1. Chronic renal failure refers to the irreversible deterioration of renal function over time that leads to the loss of kidney excretory, metabolic, and endocrine functions. 2. Treatment of chronic renal failure focuses on controlling blood pressure, correcting anemia and other complications, managing diet and fluid intake, and potentially pursuing renal replacement therapies like dialysis or transplantation. 3. The main goals of treatment are to control the primary disease, address reversible factors, manage uremic complications through conservative treatment, and utilize blood purification therapies or renal transplantation if necessary.

1. 1

2. Dr. Abdur Rahman Emoo
Medical Officer
Department of Cardiology
Dhaka National Medical College Hospital
2

3. Chronic renal failure (CRF) refers to an irreversable
deterioration in renal function classically develops over
a period of years
Initially it is manifest only as a biochemical abnormality,
loss of excretory, metabolic & endocrine function of
kidney leads to development of symptoms & signs of
CRF.
3

4. Factor 2002 2003 2004 2005
New ESRD cases 86 82 85 93
Incidence (pmp) 150 143 149 163
Age-adjusted 232 186 317 181
incidence (pmp)
Sex ratio 55/45 63/37 65/35 52/48
(male/female)
Mean age (years),
Diabetic nephropathy 46+/-15
47 50+/-10
43 47+/-13
40 46+/-12
46
6SD
(%)
ESRD=end-stage renal disease, pmp=per million population, SD = standard
deviation. 4

5.  CRF is a permanent, usually progressive,
diminution in renal function to a degree that has
damaging consequences for the patient.
 It is characterized by an increasing inability of the
kidney to maintain normal low levels of the
products of protein metabolism(such as urea),
normal blood pressure and hematocrit, and
sodium, water, potassium, and acid-base balance.
5

6.  Congenital & inherited : 5%
 Renal artery stenosis : 5%
 Hypertension : 5-25%
 Glomerular disease (IgA nephropathy is common) :
10-20%
 Interstitial disease : 5-15%
 Systemic inflammatory disease : 5% ( SLE, Vasculitis)
Diabetes mellitus : 20-40%
 Unknown : 5-20%
6

7.  Hypertension
 Reduced renal perfusion :
Renal artery stenosis
Hypotension due to drug treatment
Na & water depletion
Poor cardiac function
 Urinary tract obstruction
 Urinary tract infection
 Nephrotoxic medication
 Other infection : increased catabolism & urea production
7

8. Stages Description GFR(ml/min/1.73 Action
m2 )
1 Kidney damage > 90 Investigate
with normal or (Haematuria &
high GFR proteinurea)
2 Kidney damage 60-89 Renoprotection-
with slightly low BP control,
GFR dietary
modification
3 Kidney damage 30-59
with low GFR
4 Severe low GFR 15-29 Prepare for
renal
replacement
therapy
8
5 Kidney failure <15 or dialysis

9.  Hypothesis
 Glomerular hyperfiltration/hyperperfusion
 Glomerular hypertension
 Nephrotoxicity of lipids
 Similarities with atherosclerosis
 Glomerular hypertrophy
 Nephrotoxicity of proteinuria
 Growth factors
 Platelet-derived growth factor
 Transforming growth factor β
 Mesangial/myofibroblast differentiation
 Podocyte injury 9

10. glom vasc dis tubu-inters dis
dis
Ca × P ↑
loss of nephron
nephroarte PTH↑
riolosclero
sis adaption of remaining
nephrons
HBP
+
hyperlip glom hypertrophy
idemia
hyperperfusion
atheros GCP↑
clerosis
mes.proliferation,
focal GS, proteinuria ↑
Renovascula
r renal
tubu-inters. atrophy
failure
ESRD
Aquired renal
cystic disease 10

11. 11

12. Early Late(GFR < 15 ml/min,
BUN > 60 mg/dL)
 hypertension  cardiac failure
 anemia
 proteinuria,elevated
 serositis
BUN or sCr
 confusion, coma
 nephrotic syndrome
 anorexia
 recurrent nephritic
 vomiting
syndrome
 peripheral
 gross hematuria
neuropathy
 hyperkalemia
 metabolic acidosis 12

13. en al
ni cr ?
h ro ive
is c re ss
hy prog
W re
failu
13

14. ° Persistence of initial disease process that caused renal
injury or presence of additional factors that promote renal
injury (mineralization, infection, drugs, toxins, etc.)
z Hyperfiltration theory: progression of renal disease
despite resolution of primary insult.
a. Premise
A reduction in number of nephrons past some critical
threshold leads to failure of the remaining nephrons. CRF
has been recognized as a progressive disease.
b. Mechanism
Renal afferent arteriole vasodilation promotes glomerular
hypertension which causes further glomerular injury and
perpetuation of renal decline.
14

15. 15

16. ical
lin
fc F
o
i s n CR
es s i
en e'
og om
th dr
Pa yn
s
16

17. A. Lethargy, fatigue, nausea and depression
 The magnitude of BUN increase is usually proportional
to uremic signs and estimates degree of other retained
uremic toxins.
 Additional uremic factors: include PTH, by-products of
protein catabolism, and other metabolic derangements
B. Polyuria and compensatory polydipsia
1. Hyperfiltration
Remnant nephrons are operating under conditions of
osmotic diuresis (increased SNGFR).
2. Disruption of renal medullary gradient
Tubulointerstitial disease as well as high tubular flow rates
may prevent maintenance of hypertonic interstitium.
3. Impaired nephron response to ADH
. 17

18. C. Gastrointestinal signs
1. Uremic stomatitis
High blood levels of urea diffuse into oral cavity, bacteria
convert to ammonia = locally toxic = oral ulceration.
2. Vomiting: more common
a. Central (CNS) causes: uremic toxins stimulate
chemoreceptor trigger zone.
b. Uremic gastroenteritis
i. Local effects: urea and ammonia are locally toxic.
ii. Increased gastrin (reduced renal clearance) results in
increased gastric acid production and gastric mucosal injury.
iii. Other factors: ischemia, altered gastric mucosa turnover,
and other likely contribute to gastric injury.
3. Diarrhea: uremic enterocolitis (less common) - may occur in
part due to high ammonia levels. 18

19. D. Anemia: normocytic, normochromic, non-regenerative.
1. Decreased erythropoietin (EPO) production: predominant
cause of anemia in CRF.
Intrinsic renal disease = decreased synthesis of EPO =
decreased BM production of RBC's.
Unidentified circulating uremic inhibitors may also play a role
in inhibiting erythropoiesis.
2. Reduced RBC survival: uremic toxins decrease lifespan of
circulating RBC's.
3. Blood loss
 a. Bleeding tendency: often noted in uremic patients.
Characterized by prolonged mucosal bleeding time.
Circulating uremic toxins may cause platelet defects.
 b. Gastrointestinal bleeding: may occur in association with GI
ulceration and platelet defects.
19

20. 20

21. E. Hypertension
1. Common complication: with chronic renal disease the
incidence of HT is 50 – 93%
2. Etiology: pathogenesis not fully understood - likely
multifactorial
a. BP = cardiac output X peripheral resistance
b. Possible contributory factors
i. Sodium retention from decreased renal excretion (= increased
ECF)
ii. Activation of RAS (= vasoconstriction and ECF expansion)
iii. Sympathetic activation and endothelial factors
21

22. 22

23. 3. Clinical signs: often clinically silent.
a. Vasculature: sustained arterial HT = muscular occlusion
of small arteries = decreased perfusion (especially heart,
eyes, kidneys, and brain).
b. Heart: sustained HT may result in LVH (usually
subclinical).
c. Ocular lesions: dilated, tortuous retinal vessels, retinal
hemorrhage, detachments, and blindness.
23

24. 1. RSHP develops in patients with CRF as a result of the body's
attempt to maintain calcium and phosphorus homeostasis.
2. Sequela of RSHP
a. Phosphorus: compensatory increases in PTH act to decrease
Pi and increase serum Ca levels.
When GFR declines to < 20%, renal adaptive mechanisms
have been maximized and hyperphosphatemia occurs.
b. Calcitriol (vitamin D3)
i. Early in CRF, retained Pi = increased PTH = increased
calcitriol production.
ii. Later in CRF, loss of ability to make calcitriol = elevated set-
pt for Ca-induced suppression of PTH = PTH secretion despite
normal to high iCa.
24

25. c. Renal osteodystrophy
i. Increased PTH = mobilization of Ca/Pi from bone; if prolonged
= ROD (demineralization and replacement with fibrous tissue)
ii. Clinically evident ROD is uncommon - occurs most often in
the immature animal due to metabolically more active bone.
d. Soft tissue mineralization: most often affects the lungs,
kidneys, heart, arteries, and stomach.
Common in cases of advanced CRF. When Ca X Pi > 70 = soft
tissue mineralization may occur.
e. Other sequela of RSHP
PTH has been implicated as a "uremic toxin": malaise, anemia,
neurologic signs. Mechanism of toxicity: increase PTH =
increased Ca into cells = cell dysfunction or death.
25

26. 26

27. 1. Normal function of the kidney in acid - base regulation.
The kidney works in concert with the lungs and the blood buffer system to
maintain normal acid-base homeostasis within the body.
a. The proximal renal tubule excretes majority of acid (reabsorbs HCO3,
makes NH3).
b. The distal renal tubule excretes H+ (under influence of aldosterone), and
also makes NH3.
2. The kidney in CRF
a. Development of acidosis
Compensatory mechanisms maintain acid - base status until GFR has
decreased to < 5 - 20% of normal.
b. Role of ammonia
i. H+ excretion is sustained mostly by increasing production of NH3 (H+
trapped in urine as NH4+).
ii. Even with compensatory increase in NH3 production/nephron there is a
total decrease in NH3 production due to the overall loss of functional 27
nephrons in advanced RF.

28. H. Hypokalemia: serum K+ < 3.5 mEq/L.
Chronic acidosis promotes hypokalemia (increase H+ =
increase aldosterone = increase K+/H+ excretion).
I. Proteinuria
Urinary protein excretion typically is increased (1.5 - 2X
normal) with CRF.
Proteinuria in CRF is likely due to changes in glomerular
hemodynamics rather than structural glomerular lesions.
28

29. 29

30. 30

31. 31

32. 1. Infection
Uremia is associated with impaired CMI and neutrophil function - bacterial
infections are common complications of the patient with CRF.
2. Dyslipoproteinemias: common in people with CRF.
a. Pathogenesis: not completely understood
May be associated with increased PTH levels (suppresses insulin release
= decreased lipoprotein lipase = increased lipoproteins).
b. Clinical consequences
Lipoproteins are entrapped in mesangium of glomeruli = taken up by
macrophages = foam cells = increased production of PG's and toxic by-
products = glomerular injury = glomerulosclerosis.
3. Neurological abnormalities
May note mental dullness, lethargy, tremors, peripheral neuropathies
and uremic encephalopathy. Likely due to effects of PTH, hypertension,
electrolyte disturbances or other uremic toxins.
32

33. Acute Renal Failure Chronic Renal Failure
1. Hematocrit to increased (dehydration) Decreased (chronic anemia)
2. Azotemia/PO4 Elevated Elevated
3. Potassium Usually increased to decreased
4. Calcium Low to normal Low, normal, or high
5. Urinalysis Active sediment Inactive sediment
6. Urination Oliguria, anuria Polyuria
7. Weight Good nutritional status Weight loss
8. Kidneys to increased size Small, irregular
33

34. 34

35.  1. CBC :
May note a normocytic, normochromic,
non-regenerative anemia and variable leukocytosis
(secondary to associated stress, infection or
inflammation).
 2. Haematinics : supplementation if deficient to
optimise response to erythropoietin.
35

36.  Serum biochemistry profile :
 Characteristic findings may include *azotemia,
*hyperphosphatemia, *metabolic acidosis, *hypokalemia,
variable calcium levels, and elevations in serum amylase
and lipase (usually not greater than 2 - 4X normal).
*Indicates the four most common findings on serum
biochemistry profile.
 Parathyroid hormone
 Lipid profile
 S. Glucose level
36

37.  Ultrasonography : to confirm/refute two equal-sized
unobstructed kidneys.
 Chest X-ray : heart size, pulmonary oedema.
 ECG : if >40 yrs or risk factors for cardiac disease
 Renal artery imaging
Microbiology :
 Hepatitis & HIV serology—if dialysis is needed.
37

38.  Group & save
 Tissue typing
 Cytomegalovirus if transplantation is needed
 Epstein-Barr virus
 Varicella zoster virus
38

39. 39

40. 40

41. 41

42. Treatment
42

43.  Aim of treatment :-
 Primary disease and reversible factors treatment
 Conservative treatment
 Treatment of complications of uremia
 Blood purification
 Renal transplantation
43

44.  Enough calorie intake: 126-147KJ
 Low protein diet: 0.6-0.8g/kg/d,60% high quality protein
 Essential amino acid supplement
 α-ketoacid supplement
 Vitamin supplement: folic acid, Vit C, Vit B6, Vit D
 Fluid intake—3 lt/day associated with 5-10 g/day of NaCl
& 70 mmol/day.
44

45.  Control of Blood Pressure :-ACE inhibitor is more effective
than other therapies. Angiotensin-II receptor antagonists also
reduce glomerular perfusion pressure.
 Correction of Anaemia :- Recombinant human
erythropoietin is effective in correcting anaemia .
 Atherosclerosis :- Atherosclerosis is common & treated by
anti-lipidemic drugs.
 Hypocalcaemia :- is corrected by 1α hydroxylated synthetic
analogues of vitamin-D.
 Hyperphosphataemia :- is controlled by dietary restriction of
foods (milk, cheese, eggs etc).
 Acidosis :- is controlled by calcium carbonate (upto
3gm/day).
 Infection :- it must be recognised & treated promptly.
45

46.  GI manifestation :- to reduced by using H2 receptor or
proton-pump inhibitor.
 Neuropathy :- results from demyelination of medulated
fibres. Amitriptyline & Gabapentine used to symptom
relief.
 Myopathy :- Generalised myopathy due to
combination of poor nutrition , hyperparathyroidism ,
vit-D deficiency.Muscle cramp are common & quinine-
sulphate may be helpful. Patient ‘s legs are jumpy
during night & is often improved by clonazepam.
46

47.  Hemodialysis
 Peritoneal dialysis
47

48. Superior Vena Cava
Lung Heart
Liver Aorta
Spleen
Right Kidney Left Kidney
Large Intestine Small Intestine
Right Ureter Left Ureter
Bladder
Healthy Kidney Diseased Kidney Physical Basis Renal Replacement 48

49. Erythrocyte,
Red Blood Cell Bacteria
Albumin, as
Example of a Big
Protein Molecule Medium sized
Molecules, e.g.
β2-Microglobulin
Electrolytes
Water Flow is
Easily Possible
The semipermeable membrane functions similar to a fine sieve,
only molecules that are small enough can pass.
Healthy Kidney Diseased Kidney Physical Basis Renal Replacement 49

50. Anti-Coagulation Blood Pump
Dialyzer
Blood to
the Patient
Fresh
Dialysate
Used Blood from
Dialysate the Patient
Healthy Kidney Diseased Kidney Physical Basis Renal Replacement 50

51. Dialysate
Bundle of Inflow
Capillaries in
the Housing
Blood
Outflow
Dialysate
Outflow
Solute Transfer
across the
Capillary Walls
Blood
Inflow
The dialysate flows outside of the capillaries,
blood within the capillaries countercurrently.
Healthy Kidney Diseased Kidney Physical Basis Renal Replacement 51

52. Bag with Fresh Solution
Peritoneal dialysis
is done by filling Peritoneum
specially composed
peritoneal dialysis
solution into the
abdominal cavity.
The solute transfer Implanted
between blood and Catheter
the solution happens
by diffusion.
The water removal
from the patient is Peritoneal
an osmotic process. Dialysis
Solution
Bag for Used Solution
Healthy Kidney Diseased Kidney Physical Basis Renal Replacement 52

53. Liver
Aorta
Kidney Transplant
in the Fossa Iliaca,
Not at the Position
of Healthy Kidneys
Connection of
Renal Artery and
Vein to the Pelvic
Connection of Vessels
the Ureter to the
Bladder of the
Recipient
Healthy Kidney Diseased Kidney Physical Basis Renal Replacement 53

54. 54