Nephrotic syndrome is one of the most common glomerular disorders affecting children and adults worldwide. Corticosteroids remain the first-line therapy, but response to treatment varies. While patients with SSNS generally respond well and have a more favorable prognosis, those with SRNS face a greater risk of disease progression, complications, and long-term kidney damage. Early differentiation between the two subtypes is therefore critical for tailoring treatment strategies and preventing poor outcomes.
NGAL, a biomarker released in response to tubular injury, has gained increasing attention for its role in detecting renal damage. Unlike traditional diagnostic methods that may require invasive procedures or prolonged observation of treatment response, urinary NGAL offers a simpler, non-invasive means to assess disease severity and treatment resistance.
The meta-analysis included data from 16 studies that assessed urinary NGAL levels in patients with SSNS, SRNS, and healthy controls. The results were as follows:
- Urinary NGAL levels were significantly elevated in both SSNS and SRNS groups compared with healthy individuals.
- Patients with SSNS showed a standardized mean difference (SMD) of 0.78, while those with SRNS had a much higher SMD of 2.56.
- Urinary NGAL levels were markedly greater in SRNS compared to SSNS patients, with an SMD of 1.889, highlighting its potential to differentiate between the two forms of nephrotic syndrome.
- Receiver operating characteristic (ROC) curve analyses across multiple studies demonstrated that urinary NGAL possesses a moderate-to-strong discriminative ability in distinguishing SRNS from SSNS.
- These findings highlight urinary NGAL’s clinical value not only in diagnosis but also in risk stratification and disease monitoring.
The authors emphasized that these findings provide strong evidence supporting the role of urinary NGAL as a non-invasive tool to improve clinical decision-making. Identifying SRNS at an earlier stage may allow physicians to consider alternative therapies sooner, potentially reducing the risk of progression to chronic kidney disease and other long-term complications.
While the results are encouraging, the study also highlighted the need for larger, well-designed prospective studies to validate NGAL’s role in clinical practice. Standardizing testing methods and cutoff values would further strengthen its application in routine care.
"The comprehensive analysis establishes urinary NGAL as a valuable biomarker for distinguishing between steroid-sensitive and steroid-resistant nephrotic syndrome. By enabling earlier identification of high-risk patients, its integration into clinical practice could significantly enhance personalized management and improve outcomes in individuals living with nephrotic syndrome," the researchers concluded.
Reference:
Abdalla, A., Ali, A., Abufatima, I.O. et al. Use of urinary NGAL in steroid-resistant vs. steroid-sensitive nephrotic syndrome: a systematic review and meta-analysis. BMC Nephrol 26, 486 (2025). https://doi.org/10.1186/s12882-025-04420-9
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