Abstract

Mineralocorticoid receptor antagonists (MRA) are drugs with a potentially broad spectrum of action. They have been reported to have healing effects in many diseases, such as chronic heart failure, hypertension, or nephrotic syndrome. Numerous studies suggest that mineralocorticoid receptor activation is pathogenic and a progression factor of chronic kidney disease (CKD); however, results of studies on the use of MRA in the treatment of CKD are inconclusive. Current guidelines recommend against the use of MRA in patients with advanced CKD. Although, there is growing interest on their use in this population due to treatment benefits. In this review, we summarize studies which were purposed to evaluate the impact of MRA therapy on CKD patients. Despite many benefits of this treatment e.g., reducing cardiovascular mortality or alleviating proteinuria, steroidal MRA (such as spironolactone or eplerenone) have a low safety profile. They often lead to hyperkalemia complications which are dangerous in patients with CKD, and diabetic nephropathy, especially in hemodialysis patients. Studies on recently developed nonsteroidal MRA showed that they have fewer side effects. In our review, we discuss steroidal and nonsteroidal MRA treatment effects on the estimated glomerular filtration rate (eGFR), proteinuria, the cardiovascular system, and hyperkalemia in CKD patients. We present new content and recent publications in this field.

Highlights

  • The renin–angiotensin system (RAS) stimulates, among others, the secretion of aldosterone hormone, which participates in the control of blood pressure (BP), the volume of extracellular fluid or potassium serum levels

  • 5674 449 141 1786 patients with persistent proteinuria >1 g/24 h with any renal disease treated Angiotensinconverting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) or their combination for more than 6 months patients with type 2 diabetes and diabetic nephropathy, aged 30 to 70 years, estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 patients with diabetic nephropathy, patients with nondiabetic proteinuric chronic kidney disease (CKD), patients with resistant hypertension and diabetes mellitus, patients with hypertension and albuminuria adult patients with type 2 diabetes and CKD treated with an ACEI or ARB at the maximum dose patients with type 2 diabetes and hypertension and urinary albumin-creatinine ratio (UACR) of 45 to 15 ng/dL patients with type 2 diabetes treated

  • By means of urinary proteomics, they demonstrated the highest reduction in UACR in patients with type 2 diabetes with a higher CKD273 score after 16 weeks of spironolactone treatment. This correlation was not noticed in the group of patients taking a placebo. These results suggest that urinary proteomics may be a useful instrument to select individuals at a greater risk of progression in diabetic nephropathy (DN) and those who will benefit from Mineralocorticoid receptor antagonists (MRA) treatment, as it is a predictor of the occurrence of an albuminuria-lowering response to spironolactone treatment [34]

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Summary

Introduction

The renin–angiotensin system (RAS) stimulates, among others, the secretion of aldosterone hormone, which participates in the control of blood pressure (BP), the volume of extracellular fluid or potassium serum levels. Mineralocorticoid receptor antagonists (MRA) are an essential element in the treatment of chronic kidney disease (CKD) due to their anti-inflammatory and antifibrotic effects [2]. Among all MRA, nonsteroidal newgeneration MRA appear to have better anti-inflammatory and antifibrotic effects; they cause minimal hyperkalemia and a lesser decrease in the estimated glomerular filtration rate (eGFR) during therapy [2,3]. This treatment seems to be beneficial especially in patients with type 2 diabetes [2]. More and more data show a protective action on renal function by lowering albuminuria in patients with chronic kidney disease, especially in patients with type 2 diabetes, declining the progression of CKD and reducing cardiovascular (CV) outcomes, with an increased risk of hyperkalemia [1,7]

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