Cardiorenal syndrome: therapeutic

approaches-Ultrafiltration

Dr Pascaline ALIX Université Claude Bernard Lyon 1

Néphrologie-Hôpital E. Herriot Lyon, FRANCE

Heart failure

• Despite modern heart failure therapy, the prognosis of patients with heart failure remains poor

• Prevalence of chronic kidney disease : 32% • Worsening renal function and mortality

Damman et al, 2013 Mahon et al, 2002

Renal function

Estimated measure (MRDR, CKD-EPI)

Cystatine C +++

Bock, Circulation 2010

Ultrafiltration Type 1 cardiorenal syndrome

Isolated ultrafiltration

Isotonic ultrafiltrat

HEMOCONCENTRATION

ULTRAFILTRATION

ENTRY

EXIT

FILTER

Hydrostatic pressure gradient

Interstitial sector

UNLOAD study

CARRESS-HF study

Bart N Engl J Med. 2012

Ultrafiltration group

• Stop loop diuretics • UF 200 ml/h • The addition of intravenous vasodilators

or positive inotropic agents after randomization was prohibited

Change in creatinine

Change in weight

Cardiorenal outcomes after slow continuous ultrafiltration therapy in refractory patients with advanced decompensated heart failure.

- high incidence of subsequent transition to renal replacement therapy

- high incidence in-hospital mortality Patarroyo, JACC 2012

Continuous Ultrafiltration for Congestive

Heart Failure

Patients with congestive HF randomized to receive standard medical therapy or ultrafiltration - a lower incidence of rehospitalizations in the ultrafiltration

group - more stable renal function, unchanged furosemide dose,

and lower B-type natriuretic peptide levels - At 1 year, 7 deaths (30%) occurred in the ultrafiltration

group and 11 (44%) in the control group

Marenzi et al, JCF, 2014

Avoid trial

Chronic cardiorenal syndrom and Ultrafiltration

Peritoneal dialysis

Cicatrisation = 10-15 days Ascites delayed healing infection Anticoagulant Bleeding

Peritoneal dialysis

Ultrafiltration

Osmotic agents - Crystalloid agent - Colloid agent

Peritoneal cavity Capillary lumen Capillary lumen Peritoneal cavity

Ambulatory PD Automated PD

Ultrafiltration

Intrapéritoneal volume

Time (h) 0 2h 4h

« iso » 2liters

6h 8h

« hyper »

Blood P 148 urif 2010;30:146–152 European Journal of Heart Failure (2012) 14, 530–539 European Journal of Heart Failure (2012) 14, 540–548

• Hospitalizations Before: 3,3 ±2,6 days/patient/month After: 0,3 ±0,5 days/patient/month

Hemodialysis

HEMODIALYSE

HEMOFILTRATION

Environ 10 litres par séances

Hémodialyse • HD > PD • Retrospective study

Sens, Kidney Int. 2011

Experience in LYON

Cohorte Lyon-CARE

Nephrologists and cardiologists

Standardized evaluation

Information: prognosis, therapeutics and levels of evidence

Shared medical decision

Longitudinal follow-up

Lost n=3

Severe heart failure and kidney failure 112 patients

Inclusion criterias: -≥ 2 cardiac decompensations/year

and/or chronic congestion -Furosemide ≥ 250mg 23 patients exclus 89 included patients

86 analyzed patients

Medical treatment without UF

n=54

Information and multidisciplinary approach

UF n=32

Hemodialysis n=19

Peritoneal dialysis n=13

Cohorte Lyon-CARE :

0%

20%

40%

60%

80%

NYHA III-IV (%)

All Medical ttt HD PD 0

10

20

30

40

DFG estimé (ml/min/1,73m2)

All Medical ttt HD PD

Cohorte Lyon-CARE

Medical treatment Hemodialysis Peritoneal dialysis

Cohorte Lyon-CARE

All Medical ttt HD PD (n=86) (n=54) (n=19) (n=13)

CHARACTERISTICS Age (years) 66,3±12,6 66,4±13,7 64,1 (12,1) 68,9 (7,6) Male, n (%) 58 (67,4) 36 (66,6) 14(73,7) 8(61,5) Type 2 diabetes, n (%) 39 (45,3) 25 (46,3) 10 (52,6) 4 (30,7) Hypertension, n (%) 44 (51,1) 31 (57,4) 8 (42,1) 5 (38,5) CARDIAC FUNCTION Decompensation/year 3 ± 1,1 3 ± 1 3,2 ± 1,2 2,8 ± 1,2 FEVG<40%, n (%) 44 (51,2) 28(51,8) 10 (52,6) 6 (46,1) TAPSE (mm) 15,6 ± 5,9 15,6 ± 5,4 16,1 (6) 15,2 (8,3) IC (L/min/1,73m²) 2,1 ± 0,8 1,9 ± 0,8 2,1(0,7) 2,5 (0,8) PAPS (mmHg) 52,9 ± 14,8 50,7 ± 15,9 54,1 (13,7) 53,7 (11,5)

TREATMENT Furosemide/24h (mg) 531 ± 384 488 ± 358 690 ± 430 479 ± 390 Bitherapy diurétics, n (%) 72 (83,7) 47(87) 13(68,4) 12(92,3) Beta blokers, n (%) 58 (67,4) 36(66,6) 11(57,9) 11(84,6) IEC/ARA2, n (%) 47 (54,6) 33(61,1) 6(31,6) 8(61,5)

Cohorte Lyon-CARE

Ultrafiltration versus medical therapies in the

management of cardiorenal syndrome • Prospective, controlled, open, randomized,

multicentric trial • Primary outcome measure: death and/or

unscheduled hospitalizations • Secondary outcomes measures:

– Survival – Hospitalizations for acute decompensated heart

failure – Evolution to end stage renal disease – Cardiac parameters – Safety – Quality of life

UF-CARE

• Ultrafiltration – Peritoneal dialysis – Hemodialysis – Isolated ultrafiltration

• Enhanced medical treatment

UF-CARE • Inclusion criterias

– Severe heart failure with recurring congestive symptoms and at least one the following criteria :

• At least 2 hospitalizations during the 12 months before the inclusion, whose the latest one was in the 6 months before the inclusion

• Persistent congestive symptoms throughout 30 days before the randomization: dyspnea (class III or IV NYHA), lower limbs edema and/or ascites.

– Diuretic treatment with at least 250mg furosemide per day (or 6mg bumetamide per day)

– Cardiac medical treatment enhanced by the European cardiology society guidance (except intolerance, and/or contraindication)

– Non end stage kidney disease or kidney failure : estimated DFG (CKD-Epi formula) between 20 and 60 mL/min/1.73m² (or DFG estimated between 60 and 90 mL/min/1.73m² with proteinuria and/or hematuria) and urea rate under 50 mmol/L

Acknowledgments

• Dr Florence SENS • Dr Eric POULIQUEN • Pr Laurent JUILLARD • Pr Eric BONNEFOY