Study finds new method to detect novel biomarkers for kidney diseases with nephrotic syndrome

Boston [US], May 25 : A study has revealed a major advance in the identification and tracking of renal illnesses linked to nephrotic syndrome.

The findings of the study were published in the New England Journal of Medicine and presented at the 61st ERA Congress in Stockholm, Sweden.

By employing a hybrid methodology, scientists discovered that anti-nephrin autoantibodies serve as a dependable biomarker for monitoring the advancement of the disease, paving the way for more individualized therapeutic strategies.

Nephrotic syndrome, defined by increased urine protein levels, is associated with kidney disorders, including membranous nephropathy (MN), primary focal segmental glomerulosclerosis (FSGS), and minimal change disease (MCD). Damage to podocytes, the kidney's filtering cells, is the main cause of nephrotic syndrome because it permits protein to seep into the urine.

Children diagnosed with MCD or FSGS often receive a diagnosis of idiopathic nephrotic syndrome (INS), where the cause of the nephrotic syndrome is unknown. This is frequently because children with high protein levels in their urine rarely undergo a kidney biopsy, which is how the cause is typically determined.

Traditionally, diagnosing these conditions has posed challenges due to overlapping histological features and hesitancy to conduct invasive kidney biopsies, particularly in children. While anti-nephrin autoantibodies have been observed in certain patients with MCD and FSGS, their precise role in the advancement of these diseases is not fully understood.

The study, conducted across Europe and the USA, introduced a novel approach combining immunoprecipitation with enzyme-linked immunosorbent assay (ELISA) to reliably detect anti-nephrin autoantibodies.

The findings revealed that anti-nephrin autoantibodies were prevalent in 69 per cent of adults with MCD and 90 per cent of children with INS who had not been treated with immunosuppressive drugs. Importantly, the levels of these autoantibodies correlated with disease activity, suggesting their potential as a biomarker for monitoring disease progression. The antibodies were also rarely seen in the other diseases under examination.

To further investigate the impact of nephrin immunisation on kidney function and disease, researchers administered laboratory-made nephrin protein to mice, creating a condition akin to MCD in the mice. Immunisation led to the phosphorylation of nephrin and notable alterations in cell structure, indicating the involvement of antibodies targeting nephrin in podocyte malfunction and nephrotic syndrome.

Remarkably, unlike other models necessitating multiple immunisations, this model induced swift disease manifestation with a single immunisation, even at low antibody concentrations.

Dr Nicola M Tomas, co-lead author of the study, commented, "The identification of anti-nephrin autoantibodies as a reliable biomarker, coupled with our hybrid immunoprecipitation technique, enhances our diagnostic capabilities and opens new avenues for closely monitoring disease progression in kidney disorders with nephrotic syndrome."

Professor Tobias B. Huber, lead author of the study, furthered, "By providing insights into underlying mechanisms, these findings lay the groundwork for personalised interventions and pave the way for a new era of precision medicine for these complex conditions."

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