Patients Hospitalized for Heart Failure Have 11 Times the Risk of Kidney Failure

Hospitalizations due to heart failure (HF) were associated with a risk for kidney failure (KF), also known as end-stage renal disease (ESRD), that was 11.4-times greater compared with patients who did not have cardiovascular disease (CVD), according to the results of a study that appeared online today in the Journal of the American Society of Nephrology.

There is a bidirectional relationship between the heart and kidneys, and many studies have been performed on the effects of kidney dysfunction on the heart. Few studies, however, have been performed that look at how heart disease influences kidney function, which was the goal of the current study.

Among a group of cardiovascular diseases (CVDs) that also included atrial fibrillation (AFib), coronary heart disease (CHD), and stroke, HF had the highest risk of developing subsequent KF, according to the study results. This was the case despite there being more AFib events in the study period compared with HF events (1337 vs 1269). Meanwhile, patients who had a stroke, AFib, and CHD had 1.4, 2.7, and 3.7 times, respectively, the risk of ESRD.¹

These results “highlight the importance of protecting the kidney health of individuals diagnosed with cardiovascular disease,” stated the authors.

Their findings are the results of an investigation that covered middle- to older-age adult (at least 65 years) patients (N = 9047) enrolled in the Atherosclerosis Risk in Communities (ARIC) study between 1987 and 1989 who were followed for a median of 17.5 years. Overall, 29.0% (n = 2598) were hospitalized with at least 1 CVD and 2.3% (n = 210) developed ESRD.¹

The rate of ESRD among those who had CVD compared with patients who did not was 63.8% (n = 134) versus 36.0% (n = 76), respectively. Diving deeper, in the former group, 54% had HF and the remaining had 1 or more CVDs beyond HF. There was also a 10% rate of HF among study participants with ESRD at the 5-year mark and 15% at 10 years versus approximately 1% and less than 2%, respectively, for patients without HF.¹

Differences were even seen between the risks of ESRD and HF with preserved ejection fraction (HFpEF) (EF >50%) compared with HF with reduced ejection fraction (EF <50%), although exactly why remains unknown—especially because kidney function was comparable between the types during the study. The study investigators posited that the average older age in patients with HFpEF and their higher likelihood of comorbid conditions, especially diabetes, are contributing factors.¹

Because their study was observational, the authors could not determine the reasons for such a strong connection between ESRD and HF. But they do provide possible whys. For example, the 2 disease states share a pathway “involving inflammation, neuro-hormonal activation, metabolic changes, and anemia.” Also, low cardiac output can lead to decreased kidney function. In addition, loop diuretics, which are used to treat high blood pressure and edema from HF or kidney disease, can be toxic. Lastly, the volume overload from ESRD could lead to a HF diagnosis.

What is clear are solutions the authors suggested going forward that could positively impact clinical work and research:

1. Recognize that patients with CVD, especially HF, are at high risk for ESRD and minimize their exposure to nephrotoxic drugs (eg, nonsteroidal anti-inflammatory drugs, nephrotoxic antibiotics).
2. Consider monitoring kidney function.
3. Perform studies that explore the progression of CKD post HF.

“These findings provide important clinical implications for the management of patients following an incident CVD. Underlying mechanisms of the potentially distinct pattern in the association of HFpEF vs HFrEF with ESRD risk deserve future investigation,” the authors conclude.

Cost Implications

The cost implications of the risk relationship between the heart and the kidneys were evident well before the ARIC results came to light and deserve mention in light of the present study.

The CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) results presented in April of last year at the International Society of Nephrology 2019 World Congress of Nephrology² showed that canagliflozin (Invokana, Janssen), a sodium glucose cotransporter 2 (SGLT2) inhibitor used to treat type 2 diabetes (T2D), “easily achieved its primary endpoint,” which included reducing renal or cardiovascular (CV) death, the progression to ESRD, and doubling of serum creatinine in those with T2D. In fact, the relative risk (RR) was 30% lower among those taking 100 mg of canagliflozin.² The secondary prevention group comprised patients with histories of coronary, cerebrovascular, or peripheral vascular disease, procedures, or events. These patients had a 20% lower RR of CV death, myocardial infarction (MI), or stroke and a 39% lower RR of hospitalization for HF.

Then, after several CV outcomes trials (CVOTs), namely EMPA-REG OUTCOME, showed SGLT2 inhibitors had a class effect for CV benefits, at the 79th Scientific Sessions, held in June 2019, CREDENCE coprincipal investigator Kenneth Mahaffey, MD, Stanford, presented additional results on canagliflozin’s “important reduction in CV death and hospitalization for heart failure.”³ There were reductions all around³:

• 26% and 34% in the hazard of CV death or hospitalization for HF in the primary and secondary prevention groups, respectively
• 32% and 15% for the combined endpoint of CV death, MI, or stroke in the primary and secondary groups.

Overall, the CREDENCE and CVOT results show that canagliflozin can achieve huge savings for healthcare, especially considering that 7% of Medicare fee-for-service costs come from the 1% of patients (or 750,000) who have ESRD and that 1 year of dialysis clocks in at $89,000 per patient. That’s a potential savings of almost $67 billion. Patients with CKD automatically qualify for Medicare coverage due to the costs of dialysis and kidney transplant care.³

References

1. Ishigami J, Cowan LT, Demmer RT, et al. Incident hospitalization with major cardiovascular diseases and subsequent risk of ESKD: implications for cardiorenal syndrome [published online January 9, 2020]. J Am Soc Nephrol. doi: 10.1681/ASN.2019060574.

2. Caffrey M. CREDENCE: canagliflozin cuts risk of renal failure, death 30% in patients with type 2 diabetes, CKD. The American Journal of Managed Care^® website. ajmc.com/newsroom/credence-canagliflozin-cuts-risk-of-renal-failure-death-30-in-patients-with-type-2-diabetes-ckd?p=1. Published April 15, 2019. Accessed January 9, 2020.

3. Caffrey M. CREDENCE: first renal outcomes trial finds canagliflozin cuts risk of renal failure, death; prompts ADA updates. The American Journal of Managed Care^® website. ajmc.com/journals/evidence-based-diabetes-management/2019/june-2019/credence-first-renal-outcomes-trial-finds-canagliflozin-cuts-risk-of-renal-failure-death-prompts-ada-updates?p=1. Accessed January 9, 2020.