Combined renal dysfunction and heart failure:
CARDIORENAL SYNDROME
Richard Swartz MD
University of Michigan – Nephrology & Palliative Care
rswartz@umich.edu
Cardiorenal Syndrome . . .
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60 yo M – Hx CAD (MI & stent), Afib & Vtach (AICD), COPD, IDDM, CKD
Chest pain, mild fever and cough, increased edema, CXR w CHF
LVEF 25% and creat 2.7 (both worse), Uo < 1000ml/d, BNP 7000
Adm Meds: 160mg furosemide, b-blocker, ACEi, ASA & statin
-
Dopamine + adm meds, creat up  3.8, BNP  10,000
Uo not improving, UNa 10, FENa 0.5%, no protein or RBC in urine
Rx w IV dobutamine  milrinone, furosemide (cont infusion)
Over 2 -3 days CHF s/s improve, creat  1.9
- Ectopy develops, ? Ischemia, heart cath after N-acetylcysteine
- no new coronary lesions found, but Uo falls and creat rises
Cardiorenal Syndrome - a description:
** SPECIFIC: “decreased (> 25%) GFR, increased creatinine (> 0.5) ,
in the setting of CHF & aggressive diuresis”
** GENERAL: combined heart and kidney disease in which
too much fluid  ADHF/CHF
too little fluid  acute azotemia/”volume depletion”
CHF
ADHF
ACS
Congestive Heart Failure
Acute Decompensated Heart Failure
Acute Coronary Syndrome (ischemia)
ARF
AKI
Pre-renal
acute renal failure (“old” term)
acute kidney injury (“new” term)
physiologic decrease in GFR
Clinical Impact of ADHF/CHF
• CHF:
prevalence is 2-3% in USA
• ADHF:
re-admission rate > 50%
mortality > 20% annually
• ADHF:
associated w ARF/AKI in 20-45%
mortality higher w AKI
(Additional risks ~ age, DM, HTN, ACS)
Clinical Impact of AKI/ARF
AKI/ARF – incr creatinine, decr GFR, +/- oliguria
2 to 5% hospitalized patients w some degree of AKI/ARF
increases risk of in-hosp mortality > 2-fold
0.2 to 1% hospitalized patients w severe AKI/ARF & dialysis
in-hospital mortality is 50% overall and 70% in ICU
AKI/ARF seldom occurs in a vacuum and usually is a
complication rather than a disease entity
ATN (tubular injury, “shock”) or PRE-RENAL > 80%
GN, vasculitis, vasculopathy, AIN ~ 10%
Obstruction ~ 5-10%
“CARDIORENAL SYNDROME”
Pump Failure
Heart Failure
Vicious Cycle
Fluid Retention
Kidney Failure
The heart affects
the kidney, which
affects the heart,
which . . .
“Something goes around something, but that’s as far as I got.”
Possible pathophysiologic in cardiorenal syndrome (???)
FROM: Nat Rev Nephrol. 2013 Feb;9(2):99-111
Another way of looking at it . . . Better ??
• Cardiorenal 1 – acute ; cardiac dysf is primary
AMI, dysrhythmia, pericarditis (AKI vs Pre-renal dysf)
• Cardiorenal 2 – chronic ; cardiac dysf is primary
CMP, congenital heart dis, HTN w LVH (CKD vs Pre-renal)
• Renocardiac 3 – acute ; kidney dysf is primary
AKI, obstr, pre-renal (HTN, vol retention, CHF, symp & RAAS dysf)
• Renocardiac 4 – chronic ; kidney dysf is primary
CKD (HTN, poor vol control, anemia, vasc calcif, hyperlipidemia)
• Cardiorenal 5 – other systemic disease is primary
Amyloidosis, cirrhosis, collagen-vasc disease
Hemodynamic, renal function, plasma hormones, and body fluid compartment data
in untreated congestive heart failure.
Anand I, CJASN, Jul 2013
200% increase in
LA pressure
RV pressure
©2013 by American Society of Nephrology
Potentially Treatable “Cardiorenal” Factors
• Volume accumulation & high or low BP
• Increased RAAS w mineralo-corticoid activity
• Increased sympathetic activity
• Cardiac support – RBF delivery, Pulm HTN
• Anemia (Hgb)
• Avoiding nephrotoxicity
Diuretics (volume control)
•
•
•
•
Thiazide - HCTZ, metolazone, indapimide
Loop - furosemide, bumetanide, torsemide, ethacrynic acid
“K-sparing” - spironolactone, eplerenone, amiloride
Acetazolamide, nesiritide
Diuretic resistance limits effectiveness:
volume contraction, hypotension (decreased BP & GFR)
incr RAAS & sympath activity, renal “edema”, met alkalosis
Rx: measure PCWP (BNP) to assess impact of central volume
incr doses of loop agents  cont IV infusion
combined loop + thiazide Rx
tolvaptin, acetazolamine, +/- albumin
ULTRAFILTRATION – if all else fails, but NOT as primary Rx
** severe intrinsic parenchymal ARF/AKI w oliguria  DIALYSIS Rx**
RAAS modulation (nl or high BP)
•
•
•
•
Renin inhibitors (aliskerin)
ACE inhibitors (lisinopril)
Angiotension-receptor blockers (losartan)
Aldo-receptor blockers (spironolactone or eplerenone)
Limitations:
Hyperkalemia
Hypotension
Decreased RBF
Worse ARF/AKI
Sympathetic blockers (nl or high BP)
•
•
•
•
Beta-blockers (type, duration of action)
Alpha-blockers (for HTN control)
Combination agents (labetolol)
Other central agents (clonidine)
Limitations:
Hypotension, reduced renal perfusion
Vasodilators (periph resistance)
•
•
•
•
Calcium-channel blockers
Direct vasodilators (hydralazine, minoxidil)
Milrinone, dopamine or dobutamine
Nitrates, nitroprusside
Limitations:
Hypotension, reduced renal perfusion
Pressors, Inotropes, Hemodynamic Support
•
•
•
•
Midodrine PO
Alpha-sympathetic agents IV
Vasopressin IV
Endothelin inhibitors PO
•
•
•
•
•
•
Digoxin
Adenosine-receptor blockers (rolofylline for RBF)
Pulm arteriolar dilators (riociguat for PHT)
Calcium agonists (levosimedan as inotrope)
Erythropoietin and/or transfusion
N-acetylcysteine (as periph vasodilator)
Some “News” from Recent Literature
Comparative studies show no advantage of extracorporeal ultrafiltration vs
medical Rx (diuretic plus hemodynamic meds) for survival or further AKI (NEJM 2011)
Erythropoietin to boost Hgb in CHF does not improve survival or CHF
readmission rate, but does increase thromboembolic events by 50% (NEJM 2013)
N-acetylcysteine (for endothelial dysf) improves forearm blood flow but not
the degree of CHF or BNP level (Heart Lung Circ 2012)
BNP level predicts progression of CKD to ESRD, but nesiritide does not improve
outcome in severe CHF (Neph Dial Transpl 2012)
Vit D normalization may improve CHF (& reduce CRP), but large osteoporosis
studies do not show the same effect (Cong Ht Fail 2103; Osteopor Internat 2013)
Fatal & Non-fatal Events in ESRD ~ B Lines on US
SURVIVAL %
Zoccali et al, Clin J Amer Soc Neph, 2013
DAYS
Cardio-renal Syndrome
Limitations of Medical Rx in Cardiorenal Syndrome
•
•
•
•
•
Oliguria – refractory to diuretics, UF required
Hypotension – limits RBF and GFR pharmacoRx
Hyperkalemia – limits some medications
Uremia – ultimately requires dialysis Rx
Suitability for advanced cardiac support
Dialysis - Renal Replacement Therapy (RRT)
• Simple ultrafiltration (fluid removal) if diuretics fail
No clearance of urea, K, phos, other solutes
• Intermittent Hemodialysis for fluid & uremic s/s
Often lowers BP; intervals w fluid reaccumulation
• Continuous RRT (dialysis + hemofiltration)
Limited to ICU Rx for combined resp failure, hypotension, oliguria
• Peritoneal dialysis
Combination of ascites, low BP & poor CO, recurring CHF
• Palliative Care – when enough is enough ?
Morphine …
PD in Cardiorenal Syndrome
64 yo M, w CABD 1999, progressive CMP,
AICD Jun09, recurring hosp adm for CHF
PEA arrest Apr10 and VT w ICD shock Sep 2010
Progressive CKD, BUN 180 & creat 3.2 in Oct 2010
HD initiated w low BP and cont fluid overload (incl ascites)
PD successfully initiated, trained for home self care Dec 2010
Improved overall clinical status, control of edema & ascites
no further hosp adm for vol or CHF complications
return to part-time work & primary care of chronically ill wife
BNP 1200-3800 on HD, then 700 in 2011, 370 in 2013 on PD
Cont PD self care through Aug 2013 (PVOD, gangrene, died)
“Palliative” PD in Cardiorenal Syndrome
A 43-yr-old man with congenital heart disease and stroke, presented with
refractory CHF, low BP and renal failure (BUN 150, creat 4; both rising). He
was continuously dyspneic even when kneeling at his bedside. His sister was
his care provider and decision maker. We discussed comfort care with Hospice
support but also discussed dialysis (HD would risk hemodynamic chgs, and PD
would require home-based care). They deferred any new decision in favor of
continued supportive cardiac infusion at home.
He returned within a few days with cont’d distress and worse renal failure.
A time-limited 1-2 wk trial of PD was begun – improving his CHF so that he
could walk, sleep in bed, and function at home. He continued PD successfully
for > 14 months, eventually developing refractory arrhythmias that required
ICU treatment. When intubation became the only remaining option, his sister
chose to withdraw support and he died quietly with his sister and mother at
the beside.
In the end, Ed, most of us are carried along
by our delusions
But often we don’t have all the answers.
How many ways can you say “I don’t know” ?
“it’s a virus” “it must be genetic” “let’s see what happens”
“needs further evaluation” “several causes likely”
multifactorial idiopathic
inherent
idiosyncratic
essential
occult
primary
agnogenic cryptogenic
A Few Recent Reviews
Anand I. Cardiorenal syndrome: a cardiologist’s
perspective. Clin J Amer Soc Nephrol, Jul 2013.
House A. Cardiorenal syndrome: new developments in
understanding and pharmacology. Clin J Amer Soc
Nephrol, Aug 2013
Kim C. Cardiorenal syndrome. Electrolytes & Blood
Pressure, Jun 2013.