CHRONIC RENAL

FAILURE
 Chronic renal disease: Is a pathophysilogic
process with multiple etiologies, resulting in
loss of nephron number and function
leading to end stage renal disease.
 End stage renal disease: represents a
clinical state or a condition in which there is
irreversible loss of endogenous renal
function leading to a permanent need of
renal replacement therapy (dialysis or
transplantation) to prevent life threatening
uremia.
 Patho-physiology of CRD:
 Earliest change of forms of CRD is the loss of
renal reserve.
 When kidney function is entirely normal GFR
can be increased by 20-30% in response to
protein overload.
 This response is the first to be compromised in
patients with early renal disease in-spite of GFR
remaining normal (particularly well documented
in patients with diabetic nephropathy)
 Changes in CRD depend upon the initiating
mechanism of the underlying disease but the
progressive mechanism remains the same to all
irrespective of the etiology.
 1: Reduction of renal mass causes structural and
functional hypertrophy of surviving nephrons,
mediated by vasoactive molecules, cytokines,
and growth factors.
 Hypertrophy is due to
 Increase in the Glomerular capillary pressure
and flow leading to adaptive hyperfiltration
 This further leads to sclerosis of the remaining
normal nephron.
 Increased intrarenal activity of rennin-
angiotensin axis leads to adaptive hyper-
filtration and maladaptive hypertrophy and
sclerosis
 Common lab findings used are Serum Urea and
Creatinine, but by the time they are mildly
elevated substantial chronic nephron injury has
already occurred.
 Patients with decline of GFR by 30% of the
normal may be asymptomatic except rise in
serum urea and creatinine.
 Early clinical manifestations:
 Nocturia
 Mild anemia
 Loss of energy
 Decreasing appetite leading to disturbances in
nutritional status
 Abnormalities in calcium and phosphorus
metabolism indicating moderate renal
insufficiency.
 Once the GFR falls below 30% of normal it
leads to severe renal insufficiency.
 GFR less than 5-10% leads to end stage renal
disease (ESRD) and survival without renal
replacement therapy becomes impossible.
 Azotemia is retention of nitrogenous products
due to renal insufficiency.

 Uremia is advanced stages of progressive renal

insufficiency when complex multi-organ system
derangements clinically manifest.
 CLINICAL AND LABORATORY
MANIFESTATIONS OF CHRONIC
FAILURE AND UREMIA:
 1: Fluid and electrolyte and acid base
disorders:
 A: Sodium Homeostasis:
 In patients with normal GFR > 24000 mmolof
Na are filtered per day, < 1% of this is excreted
and remaining is reabsorbed by the tubules.
 Hence even when GFR falls as low as 10% of
the normal, the filtered load of Na still far
exceeds daily urinary Na excretion.
 Progressive nephron loss may lead to Na
retention, or Na wasting depending on the
etiology and the comorbid conditions like
cardiac failure and/or cirrhosis.
 Usually presence of normal thirst mechanism
prevents hypernatremia.
 In patients with CRD daily intake of fluid
restricted to UOP+500ml maintains serum Na
at normal levels.
 In patients with ECFV expansion diuretics with
Na restriction is the treatment of choice.
 Patients with GFR < 5-10ml/min should be
treated with dialysis and restriction of salt and
water intake between dialysis treatment.
 When CRD patients are accompanied by extra
renal causes of fluid loss like vomiting, diarrhea,
sweating, fever fluid loss should be immediately
corrected.
 B: K homeostasis: Under normal conditions
the daily filtered load of K is 700 mmol, majority
of it is reabsorbed in the tubules.
 K excretion from the GIT is increased in
patients with CRD.
 Hyperkalemia can be precipitated in following
conditions
 1: Increased dietary intake
 2: Protein catabolism
 3: Hemolysis
 4: Hemorrhage
 5: Transfusion of stored RBC
 6: Metabolic acidosis
 7: Medications like beta blockers, ACE inhibitors, K
sapring diuretics, NSAID, cyclosporine,
 Clinically significant hyperkalemia does not
occur until GFR falls < 10ml/min or unless
exposed to K overload.
 Hypokalemia in CRD is uncommon but if
present it signifies reduced dietary intake with
excessive diuretic therapy or GIT losses, or K
wasting diseases like Fanconi’s syndrome, renal
tubular acidosis, or other forms of hereditary
tubulo interstitial diseases.
 C: Metabolic acidosis:
 Dietary proteins generate 1mmol/kg per day of
H which is primarily excreted by the kidneys.
 Combination of hyperkalemia and
hyperchloremic metabolic acidosis is
characteristically seen in Diabetes Mellitus, and
tubulo interstitial disease.
 Treatment of hyperkalemia improves the
acidosis.
 In CRD patients are usually in a positive K
balance of 20-40mmol/d. The retained H is
buffered by bone salts. This can be corrected by
giving NAHCO3 with careful monitoring of Na
overload.
 D: Bone phosphate and Calcium abnormalities:
 Two types of bone disorder are observed
 Osteitis fibrosa cystica a high turnover osteodystrophy,
is associated with elevated PTH levels. Deranged PTH
synthesis in CRD is due to altered metabolism of
phosphate, calcitrol and Ca
 Osteomalacia a low turnover state leading to adynamic
bone disease
 Treatment: Secondary hyperparathyroidism and
osteitis fibrosa are prevented by reducing serum
phosphate levels by restricting diet with
phosphates, and by giving phosphate binding
agents like calcium carbonate, and calcium
acetate, some times short course of aluminium
hydroxide with calcium carbonate are used.
Daily oral calcitrol or IV exert a direct
suppressive effect
 2: Cardiovascular and pulmonary
abnormalities:
 a: Congestive heart failure
 b: Hypertension and LVH: Control
hypertension prevents the progression of CRD
and prevents the extra renal effect of
hypertension
 c: Atherosclerotic coronary and peripheral
vascular disease
 d: Pericarditis: is an absolute indication for
dialysis in CRD patients, preferably heparin free
dialysis to prevent hemorrhage into the
pericardial sac.
 3: Hematologic abnormalities
 A: Anemia of CRD:
 This is usually observed when the GFR falls
below 30ml/min. Primary cause in CRD is
insufficient production of EPO (Erythropoetin)
by the diseased kidneys.
 Other causes are
 Iron deficiency either related to or independent
of blood loss from repeated laboratory testing,
blood retention in the dialyzer and tubing
 GIT bleeding
 Severe hyperparathyroidism
 Acute and chronic inflammatory conditions
 Alluminium toxicity
 Folate deficiency
 Shortened red cell survival
 Hypothyroidism
 Hemoglobinopathies
 Recombinant EPO was approved by FDA in 1989
 Management guidelines- correction of anemia in CRD
 Erythropoietin
 SC: 80-120 units/Kg per week divided into 2-3 doses
per week
 IV: 120-180 units/Kg per week divided into 3 doses
per week
 Target Hct/Hb: 33-36%/11-12 g/dL
 Optimal rate of correction: Increase Hct by 4-6% over
4 week period ( achieve goal values within 2-3 months)
 Iron:
 Monitor iron stores by percent transferrin
saturation (TSAT) and serum ferritin
 If the patient is iron deficient (TSAT< 20%,
ferritin < 100ng/ml (100ìg/L)
 administer
 50-100mg of iron IV twice a week for 5 weeks
or for 10 successive dialysis sessions.
 If the iron indices are still low repeat the same
regimen.
 Withhold iron therapy when TSAT > 50%
and/or ferritin > 800ng/mL (> 800ìg/L)
 Anemia resistant to recommended doses of
EPO in presence of adequate iron and vitamin
factors often suggests
 Inadequate dialysis
 Uncontrolled hyper parathyroidism
 Aluminium toxicity
 Chronic blood loss or hemolysis and associated
hemoglobinopathies
 Malnutrition
 Chronic infection
 Multiple myeloma
 Other malignancy
 Blood transfusion may suppress erythropoiesis
in CRD as they increase the risk of hepatitis,
hemosiderosis, and transplant sensitization
 B: Abnormal hemostasis:
 Prolongation of the bleeding time
 Decreased activity of platelet factor III
 Abnormal platelet aggregation and adhesiveness
 Impaired prothrombin consumption contribute
to clotting defects.
 Abnormalities in platelet factor III is due to
increased levels of guanidine-succinic acid and
can be corrected by dialysis
 Abnormal bleeding time and coagulopathy in
patients with CRF can be reversed with
desmopressin, cryoprecipitate,conjugated
estrogens, and blood transfusions, and use of
EPO
 C: Enhanced susceptibility to Infection:
 Alterations in monocyte, lymphocyte, and
neutrophil function cause impairment of acute
inflammatory response, decreased delayed
hypersensitivity, and altered late immune
function.
 Uremic patients have less fever in response to
infection due to the effect of the uremia on the
hypothalamic temperature control center.
 Leukocyte function may also be impaired in
patients with CRD because of coexisting
acidosis, hyperglycemia, protein calorie
malnutrition, serum and tissue hyperosmolarity.
 In patients on hemodialysis leukocyte function is
disturbed because of the effects of bio-
incompatibility of the dialysis membrane,
activation of cytokines, and complement
cascade.
 Vascular and peritoneal access devises are the
portal of entry of infection.
 Glucocorticoids and immuno-suppressants also
increase the risk of infection
 4: Neuromuscular disorders:
 Inability to concentrate, drowsiness and
insomnia in initial phases. Asterixis, myoclonus,
and chorea are seen in terminal uremia.
 Neurologic disturbances in patients on chronic
dialysis
 Dialysis dementia: Caused mainly because of
aluminium toxicity leading to speech dyspraxia,
myoclonus, dementia, seizures and death.
 Dialysis disequilibrium: occurs in first few weeks
of dialysis with rapid reduction of urea leading
to cerebral edema and increased intracranial
pressure due to rapid shift of osmolality and pH
 5: GIT abnormalities:
 Anorexia, nausea, vomiting, hiccoughs are early
manifestations of uremia.
 Uremic fector: is uriniferous odor to the breath due to
breakdown of urea to ammonia in saliva and is
associated with metallic taste.
 Patients with polycystic kidney and CRF have an
increased incidence diverticulosis.
 Pancreatitis and angiodysplasia are more common in
patients on dialysis.
 Higher incidence of hepatitis C.
 6: Endocrine metabolic disturbances:
 Glucose metabolism is impaired. Hypoglycemics
like metformin are contraindicated when GFR
has dropped down by 25-50%, and many others
need dose adjustment.
 Estrogen levels are low leading to amenorrhea
and inability to carry on pregnancies.
 In women with ESRD reappearance of menses
is a sign of efficient dialysis.
 7: Dermatologic abnormalities:
 Signs of anemia leading to pallor, echymoses, and
hematomas,
 Calcium deposition and secondary hyperparathyroidism
leading to pruritis, excoriations.
 In advanced uremia fine white powder called uremic
frost can be seen on the skin due to excessive urea
secretion in the sweat.
 Uremic pruritis often remains a problem.
 Diagnostic approach:
 1: Establishing the etiology
 2: Physical examination:
 Blood pressure, fundoscopy, precordial
examination, abdominal examination for bruit
and palpable renal mass, examination of legs for
edema, neurologic examination for asterixis,
muscle weakness, neuropathy. Prostate size
 3: Lab investigations
 4: Imaging studies
 5: Differentiation of CRD from ARF:
 Bilaterally small kidneys (< 8.5cm), anemia,
hyperphosphatemia, hypocalcemia, elevated
PTH levels, urinary sediment that is inactive or
shows proteinuria and broad casts.
 6: Kidney biopsy
 Treatment:
 1: Specific therapy:
 2: Superimposed factors
 3: Measures to mitigate hyperfiltration injury
 a: Protein restriction
 b: Pharmacologic management of intra-
glomerular hypertension
 Guidelines for dietary restriction in CRD
GFR, Protein g/Kg/d Phosphorus
ml/min g/Kg/d

> 60 Protein restriction not usually recommended No restriction

25-60 0.6g/Kg/d including ≥ 0.35g/kg/d of HBV ≤ 10

5-25 0.6g/Kg/d including ≥ 0.35g/kg/d of HBV ≤ 10

OR 0.3g/Kg/d supplemented with EAA or KA ≤9

< 60 0.8g/kg/d (plus 1g protein/g proteinuria) OR ≤ 12

Nephrotic 0.3g/kg/d supplemented with EAA or KA (1g ≤9
syndrome protein/g proteinuria
 Guidelines for BP control in CRD
 Target BP in CRD 130/80-85 mm Hg
 With Proteinuria (> 1g/d) 125/75 mmHg
(MAP 92)
 Recommeded medications Diuretics to maintain
normovolemia
 In diabetic nephropathy or CRD with proteinuria – ACE
inhibitor ARA alone or in combination with diuretic
 In other causes of CRD, calcium entry blocker, alpha or beta
blocker as alternatives
 4: Preperation for renal replacement therapy
 Clear indications
 a: pericarditis
 b: Progressive neuropathy
 c: Encaphalopathy
 d: Muscle irritability
 e: Anorexia and nausea not relieved by reasonable
protein restriction
 f: Fluid and electrolyte abnormalities that are refractory
to conservative measures
 5: Patient education:
 Social, psychological and physical preparation
for the transition to renal replacement therapy.
 6: Only Kidney transplant offers complete
rehabilitation, because dialysis offers only 10-
15% of normal kidney function
 DIALYSIS IN THE TREATMENT OF
RENAL FAILURE
 Treatment options depend on whether the renal
failure is acute or chronic
 ARF:
 1: Hemodialysis
 2: Continuous renal replacement therapies
 3: Peritoneal dialysis
 CRF:
 1: Hemodialysis either at hospital or home
 2: Peritoneal dialysis
 a: Continuous Ambulatory Peritoneal Dialysis
(CAPD)
 b: Continuous Cyclic Peritoneal Dialysis
(CCPD)
 3: Renal transplant
 Hemodialysis is a preferred choice
 Peritoneal dialysis is preferred in younger
patients because of its convenience, better
manual dexterity, and greater visual acuity.
 Obese patients over 80Kg with truncal obesity
and previous abdominal surgery are better suited
for hemodialysis
 Hemodialysis
 Consitsts of bi-drectional diffusion across a
semi-permeable membrane.
 Movement of metabolic waste products takes
place against gradient from the circulation into
the dialysate and dialysate to the circulation.
 The rate of diffusion depends upon the
concentration gradient, membrane surface area,
thickness of the membrane, size of the solute,
and conditions of flow on two sides of
membrane
 According to law of diffusion larger the
molecule slower the diffusion.
 Urea is a smaller molecule and undergoes quick
clearance, whereas creatinine clears slowly.
 Ultrafiltration also clears some of the solutes.
Convective clearance also clears some of the
solute
 DIALYZER: consists of three components
 Dilayzer: is a plastic device with a facility to
perfuse blood and dialysate compartments at
very high flow rates.
 The surface area of the dialysis membrane in
adult patients is in the range of 0.8 to 1.2m2.
Currently there are two types of dialyzers
available; 1; hollow fiber 2; flat plate.
 1; Hollow fiber dialyzer: is most commonly
used and is composed of bundles of capillary
tubes through which blood circulates and and
the dialyzate travels outside of the fiber bundle
 2; Flat plate: less frequently used and consist of
sandwitched sheets of membrane in a parallel
plate configuration
 The advantage of hollow fiber dialyzer is the
lower priming volume 60-90ml in comparison to
100-120 ml in flat plate dialyzer and easier
reprocessing of the filter to reuse in future
dialysis treatments.
 Dialysis Membranes: There are four types of
dialysis mambranes
 1: Cellulose
 2: Substituted cellulose
 3: Cellulo-synthetic
 4: Synthetic: Polysulfone, Polymethyl
methacrylate, polyacrilonitrile. Of these
polysulfone is the most commonly used
 Presently we use only synthetic membranes as
they are more biocompatible.
 Reprocessing and reuse of hemodialyzer is done
in patients on chronic hemodialysis.
 This reduces the cost, and complement
activation, and reduce the mortality.
 Reprocessing procedure is either manual or automated.
It consists of sequential rinsing of blood and dialysate
compartments with water
 Chemical cleansing step with reverse ultrafiltration
from dialysate to the blood compartment
 Testing of patency of the dialyzer
 Disinfection of the dialyzer with formaldyhyde,
Peracetic acid hydrogen peroxide (most commonly
used), and glutaraldyhyde
 Dialysate
 Composition: Bicarbonate has replaced acetate
as a buffer in the dialysis solution leading to
fewer episodes of hypotension
 Lower dialysate concentration of sodium is
associated with frequent hypotension, cramps,
nausea, vomiting, fatigue, and dizziness.
 Sodium counterbalances the urea related
osmotic changes. Glucose 200mg/dL is used to
maintain the blood glucose level
 Approximately 120L of water is used during
each dialysis treatment which could expose the
patients to environmental contaminants.
 To prevent this dialysis water is subjected to
filtration, softening, deionization, and reverse
osmosis.
 During reverse osmosis water is forced through
a semipermeable membrane at very high
pressure to remove microbiologic contaminants
and more than 90% of dissolved ions
 Sodium (meq/L) 137-143
K (meq/L) 0 - 4.0
Chloride (meq/L) 100 - 111
Calcium (meq/L) 0 - 3.5
Magnesium (meq/L) 0.75 - 1.5
Acetate (meq/L) 2.0 - 4.5
Bicarbonate (meq/L) 30 - 35
Glucose (mg/dL) 0 - 0.25
 Blood delivery system
 Consists of
 1: Extracorporeal circuit in dialysis machine
 a: Blood pump: Uses the roller mechanism to
move the blood from access site, through the
dialyser back to the patient.
Blood flow rate may be 250-500ml/min.
Negative hydrostatic pressure on the dialysate side
is manipulated to achieve the desirable fluid
removal by ultrafiltration.
Dialysis membranes have different ultrafiltration
coefficients (ml removed/min/mmHg) so that
with hydrostatic changes fluid removal can be
varied.
 b: Dialysis solution delivery system: dilutes
the dialysate concentrate with water, and
monitors the temperature, conductivity and flow
of dialysate.
 Dialysate is delivered to the dialyzer from a
storage tank, or a proportioning system that
manufactures dialysate online.
 c: Various safety monitors
 2: Dialysis access:
 Fistula, graft, or catheter through which blood is
obtained for hemodialysis is the dialysis access.
 Native fistula is created by anastomosing cephalic vein
to the radial artery resulting arterialization of the vein
and helps to place the large bore needles to access the
circulation.
 Common complication of the fistula is thrombosis due
to intimal hyperplasia resulting in stenosis proximal to
the veinous anastomosis.
 A double lumen catheter placed in femoral vein,
internal jugular vein, or subclavian vein are the
alternatives used temporarily before the fistula is
created. Temporary access can be used for 2-3
weeks as they lead to complications like
thrombosis, low blood flow, and infection
 GOALS OF DIALYSIS
 Hemodialysis is targeted to remove both small
and large molecular weight solutes.
 The procedure consists of pumping heparinized
blood through the dialyzer at a flow rate of 300-
500 ml/min, while the dialysate moves in an
opposite counter current direction at 500-
800ml/min.
 The clearance of urea is 200-350ml/min, and â2
microglobulin is 20-25ml/min.
 Efficiency of the dialysis is decided by the blood
and dialysate flow through the dialyzer, dialyzer
characteristics
 Dose of dialysis: is the magnitude of urea
clearance in a single dialysis treatment which is
governed by patient size, residual renal function,
dietary protein intake, degree of anabolism or
catabolism, and presence of comorbid
conditions.
 Delivered dose of dialysis has direct correlation
with mortality and morbidity.
 There are two ways through which efficacy of
the dialysis can be assessed based on the
decrease in blood urea nitrogen concentration
during the dialysis, urea reduction ratio (URR)
and KT/V an index based on urea clearance
rate, k, and size of the urea pool.
 K: urea clearance rate
 V: Urea distribution volume
 T: time spent on dialysis
 Presently KT/V is the prefered marker for
dialysis
 URR of 65% and KT/V of 1.2 per treatment are
minimal standards for effective dialysis, lower
levels of dialysis are associated with increased
morbidity and mortality.
 For majority of patients with CRF 9-12 hrs
dialysis is required each week
 COMPLICATIONS DURING HEMODIALYSIS
 1: Hypotension: This is treated by stopping the
ultrafiltration and administering isotonic saline 100-
250cc, and in patients with hypoalbuminemia
administration of salt free albumin.
 Stop antihypertensive on the day prior and the day of
dialysis.
 Avoiding heavy meals during dialysis.
 Cooling of the dialysate solution.
 Sequential ultrafiltration followed by dialysis.
 2: Muscle cramps: Introduction of volumetric
controls on dialysis machines and sodium
remodeling have controlled this complication.
 Reducing volume removal during dialysis, use of
higher concentration of sodium in the dialysate,
and use of quinine sulfate 260 mg 2h before
treatment.
 3: Anaphylactoid reaction during the first dialysis
 4: Cardiovascular disease
 CONTINUOUS RENAL
REPLACEMENT THERAPY
 Better tolerated hemodynamically
 Corrects the biochemical abnormalities gradually
 Highly effective in fluid removal
 Technically simple to perform
 Clearance of toxic material occurs from convective
clearance if ultrafiltration rate is high, and by diffusive
clearance if dialysis accompanies ultrafiltration.
 Techniques
 CAVH/D with or without dialysis (continuous arterio
venous) associated with variable efficiency based on the
availability of the pressure gradient. Low pressure leads
to clotting of the extracorporeal circuit. Results in
clearance rate as low as 10-15 ml/min
 CVVH/D with or without dialysis (continuous
veno venous), do not require arterial access, and
need a blood pump in the extra corporeal circuit
as there is no systemic arterial pressure to drive
hemofiltration. Provide substantial flexibility.
Clearance rate is 30-40ml/min
 PERITONEAL DIALYSIS
 Consists of infusing 1-3L of dextrose containing
solution into the peritoneal cavity and allowing
the fluid to remain in the peritoneal cavity for 2-
4h.
 Toxic materials are removed through a
combination of convective clearance through
ultrafiltration, and diffusive clearance down a
concentration gradient.
 Effectiveness depends upon the balance
between movement of solute and water into the
peritoneal cavity versus absorption from
peritoneal cavity.
 Absorption of solutes and water from the
peritoneal cavity takes place across the
peritoneal membrane into the peritoneal
capillary circulation, and via peritoneal
lymphatics into the lymphatic circulation.
 It is altered in presence of infection, beta
blockers, calcium channel blockers, position and
exercise
 TYPES OF PERITONEAL DIALYSIS
 1: Continuous Ambulatory Peritoneal
Dialysis (CAPD): Dialysis solution is manually
infused into the peritoneal cavity during the day
and exchanged 3-4 times daily
 2: Continuous Cyclic Peritoneal Dialysis (CCPD):
Exchanges are performed in an automated fashioin
usually at night, patient is connected to the automated
cycler which performs 4-5 exchange cycles while the
patient sleeps.
 The machine automatically cycles in and out the
dialysate solution with the last cycle remaining in the
abdomen and the patient goes for his daily routine.
 3: Nocturnal Intermittent Peritoneal
Dialysis: Peritoneal fluid is instilled inside the
peritoneal cavity and remains through out the
night.
 Drainage of the spent dialysate is performed
manually with assistance of gravity.
 Patient is given approximately 10h of cycling
each night with abdomen left dry in the day
 Access to the peritoneal cavity is achieved by
 1: Acute catheter in emergency situation,
consists of straight or curved rigid tube with
several holes at its distal end. Used for short
term use and are anchored to the skin by sutures
 2: Chronic catheter; have one or two layers of
Dacron and are tunneled under the skin into the
peritoneal cavity.
 The scarring that occurs around the cuffs
anchors the catheter and seals it from bacteria
tracking from the skin surface into the
peritoneal caivity, it also prevents the external
leaking of the peritoneal fluid.
 Infusion of 2L volume of 1.5% dextrose concentration
peritoneal dialysis fluid into the peritoneal cavity within
10 minutes and allowing it to remain inside for 2.5h.
The spent dialysate is drained for 20minutes before the
next exchange is started.
 The weekly KT/V should be greater than 2.0 and the
creatinine clearance greater than 65 L/week per
1.73meter square. This is calculated by collecting the
dialysate and urine over a period of 24h
 Composition of peritoneal dialysate

Sodium (meq/L) 132

K (meq/L) 0
Chloride (meq/L) 96
Calcium (meq/L) 3.5
Magnesium (meq/L) 0.5
D,L,-lactate (meq/L) 40
Glucose (g%) 1.5,
2.5, 4.25
pH 5.2