**Author details**

by a slower decline in eGFR (WMD: −0.70 ml/min/1.73 m2

46 Renin-Angiotensin System - Past, Present and Future

approach in people with proteinuric CKD is not recommended.

), whereas add‐on MRA therapy was also associated with a significantly 3.06 times

higher risk of developing hyperkalemia (pooled RR: 3.06; 95% CI: 1.26–7.41) [33]. A subsequent updated meta‐analysis of 27 RCTs (including 1549 participants) confirmed in a larger frame of data that add‐on MRA therapy offers an additive reduction in proteinuria [standardized mean difference (SMD): −0.61; 95% CI: −1.08 to −0.13], but MRA use aggravated the risk of hyperka‐ lemia and gynecomastia [34]. In the albescence of properly designed RCTs evaluating the effect of add‐on MRA therapy on nephropathy progression, the wide use of this therapeutic

A newly introduced, selective, nonsteroidal MRA‐named finerenone offers the opportunity for similarly effective anti‐proteinuric action as compared with established steroidal MRAs (i.e., spironolactone and eplerenone), having also the advantage of causing less frequently clinically significant hyperkalemia [35]. The efficacy and safety of finerenone among patients with diabetic nephropathy was tested in the recent phase 2b ARTS‐DN study (mineralocorti‐ coid receptor antagonist tolerability study–diabetic nephropathy) [36], in which 821 diabetic patients with high or very high albuminuria already treated with an ACE inhibitor or an ARB were randomly assigned to double‐blind therapy with finerenone (1.25 up to 20 mg once daily) or matching placebo for 3 months. Finerenone dose‐dependently reduced albuminuria up to 33 and 38% in the 15 and 20 mg groups with only small increases in serum potassium (+0.17 ± 0.46 and +0.23 ± 0.37, respectively) [36]. The incidence of hyperkalemia was 4.1 and 2.6%, respectively, and not significantly different from placebo. These results suggest that finerenone may be an effective and safer approach for renoprotection in proteinuric CKD. Properly designed RCTs are warranted to fully elucidate the effect of finerenone on "hard"

Recent RCTs have provided evidence that the novel oral potassium‐binding resins patiromer and sodium zirconium cyclosilicate can effectively normalize elevated serum potassium and maintain in the long‐term the potassium levels within the normal range in hyperkalemic patients with CKD already treated with RAAS blockers [37–39]. These emerging potassium‐ lowering therapies offer promise that the reduction in the risk of drug‐induced hyperkalemia may facilitate the administration of RAAS blockade at adequate doses and enhance the cardiovascular and renal protection provided by these agents in people with proteinuric

Choice of the appropriate antihypertensive regimen in people with CKD should be individu‐ alized according to the patient clinical characteristics, with proteinuria being an important factor that needs to be taken into consideration. Among people with diabetic or nondiabetic proteinuric nephropathy, large‐scaled outcome trials provided solid evidence that ACE inhibitors and/or ARBs reduce the level of proteinuria and this anti‐proteinuric action is subsequently translated into slower nephropathy progression to ESRD requiring dialysis. In

1.73 m2

renal endpoints.

CKD [29].

**5. Conclusion**

; 95% CI: −4.73 to 3.34 ml/min/

Panagiotis I. Georgianos, Elias V. Balaskas and Pantelis E. Zebekakis\*

\*Address all correspondence to: pzebeka@med.auth.gr

Section of Nephrology and Hypertension, 1st Department of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
