Updates on New Therapies for Patients with CKD

Renin–Angiotensin–Aldosterone System: From History to Practice of a Secular Topic

“…Lastly, the UK-HARP III trial, where 414 CKD patients with an eGFR 20-60 mL/min/1.73 m 2 were randomized to either ARNI or ARB monotherapy, showed no difference between the two study groups in terms of kidney function or albuminuria [38]. As of now, ARNIs do not seem to have an additional effect on CKD when compared with ACEi/ARB while they should be considered in CKD patients with HF under strict monitoring for hypotension and hyperkalemia [35].…”

“…Despite the demonstrated renal and CV benefits of standard treatment with ACEis and ARBs, a significant risk in overall mortality still persists [34]. In particular, patients with CKD have a much higher cardiovascular risk when compared to non-CKD patients associated with an increased severity of kidney disease [35]. Apart from this, the accumulation of uremic toxins generates oxidative stress, inflammation and platelets activation, further driving cardiovascular disease [35].…”

“…In particular, patients with CKD have a much higher cardiovascular risk when compared to non-CKD patients associated with an increased severity of kidney disease [35]. Apart from this, the accumulation of uremic toxins generates oxidative stress, inflammation and platelets activation, further driving cardiovascular disease [35]. The need for additional risk reduction has led to the search for medications with similar benefits.…”

“…NEPis therefore increase the levels of these natriuretic peptides, promoting natriuresis and leading to improvement in myocardial relaxation, reduction in hypertrophy as well as blood vessel dilatation [36]. The two landmark trials PARADIGM-HF and PARAGON-HF demonstrated that ARNIs decrease CV death and heart failure hospitalization by 25-30% as compared to monotherapy with either ACEis or ARBs [35]. Therefore, the indication to use ARNI in patients with HF is justified; nevertheless, the use of ARNI over ACEis/ARBs in CKD patients still remains controversial [35].…”

“…The two landmark trials PARADIGM-HF and PARAGON-HF demonstrated that ARNIs decrease CV death and heart failure hospitalization by 25-30% as compared to monotherapy with either ACEis or ARBs [35]. Therefore, the indication to use ARNI in patients with HF is justified; nevertheless, the use of ARNI over ACEis/ARBs in CKD patients still remains controversial [35]. In PARADIGM-HF, the annual decline in eGFR was smaller in sacubitril/valsartan compared to enalapril (−1.61 [95%CI: −1.77 to −1.44] vs. −2.04 [95%CI: −2.21 to −1.88]) and also associated with increased albuminuria (1.20 mg/mmol [95%CI: 1.04-1.36] vs. 0.90 mg/mmol [95%CI: 0.77-1.03]) [47].…”