Nephrotic syndrome in children

Nephrotic syndrome is the condition in which the kidneys stop holding on to protein, so that large amounts of it are lost in the urine. With less protein in the blood, water no longer stays inside the vessels and moves out into the tissues: the child swells up. It usually starts between the ages of two and six, often a few days after an ordinary cold, and it lands on a family out of a clear blue sky — a healthy child yesterday, puffy eyes today. One thing is worth knowing from the start: in the great majority of children it responds well to treatment and does not lead to kidney failure, but it runs in waves, and it will fall to the family to learn to recognise a relapse.

What happens in the kidneys

A kidney works as a filter: it lets water and waste through and holds back the proteins of the blood, which are too big to pass. In nephrotic syndrome the filter becomes leaky and protein escapes. What is lost most is albumin, the protein that keeps water inside the blood vessels — hence the swelling.

Along with albumin other useful proteins are lost, and that explains the rest. Antibodies go, so the child becomes more open to infection. The substances that stop blood clotting inside the vessels go too, while the blood itself becomes more concentrated: the risk of clots rises. The liver responds by working harder, and cholesterol goes up.

The illness runs in waves: a relapse gives way to remission, when there is no protein in the urine and the child is well. Over the years relapses come further apart, and in most children they stop by late adolescence.

How it is noticed at home

The face is almost always what catches the eye first. Swelling starts where the tissues are loose: in the morning the eyelids look puffy, as though the eyes were half closed with sleep, and parents often think of an allergy or an insect bite. By evening the face settles and instead the lower legs and feet swell, keeping the mark of the sock elastic.

• The swelling spreads: eyelids first, then the lower legs, then the genitals, and finally the abdomen, which becomes tight and distended.
• The child puts on weight quickly — not from food but from water.
• There is less urine, and it froths as though soap had been added, with the foam slow to settle.
• The child looks pale and flat, tires quickly, complains of tummy ache and eats less.

When swelling first appears the child needs to be seen, and better the same day than in a week's time: a urine dipstick for protein takes a minute and immediately points the way.

Why it happens

In nine children out of ten there is no outside cause. That version is called idiopathic, and under the microscope the kidney looks almost normal — which is where the name minimal change disease comes from. What breaks the filter is not known; a fault in the immune cells is suspected. This is the form most preschool children have, and the one that responds best to steroids.

Less often it is the consequence of another illness, and then it is that illness which is treated:

• inflammatory disease of the filtering units of the kidney themselves;
• scarring of part of those units, a form that responds less well to steroids;
• lupus and other systemic diseases;
• viral infections: hepatitis B and C, HIV;
• diabetes and sickle cell disease, both uncommon in childhood;
• certain medicines.

A separate and important group is congenital nephrotic syndrome, where the swelling appears in the first months of life. It is caused by a fault in the genes that build the filter, does not respond to steroids and needs a different approach altogether, which is why nephrotic syndrome in a baby under a year is always looked at separately, with genetic testing. Boys are affected somewhat more than girls, and the condition is a little more common in children of South Asian background, for reasons that are not understood.

How the diagnosis is confirmed

The diagnosis rests on three things: a lot of protein in the urine, a low albumin in the blood, and swelling. They are confirmed like this:

• A urine dipstick for protein, the simplest test of all; here it reads 3+ or 4+.
• The protein to creatinine ratio in a single urine sample — a number for the size of the loss, more reliable than the stick. It shows how serious things are and is used to follow progress.
• Blood chemistry: albumin (markedly low), total protein, cholesterol (raised), creatinine and urea, electrolytes.
• Urine microscopy: whether red cells are present. Blood in the urine usually means this is not minimal change disease.
• Blood pressure at every visit: persistently high pressure is another reason to look for a different form.
• Further tests — complement levels, antibodies where lupus is suspected, and hepatitis and HIV tests where there is reason for them.

When a kidney biopsy is needed. A typical preschool child who has responded well to steroids does not have one: the diagnosis is clear and the result would not change the treatment. A piece of kidney tissue is taken if the child is under a year or over ten to twelve, if there is blood in the urine, if blood pressure stays high or kidney function is worse, if complement is low and, above all, if after a full course of steroids the protein has not gone from the urine. A biopsy is done when the illness is not behaving as expected.

How it is treated

The mainstay is a steroid, almost always prednisolone. The dose is worked out from the child's weight or body surface, given daily for some weeks, then switched to alternate days and tapered over two to three months. In most children the protein clears from the urine within one or two weeks and the swelling goes down.

The course is not stopped as soon as things improve: a short course is paid for with frequent relapses. Nor are steroids stopped abruptly — they are reduced only to the schedule the doctor has set out.

Added to that:

• Diuretics, for marked swelling and always with care: they draw water out of the vessels as well as the tissues, and with a low albumin that risks a sharp drop in blood volume and a clot. They are never given on a family's own initiative.
• Albumin into a vein, in hospital, for severe swelling and usually together with a diuretic.
• A penicillin-type antibiotic at a preventive dose during a relapse: it guards against pneumococcus, to which these children are particularly vulnerable.
• Cutting down salt while there is swelling, and sometimes fluid as well. Protein in the diet, by contrast, is not restricted.
• Medicines that damp down the immune system, if relapses follow one another, if remission holds only on steroids, or if the side effects have become too hard to live with. These are levamisole, cyclophosphamide, calcineurin inhibitors, mycophenolate and rituximab; the paediatric kidney specialist chooses, and all of them need regular blood monitoring.

Complications that will not wait

The danger is not the swelling itself but what can happen while it is there.

Call an ambulance (in Spain, Italy, Portugal, Poland and Ukraine the single number is 112) if the child has:

• severe tummy pain, especially with fever and vomiting, with a hard abdomen that hurts to touch — this is how inflammation of the lining of the abdomen shows itself, and these children are prone to it;
• sudden breathlessness, chest pain or coughing up blood;
• swelling, pain and redness in one leg or arm, with the veins standing out;
• a severe headache, a seizure, confusion or disturbed vision;
• pallor, cold hands and feet, a fast pulse and dizziness on standing — despite all the swelling, this is a sign that there is not enough fluid inside the vessels;
• fever with shivering and a sudden deterioration.

Contact the doctor the same day if a temperature starts; if a painful, hot red patch appears on the skin; if the child has been in contact with chickenpox or measles and is not immune; if diarrhoea and vomiting begin and the child cannot keep fluids down; if the amount of urine drops sharply.

Life between relapses

Dipsticks and a diary. The urine is tested with a stick, usually in the morning, and the result written down: negative, trace, 1+, 2+, 3+, 4+. The same book holds the weight, the doses and how the child seems. A reading of 3+ or more on three days running means a relapse: contact the doctor and follow the plan agreed in advance rather than waiting for the next appointment.

Vaccinations. The pneumococcal vaccine and a yearly flu vaccine matter particularly; chickenpox vaccination is discussed separately. Live vaccines are not given while a child is on high-dose steroids or immune-damping medicines — they are put off until a remission off treatment. Timing is agreed with the kidney specialist, and the schedule differs from country to country.

Ordinary life. Between relapses the child goes to nursery and school and moves and plays without restriction. Salt is limited while there is swelling and while steroids are being taken; a permanently salt-free diet is not needed. Long courses of steroids affect growth, bones, blood pressure and blood sugar, so the doctor keeps an eye on all of that and discusses with the family how to soften it.

When the illness does not yield to steroids

In roughly one child in ten the protein does not clear from the urine after a full course. This is steroid-resistant nephrotic syndrome, and the approach differs: a kidney biopsy, genetic testing, and a choice of immune-damping medicines — which in the inherited forms are not counted on at all. Medicines that reduce protein loss and protect the kidney are added. It is in this group that kidney function may deteriorate gradually over the years, which is why follow-up here is closer.

Congenital nephrotic syndrome is the most severe form. The baby loses protein from the first weeks and needs frequent albumin infusions, special feeding and treatment to support growth. Sometimes, to stop those enormous losses and reduce the risk of clots, the kidneys are removed, the child goes onto dialysis and is prepared for a transplant. Here a transplant is not a last resort but a planned goal: with a transplanted kidney the illness usually does not return.

Online consultation with a doctor

A remote appointment suits everything that surrounds this illness between visits to the kidney specialist. Going through results and diary entries, working out whether this is a relapse or a trace of protein after a cold, talking about reducing the steroid dose and about side effects, about vaccinations and timing, about travel, nursery and school, about meals and salt.

The limits are obvious. Swelling, the abdomen and blood pressure are assessed by hand, tests cannot be done through a screen, and with abdominal pain, breathlessness, swelling of one leg or a sudden deterioration what is needed is not a conversation but an ambulance.

This material is for information only and does not replace medical advice.