2. Universidad Cardenal Herrera-CEU

Chronic kidney disease (CKD) has been increasing over the last years, with a rate between 0.49% to 0.87% new cases per year. Currently, the number of affected people is around 850 million worldwide. CKD is a slowly progressive disease that leads to irreversible loss of kidney function, end-stage kidney disease, and premature death. Therefore, CKD is considered a global health problem, and this sets the alarm for necessary efficient prediction, management, and disease prevention. At present, modern computer analysis, such as in silico medicine (ISM), denotes an emergent data science that offers interesting promise in the nephrology field. ISM offers reliable computer predictions to suggest optimal treatments in a case-specific manner. In addition, ISM offers the potential to gain a better understanding of the kidney physiology and/or pathophysiology of many complex diseases, together with a multiscale disease modeling. Similarly, -omics platforms (including genomics, transcriptomics, metabolomics, and proteomics), can generate biological data to obtain information on gene expression and regulation, protein turnover, and biological pathway connections in renal diseases. In this sense, the novel patient-centered approach in CKD research is built upon the combination of ISM analysis of human data, the use of in vitro models, and in vivo validation. Thus, one of the main objectives of CKD research is to manage the disease by the identification of new disease drivers, which could be prevented and monitored. This review explores the wide-ranging application of computational medicine and the application of -omics strategies in evaluating and managing kidney diseases.

Diabetic kidney disease (DKD) is the leading cause of chronic and end-stage kidney disease worldwide. Its pathogenic mechanism is complex, and it can affect the entire structures of the kidneys such as the glomerulus, tubules and interstitium. Currently, the urinary albumin excretion rate and the estimated glomerular filtration rate are widely accepted as diagnostic criteria. However, some studies have reported a different or non-classical clinical course of DKD, with some patients showing declined kidney function with normal levels of albuminuria, known as the 'non-albuminuric DKD' phenotype. The pathogenesis of this phenotype remains unclear, but some clinical and pathological features have been postulated. This review explores the evidence regarding this topic.

Introduction: Secondary hyperparathyroidism (SHP) is frequent in patients with chronic kidney disease (CKD), particularly in those in dialysis. To treat this complication, the current options available include phosphorus restriction, phosphate binders, the inhibition of parathyroid hormone (PTH) synthesis and secretion by the supplementation of vitamin D or VDR activators, or the use of calcimimetics. Beyond the control of PTH, the effects of the treatment of SHP on other biomarkers of risk may represent an additional benefit for this population. In this study, we explore the benefits of current SHP treatment options, mainly paricalcitol and/or etelcalcetide in the inflammatory state of hemodialysis (HD) patients. Results: the study finally included 142 maintenance HD patients (5 patients were excluded) followed for 6 months (dialysis vintage 26 ± 30 months, mean age 70 years old, 73% women, 81% Spanish white, 47% diabetic). In this case, 52 patients were on regular treatment with paricalcitol for SHP and 25 patients were eligible to initiate etelcalcetide. The baseline serum levels of Ca, P, PTH, Ferritin, albumin, C-reactive protein (CRP), and other variables were measured. We found serum PTH levels showed an improvement after the treatment with etelcalcetide again paricalcitol and no treatment (p < 0.04). Of note, serum levels of CRP were significantly lower in a small group of patients (n = 11) receiving paricalcitol + etelcalcetide compared to paricalcitol or etelcalcetide alone. The proportion of patients with CRP within target ranges (≤1.0 mg/dL) increased significantly after combined treatment (p < 0.001). Conclusions: etelcalcetide proved to safely reduce the PTH levels without significant adverse events and the possibility of a synergic anti-inflammatory effect with the simultaneous use of Paricalcitol in HD patients.

Type 2 diabetes mellitus (T2DM) affects an estimated 463 million people worldwide, equivalent to 1 in 11 adults. Moreover, the rapid growth of this disease has resulted in a high incidence of diabetic kidney disease (DKD), which, together with hypertension, is the main cause of chronic kidney disease (CKD). Hyperglycaemia, low-grade inflammation, altered lipid metabolism and hyperactivation of the renin–angiotensin–aldosterone system (RAAS) seem to be interrelated mechanisms contributing to both T2DM and microvascular complications. The introduction of drugs such as sodium–glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists has improved the ability to slow the progression of DKD, and has also demonstrated benefits in cardiovascular disease. Beyond the effects of these novel antidiabetic drugs, a body of evidence suggests that the overactivation of the mineralocorticoid receptor also contributes to CKD progression. Moreover, new and ongoing trials have demonstrated that the selective nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone improves the risk of CKD progression and cardiovascular events in patients with CKD and T2DM and optimized RAAS blockade. We review the rationale for the development and use of MRA drugs to slow CKD progression in patients with DKD, as well as other pleiotropic effects, and highlight the warnings associated with these agents.

Background. Over the last few years, the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) has increased substantially in medical practice due to their documented benefits in cardiorenal and metabolic health. In this sense, and in addition to being used for glycemic control in diabetic patients, these drugs also have other favorable effects such as weight loss and lowering blood pressure, and more recently, they have been shown to have cardio and renoprotective effects with anti-inflammatory properties. Concerning the latter, the individual or associated use of these antihyperglycemic agents has been linked with a decrease in proinflammatory cytokines and with an improvement in the inflammatory profile in chronic endocrine-metabolic diseases. Hence, these drugs have been positioned as first-line therapy in the management of diabetes and its multiple comorbidities, such as obesity, which has been associated with persistent inflammatory states that induce dysfunction of the adipose tissue. Moreover, other frequent comorbidities in long-standing diabetic patients are chronic complications such as diabetic kidney disease, whose progression can be slowed by SGLT2i and/or GLP-1RA. The neuroendocrine and immunometabolism mechanisms underlying adipose tissue inflammation in individuals with diabetes and cardiometabolic and renal diseases are complex and not fully understood. Summary. This review intends to expose the probable molecular mechanisms and compile evidence of the synergistic or additive anti-inflammatory effects of SGLT2i and GLP-1RA and their potential impact on the management of patients with obesity and cardiorenal compromise.