1. Andrew Durward
2017
Orlando
Cardio Renal Syndrome

2. In heart failure, worse renal function = worse outcome
Renal function = mortality risk with heart failure
Multiple processes
Systemic haemodynamics (hypertension or hypotension)
Neurohormonal activation (Renin angiotensin)
Intrarenal microvascular
Cellular dysregulation
Oxidative stress
Krumholtz Am J Cardiol. 2000;85:1110–1113.

3. AKI doesn’t mean ATN Pathogenesis Systemic effect
Systemic effect with distal organ damage possible
12% PICU severe AKI
11% mortality AKI
vs 2.5% without
23% shock
NEJM 2017 Kaddourah
troponin
Humoral Inflammatory
Epinephrine
Angiotensin
ADH
Endothelin
GENETIC RISK
Local effect
Altered
sensitivity
BNP NO
Urodilatin
Apoptosis
Necrosis
Hibernation

4. Diuresis resistance – kidneys don’t work
ARF post liver transplant
URODILATIN
Local renal natriuretic peptide
Infusion improves
Urine output
LOCAL EFFECT
European Journal of Clinical Investigation (1994) 24,

5. Cardio-renal or Reno-cardiac Definition (which comes first?)
Acute or chronic

6. Type 1) Acute cardio-renal (worsening cardiac function leads to AKI)
Definition and classification (which comes first?)
Type 1) Acute cardio-renal (worsening cardiac function leads to AKI)
Type 2) Chronic cardio-renal
Type 3) Acute reno-cardiac (fluid overload, arrhythmia K+, uremia)
Type 4) Chronic reno-cardiac
Type 5) Secondary systemic disease
Sepsis, hepato – renal syndrome and immune mediated disease
Acute hypertensive pulmonary oedema, cardiomyopathy
Acute glomerular disease / nephritis
Chronic glomerular disease
Nephrol Dial Transplant (2010) 25: 1416–1420

7. Global versus regional haemodynamics
13% blood volume
13%
Blood
volume

8. SYSTEMIC VS REGIONAL PERFUSION
GLOBAL Sys BP
CVP
Acid base
Lactate
Mix Venous
NIRS Biomarkers
REGIONAL
Driving pressure
= mean pressure - CVP
J Clin Invest. 2011;121(11):
Renal medulla ischaemia

9. Renal medullary ischaemia (Kidneys at limit of hypoxia)
Renal ischaemic perfusion injury
Oxidative stress and inflammation
Molecular adaptive responses
Haem Oxygenase
ANP
Angiopoetin
REPERFUSION INJURY
Regener Curr Opin Nephrol Hypertens ; 21(1): 33–38

10. Polyuric
oliguric
polyuric
Expected post bypass response is avid water retention (ADH)
Polyuria can be pathologic (loss of renal concentrating capacity)

11. Cardiac bypass and AKI

12. Type 1 Cardio-renal syndrome (heart drives renal injury)
Worsening renal function with acute decompensated heart failure
25 to 33% with acute decompensated heart failure
Associated with poor outcomes
Timing and onset important
(preventative strategies)
75% AKI in 1st 4 days PICU
Basu NEJM 2017;376

13. Treatment- avoid hypotension (thresholds?)
Inotropes may AKI 73
Poukkanen et al. Critical Care 2013, 17:R295

14. Role of high CVP in AKI 64% blood venous
Mullens J Am Coll Cardiol. 2009

15. Optimise diuretics Fluid unloading Cytoprotection Vasodilators
Vasodilation
Fluid overload
High CVP
Diuresis
Hypovolaemia
Renal impairment

16. Optimise diuretics Fluid unloading Cytoprotection Vasodilators
Higher vs lower
Dose loop diuretics
Loop diuretic infusions
Combination therapy
Adenosine blocker
GTN (venodilator)
Nitroprusside
Nesiritide (BNP)
Diuretics +
CVVH
Hypertonic saline
Vasodilation
Fluid overload
High CVP
Diuresis
Hypovolaemia
Renal impairment

17. Optimising diuretics : Adenosine blocker
Plasma adenosine raised heart failure – local vasoconstrictor
Locally produced in kidney (stress signal)
Furosemide alone
reduces GFR
Gottlieb Circulation. 2002;105:

18. Vasodilators and Nesiritide (recombinant BNP)
Meta-analysis of Nesiritide = worsened cardiac failure
(Sackner-Bernstein. Circulation 2005;111: )
Low doses of nesiritide potentially renal protective
Controversial
N=7141
O’Connor N Engl J Med 2011;365:32-43

19. Fluid unloading : UNLOAD trial (adults)
Ultrafiltration (500ml/hr) versus Intravenous (IV) Diuretics for Patients Hospitalized for Acute Decompensated Congestive Heart Failure
The ultrafiltration group = greater weight loss and volume removal at 48 h
Dyspnoea score in both groups improved.
Rehospitalisation and the total days of hospitalization were significantly lower in the ultrafiltration group at 3 months
No change renal function long term

20. Fluid unloading : Ultrafiltration
N=188 adult patients acute decompensated heart failure
Change serum Cr and body weight at 96hrs
Ultrafiltration group
Higher adverse events
72% vs 57%
at 60 days
Bart N Engl J Med 2012; 367:

21. Vasodilator: Vasopressin blocker (adults)
Selective V2 antagonists (tolvaptan) to mobilize aquaresis
Efficacy of Vasopressin Antagonist in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial
4133 patients (359 centers in 20 countries)
Produced weight loss (sodium increase)
No long-term benefit vs placebo groups
1 year mortality 25.0% in the tolvaptan group and 26.0% in the placebo

22. Hypertonic saline: cardiac bypass (children)
7.2% Saline 6% HES
vs 0.9% saline (4ml/kg)
52 children post cardiac bypass (VSD)
Favourable haemodynamic effect
Without added risk of tissue oedema

23. Paediatric ECMO and AKI
N=154 children CVVH On ECMO (44%)
44% survived
26% Ongoing CCRT
96% recovered renal function at discharge
N=43 children ECMO
32% needed dialysis for ARF (double creatinine)
Survival only 19%
vs 92% if no renal injury
Weber Ann Thorac Surg. Nov; (5):720–3
Padden Pediatr Crit Care Med. 2011; 12(2): 153–158

24. Outcome Cardiorenal Syndrome (Children)
N=47 (Nigeria)
34% Mortality
20% Malaria
Olowu, 2011, International Journal of Nephrology

25. Cell death rare in sepsis-induce cardiac dysfunction
focal cardiac mitochondrial injury
Renal tubular injury common but present focally; renal tubular regeneration can occur
Organ injury is potentially reversible (hibernation)
TUBULAR CELL ADAPTATION
Am J Respir Crit Care Med Vol 187, Iss. 5, pp 509–517, 2013

26. Cardiorenal syndrome UNIFIED THEORY
SYSTEMIC PROCESS
Inflammation
Hypertension/Hypotension
Cardiac hormonal axis activated
LOCAL PROCESS
Microcirculatory dysfunction
Bioenergetic failure
TUBULAR CELL
ADAPTATION
80% sepsis deaths unresolved infectious focus (autopsy)
50% undetected pneumonia
Torgersen Anesth Analg 2009;108:1841–7

27. Conclusion – Cardio Renal syndrome
Heart failure with worsening renal function 
Varying chronicity and presentation
Pathogenesis complex (haemodynamic and local renal factors)
Poor outcome if untreated
Therapeutic potential ( treat cause and supportive treatment)