Cardiorenal syndrome

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  • Cardiorenal syndromes (CRS) are disorders of the heart and kidneys whereby acute or long-term dysfunction in one organ may induce acute or long-term dysfunction of the other
  • CRS is characterised by the triad of concomitant decreased kidney function, therapy-resistant heart failure with congestion (ie, diuretic resistance), and worsening kidney function during heart failure therapy
  • acute increase in serum creatinine level accompanies 21%-45% of hospitalizations for ADHF
  • 50% of CHF pateints have decreased renal function


  • CRS type 1 — Acute decompensated heart failure -> Acute kidney injury
  • CRS type 2 — Chronic heart failure -> Chronic kidney disease
  • CRS type 3 — Acute kidney injury -> Acute heart failure
  • CRS type 4 — Chronic kidney disease -> Chronic heart failure
  • CRS type 5 — Codevelopment of heart failure and chronic kidney disease


  • elderly
  • comorbid conditions (diabetes mellitus, uncontrolled hypertension, and anemia
  • Medications: NSAIDS, diuretics (thiazides, loop diuretics), ACE inhibitors/angiotensin receptor blockers, aldosterone receptor antagonists
  • History of heart failure or impaired left ventricular ejection fraction
  • Prior MI
  • NYHA functional class
  • Elevated cardiac troponin
  • Chronic kidney disease (reduced eGFR, elevated BUN, creatinine, or cystatin)

ACUTE CRS (type 1)


  • typically presents with ADHF and experiencing worsening renal function (acute increase in Cr and/or oliguria)
  • ADHF characterised by rapid worsening of heart failure symptoms and signs (APO, right heart failure, and/or cardiogenic shock) — 1/3 precipitated by ACS

Proposed mechanism(s)

  • renal venous congestion (high venous pressures and intra-abdominal pressures)
  • hypotension and decreased cardiac output with activation of SNS and renin-angiotensin-aldosterone system (RAAS)
  • cytokine signalling injury
  • persistent renal vasoconstriction from tubuloglomerular feedback and various vasoactive substances (adenosine and endothelin), decreased renal responsiveness to natriuretic peptides, and impaired autoregulation of GFR
  • diuretic resistance due to: decreased solute delivery to tubules caused by decreased RBF, decreased GFR, hypoalbuminemia, and the phenomenon of diuretic “braking” caused by enhanced sodium reabsorption and distal tubular hypertrophy

See diagram from House et al, 20010

CHRONIC CRS (type 2)

Concomitant decreased kidney function in patients with heart failure is very common, with a negative influence of long-term cardiac dysfunction on kidney function (type 2 CRS). The prevalence of GFR <60 mL/min/1.73 m2 (CKD stage 3 or higher) is overrepresented in chronic heart failure and may be as high as 30%-40%.28, 29, 30 However, in patients hospitalized for ADHF, the prevalence of GFR <60 mL/min/1.73 m2 on admission is up to 70%,10, 31, 32, 33 likely reflecting a combination of patients with CKD and those with superimposed acute kidney injury.


  • CHF
  • increased arterial BP
  • gradually worsening kidney function with heightened susceptibility to complications of therapy (worsening GFR and electrolyte disturbance)
  • diuretic resistance with peripheral edema

Proposed mechanism(s)

  • chronic overactivation of the RAAS and SNS
  • increased levels of inflammatory substances and markers of cardiac stress
  • Long-term upregulation of endothelin 1 followed by increased TGF β and nuclear factor-κB activity lead to renal fibrosis and glomerulosclerosis

See diagram from House et al, 2010


CRS Type 1

  • diuretics (loop more efficacious than thiazides) — natriuresis, decrease in fluid overload, sodium and water elimination
  • nitrates — venodilation, decreased cardiac ischemia, decreased afterload
  • nitroprusside if elevated BP— arterial and venous dilation, decreased preload, afterload
  • inotropes if severe low cardiac output (e.g. dobutamine, milrinone, levosimendin) — may exacerbate myocardial ischemia and oxygen demand, no proven benefit

CRS Type 2


non-pharmacological management



  • Decreased kidney function is one of the most powerful predictors of impaired prognosis in heart failure
  • In patients with acute decompensated heart failure (ADHF), an acute increase in serum creatinine level >0.3 mg/dL (>26.5 μmol/L) is associated with increased mortality, longer hospital stays, and more frequent readmissions
  • In both ADHF and CHF small decreases in GFR are associated with adverse outcome


  • CARESS-HF: RCT that found that ultrafiltration was no better that protocolised diuretic use with inotropic support if needed in ADHF
  • OPTIME-CHF: RCT of milrinone in patients with ADHF found higher incidence of hypotension, more arrhythmias, no benefit on mortality or hospitalization; suggestion of worse outcomes on subgroup analysis of pateints with ischemic cardiomyopathy

References and Links

Journal articles

  • Bart BA, et al; Heart Failure Clinical Research Network. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012 Dec 13;367(24):2296-304. doi: 10.1056/NEJMoa1210357. Epub 2012 Nov 6. PubMed PMID: 23131078; PubMed Central PMCID: PMC3690472.
  • Cuffe MS, et al; Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) Investigators. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA. 2002 Mar 27;287(12):1541-7. PubMed PMID: 11911756. [Free Full Text]
  • House AA, Haapio M, Lassus J, Bellomo R, Ronco C. Therapeutic strategies for heart failure in cardiorenal syndromes. Am J Kidney Dis. 2010 Oct;56(4):759-73. doi: 10.1053/j.ajkd.2010.04.012. Epub 2010 Jun 16. Review. PubMed PMID: 20557988. [Free Full Text]
  • Viswanathan G, Gilbert S. The cardiorenal syndrome: making the connection. Int J Nephrol. 2010 Oct 4;2011:283137. doi: 10.4061/2011/283137. PubMed PMID: 21151533; PubMed Central PMCID: PMC2989717.

CCC 700 6

Critical Care


Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

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