Pediatric UTI: Renal Scarring and Long-Term Outcome

During a febrile urinary tract infection (UTI) the renal parenchyma — the functioning tissue of the kidney — is inflamed, and in most children that inflammation resolves with treatment and leaves nothing behind. In a minority it ends as a renal scar: a focal area of cortical loss where functioning tubules have been replaced by fibrous tissue. On dimercaptosuccinic acid (DMSA) scintigraphy, a nuclear scan whose tracer is taken up by functioning tubular cells, a scar shows as a photopenic defect, a patch with no tracer uptake. It matters which children belong to that minority, and what the scar means over the following decades.

An acute lesion is not yet a scar

The scan taken during the acute illness and the scan taken months later answer different questions. Acute DMSA shows which parts of the kidney are involved in the infection, but a defect seen then may disappear as the inflammation settles. The scan that identifies permanent damage is done 4–6 months after the infection, once healing is complete: more than 90% of defects still visible on a scan at least 5 months after the episode persist. A scar found on a late scan is therefore a scar for life; a defect seen only during the acute illness is not.

How often scarring happens

The first row comes from a systematic review of children imaged after a first UTI, not all of them strictly febrile; the other three come from an analysis of 345 children whose infections were all febrile. Both describe the same pattern: recurrence, not the first episode, drives scarring. In that analysis the odds of scarring after a second febrile infection were about 12 times higher than after a single one. Restated from the other direction, approximately 85% of children recover without scarring after a first infection, and the risk then rises sharply with each further febrile episode.

Which children are at risk

Given that some children scar and most do not, the next question is how to tell them apart early. A pooled analysis of individual patient data from 1,280 children with a first UTI, all scanned at least 5 months later, identified the findings that predict scarring. The results are expressed as odds ratios: how many times higher the odds of scarring are in children with a finding than in children without it. They are worth knowing because they change how closely a child is watched.

• Vesicoureteral reflux, the backflow of urine from the bladder towards the kidney, has a strong grade dependence. Grade IV or V reflux was the strongest predictor, with odds of scarring about 22 times those of a child without reflux, and roughly two-thirds of the children with that grade scarred. Grade III reflux carried about a 3.6-fold increase, while grades I and II were only marginally above no reflux at all. High-grade reflux was uncommon, present in about 4% of the children.
• An abnormal ultrasound — dilatation, abnormal parenchyma or a bladder abnormality — raised the odds about 3.8-fold.
• Markers of a more intense infection also counted: a temperature of at least 39°C (odds ratio about 2.3), an organism other than E. coli (about 2.3), a C-reactive protein (an inflammatory marker in the blood) above 40 mg/L (about 3.0) and a polymorphonuclear (neutrophil) cell count above 60% (about 1.9).
• Age, sex and the duration of fever before presentation were not associated with scarring. Older age and female sex were, if anything, weakly predictive, which runs against older studies that identified the youngest children and boys as being at greatest risk of a scar.

The clinically useful form of this is simple: a child with an abnormal ultrasound, or with both a temperature of at least 39°C and a non-E. coli organism, has roughly twice the baseline risk of scarring, and about one child in three in that group scars.

Why recurrence is the lever

The mechanism behind the recurrence effect is nephron reserve. A kidney starts with on the order of 1 million nephrons, the filtering units of the kidney, with wide individual variation, and surviving nephrons compensate by hyperfiltrating — each filtering more than before — after a segment is lost. One scar is usually absorbed without a measurable fall in glomerular filtration rate (GFR), the standard measure of kidney function; repeated scars exhaust that reserve until GFR declines and hypertension or proteinuria (protein in the urine) appears. This is why prevention is aimed at the second and third febrile UTI rather than at the first, which is the event that reveals the underlying substrate.

The measures that reduce the chance of a further episode are general ones. Constipation and dysfunctional elimination are treated, because a bladder that empties incompletely keeps producing infections; children are encouraged to drink enough to avoid dehydration; and they are given access to clean toilets without having to postpone voiding until it is unavoidable. Antibiotic prophylaxis is not given routinely after a first UTI, and it is not given for asymptomatic bacteriuria (bacteria in the urine without symptoms or inflammation). Where reflux is present the decision is different and more finely balanced: prophylaxis reduces recurrent infection but has not been shown to reduce new scarring, so it is reserved for selected higher-risk children. Any suspicion of a recurrence is assessed promptly, since the next febrile episode is the one that adds to the damage.

What a scar means in adult life

Most children who scar do well. A review of the long-term evidence concluded that children whose kidney function and renal imaging are normal at baseline rarely lose kidney function over years of follow-up, and that the risk of hypertension is low and largely confined to those who already had renal damage. Part of what was once called post-infectious scarring has since turned out to be congenital dysplasia — kidney tissue that formed abnormally before birth — visible on antenatal ultrasound. That is one reason the old assumption that childhood urinary infection is a common route to kidney failure is now debated, and why the proportion of end-stage renal disease (kidney failure requiring dialysis or transplantation) attributable to childhood UTI appears to be small.

Where damage is established from the start, the outlook is less benign. In a 27-year follow-up of 30 adults who had non-obstructive focal scarring after childhood pyelonephritis, 7 had developed hypertension, 3 had reached end-stage renal disease, and 2 of the 16 women had a history of toxaemia in pregnancy (an older term for pre-eclampsia); even the patients who had escaped surgery or kidney failure had a lower glomerular filtration rate than age-matched controls. That series is small, selected and decades old, so it describes the severe end of the spectrum rather than the average outcome. Blood pressure is the earliest measurable signal, and children with higher grades of scarring show day- and night-time blood pressure elevation. Pregnancy is the other occasion on which a reduced renal reserve becomes visible; controlled cohorts have not found an overall increase in first-pregnancy complications among women who had a childhood UTI, with the risks concentrated in women whose kidneys carried measurable damage.

What follow-up consists of

Follow-up is matched to the amount of damage rather than offered uniformly, but two findings reliably trigger specialist assessment: abnormal imaging, and recurrent UTI. Recurrence has a specific definition here, built on the distinction between acute upper UTI (pyelonephritis, infection that has reached the kidney) and lower UTI (cystitis, infection confined to the bladder): two or more episodes of acute upper UTI, or one upper UTI together with at least one lower UTI, or three or more lower UTIs.

Beyond that referral point, the intensity of follow-up is set by what the kidney shows:

• A child with a renal parenchymal defect is assessed with height, weight, blood pressure and routine testing for proteinuria.
• Minor, unilateral defects do not need long-term follow-up unless the child has recurrent UTI, a family history of hypertension, or lifestyle risk factors for hypertension.
• Bilateral abnormalities, impaired kidney function, raised blood pressure or proteinuria warrant monitoring and management by a paediatric nephrologist, with the aim of slowing the progression of chronic kidney disease.
• Urine is not retested routinely in a child who is asymptomatic after an episode, and asymptomatic bacteriuria is not a reason for follow-up.

At a glance

• A delayed DMSA scan at 4–6 months defines a scar; more than 90% of defects present at 5 months persist.
• About 15% of children scar after a first UTI, but the risk is 2.8% after one febrile episode, 25.7% after two and 28.6% after three or more — recurrence is the driver.
• The strongest predictors are grade IV–V reflux, an abnormal ultrasound, and the combination of a temperature of at least 39°C with a non-E. coli organism; age and sex do not predict scarring.
• Prevention targets the next febrile episode, through bowel and bladder management, adequate fluids, prompt voiding and selective use of prophylaxis in reflux.
• A single small scar usually leaves kidney function normal; blood pressure, proteinuria and kidney function are monitored closely where the damage is bilateral or function is already reduced.