Introduction

It is common for cardiac disorders and renal disorders to coexist in small animal patients. Several practical questions with important implications arise from this duality, including:

• Should a patient with a heart murmur receive a smaller volume of parenteral fluids?
• Should a cardiac patient who is azotemic be given fluid therapy as a form of renal protection?
• What is the best form of fluid therapy for a chronic renal failure patient who also has heart disease?
• Are there early warning signs that can be identified prior to respiratory problems if one is especially concerned about IV fluid intolerance in a cardiac-renal patient?

The cardiorenal syndrome has been defined as “worsening renal function limiting diuresis despite obvious clinical volume overload”.¹ This syndrome presents difficulties in treatment, since certain treatments aimed at resolving one disorder may cause decompensation of the other.² The problem of suboptimal renal function in small animal patients with heart disease is a widely prevalent one, likely with adverse consequences similar to those seen in human medicine.^1-6 The cardiorenal syndrome, then, presents at least two aspects of care that are of interest to use as small animal clinicians: approaches that can help avoid or delay its onset, and methods for managing patients who have developed it despite precautions and optimal care.

Natural History and Pathophysiology

In dogs with myxomatous mitral valve disease, a significant increase in number of azotemic dogs is noted as disease severity worsens from compensated stages to advanced CHF.⁷ Blood urea nitrogen (BUN) and serum creatinine levels are elevated minimally if at all during the compensated, “murmur-only” stage of the disease.^7-9 These patients’ renal values rise significantly at the onset of CHF, at which time the confounding influence of diuretics may also contribute to azotemia.8 BUN (but not necessarily creatinine) is elevated thereafter.^7,9 Later, recurrent CHF prompts increases in diuretic dosage and other treatments; together with worsening renal perfusion due to forward failure and adaptive mechanisms, serum creatinine levels rise and BUN levels continue to increase.

Eventually, the dichotomy between preserving adequate renal perfusion and avoiding fluid congestion/CHF marks the onset of the cardiorenal syndrome. A similar pattern of evolution is apparent in cats with heart disease, although supportive data are lacking.

Chronic kidney disease is an umbrella term that encompasses progressive loss of nephron function often due to unidentified processes, but which ultimately lead to chronic tubulointerstitial nephritis or other nonspecific, irreversible lesions. With ongoing nephron loss, azotemia becomes detectable when glomerular filtration rate falls below 25% of normal. Anemia of chronic disease, compounded by erythropoietin-deficient anemia of chronic kidney disease and possibly gastrointestinal (GI) blood loss from uremic GI effects, decreases circulating red blood cell mass. Systemic hypertension occurs in a variable proportion of cases, as a result of mechanisms that also may contribute further to loss of nephron function. These mechanisms include increased activity of the renin-angiotensin-aldosterone system (RAAS), causing vasoconstriction, sympathetic activation, sodium retention, and potentiation of oxidative stress; endothelial dysfunction; and defective nitric oxide metabolism.

In concert, coexisting heart disease and kidney disease can produce cumulatively detrimental effects:

• Decreased renal perfusion due to renal afferent arteriolar constriction in heart disease
• Renal effects triggered by low-pressure cardiopulmonary baroreceptors³
• Vasopressin/antidiuretic hormone release in advanced heart disease
• Decreased renal perfusion with heart disease (decreased arterial blood pressure; hypovolemia due to diuretics; others) leading to sodium retention
• Systemic hypertension from chronic renal disease augmenting afterload
• Tense ascites causing abdominal compartment syndrome, reducing renal perfusion
• Sympathetic and renin-angiotensin-aldosterone system activation as compensatory cardiac mechanisms worsening renal disease

The Cardiorenal Syndrome in Small Animal Practice

How do we first suspect individuals at risk?

Usually, a patient is presented for evaluation, and from the history, physical exam and diagnostic tests, the clinician establishes that abnormalities involving dysfunction of both the heart and the kidneys are present. The degree of compromise of each system is variable.

One generally predominates—i.e., usually there is a greater concern regarding one system, and dysfunction of the other mainly stands as an obstacle impeding vigorous treatment of the primary problem.

What is the concern of having concurrent kidney and heart disease?

Treatments for heart disease and for kidney disease may be mutually antagonistic in at least one respect: extracellular volume. Increasing extracellular volume with intravenous fluid therapy to improve renal perfusion and promote fluid diuresis can help kidney function but precipitate congestive heart failure iatrogenically; conversely, decreasing extracellular volume with diuretics can help with congestive heart failure but decrease renal perfusion, precipitating a uremic crisis. Optimal treatment is essential—but often difficult—since withholding therapy can be as detrimental as overzealous treatment. Undertreatment can allow deterioration of the patient’s state due to progression of the dominant disorder, whereas overtreatment may cause the lesser problem to emerge suddenly as the worse of the two because of iatrogenic decompensation of the previously latent condition.

What are some practical management approaches?

Proposed partial checklists for management of patients with azotemia and congestive heart failure, acute decompensation of one system (CHF or uremia) in a patient with disorders involving both systems:

• Identify and address reversible causes (CHF: e.g., recent sodium-rich dietary indiscretion; uremia: e.g., pyelonephritis; aortic thromboembolism causing renal infarction).
• Assess patient for onset of gallop sound during fluid therapy, suggesting iatrogenic CHF.
• Use fluid type that matches needs (e.g., no replacement fluids like lactated Ringer’s solution/0.9% NaCl when patient is euvolemic/well-hydrated).
• Manage coexistent electrolyte abnormalities, especially hypokalemia which can lead to ventricular tachyarrhythmias while also causing refractoriness to antiarrhythmics like lidocaine.
• Consider diuretic constant rate infusion instead of intermittent injections for superior natriuresis.
• Change medications to injectable form (e.g., diuretic) while managing crisis in-hospital, and suspend administration of oral medications with benefits that are long term only, not short term (e.g., ACE inhibitors).
• Confirm suspicions. Is dyspnea from pulmonary edema? Thoracic radiographs are indicated regardless of pulmonary crackles, intensity of murmur, etc.—films may be normal (e.g., pulmonary thromboembolism in patient with nephrotic syndrome), may show pleural effusion instead (which can be centered, reducing or avoiding acute doses of diuretics), etc.
• Have radiographs interpreted by radiologist/cardiologist if uncertain (both false-positive and false-negative results are common for pulmonary edema, cardiomegaly, and other relevant cardiovascular interpretations).
• Look to remainder of physical exam to offer clues regarding whether heart or kidney problem is worse at that moment.
• E.g., the presence of respiratory sinus arrhythmia generally signifies that cardiogenic pulmonary edema is not present.
• However, avoid overinterpretation of lung sounds. Crackles do not equate to pulmonary edema (e.g., pulmonary interstitial fibrosis)
• Removal of large-volume body cavity effusions in acute states: centesis is generally superior to diuretics for both efficacy and lesser degree of adverse effect.
• Positive inotropes—Dobutamine unconvincing, pimobendan promising, dopamine if hypotensive.

Chronic management of coexisting cardiac and renal disorders:

• Verify client compliance with drug administration (both client diligence and patient co-operation).
• Identify diuretic resistance.
• Measure urine-specific gravity.
• Have owner measure water intake, confirm > 20 cc/lb/day (45 cc/kg/day).
• Identify systemic hypertension and treat if present and if attributed only to renal disease.
• With good client comprehension, taper diuretic to lowest effective dosage.
• Consider dual-diuretic therapy (e.g., furosemide + spironolactone, except in Maine Coon cats due to breed-associated adverse effects associated with spironolactone [facial dermatitis]).
• Manage coexistent electrolyte abnormalities, especially hypokalemia (which could lead to ventricular tachyarrhythmias while also causing refractoriness to antiarrhythmics like lidocaine).
• Differentiate between advanced chronic renal disease and acute-on-chronic process: anemia, hyperphosphatemia, and small kidneys (exceptions: polycystic kidney disease, lymphoma) suggest chronic kidney disease; their absence offers the possibility of an acute, potentially reversible superimposition on chronic kidney disease (e.g., occult urinary tract infection: up to 72% prevalence in cats with chronic kidney disease).
• Manage anemia (with chronic kidney disease, anemia can arise due to chronic illness, erythropoietin deficiency, uremic gastrointestinal blood loss, or a combination of these factors).
• Have radiographs interpreted by radiologist/cardiologist if uncertain (both false-positive and false-negative results are common for pulmonary edema, cardiomegaly, and other relevant cardiovascular interpretations).
• Look to remainder of physical exam to offer clues regarding whether heart or kidney problem is worse at that moment; e.g., respiratory sinus arrhythmia generally does not coexist with cardiogenic pulmonary edema.
• Removal of large-volume, recurrent body cavity effusions in chronic states: periodic centesis/drainage may be superior to higher-dose diuretics for both efficacy and lesser degree of adverse effect.
• Positive inotropes: role still to be defined. Like many veterinarians, the author has treated severely ill, “end-stage” cardiorenal patients with pimobendan, resulting in improved azotemia and uremia and prolonged survival due to delay in the owner’s decision to euthanize. This response is variable and unpredictable, with some dogs improving dramatically and others deteriorating despite similar therapy. However, all dogs that demonstrated a visible positive response to pimobendan did so within the first several days of treatment, an observation that offers the opportunity for a therapeutic trial.

References

1.  Stevenson LW, Nohria A, Mielniczuk L (2005). Torrent or torment from the tubules? Challenge of the cardiorenal connections. J Am Coll Cardiol. 45: 2004–7.

2.  Pouchelon JL, Atkins CE, Bussadori C, et al. (2015). Cardiovascular-renal axis disorders in the domestic dog and cat: a veterinary consensus statement. J Small Anim Pract. 56: 537–52.

3.  Weinfeld MS, Chertow GM, Stevenson LW (1999). Aggravated renal dysfunction during intensive therapy for advanced chronic heart failure. Am Heart J. 138: 285–90.

4.  Schiffrin EL, Lipman ML, Mann JF (2007). Chronic kidney disease: effects on the cardiovascular system. Circulation. 116: 85–97.

5.  Liang KV, Williams AW, Greene EL, et al. (2008). Acute decompensated heart failure and the cardiorenal syndrome. Crit Care Med. 2008; 36: S75–88.

6.  Oyama MA, Vaden SL, Atkins CE. Heart disease and kidney disease. In: Ettinger SJ, Feldman EC, Côté E, eds. Textbook of Veterinary Internal Medicine, 8e (St. Louis: Elsevier Saunders, 2017). 2161–4.

7.  Nicolle AP, Chetboul V, Allerheiligen T, et al. (2007). Azotemia and glomerular filtration rate in dogs with chronic valvular disease. J Vet Intern Med. 21: 943–9.

8.  Atkins CE, Brown WA, Coats JR, et al. (2002). Effects of long-term administration of enalapril on clinical indicators of renal function in dogs with compensated mitral regurgitation. J Am Vet Med Assoc. 221: 654–8.

9.  Boswood A, Murphy A (2006). The effect of heart disease, heart failure and diuresis on selected laboratory and electrocardiographic parameters in dogs. J Vet Cardiol. 8: 1–9.