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Renin–angiotensin–aldosterone system (RAAS) inhibitors are standard care in patients with hypertension, heart failure or chronic kidney disease (CKD). Although we have studied the RAAS for decades, there are still circumstances that remain unclear. In this review, we describe the evolution of the RAAS and pose the question of whether this survival trait is still necessary to humankind in the present age. We elucidate the benefits on cardiovascular health and kidney disease of RAAS inhibition and present promising novel medications. Furthermore, we address why more studies are needed to establish a new standard of care away from generally prescribing ACEi or ARB toward an improved approach to combine drugs tailored to the needs of individual patients.

Diabetic kidney disease (DKD) is a major cause of morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether albumin structural alterations correlate with DKD severity and evaluate whether native and reduced albumin concentrations could complement the diagnosis of DKD. To this end, one hundred and seventeen T2DM patients without (n = 42) and with (n = 75) DKD (DKD I-III upon KDIGO classification) were evaluated; the total albumin concentration (tHA) was quantified by a bromocresol green assay, while structural alterations were profiled via liquid chromatography–high-resolution mass spectrometry (LC-HRMS). The concentrations of native albumin (eHA, effective albumin) and reduced albumin (rHA) were subsequently assessed. The HRMS analyses revealed a reduced relative amount of native albumin in DKD patients along with an increased abundance of altered forms, especially those bearing oxidative modifications. Accordingly, both eHA and rHA values varied during the stages of progressive renal failure, and these alterations were dose-dependently correlated with renal dysfunction. A ROC curve analysis revealed a significantly greater sensitivity and specificity of eHA and rHA than of tHA for diagnosing DKD. Importantly, according to the multivariate logistic regression analysis, the eHA was identified as an independent predictor of DKD.

Chronic kidney disease (CKD) is a complex and multifactorial disease, and one of the most prevalent worldwide. Chronic kidney disease–mineral bone disorders (CKD–MBD) with biochemical and hormonal alterations are part of the complications associated with the progression of CKD. Pathophysiology of CKD–MBD focused on abnormalities in serum levels of several biomarkers (such as FGF-23, klotho, phosphate, calcium, vitamin D, and PTH) which are discussed in this review. We therefore examine the prognostic association between CKD–MBD and the increased risk for cardiovascular events, mortality, and CKD progression to end-stage kidney disease (ESKD). Lastly, we present specific treatments acting on CKD to prevent and treat the complications associated with secondary hyperparathyroidism (SHPT): control of hyperphosphatemia (with dietary restriction, intestinal phosphate binders, and adequate dialysis), the use of calcimimetic agents, vitamin D, and analogues, and the use of bisphosphonates or denosumab in patients with osteoporosis.

Vitamin D belongs to the group of liposoluble steroids mainly involved in bone metabolism by modulating calcium and phosphorus absorption or reabsorption at various levels, as well as parathyroid hormone production. Recent evidence has shown the extra-bone effects of vitamin D, including glucose homeostasis, cardiovascular protection, and anti-inflammatory and antiproliferative effects. This narrative review provides an overall view of vitamin D’s role in different settings, with a special focus on chronic kidney disease and kidney transplant.

Increasing potassium intake ameliorates blood pressure (BP) and cardiovascular (CV) prognoses in the general population; therefore the World Health Organization recommends a high-potassium diet (90–120 mEq/day). Hyperkalaemia is a rare condition in healthy individuals due to the ability of the kidneys to effectively excrete dietary potassium load in urine, while an increase in serum K+ is prevalent in patients with chronic kidney disease (CKD). Hyperkalaemia prevalence increases in more advanced CKD stages, and is associated with a poor prognosis. This scenario generates controversy on the correct nutritional approach to hyperkalaemia in CKD patients, considering the unproven link between potassium intake and serum K+ levels. Another concern is that drug-induced hyperkalaemia leads to the down-titration or withdrawal of renin-angiotensin system inhibitors (RASI) and mineralocorticoids receptors antagonists (MRA) in patients with CKD, depriving these patients of central therapeutic interventions aimed at delaying CKD progression and decreasing CV mortality. The new K+-binder drugs (Patiromer and Sodium-Zirconium Cyclosilicate) have proven to be adequate and safe therapeutic options to control serum K+ in CKD patients, enabling RASI and MRA therapy, and possibly, a more liberal intake of fruit and vegetables.

Diabetes is the leading cause of kidney failure and specifically, diabetic kidney disease (DKD) occurs in up to 30% of all diabetic patients. Kidney disease attributed to diabetes is a major contributor to the global burden of the disease in terms of clinical and socio-economic impact, not only because of the risk of progression to End-Stage Kidney Disease (ESKD), but also because of the associated increase in cardiovascular (CV) risk. Despite the introduction of novel treatments that allow us to reduce the risk of future outcomes, a striking residual cardiorenal risk has been reported. This risk is explained by both the heterogeneity of DKD and the individual variability in response to nephroprotective treatments. Strategies that have been proposed to improve DKD patient care are to develop novel biomarkers that classify with greater accuracy patients with respect to their future risk (prognostic) and biomarkers that are able to predict the response to nephroprotective treatment (predictive). In this review, we summarize the principal prognostic biomarkers of type 1 and type 2 diabetes and the novel markers that help clinicians to individualize treatments and the basis of the characteristics that predict an optimal response.