Novel Technique Detects Biomarkers for Kidney Diseases with Nephritic Syndrome

Nephrotic syndrome is associated with several kidney diseases such as minimal change disease (MCD), primary focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), and is characterized by high levels of protein in the urine. This condition primarily stems from damage to podocytes, the cells that filter blood in the kidneys, which results in protein leakage into the urine. Often, children diagnosed with MCD or FSGS are categorized under idiopathic nephrotic syndrome (INS), indicating an unknown cause. This is typically because children with elevated urinary protein levels seldom undergo kidney biopsies, which are the standard method for determining the underlying cause. Traditionally, the diagnosis of these conditions has been complicated due to their similar histological features and a general reluctance to perform invasive kidney biopsies, especially in children. Although anti-nephrin autoantibodies have been detected in some patients with MCD and FSGS, their exact role in the progression of these diseases remains unclear. A groundbreaking study recently presented at the 61st ERA Congress has made a significant breakthrough in diagnosing and monitoring kidney diseases linked to nephrotic syndrome.

Researchers at the University Medical Center Hamburg-Eppendorf (Hamburg, Germany) utilized a hybrid method to identify anti-nephrin autoantibodies as a reliable biomarker for tracking the progression of these diseases, paving the way for tailored treatment strategies. The study, which spanned across Europe and the USA, employed a novel combination of immunoprecipitation and enzyme-linked immunosorbent assay (ELISA) to accurately detect anti-nephrin autoantibodies. The results showed that these autoantibodies were present in 69% of adults with MCD and 90% of children with INS who had not received immunosuppressive treatments. The levels of these antibodies also correlated with the activity of the disease, indicating their potential as a biomarker for monitoring disease progression. These antibodies were seldom found in other diseases being studied.

In further experiments, researchers introduced laboratory-synthesized nephrin protein to mice, simulating conditions similar to MCD. This immunization led to phosphorylation of nephrin and significant changes in cellular structures, suggesting that antibodies targeting nephrin play a role in podocyte dysfunction and the onset of nephrotic syndrome. Remarkably, this model required only a single immunization to trigger rapid disease onset, even with low concentrations of antibodies, unlike other models that need multiple immunizations.

“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,” said Dr. Nicola M. Tomas, co-lead author of the study.

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

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University Medical Center Hamburg-Eppendorf

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