The nervous system and the kidneys are linked under physiological states to maintain normal body homeostasis. In chronic kidney disease (CKD), damaged kidneys can impair the central nervous system, including cerebrovascular disease and cognitive impairment (CI). Recently, kidney disease has been proposed as a new modifiable risk factor for dementia. It is reported that uremic toxins may have direct neurotoxic (astrocyte activation and neuronal death) and/or indirect action through vascular effects (cerebral endothelial dysfunction, calcification, and inflammation). This review summarizes the evidence from research investigating the pathophysiological effects of phosphate toxicity in the nervous system, raising the question of whether the control of hyperphosphatemia in CKD would lower patients’ risk of developing cognitive impairment and dementia.

Atherosclerosis is a closely related complication of diabetes mellitus (DM), driven by endothelial dysfunction, inflammation, and oxidative stress. The progression of atherosclerosis is accelerated by hyperglycemia, insulin resistance, and hyperlipidemia. Novel antidiabetic agents, SGLT2 inhibitors, and GLP-1 agonists improve glycemic control and offer cardiovascular protection, reducing the risk of major adverse cardiovascular events (MACEs) and heart failure hospitalization. These agents, along with nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), promise to mitigate metabolic disorders and their impact on endothelial function, oxidative stress, and inflammation. This review explores the potential molecular mechanisms through which these drugs may prevent the development of atherosclerosis and cardiovascular disease (CVD), supported by a summary of preclinical and clinical evidence.

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone produced mainly in osteocytes. In chronic kidney disease (CKD) FGF23 levels increase due to higher production, but also as the result of impaired cleavage and reduced excretion from the body. FGF23 has a significant role in disturbed bone and mineral metabolism in CKD, which leads to a higher cardiovascular risk and mortality in these patients. Current research has emphasized the expression of FGF23 in cardiac myocytes, fibroblasts, and endothelial cells, and in addition to the effects on the kidney, its primary role is in cardiac remodeling in CKD patients. Recent discoveries found a significant link between increased FGF23 levels and anemia development in CKD. This review describes the FGF23 role in cardiac hypertrophy and anemia in the setting of CKD and discusses the best therapeutical approach for lowering FGF23 levels.

Cardiovascular (CV) disease is highly prevalent in the population with chronic kidney disease (CKD), where the risk of CV death in early stages far exceeds the risk of progression to dialysis. The presence of chronic kidney disease-mineral and bone disorder (CKD-MBD) has shown a strong correlation with CV events and mortality. As a non-atheromatous process, it could be partially explained why standard CV disease-modifying drugs do not provide such an impact on CV mortality in CKD as observed in the general population. We summarize the potential association of CV comorbidities with the older (parathyroid hormone, phosphate) and newer (FGF23, Klotho, sclerostin) CKD-MBD biomarkers.

Although rare, hereditary diseases, such as autosomal dominant polycystic kidney disease (ADPKD) and Fabry disease (FD) may significantly progress towards severe nephropathy. It is crucial to characterize it accurately, predict the course of the illness and estimate treatment effectiveness. A huge effort has been undertaken to find reliable biomarkers that might be useful for an early prevention of the disease progression and/or any invasive diagnostic procedures. The study of proteomics, or the small peptide composition of a sample, is a field of study under continuous development. Over the past years, several strategies have been created to study and define the proteome of samples from widely varying origins. However, urinary proteomics has become essential for discovering novel biomarkers in kidney disease. Here, the extracellular vesicles in human urine that contain cell-specific marker proteins from every segment of the nephron, offer a source of potentially valuable urinary biomarkers, and may play an essential role in kidney development and kidney disease. This review summarizes the relevant literature investigating the proteomic approaches and potential applications in the regular studies of ADPKD and FD.