Hemodialysis in AKI

Dr. Sherif M. Shaaban

Specialist, internal medicine

and nephrology

Port Fouad General Hospital

Hemodialysis

A form of renal replacement therapy (RRT).

An extracorporeal therapy that is prescribed to reduce the

signs and symptoms of uremia and to replace partially a

number of key functions of the kidneys when kidney

function is no longer sufficient to maintain the patient well-

being or life.

Other forms of RRT include peritoneal dialysis (PD) and renal

transplantation (RTx).

Functions Of The Kidneys

Maintenance of body composition: regulation of body fluid

volume, osmolality, acidity, electrolyte content (sodium,

potassium, magnesium, chloride, phosphate, calcium), and

concentration.

Excretion of metabolic end-products and foreign

substances: most notably urea, some toxins and drugs.

Production and secretion of enzymes and hormones: renin,

erythropoietin, 1,25 (OH)2 D3.

Metabolic functions: elimination of insulin, gluconeogenesis.

Dialysis

Dialysis is a process whereby the solute composition of a

solute A, is altered by exposing solute A to a second solute,

B, through a semi-permeable membrane.

Dialysis

Water molecules and low-molecular-weight solutes in the

two solutions can pass through the membrane pores and

intermingle, but larger solutes (such as proteins) cannot

pass through the semi-permeable barrier, and the

quantities of high-molecular-weight molecules on either

side of the membrane will remain unchanged.

Mechanisms of solute transport

Convection

(ultrafiltration; UF)

Diffusion

Diffusion

Due to random molecular motion.

The larger the molecular weight of a solute, the

slower will be its rate of transport through a semi-

permeable membrane even if they fit into the

ports of the membrane, and vice versa.

Convection (UF)

Occurs when water driven by hydrostatic or osmotic force

is pushed through the membrane.

Solutes that can pass easily through the membrane pores

are swept along with the water (i.e., solvent drag).

The water being pushed through the membrane is

accompanied by such solutes at close to their original

concentrations.

Hemodialysis Apparatus

Blood circuit.

Dialysis solution circuit.

Both meet at the dialyzer.

Blood Circuit

Begins at the vascular access.

Blood is pumped from the access through the ‘arterial

blood line’ into the dialyzer.

Blood is returned from the dialyzer to the patient via a

‘venous blood line’.

Various chambers, side ports, and monitors are connected

to the inflow and outflow blood lines. They are used to

infuse heparin or saline, measure pressures and detect the

presence of air.

Blood Circuit

Blood is moved through the dialyzer by a spring-loaded

roller pump which moves blood by totally occluding a

segment of the tubing then rolling the occluded

segment forwards (like milking a straw).

The blood flow through the dialyzer is a function of the

roller pump rotation rate and the diameter and the

length of the blood line roller pump segment.

Dialysis Solution Circuit

Includes the dialysis solution

(dialysate) supply system,

which makes dialysate by

online mixing of treated

water with concentrated

dialysis solutions.

The final dialysate is pumped

through the dialysate

compartment of the

dialyzer.

Dialysis Solution Circuit

The dialysis solution circuit includes various

monitors that ensure that the dialysate has the

right temperature ad a safe concentration of

dissolved components.

A blood leak detector ensures detection of blood

products in the outflow dialysate.

Dialyzer

Is where the blood

and dialysis fluid

interact and where

the movement of the

molecules between

dialysis solution and

blood across a semi-

permeable

membrane occurs.

Dialyzer Efficiency and Flux

The ability of the dialyzer to remove small-

molecular-weight solutes is a function of its

surface area multiplied by the permeability of the

membrane to urea.

Dialyzer Efficiency

A high efficiency dialyzer is a dialyzer with a large

surface area that has a high ability to remove

urea.

High-efficiency dialyzers have large or small pores

and thus can either have a high or low clearance

of large-molecular-weight molecules such as B2-

microglobulin and Vitamin B12.

Dialyzer Flux

High-flux dialyzers are those with large pores that

allow larger molecules, e.g., B2 microglobulin, to

pass through.

High-flux membranes also have high water

permeability.

Vascular Access In the acute setting, venous catheters are commonly used in

the following situations:

1. AKI

2. HD or hemoperfusion for overdose or toxication.

3. Late stage CKD patients requiring urgent dialysis.

4. ESRD patients who don’t have vascular access or who have

lost their permanent access (e.g., infection, thrombosis).

5. RTx patients who need temporary HD during episodes of

rejection.

6. PD patients in episodes of peritonitis.

7. HF

Types of catheter types

1. Uncuffed

2. Cuffed

Selected factors favoring different temporary

(non-tunneled) hemodialysis catheterinsertion sites

E G Clark,J H Barsuk. Temporary hemodialysis catheters: recent advances. Kidney International (2014) 86, 888–895; doi:10.1038/ki.2014.162

Anticoagulation

Exposure of blood to tubing, dialyzer, drip chambers and air

predisposes to clotting.

Thrombosis may cause occlusion or malfunction of the

extracorporeal circuit, causing loss of dialyzer and tubing as

well as 100 – 180 ml of blood.

Heparin is the most common anticoagulant used. LMWH is

also used.

Heparin-free dialysis in patients with high risk of bleeding

e.g., AKI patients.

AKI: Classification

AKI: Classification Over the last few decades, more than 35 different

definitions have been used to define acute kidney injury(AKI). Many of those definitions were complex.

The more commonly used were based on urine output (UO)

and/or serum creatinine (SCr) criteria.

An increase in basal SCr of at least 0.5 mg/dL, a decrease

in Cr clearance of at least 50% or the need for renal

replacement therapy (RRT) were the most frequent

definitions used for AKI in clinical practice.

Where UO has been used to define AKI, it is generally

considered that a value less than 400–500 mL/day could bean indicator.

J A Lopez, S Jorge. The RIFLE and AKIN classifications for acute kidney injury: a critical and comprehensive review. Clin Kidney J (2013) 6 (1): 8:14.

AKI: Classification

RIFLE (Risk, Injury, Failure, Loss of kidney function, and

End-stage kidney disease) classification for AKI

definition emerged, which was published in May

2004 in Critical Care.

eGFR

RIFLE classification: Strengths

Largely validated in terms of determining the

incidence of AKI and its prognostic stratification in

several settings of hospitalized patients.

Facilitated the identification of a large proportion of

AKI patients.

An independent and stepwise increase in mortality as

AKI severity increased.

RIFLE classification: Strengths

Enables monitoring of the progression of AKI

severity during hospitalization. RIFLE classes are

strongly associated with increased lengths of stay,

RRT requirement, renal function recovery and

discharge from hospital to a care facility.

RIFLE classification: Limitations

Baseline SCr is necessary to define and classify AKI; this

baseline value is frequently unknown in clinical practice.

In this situation, the ADQI work group propose estimating

the baseline SCr using the MDRD equation, assuming a

baseline GFR of 75 mL/min/1.73m2.

In CKD patients, baseline SCr determined assuming a GFR

of 75 mL/min/1.73m2 has a low correlation with the real

value of SCr and results in an overestimation of AKI

incidence.

RIFLE classification: Limitations

The MDRD formula has been validated in CKD

patients with stable renal function, not in AKI

patients.

RIFLE classification: LimitationsSCrDetermination of renal function using SCr has

several other limitations:

S.Cr is influenced by multiple factors, namely

age, gender, diet, and muscle mass;

10 to 40% of Cr elimination is performed bytubular secretion and this mechanism is amplified

as the GFR diminishes, thus, overestimating renal

function in AKI patients;

many medications inhibit tubular secretion of Cr

(i.e. trimethoprim, cimetidine), causing a

temporary increase in SCr;

RIFLE classification: LimitationsSCr

various factors can interfere with SCr

determination (i.e. acetoacetate accumulated in

diabetic ketoacidosis can interfere with the

alkaline picrate method), causing a false

elevation in SCr.

Cr is a marker of renal function, and not of renal

lesion.

RIFLE classification: Limitations UO

Decrease in the UO is sensitive and frequent in AKI;

however, it also has some important limitations indefining and staging AKI:

Sensitivity and specificity of UO can be

significantly changed by the use of diuretics, andthis issue is not specifically considered in the RIFLE

classification;

the UO can only be determined in patients with abladder catheter in place, which, despite being

common in ICU patients, is not frequent in otherhospitalized patients;

RIFLE classification: LimitationsUO

It is possible that the predictive ability of UO could

be inferior to that of SCr, which can explain the

difference in terms of mortality between the same

classes defined by each one of those criteria,

observed in studies that utilized both criteria to

define and classify AKI.

RIFLE classification: Limitations

The aetiology of AKI and the requirement for RRT

are not considered in the RIFLE classification.

AKIN Classification

Published in March 2007 in Critical Care.

It is a later version of the RIFLE classification with some

modifications:

the diagnosis of AKI is only considered after achieving an

adequate status of hydration and after excluding urinary

obstruction;

only relies on SCr and not on GFR changes;

baseline SCr is not necessary, and

it requires at least two values of SCr obtained within a periodof 48 h.

AKIN Classification

These modifications were based on the cumulative

evidence that even small increases in SCr are associated

with a poor outcome

The advantages of the RIFLE modifications have not

been proven.

In fact, the AKIN classification compared with the RIFLE

classification did not exhibit a better prognostic acuity in

terms of in-hospital mortality, although it enabled the

identification of more AKI patients.

RRT in AKI

Early detection and accurate prediction of

patients that ultimately will require RRT may allow

earlier initiation in those who need it and, at the

same time, prevent harm in those who do not.

RRT in AKI

The optimal timing of dialysis for AKI is not defined.

In current practice, the decision to start RRT is based most

often on clinical features of volume overload and

biochemical features of solute imbalance (azotemia,

hyperkalemia, severe acidosis).

However, in the absence of these factors there is

generally a tendency to avoid dialysis as long as

possible, a thought process that reflects the decisions

made for patients with CKD Stage 5.

RRT in AKI

Clinicians tend to delay RRT

when they suspect that patients may recover on their own,

and

because of concern for the well-known risks associated with

the RRT procedure, including hypotension, arrhythmia,

membrane bio-incompatibility, and complications of vascular

access and anticoagulant administration.

RRT in AKI

There is also some concern that RRT may compromise

recovery of renal function, and increase the progression of

CKD. Whether these risks outweigh the potential benefits of

earlier initiation of RRT is still unclear.

Palevsky PM, Baldwin I, Davenport A, et al. Renal replacement therapy and

the kidney: minimizing the impact of renal replacement therapy on recovery

of acute renal failure. Curr Opin Crit Care 2005; 11: 548–554.

RRT in AKI

The treatment of AKI with RRT has the following goals:

i) to maintain fluid and electrolyte, acid-base,and solute homeostasis;

ii) to prevent further insults to the kidney;

iii) to permit renal recovery; and

iv) to allow other supportive measures (e.g.,

antibiotics, nutrition support) to proceed withoutlimitation or complication.

RRT in AKI

5.1.1: Initiate RRT emergently when life-threatening

changes in fluid, electrolyte, and acid-base balance

exist. (Not Graded).

5.1.2: Consider the broader clinical context, the

presence of conditions that can be modified with RRT,

and trends of laboratory tests—rather than single BUN

and creatinine thresholds alone—when making the

decision to start RRT. (Not Graded)

RRT in AKI

While no RCTs exist for dialysis for life-threatening

indications, it is widely accepted that patients with

severe hyperkalemia, severe acidosis, pulmonary

edema, and uremic complications should be dialyzed

emergently.

Timing

Only one RCT has evaluated the effect of timing of

initiation of RRT on outcome. Bouman et al. randomized

106 critically ill patients with AKI to early vs. late initiation

of RRT.

The early initiation group started RRT within 12 hours of

oliguria (<30 ml/h for 6 hours, not responding to diuretics or

hemodynamic optimization), or CrCl<20 ml/min.

The late-initiation group started RRT when classic

indications were met.

Timing

The study did not find differences in ICU or hospital

mortality, or in renal recovery among survivors, but was

clearly too small to allow for definitive conclusions.

Timing The remaining data come from observational studies.

A prospective multicenter observational cohort study

performed by the Program to Improve Care in Acute

Renal Disease (PICARD) analyzed dialysis initiation—as

inferred by BUN concentration—in 243 patients from five

geographically and ethnically diverse clinical sites.

Adjusting for age, hepatic failure, sepsis,

thrombocytopenia, and SCr, and stratified by site and

initial dialysis modality, initiation of RRT at higher BUN (>76

mg/dl) was associated with an increased risk of death (RR

1.85; 95% CI 1.16–2.96).

Timing

The most recent study on this subject is the analysis of

surgical ICU patients with AKI, showing that late

initiation of RRT (defined as RIFLE-I or -F) was an

independent predictor of mortality (HR 1.846; CI 1.07–

3.18).

Shiao CC, Wu VC, Li WY, et al. Late initiation of renal replacementtherapy is associated with worse outcomes in acute kidney injuryafter major abdominal surgery. Crit Care 2009; 13: R171.

Metabolic Acidosis and RRT

Metabolic acidosis is a frequent clinical problem

in patients with severe AKI.

Metabolic acidosis associated with AKI can

usually be corrected with bicarbonate and should

rarely require urgent dialysis if not accompanied

by volume overload or uremia.

Gauthier PM, Szerlip HM. Metabolic acidosis in the intensive care unit. Crit Care Clin 2002; 18: 289–308.

Metabolic Acidosis and RRT

As the pH and bicarbonate values to initiate dialysis for

metabolic acidosis are not supported by evidence, no

standard criteria for initiating dialysis for acidosis exist.

A variety of poisons, drug overdoses, and toxic

compounds (e.g., salicylates, ethylene glycol,

methanol, metformin) can contribute to acid-base

problems and also lead to AKI. In these circumstances,

RRT may also facilitate removal of the offending drug.

Fluid overload

There is increasing evidence that fluid overload in critical

illness and AKI is associated with adverse outcomes.

Data from the PICARD group examining 396 ICU patients

with AKI requiring RRT further supports these findings.

Survivors had lower fluid accumulation at dialysis initiation

compared to non-survivors (8.8% vs. 14.2% of baseline body

weight. The adjusted OR for death associated with fluid

overload at dialysis initiation was 2.07 (95% CI 1.27–3.37).

These data suggest that fluid overload should be further

evaluated as parameter to guide the initiation of RRT.

Other factors that might influence the decision of

when to start RRT are:

• the severity of the underlying disease (affecting the

likelihood of recovery of kidney function),

• the degree of dysfunction in other organs (affecting the

tolerance to e.g., fluid overload),

• the prevalent or expected solute burden (e.g., in tumor lysis

syndrome), and

• the need for fluid input related to nutrition or drug therapy .

Dialysis As A Form Of Renal Support

It may be more appropriate to consider dialytic

intervention in the ICU patient as a form of renal

support rather than renal replacement.

For instance, massive volume overload resulting from

volume resuscitation may be an indication for RRT

even in the absence of significant elevations in BUN

or SCr.

Thank You