19. (Illustrated) Kidney disorders - Proteinuria Flashcards
Proteinuria
Transient proteinuria may occur…
Persistent proteinuria should be quantified by measuring…
What is orthostatic proteinura and how is it diagnosed?
Transient proteinuria may occur during febrile illnesses
or after exercise and does not require investigation.
Persistent proteinuria is significant and should be
quantified by measuring the urine protein-to-creatinine
ratio in an early morning sample (normal protein-to-creatinine
ratio <20 mg/mmol).
A common cause is orthostatic (postural) proteinuria
when proteinuria is only found when the child is
upright during the day. It can be diagnosed by measuring
the urine protein-to-creatinine ratio in a series of
early morning urine specimens. The prognosis is excellent
and further investigations are not necessary. Other
causes of proteinuria, which need further evaluation,
are listed in Box 19.2.
Nephrotic syndrome
Heavy proteinuria results in…
Secondary causes of nephrotic syndrome
Clinical signs of the nephrotic syndrome (5)
In nephrotic syndrome, heavy proteinuria results in a
low plasma albumin and oedema.
The cause of the condition is unknown, but a few cases are secondary to
systemic diseases such as Henoch–Schönlein purpura
and other vasculitides, e.g. SLE (systemic lupus erythematosus),
infections (e.g. malaria) or allergens (e.g. bee sting).
Clinical signs of the nephrotic syndrome are:
• periorbital oedema (particularly on waking) which
is often the earliest sign
• scrotal or vulval, leg, and ankle oedema (Fig. 19.16)
• ascites
• breathlessness due to pleural effusions and
abdominal distension
• infection such as peritonitis, septic arthritis, or
sepsis due to loss of protective immunoglobulins
in the urine.
Case history 19.3 shows typical presentation, and initial
investigations are listed in Box 19.3.
Steroid-sensitive nephrotic syndrome
In most children with nephrotic syndrome, proteinuria is resolved with…
It is often precipitated by…
Features suggesting steroid-sensitive nephroptic syndrome (5)
In 85–90% of children with nephrotic syndrome,
the proteinuria resolves with corticosteroid therapy
(steroid-sensitive nephrotic syndrome).
These children do not progress to chronic kidney disease. It is
more common in boys than in girls, in Asian children
than in Caucasians, and there is an association with
atopy. It is often precipitated by respiratory infections.
Features suggesting steroid-sensitive nephrotic
syndrome are:
- age between 1–10 years
- no macroscopic haematuria
- normal blood pressure
- normal complement levels
- normal renal function.
Management (1/2)
The most widely used protocol is…
The median time for the urine to become free of protein is…
Children that don’t respond to 4-6 weeks of corticosteroid therapy or have atypical features…
How is minimal change disease diagnosed?
The most widely used protocol is to initially give oral corticosteroids (60 mg/m2 per day of prednisolone), unless there are atypical features. After 4 weeks, the dose is reduced to 40 mg/m2 on alternate days for 4 weeks and then weaned or stopped.
The median time for the urine to become free of protein is 11 days.
However, there is now good evidence that extending the initial course of steroids by gradually tapering the alternate day part of the course leads to a marked reduction in the proportion of children who develop a frequently relapsing or steroid-dependent course, although there are increased side-effects from steroid treatment.
Children who do not respond to 4–6 weeks of corticosteroid therapy or have atypical features may have a more complex diagnosis and require a renal biopsy.
Renal histology in steroid-sensitive nephrotic syndrome is usually normal on light microscopy but fusion of the specialized epithelial cells that invest the glomerular capillaries (podocytes) is seen on electron microscopy. For this reason, it is called minimal change disease.
Management (2/2)
Serious complications at presentation or relapse of Nephrotic syndrome
Hypovolemia
Characteristically complains of…
What are indications of hypovolemia?
Requires treatment with…
Is at risk of…
If severe, this may need treatment with…
Thrombosis
What factors can cause thrombosis?
Infection
Children in relapse are at risk of…
Hypercholesterolaemia
Correlates inversely with…
The child with nephrotic syndrome is susceptible to
several serious complications at presentation or relapse
• Hypovolaemia – during the initial phase of oedema
formation, the intravascular compartment may
become volume depleted. The child who becomes
hypovolaemic characteristically complains of
abdominal pain and may feel faint. There is
peripheral vasoconstriction and urinary sodium
retention. A low urinary sodium (<10 mmol/L) and
a high packed cell volume of red blood cells are
indications of hypovolaemia, which requires
urgent treatment with intravenous fluid (0.9%
saline or 4.5% albumin solution)as the childis at
risk of vascular thrombosis and shock. Increasing
peripheral oedema, assessed clinically and by daily
weight, may cause discomfort and respiratory
compromise. If severe, this may need treatment
with intravenous 20% albumin infusion with
furosemide. Care must be taken with the use of
20% albumin as it may precipitate pulmonary
oedema and hypertension from fluid overload, and
also with diuretics, which may cause or worsen
hypovolaemia.
• Thrombosis – a hypercoagulable state, due to
urinary losses of antithrombin III, thrombocytosis
which may be exacerbated by steroid therapy,
increased synthesis of clotting factors, and
increased blood viscosity from the raised
haematocrit, all predispose to thrombosis.
This may affect the lungs, brain, limbs, and
splanchnic circulation with potentially
catastrophic results.
• Infection – children in relapse are at risk of
infection with capsulated bacteria, especially
Pneumococcus. Spontaneous peritonitis may
occur. Pneumococcal and seasonal influenza
vaccination is widely recommended.
Chickenpox and shingles should be treated
with aciclovir.
• Hypercholesterolaemia – this correlates inversely
with the serum albumin, but the cause of the
hyperlipidaemia is not fully understood.
Prognosis (Steroid-sensitive nephrotic syndrome)
Side-effects of corticosteroid therapy may be reduced by…
Possible steroid-sparing agents include…
This is summarized in Fig. 19.18. Relapses are identified
by parents on urine testing. The side-effects
of corticosteroid therapy may be reduced by an
alternate-day regimen. If relapses are frequent, or if a
high maintenance dose is required, involvement of a
paediatric nephrologist is advisable as steroid-sparing
agents may be considered to enable reduction in
steroid use. Possible steroid-sparing agents include
the immunomodulator levamisole, alkylating agents
(e.g. cyclophosphamide), calcineurin inhibitors such as
tacrolimus and cyclosporin A, the immunosuppressant
mycophenolate mofetil, and for difficult cases the anti-
B-cell monoclonal antibody rituximab.
Steroid-resistant nephrotic syndrome
Management of oedema is by…
These children should be referred to a paediatric nephrologist
(Table 19.4).
Management of the oedema is by
diuretic therapy, salt restriction, angiotensin-converting
enzyme inhibitors, and sometimes nonsteroidal antiinflammatory
drugs, which may reduce proteinuria.
Genetic testing for steroid-resistant nephrotic syndrome
is available and helps in the management of
children, e.g. withdrawal of immunosuppression or
supplementation of CoQ10 if there is a CoQ10 pathway
defect.
Congenital nephrotic syndrome
Presents in…
Gene frequency is particularly high in…
Associated with a high mortality, usually due to…
What may be necessary due to the severe albuminuria?
Congenital nephrotic syndrome presents in the first 3
months of life.
It is rare. The most common kind is recessively
inherited and the gene frequency is particularly
high in Finns. In the UK, it is more common in consanguineous
families.
It is associated with a high mortality,
usually due to complications of hypoalbuminaemia
rather than progressive chronic kidney disease.
The albuminuria is so severe that unilateral nephrectomy
may be necessary for its control, followed by dialysis
for stage 5 (most severe) chronic kidney disease, which
is continued until the child is no longer nephrotic and
old enough for renal transplantation.
