End-Stage Renal Failure
End-stage renal failure (ESRF), as evidenced by a decline in
glomerular filtration rate (GFR) such that function is inadequate for health, is relatively common and
the prevalence increases with age. It can be classified in two ways, either,
according to its temporal progression, or according to its cause.
Classification by temporal progression
The rapid onset of renal failure over a period of days or weeks is
termed ‘acute renal failure’ or ‘acute
kidney injury’ (AKI), whereas a decline in GFR occurring over months to years
is termed ‘chronic renal failure’ or ‘chronic
kidney disease’ (CKD).
Classification of renal failure by cause
The cause of renal failure can be classified using the terms:
• pre-renal
• renal
• post-renal.
These indicate the anatomical site at which the aetiological
factor is acting. For example, systemic hypotension due to blood loss
will compromise the renal
blood flow and
is a ‘pre-renal’ cause
of renal failure. In contrast, inflammatory disease of the glomerulus (glomerulonephritis,
GN) is
a ‘renal’ cause
of renal failure. Enlargement of the prostate causing
obstruction to the outflow of urine is a ‘post-renal’ cause of renal failure.
Acute kidney injury
The most common cause of AKI is pre-renal failure, which if left
untreated will progress to acute tubular
necrosis (ATN). ATN occurs if
there is
persistent
hypotension/hypovolaemia and/or exposure to nephrotoxins or sepsis. It
is the cause of 60–80% of cases of AKI. ATN is quite common because the renal tubular blood supply is relatively
precarious, so that any drop
in blood pressure (secondary to hypovolaemia or reduced peripheral vascular resistance as seen in sepsis)
can lead to
tubular ischaemia. This is a direct result of the anatomical arrangement of the
blood supply, which comes to the tubules only after it has passed through
the glomerular capillary bed. Thus, there is always relative hypoxia in the renal medulla compared
with the cortex. When the mean arterial pressure
falls, there will
be a reduced
blood flow into the glomerulus via the afferent
arteriole and a consequent fall in GFR. This prompts an increase in
vasoconstriction in the efferent glomerular arteriole in an attempt
to maintain GFR, which will further compromise the blood supply to the medulla,
leading to increased hypoxia
and tubular ischaemia.
Tubular cells are also very metabolically active, with
a number of energy-requiring electrolyte pumps. All of these factors contribute
to susceptibility
to ATN.
Histologically, ATN is manifest as ragged, dying tubular cells,
which lose their
nuclei and begin
to slough off
into the tubular lumen. Patients
with pre-renal failure
should be given
fluid to restore intravascular volume
and nephrotoxins (non-steroidal anti-inflammatory
drugs [NSAIDs], gentamicin or ACEi) should be
removed. ATN usually recovers
spontaneously, although
the patient may temporarily require renal replacement therapy (RRT).
Some patients
sustain irreversible tubular atrophy and a degree of chronic kidney damage.
Other causes of
AKI include GNs
(5–10%), obstruction (5– 10%), and acute tubulointerstitial nephritis
(TIN) (<5%).
GNs are named according to the appearance of the renal biopsy.
For example, in
minimal change GN there
is no abnormality in the biopsy when viewed with a
light microscope; in membranous GN there is
thickening of the
glomerular basement membrane. IgA
nephropathy is characterised by the
deposition of IgA in the mesangium, etc. Some primary and
secondary GNs commonly present with an acute decline in renal function,
while others commonly result in CKD (see below). GNs presenting as AKI include:
• Primary – pauci immune crescentic GN, anti-glomerular
basement membrane disease (Goodpasture’s disease).
• Secondary –
lupus nephritis, antineutrophil
cytoplasmic anti- body (ANCA)-associated vasculitis.
Patients with acute GN may require RRT as well as treatment for
the underlying disease (e.g.
immunosuppression +/– plasma
exchange). The success
of these treatments
is variable; some patients
partially regain renal function while others become permanently
dialysis-dependent.
Acute TIN often occurs as the result of an ‘allergic reaction’ to
medications, both prescription drugs such as proton pump inhibitors or
antibiotics, and herbal
remedies. Renal biopsy
demonstrates an
intense lymphocytic infiltrate in the interstitium, including
numerous eosinophils. Management involves removal of the likely causative agent
and the administration of oral corticosteroids
to reduce renal
inflammation. This usually
results in the resolution of acute inflammation, but
some patients are left with irreversible
interstitial fibrosis and
tubular atrophy, which
may contribute to the subsequent development of CKD.
CKD
CKD can be
completely asymptomatic until
its very terminal stages. Eventually anaemia (manifest
as tiredness or even congestive cardiac failure), uraemia (resulting in nausea,
reduced appetite and confusion), phosphate build-up (leading to itchiness)
and/or severe hypertension (causing
headache or blurred
vision) may prompt the
patient to seek
medical attention, where
a routine blood test reveals high
urea and creatinine due to a reduced GFR. In contrast to AKI, where pre-renal
and post-renal causes predominate, the causes of CKD tend to be renal in
origin. These include:
• diabetes mellitus with
associated diabetic nephropathy
• hypertensive nephropathy
• obstructive uropathy
(often secondary to prostatic hypertrophy)
• chronic primary GN, e.g.
IgA nephropathy or focal segmental glomerulosclerosis (FSGS)
• chronic secondary GN,
e.g. lupus nephritis
• adult polycystic kidney
disease (APKD)
• chronic pyelonephritis
• renovascular disease.
CKD is classified into different stages according to the patient’s
GFR and the presence of urine dipstick abnormalities. These have allowed the
development of management
guidelines for patients with stable CKD, and facilitate the
provision of consistent care.
Diseases that recur in the transplant
A number of causes of renal failure may reoccur in the allograft.
These include:
• structural problems –
bladder outflow obstruction
• renal calculi
• urinary tract infections
with associated chronic pyelonephritis
• primary GNs – IgA, FSGS,
mesangiocapillary glomerulonephritis (MCGN)
• secondary GNs –
ANCA-associated vasculitis, lupus nephritis, diabetic nephropathy.
