Chronic Renal Failure

And
Replacement Therapy
Dr. May Honey Ohn
Emergency Physician
Senior Lecturer
UMS
 Functions of Kidney
• Excretion of nitrogenous wastes urea, from protein catabolism, and uric
acid, from nucleic acid metabolism.
• Acid-base homeostasis by reabsorbing bicarbonate from and to excrete
hydrogen ions into urine
• Osmolality regulation: The antidiuretic hormone (ADH) secreted from
the posterior pituitary gland, binds to principal cells in the collecting duct
of kidney resulting in water reabsorption and concentrated urine
formation.
• Blood pressure regulation by Renin-angiotensin system
• Hormone secretion, including erythropoietin and renin. Erythropoietin
stimulates erythropoiesis (production of red blood cells) in the bone
marrow.
• Calcitriol is produced in the cells of the proximal tubule of the nephron
by conversion of 25-hydroxycholecalciferol by 1-alpha-hydroxylase
enzyme into 1,25-Dihydroxycholecalciferol. This Calcitriol is important
control point in Ca2+ homeostasis.
• Calcitriol, the activated form of vitamin D (1,25-
Dihydroxycholecalciferol), promotes intestinal absorption of calcium and
the renal reabsorption of phosphate--
CRF
 Chronic kidney disease/chronic renal failure
• Chronic kidney disease (CKD) refers to an
irreversible deterioration in renal function
which classically develops > 3 months
• Initially, it is manifest only as a biochemical
abnormality. Eventually, loss of the excretory,
metabolic and endocrine functions of the
kidney leads to clinical symptoms and signs
of renal failure, which are referred to as
uraemia.
 The stages of Chronic Kidney Disease
Stage 1
• Slightly diminished function; Kidney damage with normal or
relatively high GFR (≥90 mL/min/1.73 m2)
Stage 2
• Mild reduction in GFR (60-89 mL/min/1.73 m2) with kidney
damage
Stage 3-azotemic stage
• Moderate reduction in GFR (30-59 mL/min/1.73 m2).British
guidelines distinguish between stage 3A (GFR 45-59) and
stage 3B (GFR 30-44) for purposes of screening and referral.
Stage 4-uremic stage
• Severe reduction in GFR (15-29 mL/min/1.73
m2).Preparation for renal replacement therapy
Stage 5
• Established kidney failure (GFR <15 mL/min/1.73 m2, or
permanent renal replacement therapy (RRT)
 The stages of Chronic Kidney Disease
• All individuals with a Glomerular filtration rate (GFR) <60
mL/min/1.73 m2 for 3 months are classified as having chronic
kidney disease, irrespective of the presence or absence of kidney
damage.
• All individuals with kidney damage are classified as having chronic
kidney disease, irrespective of the level of GFR. Kidney damage is
defined as pathologic abnormalities or markers of damage,
including abnormalities in blood or urine test or imaging studies.
• The loss of protein in the urine is regarded as an independent
marker for worsening of renal function and cardiovascular
disease. Hence, British guidelines append the letter "P" to the
stage of chronic kidney disease if there is significant protein loss.
The common causes of End-stage renal disease
• Diabetes mellitus – 20-40%
• Hypertension – 5-20%
• Glomerular disease (IgA nephropathy is most common) – 10-
20%
• Interstitial diseases (Glomerulonephritis, pyelonephritis,
drugs, etc.)-20-30%
• Systemic inflammatory diseases (SLE, vasculitis) – 5-10%
• Renal artery stenosis 5%
• Congenital and inherited (polycystic kidney disease, Alport’s
syndrome)- 5%
• Obstructive such as with bilateral kidney stones and diseases
of the prostate
• Unknown 5-20%
Risk factors for chronic kidney disease
• Hypertension
• >65 year old
• Family history of stage 5 CKD or hereditary kidney
disease
• Structural renal tract disease , renal calculi or
prostatic hypertrophy
• Chronic use of NSAID or other nephrotoxic drugs
• Multisystem disease with potential kidney
involvement
Pathophysiology & clinical
manifestation
 Clinical features of CKD

CKD is initially without specific symptoms and can only be

detected as an increase in serum creatinine or protein in the
urine. As the kidney functions decreases:
• High blood pressure due to fluid overload and activation of renin-
angiotensin system
• Urea accumulates, leading to azotemia and ultimately uremia
(symptoms ranging from lethargy to pericarditis and
encephalopathy). Urea is excreted by sweating and crystallizes on
skin ("uremic frost").
• Hyperkalaemia may develop with a range of symptoms including
malaise and potentially fatal cardiac arrhythmias
• Anaemia due to decreased production of Erythropoietin and
decrease absorption of Iron, toxic effect of uraemia.
• Fluid volume overload - symptoms may range from mild oedema,
raised JVP to life-threatening pulmonary oedema
 other features of CKD
• Hypocalcaemia due to lack of 1,25-Dihydroxycholecalciferol
• Hyperphosphatemia - due to reduced phosphate excretion, associated with
hypocalcaemia
• Metabolic acidosis, due to accumulation of sulphates, phosphates, uric acid etc.
• Accelerated atherosclerosis and Vascular calcification
• Renal osteodystrophy – osteomalacia, hyperparathyroid bone disease (osteitis
fibrosa), osteoporosis, osteosclerosis.
• CRF  Calcium phostate PTH  SHPT  bone,heart,blood,nerves injury

• There may be brown line pigmentation of nails, excoriation of pruritus, easy bruising,
Neuropathy
• Central nervous system
Tiredness, insomnia, agitation, irritability,
depression, regression, rebellion
• Peripheral nervous system-peripheral neuropathy
Restless leg syndrome the patient’s legs are
jumpy during the night, painful paresthesis of extremities, twitching, loss of deep
tendon reflexes , musclar weakness, sensory deficits
 Suggested Investigations in
Chronic Kidney Disease
• Serum urea and creatinine
• Urinalysis for proteinuria, haematuria
• Serum Electrolytes: potassium , sodium  ,calcium ,phosphate 
• Metabolic acidosis,magnesium , parathyroid hormone
• Serum albumin
• Full blood count(± Fe, ferritin, folate, B12)
• Serum fasting lipid profile, glucose± HbA1c (Cardiovascular risk in high in
CKD)
• Renal ultrasound
 Small kidneys with loss of cortico-medulary differentiations
 Asymmetric kidneys suggest renovascular or developmental disease
 Hydronephrotic changes suggests obstructive kidney disease
• ECG – if patient is > 40 years or hyperkalaemia, or there are risk factors
for cardiac diseases
• Hepatitis and HIV serology – if dialysis or transplant is planned, hepatitis
B vaccination recommended if seronegative
 Other relevant investigations
• Additional tests may include nuclear medicine MAG3 scan to
confirm blood flows and establish the differential function
between the two kidneys. DMSA scans are also used in renal
imaging.
• Screening should include calculation of estimated GFR/1.73
m2 from the serum creatinine level, and measurement of
urine-to-albumin creatinine ratio in a first-morning urine
specimen as well as dipstick screen for hematuria.
 Nephrology referral is useful when eGFR/1.73m2 is less than
30 or decreasing by more than 3 mL/min/year, when urine
albumin-to-creatinine ratio is more than 300 mg/g, when
blood pressure is difficult to control, or when hematuria or
other findings suggest either a primarly glomerular disorder
or secondary disease amenable to specific treatment
 Management of CRF
Non-dialysis
Dialysis

Non-dialysis
• Diet therapy
• Treatment of reversible factors
• Treatment of the underlying disease
• Treatment of complcations
 CRF
Diet therapy
• Protein restriction (0.5-0.8mg/kg/d)
• Adequte intake of calories(30-35kcal/kg/d)
• Fluid intake:urine volume +500ml
• Low sodium, phosphate diet
• Supplement of EAA(ketosteril)
 CRF
Reversible factors in CRF
• Hypertension
• Reduced renal perfusion (renal artery stenosis,
hypotension , sodium and water depletion, poor
cardiac function)
• Urinary tract obstruction
• Infection
• Nephrotoxic medications
• Metabolic factors(calcium phosphate products )
 Management
Identify reversible factors and proper treatment
to prevent further renal damage

a)Control of Blood Pressure:

• Maximum target 130/80 mmHg

• 120/75 mmHg in DM and proteinuria

(PCR> 100mg/ mmol, ACR > 70 mg/ mmol )

• ACE inhibitors or Angiotensin receptor blocker (ARBs) are more

effective in reducing proteinuria and progression of kidney
disease
 Management -continue
b) Strict control of blood glucose
• Metformin should be withdrawn when
creatinine is >150μ mol/L (1.7mg/dL)
• Long acting sulphonylurea should be replaced
by short acting agents
• Mean HbA1c < 7%
• Fasting blood glucose target 4-7 m mol/L
• 2hours after meal target 4-10 m mol/L
 Management -continue
e) Identify factors which makes renal function
worse, for prompt treatment, such as
• Urinary Tract Obstruction
• Urinary Tract Infection
• Hypotension
• Salt and water depletion
• Nephrotoxic medications
 CRF
Management of complications
1. Hyperkalemia
• Identify treatable causes
• Inject 10-20ml 10% calcium gluconate
• 50% calcium gluconate 50-100ml i.v.+insulin 6-12u
• Infusion 250ml 5% sodium bicarbonate
• Use exchage resin
• Hemodialysis or peritoneal dialysis
Fluid overload-Diuretics, dialysis
Anemia-Recombinant human erythropoietin(rhEPO)
Antihypertensive therapy
Target blood pressure 130/85mmHg
• ACE inhibitors
• Angiotension II receptor antagonists
 CRF
Side effects of rhEPO
• Hypertension
• Hypercoagulation
• Thrombosis of the AVF
 CRF
rhEPO resistant
• Iron deficiency
• Active inflamation
• Malignancy
• Secondary hyperparathyroid
• Aluminum overload
• Pure red cell aplasia
 CRF

Treatment of renal osteodystropy

Low phosphate diet
Calcium carbonate (1-6g/d)
Vitamin D (0.25ug/d for prophylactic, 0.5ug/d
for symptomatic, pulse therapy 2-4ug/d for
severe cases)
parathyroidectomy
 Limiting the adverse effects of CKD -continue
b) Fluid and electrolyte balance
• Fluid restriction to prevent overload, may lead
to pulmonary oedema
• Limit sodium intake 100m mol/day
• Loop diuretics for correction of fluid overload
• In case of salt wasting disease may require high
sodium and water
• In hyperkalaemia- avoid potassium sparing
diuretics, ACE inhibitors, ARBs
• Limited potassium intake 70m mol/day
• Use of calcium resonium
 Limiting the adverse effects of CKD -continue
c) Acidosis
• Plasma bicarbonate should be > 22m mol/L by
giving sodium bicarbonate supplements (1g
8hourly, increasing as required
d) Calcium carbonate up to 3g daily used to bind
dietary phosphate
e) Renal osteodystrophy
• Correction of hypocalcaemia by giving 1α-
hydroxylated vitamin D
• Correction of hyperphosphataemia by restricted
diet and phosphate binding drugs
• Parathyroidectomy some times required
 Renal replacement therapy

Renal replacement therapy is the life-

supporting treatments for renal failure.
It includes:
1. Haemodialysis,
2. Peritoneal Dialysis
3. Haemofiltration and
4. Renal Transplantation
The RRT replace some functions of the
kidney artificially, specially maintain the
plasma biochemistry by

#Removing uraemic toxins

#Electrolyte balance
#Acid base balance
#Remove fluids from circulation by
ultrafiltration to maintain euvolaemia
# It does not replace the endocrine and
metabolic function
 Haemodialysis

• Haemodialysis is a method for removing

waste products such as creatinine and urea,
as well as free water from the blood in renal
failure.
• Used in both acute and chronic renal failure
 The principle of Haemodialysis

• Diffusion of solutes across a semi permeable

membrane
• The semi permeable membrane allows small solute
clearance 160mL/min
• Haemodialysis utilizes counter current flow where the
dialysate is flowing in the opposite direction to blood
flow in the extracorporeal circuit.
• Counter-current flow maintains the concentration
gradient across the membrane at a maximum and
increases the efficiency of the dialysis.
 Hemodialysis
弥散 Diffussion

渗透 Dialysis
 The principle of Haemodialysis
• Fluid removal (ultrafiltration) is achieved by altering the
hydrostatic pressure of the dialysate compartment,
causing free water and some dissolved solutes to move
across the membrane along a created pressure gradient.

• The dialysis solution that is used may be a sterilized

solution of mineral ions. Urea and other waste products,
potassium and phosphate diffuse into the dialysis
solution. However, concentrations of sodium and chloride
are similar to those of normal plasma to prevent loss.
Sodium bicarbonate is added in a higher concentration
than plasma to correct blood acidity. A small amount of
glucose is also commonly used.
Hemodialysis
 The access for Haemodialysis
Three primary methods are used to gain access
to the blood:
• Intravenous catheter
• Arteriovenous (AV) fistula
• Synthetic graft

Intravenous catheter – Central Venous Catheter is

inserted into a large vein, usually the vena cava,
via the internal jugular vein or the femoral vein
Arteriovenous
(AV) fistula
•To create a fistula, a
vascular surgeon
joins an artery and a
vein together
through anastomosis

•Since this bypasses

the capillaries, blood
flows rapidly through
the fistula
Arteriovenous
graft
•An artificial vessel is used
to join the artery and vein.
•The graft usually is made
of a synthetic material
•Sometimes chemically
treated, sterilized veins
from animals are used
•Grafts are inserted when
the patient's native
vasculature does not
permit a fistula
 CRF
Indications of HD
• GFR<10ml/min
• the uremic syndrome
• hyperkalemia
• acidosis
• fluid overload
 Side effects and complications of Haemodialysis
• Removing too much fluid and/or removing fluid too rapidly include
low blood pressure, fatigue, chest pains, leg-cramps, nausea and
headaches.
• During haemodialysis microbes can entre to the circulatory system,
which can lead to sepsis, endocarditis, osteomyelitis, etc.
• Bleeding may also occur as anticoagulant like heparin is used
• Heparin allergy can infrequently be a problem and can cause a low
platelet count. In patients at high risk of bleeding, dialysis can be
done without anticoagulation.
• Rare but severe anaphylactic reaction, First Use Syndrome may
occur. Its symptoms include sneezing, wheezing, shortness of
breath, back pain, chest pain, or sudden death.
• Long term complications of haemodialysis include amyloidosis,
neuropathy and various forms of heart disease.
• Venous stenosis is a serious problem with catheter access
 Peritoneal dialysis
• This process uses the patient's peritoneum as a
membrane across which fluids and dissolved
substances (electrolytes, urea, glucose, albumin
and other small molecules) are exchanged from
the blood.

• Fluid is introduced through a permanent tube in

the abdomen and flushed out either every night
while the patient sleeps (automatic peritoneal
dialysis) or via regular exchanges throughout the
day (continuous ambulatory peritoneal dialysis).
Peritoneal dialysis
This process uses the
patient's peritoneum as a
membrane across which
fluids and dissolved
substances (electrolytes,
urea, glucose, albumin
and other small
molecules) are exchanged
from the blood.
 Dialysis process

Hookup- access to peritoneal Infusion – Fluid containing

cavity via ‘Tenckhoff’ catheter an osmolar compound
(typically glucose)
 Dialysis process
Diffusion – Water move down an Diffusion – Solutes move down a
osmotic gradient concentration gradient
Drainage
 Types of peritoneal dialysis

• Continuous Ambulatory Peritoneal Dialysis

(CAPD): typically 4 exchanges of 2 L of fluid a
day 4-6 hours apart

• Automated Peritoneal Dialysis (APD): uses a

machine to perform exchanges overnight (8-
10hours)

Used mostly in chronic renal failure

 CRF
Indications of CAPD
child
old people with cardiovascular disease
dibetic nephropathy
trouble of AVF
 Complications
• Excessive loss of fluid can result in hypovolemic shock or
hypotension
• Excessive fluid retention can result in hypertension and oedema
• The presence of pink or bloody effluent suggests bleeding inside the
abdomen
• Feces indicate a perforated bowel
• Cloudy fluid suggests infection
• The patient may also experience pain or discomfort if the dialysate is
too acidic, too cold or introduced too quickly
• Hernia or leaking fluid due to high pressure within the abdomen
• A potentially fatal complication estimated to occur in roughly 2.5%
of patients is encapsulating peritoneal sclerosis, in which the bowels
become obstructed due to the growth of a thick layer of fibrin within
the peritoneum.
 Risks
• PD is less efficient at removing wastes from the
body than haemodialysis

• The presence of the tube presents a risk of

peritonitis due to introduce bacteria to the
abdomen

• Large amounts of albumin are removed which

requires constant monitoring of nutritional status

• PD equipment is cheaper but the costs associated

with peritonitis are higher.
 Benefits
• The primary advantage being the ability to undertake
treatment without visiting a medical facility

• PD allows greater patient mobility, produces fewer swings

in symptoms due to its continuous nature

• Phosphate compounds are better removed

• PD may also be used for patients with cardiac instability

as it does not result in rapid and significant alterations to
body fluids

• Provide temporary renal replacement for patients with no

other options
 治疗

Choice of HD or CAPD

HD PD
Age young eldly
Cardiovascular disease no yes
Blood No bleeding Bleeding
Vascular condition good poor
Ecnomic situation better poor
 Haemofiltration
• There is filtration of water from plasma to ultrafiltrate across
a more porous semipermeable membrane down a pressure
gradient with removal of solutes by convection
• Replacement fluid of chosen electrolytic composition is
added to the blood circuit after the filter. If fluid removal is
required, less is replaced than filtered.
• Typical small solute clearance (2L/hour exchanges) 33mL/min
• It is a slow continuous therapy in which sessions usually last
between 12 to 24 hours and are usually performed daily.
• Less circulatory instability than haemodialysis
• It is used almost exclusively in the intensive care setting
• Used mostly in acute renal failure
 Kidney transplantation
• Kidney transplantation is the organ transplant of a kidney into a
patient with ESRD, glomerular filtration rate <15ml/min/1.73 sq.m.
regardless of the primary cause

• Kidney transplantation is typically classified as deceased-donor

(formerly known as cadaveric) or living-donor transplantation
depending on the source of the donor organ

• In the transplant operation, donor vessels are anastomosed to the

recipient iliac artery and vein, and the donor ureter to the bladder

• A functioning transplant replaces all of the functions of the failed

kidneys
• Successful transplantation extends the life expectancy of patients
with end-stage CKD
• Requires long-term use of immunosuppressive with attendant risks
 CRF
Indications of RT
• maitenance dialysis patients without
contraindications of RT
• age<60 years
 Absolute contraindications

• Active malignancy: a period of at least 2

years of complete remission recommended
for most tumours

• Active vasculitis or recent anti-GBM disease

• Severe heart disease

• Severe occlusive aorto-iliac vascular disease

 Relative contraindications
• Age: transplants are not routinely offered to very
young children (< 1year) or older people (>
75years)

• High risk of disease recurrence in the transplant

kidney

• Disease of the lower urinary tract: in patient with

impaired bladder function, en ileal conduit may
be considered

• Significant comorbidity
 Complications
• Transplant rejection (hyperacute, acute or chronic)

• Infection and sepsis due to the immunosuppressant drugs that are

required to decrease risk of rejection

• Post-transplant lymphoproliferative disorder (a form of lymphoma

due to the immune suppressants)

• Imbalances in electrolytes including calcium and phosphate which can

lead to bone problems amongst other things

• Other side effects of medications including gastrointestinal

inflammation and ulceration of the stomach and esophagus,
hirsutism (excessive hair growth in a male-pattern distribution), Hair
loss, obesity, acne, diabetes mellitus type 2, dyslipidaemia , and
others.
Take home massage