SuPAR : IS IT THE IDEAL MARKER OF FSGS ?

INTRODUCTION AND RATIONALE Focal and segmental glomerulosclerosis(FSGS) is defined as a clinicopathological syndrome characterized by proteinuria often in the nephrotic range,associated with lesions of focal and segmental glomerulosclerosis and foot process effacement on biopsy. It is also associated with steroid resistance, hypertension, and high probability of progression to renal failure. FSGS can be classified as primary(or idiopathic) and secondary based on etiology. Primary FSGS must be differentiated from secondary forms with recognized etiologic associations, including genetic mutations in podocyte-associated proteins, viruses ,drug toxicities and structural-functional adaptations in conditions like obesity, reduced renal mass.1 Over the six decades since the first description of FSGS by Arnold Rich2 in 1957, pathogenesis of primary FSGS has been evaluated in various studies.The concept of circulating permeability factor evolved from evidences including: 1. Recurrence of primary FSGS rapidly after renal transplantation (30% of cases in adults, 50% in children).3,4 2. Injection of plasma or plasma fractions from patients with FSGS into rats causes Proteinuria.5 3. Sera from patients with FSGS increase albumin permeability in an isolated glomerulus model ex vivo.6 4. FSGS can be prevented or delayed in high-risk patients with pretransplantation plasmapheresis, probably due to removal of the factors from the circulation.7 Many molecules like Cardiotropin like cytokine(CLC-1)8 were proposed as putative permeability factors since then, but none was confirmed authentically in clinical trials. The major breakthrough was identification of suPAR as the FSGS permeability factor by Wei et al.9 They demonstrated that suPAR levels were increased in two thirds of pediatric and adult patients with biopsy proven FSGS, including both native and recurrent FSGS cases in a cohort of 78 post transplant patients using commercially available ELISA Kit. These results were upheld by many studies and they also suggest that suPAR could be used as a biomarker to diagnose and assess the disease activity in FSGS.10,11 Recently reports are coming against this findings saying that suPAR is not specific for primary FSGS.12-14 Most of these studies used suPAR level 3ng/ml as the cutoff as there was significant difference in the suPAR level between FSGS patients and controls and came out with conflicting results. In our study, we aimed to test whether the plasma suPAR level in patients with FSGS is significantly different from controls and if so, we would like to assess the sensitivity and specificity of higher cutoff values of suPAR for diagnosing primary FSGS.