3. DEFINITION
Chronic renal failure is a syndrome characterized
by progressive and irreversible deterioration of
renal function due to slow destruction of renal
parenchyma, eventually terminating in death when
sufficient number of nephrons have been damaged.
Acidosis is the major problem in CRF with
development of biochemical azotaemia and clinical
uraemia syndrome.
4. CKD is categorized by the level of kidney
function, based on glomerular filtration rate
(GFR), into stages 1 to 5, with each increasing
number indicating a more advanced stage of
the disease, as defined by a declining GFR.
This classification system from the National
Kidney Foundation’s Kidney Dialysis
Outcomes and Quality Initiative(K/DOQI)
also accounts for structural evidence of kidney
damage.
5. O CK
STAGE GFR DESCRIPTION TREATMENT
1 90+ Normal kidney
function, but urine
findings or
structural
abnormalities or
genetic trait point
to kidney disease
2 60-89 Mildly reduced
kidney function,
and other findings
(as for stage 1)
point to kidney
disease
Observation,
control of blood
pressure.
Observation,
control of blood
pressure and risk
factors.
6. 3A 45-59 Moderately reduced kidney function Observation, control of
3B 30-44 blood pressure and risk
factors
4 15-29 Severely reduced kidney function Planning for end stage renal
failure
5 <15 or Very severe, or end stage kidney failure Treatment choices.
on (sometimes call established renal
dialysis failure)
7. IO E I
The diseases leading to CRF can generally be classified
into two major groups: those causing glomerular
pathology, and those causing tubulointerstitial pathology.
DISEASE CAUSING GLOMERULAR PATHOLOGY
1. Primary glomerular pathology : Glomerulonephritis,
membranous glomerulonephritis, membranoproliferative
glomerulonepritis and anti-glomerular basement
membrane nephritis.
8. 2. SYSTEMIC GLOMERULAR PATHOLOGY: Systemic lupus
erythematosus, serum sickness nephritis and diabetic nephropathy
DISEASE CAUSING TUBULOINTERSTITIAL
PATHOLOGY
1. Vascular causes: Long-standing primary or essential
hypertension produces characteristic changes in renal arteries
and arterioles referred to as nephrosclerosis . Nephrosclerosis
causes progressive renal vascular occlusion terminating in
ischaemia and necrosis of renal tissue.
2. Infectious causes: Chronic pyelonephritis
9. 3.Toxic causes:The most common example is intake of high doses of
analgesics such as phenacetin, aspirin and acetaminophen (chronic
analgesicnephritis). Other substances that can cause CRF after
prolonged exposure are lead, cadmium and uranium.
4. Obstructive causes: Chronic obstruction in the urinary tract leads to
progressive damage to the nephron due to fluid backpressure. The
examples of this type of chronic injury are stones, blood clots, tumours,
strictures and enlarged prostate. Regardless of the initiating cause,
CRF evolves progressively through 4 stages:
Decreased renal reserve
Renal insufficiency
Renal failure
End stage kidney
10.
11. I ICAL FEA U
Clinical manifestations of fullblown CRF culminating in
uraemic syndrome are described under 2 main headings:
primary (renal) uraemic manifestations and secondary
(systemic or extra-renal) uraemic manifestations.
• Primary uraemic manifestations:
1. Metabolic acidosis
2. Hperkalaemia
3. Sodium water imbalance
4. Hyperuricaemia
5. Azotaemia
12. • Secondary uraemic (extra renal) manifestations:
1. Anaemia
2. Integumentary system: Deposit of urinary pigment
such as urochrome in the skin causes sallow-yellow
colour. The urea content in the sweat as well as in
the plasma rises. On evaporation of the perspiration,
urea remains on the facial skin as powdery ‘uraemic
frost’.
3. Cardiovascular system: Hypervolaemia and
eventually CHF
4. Respiratory system: Hypervolaemia and heart failure
cause pulmonary congestion and pulmonary oedemato
back pressure.
13. 5. Digestive system: Azotaemia directly induces mucosalr
ulcerations in the lining of the stomach and intestines.
Subsequent bleeding can aggravate the existing
anaemia. Gastrointestinal irritation may cause nausea,
vomiting and diarrhoea.
6. Skeletal system: The skeletal manifestations of renal
failure are referred to as renal osteodystrophy .
i. Osteomalacia
ii. Osteitis fibrosa
14. DIAGNOSTIC TEST RESULTS
a. Creatinine clearance may range from 0 to 90 mL/min,
reflecting renal impairment.
b. Blood tests typically show
(1) Elevated BUN and serum creatinine concentration.
(2) Reduced arterial pH and bicarbonate concentration.
(3) Reduced serum calcium level.
(4) Increased serum potassium and phosphate levels.
(5) Possible reduction in the serum sodium level.
(6) Normochromic, normocytic anemia (hematocrit 20%
to 30%).
15. c. Urinalysis may reveal glycosuria,
proteinuria, erythrocytes, leukocytes, and casts.
Specific gravity is fixed at 1.010.
d. Radiographic findings. Kidney, ureter, and
bladder radiography, IV pyelography, renal
scan, renal arteriography, and
nephrotomography may be performed.
Typically, these tests reveals mall kidneys (less
than 8 cm in length).
16. Structural assessments of the kidney may be
performed using a number of imaging
procedures, including:
• ultrasonography
• intravenous urography (IVU)
• plain abdominal radiography
• computed tomography (CT), magnetic
resonance imaging (MRI) and magnetic
resonance angiography (MRA).
17. NT
• Treatment objectives:
1. Improve patient comfort and prolong life.
2. Treat systemic manifestations of CKD.
3. Correct body chemistry abnormalities.
NONPHARMACOLOGIC THERAPY
• A low-protein diet (0.6 to 0.75 g/kg/day) can delay
progression of CKD in patients with or without diabetes,
although the benefit is relatively small. Management of the
CKD patient is generally conservative. Dietary measures and
fluid restriction relieve some symptoms of CKD and may
increase patient comfort and prolong life until dialysis or renal
transplantation is required or available.
18. PHARMACOLOGICAL TREATMENT
1. Treatment of edema: Angiotensin-converting enzyme
(ACE) inhibitors and diuretics: may be given to manage
edema and CHF and to increase urine output.
a. ACE inhibitors—captopril, enalapril , lisinopril
,fosinopril
b. (1) Osmotic and loop diuretics
(2) Thiazide-like diuretics. Metolazone is the most
commonly used thiazide diuretic in CKD.
19. 2. Treatment of hypertension.: Antihypertensive agents
may be needed if blood pressure becomes dangerously high
as a result of edema and the high renin levels that occur in
CKD.
a. ACE inhibitors—captopril, enalapril, lisinopril,
fosinopril
b. calcium-channel blockers, including amlodipine and
felodipine , have similar eff ects and may be used instead of
ACE inhibitors.
c. βAdrenergic blockers, including propranolol and
atenolol , reduce blood pressure through various
mechanisms.
d. Other antihypertensive agents are sometimes used in the
treatment of CKD, including (-adrenergic drugs, clonidine ,
and vasodilators, such as hydralazine .
20. 3. Treatment of hyperphosphatemia :involves
administration of a phosphate binder, such as
aluminum hydroxide or calcium carbonate.
4. Treatment of hypocalcemia:
a. Oral calcium salts.
b. Vitamin D
Choice of agent: For the treatment of hypocalcemia
in CKD and other renal disorders, calcitriol (vitamin
D3, the active form of vitamin D) is the preferred
vitamin D supplement because of its greater efficacy
and relatively short duration of action. Other single-
entity preparations include dihydrotachysterol,
ergocalciferol , doxercalciferol and paricalcitol .
21. 5. Treatment of other systemic manifestations of CKD
a. Treatment of anemia includes administration of iron (e.g.,
ferrous sulfate), folate supplements, and epoetin alfa.
(1) Severe anemia may warrant transfusion with packed red
blood cells.
(2) Epoetin alfa stimulates the production of red cell
progenitors and the production of hemoglobin. It also
accelerates the release of reticulocytes from the bone marrow.
(3) Darbepoetin is an epoetin alfa analogue
(4) Intravenous iron products may be given to replete iron
stores. Iron dextran is commonly used. Newer iron products
include sodium ferric gluconate and iron sucrose, which are
better tolerated and can be infused more rapidly compared to
iron dextran.
22. b. Treatment of GI disturbances
(1) Antiemetics help control nausea and vomiting.
c. Treatment of skin problems. An antipruritic agent,
such as diphenhydramine, may be used to alleviate
itching.
23. D
a. Hemodialysis: is the preferred dialysis method for patients
with a reduced peritoneal membrane, hypercatabolism, or
acute hyperkalemia.
(1) This technique involves shunting of the patient’s blood
through a dialysis membrane containing unit for diffusion,
osmosis, and ultrafiltration. The blood is then returned to the
patient’s circulation.
(2) Vascular access may be obtained via an arteriovenous
fistula or an external shunt.
(3) The procedure takes only 3 to 8 hrs; most patients need
three treatments a week. With proper training, patients can
perform hemodialysis at home
24. (4) The patient receives heparin during hemodialysis to
prevent clotting.
(5) Various complications may arise, including clotting of
the hemofilter, hemorrhage, hepatitis, anemia, septicemia,
cardiovascular problems, air embolism, rapid shift s in
fluid and electrolyte balance, itching, nausea, vomiting,
headache, seizures, and aluminum osteodystrophy.
25. b. Peritoneal dialysis is the preferred dialysis method for
patients with bleeding disorders and cardiovascular disease.
(1) The peritoneum is used as a semipermeable membrane. A
plastic catheter inserted in to the peritoneum provides access
for the dialysate, which draws fluids, wastes, and electrolytes
across the peritoneal membrane by osmosis and diffusion.
(2) Peritoneal dialysis can be carried out in three different
modes.
(a) Intermittent peritoneal dialysis :Is an automatic cycling
mode lasting 8 to 10 hrs, performed three times a week. This
mode allows night time treatment and is appropriate for
working patients.
26. (b) Continuous ambulatory peritoneal dialysis : is
performed daily for 24 hrs with four exchanges daily. The
patient can remain active during the treatment.
(c) Continuous cyclic peritoneal dialysis : may be used if
the other two modes fail to improve creatinine clearance.
Dialysis takes place at night; the last exchange is retained
in the peritoneal cavity during the day, then drained that
evening.
(3) Advantages of peritoneal dialysis include a lack of
serious complications, retention of normal fluid and
electrolyte balance, simplicity, reduced cost, patient
independence, and a reduced need (or no need) for heparin
administration.
27. (4) Complications of peritoneal dialysis include
hyperglycemia, constipation, and inflammation or
infection at the catheter site. Also, this method carries a
high risk of peritonitis.
28. Renal transplantation:
This surgical procedure allows some patients with end-
stage renal disease to live normal and, in many cases,
longer lives.
a. Histocompatibility must be tested to minimize the risk
of transplant rejection and failure. Human leukocyte
antigen (HLA) type, mixed lymphocyte reactivity, and
blood group types are determined to asses
histocompatibility.
b. Renal transplant material may be obtained from a
living donor or a cadaver.
29. c. Three types of graft rejection can occur.
(1) Hyperacute (immediate) rejection results in graft loss
within minutes to hours after transplantation.
(a) Acute urine flow cessation and bluish or mottled
kidney discoloration are intraoperative signs of hyperacute
rejection.
(b) Postoperative manifestations include kidney
enlargement, fever, anuria, local pain, sodium retention,
and hypertension.
(c) Treatment for hyperacute rejection is immediate
nephrectomy.
(2) Acute rejection may occur 4 to 60 days after
transplantation.
30. (3) Chronic rejection occurs more than 60 days after
transplantation.
(a) Signs and symptoms include low-grade fever, increased
proteinuria, azotemia, hypertension, oliguria, weight gain,
and edema.
(b) Treatment may include alkylating agents, cyclosporine,
antilymphocyte globulin, and corticosteroids. In some cases,
nephrectomy is necessary
31. d. Complications include
(1) infection,diabetes, hepatitis, and leukopenia, resulting
from immunosuppressive therapy.
(2) hypertension, resulting from various causes.
(3) cancer (e.g., lymphoma, cutaneous malignancies, head
and neck cancer, leukemia, colon cancer).
(4) pancreatitis and mental and emotional disorders (e.g.,
suicidal tendencies, severe depression, brought on by
steroid therapy).