Regarding Maas’s editorial letter on serum suPAR levels

To the Editor

On the basis of data from a cohort of 23 adult patients, the letter from Maas et al.¹ concludes that serum soluble urokinase–type plasminogen activator receptor (suPAR) levels do not discriminate between primary focal segmental glomerulosclerosis (FSGS), secondary FSGS, and minimal change disease (MCD), and cannot be used to predict the response to a therapeutic course of corticosteroids. They further note an inverse correlation between the suPAR concentration and estimated glomerular filtration rate (eGFR). We advise caution in the interpretation and application of these findings for several reasons. First, the patients appear not to be adequately characterized. For example, there is neither comment about whether there was biopsy confirmation of all the cases with FSGS nor clarification of the criteria used to distinguish primary from secondary FSGS. The patient with the highest suPAR is categorized as having steroid-resistant MCD. However, cross-referencing Figures 1 and 2 indicates that this patient had the lowest eGFR, presumably <15 ml/min. Such an adverse renal function outcome is very unexpected in patients with MCD and thus this patient is likely representative of a FSGS case. Appropriate reclassification of some of the patients by Maas et al.² may facilitate a more precise comparison between suPAR and clinical outcomes. Second, the authors’ conclusions are based on a small sample from a single institution. In the original paper by Wei et al., data and conclusions were based on a multicenter biopsy-proven cohort including 78 pediatric and adult FSGS patients. In addition, we have presented data from two large well-characterized patients cohorts—the FSGS PodoNET and Clinical Trial—in which 55–85% of the patients with primary FSGS had an elevated serum suPAR concentration.³ Although we welcome ongoing investigation in this novel area, we suggest that information collected in larger clinical studies involving well-phenotyped patients should take precedence over data gathered in small single-center studies where the phenotypic characterization may be improved. Finally, we point out that MCD and FSGS are classifications of diseases that lack specificity and that may be amended with a molecular phenotyping approach involving molecules such as suPAR. Using this strategy, patients with elevated suPAR levels and poor renal outcomes may indeed confirm previous publications suggesting suPAR may be a major cause of FSGS and a biomarker for a poor prognosis in native and post-transplant recurrent FSGS and nephrotic syndrome.