Together with the brain, the kidney is potentially the
most serious organ involved in lupus. Serious in that it
may be "silently" involved - the patient not knowing that
there is disease going on, and because it may lead to
kidney failure. The early diagnosis of lupus in patients
throughout the world has contributed more than
anything else to the improved prognosis. It is now
known that if caught in time, kidney inflammation can
be treated successfully.
How frequent is kidney involvement?
Estimates vary depending on the type of clinic and the
patients studied, but it is usually said that
approximately half of all lupus patients at some stage
will have clinical evidence of kidney inflammation. It
may be that with a diagnosis of milder cases of lupus,
this percentage will fall. Fortunately, severe kidney
disease requiring kidney dialysis and even
transplantation is extremely rare in lupus.
Symptoms and signs
Kidney involvement in lupus rarely causes discomfort or
pain (as distinct, for example, from kidney stones or
infection). The most common major kidney problem is
that of protein (albumin) leakage in the urine. This can
be mild and detected only on testing, or severe
gradually leading to a lowering of the protein level in the
blood (a low plasma albumin level). When this happens
there is a tendency to ankle swelling, to fluid retention
and to general fluid "bloating".
When the kidney is inflamed the blood pressure
frequently rises and blood pressure measurement is
one of the important parts of the physical examination
of lupus patients. When the kidney is more severely
damaged its normal filtering process is grossly
impaired and toxic elements such as urea and
creatinine, normally present in the blood in small
amounts, build up, leading to weight loss, nausea and
Simple "outpatient" urine testing involves the use of a
dip-stick. Modern urine testing sticks check for a
variety of constituents in the urine including urine
sugar, albumin, blood and so on. The test simply
involves the dipping of the stick in the urine and
comparing the colour changes with a colour chart. If
the lupus patient is losing protein in the urine
("proteinuria") then the amount may need to be
quantified. These days this is done by comparing the
ratio of albumin and creatinine in a sample of urine
(albumin: creatinine ratio), which is much easier than
measuring the total protein in all the urine passed over
24-hours that used to be done. The urine sample
may also be sent to the laboratory to allow detection
of infection and for microscopic examination. Normal
urine under the microscope is clear but when there is
inflammation anywhere in the urinary tract (in the
kidneys or the bladder) cells are present, either red
cells or white cells. More important is the presence of
clumps of cells called "casts". These clumps - looking
rather like a railway train of goods wagons - are
indicative of kidney inflammation rather than bladder
inflammation and are very helpful in the diagnosis and
assessment of the kidney.
What the blood tests show
Much information concerning kidney function is
obtained from simple blood tests. The three main
blood tests affected by kidney function are the blood
urea (sometimes called blood urea nitrogen or BUN),
the creatinine and the albumin. The creatinine can be
used to complete a measurement called the eGFR
(estimated glomerular filtration rate), which helps to
grade the severity of kidney disease into 5 stages
where stage 1 is the mildest and stage 5 the worst. If
the vital filtering function of the kidney is impaired then
urea and creatinine levels start to rise and eGFR falls.
The blood level of albumin (protein) falls if leakage of
the protein in the urine is present.
In addition to these tests a number of other blood
tests give important information. These include the
sodium, potassium, calcium and phosphate levels
and the blood haemoglobin - all directly or indirectly
affected by altered kidney function.
More complicated tests
A kidney ultrasound may be done to check that two
kidneys are present and to check their size.
Sometimes other tests may be undertaken such as an
isotope renogram, which can give additional
information such as the extent that each kidney
contributes to overall function.
In some patients the only way of determining precisely
the degree of disease activity is to perform a kidney
biopsy. This is now a routine procedure in hospitals
throughout the world. It is most safely carried out
under ultrasound scanning. Following a local
anaesthetic given in the loin, a needle is inserted into
the kidney and a small core is obtained. The patient is
usually kept in hospital overnight as there is a small risk
of bleeding following biopsy. The procedure has a very
high safety margin and does not adversely affect
kidney function. The interpretation of the kidney biopsy
by the pathologist takes a lot of expertise. Put at its
most simple, the first signs are those of inflammation
(cells are seen around the filters). The second and
more serious stage is damage to the filters (glomeruli).
The most severe stage is when all the glomeruli are
scarred. There are international conventions about "staging" the severity of the kidney biopsy and
pathologists are able to judge the chances of response
to treatment from their reading of the biopsy.
It is now widely agreed that when there is kidney
inflammation a combination of steroids and an "immunosuppressive" medicine is required. For active
or severe kidney disease the most widely used
immunosuppressive is cyclophosphamide given
intermittently by injection. In the past,
cyclophosphamide was given as a tablet but this
produced more side-effects and most units have now
converted to giving intermittent "pulses". This comes in
the form of a drip given into the vein. Doses vary from
clinic to clinic but the more modern fashion has been to
use lower doses than those previously used and this
has the benefit of far less side-effects. These sideeffects
are outlined in the fact sheet Lupus and
Medication. A milder and very widely used
immunosuppressive is azathioprine given as tablet-form
usually at a dose of about 2mg/kg body weight. A
tablet that is becoming more widely used is called
mycophenolate mofetil. Studies are underway to see if
it might replace cyclophosphamide, which would be
advantageous as it does not cause as many serious
side effects as cyclophosphamide. It is also useful if a
patient does not tolerate azathioprine.
All immunosuppressives can affect the blood count and
regular blood counts are mandatory. Other
immunosuppressive drugs such as cyclosporin-A are
increasingly used but the two mainstays of treatment
remain cyclophosphamide and azathioprine.
Is dialysis helpful?
If the kidney damage reaches a stage where toxic
chemicals build up then dialysis is vital. Dialysis has
been one of the major advances in 20th century
medicine and either haemodialysis or peritoneal dialysis
has kept thousands of patients with renal failure stable.
This includes a number of patients with lupus.
Does renal transplant work?
The answer is very definitely yes. One of the surprises
in the early days of transplantation in lupus was that the
lupus did not return to damage the transplanted kidney.
The reasons for this are obscure, possibly related to the
strong treatment used for transplantation but possibly to
other factors. It is a striking fact that patients with lupus
who do have renal transplantation in general do very