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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2683_Библиотеки_им_академика_М_И_Перельмана.pdf
Renal, genitourinary and sexual health medicine
tubular necrosis the patient cannot concentrate the urine
or conserve sodium, an urinary sodium level is more than
40 mmol/L and the urine is dilute. These parameters are less
reliable if the patient is taking diuretics.
CLINICAL NOTES
Be suspicious, as the first presentation for
myeloma can be with an acute kidney injury.
Request urinary electrophoresis for Bence Jones
protein if you are considering an underlying
myeloma.
RED FLAG
Blood and protein (if the absence of infection) on
urine analysis suggests underlying glomerular
disease. Consider rapidly progressive
glomerulonephritis if this is occurring with an AKI.
Blood tests
• Full set of blood tests; FBC, renal and bone profile, liver
function tests (with attention to albumin), CRP and
bicarbonate. The renal profile and bicarbonate level
should be monitored at least daily.
HINTS AND TIPS
It is important to ascertain a patient’s baseline renal
function. This may require detective work (i.e. calls
to GP, and rummaging through old notes). Look for
whether the patient has previously had an acute
kidney injury, and in what context.
RED FLAGS
In any patient with renal failure pay careful
attention to the potassium level; a high potassium
level is life-threatening. Be concerned about a
potassium level above 5.8 mmol/L; a potassium
level above 6.5 mmol/L can lead to arrhythmias
and cardiac arrest. Worry most about a short-term
rise from the patient’s normal potassium level.
Other tests
• For specific blood tests, the earlier discussion of see
haematuria/proteinuria.
• Electrocardiogram (ECG) can show the precipitating
cause (e.g. myocardial infarction) or complications
such as pericarditis (saddle-shaped ST segments) or
hyperkalaemia (peaked T waves).
• Chest X-ray (CXR) if fluid overload is suspected; look
for underlying infection or pulmonary haemorrhage.
• Renal ultrasound scan to rule out hydronephrosis (i.e.
postrenal cause); pay attention to kidney size; large size
(i.e. >14 cm) in polycystic kidney disease, and often
with diabetes or HIV; small size (<10 cm) suggests
chronic renal impairment.
• Renal Doppler scan. This can establish if there is
underlying renal artery stenosis, a cause of prerenal
failure. MRA is less operator dependent and is often
used. MRA uses a gadolinium-based contrast agent.
This is different from the iodinated contrast agent used
with a CT scan. The gadolinium is not nephrotoxic
like the contrast agent used with the CT scan, but does
have a potential to cause nephrogenic systemic fibrosis,
which is seen more commonly in patients with renal
dysfunction; this is a rare but serious condition.
• Renal biopsy. This invasive test is often performed
to establish an underlying diagnosis if intrinsic renal
disease is suspected.
Management
Once the presence of AKI has been established, treatment
is supportive. Attention should be placed on confirming the
underlying cause of AKI and minimizing ongoing injury.
Pay attention to careful fluid management and avoidance
of nephrotoxic medications; aim to avoid contrast imaging,
prevent hypotension, treat obstruction and treat the underlying cause (e.g. sepsis, cardiac or liver failure).
CLINICAL NOTES
Indications for urgent dialysis:
• resistant hyperkalaemia
• pulmonary oedema
• uraemic pericarditis
• severe acidosis
Hyperkalaemia
Hyperkalaemia is life-threatening if potassium level is greater
than 6.5 mmol/L. Stop the use of any drugs that could be
contributing (e.g. angiotensin-converting enzyme (ACE) inhibitors, spironolactone, intravenous fluid containing potassium, e.g. Hartmann solution). Perform an ECG to look for
evidence of myocardial irritability. If ECG changes are present,
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Chronic kidney disease
3030
give 10 mL of 10% calcium gluconate (see Chapter 31).
Medical treatment begins with the ABCDE approach. Seek senior help, and give 10 units of insulin (as Actrapid) with 50 mL
of 50% dextrose through a large-bore cannula, as high dextrose concentrations can cause thrombophlebitis. You may see
100 mL of 20% dextrose being used as this is less likely to cause
this complication. Repeat potassium measurement every 4–6
hours. Salbutamol nebulizers can also be used in addition to
the insulin. These therapies are just a holding measure and
act by shifting potassium intracellularly. However, potassium
wasting can be achieved through use of diuretics, to increase
renal potassium loss (e.g. with furosemide). This can be used
if the patient is still passing urine. Calcium Resonium (a calcium polystyrene sulfonate resin) taken with regular lactulose,
removes potassium via the gastrointestinal tract; however, this
has a slow affect, and it should not be used as a therapy in
the acute setting. Recently novel potassium binders have been
introduced, such as Patiromer, which acts to increase faecal
potassium excretion. Hyperkalaemia resistant to medical
treatment is an indication for dialysis.
Acidosis
A persistent severe acidaemia is an indication for dialysis.
Sodium bicarbonate replacement can be used in the first instance to help correct the acidosis; it will also lower the potassium level in the context of an acidaemia. Venous blood
gases are a rapid way to check pH.
modynamic compromise. All renal replacement therapies correct the electrolyte imbalances, remove toxins and can remove
fluid, albeit at different rates. Haemodialysis treatments require
central venous access using a large-bore cannula; peritoneal dialysis requires insertion of a peritoneal catheter (a Tenckhoff
catheter) into the peritoneal space.
Supportive management
The prognosis of patients with AKI depends on the cause,
the presence of any other organ impairment and the patient’s premorbid state. They are at risk of further AKI and
developing CKD.
Summary
AKI is often predictable and avoidable.
It is often multifactorial; pay attention to fluid status,
drugs, contrast agent and relative hypotension.
Perform a urine dipstick test to establish whether there is
intrinsic renal disease.
If you are considering obstruction, a renal ultrasound
scan should be performed within 24 hours to rule out hydronephrosis; if you are considering pyonephrosis (infected
and obstructed kidney), a renal ultrasound scan should be
performed within 6 hours.
Hyperkalaemia is an emergency and needs prompt recognition and treatment.
Pulmonary oedema
This may be life-threatening, particularly in patients with a
reduced urine output. Conventional therapies may be used:
high-flow oxygen, diuretics (high doses may be necessary),
nitrates and opiates (caution: use low doses as these drugs
are excreted renally). Noninvasive positive pressure ventilation may be helpful. In the absence of a reasonable urine
output, renal replacement therapy will be required.
COMMON PITFALLS
Diuretic use to drive urine output does not improve renal function. Diuretics can help with the management
of pulmonary oedema and hyperkalaemia in the patient
with salt and fluid overload, if urine is still being passed.
Renal replacement therapies
Emergency dialysis can include use of intermittent haemodialysis, emergency peritoneal dialysis (less frequently used, see the
discussion on CKD later) and haemofiltration. Haemodialysis
is intermittent treatment, generally lasting 3–4 hours and can
be performed on the ward (it is also used in an outpatient setting in chronic dialysis. Fast electrolyte shift and fluid removal
can result in haemodynamic compromise. Generally, haemofiltration is performed in a high-dependency or critical care
environment; it is slow and continuous and results in less hae-
CHRONIC KIDNEY DISEASE
‘Chronic kidney disease’ (CKD) describes an irreversible reduction in renal function. It is classified in stages in relation
to the eGFR and ACR. CKD is a risk factor for cardiovascular disease. This is the leading cause of death in people
with renal impairment. As a rough guide, patients start to
need activated vitamin D, phosphate control and anaemia
management at CKD stage IV (Table30.5). At CKD stage
V the patient may start getting symptoms of uraemia, and
renal replacement therapy is started.
Most patients with CKD are managed in primary care,
and the management is focused on prevention of cardiovascular disease and blood pressure control. The following
groups of patients need to be referred to secondary care:
• severe renal failure (eGFR <30 mL/min per 1.73 m2);
• ACR of 70 mg/mmol or ACR greater than 30 mg/mmol
with haematuria;
• progressive loss of renal function, sustained decrease of
GFR of 15 mL/min/1.73 m2 or more within 12months,
or a sustained decrease in GFR of 25%;
• hypertension that remains poorly controlled despite
the use of at least four antihypertensive drugs at a
therapeutic dose;
• suspected rare or genetic causes of CKD;
• suspected renal artery stenosis
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Renal, genitourinary and sexual health medicine
Table30.5 Classification of chronic kidney disease
GFR
category
G1 >90 Normal or high
G2 60–89 Mildly decreased
G3a 45–59 Mildly to moderately
G3b 30–44 Moderately to severely
G4 15–29 Severely decreased
G5 <15 Kidney failure
GFR, Glomerular filtration rate.
Reproduced with permission from Of, O.J.O.S., 2013. Kidney
Disease: Improving Global Outcomes (KDIGO) CKD Work Group.
KDIGO 2012 clinical practice guideline for the evaluation and
management of chronic kidney disease. Kidney Int Suppl, 3(1),
pp. 5–14.
GFR (mL/
min/1.73 m2) Terms
decreased
decreased
CLINICAL NOTES
You should pay great attention to whether your
patient has proteinuria. The albumin-to-creatinine
ratio is used to prognosticate. The greater the
proteinuria, the higher the risk of progressive renal
failure, and the presence of proteinuria increases
the risk of cardiovascular death. See Table30.6
Aetiology
Identifying the cause of CKD is important to guide specific
treatments, establish the risk to other family members and
establish the risk of recurrence after renal transplantation.
Common causes include:
• diabetes mellitus: hypertension;
Table30.6 Classification of albumin-to-creatine ratio
categories in chronic kidney disease
ACR category ACR (mg/mmol) Terms
A1 <3 Normal to mildly
A2 3–30 Moderately
A3 >30 Severely
Including nephrotic syndrome (ACR usually >250 mg/mmol)
ACR, Albumin-to-creatine ratio,
Reproduced with permission from Of, O.J.O.S., 2013. Kidney
Disease: Improving Global Outcomes (KDIGO) CKD Work Group.
KDIGO 2012 clinical practice guideline for the evaluation and
management of chronic kidney disease. Kidney Int Suppl, 3(1),
pp. 5–14.
increased
increased
increased
• glomerulonephritis: both primary and secondary (see
later);
• infective, obstructive and reflux nephropathies;
• renovascular causes (e.g. renal artery stenosis);
• interstitial nephritis: generally from drugs, including
NSAIDs, proton pump inhibitors and antibiotics;
• inherited disease (e.g. autosomal dominant polycystic
kidney disease) and Alport disease (type IV collagen
defect associated with sensorineural deafness);
• multisystem diseases (e.g. SLE);
• hypercalcaemia;
• neoplasms (e.g. myeloma);
• amyloidosis.
HINTS AND TIPS
IS IT AN ACUTE KIDNEY INJURY OR CHRONIC
KIDNEY DISEASE?
The single best test to help is a renal ultrasound
scan. Small scarred kidneys suggest chronic
kidney disease (CKD). In acute kidney injury (AKI)
the kidneys generally have a normal appearance.
Look for historical blood test results; this may
involve a degree of detective work.
If your patient has a long-standing history of malaise,
fatigue, poor appetite, itch and cramps, this suggests
CKD. Anaemia also points towards a more chronic
picture, as do biochemical disturbances, including
calcium and phosphate level derangements, although
these can still be seen with an AKI.
Clinical features
Progressive loss of renal function per se does not cause
symptoms until the eGFR falls to very low levels (<30 mL/
min/1.73 m2; i.e. stage IV or stage V CKD). These patients
should be managed in renal clinics. Under these circumstances patients may develop fatigue, nausea, taste disturbance, cramps, itching and inability to concentrate their
urine overnight (i.e. increased nocturnal micturition and
fluid balance disorders, e.g. leg oedema). Symptom relief
can be given for itch and cramps, and fluid imbalances can
be corrected through reduction of salt intake, fluid restriction and use of diuretics.
With progressive stage IV or stage V CKD, preparations
should be made for the patient’s chosen renal replacement
therapy (e.g. peritoneal dialysis, haemodialysis or
transplantation). This should include patient education,
counselling and the involvement of the multidisciplinary
team if they have not already been introduced to the
patient.
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Chronic kidney disease
3030
When examining the CKD patient, focus your examina-
tion on:
• the underlying cause of renal dysfunction (e.g.
vascular complications, diabetic complications, signs
of hypertension, features of active lupus or vasculitis);
• reversible causes: assess fluid status, renal bruit
indicative of renal artery stenosis, renal outflow
obstruction (e.g. palpable bladder);
• Indications of progressing towards need of renal
replacement therapy/reaching end stage renal disease:
such as disorders of fluid balance with salt and fluid
overload, (ask about paroxysmal nocturnal dyspnoea
and orthopnoea), fatigue, weight loss, poor appetite,
vomiting, severe itch, uraemic flap, and pericarditis.
Investigations
The same initial investigations used in AKI should be requested (see earlier). Urine ACR are PCR are important in
the patient with chronic renal failure.
Management
The aims of treatment are to minimize further deterioration
CLINICAL NOTES
If renal function declines faster than anticipated,
consider reversible causes (e.g. infection or
obstruction). You should repeat a renal ultrasound
scan to exclude acute hydronephrosis.
in renal function and to prevent or treat the complications of
renal failure. The most significant complication of CKD is premature cardiovascular disease. This accounts for the high mortality in this group and explains why a large proportion of these
patients do not survive long enough to develop stage V CKD.
Use of nephrotoxic drugs should be discontinued,
and use of drugs that are excreted renally may need to be
stopped or their dose may need to be reduced.
Prevention of decline in renal function
Blood pressure, glucose level and acidosis should be tightly
controlled as these factors can affect the rate of deterioration of kidney function. Keep the blood pressure below
140/90 mmHg (if ACR >70 mg/mmol or if the patient is diabetic the target is <130/80 mmHg) and the haemoglobin
A1c level between 48 and 58 mmol/L. If there is proteinuria
or if diabetes is present, then ARBs should be the drug of
choice. Watch out for intercurrent infection and any nephrotoxic medications as these can hasten the deterioration in
kidney function.
Prevention of complications
Cardiovascular
Control of hypertension is the mainstay of reducing the rate
of progression of renal failure and preventing cardiovascular
complications. High cholesterol levels should be aggressively
treated. All patients with CKD should be offered atorvastatin, 20 mg (National Institute for Health and Care Excellence
[2011, updated 2017] Chronic kidney disease in adults. NICE
quality standard 5). All patients should receive lifestyle advice, including smoking cessation and exercise advice.
Renal osteodystrophy
Renal bone disease is due to a combination of disturbed
vitamin D metabolism, decreased ability to renally excrete
phosphate and secondary hyperparathyroidism. Serum
phosphate levels are raised; vitamin D is unable to be activated in the kidney, resulting in a fall in serum calcium level,
and an appropriate rise in PTH level. Treatment revolves
around giving synthetic vitamin D analogues (increases calcium and phosphate levels and will lower PTH level), and
reducing phosphate level to the normal range through diet
modification and phosphate binders taken with meals. If attention is not given to give synthetic vitamin D and control
of serum phosphate level, then tertiary hyperparathyroidism (i.e. autologous PTH production) can ensue. Cinacalcet
(a calcium mimetic) or parathyroidectomy may be required
to treat this.
RED FLAGS
Pay attention to diabetic medications. As renal
impairment advances, your patient is likely to need
less insulin. Ask about hypoglycaemia. Stop use of
metformin at an estimate glomerular filtration rate
of less than 30 mL/min/1.73 m2 as there is a risk of
lactic acidosis. Pay attention to opiate medications
as these are excreted renally and may accumulate,
causing drowsiness or even a reduced Glasgow
Coma Score (GCS).
CLINICAL NOTES
A high phosphate level and a high calcium level are
additional risk factors for cardiovascular disease.
Careful attention must be paid to keeping the
phosphate level within the normal range.
Acidosis
Systemic acidosis accompanies declining renal function. It increases myocardial excitability, accelerates renal bone disease
and may contribute to increased potassium levels. Sodium
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Renal, genitourinary and sexual health medicine
bicarbonate supplements will help to maintain serum bicarbonate levels within the normal range, (>22 mmol/L).
Correction of acidosis may help prevent loss of renal function.
Anaemia
In renal failure, there is a normochromic normocytic anaemia due to the kidneys’ inability to produce erythropoietin.
However, be suspicious of blood loss if the anaemia is disproportionate to the degree of renal impairment. Ferritin,
vitamin B12 and folate deficiency should be corrected.
Recombinant human erythropoietin (epoetin) is generally
required in stage IV/V CKD and the dose should be adjusted to maintain a target haemoglobin level of 100–120
g/L. This can relieve symptoms related to anaemia, and
decrease the need for blood transfusions, but epoetin can
cause hypertension.
Hyperkalaemia
Correction of acidosis and dietary restrictions help to control potassium levels. Always pay attention to serum potassium level in CKD. High-risk groups are those with stage
IV/V CKD, those with diabetes and those taking ACE inhibitors/ARBs and aldosterone antagonists (e.g. spironolactone). Chocolate, crisps and fresh fruits (e.g. bananas and
oranges) are examples of foods high in potassium.
End-stage renal failure
End-stage renal failure (ESRF) is identified on biochemical
and clinical grounds as the point when, despite conservative measures, the patient will die without the institution of
renal replacement therapy. When renal replacement therapy is initiated in a patient with stage V CKD the patient
is defined as having reached ESRF. Specific indications
for starting dialysis include symptomatic uraemia, hyperkalaemia, metabolic acidosis, pericarditis and inability
to control fluid status and blood pressure with advanced
renal failure. The need for dialysis is generally predictable, allowing the creation of access (e.g. fistula creation/
peritoneal tube insertion) and education, counselling and
home adjustments before it is required. Renal replacement
includes peritoneal dialysis where a Tenckhoff catheter is
placed into the abdomen to allow fluid to flow in and out,
and uses the peritoneal membrane as the dialysis membrane. Peritoneal dialysis can allow manual exchanges
of fluid (continuous ambulatory peritoneal dialysis), or
night-time automated exchanges (automated peritoneal
dialysis). Haemodialysis uses either a fistula or, less optimally, an indwelling dual-lumen central venous catheter.
The fistula is favoured as it is associated with fewer infections and improved survival. Haemodialysis generally
occurs in a hospital- or community-based dialysis unit,
with individuals attending for 4 hours three times a week.
Home haemodialysis, with the option of overnight dialysis, is also growing in popularity for certain motivated
patient groups. Problems with dialysis include loss of vascular access, infection, hypotension and the maintenance
of fluid and electrolyte balance.
Renal transplantation is associated with the greatest survival advantage. The patient needs to be fit enough for the
surgery and to tolerate the immunosuppressive regimen.
Generally, a triple regimen of a calcineurin inhibitor (e.g.
tacrolimus), an antiproliferative (e.g. mycophenolate mofetil)
and a steroid (e.g. prednisolone) is used. This is used to prevent rejection but predisposes the individual to infection
and malignancies. Nephrologists trend a fine line, balancing
under-immunosuppression, which can result in graft rejection, and over-immunosuppression, risking nephrotoxicity
from high levels of calcineurin inhibitor, opportunistic infections and malignancies. Other complications of transplantation include transplant renal artery stenosis, graft thrombosis,
obstruction of the ureteric anastomosis, de novo glomerulonephritis, recurrence of original disease and gradual loss of
function with time (chronic allograft nephropathy, thought
to be due to chronic rejection and calcineurin inhibitor use).
GLOMERULAR DISEASE
Glomerular disease may be primary or secondary (i.e. a
manifestation of systemic disease) (Box30.19). It may present acutely with an AKI or be picked up incidentally and
cause CKD.
CLINICAL NOTES
Systemic disorders that can involve the glomerulus:
• diabetes
• amyloidosis
• systemic lupus erythematosus
• rheumatoid arthritis
• ankylosing spondylitis
• neoplasia
• myeloma
• vasculitic syndromes
• liver disease
• sarcoidosis
• partial lipodystrophy
Clinical features
Glomerular disease is associated with the presence of blood
and protein on urine analysis and hypertension (Table30.7).
Glomerulonephritis is often categorized as nephritic and
nephrotic syndromes. Nephritic syndromes include diseases which cause damage to the glomerulus, mesangium,
glomerular endothelium or basement membrane. They are
associated with nonvisible haematuria, protein leak below
the nephrotic range (<3 g/day), impaired renal function
and, often, hypertension. They include diseases that can
262
Glomerular disease
Table30.7 Relationship between glomerular diseases and clinical presentations
Proteinuria/
Minimal change + − − ± − −
FSGS + − − ± + +
Membranous + − ± − + +
IgA nephropathy ± + ± ± + +
MCGN + + − + + +
Diffuse/proliferative − + − + − +
RPGN − + − + − +
Any given disease may present in a number of ways and, conversely, a particular clinical presentation may have a number of possible
causes.
AKI, Acute kidney injury; CKD, chronic kidney disease; FSCS, focal segmental glomerulosclerosis; MCGN, mesangiocapillary
glomerulonephritis; RPGN, rapidly progressive glomerulonephritis.
nephrotic syndrome
Haematuria/
nephritic
syndrome Renal pain AKI CKD Hypertension
3030
range from slow grumbling glomerulonephritis to a rapidly progressive glomerulonephritis, a renal emergency.
Nephrotic syndrome, caused through dysfunction of podocytes, results in heavy protein leak but generally with a
preserved excretory renal function (i.e. normal creatinine
level). However, proteinuria is nephrotoxic and will lead to
renal impairment if left untreated.
Nephritic syndrome
‘Nephritic syndrome’ refers to the combination of proteinuria, haematuria on urine analysis (referred to as an ‘active
urinary sediment’), renal failure and often hypertension.
Many renal diseases can give this nephritic picture.
RED FLAG
Blood and protein with an acute kidney injury
should raise alarm bells. Is this a rapidly
progressive glomerulonephritis? If it is and it is left
untreated, the patient could have end-stage renal
failure within days.
Nephrotic syndrome
Nephrotic syndrome is the triad of significant proteinuria
(protein >3 g/day), hypoalbuminaemia (albumin <30 g/L)
and peripheral oedema. Many cases are due to primary
glomerulonephritis (e.g. minimal change disease), membranous glomerulonephritis and focal segmental glomerulosclerosis (FSGS). Examples of secondary causes include
diabetes, amyloid, HIV and SLE. Other clinical features
include hyperlipidaemia due to increased hepatic synthesis, a prothrombotic tendency due to urinary loss of antithrombin III, protein C and protein S, and increased risk
of infection due to urinary loss of immunoglobulins. Renal
biopsy is indicated in most adults to establish a histological
diagnosis. Treatment is aimed at inducing remission and
preventing relapse. ACE inhibitors and ARBs are often prescribed to help reduce proteinuria.
History
It is important to ask about any urinary symptoms, any change
in volume and any visible haematuria or frothy urine. Other
symptoms can help point towards the underlying disease
(e.g. rapidity of onset (rapid-onset renal failure in anti-GBM
disease, with often minor symptoms; in minimal change disease, there is often rapid onset of oedema)). Ask about an
associated upper respiratory tract illness: poststreptococcal
glomerulonephritis classically presents around 2weeks following a streptococcal infection; visible haematuria tends
to occur few days after an upper respiratory tract infection
in IgA disease. Ask specifically about any rashes, haemoptysis, epistaxis nasal crusting or hearing abnormalities, (these
are typical features of granulomatous with polyangiitis vasculitis). There may be a medical history of nephritis, UTIs
or renal stones. Ask about associated systemic diseases (e.g.
diabetes, hypertension, arthritis, valvular abnormalities or
evidence of malignancy). A full drug history should be taken;
pay attention to NSAID use and include exposure to toxins.
Hearing impairment is present in Alport syndrome, and
there may be a family history of renal disease. Ask about
travel and associated infectious diseases (e.g. HIV infection,
hepatitis B and hepatitis C).
CLINICAL NOTES
Take a thorough drug history, and when
drug treatment was started in relation to any
deterioration in renal function. Ask directly about
illicit drugs, over-the-counter medication and
herbal remedies.
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Renal, genitourinary and sexual health medicine
Investigations
The following investigations are important in the patient
with glomerular disease.
Urine
• Urine dipstick and spot ACR or PCR.
• Urine microscopy for red blood cell casts and
dysmorphic red cells indicating glomerular
disease (this is rarely performed in clinical
practice).
• Urine for Bence Jones protein.
Blood tests
• FBC, urea and electrolytes, liver function tests and
bone profile.
• Fasting blood glucose: to exclude diabetes mellitus.
• Inflammatory markers: ESR, CRP.
• ANCAs are classically present in microscopic
polyangiitis and granulomatosis with polyangiitis
(formally called ‘Wegener granulomatosis’) and
eosinophilic polyangiitis (Churg–Strauss
syndrome).
• Anti-double-stranded DNA and antinuclear antibodies
(ANA) in SLE.
• Anti-GBM antibodies for the diagnosis of Goodpasture
disease.
• Hepatitis B and hepatitis C serology, HIV.
• Antistreptolysin O titre: recent streptococcal infection.
• Serum immunoelectrophoresis to exclude
myeloma. Perform along side urine analysis for Bence
Jones protein.
• Cryoglobulins and rheumatoid factor.
• Blood cultures if the patient reports having fevers.
• Serum complement levels: C3 and C4 levels are
classically reduced in active SLE, as well as in
cryoglobulinaemia.
CLINICAL NOTES
Hepatitis C mainly causes a glomerulonephritis
through formation of cryoglobulins. Hepatitis B can
cause a membranous glomerulonephritis. In both
instances it is important to treat the underlying
virus.
Renal biopsy
• Renal biopsy: to make a histological diagnosis if
intrinsic renal disease is suspected. It can ascertain
the likely disease process, the degree of activity of the
disease and background scarring. This can help guide
how aggressively to treat the disease and help give a
prognosis for renal recovery.
HINTS AND TIPS
There will be a raised transfer factor level on lung
function testing in the presence of pulmonary
haemorrhage.
Management
All patients with suspected glomerulonephritis should be seen
by a nephrologist. The correct treatment will be specific to the
underlying cause of the glomerulonephritis. Certain general
principles apply: tight blood pressure control and if ACR is
greater than 70 mg/mmol or PCR is greater than 100 mg/
mmol, ARBs should be used to help reduce proteinuria.
The general principle of treating nephrotic syndrome is to
diurese the patient and turn off the protein leak. Fluid removal
is achieved through reducing salt intake, restricting fluid intake and administering diuretics. Often intravenous diuretics
are required at a high dose, and a combination of different
classes of diuretic agents is used to achieve sequential nephron
blockade. There is a high risk of AKI in nephrotic syndrome.
HINTS AND TIPS
Monitor urea and electrolyte levels daily, aim to
achieve a maximum fluid loss of 1 kg/day, treat
intercurrent infections promptly and be alert to a
high risk of thrombosis. Reduction of protein leak is
achieved through targeting the underlying cause of
the nephrotic syndrome and good blood pressure
control. Use of a renin angiotensin system blocking
drug can also help reduce proteinuria.
Imaging
• CXR: this may show pulmonary oedema,
malignancy, pulmonary haemorrhage or cavitation in
granulomatosis with polyangiitis or anti-GBM disease,
or it may show features of sarcoidosis.
• Renal ultrasound scan to exclude obstruction and
assess renal size/symmetry.
264
RED FLAG
Patients with nephrotic syndrome are highly
coagulopathic. Warfarin treatment is generally
started when the albumin level is less than 20
g/L. In patients with nephrotic syndrome, loin
pain and an acute kidney injury rule out renal vein
thrombosis.
Glomerular disease
3030
Important primary and secondary glomerular diseases
Rapidly progressive glomerulonephritis
Rapidly progressive glomerulonephritis, or crescentic
glomerulonephritis, is usually an aggressive process and
presents with renal failure, haematuria, oliguria and hypertension. It is a medical emergency. Renal biopsy shows severe acute inflammation in the glomerulus with necrotizing
‘crescent’ formation. It may occur in SLE, in anti-GBM disease, in ANCA-associated vasculitis and very occasionally
with IgA nephropathy. Treatment is with immunosuppression, commonly high-dose hydrocortisone, cyclophosphamide and often plasma exchange. Unless treatment is
instituted sufficiently early, the prognosis is usually poor.
RED FLAG
Be suspicious, time is nephrons, suspect the
possibility of rapidly progressive glomerulonephritis
in any acute kidney injury with an active urine
sediment (i.e. blood and protein on urine dipstick)
Antineutrophil cytoplasmic antibodypositive vasculitis
This is typically either granulomatosis with polyangiitis,
(cytoplasmic ANCA (cANCA) against proteinase 3 [PR3],
formerly known as ‘Wegner granulomatosis’) or microscopic polyangiitis (perinuclear ANCA [pANCA] against
myeloperoxidase [MPO]), or eosinophilic granulomatosis
with polyangiitis (previously known as Churg–Strauss syndrome, a triad of raised levels of eosinophils, asthma and
renal failure and generally pANCA with antibodies directed
against MPO). They are all small-vessel vasculitides. They
may affect only the kidney (renally limited disease) or may
affect any other organ, including lungs, skin, gut, heart and
the neurological system. Granulomatosis with polyangiitis
causes granulomatous lesions and commonly has upper airway involvement. Ask about nasal crusting, epistaxis, hearing changes and haemoptysis. Anti-GBM disease can also
cause both renal impairment and pulmonary haemorrhage
(pulmonary–renal syndrome). All forms of vasculitis can
cause a rapidly progressive glomerulonephritis.
Symptoms can be nonspecific, including malaise and
poor appetite. Any organ system may be affected, and the
patient may have been seen in many different specialty
clinics already. CXR may show pulmonary haemorrhage.
Diagnosis is made serologically with the presence of ANCA.
A renal biopsy is performed to establish the degree of active
glomerulonephritis and background scarring. Vasculitis
has high associated mortality and risk of ESRF if not treated
aggressively. High-dose immunosuppression is given to induce remission, followed by a maintenance dose to prevent
recurrence. Initial treatment involves high-dose steroid and
cyclophosphamide; initial treatment involves high dose
steroids, cyclophosphamide and consideration of plasma
exchange. Maintenance treatment classically involves a
lower-dose steroid and azathioprine. Dialysis therapy may
be required. Rituximab, a CD20 monoclonal antibody, is
used for cyclophosphamide-resistant cases, or where cyclophosphamide is contraindicated.
RED FLAG
Cyclophosphamide can affect fertility, cause
myelosuppression and increase the risk of future
malignancy. Watch out for haemorrhagic cystitis, a
potential side effect of cyclophosphamide.
Antiglomerular basement membrane disease
This condition (also known as ‘Goodpasture disease’) is associated with the presence of circulating antibodies against
collagen resulting in damage to the alveolar and glomerular
basement membranes. It can be limited to causing just lung
injury or renal injury or can cause both. Other ‘pulmonary–
renal syndromes’ include SLE, granulomatosis with polyangiitis and microscopic polyangiitis. Anti-GBM disease
classically has a very rapid onset. Treatment is very aggressive, but once remission is achieved, relapse is very rare.
Treatment includes plasma exchange and immunosup-
pressive therapy.
RED FLAG
If you see a patient with haemoptysis and
renal failure, send urgent blood tests including
antineutrophil cytoplasmic antibodies (ANCA),
antinuclear antibody (ANA) and glomerular
basement membrane antibody (anti-GBM), and get
an urgent renal opinion.
IgA nephropathy
IgA nephropathy (Berger disease) is the most common glomerulonephritis worldwide. This condition is classically associated with ‘synpharyngitic’ haematuria (i.e. macroscopic
haematuria 1–2 days after an upper respiratory tract infection). In contrast, poststreptococcal glomerulonephritis
usually follows a delay of 1–2weeks. Other presentations
include nonvisible haematuria, proteinuria and renal impairment. Individuals with nonvisible haematuria, normal
renal function, no proteinuria and normal blood pressure
are at very low risk of progressive renal disease. In this
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Renal, genitourinary and sexual health medicine
group a renal biopsy is rarely performed, and follow-up is
in general practice with annual blood pressure and electrolyte monitoring. Individuals with proteinuria, renal impairment or hypertension are at a higher risk of progressive
renal disease. IgA may very occasionally cause a rapidly progressive glomerulonephritis, and, in this instance, would be
treated with aggressive immunosuppression. Typically, IgA
nephropathy follows a slow grumbling course. Treatment is
aimed at reducing blood pressure and the level of proteinuria.
Henoch–Schönlein purpura has much in common with IgA
nephropathy, and can be thought of as its systemic cousin.
Lupus nephritis
SLE is a multisystem disease, and the kidneys are commonly
affected. The changes are classified by the World Health
Organization from I–V on the basis of histology. The different types lead to presentations ranging from nephritis
to nephritic syndrome. Typically, the anti-double-stranded
DNA titres are raised and C3 and C4 levels are low in active lupus. Treatment includes immunosuppression, which
may consist of steroid, cyclophosphamide, mycophenolate
mofetil (MMF), and in some centres, rituximab.
CLINICAL NOTES
Lupus nephritis follows a relapsing and remitting
course. It often affects women of childbearing age.
Pregnancy can both affect which medications can be
safely used to manage the condition and put extra
strain on the kidneys. Lupus often affects patients
differently, and classically presents in a similar way in
each patient. Ask them how their lupus affects them.
Minimal change nephropathy
This accounts for 80% of children and 20% of adults in the
United Kingdom who present with nephrotic syndrome. It
classically presents with sudden-onset swelling. Renal biopsy is not always indicated in children. Light microscopy
findings are normal (hence the name) but electron microscopy shows podocyte foot process effacement. There is
nephrotic range proteinuria, which responds to corticosteroid therapy in 90% of paediatric patients and 75% of adult
patients. Relapsing episodes are treated with cyclophosphamide or a calcineurin inhibitor, commonly tacrolimus.
The development of renal failure is rare (<1%), and is more
likely to occur when disease remission is hard to obtain.
is also associated with a wide range of systemic diseases
(e.g. HIV infection), pamidronate and sickle cell disease.
HIV-associated nephropathy is increasingly common and
causes a characteristic ‘collapsing’ FSGS.
Treatment is directed at the underlying cause. FSGS requires prolonged treatment with high-dose steroids. If proteinuria cannot be controlled, then progression to ESRF is
common. It is thought that some steroid-resistant minimal
change disease may in fact be missed cases of FSGS.
FSGS commonly reoccurs after transplantation (quoted
at 30%); inherited forms, however, are unlikely to reoccur.
CLINICAL NOTES
‘Secondary focal segmental glomerulosclerosis’
is a term used for focal sclerosis seen on renal
biopsy. In this case the underlying process is not
immune mediated, but is from increased pressure
on the glomeruli. This is seen with obesity,
hypertension or where there are fewer nephrons
(e.g. a single kidney or small kidneys). Treatment
in this instance is by blood pressure control and
weight loss.
Membranous glomerulonephritis
This is the most common cause of nephrotic syndrome in
adults. Renal biopsy will show a characteristic diffuse thickening of the glomerular basement membrane and immune
complexes deposited in the subepithelial space causing a spike
formation. The condition if primary is associated with a circulating phospholipase A2 receptor antibody, and treatment is
with immunosuppression. Secondary causes may include an
underlying malignancy, drugs (e.g. gold), autoimmune conditions such as class V SLE or rheumatoid arthritis, and infections. Treatment is focused on treating the underlying cause.
If left untreated, 30% of cases will resolve spontaneously; 30%
will have a partial response and 30% will progress to ESRF.
RED FLAG
Membranous disease may be the first presentation
of an underlying malignancy. Perform a
thorough investigation to exclude underlying
neoplasm. These patients are at very high risk of
thromboembolic disease.
Focal segmental glomerulosclerosis
This also causes nephrotic syndrome but classically with
less oedema. Nonvisible haematuria is generally found.
It is diagnosed on renal biopsy, where areas of the kidney
show focal sclerosis. It can be idiopathic or familial but
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Membranoproliferative glomerulonephritis
This condition, also known as ‘mesangiocapillary glomerulonephritis’, is characterized by immunocomplex deposits
in the glomerular mesangium and basement membrane
thickening. It is uncommon, and is associated a nephritic or
Urinary tract infections
3030
nephrotic syndrome and low C3 and/or C4 level. Secondary
forms are associated with chronic infections, SLE, cryoglobulins and hepatitis C. Treatment of membranoproliferative glomerulonephritis focuses on treating the underlying
disease. If a patient presents with nephrotic syndrome and
progressively declining renal function, aggressive immunosuppression should be given. Prognosis is poor—50% of
patients develop ESRF at 10years.
Poststreptococcal glomerulonephritis
This condition, also known as ‘diffuse proliferative glomerulonephritis’, is a complication of streptococcal pharyngitis (strep
throat) or impetigo. Clinically, it is characterized by sudden
onset nephritic syndrome: haematuria, proteinuria, oedema,
and hypertension. There is commonly a latent period after the
infection; 1–2weeks for strep throat and typically 6–8weeks
for impetigo. Treatment is symptomatic (i.e. treat hypertension, oedema and hyperkalaemia). Immunosuppression is not
indicated. Prognosis is good in children; a small proportion of
adults may develop renal impairment.
URINARY TRACT INFECTIONS
Urinary tract infections (UTIs) are one of the most common infections encountered in medical practice. In the elderly population they can present atypically and can rapidly
cause sepsis. Women are more prone to UTIs than men,
except during the first few months of life and in old age.
Approximately 25%–35% of all women describe symptoms
of a UTI at some stage in their lives.
‘Urinary tract infection’ (UTI) is a general term referring
to the presence of microorganisms in the urine. Significant
bacteriuria is defined as urine that yields a pure growth
of more than 100,000 organisms per millilitre on culture.
Predisposing factors for UTI are given in Box30.32. Broadly
speaking, UTIs are divided into those affecting the lower
urinary tract (urethra, prostate, and bladder) and those affecting the upper urinary tract (kidneys). A further distinction is made between uncomplicated (normal renal tract and
function) and complicated (abnormal renal or genitourinary
tract, impaired host defences or virulent organism) UTIs.
CLINICAL NOTES
Precipitating causes of urinary tract infection:
• stones
• obstruction
• polycystic kidneys
• papillary necrosis
• diabetes mellitus
• analgesic nephropathy
• sickle cell disease
• sexual intercourse
• pregnancy
• bladder catheterization
Lower urinary tract infections
Lower urinary tract infections may take the following forms:
• Cystitis: a symptomatic infection of the bladder with
significant bacteriuria.
• Asymptomatic bacteriuria: the patient has no
symptoms, but urine culture yields a growth of more
than 100,000/mL.
• Acute urethral syndromes: symptomatically like
cystitis, but the urine culture may be sterile.
Upper urinary tract infections
Upper urinary tract infections may take the following forms:
• Acute pyelonephritis: an inflammatory process within
the renal parenchyma, most commonly caused by
bacterial infection.
• Chronic pyelonephritis: this is usually the result of
long-standing or recurrent bacterial infection with
eventual parenchymal scarring characteristic of chronic
pyelonephritic kidneys. Vesicoureteric reflux and
obstruction also contribute. Hypertension and chronic
renal failure may ensue. It is more common in children.
Infection usually occurs by ascent of the invading organism from the urethra into the bladder. Colonization of the
ureters may occur, and from there to the kidneys. The haematogenous route of infection is less common but may occur secondarily to bacteraemia, septicaemia or endocarditis.
Clinical features
Symptoms of lower urinary tract infections include suprapubic pain, frequency, nocturia and dysuria (classically
‘burning’). Upper urinary tract infections such as acute
pyelonephritis or renal abscesses present with fever, rigors,
loin pain, vomiting and weight loss. Macroscopic haematuria can occur in one-third of severe cases. In the elderly, the
presentation may be very nonspecific with mild cognitive,
behavioural and mobility changes.
Investigations
A clean, midstream urine sample should be obtained for a
dipstick test done for blood, protein, leucocytes and nitrites,
and it should be sent to the laboratory for microscopy and culture. White cell count and CRP level will be raised in infection.
Obvious predisposing factors such as pregnancy, diabetes or
an indwelling catheter should be considered. Indications for
further investigations include recurrent infections, childhood
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