Treatment of Acute

Renal Failure
Bad Homburg

Treatment of ARF
Acute renal failure
Indications
Diffusion and convection
Possible treatment modes
Intermittent or continuous?
Dose of renal replacement therapy
Anticoagulation
Lactate or bicarbonate?

Patients With ARF

Specific problems
(compared to chronic renal failure)

More co-morbid conditions

More problems with hypotension
Often additional organ failures
which require, e.g.,
Mechanical ventilation,
Infusion of catecholamine's

Therapeutic consequences

Early start of therapy

Prolonged or continuous treatments
Intensified renal replacement therapy

Aetiology of Severe ARF

50

patients [%]

40
30
20
10
0

ischaemia /
low blood
pressure

sepsis

septic
shock

rhabdomyolysis

nephrotoxins

other

main cause of ARF

Severe ARF = renal replacement therapy clinically required

Sylvester W et al.
Crit Care Med 29:1910-1915, 2001

Mortality of Patients with ARF

MOF: Multi-organ failure

Liao F et al.
Kidney Int Suppl 66:S16-24, 1998

Long-term Results
After ARF Therapy
979 ICU-patients with ARF needing CRRT,
301 surviving to discharge
Questionnaire sent to surviving patients,
response rate: 89%
Survival rate

77 % surviving patients after 6 month

67 % surviving patients after 12 month
50 % surviving patients after approx. 5 years

Post discharge quality of life

Most patients self-sustaining, physically active,
and psychologically balanced

=> Effort justified!

Morgera S et al.
Am J Kidney Dis 40:275-279, 2002

Indications to Start Renal

Replacement Therapy
Absolute indications
Hyperkalemia
(> 6,5 mmol/l)
Acidosis
(pH < 7,20 7,25; BE < - 8)
Unmanageable
hypervolemia
Signs of uraemia
Pericarditis
Neurological symptoms

Relative indications
Electrolyte disturbances
Hyponatremia
Hyperkalemia

Oliguria / Anuria
Azotemia
Urea > 100 mg/dl
Fast rise of creatinine
> 100 mol/l (1 mg/dl) per day

Peritonitis
Bleeding tendency

If possible start of therapy

prior to obvious signs of uraemia!

When to start?
BUN at start > 60 mg/dl (ca. 130 mg/dl urea)
Late start, after 19,4 days of hospitalization, n=59
20.3 % survival

BUN at start < 60 mg/dl (ca. 130 mg/dl urea)

Early start, after 10.5 days of hospitalization, n=41
39.0 % survival

only patients with post-traumatic ARF

Gettings LG et al.
Intensive Care Med 25:805-813, 1999

Physical Mechanisms
Semi-permeable Membrane
A very fine sieve

Diffusion

Concentration equilibrate over time

Ultrafiltration

Filtration of Water due to a pressure gradient

Convection (solvent drag)

Solved substances are transported with the filtered water

Semi-permeable Membrane

erythrocyte,
red blood cell

water passes the

membrane easily
small molecules,
e.g. urea

large proteins,
e.g. albumin
leukocyte,
white blood cell

Cells are not drawn at scale, in fact they are

much larger than the pores.

middle molecules,
e.g. cytokines

Microscopic Structure of a
Capillary
symmetric: pore size blood side = pore size dialysate side
e.g. Cuprophan, AN69

asymmetric: pore size blood side < pore size dialysate side
e.g. Fresenius Polysulfone

Diffusion
start:

end:

different
concentrations
of solutes

time

concentrations of solutes
on both sides of the
membrane equilibrated

driving force: random movement of all molecules

(Browns molecular movement)
Note: Diffusion is faster for smaller molecules!

Question

Are we able to regulate diffusion?

We want, e.g.:
- eliminate a lot of urea from the blood
- lower plasma potassium a little bit
- keep plasma sodium approx. constant
Ho do we achieve these goals?

Renal Replacement Therapies

used with ARF
Peritoneal dialysis

e.g. small children, no vascular access

PD

CAPD

Various forms of blood purification

Dominantly used approach

Distinguished by mode of application
iHD CRRT
intermittent or continuous
Distinguished by vascular access
CAVH CVVH
arterio-venous or veno-venous
Distinguished by location of fluid application
without, pre-filter, into the filter, post-filter or combinations
SCUF Pre-dilution

CVVHD

Post-dilution

CVVHDF

Preferred Treatment
ICU vs. non-ICU

ICU

non-ICU

iHD

23%

89%

CRRT

72%

7%

5%

4%

PD

data from Madrid (Spain) 10/91-6/92

Liao F et al,
Kidney Int, 50:811-818 (1996)

CVVHD
blood inlet
arterial side

blood outlet
venous side

ultrafiltrate
+ dialysis fluid

dialysis fluid

CVVHD: continuous veno-venous haemodialysis

application of the solution within the filter
similar effectivity for small uraemic toxins (e.g. urea, potassium)
as post-dilution CVVH (if identical volumes are used)

for larger toxins (e.g. cytokines, mediators) effectivity

comparable with pre-dilution CVVH

Postdilution CVVHDF
substitution solution
blood inlet
arterial side

blood outlet
venous side

ultrafiltrate
+ dialysis fluid

dialysis fluid

CVVHDF: continuous veno-venous Haemodiafiltration

application of solution within and after the filter
enables further increase of effectivity, if the exchange volume
with post-dilution CVVH cannot (or shall not) be further
increased, e.g. because of haemoconcentration

Therapy:
Continuous or Intermittent?

continuous haemodialysis
daily, intermittent haemodialysis

CVVH Avoids Hypotensive Episodes

Ronco C et al
Kidney Int 56 [Suppl 72]: S-8-S-14, 1999

Anticoagulation with CRRT

Heparin

Standard for systemic anticoagulation

(in combination with Protamin regional anticoagulation possible, but
reduction of bleeding risk with this approach not shown)

Prostacyclin

Inhibition of platelet aggregation

Used alone or in combination with systemic anticoagulants

Danaparoid (Orgaran), Hirudin, Argatroban

Also systemic anticoagulation

Often used in patients with Heparin Induced Thrombocytopenia (HIT),
specifically type II (HIT II)

Citrate

Regional anticoagulation, established in some centres (often locally

established device combinations)

Without anticoagulation

Sometimes possible in patients with a high bleeding risk

Anticoagulation for CRRT

Unfractionated Heparin
Standard approach,
exceptions are heparin contraindications, e.g.:
heparin induced thrombocytopenia type II (HIT II)
high risk of bleeding

Anti-thrombin III required, sometimes need for substitution

Best comprise between
long filter life time and risk of bleeding
with an aPTT between 35s and 45s

Abramson S & Niles JL

Curr Opin Nephrol Hypertens 8:710-707, 1999

Target range 60-80 s

No consensus in the literature

Reeves JH et al
Crit Care Med 27:2224-2228, 1999

Recommendations for
Anticoagulation during CVVH
Standard heparin,
unfractionated

Risk of
thromboembolism

No risk

Bleeding risk

Priming with
5,000-10,000 IU/l
iv-bolus prior
to CVVH [IU/kg]

30 70

15 25

0 10

Continuous infusion
during CVVH [IU/kg/h]

10 20

5 15

5 10

Prolongation of
activated clotting time
(ACT) aimed for [%]

100

50

25

Bleeding risk: platelets < 60 G/l, aPTT > 60 s, disseminated

intravascular coagulation, or spontaneous bleeding
Priming:
anticoagulant plus saline for 15 30 min,
Kozeck-Langenecker SA
thereafter rinse with saline for 15 30 min
Anaesthetist 51:210-217, 2002

Renal Regeneration of
Bicarbonate Buffer
Metabolism

Fixed Acid

Bicarbonate

Buffer consumption
Carbonic Acid
(removed by ventilation)

Acid-anion
Buffer regeneration
Excretion of the acid-anion-

Acid-anion
(excreted in the urine; together with a cation, e.g., NH4+)

Which Buffer Base

in HF solutions?
Direct buffer base: bicarbonate

Optimal, physiological buffer

Stability of bicarbonate solutions
Potential problem: precipitations after loss of CO2
Technical solution: double chamber bag and mixing
directly before use

Indirect buffer bases: lactate, acetate, citrate

Anions of organic acids

Metabolism of these anions removes acid equivalents
Removal of acid equivalents = Conversion to bicarbonate
Metabolism requires sufficient oxygen supply
Lactate most frequently used
(high lactate levels during physical exercise physiological)

Treatment of ARF
Summary
Severely ill patients
Different renal replacement therapies possible
Transport through the membrane: Diffusion and convection
Continuous renal replacement therapies (CRRT)
Post dilution CVVHDF as generally suitable treatment mode,
other CRRT Modes for specific situations
Standard anticoagulation with heparin

Present dose recommendation: 1.5 2.5 L/h,

with severely ill patients also higher doses

Reduced hepatic function / cardiac aetiology of ARF:

Bicarbonate advantageous