A study has revealed major advances in identifying and tracking kidney diseases associated with nephrotic syndrome.
The study findings were published in the New England Journal of Medicine and presented at the 61st ERA Congress held in Stockholm, Sweden.
Also read: Kidney failure: Main causes; warning symptoms
Using a hybrid approach, the scientists found that anti-nephrin autoantibodies serve as a reliable biomarker for monitoring disease progression, paving the way for more personalized therapeutic strategies.
Also Read: Chronic kidney disease in children: Warning signs and symptoms, causes and treatment
What is nephrotic syndrome?
Nephrotic syndrome, which is defined by increased levels of urine protein, is associated with kidney disorders, including membranous nephropathy (MN), primary focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Damage to the kidney’s filtering cells, the podocytes, is the main cause of nephrotic syndrome as it allows protein to leak into the urine.
Children with MCD or FSGS often receive a diagnosis of idiopathic nephrotic syndrome (INS), where the cause of the nephrotic syndrome is unknown. This is often because children who have high levels of protein in their urine rarely undergo a kidney biopsy, which usually leads to the discovery of the cause.
Traditionally, there have been challenges in diagnosing these conditions because of overlapping histological features and hesitancy to perform invasive kidney biopsies, especially in children. While anti-nephrin autoantibodies have been observed in some patients with MCD and FSGS, their exact role in the progression of these diseases is not fully understood.
This study, conducted in Europe and the United States, presented a new method combining immunoprecipitation with enzyme-linked immunosorbent assay (ELISA) to reliably detect anti-nephrin autoantibodies.
The findings showed that anti-nephrin autoantibodies were present in 69 percent of adults with MCD and 90 percent of children with INS who were not treated with immunosuppressive drugs. Importantly, the levels of these autoantibodies were related to disease activity, suggesting their potential as biomarkers for monitoring disease progression. The antibodies were also rarely seen in the other diseases under investigation.
To further investigate the effect of nephrin vaccination on kidney function and disease, the researchers administered laboratory-produced nephrin protein to mice, which induced an MCD-like condition in the mice. Vaccination caused phosphorylation of nephrin and significant changes in cell structure, indicating the involvement of antibodies targeting nephrin in podocyte malfunction and nephrotic syndrome.
Remarkably, unlike other models that require multiple vaccinations, this model produced rapid manifestation of disease with a single vaccination, 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, combined with our hybrid immunoprecipitation technique, expands 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, added, “By providing insights into the underlying mechanisms, these findings lay the groundwork for personalized interventions and pave the way to a new era of precision medicine for these complex conditions.”
