870 catheter-days were evaluated and the median was 384 (interquartile range, 262–605) catheter-days. Fewer catheters were removed in the right EJV group than in the left IJV group (P = 0.007). Mean cumulative catheter patency was higher in the right EJV group compared with the left IJV group (P = 0.031). There was no significant difference between the two groups in the incidence of CRBSI, primary catheter patency or proportion of patients that never required urokinase use. Total indwell time of antecedent catheters was identified as an independent risk factor for cumulative catheter patency by Cox regression hazards test with an HR of 2.212 (95% CI, 1.363–3.588; p = 0.001). Right EJV might be superior to left IJV as an alternative insertion route for TDC placement in hemodialysis patients whose right IJVs are unavailable.