Chronic renal failure refers to the irreversible deterioration of renal function over years. It initially presents as biochemical abnormalities and eventually leads to uraemic symptoms as the excretory, metabolic and endocrine functions of the kidneys fail. Common causes include diabetes, hypertension, and glomerulonephritis. Management involves identifying and treating the underlying disease, slowing progression, managing complications, and renal replacement therapy for end-stage disease.

1. CHRONIC RENAL FAILURE

2. CHRONIC RENAL FAILURE
Chronic renal failure (CRF) refers to an irreversible deterioration in
renal function which classically develops over a period of years .

3. • Initially, CRF manifest only as a biochemical abnormality.
• Eventually, loss of the excretory, metabolic and endocrine
functions of the kidney leads to the development of the
clinical symptoms and signs of renal failure, which are
referred to as uraemia.
• End stage renal disease (ESRD):renal failure which need renal
replacement therapy.
• When death is likely without renal replacement therapy, it is
called end-stage renal failure (ESRF).

4. Aetiology of CRF
• CRF may be caused by any condition which destroys the
normal structure and function of the kidney.

5. Common causes of Chronic Renal
Failure
• Diabetes Mellitus
• Hypertension
• Glomerulonephritis
• Chronic pylonephritis/reflux 10%
• Polycystic kidney disease
• Interstitial nephritis
• Obstruction
• Unknown

6. Diabetes (most common cause) Hypertension
Chronic Glomerulonephritis
Polycystic Kidney Disease

7. Pathogenesis of CRF
• Disturbances in water, electrolyte and acid-base balance
contribute to the clinical picture in patients with CRF, but the
exact pathogenesis of the clinical syndrome of uraemia is
unknown.
• Many substances present in abnormal concentration in the
plasma have been suspected as being 'uraemic toxins', and
uraemia is probably caused by the accumulation of various
intermediary products of metabolism.

8. Clinical Features of CRF

9. Major manifestations of Uremic
Syndrome
The Uremic Syndrome:
Gastrointestinal
-Anorexia , Nausea , Vomiting , Disturbance of taste , Gastritis
Peptic ulcer , GI bleeding.
Cardiovascular
- Cardiomegally , arrhythmias , pericarditis , accelerated
atherosclerosis.
Pulmonary
-Pneumonitis , pleuritis, pleural effusion , non-cardiogenic
pulmonary oedema.
Haematologic
- Anaemia , bleeding disorders , leukocyte dysfunction.

10. Skin
-Pruritus , yellow pigmentation , earthy colour face.
Musculoskeletal
-Muscle weakness , gout & pseudogout , renal osteodystrophy .
Endocrine / Metabolic
-Hyperparathyroidism , amenorrhea , impotence , hyperlipidemia
increased insulin resistance.
Acid base / Electrolytes
-Acidosis , hyperkalemia , fluid overload , hypocalcemia
, hyperphosphatemia , hypermagnesemia.
Nervous system
-Central : irritability , insomnia , lethargy , seizures , coma.
-Peripheral : glove-and stocking sensory loss , restless leg
, foot drop or wrist drop.

11. Clinical assessment
• Renal failure may present as a raised blood urea and
creatinine found during routine examination, often
accompanied by hypertension, proteinuria or anaemia.
• When renal function deteriorates slowly, patients may remain
asymptomatic until GFR falls below 20 - 30 ml/minute(
normal range 80 – 120 mL/ min ).
• Nocturia, due to the loss of concentrating ability and
increased osmotic load per nephron, is often an early
symptom.
• Thereafter, due to the widespread effects of renal
failure, symptoms and signs may develop that are related to
almost every body system .

12. • Patients may present with complaints which are not
obviously renal in origin, such as tiredness or
breathlessness.
• In ESRF (stage 5) patients appear ill and anaemic.
• There may be unusually deep respiration related to
metabolic acidosis (Kussmaul's respiration), anorexia and
nausea.
• Later, hiccoughs, pruritus, vomiting, muscular
twitching, fits, drowsiness and coma ensue.

13. • Specific manifestations of Uremia

14. Specific manifestations of Uremia
• Gastrointestinal manifestations
• Are common at low GFRs, including:
• anorexia followed by nausea, and vomiting is commonly seen.
• There is a higher incidence of peptic ulcer disease in uraemic
patients.

15. Anaemia
• Anaemia is common in CRF; it usually correlates with the severity
of renal failure and contributes to many of the non-specific
symptoms of CRF.
• Several mechanisms are implicated(causes of anaemia inCRF):
1- Relative deficiency of erythropoietin
2- Diminished erythropoiesis due to toxic effects of uraemia on
marrow precursor cells
3- Reduced red cell survival
4- Increased blood loss due to capillary fragility and poor platelet
function
5- Reduced dietary intake and absorption of iron and other
haematinics.

16. • Plasma erythropoietin is usually within the normal range
and thus inappropriately low for the degree of anaemia.
• In patients with polycystic kidneys, anaemia is often less
severe or absent, while in some interstitial disorders it
appears disproportionately severe for the degree of renal
failure. This is probably because of the effects of these
disorders on the interstitial fibroblasts that secrete
erythropoietin

17. Acidosis
Declining renal function is associated with metabolic
acidosis , which is often asymptomatic. There may be
unusually deep respiration related to metabolic acidosis
(Kussmaul's respiration).
Effects of metabolic acidosis :
• Sustained acidosis results in protons being buffered in
bone in place of calcium, thus aggravating metabolic
bone disease.
• Acidosis may also contribute to reduced renal function
and increased tissue catabolism.

18. Cardiovascular disease and lipids
• CRF is an independent risk factor for occlusive cardiovascular
disease.
• Hypertension develops in approximately 80% of patients
with CRF.
In part, this is caused by sodium retention.
Chronically diseased kidneys also tend to hypersecrete
renin, leading to high circulating concentrations of
renin, angiotensin II and aldosterone.
This is exaggerated if there is renal under-perfusion related to
renal vascular disease.
Hypertension must be controlled, as it causes further vascular
and glomerular damage and worsening of renal failure
• Atherosclerosis is common and may be accelerated by
hypertension.

19. • Pericarditis is common in untreated or inadequately
treated ESRF.
It may lead to pericardial tamponade and, later, constrictive
pericarditis.
• Hypercholesterolaemia
is almost universal in patients with significant proteinuria, and
increased triglyceride levels are also common in patients with
CRF.
It has been suggested that as well as influencing the
development of vascular disease, this may accelerate the
progression of chronic renal disease.

20. Renal osteodystrophy
• This metabolic bone disease which accompanies CRF
consists of a mixture of osteomalacia, hyperparathyroid
bone disease (osteitis fibrosa), osteoporosis and
osteosclerosis .
Osteomalacia
• Results from diminished activity of the renal 1α-
hydroxylase enzyme, with failure to convert
cholecalciferol to its active metabolite, 1,25-
dihydroxycholecalciferol.
• A deficiency of the latter leads to diminished intestinal
absorption of calcium, hypocalcaemia and reduction in
the calcification of osteoid in bone.

21. • Osteitis fibrosa results from this secondary hyperparathyroidism
.
• The parathyroid glands are stimulated by the low plasma
calcium, and also by hyperphosphataemia.
• In some patients tertiary or autonomous hyperparathyroidism with
hypercalcaemia develops.
• Osteoporosis occurs in many patients , possibly related to
malnutrition.
• Osteosclerosis is seen mainly in the sacral area, at the base of the
skull and in the vertebrae; the cause of this unusual reaction is not known.

22. Myopathy
• Generalised myopathy is due to a combination of
poor nutrition, hyperparathyroidism, vitamin D
deficiency and disorders of electrolyte metabolism.
• Muscle cramps are common, and quinine sulphate may
be helpful.
• The 'restless leg syndrome', in which the patient's
legs are jumpy during the night, may be troublesome and is
often improved by clonazepam

23. Neuropathy
• Neuropathy results from demyelination of medullated
fibres, with the longer fibres being involved at an earlier
stage.
• Sensory neuropathy may cause paraesthesiae. Amitriptyline
and gabapentin may provide some symptom relief.
• Motor neuropathy may present as foot drop.
• Uraemic autonomic neuropathy may cause delayed gastric
empty-ing, diarrhoea and postural hypotension.
• Clinical manifestations of neuropathy appear late in the
course of CRF but may improve or even resolve once dialysis
is established.

24. Endocrine Function
A number of hormonal abnormalities may be present of
which the most important are hyperprolactinaemia &
hyperparathyroidism .
• In both sexes there is loss of libido and sexual
function, related at least in part to hyperprolactinaemia .
In women amenorrhoea is common.
• The half-life of insulin is prolonged in CRF due to reduced
tubular metabolism of insulin; insulin requirements may
therefore decline in diabetic patients in end-stage CRF.
• However, there is also a post-receptor defect in insulin
action, leading to relative insulin resistance.
• This latter abnormality is improved by dialysis treatment.

25. Bleeding
• There is an increased bleeding tendency in renal failure which
manifests in patients with advanced disease as cutaneous
ecchymoses and mucosal bleeds.
• Platelet function is impaired and bleeding time prolonged.
• Adequate dialysis treatment partially corrects the bleeding
tendency.

26. Infection
• Cellular and humoral immunity are impaired, with increased
susceptibility to infection.
• Infections are the second most common cause of death in
dialysis patients, after cardiovascular disease; they must be
recognised and treated promptly.

27. Acute or Chronic Renal failure?
• History
• Previous renal function test.
• Small kidneys on u/s
• Anaemia.
• Bone changes.

28. • Investigations and management of CRF

29. Investigations and management of CRF
• There are several aspects to the management
of CRF:
• Identify the underlying renal disease.
• Look for reversible factors which are making renal
function worse .
• Attempt to prevent further renal damage.
• Attempt to limit the adverse effects of the loss of renal
function.
• Institute renal replacement therapy (dialysis or
transplantation)

30. .At presentation the nature of the underlying
disease should be determined, if possible, by
history, examination, testing of
biochemistry, immunology, radiology and
biopsy .
• The degree of renal failure is assessed and
complications are documented.

31. Investigations
-Blood urea & serum creatinine : increased
- Serum electrolytes
.serum calcium :decreased
.serum potassium : increased ( risky )
.serum uric acid : increased(but rarely cause gout )
.serum phosphate : increased
General urine examination: for: protein , RBC , features of UTI ( may
need urine culture ) , cast ( waxy broad cast is characteristic for CRF)
Complete blood picture: usually there is anaemia.
PH of blood : metabolic acidosis.
Viral markers : HBsAg , Anti-HCV Ab & HIV test (if the patient need
dialysis ) (vaccination against hepatitis B if no previous infection;
isolation of dialysis machine if positive) .

32. ECG: look for
-Features of hyperkalemia (hyperacute T- wave ,then prolongation
of PR- interval & QRS ,then loss of P-wave , & if not managed may
cause asystole )
-Features of pericardial effusion( low voltage ECG ).
-Features of IHD.
Echocardiography: look for any evidence of pericardial effusion
or cardiomyopathy ( DCMP).
CXR: look for features of pulmonary oedema , pleural effusion , chest
infection , enlarged cardiac shadow.
Abdominal Ultrasoud : look for the size & ecchogenecity of the
kidneys & if there is ascitis.
In CRF , usually bilateral small kidneys (except polycystic kidney
disease , amyloidosis , hydronephrosis , diabetic nephropathy )

33. X- ray of bone : for evidence of renal osteodystrophy.
GFR
Renal biopsy : only indicated in CRF with normal size kidneys
( not indicated in CRF with small size kidneys ).
Patients often have bilateral small kidneys at presentation, and
in such a situation renal biopsy is usually inadvisable because
of the difficulty in making a histological diagnosis in severely
damaged kidneys and the fact that treatment is unlikely to
improve renal function significantly.

34. • If diagnosis is not known further investigation
needed as :
• Immunoglobulins and protein electrophoresis
• Urinary Bence Jones protein
• Complement
• ANA: and dsDNA if ANA is positive
• Rheumatoid factor
• ANCA: in all possible inflammatory renal disease
• Anti-GBM: in all possible inflammatory renal disease
• Cryoglobulins: if cryoglobulinaemia is clinically suspected

35. Hyperkalemia & EKG
• K > 5.5 -6
• Tall, peaked T’s
• Wide QRS
• Prolong PR
• Diminished P
• Prolonged QT
• QRS-T merge – sine
wave

37. Chronic Kidney Disease Staging
Stage Description GFR
(ml/min/1.73 m2)
1 Kidney damage with normal or   90
GFR
Kidney damage with mild  GFR 60-89
2
Moderate  GFR 30-59
3
Severe  GFR 15-29
4
Kidney failure < 15
5
(or dialysis)

38. Retarding the progression of CRF
• Unless dialysis or transplantation is provided , CRF is
eventually fatal.
• Once the plasma creatinine exceeds about 300 μmol/l (3.4
mg/dl), there is usually progressive deterioration in renal
function, irrespective of aetiology.

39. REVERSIBLE FACTORS IN CHRONIC
RENAL FAILURE
1- Hypertension
2- Reduced renal perfusion
– Renal artery stenosis
– Hypotension due to drug treatment
– Sodium and water depletion
– Poor cardiac function
3- Urinary tract obstruction
4- Urinary tract infection
5- Other infections: increased catabolism and urea production
6- Nephrotoxic medications
• CRF is usually irreversable , by controlling the reversable factors
we may delay the progression of renal impairement to ESRD.

40. Control of blood pressure
In many types of renal disease, particularly in diseases affecting
glomeruli (particularly those associated with heavy
proteinuria), control of blood pressure may retard
deterioration of GFR & delay the progression to ESRD.
The target blood pressures is 130/85 mmHg for CRF alone, &
lowered to 125/75 mmHg for those with proteinuria > 1
g/day.
Drugs can be used :
ACE inhibitors like captopril
Angiotensin II receptor antagonists like valsartan
calcium channel blockers like diltizem , amlodipine …

41. • ACE inhibitors like captopril have been shown to be more
effective at retarding the progression of renal failure , because
they reduce glomerular perfusion pressure by dilating the
efferent arteriole & reduce proteinuria
• ACE inhibitors should be used, where tolerated (check
creatinine and potassium), in all patients with diabetic
nephropathy or protein-uria > 1 g/day independent of the
presence of hypertension.
• Using ACE inhibitors need monitoring of serum potassium.
• ACE inhibitors should not be used when there is renal artery
stenosis

42. Diet
Dietary protein
For patients on renal replacement therapy , severe protein
restriction is not recommended because carry a risk of
inducing malnutrition.
Moderate restriction (to 60 g protein per day) should be
accompanied by an adequate intake of calories
calories(30-35kcal/kg/d) to prevent malnutrition.
Anorexia and muscle loss may indicate a need to
commence dialysis treatment.

43. Treatment of Anaemia of CRF
Recombinant human erythropoietin (Eprex ) is effective in
correcting the anaemia of CRF .
dose : 50 Iu / kg once or twice wk.ly
route : subcutaneously (or IV for patients on haemodialysis ).
The target haemoglobin is usually between 10 and 12 g/dl.
Complications of treatment include increased blood pressure, and
adjustment of antihypertensive medication is often necessary.
There is also an increase in blood coagulability and an increased
incidence of thrombosis of the arteriovenous fistulae used for
haemodialysis.

44. Erythropoietin is less effective in the presence of :
iron deficiency, active inflammation or malignancy, or in patients with
aluminium overload which may occur in dialysis.
Causes of Erythropoietin resistant
• Iron deficiency
• Active inflamation
• Malignancy
• Secondary hyperparathyroid
• Aluminum overload
• Pure red cell aplasia
These factors should be sought and, if possible, corrected before
treatment.
Iron supplementation should be used to keep ferritin > 100 μg/l and
transferrin saturation > 20%.

45. Fluid and electrolyte balance
• Due to the reduced ability of the failing kidney to concentrate the
urine, a relatively high urine volume is needed to excrete products
of metabolism and a fluid intake of around 3 litres/day is desirable
( when there is no fluid overload “ no oedema “ ) fluid retention
sometimes lead to episodic pulmonary oedema .
• Fluid intake:urine volume +500ml
.Limitation of potassium intake (e.g. 70 mmol/day) and
sodium intake (e.g. 100 mmol/day) may be required in late CRF if
there is evidence of accumulation
.Low phosphate diet(600-1000mg/d)

46. Hyperkalemia Treatment
• Calcium gluconate
• Sodium Bicarbonate
• Insulin/glucose
• Sodium bicarbonate
• Frusemide
• Salbutamol
• Hemodialysis

47. • Some patients with so-called salt-wasting' disease
may require a high sodium and water intake, including
supplements of sodium salts, to prevent fluid depletion and
worsening of renal function.
• This is most often seen in patients with renal cystic
disease, obstructive uropathy, reflux nephropathy or other
tubulo-interstitial diseases, and is not seen in patients with
glomerular disease.

48. Treatment of Acidosis
• The plasma bicarbonate should be maintained above 22
mmol/l by giving sodium bicarbonate supplements
(starting dose of 1 g 8-hourly, increasing as required).
• The increased sodium intake may induce hypertension or
oedema.
• calcium carbonate (up to 3 g daily) is an alternative that
is also used to bind dietary phosphate.

49. Treatment of Hypercholesterolaemia
• Statin ( as simvastatin ) achieve substantial
reductions in lipids in chronic renal disease.
Hyperlipidemia is more if the CRF is due to glomerular diseases due
to the increased hepatic lipoprotein synthesis that is triggered by
reduced oncotic pressure .

50. Treatment of Bleeding
• Adequate dialysis treatment partially corrects the bleeding
tendency.

51. Renal osteodystrophy
• To minimise the effects of CRF on bone, plasma calcium and
phosphate should be kept as near to normal as possible.
• Treatment of Hypocalcaemia
• is corrected by giving 1α-hydroxylated synthetic analogues of
vitamin D. The dose is adjusted to avoid hypercalcaemia. This
will usually prevent or control osteomalacia.
• .

52. • Treatment of Hyperphosphataemia
• Is controlled by dietary restriction of foods with high
phosphate content (milk, cheese, eggs)
• The use of phosphate-binding drugs administered with
food.
• These agents form insoluble complexes with dietary
phosphate and prevent its absorption (e.g. calcium
carbonate 500 mg with each meal and aluminium
hydroxide 300 – 600 mg before each meal).we should
avoid aluminium toxicity.
• Secondary hyperparathyroidism is usually prevented or
controlled by these measures but, in severe bone disease
with autonomous parathyroid
function, parathyroidectomy may become necessary

53. Treatment of renal osteodystropy
Vitamin D (0.25ug/d for prophylactic, 0.5ug/d
for symptomatic)
Low phosphate diet
Calcium carbonate (1-6g/d)
parathyroidectomy

54. Treatment of Myopathy
• Muscle cramps are common, and quinine sulphate may be
helpful.
• The 'restless leg syndrome', in which the patient's legs are
jumpy during the night, may be troublesome and is often
improved by clonazepam

55. Treatment of Neuropathy
• Clinical manifestations of neuropathy appear late in the
course of CRF but may improve or even resolve once dialysis
is established.
• Sensory neuropathy may cause paraesthesiae. Amitriptyline
and gabapentin may provide some symptom relief.

56. Treatment of Endocrine disorders
• Treatment with dopamine agonists is sometimes
useful for amenorrhoea or galactorrhoea in women
• Insulin requirements usually decline in diabetic
patients in end-stage CRF ( CRF patients are liable for
hypoglycemia ).
• insulin resistance is improved by dialysis treatment.

57. Gastrointestinal manifestations
• Are common at low GFRs, including anorexia followed by
nausea, and vomiting is commonly seen & improve by
dialysis.
• There is a higher incidence of peptic ulcer disease in uraemic
patients and H2-receptor antagonists or proton pump
inhibitors are commonly used.

58. Depression
• Depression is common in patients on or
approaching renal replacement therapy and
support should be provided for both them and
their relatives