Top

Pediatric Nephrology

Published in:

01-12-2014 | Brief Report

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

Authors: Jutta Gellermann, Franz Schaefer, Uwe Querfeld

Published in: Pediatric Nephrology | Issue 12/2014

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.

Available only for authorised users

Wei C, El Hindi S, Li J, Fornoni A, Goes N, Sageshima J, Maiguel D, Karumanchi SA, Yap HK, Saleem M, Zhang Q, Nikolic B, Chaudhuri A, Daftarian P, Salido E, Torres A, Salifu M, Sarwal MM, Schaefer F, Morath C, Schwenger V, Zeier M, Gupta V, Roth D, Rastaldi MP, Burke G, Ruiz P, Reiser J (2011) Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med 17:952–960PubMedCrossRefPubMedCentral

Wei C, Trachtman H, Li J, Dong C, Friedman AL, Gassman JJ, McMahan JL, Radeva M, Heil KM, Trautmann A, Anarat A, Emre S, Ghiggeri GM, Ozaltin F, Haffner D, Gipson DS, Kaskel F, Fischer DC, Schaefer F, Reiser J (2012) Circulating suPAR in two cohorts of primary FSGS. J Am Soc Nephrol 23:2051–2059PubMedCrossRefPubMedCentral

Huang J, Liu G, Zhang YM, Cui Z, Wang F, Liu XJ, Chu R, Chen Y, Zhao MH (2013) Plasma soluble urokinase receptor levels are increased but do not distinguish primary from secondary focal segmental glomerulosclerosis. Kidney Int 84:366–372PubMedCrossRef

Bock ME, Price HE, Gallon L, Langman CB (2013) Serum soluble urokinase-type plasminogen activator receptor levels and idiopathic FSGS in children: A single-center report. Clin J Am Soc Nephrol 8:1304–1311PubMedCrossRefPubMedCentral

Wada T, Nangaku M, Maruyama S, Imai E, Shoji K, Kato S, Endo T, Muso E, Kamata K, Yokoyama H, Fujimoto K, Obata Y, Nishino T, Kato H, Uchida S, Sasatomi Y, Saito T, Matsuo S (2014) A multicenter cross-sectional study of circulating soluble urokinase receptor in Japanese patients with glomerular disease. Kidney Int 85:641–648PubMedCrossRef

Meijers B, Maas RJ, Sprangers B, Claes K, Poesen R, Bammens B, Naesens M, Deegens JK, Dietrich R, Storr M, Wetzels JF, Evenepoel P, Kuypers D (2014) The soluble urokinase receptor is not a clinical marker for focal segmental glomerulosclerosis. Kidney Int 85:636–640PubMedCrossRef

Sinha A, Bajpai J, Saini S, Bhatia D, Gupta A, Puraswani M, Dinda AK, Agarwal SK, Sopory S, Pandey RM, Hari P, Bagga A (2014) Serum-soluble urokinase receptor levels do not distinguish focal segmental glomerulosclerosis from other causes of nephrotic syndrome in children. Kidney Int 85:649–658PubMedCrossRef

Sever S, Trachtman H, Wei C, Reiser J (2013) Is there clinical value in measuring suPAR Levels in FSGS? Clin J Am Soc Nephrol 8:1273–1275PubMedCrossRefPubMedCentral

Pliyev BK, Menshikov MY (2010) Release of the soluble urokinase-type plasminogen activator receptor (suPAR) by activated neutrophils in rheumatoid arthritis. Inflammation 33:1–9PubMedCrossRef

10.

Kengne-Wafo S, Massella L, Diomedi-Camassei F, Gianviti A, Vivarelli M, Greco M, Stringini GR, Emma F (2009) Risk factors for cyclosporin A nephrotoxicity in children with steroid-dependant nephrotic syndrome. Clin J Am Soc Nephrol 4:1409–1416PubMedCrossRef

11.

Gellermann J, Querfeld U (2004) Frequently relapsing nephrotic syndrome: treatment with mycophenolate mofetil. Pediatr Nephrol 19:101–104PubMedCrossRef

12.

Maas RJ, Wetzels JF, Deegens JK (2012) Serum-soluble urokinase receptor concentration in primary FSGS. Kidney Int 81:1043–1044PubMedCrossRef

13.

Gellermann J, Weber L, Pape L, Tonshoff B, Hoyer P, Querfeld U (2013) Mycophenolate mofetil versus cyclosporin A in children with frequently relapsing nephrotic syndrome. J Am Soc Nephrol 24:1689–1697PubMedCrossRefPubMedCentral

14.

Pawlak K, Ulazka B, Mysliwiec M, Pawlak D (2012) Vascular endothelial growth factor and uPA/suPAR system in early and advanced chronic kidney disease patients: a new link between angiogenesis and hyperfibrinolysis? Transl Res 160:346–354PubMedCrossRef

15.

Zhang B, Shi W, Ma J, Sloan A, Faul C, Wei C, Reiser J, Yang Y, Liu S, Wang W (2012) The calcineurin-NFAT pathway allows for urokinase receptor-mediated beta3 integrin signaling to cause podocyte injury. J Mol Med (Berl) 90:1407–1420CrossRef

Title: Serum suPAR levels are modulated by immunosuppressive therapy of minimal change nephrotic syndrome
Authors: Jutta Gellermann
Franz Schaefer
Uwe Querfeld
Publication date: 01-12-2014
Publisher: Springer Berlin Heidelberg
Published in: Pediatric Nephrology / Issue 12/2014
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-014-2913-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 12/2014

Cisplatinum nephrotoxicity in oncology therapeutics: retrospective review of patients treated between 2005 and 2012

Calcific uraemic arteriolopathy: a rare disease with a potentially high impact on chronic kidney disease–mineral and bone disorder

Urinary angiotensinogen and urinary sodium are associated with blood pressure in normoalbuminuric children with diabetes

Biology of sepsis: Its relevance to pediatric nephrology

Clinicopathological characteristics and outcomes of pediatric patients with systemic small blood vessel vasculitis

12th Asian Congress of Pediatric Nephrology