Late diagnosis of CKD and associated survival after initiation of renal replacement therapy in Kazakhstan: analysis of nationwide electronic healthcare registry 2014-2019.

Chronic kidney disease (CKD) presents a significant global health challenge, often progressing to end-stage renal disease (ESRD) necessitating renal replacement therapy (RRT). Late referral (LR) to nephrologists before RRT initiation is linked with adverse outcomes. However, data on CKD diagnosis and survival post-RRT initiation in Kazakhstan remain limited. This study aims to investigate the impact of late CKD diagnosis on survival prognosis after RRT initiation. Data were acquired from the Unified National Electronic Health System (UNEHS) for CKD patients initiating RRT between 2014 and 2019. Survival post-RRT initiation was assessed using the Cox Proportional Hazards Model. Totally, 211,655 CKD patients were registered in the UNEHS databases and 9,097 (4.3%) needed RRT. The most prevalent age group among RRT patients is 45-64 years, with a higher proportion of males (56%) and Kazakh ethnicity (64%). Seventy-four percent of patients were diagnosed late. The median follow-up time was 537 (IQR: 166-1101) days. Late diagnosis correlated with worse survival (HR = 1.18, p < 0.001). Common comorbidities among RRT patients include hypertension (47%), diabetes (21%), and cardiovascular diseases (26%). The history of transplantation significantly influenced survival. Regional disparities in survival probabilities were observed, highlighting the need for collaborative efforts in healthcare delivery. This study underscores the substantial burden of CKD in Kazakhstan, with a majority of patients diagnosed late. Early detection strategies and timely kidney transplantation emerge as crucial interventions to enhance survival outcomes.

Re-Sensitizing Cancer Stem Cells to Conventional Chemotherapy Agents.

Cancer stem cells are found in many cancer types. They comprise a distinct subpopulation of cells within the tumor that exhibit properties of stem cells. They express a number of cell surface markers, such as CD133, CD44, ALDH, and EpCAM, as well as embryonic transcription factors Oct4, Nanog, and SOX2. CSCs are more resistant to conventional chemotherapy and can potentially drive tumor relapse. Therefore, it is essential to understand the molecular mechanisms that drive chemoresistance and to target them with specific therapy effectively. Highly conserved developmental signaling pathways such as Wnt, Hedgehog, and Notch are commonly reported to play a role in CSCs chemoresistance development. Studies show that particular pathway inhibitors combined with conventional therapy may re-establish sensitivity to the conventional therapy. Another significant contributor of chemoresistance is a specific tumor microenvironment. Surrounding stroma in the form of cancer-associated fibroblasts, macrophages, endothelial cells, and extracellular matrix components produce cytokines and other factors, thus creating a favorable environment and decreasing the cytotoxic effects of chemotherapy. Anti-stromal agents may potentially help to overcome these effects. Epigenetic changes and autophagy were also among the commonly reported mechanisms of chemoresistance. This review provides an overview of signaling pathway components involved in the development of chemoresistance of CSCs and gathers evidence from experimental studies in which CSCs can be re-sensitized to conventional chemotherapy agents across different cancer types.