The role of novel biomarkers in childhood idiopathic nephrotic syndrome: a narrative review of published evidence

Abstract

Two histological subtypes of idiopathic nephrotic syndrome are commonly recognized in children, namely minimal change nephropathy and focal segmental glomerulosclerosis. Children with minimal change nephropathy (the majority of whom are steroid-sensitive) and focal segmental glomerulosclerosis (the majority of whom are steroid-resistant) require early identification in order to ensure appropriate therapeutic intervention and better outcome. Although renal biopsy and histology remain the ideal diagnostic steps to identify these histological subtypes, reports indicate that serum and urinary biomarkers are now being utilized in the investigation of childhood idiopathic nephrotic syndrome. This paper aims to review the diagnostic and prognostic utility of novel biomarkers in childhood idiopathic nephrotic syndrome and to highlight their role in differentiating steroid-sensitive nephrotic syndrome (SRNS) from steroid-resistant nephrotic syndrome (SSNS). Using the terms "idiopathic nephrotic syndrome," "children," and "biomarkers" the PubMed database was searched for relevant studies related to the topic. Biomarkers such as adiponectin, neopterin, β2-microglobulin, and N-acetyl-β-D glucosaminidase were reported as diagnostic markers. In addition to neopterin and N-acetyl-β-D glucosaminidase, urine vitamin D-binding protein and α1β-glycoprotein were shown to differentiate SRNS from SSNS while N-acetyl-β-D glucosaminidase and β2-microglobulin could predict steroid responsiveness and renal outcome in SRNS. Although progress has been made in demonstrating the diagnostic and prognostic utility of these biomarkers, their limited availability in most laboratories has precluded a complete paradigm shift from the conventional renal biopsy. Nevertheless, further longitudinal studies are required to establish their usefulness as noninvasive predictors of disease response to immunosuppressive therapy.

Biomarkers of Common Childhood Renal Diseases

“…Several novel biomarkers have also been identified in the evaluation of childhood CKD: especially CKD secondary to idiopathic nephrotic syndrome and diabetic nephropathy (DN) [2,50].…”

“…The use of biomarkers in childhood idiopathic nephrotic syndrome has been well documented [2]. It represents a non-invasive approach in diagnostic nephrology, as these markers can be used in the prediction and prognostic evaluation of the disease, as well as in differentiating steroid-resistant nephrotic syndrome (SRNS) from steroid-sensitive nephrotic syndrome (SSNS).…”

“…Novel biomarkers are now utilized in the diagnostic and prognostic evaluation of common kidney diseases in children [1][2][3]. Unlike in developing countries where they are scarcely used in medical diagnostics, they are currently used as site-of-care and laboratory tools for disease evaluation in developed settings although some of them have not been fully validated for routine clinical use.…”

Endothelin‐1 rs9296344 associates with the susceptibility of childhood primary nephrotic syndrome

“…The cause of CPNS is not known in most cases. However, recent studies suggested that genetic factors, such as single nucleotide polymorphisms (SNPs), might contribute to the susceptibility of CPNS …”

The Metabolomics Signature Associated with Responsiveness to Steroid Therapy in Focal Segmental Glomerulosclerosis: A Pilot Study

“…The idiopathic type of FSGS is diagnosed after ruling out these mentioned causes; otherwise, it is diagnosed as secondary type 2 . Clinically, FSGS is often associated with nephrotic syndrome, which is characterized by proteinuria of > 1 g/ m 2 /24 h, hypoalbuminemia, generalized edema, and hyperlipidemia 5,6 . The other clinical presentations of FSGS are hypertension, microscopic hematuria, renal failure, and serum creatinine increment 7 .…”