Presence and Intensity of Leptin Expression in the Kidney in Focal Segmental Glomerulosclerosis: Can It Shed Light on the Pathogenesis and Prognosis of the Disease?

Background: Focal segmental glomerulosclerosis (FSGS) is a primary glomerulopathy often progressing to chronic kidney failure. It can be primary or secondary to factors like drugs, substance use, sickle cell anemia, HIV, parvovirus B19, genetic factors, and obesity. Leptin, a hormone produced by adipose tissue, binds to receptors in endothelial and mesangial cells, inducing cellular proliferation, extracellular matrix accumulation, and type IV collagen production. These effects of leptin are significant in FSGS pathogenesis. This study evaluates the impact of leptin expression in kidney biopsy on renal survival and differentiation between primary and secondary FSGS. Methods: Patients with FSGS, followed at Gazi University Faculty of Medicine Hospital's Adult Nephrology Clinic for at least two years and who had undergone diagnostic kidney biopsy, were included. Kidney biopsies were stained immunohistochemically with leptin. Demographic characteristics, clinical and laboratory findings, and medical treatments were recorded. The relationship between immunohistochemical staining and clinical findings was evaluated. Results: A total of 105 patients were evaluated. 23% were Leptin (-), 62% were Leptin (+), and 15% were Leptin (++). Demographic characteristics were similar across groups. There was no relationship between leptin positivity and body weight. Leptin negativity was significantly associated with a good treatment response, while severe leptin positivity was significantly associated with a poor treatment response (both p<0.05). Most patients with secondary FSGS showed severe leptin positivity. Among patients with severe leptin positivity, 92% were non-responsive to treatment, compared to 20% in leptin-negative patients. Conclusion: The role of leptin in kidney diseases has been known, but no prior study demonstrated leptin expression in glomerular diseases. Our study is the first to show leptin expression in the kidneys of FSGS patients and evaluate disease etiology and prognosis based on expression intensity. Leptin can be a guiding biomarker and therapeutic target in terms of renal survival and treatment response in FSGS. Evaluating leptin expression in the kidney can shed light on pathogenesis, assist in individualized treatment, and provide insights into poor renal prognosis, guiding future studies. Funding: Private Foundation Support