A Urine Test That Might One Day Warn Doctors Sooner When a Newborn's Kidneys Are Struggling

What a 2025 review of 13 studies on urinary kidney injury molecule-1 found, and what it honestly does not yet tell families

Researchers combined 13 small studies of 552 newborns to ask whether a protein in a baby's urine, called kidney injury molecule-1, is raised when the kidneys have been injured. It was — but only moderately, and the studies disagreed a great deal, so the researchers rated their own confidence in the finding as low. It is an encouraging early signal, not a test that hospitals can offer today.

That review, published in the journal Life in 2025 [1], is the subject of this article. To understand why it matters — and why it is not yet a test anyone can ask for — it helps to start with what kidneys do for a newborn.

Why kidneys matter so much in the first days of life

Kidneys do quiet, essential work: they filter waste out of the blood, decide how much water and salt the body keeps, help control blood pressure, and keep the chemistry of the blood in balance. In a newborn — especially one born early — this system is doing all of that while still finishing its own development, and its filtering power climbs steadily over the first weeks and months of life [2].

When a newborn becomes seriously ill, the kidneys are often among the first organs to suffer. Doctors call this acute kidney injury: a sudden reduction in how well the kidneys are filtering. It is usually not permanent, and many babies recover well. But it needs to be spotted, because fluid plans, medicine choices and doses, and how closely a baby is watched all depend on knowing the kidneys are under strain.

How doctors used to see this — and why they saw it late

For a long time, kidney trouble in newborns was something clinicians noticed rather than diagnosed. There was no agreed definition and no grading system, so a baby with a worrying blood result was simply described as having "renal failure", and it was assumed to be a consequence of how sick the baby already was rather than a problem in its own right. Specialists eventually argued that newborns needed a proper, standard definition of kidney injury, the way adults and older children already had [3].

The study that changed minds was called AWAKEN, a large study that gathered information on babies admitted to intensive care units across several hospitals in more than one country. It found that a substantial share of babies admitted to a neonatal intensive care unit develop acute kidney injury — far more than most clinicians had assumed — and that babies who developed it were more likely to die, even after accounting for how unwell they had been in the first place [4]. Kidney injury stopped being a footnote and became something worth catching early. But catching it early ran into a stubborn obstacle, and it is the obstacle this whole field of research exists to solve.

The problem with the current blood test

The standard way to check a newborn's kidneys is a blood test for a waste product called creatinine. Healthy kidneys clear creatinine out of the blood, so if the level is high or rising, filtering may be impaired. In a newborn, though, this signal has two serious flaws.

The first is that it is borrowed. During pregnancy, creatinine passes from the mother across the placenta into the baby, so in the first days after birth a baby's level is partly the mother's, and it takes days — sometimes weeks in a very preterm baby — to settle to a level that genuinely reflects the baby's own kidneys [2].

The second flaw is timing. Creatinine measures how well the kidneys are working, not whether they have been damaged, and it only rises once a large share of filtering capacity has already been lost. By the time the blood test looks abnormal, the injury happened some time ago. Reviews of newborn kidney care still describe this as the field's central unsolved problem [5]. Hence the search for something different: a substance that appears when kidney cells are actually hurt, rather than one that appears when the kidneys have already stopped keeping up.

What kidney injury molecule-1 is

Kidney injury molecule-1 — usually shortened to KIM-1 — sits on the surface of cells in a part of the kidney called the proximal tubule. When those cells are injured, they produce a great deal more of it, and a piece of the molecule breaks off and washes out in the urine [6]. In principle, that makes it an early alarm rather than a late consequence.

For newborns there is a second, very practical attraction: measuring KIM-1 in urine (written uKIM-1) means no needle. A sample can be collected from a nappy or a small bag, with no blood taken from a baby whose total blood volume may be only a few tablespoons. Many rival markers require blood draws.

What this new research did

A team of researchers in Thailand and Taiwan carried out what is called a systematic review and meta-analysis [1]. They did not study babies themselves. Instead, they registered a plan in advance, searched five major medical databases up to 17 September 2025, screened 291 records, and ended up with 13 studies that met their criteria, covering 552 newborns — 192 who developed acute kidney injury and 360 who did not. The studies came from the United States, Turkey, South Korea, Iran, Chile, Egypt and Greece, and all were carried out in neonatal intensive care units. The babies included premature infants, very small infants, babies who had been short of oxygen at birth, and babies who had undergone heart surgery.

What they found — and what it means

Pooling everything together, urinary KIM-1 was indeed higher in the babies who had kidney injury. The difference was statistically real but moderate in size, and it is important to understand what "moderate" means here. The result describes the gap between the average level in one group and the average level in the other; the two groups still overlap a great deal, and it does not tell you what a particular baby's result means.

That distinction is the heart of the honest reading of this paper. Nowhere in the paper is there a number for how often the test would correctly flag a baby with kidney injury, how often it would raise a false alarm, or what level should count as "high". Without those, there is no threshold a doctor could act on — which is why nobody should ask for this test on the basis of this study.

The studies also disagreed with each other a great deal. The researchers checked whether the disagreement could be explained by study design, by when the urine was collected, or by which definition of kidney injury was used, and none of those explained it. One grouping did stand out — studies by continent — but that result came from a single study in Egypt, and one study cannot establish a genuine geographic difference. The researchers formally graded their overall confidence in the finding as low.

There is also a circular puzzle built into the question. Kidney injury, in every one of these 13 studies, was defined by a rise in creatinine — the very test KIM-1 is supposed to beat. If KIM-1 correctly spots damage before creatinine moves, it is recorded as a mistake. Judging a better test against an imperfect one will always undersell it.

Some things are genuinely reassuring. When the researchers removed each study in turn and recalculated, the result stayed significant every time, so it does not rest on any single study. Two statistical checks for unpublished disappointing results were both negative, and eleven of the 13 studies were rated high quality. This cluster's Source Transparency Report also records several places where the paper's own text is inconsistent with itself.

What this means for your baby

Practically: nothing changes today. This is not a test your baby can have, and a clinician declining to order it is following the current evidence, not a limitation of your hospital.

What does matter is the care that already exists and works. Babies at higher risk of kidney injury are those who were short of oxygen around the time of birth [7], those who have had heart surgery [8], those born very early, and those receiving medicines that are hard on the kidneys — certain antibiotics and anti-inflammatory drugs, for example, which are sometimes unavoidable and are used because the infection or condition they treat is more dangerous than the risk they carry [9]. Neonatal teams track these babies closely: daily weights, careful fluid records, measuring urine output, checking blood levels of medicines, and adjusting doses. One hospital programme built around systematically watching babies on kidney-stressing medicines, known as Baby NINJA, reduced kidney injury linked to those drugs [10]. That kind of vigilance is today's version of early detection.

If your baby did have kidney injury in the neonatal unit, it is reasonable to ask about follow-up. Being born early and having early kidney injury are both linked to a somewhat higher chance of high blood pressure or kidney problems later in childhood [11]. Most children do well, but a simple blood pressure and kidney check as they grow is sensible, and asking for that plan before discharge is a good question to bring to a ward round.

What researchers are working on next

The next step is not another study of the same kind. What is needed is research measuring how accurately uKIM-1 identifies kidney injury in an individual baby: agreeing on one laboratory method and one set of units, collecting samples at consistent times after birth, proposing a specific level that counts as abnormal, and testing that level in a new group of babies. Researchers also want to link the marker to outcomes that do not depend on the creatinine blood test at all — whether a baby needed dialysis, or how their kidneys are doing years later. And because several other blood and urine markers have been studied alongside KIM-1 in babies short of oxygen at birth [12], the answer may be a combination of markers rather than one. The same formal systems used to grade this review's certainty as low will then be applied to that new work [13].

That will take years. In the meantime, this study is best read as a signpost: the biology is sound, the early signal is real, and the field now knows precisely which question it still has to answer.

References

  1. Praditaukrit M, Chatatikun M, Tedasen A, et al. Urinary KIM-1 for Early Detection of Acute Kidney Injury in Neonates: A Systematic Review and Meta-Analysis. Life. 2025;15(12):1842. doi:10.3390/life15121842 ↩
  2. Iacobelli S, Guignard JP. Maturation of glomerular filtration rate in neonates and infants: an overview. Pediatr Nephrol. 2021;36(6):1439–1446. doi:10.1007/s00467-020-04632-1 ↩
  3. Selewski DT, Charlton JR, Jetton JG, et al. Neonatal Acute Kidney Injury. Pediatrics. 2015;136:e463. doi:10.1542/peds.2014-3819 ↩
  4. Jetton JG, Boohaker LJ, Sethi SK, et al. Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study. Lancet Child Adolesc Health. 2017;1:184–194. doi:10.1016/S2352-4642(17)30069-X30069-X) ↩
  5. Todo Bom Costa S, Mendes Graça A, Costa Reis P. Neonatal acute kidney injury: where are we now? Pediatr Nephrol. 2026;41(7):1951–1966. doi:10.1007/s00467-025-06978-w ↩
  6. Ichimura T, Bonventre JV, Bailly V, et al. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem. 1998;273(7):4135–4142. doi:10.1074/jbc.273.7.4135 ↩
  7. Kirkley MJ, Boohaker L, Griffin R, et al. Acute kidney injury in neonatal encephalopathy: an evaluation of the AWAKEN database. Pediatr Nephrol. 2019;34(1):169–176. doi:10.1007/s00467-018-4068-2 ↩
  8. AlAbbas A, Campbell A, Skippen P, et al. Epidemiology of cardiac surgery-associated acute kidney injury in neonates: a retrospective study. Pediatr Nephrol. 2013;28(7):1127–1134. doi:10.1007/s00467-013-2454-3 ↩
  9. Steflik HJ, Charlton JR, Briley M, et al. Neonatal nephrotoxic medication exposure and early acute kidney injury: results from the AWAKEN study. J Perinatol. 2023;43(8):1029–1037. doi:10.1038/s41372-023-01684-7 ↩
  10. Stoops C, Stone S, Evans E, et al. Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action): Reduction of Nephrotoxic Medication-Associated Acute Kidney Injury in the Neonatal Intensive Care Unit. J Pediatr. 2019;215:223–228.e6. doi:10.1016/j.jpeds.2019.08.046 ↩
  11. Carmody JB, Charlton JR. Short-term gestation, long-term risk: prematurity and chronic kidney disease. Pediatrics. 2013;131:1168–1179. doi:10.1542/peds.2013-0009 ↩
  12. Sarafidis K, Tsepkentzi E, Agakidou E, et al. Serum and urine acute kidney injury biomarkers in asphyxiated neonates. Pediatr Nephrol. 2012;27(9):1575–1582. doi:10.1007/s00467-012-2162-4 ↩
  13. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–926. doi:10.1136/bmj.39489.470347.AD ↩