Nanocarrier-Based Drug Delivery Systems Targeting Kidney Diseases.

BACKGROUND: The potential applications of nanotechnology in the medical field have become increasingly recognized in recent years. Nanocarriers have emerged as a versatile tool, offering a wide range of applications due to their unique properties. In addition to the targeted drugs delivery, nanocarriers have also proven to be extremely effective in imaging and diagnostics. Continuous advances in nanotechnology have paved the way for innovative solutions to complex challenges in human health, shaping the future of nanotechnology and its applications. SUMMARY: By exploring different types of nanoparticles, this review delves into the different characteristics that can be tailored to enhance their kidney access. Although the structural complexity of the kidney may prevent nanocarriers passage, optimization of nanocarrier characteristics such as shape, size, charge, and surface modifications may overcome these barriers, allowing for targeted delivery. By harnessing the potential of nanoparticles, researchers aim to develop targeted and efficient therapies that can address various kidney-related disorders. KEY MESSAGES: This review highlights the promising advancements in nanotechnology and their potential impact on improving the therapeutic outcomes for several kidney diseases.

Impact of Kono-S anastomosis on quality of life after ileocolic resection in Crohn's disease: an analysis from the SuPREMe-CD trial.

AIM: Crohn's disease has debilitating effects on patients' quality of life. Currently, there are limited data on the effect of anastomotic configuration on health-related quality of life after ileocaecal resection for Crohn's disease. This study aimed to assess the impact of Kono-S anastomosis on quality of life after ileocolic resection, compared to the conventional side-to-side anastomosis. METHOD: Patients with primary or recurrent Crohn's disease participating in the ongoing SuPREMe-CD trial were interviewed about quality of life using the Inflammatory Bowel Disease Questionnaire (IBDQ). The primary endpoint was disease-specific quality of life, assessed with IBDQ. Secondary outcomes were quality of life related to bowel symptoms, systemic symptoms, social function and emotional function. RESULTS: Of the 94 patients included, 51 (54%) received the conventional side-to-side anastomosis and 43 (46%) the Kono-S anastomosis. Demographics were comparable between the two groups. The IBDQ was assessed at a mean follow-up of 54.0 ± 18.7 months from surgical intervention. The mean total IBDQ score was 155.1 ± 28.07 in the conventional group and 163.8 ± 25.23 in the Kono-S group (P = 0.11). When considering bowel symptoms and social function, mean scores were 50.7 and 23.5 in the conventional group, and 56.3 and 26.5 in the Kono-S group (P = 0.002 and P = 0.02, respectively). Kono-S anastomosis was independently associated with improved quality of life regarding bowel symptoms (P = 0.006) and social function (P = 0.03) after correcting for other confounding factors on linear regression analysis. CONCLUSION: Compared to conventional side-to-side anastomosis, patients with Kono-S anastomosis presented significantly better bowel symptoms and social function scores at 54 months after surgery.

The SGLT2 inhibitor dapagliflozin improves kidney function in glycogen storage disease XI.

Glycogen storage disease XI, also known as Fanconi-Bickel syndrome (FBS), is a rare autosomal recessive disorder caused by mutations in the SLC2A2 gene that encodes the glucose-facilitated transporter type 2 (GLUT2). Patients develop a life-threatening renal proximal tubule dysfunction for which no treatment is available apart from electrolyte replacement. To investigate the renal pathogenesis of FBS, SLC2A2 expression was ablated in mouse kidney and HK-2 proximal tubule cells. GLUT2Pax8Cre+ mice developed time-dependent glycogen accumulation in proximal tubule cells and recapitulated the renal Fanconi phenotype seen in patients. In vitro suppression of GLUT2 impaired lysosomal autophagy as shown by transcriptomic and biochemical analysis. However, this effect was reversed by exposure to a low glucose concentration, suggesting that GLUT2 facilitates the homeostasis of key cellular pathways in proximal tubule cells by preventing glucose toxicity. To investigate whether targeting proximal tubule glucose influx can limit glycogen accumulation and correct symptoms in vivo, we treated mice with the selective SGLT2 inhibitor dapagliflozin. Dapagliflozin reduced glycogen accumulation and improved metabolic acidosis and phosphaturia in the animals by normalizing the expression of Napi2a and NHE3 transporters. In addition, in a patient with FBS, dapagliflozin was safe, improved serum potassium and phosphate concentrations, and reduced glycogen content in urinary shed cells. Overall, this study provides proof of concept for dapagliflozin as a potentially suitable therapy for FBS.