Review Article

Pharmacological Management of Cardiorenal Syndromes

Table 1


CRS subtypeGeneral considerations and recommended therapiesCaveats/areas for future investigation

Acute cardio-renal (CRS 1)Reduce congestion with diuretics, balance negative fluid balance with intravascular refillingInfusion versus bolus; dose; electrolyte concerns
Renin-angiotensin blockade may need to be reduced or even withheld with worsening renal function
With preserved or elevated blood pressure, empiric use of vasodilatorsLimited data from uncontrolled trials; nitroprusside limited by toxicity
Nesiritide may improve cardiac output and cause significant diuresisConflicting results of clinical trials; ongoing trials to determine safety, efficacy, and dose
With low pressure, poor cardiac output, inotropes may be required as a bridge to recovery or transplantationIntropes may provoke ischemia or arrhythmia; increased mortality in some studies; mechanical support (balloon pump, ventricular assist device, etc.) may be required

Chronic cardio-renal (CRS 2)Renin-angiotensin blockade is of primary importance; may need to be reduced or withheld with significantly worsening renal functionMost studies have excluded patients with significant kidney disease; increase in creatinine >30% or potassium >5.0 mmol/L cause for concern
Aldosterone antagonists may be cautiously consideredCreatinine >2.5 mg/dL (>220 μmol/L) or potassium >5.0 mmol/L were exclusions in clinical trials
Beta-blockers are important adjuncts in congestive heart failure and/or ischemic heart diseaseSome agents (atenolol, nadolol, sotalol) have altered pharmacokinetics; carvedilol may have an advantage over older drugs
Concomitant anemia may worsen symptoms and outcomesUnclear role of erythropoiesis-stimulating agents; parenteral iron encouraging in terms of symptoms as well as improved renal function

Acute reno-cardiac (CRS 3)Contrast nephropathy is a common example of CRS 3; prevention is likely the best strategy
Numerous strategies tested; isotonic fluids and possibly N-acetylcysteine have the best evidence to datePreexisting chronic kidney disease, age, diabetes, and volume contraction are amongst risks that predispose to contrast nephropathy
Low osmolar, nonionic contrast may reduce risk of CRS 3

Chronic reno-cardiac (CRS 4)Multifaceted disorder with both traditional and non-traditional risk factors; graded risk based on degree of chronic kidney diseaseLifestyle modification (smoking, weight control, activity, and nutrition) of probable benefit but limited evidence
Anemia closely related to poor outcomes; current guidelines recommend starting for sustained hemoglobin <10 g/dL (100 g/L) and targeting 10–12 g/dL (100–120 g/L)Studies showed increased harm from higher targets; concerns have been raised about stroke risk, and risk in patients with cancer
Management of chronic kidney disease-related mineral and bone disorders; phosphate binders, vitamin D analogs, controlling PTHAs yet, efficacy largely limited to putative surrogate endpoints; ongoing trials with hard cardiovascular endpoints awaited
Lipid lowering with statinsEfficacy in dialysis-dependent patients is questioned; in lesser degrees of chronic kidney disease risk reduction is clearly established

Secondary cardio-renal (CRS 5)Sepsis is a common example of CRS 5; management needs to focus on protecting/optimizing both cardiac and renal functionOther secondary causes of CRS 5 are a fruitful area for ongoing research
Volume and pressor support to achieve a mean arterial pressure ≥65 mmHg and central venous pressure of 8 to 12 mmHg and adequate oxygen deliveryEarly protocol-driven interventions lower risk of adverse renal outcomes and death due to cardiovascular collapse
Norepinephrine preferred over dopamine in a randomized controlled trial (most patients had septic shock)Higher incidence of cardiac arrhythmia and trend to increased need for dialysis with dopamine
Addition of low-dose vasopressin in select patientsMay decrease risk of adverse cardiac and renal outcomes