Serum suPAR levels are modulated by immunosuppressive therapy of minimal change nephrotic syndrome

Abstract

Background: Soluble urokinase-type plasminogen activator receptor (suPAR) could be a causative factor in idiopathic focal segmental glomerulosclerosis (FSGS). It is currently unknown to what extent suPAR levels could be affected by treatment with immunosuppressive drugs such as cyclosporin A (CsA) and mycophenolate mofetil (MMF). Treatment with CsA, but not MMF, is accompanied by nephrotoxicity, and since suPAR levels correlate with glomerular filtration rate (GFR), treatment with these drugs could indirectly modulate suPAR levels by their effect on renal function. Methods: We measured suPAR levels in a recent prospective multicenter crossover trial comparing the efficacy of MMF and CsA in pediatric patients with minimal change disease (MCD) and frequently relapsing steroid-sensitive nephrotic syndrome (FR-SSNS). All patients had biopsy-proven MCD and normal renal function; they were treated with each drug for 1 year in a crossover study design. Serum suPAR levels were measured before and after 1 year of therapy with MMF (n = 40) and CsA (n = 35). Results: The suPAR levels decreased after 1 year of treatment with MMF (p < 0.05). Conversely, suPAR levels increased after 1 year of treatment with CsA in the same patients (p = 0.01). These changes in suPAR levels were not correlated to the estimated glomerular filtration rate (eGFR) or changes in the GFR. Conclusions: Data from this prospective randomized trial suggest that treatment with MMF and CsA is associated with different effects on suPAR levels in children with MCD and that these are independent of their effects on GFR.