comorbidities in AHF Kidney disease

1. Comorbidities in Acute Heart Failure
Kidney Disease
How to protect the kidney ?
Kevin Damman, MD, PhD
University Medical Center Groningen
Groningen, The Netherlands
k.damman@umcg.nl

2. Disclosures
Supported by the Netherlands Heart Institute (ICIN) and a HFA
Research Grant

3. Background
Chronic Kidney Disease (CKD) is one of the most prevalent
comorbidities in acute (and chronic) Heart Failure
Presence of an impaired renal function / reduced glomerular
filtration rate (GFR) is strongly associated with worse outcomes
Pathophysiology of impaired renal function multifactorial, and
probably slightly different form chronic HF

4. Background
EVEREST
(2007)
VERITAS
(2009)
PROTECT
(2010)
ASCEND-HF
(2011)
RELAX
(2012)
N 4133 1448 2033 7141 1161
Age (years) 66 70 70 67 72
Male (%) 74 61 67 66 62
Creatinine (μmol/L) 124 118 124 106 NA
eGFR (mL/min/1.73m2) NA 57 50 62 53
CKD (%) 53 37 67 52 72
WRF (%) 14 20 18 13 NA

5. Background
EVEREST
(2007)
VERITAS
(2009)
PROTECT
(2010)
ASCEND-HF
(2011)
RELAX
(2012)
CKD (%) 53 37 67 52 72
Hypertension (%) 71 80 79 72 87
Diabetes (%) 40 48 46 41 47
COPD (%) 10 NA 20 NA 15
AF (%) 43 37 56 38 52

6. CKD and prognosis
Smith et al Circulation 2005

7. CKD and prognosis
Heywood et al J Card Fail 2007, Blair et al Eur Heart J 2011
ADHERE EVEREST

8. CKD and Prognosis
Damman et al Eur Heart J 2014
Overall OR: 2.39 , 95% CI 2.25 to 2.54 (N=812139)

9. CKD and Prognosis
CKD present in 40 – 70% of (selected) AHF patients
Baseline CKD associated with strongly increased mortality

10. Cardiorenal Syndrome
Ronco et al JACC
“Cardiorenal Syndrome type I”
Classification based on epidemiology
Great for:
- Creating Awareness
- Popular term
- Hype
However:
- Does not help for
treatment
- “CRS type I” very diverse

11. Pathophysiology
GFR
↓
RBF ↓
Cardiac
Output↓
CVP ↑
Salt and water
retention ↑
• Interplay between:
Comorbid organ dysfunction:
Hypertension
Diabetes
CKD
Peripheral artery disease
Hemodynamics:
Reduced Cardiac Output
Reduced Renal Blood Flow
Increased Central Venous Pressure
Increased Renal Venous Pressure
Intra-abdominal pressure
Therapy (Inotropes, vasodilators, diuretics)
Damman et al Progr Cardiovasc Dis 2011

12. Pathophysiology
Damman, Tang, Testani, McMurray Eur Heart J 2014

13. Renal Hemodynamics
Heart failure + ACEi/Diuretic
RVP ↑↑
RVP ↑↑RVP ↓
RVP ↑↑
Damman et al Progr Cardiovasc Dis 2011

14. Renal Hemodynamics
Mullens et al JACC 2011
Relative Importance CI/CVP

15. WRF and Prognosis
Damman et al Eur Heart J 2014
Overall OR: 1.75 , 95% CI 1.47to 2.08

16. Predictors of WRF
Damman et al Eur Heart J 2014

17. Predictors of WRF
Damman et al Eur Heart J 2014

18. Not all WRF equal
Testani et al AJC 2010, Metra et al Circ HF 2012
Any change (no) residual congestion

19. Not all WRF equal
Valente et al Eur Heart J 2014
Uncoupling between WRF,
Diuretic Response and mortality

20. CKD and Diuretic Response
Singh J Card Fail 2014

21. AKI ≠ WRF
• Acute kidney injury is a condition in nephrology/intensive
care/shock
• Often intrinsic renal ‘hit’
• Very large increases in serum creatinine
• Associated with azotemia
• WRF can deteriorate in AKI

22. Terminology
Damman, Tang, Testani, McMurray Eur Heart J 2014

23. Terminology
Suggested Definition
Serum Creatinine / eGFR Additional Criteria
Chronic HF (WRF)*
≥26.5 μmol/L and ≥ 25% increase in sCr#
OR
≥ 20% decrease in eGFR
over 1 to 26 weeks
Deterioration in HF status but
not leading to hospitalization
Acute HF (WRF/AKI)*
Increase 1.5 - 1.9 times baseline sCr within 1-7
days before or during hospitalization
OR
≥ 26.5 μmol/L increase in sCr# within 48 hours
OR
Urine output < 0.5 mL/kg/h for 6-12 hours
Deterioration in HF status or failure to
improve
OR
Need for inotropes, ultrafiltration or renal
replacement therapy
Damman, Tang, Testani, McMurray Eur Heart J 2014

24. Pseudo WRF
• ‘Unprovoked’ WRF associated with poor outcome
• WRF that occurs in patients with good Diuretic Response:
Often transient
No association with poor outcome
Could be called “Pseudo WRF”
Damman, Tang, Testani, McMurray Eur Heart J 2014

25. (Pseudo) WRF and AKI
Damman and Testani Eur Heart J 2015

26. Approach to (Pseudo) WRF
Damman and Testani Eur Heart J 2015

27. Dopamine
Chen JAMA 2013 ROSE-AHF study
Placebo Dopamine P-value
N 119 122
Urine volume (72h, mL) 8296 8524 0.59
Change in Cystatin C (mg/L) 0.11 0.12 0.72
Change in Creatinine (µmol/L) 1.8 0 0.78
WRF (%) 22 22 0.88
Sodium excretion (72h, mmol) 540 527 0.75
Weight change (72h, kg) -3.5 -3.3 0.82

28. Ultrafiltration
Bart et al NEJM 2012 CARRESS-HF study

29. Consider Paracentesis
Mullens et al JACC 2008 and J Card Fail 2008

30. Renal Spectrum in AHF
Decreased Renal Blood Flow
Increased (Renal) Venous Pressure
Decreased GFR and renal reserve
Tubular and glomerular injury
Worsening Renal Function and Diuretic Resistance
Acute Kidney Injury / Azotemia
Renal Replacement Therapy / Ultrafiltration
Death

31. CKD/WRF in AHF
• CKD at baseline strongly prevalent in AHF (50-70%)
• During admission, up to 20% experience WRF
However, WRF not always an omnious sign: Pseudo WRF
Risk stratify on WRF and diuretic response/efficiency
AKI is not the same as WRF
• Pathophysiology of both CKD and WRF is multifactorial
Decreased renal perfusion and increased renal venous pressure
Including abdominal hypertension (ascites)
• Treat the Heart – Don’t mind the Kidneys!*
(up to certain limits, and only if diuretic response is good)
* Ruggenenti et al Eur J Heart Fail 2011

32. Thank you for your attention!
k.damman@umcg.nl