Abstract
Purpose
Acute pyelonephritis is associated with considerable morbidity and potential for renal scarring. Pentraxin3 (PTX3) is a recently discovered mediator of inflammation. The objective of this study was to investigate the changes in serum and urine PTX3 levels in children who had a history of pyelonephritis and were diagnosed with renal parenchymal scar (RPS) and/or vesicoureteral reflux (VUR).
Methods
The study included 88 children (31 males, 57 females) aged between 3 months and 18 years. The children included in the study were divided into four groups: VUR with RPS (Group 1), RPS without VUR (Group 2), VUR without RPS (Group 3), and healthy children without a history of hydronephrosis or UTI history (Group 4). After the initial evaluation, the participants were further divided into two more groups and re-evaluated: Children with RPS (Group 1 + 2), children without RPS (Group 3 + 4), children with VUR (Group 1 + 3), and children without VUR (Group 2 + 4).
Results
We found that urine pentraxin 3 (uPTX3) and uPTX3/Creatinine levels were significantly higher in the groups with renal scar with or without VUR than the ones without RPS [mean uPTX3, 3.5 pg/ml (min–max 0.0022–12.3668) vs. 2.2 pg/ml (min–max 0.0022–18.5868) and uPTX3/creatinine, 10.5 pg/mg (min–max 0.0035–51.1) vs. 5.8 pg/mg (min–max 0.0004–78.7), p < 0.01]. uPTX3 levels were not different among the groups with and without VUR. In addition, serum PTX3 levels were not different among the groups.
Conclusions
We showed that urinary PTX3 increased only in patients with scarred kidneys. These results might be helpful to predict RPS due to past pyelonephritis.
Similar content being viewed by others
References
Williams G, Fletcher JT, Alexander SI, Craig JC (2008) Vesicoureteral reflux. J Am Soc Nephrol 19:847–862
Kaack MB, Dowling KJ, Patterson GM, Roberts JA (1986) Immunology of pyelonephritis VIII. E. coli causes granulocytic aggregation and renal ischemia. J Urol 136:1117–1122
Roberts JA (1995) Mechanisms of renal damage in chronic pyelonephritis (reflux nephropathy). Curr Top Pathol 88:265–287
Roberts JA, Domingue GJ, Martin LN, Kim JC (1981) Immunology of pyelonephritis in the primate model: live versus heat-killed bacteria. Kidney Int 19:297–305
Galanakis E, Bitsori M, Dimitriou H, Giannakopoulou C, Karkavitsas NS, Kalmanti M (2006) Urine interleukin-8 as a marker of vesicoureteral reflux in infants. Pediatrics 117:863–867
Imai N, Nishi S, Yoshita K, Ito Y, Osawa Y, Takahashi K et al (2012) Pentraxin-3 expression in acute renal allograft rejection. Clin Transplant 26:25–31
Bottazzi B, Garlanda C, Cotena A, Moalli F, Jaillon S, Deban L et al (2009) The long pentraxin PTX3 as a prototypic humoral pattern recognition receptor: interplay with cellular innate immunity. Immunol Rev 227:9–18
Fazzini F, Peri G, Doni A, Dell’Antonio G, Dal Cin E, Bozzolo E et al (2001) PTX3 in small-vessel vasculitides: an independent indicator of disease activity produced at sites of inflammation. Arthritis Rheum 44:2841–2850
Alberti L, Gilardini L, Zulian A, Micheletto G, Peri G, Doni A et al (2009) Expression of long pentraxin PTX3 in human adipose tissue and its relation with cardiovascular risk factors. Atherosclerosis 202:455–460
Tong M, Carrero JJ, Qureshi AR, Anderstam B, Heimbürger O, Bárány P et al (2007) Plasma pentraxin 3 in patients with chronic kidney disease: associations with renal function, protein-energy wasting, cardiovascular disease, and mortality. Clin J Am Soc Nephrol 2:889–897
Lebowitz RL, Olbing H, Parkkulainen KV, Smellie JM, Tamminen-Möbius TE (1985) International system of radiographic grading of vesicoureteric reflux. International Reflux Study in Children. Pediatr Radiol 15:105–109
Imperiale A, Olianti C, Sestini S, Materassi M, Daniela S, Ienuso R, La Cava G (2003) 123I-Hippuran renal scintigraphy with evaluation of single-kidney clearance for predicting renal scarring after acute urinary tract infection: comparison with 99mTc-DMSA scanning. J Nucl Med 44:1755–1760
Merrikhi AR, Keivanfar M, Gheissari A, Mousavinasab F (2012) Urine interlukein-8 as a diagnostic test for vesicoureteral reflux in children. J Pak Med Assoc 62:52–54
Gokce I, Alpay H, Biyikli N, Unluguzel G, Dede F, Topuzoglu A (2010) Urinary levels of interleukin-6 and interleukin-8 in patients with vesicoureteral reflux and renal parenchymal scar. Pediatr Nephrol 25:905–912
Haraoka M, Senoh K, Ogata N, Furukawa M, Matsumoto T, Kumazawa J (1996) Elevated interleukin-8 levels in the urine of children with renal scarring and/or vesicoureteral reflux. J Urol 155:678–680
Jutley RS, Youngson GG, Eremin O, Ninan GK (2000) Serum cytokine profile in reflux nephropathy. Pediatr Surg Int 16:64–68
Sabasiñska A, Zoch-Zwierz W, Wasilewska A, Porowski T (2008) Laminin and transforming growth factor β-1 in children with vesicoureteric reflux. Pediatr Nephrol 23:769–774
Bottazzi B, Doni A, Garlanda C, Mantovani A (2010) An integrated view of humoral innate immunity: pentraxins as a paradigm. Annu Rev Immunol 28:157–183
He X, Han B, Liu M (2007) Long pentraxin 3 in pulmonary infection and acute lung injury. Am J Physiol Lung Cell Mol Physiol 292:1039–1049
Deban L, Jaillon S, Garlanda C, Bottazzi B, Mantovani A (2011) Pentraxins in innate immunity: lessons from PTX3. Cell Tissue Res 343:23–49
Jaillon S, Moalli F, Ragnarsdottir B, Bonavita E, Puthia M, Riva F (2014) The Humoral Pattern Recognition Molecule PTX3 Is a Key Component of Innate Immunity against Urinary Tract Infection. Immunity 40:621–632
Salio M, Chimenti S, De Angelis N, Molla F, Maina V, Nebuloni M (2008) Cardioprotective function of the long pentraxin PTX3 in acute myocardial infarction. Circulation 117:1055–1064
Lech M, Römmele C, Gröbmayr R, Eka Susanti H, Kulkarni OP, Wang S (2013) Endogenous and exogenous pentraxin-3 limits postischemic acute and chronic kidney injury. Kidney Int 83:647–661
Bassi N, Ghirardello A, Blank M, Zampieri S, Sarzi-Puttini P, Mantovani A (2010) IgG anti-pentraxin 3 antibodies in systemic lupus erythematosus. Ann Rheum Dis 69:1704–1710
Nauta AJ, Bottazzi B, Mantovani A, Salvatori G, Kishore U, Schwaeble WJ (2003) Biochemical and functional characterization of the interaction between pentraxin 3 and C1q. Eur J Immunol 33:465–473
Deban L, Russo RC, Sironi M, Moalli F, Scanziani M, Zambelli V et al (2010) Regulation of leukocyte recruitment by the long pentraxin PTX3. Nat Immunol 11:328–334
Bussolati B, Peri G, Salvidio G, Verzola D, Mantovani A, Camussi G (2003) The long pentraxin PTX3 is synthesized in IgA glomerulonephritis and activates mesangial cells. J Immunol 170:1466–1472
Yüksel S, Çağlar M, Evrengül H, Becerir T, Tepeli E, Ergin A (2015) Could serum pentraxin 3 levels and IgM deposition in skin biopsies predict subsequent renal involvement in children with henoch-schölein purpura? Pediatr Nephrol 30:969–974
Nauta AJ, de Haij S, Bottazzi B, Mantovani A, Borrias MC, Aten J et al (2005) Human renal epithelial cells produce the long pentraxin PTX3. Kidney Int 67:543–553
Hung TW, Tsai JP, Lin SH, Lee CH, Hsieh YH, Chang HR (2016) Pentraxin 3 activates JNK signaling and regulates the epithelial-to-mesenchymal transition in renal fibrosis. Cell Physiol Biochem 40:1029–1038
Parmaksız G, Noyan A, Dursun H, İnce E, Anarat R, Cengiz N (2016) Role of new biomarkers for predicting renal scarring in vesicoureteral reflux: NGAL, KIM-1, and L-FABP. Pediatr Nephrol 31:97–103
Funding
This research has been supported by Pamukkale University Research Fund (Number 2015HZL007).
Author information
Authors and Affiliations
Contributions
TB conceptualized and designed the study, drafted the initial manuscript. TB, HE, and YE carried out the initial analyses, reviewed, and revised the manuscript. AE supervised the statistics. SY made critical revision of the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
Corresponding author
Ethics declarations
Conflict of interest
No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.
Ethical approval
The study was approved by the Pamukkale University Ethics Committee (IRB number 60116787-020/549639).
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Becerir, T., Yüksel, S., Evrengül, H. et al. Urinary excretion of pentraxin-3 correlates with the presence of renal scar following acute pyelonephritis in children. Int Urol Nephrol 51, 571–577 (2019). https://doi.org/10.1007/s11255-019-02102-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11255-019-02102-8