Chronic renal failure
Dr.H.N.Sarker
FCPS(Medicine),MACP(USA),
MRCP(UK),FRCP(GLASGO)
Associate Professor.
Medicine
Introduction
Chronic renal failure (CRF) refers
to an irreversible deterioration in
renal function which classically
develops over a period of years .
Introducttion
Initially, it is manifested 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.
Introducttion
When death is likely without renal
replacement therapy, it is called end-stage
renal failure (ESRF).
Introducttion
The Kidney Disease Outcomes Quality
Initiative (K/DOQI) of the National Kidney
Foundation (NKF) defines chronic kidney
disease as either kidney damage or a
decreased kidney glomerular filtration rate
(GFR) of less than 60 mL/min/1.73 m2 for
3 or more months.
Introducttion
Whatever the underlying etiology, the
destruction of renal mass with irreversible
sclerosis and loss of nephrons leads to a
progressive decline in GFR. The different
stages of chronic kidney disease form a
continuum in time; prior to February 2002,
no uniform classification of the stages of
chronic kidney disease existed.
Introducttion
At that time, K/DOQI published a
classification of the stages of chronic
kidney disease, as follows:
Stage 1: Kidney damage with normal or
increased GFR (>90 mL/min/1.73 m2)
Stage 2: Mild reduction in GFR (60-89
mL/min/1.73 m2)
Introducttion
Stage 3: Moderate reduction in GFR (3059 mL/min/1.73 m2)
Stage 4: Severe reduction in GFR (15-29
mL/min/1.73 m2)
Stage 5: Kidney failure (GFR <15
mL/min/1.73 m2 or dialysis)
Introducttion
In stage 1 and stage 2 chronic kidney
disease, GFR alone does not clinch the
diagnosis. Other markers of kidney
damage, including abnormalities in the
composition of blood or urine or
abnormalities in imaging tests, should also
be present in establishing a diagnosis of
stage 1 and stage 2 chronic kidney
disease.
Pathophysiology
Approximately 1 million nephrons are
present in each kidney, each contributing
to the total GFR. Regardless of the
etiology of renal injury, with progressive
destruction of nephrons, the kidney has an
innate ability to maintain GFR by
hyperfiltration and compensatory
hypertrophy of the remaining healthy
nephrons.
Pathophysiology
This nephron adaptability allows for
continued normal clearance of plasma
solutes so that substances such as urea
and creatinine start to show significant
increases in plasma levels only after total
GFR has decreased to 50%, when the
renal reserve has been exhausted. The
plasma creatinine value will approximately
double with a 50% reduction in GFR.
Pathophysiology
A rise in plasma creatinine from a baseline
value of 0.6 mg/dL to 1.2 mg/dL in a
patient, although still within the reference
range, actually represents a loss of 50% of
functioning nephron mass.
Types and causes
Chronic renal failure (CRF) can be
classified by the site (location) of primary
damage:
Pre-renal CRF
Renal CRF
Post-renal CRF (obstructive uropathy)
Pre-Renal CRF
Some medical conditions cause continuous
hypoperfusion (low blood flow) of the
kidneys, leading to kidney atrophy
(shrinking), loss of nephron function, and
chronic renal failure (CRF).
Pre-Renal CRF
These conditions include
poor cardiac function,
chronic liver failure,
and
atherosclerosis ("hardening") of the
renal arteries.
Each of these conditions can induce
ischemic nephropathy
Renal CRF
Chronic renal failure caused by changes
within the kidneys, is called renal CRF,
and is broadly categorized as follows:
Diabetic nephropathy- kidney disease
associated with diabetes; the most
common cause of CRF
Renal CRF
Hypertensive nephrosclerosis- the
second leading cause of CRF
Chronic glomerulonephritis, a condition
caused by diseases that affect the
glomeruli and bring about progressive
dysfunction –
Membranous nephropathy,
immunoglobulin A (IgA) nephropathy,
Renal CRF
focal and segmental glomerulosclerosis
(FSGS),
membranoproliferative glomerulonephritis,
rapidly progressive (crescentic)
glomerulonephritis
Renal CRF
Chronic interstitial nephritis- a condition
caused by disorders that ultimately lead to
progressive scarring of the interstitium
Renal vascular CRF- large vessel
abnormalities such as renal artery
stenosis (narrowing of the large arteries
that supply the kidneys)
Renal CRF
Vasculitis, inflammation of the small blood
vessels– systemic lupus erythematosus
– scleroderma
– Goodpasture syndrome
– Wegener granulomatosis
– mixed cryoglobulinemia
– Henoch-Schönlein purpura,
Renal CRF
Cystic kidney disease, kidney disease
distinguished by multiple cysts
(Polycystic kidney disease )
Hereditary diseases of the kidney, such as
Alport's syndrome
Post-Renal CRF
Interference with the normal flow of urine
can produce backpressure within the
kidneys, can damage nephrons, and lead
to obstructive uropathy, a disease of the
urinary tract.
Abnormalities that may hamper urine flow
and cause post-renal CRF include the
following:
Post-Renal CRF
Bladder outlet obstruction due to an
enlarged prostate gland or bladder stone
Neurogenic bladder, an overdistended
bladder caused by impaired communicator
nerve fibers from the bladder to the spinal
cord
Post-Renal CRF
Kidney stones in both ureters .
Retroperitoneal fibrosis.
Vesicoureteral reflux (VUR), the
backward flow of urine from the bladder
into a ureter
Pathogenesis
Disturbances in water, electrolyte and acidbase balance contribute to the clinical
picture in patients with CRF, but the exact
pathogenesis of the clinical syndrome of
uraemia is unknown.
Pathogenesis
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.
Clinical Feature
Patients with chronic kidney disease
stages 1-3 (GFR >30 mL/min) are
generally asymptomatic and do not
experience clinically evident disturbances
in water or electrolyte balance or
endocrine/metabolic derangements.
Clinical Feature
Generally, these disturbances clinically
manifest with chronic kidney disease
stages 4-5 (GFR <30 mL/min). Uremic
manifestations in patients with chronic
kidney disease stage 5 are believed to be
primarily secondary to an accumulation of
uraemic toxins .
Clinical Feature
Patient usually presents with features of
hyperkalemia , metabolic acidosis and
uremia.
Clinical Feature
Uraemic symptoms can affect every organ
system, most noticeably the following:
Gastrointestinal system–
anorexia,nausea, vomiting, food distaste
(often described as bland, metallic, "like
cardboard"), hiccup .
Clinical Feature
Neurological system–cognitive
impairment, personality change, asterixis
(motor disturbance that affects groups of
muscles), muscular twitching, fits,
drowsiness and coma.
Clinical Feature
Blood-forming system–anemia due to
relative deficiency of erythropoietin
diminished erythropoiesis due to toxic effects of
uraemia on marrow precursor cells
reduced red cell survival
increased blood loss due to capillary fragility and
poor platelet function
reduced dietary intake and absorption of iron and
other haematinics
– easy bruising and bleeding due to abnormal platelets
Clinical Feature
Pulmonary system–fluid in the lungs,
with breathing difficulties
Cardiovascular system –chest pain due
to inflammation of the sac surrounding the
heart (pericarditis) and pericardial effusion
(fluid accumulation around the heart)
Skin –generalized itching, pruritus.
Myopathy.
Clinical Feature
Renal osteodystrophy -This metabolic
bone disease which accompanies CRF
consists of a mixture of osteomalacia,
hyperparathyroid bone disease (osteitis
fibrosa), osteoporosis and osteosclerosis .
Clinical Feature
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.
Clinical Feature
The physical examination often is not very
helpful but may reveal findings
characteristic of the condition underlying
chronic kidney disease (eg,
hypertension,diabetis, severe
arteriosclerosis , lupus)or complications of
chronic kidney disease (eg, anemia,
bleeding diathesis, pericarditis).
Investigations
Haematology
Full blood count
UrinanalysisDipstick proteinuria may suggest a
glomerular or tubulointerstitial problem.
The urine sediment finding of RBCs, RBC
casts, suggests proliferative glomerulonephritis.
Investigations
Urinanalysis- Pyuria and/or WBC casts
are suggestive of interstitial nephritis
(particularly if eosinophiluria is present) or
urinary tract infection.
Twenty-four–hour urine collection for total
protein and CrCl
Investigations
Biochemistry
Urea, electrolytes and creatinine
Calcium, phosphate and albumin
Parathyroid hormone
Lipids, glucose ± HbA1c
Investigations
ImagingRenal ultrasound- Small echogenic
kidneys are observed in advanced renal
failure. Structural abnormalities, such as
polycystic kidneys, also may be observed.
This is a useful test to screen for
hydronephrosis.
Investigations
Chest X-ray: heart size, pulmonary
oedema
ECG: if > 40 years or there are risk factors
for cardiac disease
Renal artery imaging: if renovascular
disease is suspected
Investigations
Histology- Renal biopsy.
Microbiology-Hepatitis and HIV serology:
if dialysis is needed (vaccination against
hepatitis B if no previous infection;
isolation of dialysis machine if positive)
Investigations
Immunology -
Group and save
Tissue typing
Cytomegalovirus,Epstein-Barr virus,
varicella zoster virus
Investigations
if transplantation is considered If diagnosis
is not knownImmunoglobulins and protein
electrophoresis
Urinary Bence Jones protein
Complement
Investigations
ANA: and dsDNA if ANA is positive
ENA: if a connective tissue disorder is
suspected
Rheumatoid factor ANCA: in all possible
inflammatory renal disease
Anti-GBM: in all possible inflammatory
renal disease
Management
Once CRF has been diagnosed, the
physician attempts to determine the cause
and, if possible, plan a specific treatment.
Nonspecific treatments are implemented
to delay or possibly arrest the progressive
loss of kidney function.
Management
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,
transplantation) when appropriate.
Management
Treatment of the underlying causesome causes of CRF are amenable to
treatment eg. Glomerulonephritis with
immunosuppressive therapy.
Management
Retarding the progression of CRFControl of blood pressure -control of
blood pressure may retard deterioration of
GFR. Various target blood pressures have
been suggested: for example, 130/85
mmHg for CRF alone, lowered to 125/75
mmHg for those with proteinuria > 1 g/day.
Management
ACE inhibitors have been shown to be more
effective at retarding the progression of renal
failure than other therapies which lower
systemic blood pressure to a similar degree .
This may be because they reduce glomerular
perfusion pressure by dilating the efferent
arteriole. Angiotensin II receptor antagonists
also reduce glomerular perfusion pressure
and can be used.
Management
Diet -Restrict dietary protein,Moderate
restriction for a CRF patient is about 0.6 to
0.8 gm/kg/day(to 60 g protein per day) and
this should be accompanied by an
adequate intake of calories to prevent
malnutrition.
Management
Limiting the adverse effects of CRF –
Anaemia -Anaemia is common; it
usually correlates with the severity of renal
failure and contributes to many of the nonspecific symptoms of CRF.
Recombinant human erythropoietin is
effective in correcting the anaemia of CRF.
The target haemoglobin is usually
between 100 and 120 g
Management
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.
Management
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. These patients benefit from taking 5-10
g/day (85-170 mmol/day) of sodium chloride by
mouth.
Management
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.
Management
Infection - they must be recognised and
treated promptly.
Renal osteodystrophy- plasma calcium
and phosphate should be kept as near to
normal as possible.
Hypocalcaemia is corrected by giving 1αhydroxylated synthetic analogues of
vitamin D. The dose is adjusted to avoid
hypercalcaemia.
Management
Hyperphosphataemia is controlled by dietary
restriction of foods with high phosphate content
(milk, cheese, eggs) and the use of phosphatebinding drugs administered with food (e.g.
calcium carbonate and aluminium hydroxide).
Secondary hyperparathyroidism is usually
prevented or controlled by these measures but,
in severe bone disease with autonomous
parathyroid function, parathyroidectomy may
become necessary.
Management
Renal replacement therapy (RRT)
Early preparation is important. The health
care team educates the patient about the
different procedures involved in RRT,
which include the following:
Hemodialysis—removal of toxic
elements from the blood, which is filtered
through a membrane while circulated
outside of the body
Management
Peritoneal dialysis—filtration through the
lining membrane of the abdominal cavity;
fluid is instilled into the peritoneal space,
then drained
kidney transplantation.