Preventing and Managing Cardiorenal Syndromes


diuresis is reasonable until more clinical trial evidence is available. Finally, the early use of ultrafiltration or other forms of continuous renal replacement therapies (CRRT) should be considered for patients with advanced type 1 CRS on admission where the combination of azotemia and other clinical factors anticipates a poor response to diuretics.


Chronic Cardiorenal Syndrome (Type 2)


Chronic abnormalities in heart function leading to kidney injury and/or dysfunction. This subtype refers to a more chronic state of kidney disease complicating chronic heart disease. This syndrome is common and has been reported in 63% of patients hospitalized with heart failure.6


Chronic


kidney disease (CKD) is associated with higher all-cause and cardiac- specific mortality.6


A ‘dose-response’ or graded association between decline in GFR and worsening clinical outcome is generally noted. An example of type 2 CRS is chronic heart failure, where chronic cardiac dysfunction can result in adaptive alterations in kidney perfusion and neurohormonal activation. In a study of 1,102 adult patients with heart failure, over 50% had evidence of kidney dysfunction; 9% had GFR <60ml/min/1.73m2, and this was associated with a three-fold increase in mortality.7


It is recognized that patients may transition between type 1 and 2 CRS at various stages in their disease when the syndrome has persisted for more than 90 days (acute to chronic).


Initiation of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may cause a mild increase (~15%) in serum creatinine, but do not contribute to CRS. Other causes contributing to real decline of renal function include excessive diuresis, persistent hypotension, prescriptions for nephrotoxic agents, vasodilators, and underlying renovascular disease. Anemia is a common finding in patients with type 2 CRS due to relative or absolute erythropoietin deficiency combined with a functional decrease in iron utilization as a result of increased hepcidin levels which block iron transfer to hematoblasts. Correction of the anemia may improve symptoms but has not been shown to reduce clinical end-points or mortality.


Preventive approaches for type 2 CRS include early initiation of chronic ACEIs or ARBs, use of aldosterone receptor antagonists, blood pressure control to a systolic blood pressure goal of <130mmHg, glycemic control for diabetes to a glycohemoglobin target of <7.5%, and other treatments for the specific form of CKD. Patients with type 2 CRS should have laboratory assessments at least every 90 days, and since clinical events occur at very high frequencies, consideration should be made for monthly office visits.


Acute Renocardiac Syndrome (Type 3)


Acute worsening of kidney function leading to heart injury and/or dysfunction. This illness refers to abnormalities in cardiac function that result from or are a consequence of AKI. The pathophysiologic mechanisms contributing to acute dysfunction of the heart likely go beyond simple volume overload to include uremic changes, hyperkalemia, sodium retention, neurohormonal activation, and systemic inflammation. Untreated uremia depresses myocardial contractility and contributes to pericardial inflammation; hyperkalemia can precipitate arrhythmias and cardiac arrest, while acidemia results in negative inotropic effects and an increased risk of arrhythmias. Renal ischemia itself may precipitate activation of systemic oxidative stress by


US NEPHROLOGY


Some patients with contrast-induced AKI develop progressive renal failure, volume overload, and ADHF requiring intensive care treatment and/or transient and sometimes permanent dialysis.9


Solomon et al.10 identified


that patients with contrast-induced AKI (CI-AKI) were almost twice as likely to suffer subsequent adverse cardiovascular events in the year following the contrast exposure, indicative of the serious consequences of type 3 CRS.


The methods of preventing type 3 CRS are predicated on either preventing or ameliorating AKI. To date, there are no approved pharmacologic agents or devices for the prevention of AKI. Agents that improve renal blood flow such as dopamine, fenoldopam, and rolofylline have not been proved to reduce AKI. Thus, it appears that renal protection on a more fundamental, cellular, or tissue level is needed to render the kidneys less susceptible to ischemic or chemotoxic injury.


Chronic Renocardiac Syndrome (Type 4)


CKD leading to progressive decline in cardiac function. This subtype refers to disease or dysfunction of the heart which occurs secondary to CKD. Cardiac disease in CKD patients is common and cardiac-specific mortality rates are 10- to 20-fold higher compared with age- and sex-matched non- CKD populations.11


the liberation of catalytic or unbound iron from renal tubular cells leading to apoptosis of cardiomyocytes.


where AKI contributes to fluid overload and worsened left ventricular (LV) pump mechanics. It is appreciated that CSA-AKI may also represent type 1 CRS.


An example of type 3 CRS is the development of an ACS, arrhythmia, or ADHF after the onset of AKI such as acute glomerulonephritis or acute tubular necrosis. Another common scenario is cardiac surgery- associated AKI (CSA-AKI), with a reported incidence between 0.3 and 29.7%,8


Several observational studies have found a graded


increase in the prevalence of CKD and heart failure, along with a higher risk of subsequent cardiac events associated with the degree of decline in kidney function.12


This dose-response trend also translates into similar trends for the risk of cardiac-specific and all-cause mortality.12


Type 4 CRS involves the progression of CKD, often due to diabetes mellitus and hypertension, with accelerated calcific atherosclerosis, anemia, progressive LV hypertrophy, and the development of diastolic and systolic dysfunction. Sodium retention occurs in progressive CKD from reduced renal excretion, and in patients on hemodialysis due to dietary noncompliance, inappropriately high dialysate sodium, and the inability to achieve target or ‘dry’ weight. The dialysis procedure itself has been implicated in chronic myocardial injury and the activation of multiple proteinases that could be destabilizing to atherosclerotic plaque. However, it has been observed that most of the cardiac mortality in dialysis patients is not attributed to coronary ischemia but is more consistent with pump failure or lethal arrhythmias as the terminal events.


Optimal treatment of CKD is needed to prevent these downstream sequelae of CKD. Many forms of treatment benefit both organ systems at the same time, including inhibition of the renin-angiotensin system and blood pressure control. It is unlikely that type 4 CRS can be completely


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