RENAL REPLACEMENT THERAPY

Options of RRT:
1. Renal transplantation is the best form of RRT.
2. Dialysis; hemodialysis or peritoneal dialysis.
Conservative management esp. in very elderly patients with significant
comorbidities for whom no RRT is acceptable. It focuses on symptomatic
control and delaying the progression of disease.
The mean GFR at which RRT is initiated is 8-10 mL/min/1.73 m2.
Note that it is important to prepare these patients before starting RRT with
psychological, nursing, dietetic and medical input to help them make
difficult decisions.
Dialysis:
Definition:
It is the artificial mechanism by which fluid and toxic solutes are
removed from the circulation when the kidneys cant do so efficiently.
In all forms of dialysis the blood interfaces with an artificial solution
resembling human plasma (called the dialysate) and diffusion of fluid
and solutes occurs across a semipermeable membrane.
Settings in which dialysis is considered:
1. AKI: dialysis is required as a temporary measure until the patients
Absolute indications of renal function improves.
dialysis: AEIOU 2. CKD: dialysis serves as a bridge to renal transplantation or as a
1.Acidosis: significant permanent treatment when the patient is not a transplantation
intractable metabolic candidate.
acidosis. 3. Overdose of some medications or substances cleared by the
2.Electrolytes: severe kidneys. Dialyzable substances include salicyclic acid, lithium,
persistent hyperkalemia. ethylene glycol, magnesium containing laxatives.
Indications for dialysis:
3.Intoxication: lithium,
methanol, aspirin,
1. Nonemergent indications:
ethylene glycol Cr and BUN are not absolute indications for dialysis.
Symptoms of uremia:
4.Overload: hypervolemia
not managed by other N&V
measures. Pericarditis
Lethargy, deterioration in mental status,
5.Uremia ( severe) based
on clinical presentation not encephalopathy, seizures.
laboratory values ( uremic 2. Emergent indications:
syndrome and uremic

Life-threatening manifestations of
volume overload:
Pulmonary edema
Hypertensive emergency refractory to
antihypertensive agents
 RENAL REPLACEMENT THERAPY

Severe, refractory electrolyte

disturbances ( hyperkalemia, hypermagnesemia).

Severe metabolic acidosis

Drug toxicity/ingestion esp. in patients

with renal failure ( methanol, ethylene glycol, aspirin,
lithium).
All patients must be screened in advance for hepatitis B and C and
HIV and vaccinated against hepatitis B if they are not immune.
Hemodialysis:
Process:
The patients blood is pumped by an artificial pump outside of
the body through the dialyzer which consists of fine capillary
networks of semiperameable membrane. The dialysate flows
on the outside of these networks in the opposite direction and
the blood is always meeting a less concentrated solution and
diffusion of fluid and small solutes occurs across the
membrane down the concentration gradient. ( ultrafiltration
creates a negative transmembarne pressure and is used to
clear excess fluid)
The patients blood must be heparinized to prevent clotting in
the dialyzer.
Frequency:
Patients require 3 to 5 hours dialysis 3 days per week either
at home or in or in an outpatient dialysis unit.
The intensity and frequency of dialysis should be adjusted
to achieve urea reduction ratio over 65%.
 RENAL REPLACEMENT THERAPY

More intense dialysis: short more frequent dialysis sessions

of 2-3 hours 5-7 times per week or nocturnal dialysis ( low
blood-pump speeds and single needle dialysis are used for
approximately 8 hours overnight 5-6 times per week.
Access:
1. Arteriovenous fistula: is the best form permanent
dialysis access.
It requires vascular surgery to connect the radial or
brachial artery to cephalic veins in the forearm. An
audible bruit over the fistula indicates that it is patent. It
should be done up to a year before dialysis is
contemplated. After 4-6 weeks increased pressure
transmitted from the artery to the vein via the fistula
causes distension and thickening of the vessel wall
(arterialisation).then large bore needles can be inserted
into the veins to provide access for each hemodialysis
treatment.
2. Implantable graft made of PTFE polytetrafluoroethylene
is an alterantive to AV fistula. Done of the patient has
small veins.
A graft does not need to develop as a fistula does, so a
graft can sometimes be used as soon as 1 week after
placement. An AV graft is more likely to have problems
with infection and blood clots. The repeated formation of
blood clots can block the flow of blood through the AV
graft and make it hard or impossible to do the
hemodialysis treatment.
3. Central venous catheter in the jugular vein for
temporary access. The catheter can be tunneled; placed
under the skin to lower the rate of infection and these
are suitable for use up to 6 months.
Note that subclavian lines are avoided where possible as
thromboses or stenosis here will compromise the ability
to form a functioning fistula in the arm.
Alternative to traditional hemodialysis:
o Continuous arteriovenous hemodialysis CAVHD and
continuous venovenous hemodialysis CVVHD.
o Used in hempdynamically unstable patients such as
ICU patients with AKI; run 12-24 hours.
o Lower flow rate of blood and dialysate enable dialysis
to occur while minimizing rapid shifts in volume and
osmolality.
o CAVHD: blood is taken from the artery ( femoral
artery) and returned to patients vein ( systemic blood
pressure propels the blood).
 RENAL REPLACEMENT THERAPY

o CVVHD: blood is taken from the vein and returned to

the same vein; pump with adjusted flow rate is
needed to propel the blood.
Advantages of hemodialysis:
1. It is more efficient than peritoneal dialysis; high flow
rates and efficient dialyzers shorten the period of time
required for hemodialysis.
2. It can be initiated more quickly than peritoneal dialysis
using temporary vascular access in emergency setting.
Disadvantages:
1. Requires vascular access.
2. It is less similar to the physiology of natural kidney
function than in peritoneal dialysis; predisposing the
patient to the following:
o Hypotension due to rapid removal of intravascular
volume leading to rapid shifts from extravascular
space into cells.
o Hypo-osmolality due to solute removal.

Complications of hemodialysis:

Problem Clinical features Cause Treatment

Hypotension during Sudden drop in BP, Fluid removal and Saline infusion,
dialysis fatigue,often leg hypovolemia exclude cardiac
cramps, sometimes ischemia, quinine
chest pain may help cramps.
(myocardial
ischemia).
Dialysis N&V, headache, and -Stop HD and treat
disequilibrium rarely seizures or Cerebral edema seizures if present.
syndrome (rare) coma. resulting from urea -Prevention: IV
removal from the mannitol 20% at 50
blood more rapidly ml/hr with
than from the CSF intravenous
and brain tissue diazepam- simplest
generating a urea way to prevent DDS
osmotic gradient in high risk patients.*
responsible for water
 RENAL REPLACEMENT THERAPY

moving into brain

cells. (relative hypo-
osmolality of ECF
compared with the
brain).

First use syndrome Chest pain, back allergic reaction to Stop dialysis and
(Dialyzer pain, and dialysis membrane or change to a different
hypersensitivity) rare anaphylaxis and sterilisant artificial kidney.
but severe acute circulatory
complication collapse occurring
immediately after
the patient uses a
new dialysis
machine.
Hemorrhage Blood loss (occult or Anticoagulation Stop dialysis, seek
overt) ; hypotension therapy ( can cause the source of
hematoma as well) bleeding and
Venous needle consider heparin-free
disconnection treatment.
Air embolism Circulatory collapse; Disconnected or Stop dialysis
cardiac arrest faulty lines and
equipment
malfunction.
Cardiac arrhythmias Hypotension, Potassium and acid Check potassium and
sometimes chest base shifts arterial blood gases;
pain review dialysis
prescription, stop
dialysis.
Between treatment; Ultrafiltration+/-
Pulmonary edema Breathlessness Fluid overload dialysis

Vascular access site Rigors, fever, Usually involves Blood cultures and
infection and hypotension vascular access antibiotics
possible sepsis devices ( catheter or
fistula)
Long-term A traid of carpal gradual Renal transplantation
complication tunnel syndrome, accumulation is the treatment of
Hemodialysis shoulder pain, and of 2 microglobulin, choice.
associated flexor tenosynovitis a serum protein, in Symptomatic
amyloidosis in the hand. After 5 the blood because it treatment (as in
years on HD is unable to cross the rheumatology ya
dialysis filter. It know ;P)
accumulates in
bones and joints.

Vascular access problems:
- AV fistula: thrombosis, stenosis, steal syndrome
- Tunneled venous access line: infection, blockage, recirculatoon of blood.
DDS: most commonly occurs in:
First few dialysis sessions
Elderly and pediatric
patients
Patients with pre-existing
CNS lesions (recent
stroke, head trauma) or
conditions characterized
by cerebral edema
(malignant hypertension,
hyponatremia, hepatic
Problem
Peritonitis
Catheter exit site infection
Peritoneal membrane
failure over time
RENAL REPLACEMENT THERAPY
Peritoneal dialysis:
Process:
The peritoneal membrane acts as dialysis membrane.
Dialysate fluid in infused into the peritoneal cavity, then
fluids and solutes from the peritoneal capillaries diffuse into
the dialysate fluid which is drained from the abdomen.
Ultrafiltration can be achieved by adding osmotic agents
such as glucose and water is removed from the blood via
osmosis.
Frequency:
Dialysate fluid is drained every and replaced every hour in
acute peritoneal dialysis but only once every 4 to 8 hours in
continuous ambulatory peritoneal dialysis CAPD.
Access :
o With CAPD, dialysate is infused into the peritoneal
fluid via an implanted catheter.
o A temporary catheter is used for acute peritoneal
dialysis.
Advantages:
1. The patients can learn to perform dialysis on their own.
2. It mimics the physiology of normal kidney function more
closely than hemodialysis in that it is more continuous.
Disadvantages:
1. Peritonitis is a significant complication.
2. High glucose may lead to hyperglycemia and
hypertriglyceridemia.
3. The patient must be highly self motivated to self-
administer it.
4. Cosmetic- there is increased abdominal girth due to
dialysate fluid.
Complications:
Clinical features Cause Treatment
Fever, abdominal pain and Usually enetry of skin Culture of peritoneal
cloudy peritoneal fluid contaminants via the dialysate fluid,
drainage is a key sign/ catheter; bowel organisms intraperitoneal antibiotics
systemic sepsis are less common (tobramycin, vancomycin)
Catheter removal
sometimes required
Erythema and pus around Usually skin organisms Antibiotics; sometimes
the exit site surgical drainage
Inadequate clearance of Scaring/ damage to Switch to other forms of
urea etc. peritoneal membrane RRT
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Ultrafiltration failure Fluid overload Damage to peritoneal Replace glucose with

membrane leading to rapid synthetic poorly absorbed
transport of glucose and polymers for some
loss of osmotic gradient exchanges (icodextrin)
Sclerosing peritonitis Intermittent bowel Unknown; typically occurs Switch to HD ( may still
obstruction and after many years progress ) surgery and
malnutrition tamoxifen may be used
Increased risk of Abdominal and inguinal hernia due to elevated intra-abdominal pressure.

Hyperglycemia esp. in diabetic patients

Limitations of dialysis:
Dialysis doesnt replace the kidneys synthetic function therefore dialysis
patients are still prone to erythropoietin and VitD deficiency and their
associated complications.

Complications of RRT:
1. Annual mortality is 20% mostly due to cardiovascular disease; MI and CVA
are more common in dialysis patients due to combination of HTN and
calcium/phosphate dysregulation.
 RENAL REPLACEMENT THERAPY

2. Protein-calorie malnutrition common in HD and associated with high

mortality and morbidity.
3. Renal bone disease ( see limitations)
4. Infections due to uremia and sepsis related mortality.
5. Amyloid accumulation in long term dialysis may acsue carpal tunnel
syndrome, arthralgia and fractures.
6. Malignancy

Stopping dialysis: due to its

effect on quality of life
8-20% mortality in dialysis patients is due to its withdrawal.

Renal transplantation:
It is the treatment of choice for ESRF. However, it is a major surgery with
long-term immunosupression and number of complications.
The patient must be physically and psychologically suitable for a
transplant.
Anesthetic assessment is key along with investigations of others systems
( cardiac testing, lung function testing.)

Absolute contraindications:
1. Active infection
2. Active malignancy: a period of at least 2 years of complete remission
recommended for most tumors.
3. Severe heart disease
4. Severe occlusive aorto-iliac vascular disease.
5. Active vasculitis or recent anti-GBM disease.

Relative contraindications:
1. Age: transplants are not routinely offered to very young children (
1 year) or older people 75 years.
2. High risk of disease recurrence in the transplant kidney.
3. Disease of the lower UT
 RENAL REPLACEMENT THERAPY

4. Significant co-morbidities.

Types of graft:
1. Donor after cardiac death DCD:
Patients who dont meet the criteria for brainstem death.
Retrieval of organs only begins after when cardiac output has
ceased.
Disadvanage: high risk of delayed graft function ( see the
complications) due to long warm ischemic time.
2. Donor after brainstem death DBD:
Patients who meet the criteria for brainstem death and
therefore remain on cardio-respiratory support for retrieval.
Much reduced risk of delayed graft function.
3. Living donor grafts LD:
Better outcomes
Can be related or unrelated.
All live donor transplants must be assessed by an
Independence Assessor from the Human tissue authority before
permission can be given to the surgical center to go ahead with
the transplantation. For all donors this involves a psychological
assessment ensuring they understand the risks of
transplantation.

Immunosuppressi
on:
1. Induction: conventional induction with anti-IL2R monoclonal
antibody basiliximab. Many centers are now using alemtuzumab
(Campath) which provides broad immunosuppression and allows a
steroid free maintenance regimen ( particularly useful in diabetics).
2. Maintenance: triple therapy with:
Calcineurin inhibitos(tacrolimus) or cyclosporine
Antimetabolite: azathioprine or mycophenolate
 RENAL REPLACEMENT THERAPY

Prednisolone

Complications:
1. Surgical: bleeding, infection, urinary leaks, lymphocele, hernia.
2. Delayed graft function (40% of grafts): ATN in graft due to ischemia-
reperfusion injury.
3. Drug toxicity:
Calcineurin inhibitirs: neurologic SE; tremor and confusion
New onset diabetes after transplant NODAT
Ciclosporin: gum hypertrophy and hirsutism
Antimetabolites: agranulocytosis and hepatitis
Corticosteroids: weight gain, HTN, osteoporosis, skin striae,
diabetes
4. Infections: increased risk of all infection esp. opportunistic and viral
infections due to poor T cell response ( HSV, CMP, candida,
Pneumocystis Jiroverci)
5. Malignancy:
5-fold increased risk of cancer with immunosuppression
Esp. skin and viral associated cancers.
Women should have regular cervical smears
EBV associated post-transplant lymphoproliferative disorder is
particularly problematic.
6. Cardiovascular diseases: are the leading casue of death in
transplant patients
HTN develops in more than 50% of grafts due to donor
vascular disease in the graft plus immunosupression.
7. Rejection:
Clinical staging of rejection:
1. Hyperacute rejection: occurs within minutes to hours of
transplantation via humeral mediated mechanisms. The
recipient has pre-existing antibodies against the graft ( from
prior blood transfusion, multiple pregnancies, prior transplant.
 RENAL REPLACEMENT THERAPY

Ab-Ag complex activate the complement system causing

thrombosis of the capillaries which destroy the vascularization of
the graft.
2. Acute rejection: in the first 6 months after transplantation
Could be:
Acute cellular rejection: the donor lymphocytes (dendritic
cells)enter the circulation and act as antigen presenting cells
and activate the lymphocytes of the recipient. This type is
more common.
Acute humeral rejection: developmet of anti-donor antibodies
after transplantation.
Treatment for acute rejection is high dose IV
methylprednisolone and intensification of
immunosuppression.
3. Chronic allograft nephropathy:
Occurs months to years after transplantation
Chronic low grade antibody response + vascular changes +CNIs
Manifest as scaring and fibrosis
Generally doesnt respond to treatment but sometimes
Prognosis: progression can be slowed by switching CNIs to sirolimus.
factors increase the risk of chronic rejection :
1 year graft survival 1.Previous episode of acute rejection
2. Inadequate immunosuppression
- DCD : 91%- 96 3. Initial delayed graft function
- LD: 96-99% 4. Donor-related factors (eg, old age, hypertension)
5. Reperfusion injury to organ
10 year survival
6. Long cold ischemia time
7. Recipient-related factors (eg, diabetes,
- DCD: 60%
- LD: 80% hypertension, hyperlipidemia)
8. Posttransplant infection (eg, cytomegalovirus [CMV].