Neutrophil gelatinase-associated lipocalin (NGAL), a biomarker released in response to tubular injury, may serve as a noninvasive tool for measuring kidney injury.

A new systematic review and meta-analysis suggests that urinary NGAL is significantly elevated in patients with steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS) compared with healthy control individuals, and that NGAL levels are higher in SRNS than in SSNS. If validated, urinary NGAL could help identify steroid resistance early and guide management in idiopathic nephrotic syndrome.

“This may help personalize therapy and help monitor cyclosporine toxicity,” said corresponding author Sagad O.O. Mohamed, MBBS, Faculty of Medicine, University of Khartoum, Khartoum, Sudan.

Literature Review Reveals a Strong Trend

Investigators screened 155 studies (2010-2023) using PRISMA guidelines and a comprehensive, multi-database search. Sixteen studies met inclusion criteria; all evaluated pediatric patients from seven countries, and several included healthy control individuals. Patients with idiopathic nephrotic syndrome were classified as SSNS and SRNS.

Using a random effects model, the authors estimated a standardized mean difference (SMD). SRNS showed markedly higher urinary NGAL levels than SSNS (SMD = 1.889; 95% CI, 0.819-2.959; P < .001). Several studies used reported receiver operating characteristic performance, with area under the curve values generally indicating moderate-to-strong discrimination for distinguishing SRNS from SSNS using urinary NGAL or NGAL/creatine ratios.

The findings support urinary NGAL’s diagnostic accuracy, biological plausibility, and cross-population relevance, strengthening the case for its inclusion in clinical assessment protocols. It is theorized that NGAL could enable more personalized treatment strategies, minimize unnecessary steroid exposure, and improve outcomes in pediatric patients with nephrotic syndrome.

Earlier Detection May Improve Outcomes

Early differentiation between SSNS and SRNS is crucial because SRNS is associated with poorer long-term outcomes.

Mohamed noted that all included patients were aged 1-18 years, and therefore the findings may not be applicable to adults. Even so, the robust results indicate that high urinary NGAL could flag SRNS, prompting biopsy or earlier use of immunosuppressants and thereby avoiding steroid toxicity. NGAL may also help monitor tubular injury and be combined with estimated glomerular filtration rate or creatinine to fine-tune treatment in SSNS and SRNS.

“It’s a step toward precision medicine. NGAL’s ability to predict steroid resistance enables tailored therapy,” Mohamed told Medscape Medical News.

Trends were consistent across diverse pediatric cohorts drawn from studies conducted in India, Egypt, Europe, and North America. However, the authors stressed that future studies need to establish standardized cutoff thresholds for urinary NGAL and to assess its performance across diverse clinical settings. There is a possibility that sampling during various disease phases or in patients receiving concurrent therapies may confound biomarker interpretation.

They added that future work should investigate NGAL alongside other emerging biomarkers (eg, kidney injury molecule-1) to build diagnostic panels that improve specificity and better capture disease heterogeneity. Longitudinal studies are warranted to define NGAL’s utility for predicting relapse, remission, and treatment response, including kinetics during immunosuppressive therapy and its relationship with histopathologic progression. Urinary NGAL may also help predict nephrotoxicity and resistance profiles in vulnerable pediatric populations where therapeutic precision is critical.

‘Highly Sensitive and Specific’

Commenting on the review, Gebhard Wagener, MD, professor of anesthesiology, College of Physicians & Surgeons of Columbia University in New York City, said he was not surprised by the finding, as elevated urinary NGAL is consistent with tubular injury that portends a poorer prognosis.

“Urinary NGAL is an excellent marker of renal injury and is highly sensitive and specific. Serum creatinine — the current standard to define acute kidney injury — is a marker of function, not injury, and usually rises slowly, often when it is too late to intervene,” said Wagener, who was not involved in the study. “Serum creatinine will increase in many conditions that are not necessarily associated with injury, and using serum creatinine as a marker to define acute kidney injury has hindered progress in treating it. This study exemplifies how better a marker for renal injury can advance treatment and allow early and targeted intervention.”

The study was published online in BMC Nephrology.

Mohamed and Wagener reported having no relevant financial disclosures.

John Schieszer, MA, is an award-winning national journalist and podcast broadcaster of The Medical Minute. He can be reached at medicalminutes@gmail.com.