The unmet need of evidence-based therapy for patients with advanced chronic kidney disease and heart failure: Position paper from the Cardiorenal Working Groups of the Spanish Society of Nephrology and the Spanish Society of Cardiology

Abstract

Despite the high prevalence of chronic kidney disease (CKD) and its high cardiovascular risk, patients with CKD, especially those with advanced CKD (stages 4-5 and patients on kidney replacement therapy), are excluded from most cardiovascular clinical trials. It is particularly relevant in patients with advanced CKD and heart failure (HF) who have been underrepresented in many pivotal randomized trials that have modified the management of HF. For this reason, there is little or no direct evidence for HF therapies in patients with advanced CKD and treatment is extrapolated from patients without CKD or patients with earlier CKD stages. The major consequence of the lack of direct evidence is the under-prescription of HF drugs to this patient population. As patients with advanced CKD and HF represent probably the highest cardiovascular risk population, the exclusion of these patients from HF trials is a serious deontological fault that must be solved. There is an urgent need to generate evidence on how to treat HF in patients with advanced CKD. This article briefly reviews the management challenges posed by HF in patients with CKD and proposes a road map to address them.

Keywords: advanced chronic kidney disease; heart failure; kidney failure; kidney replacement therapy.

FIGURE 1:

Prevalence and incidence of HF in patients with CKD. (A) Prevalence of HF in patients without CKD and in patients with different stages of CKD. (B) Prevalence of HF in patients in the different modalities of KRT: HD, PD and KT. (C) Two-year cumulative incidence of HF in patients on the different modalities of KRT (adapted from USRDS [8] with permission).

FIGURE 2:

Simplified view of the pathophysiology of HF in patients with advanced CKD and impact of KRT. Note the bidirectionality of the detrimental impact of both CKD and KRT on the failing heart.

FIGURE 3:

All-cause mortality crude rates in patients with different stages of CKD and HFrEF and in patients with CKD and HFpEF. Patients in CKD stage 5 (eGFR <15 mL/min/1.73 m²) were not on dialysis (adapted from McAlister et al. [34] with permission).

FIGURE 4:

Hospitalization for HF crude rates in patients with different stages of CKD and HF. Patients in CKD stage 5 (eGFR <15 mL/min/1.73 m²) were not on dialysis. Error bars represent 95% confidence limits (adapted from Go et al. [35] with permission).

FIGURE 5:

Percentage of trials on all types of HF, HFrEF and HFpEF that excluded patients with any stage of CKD (adapted from Konstantinidis et al. [10] with permission).

FIGURE 6:

(A) Prevalence of CKD in the adult population of Spain as estimated in 2010 and as projected for 2040. (B) Prevalence of HF in the adult population of Spain as estimated in 2010 and as projected for 2040 (adapted from Savarese and Lund [51], Otero et al. [53], Ortiz [54] and Gomez-Soto et al. [55]).