The heart and the kidney are in constant communication with each other through released peptides and other neurohormonal mechanisms. This delicate relationship is responsible for regulating blood volume, vascular tone, and ultimately organ perfusion. The leading causes of kidney disease are diabetes, hypertension, and CVD; similarly, the leading causes of HF are diabetes, hypertension, coronary artery disease, and kidney disease. The so-called “traditional” CV risk factors are advanced age, diabetes, hypertension, and dyslipidemia with “nontraditional” CKD-specific risk factors being volume overload, anemia, and inflammation. However, the connection between these two pathologies extends beyond risk factors. In fact, kidney disease and heart failure are interrelated such that derangement of one organ consequently promotes derangement of the other. If dysfunction occurs in the intimate relationship between the heart and the kidneys, it is known as the cardiorenal syndrome. Figure 23.1 depicts this relationship.

The overwhelming prevalence of kidney disease in the heart failure population was demonstrated by Smith et al. [11]. In a meta-analysis of 16 studies including 80,098 patients with heart failure, Smith et al. discovered that 63 % of the patients with heart failure had concomitant renal impairment (defined as creatinine >1.0 mg/dL, creatinine clearance or estimated GFR <90 mL/min, or cystatin-C >1.03 mg/dL), while 29 % had moderate to severe renal impairment (defined as creatinine ≥1.5 mg/dL, creatinine clearance or estimated GFR <53 mL/min, or cystatin-C ≥1.56 mg/dL) [11]. Additionally, Smith et al. demonstrated that mortality increased as renal function decreased [11]. Specifically, there was a 15 % increased risk of mortality for every 0.5 mg/dL increase in creatinine and a 7 % increased risk of mortality for every 10 mL/min decrease in estimated GFR [11]. With continued advancements in medicine, patients with CVD are surviving longer and thus developing heart failure, similarly, CKD patients are surviving longer, and therefore, it is estimated that patients with combined heart and kidney disease will become even more prevalent.

The pathophysiological mechanisms which hasten LV failure in CKD are numerous. At least three mechanisms have been implicated including pressure overload from long-standing hypertension and vascular stiffness, volume overload from CKD, and non-hemodynamic factors such as inappropriate renin-angiotensin-aldosterone system (RAAS) activation which alters the myocardium [12]. Other than systolic dysfunction, diastolic dysfunction is common in CKD even in early stages and increases the risk of CHF and mortality [12, 13].

Several studies have demonstrated that renal impairment is strongly associated with poor outcomes in heart failure patients with systolic and diastolic dysfunction [14]; therefore, it is imperative to treat underlying kidney disease when managing heart failure. In fact, the reversal of renal dysfunction has been shown to improve cardiac function. Wali et al. demonstrated that hemodialysis patients with heart failure and a left ventricular ejection fraction (LVEF) of ≤40 % undergoing renal transplantation had a mean LVEF increase of 20 % 1 year post-renal transplantation, increasing from a mean LVEF of 32 % to a mean LVEF of 52 % [15]. Additionally, 70 % of the transplanted patients achieved normalization of cardiac function, defined as an LVEF ≥50 % [15]. This data demonstrates that renal insufficiency has a contributory role in heart failure progression.

Additionally, a study of 1,906 patients with heart failure concluded that impaired renal function was a better predictor of mortality than either heart failure class or LVEF [16]. It is important to note that the heart is not a victim in this relationship; in fact, the most common cause of mortality in CKD is CVD [17]. Therefore, the treatment of one organ system can dramatically improve the other. Figure 23.2 demonstrates how cardiac dysfunction or renal dysfunction can produce dysfunction in the other organ. Attenuating or even halting the vicious cardiorenal cycle requires therapies that can interrupt the cycle at any point depicted. Table 23.2 lists the types of cardiorenal syndrome.

Although there are well-established guidelines for managing heart failure alone and kidney disease alone, the management of their copresentation in the emergency department remains largely empirical due to the lack of significant randomized clinical trials. Most trials which evaluated heart failure management excluded patients with renal dysfunction out of concern that investigational treatments would potentially cause worsening renal function [18]. Therefore, there is a paucity of recommendations and guidelines for the management of HF patients with CKD, which represents a very high-risk patient population that is often overlooked and undertreated. However, medical therapy in HF patients with CKD is similar to those without CKD but with several important differences. Thus, most of the following are suggested management options without significant evidence-based guidelines accompanying them.

Managing heart failure in the emergency department is challenging but is made even more complex in the setting of kidney disease. It is important to understand the subtle differences when managing this specific patient population compared to heart failure patients alone. The management of cardiorenal syndrome in the emergency department requires individualized therapy. This involves a multifaceted approach in order to optimally manage both heart failure and kidney disease. Earlier chapters have indicated the proper management of heart failure in the ED and short-stay unit; therefore, this chapter will focus on the additional therapies recommended for patients with heart failure complicated by underlying kidney disease. Additionally, this chapter will focus on New York Heart Association (NYHA) heart failure classes 1–3 with CKD. Those with NYHA heart failure class 4 and those with CKD stage 5 or ESRD are considered high risk and are usually not appropriate for admission to a short-stay observation unit and thus will not be discussed in this presentation.

The plasma levels of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are useful markers for the diagnosis and prognosis of heart failure. Since volume overload causing LV wall distention causes release of these peptides, their levels can be used to aid in the diagnosis and prognosis of acute exacerbation of heart failure. Many studies have demonstrated the diagnostic and prognostic value of BNP and NT-proBNP in heart failure (discussed in prior chapters). However, the utility of these markers is not as well established in the CKD population with HF. BNP and NT-proBNP have been shown to be useful diagnostic and prognostic markers in HF patients with CKD, but higher cutoff values may be required [19, 20]. Several mechanisms have been proposed for the elevated BNP and NT-proBNP in patients with CKD and HF, including reduced renal clearance of the peptides due to CKD or increased peptide release by the myocytes due to advanced cardiac damage in renal dysfunction [19]. However, current studies suggest that BNP and NT-proBNP are increased mainly due to advanced cardiac pathology rather than impaired renal clearance [19]. Additionally, one study suggested that LV structural and functional changes in CKD are the primary cause of increased BNP levels in dialysis patients rather than a reduced plasma clearance [1, 21]. This is supported by another study where NT-proBNP and BNP were significantly higher, while LVEF was lower in patients with renal dysfunction [22]. It can be argued that higher levels of these peptides in this population signify a worse cardiac substrate. Furthermore, BNP and NT-proBNP were independent predictors of 1-year mortality in renal disease patients [22].

The role of myoglobin in predicting myocardial ischemia is not appropriate in renal impairment. Several studies have demonstrated that myoglobin is falsely elevated in renal dysfunction, although CK-MB and troponin are not, due to different clearance mechanisms [23]. This is true for populations in which AMI was ruled in or ruled out [23]. In a study by McCullough et al., myoglobin was falsely elevated 100 % of the time in patients with advanced renal function (GFR <47 mL/min) [23]. The recommendation of the use of the multimarker approach still achieves the best negative predictive value for the presence of underlying ACS [24]. Cardiac troponins (cTn) can accumulate in CKD patients with CHF making elevated cTn in this population difficult to interpret; however, it remains a good predictor of mortality [25]. Evaluating a trend via serial sampling or comparing levels to a prior baseline is more informative.

The lack of evidence-based guidelines explains why management is variable in this population. In general, the management of heart failure in patients with concomitant kidney disease in the short-stay unit requires, first and foremost, the optimal treatment of the acute exacerbation of heart failure. Medical management of HF with CKD requires monitoring of fluid status. This requires physician awareness of the consequences of each drug used on both HF and kidney disease. Overly aggressive fluid reduction may damage renal function due to reduced perfusion. Yet increasing plasma volume to improve renal perfusion is detrimental to heart failure. Therefore, any changes in hemodynamics of this patient population must be closely observed. Fortunately, upon administration in the ED, many of the therapies initiated can be continued and monitored in the short-stay unit.

Diuretics are a mainstay therapy in HF management. Often, higher doses of diuretics are required to achieve appropriate diuresis in those with CKD [12]. In those with lower GFR, loop diuretics should be the first-line treatment as thiazide diuretics are less efficacious [26]. Intravenous administration is most effective due to the reduced bioavailability of oral agents in a hypoperfused edematous small bowel that may be present in heart failure. Diuretic resistance is a common therapeutic roadblock encountered in HF patients with CKD, in which the diuretic response is reduced even with “therapeutic” doses. Diuretic resistance can be due to reduced renal perfusion and delivery of drug to the kidney, tachyphylaxis and tubular resistance from chronic diuretic use, secondary hyperaldosteronism, or inadequate dosing [26, 27]. To overcome diuretic resistance, higher doses of diuretic are often required. Additionally, coadministration of loop diuretics with a thiazide diuretic such as metolazone can improve diuresis in this setting. However, volume and electrolyte derangements (hyponatremia and hypokalemia) are common and should be closely monitored. Unfortunately, the aggressive use of diuretics can result in worsening renal function via activation of neurohormonal systems.

There is limited evidence about beta-blocker use in CKD and HF. It is thought that overactive sympathetic drive plays a role in LV hypertrophy and underlying cardiac substrate derangement in CKD. In a large systematic review, beta-blocker therapy was found to improve all-cause mortality by 28 % and cardiovascular mortality by 34 % in patients with CKD and chronic systolic heart failure although there was an increased risk of bradycardia and hypotension [28]. Multiple other studies have demonstrated that in patients with CKD and systolic heart failure, beta-blockers reduce mortality and hospitalizations [29]. In the short-stay unit, however, initiation of beta-blocker in acute heart failure should be used with extreme caution as explained in prior chapters.

The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in HF has been well established [30]. Unfortunately, their role in patients with HF and CKD is not well established. This is due to the relatively low number of randomized trials dealing with this patient population and the fear physicians have in exacerbating renal failure and hyperkalemia. Several studies, including that by McAlister et al., demonstrated that patients with renal insufficiency were less likely to receive ACEI, β-blockers, or spironolactone [14]. However, several studies have demonstrated the benefits of ACEI and ARB in this patient population. One analysis of the Minnesota Heart Survey demonstrated a statistically significant reduction in 30-day and 1-year mortality in CHF patients with renal dysfunction not on dialysis who were given ACEI or ARB during their hospital stay [31].

In a review of 12 randomized clinical trials looking at ACEI use in patients with renal insufficiency, the authors demonstrated a 55–75 % risk reduction in the progression of renal disease among those on ACEI compared to those not on ACEI [32]. They also concluded that although serum creatinine levels increased by up to 30 %, they stabilized within the first 2 months of ACEI administration, and there was long-term preservation of renal function [32]. A worsening of renal function at initiation of an ACEI should be expected. However, the withdrawal of an ACEI should occur when creatinine rises 30 % above baseline or hyperkalemia (>5.5 mmol/L) develops within the first 2 months of ACEI treatment [32]. Another study demonstrated reduced 1-year mortality associated with ACEI and β-blocker use in heart failure patients, even after adjustment for serum creatinine, age, gender, NYHA class, hemoglobin, and other medications [14]. This was true for creatinine clearances <60 and ≥60 mL/min [14]. Khan et al. demonstrated that in HF patients with CKD, ACEIs were associated with reduced mortality and did not have adverse effects on renal function [33].