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J Pediatr Infect Dis 2022; 17(03): 155-162
DOI: 10.1055/s-0042-1748922
Original Article

Diagnostic Value of Urine Ribonuclease 7 (RNase 7) to Creatinine Ratio for Detecting Urinary Tract Infection in Children with Pyuria

Nuran Cetin 
1   Department of Pediatric Nephrology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
,
Zeynep Kusku Kiraz 
2   Department of Biochemistry, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
,
Aylin Gencler 
1   Department of Pediatric Nephrology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey
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Abstract

Objective Ribonuclease 7 (RNase 7) is one of the members of the antimicrobial peptides playing a role in maintaining urinary tract sterility. We aimed to investigate the predictive value of the urine RNase 7 levels in children with pyuria and associations between RNase 7 and vesicoureteral reflux (VUR) and renal scarring.

Methods This study included 109 children with pyuria (46 febrile urinary tract infections [UTIs], 38 nonfebrile UTIs, and 25 sterile pyuria) whose RNase 7 levels were measured by enzyme-linked immunoassay. The results for urine RNase 7 concentrations were expressed as micrograms per milligrams creatinine.

Results RNase 7/Cr levels were higher in patients with both febrile and nonfebrile UTIs than the patients with sterile pyuria (p = 0.001). RNase 7/Cr had predictive values of diagnosis of febrile and nonfebrile UTIs (cut-off value: 2.92 µg/mg, p = 0.003; cut-off value: 3.67 µg/mg, p < 0.001, respectively). RNase 7/Cr had higher levels in the patients with VUR than without VUR (cut-off value: 4.28 µg/mg, p = 0.037). The patients with renal scarring had higher urine RNase 7/Cr than those without scarring (cut-off value: 4.54 µg/mg, p = 0.041).

Conclusion The evaluation of RNase 7/Cr may help prevent unnecessary and/or inappropriate antibiotic use in children with pyuria. The higher RNase 7 levels in patients with VUR and renal scarring may reflect long-term inflammation or greater inflammatory response during acute infection.

Keywords

children - renal scarring - ribonuclease 7 - urinary tract infection - vesicoureteral reflux


Publication History

Received: 23 December 2021

Accepted: 29 March 2022

Article published online:
10 June 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Nuutinen M, Uhari M. Recurrence and follow-up after urinary tract infection under the age of 1 year. Pediatr Nephrol 2001; 16 (01) 69-72
    CrossrefPubMedGoogle Scholar
  • 2 Jacobson SH, Eklöf O, Eriksson CG, Lins LE, Tidgren B, Winberg J. Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up. BMJ 1989; 299 (6701): 703-706
    CrossrefPubMedGoogle Scholar
  • 3 Ali AS, Townes CL, Hall J, Pickard RS. Maintaining a sterile urinary tract: the role of antimicrobial peptides. J Urol 2009; 182 (01) 21-28
    CrossrefPubMedGoogle Scholar
  • 4 Spencer JD, Schwaderer AL, Wang H. et al. Ribonuclease 7, an antimicrobial peptide upregulated during infection, contributes to microbial defense of the human urinary tract. Kidney Int 2013; 83 (04) 615-625
    CrossrefPubMedGoogle Scholar
  • 5 Mori R, Lakhanpaul M, Verrier-Jones K. Diagnosis and management of urinary tract infection in children: summary of NICE guidance. BMJ 2007; 335 (7616): 395-397
    CrossrefPubMedGoogle Scholar
  • 6 Polito C, La Manna A, Rambaldi PF, Nappi B, Mansi L, Di Toro R. High incidence of a generally small kidney and primary vesicoureteral reflux. J Urol 2000; 164 (02) 479-482
    CrossrefPubMedGoogle Scholar
  • 7 MacKenzie JR, Fowler K, Hollman AS. et al. The value of ultrasound in the child with an acute urinary tract infection. Br J Urol 1994; 74 (02) 240-244
    CrossrefPubMedGoogle Scholar
  • 8 Roberts KB. Subcommittee on Urinary Tract Infection, Steering Committee on Quality Improvement and Management. Urinary tract infection: clinical practice guideline for the diagnosis and management of the initial UTI in febrile infants and children 2 to 24 months. Pediatrics 2011; 128 (03) 595-610
    CrossrefPubMedGoogle Scholar
  • 9 Su RR, Palta M, Lim A, Wald ER. Pyuria as a marker of urinary tract infection in neurogenic bladder: is it reliable?. Pediatr Infect Dis J 2019; 38 (08) 804-807
    CrossrefPubMedGoogle Scholar
  • 10 Stamm WE. Measurement of pyuria and its relation to bacteriuria. Am J Med 1983; 75 (1B): 53-58
    CrossrefPubMedGoogle Scholar
  • 11 Dieter RS. Sterile pyuria: a differential diagnosis. Compr Ther 2000; 26 (03) 150-152
    CrossrefPubMedGoogle Scholar
  • 12 Hooker JB, Mold JW, Kumar S. Sterile pyuria in patients admitted to the hospital with infections outside of the urinary tract. J Am Board Fam Med 2014; 27 (01) 97-103
    CrossrefPubMedGoogle Scholar
  • 13 Shaikh N, Hoberman A, Hum SW. et al. Development and validation of a calculator for estimating the probability of urinary tract infection in young febrile children. JAMA Pediatr 2018; 172 (06) 550-556
    CrossrefPubMedGoogle Scholar
  • 14 Abraham SN, Miao Y. The nature of immune responses to urinary tract infections. Nat Rev Immunol 2015; 15 (10) 655-663
    CrossrefPubMedGoogle Scholar
  • 15 Spencer JD, Schwaderer AL, Becknell B, Watson J, Hains DS. The innate immune response during urinary tract infection and pyelonephritis. Pediatr Nephrol 2014; 29 (07) 1139-1149
    CrossrefPubMedGoogle Scholar
  • 16 Zasloff M. The antibacterial shield of the human urinary tract. Kidney Int 2013; 83 (04) 548-550
    CrossrefPubMedGoogle Scholar
  • 17 Becknell B, Spencer JD. A review of ribonuclease 7's structure, regulation, and contributions to host defense. Int J Mol Sci 2016; 17 (03) 423
    CrossrefPubMedGoogle Scholar
  • 18 Kjölvmark C, Åkesson P, Påhlman LI. Urine concentrations of human beta-defensins and ribonuclease 7 in urinary tract infection and asymptomatic bacteriuria. Diagn Microbiol Infect Dis 2017; 89 (01) 58-60
    CrossrefPubMedGoogle Scholar
  • 19 Toker A, Ziypak T, Orsal E, Laloglu E, Bedir F, Aksoy Y. Is urinary kidney injury molecule-1 a noninvasive marker for renal scarring in children with vesicoureteral reflux?. Urology 2013; 81 (01) 168-172
    CrossrefPubMedGoogle Scholar
  • 20 Strutz F, Neilson EG. New insights into mechanisms of fibrosis in immune renal injury. Springer Semin Immunopathol 2003; 24 (04) 459-476
    CrossrefPubMedGoogle Scholar
  • 21 Jutley RS, Youngson GG, Eremin O, Ninan GK. Serum cytokine profile in reflux nephropathy. Pediatr Surg Int 2000; 16 (1-2): 64-68
    CrossrefPubMedGoogle Scholar
  • 22 Becknell B, Schwaderer A, Hains DS, Spencer JD. Amplifying renal immunity: the role of antimicrobial peptides in pyelonephritis. Nat Rev Nephrol 2015; 11 (11) 642-655
    CrossrefPubMedGoogle Scholar
  • 23 Sheu JN, Wu KH, Chen SM, Tsai JD, Chao YH, Lue KH. Acute 99mTc DMSA scan predicts dilating vesicoureteral reflux in young children with a first febrile urinary tract infection: a population-based cohort study. Clin Nucl Med 2013; 38 (03) 163-168
    CrossrefPubMedGoogle Scholar
  • 24 Song J, Abraham SN. Innate and adaptive immune responses in the urinary tract. Eur J Clin Invest 2008; 38 (Suppl. 02) 21-28
    CrossrefPubMedGoogle Scholar
  • 25 Rodríguez LM, Robles B, Marugán JM, Suárez A, Santos F. Urinary interleukin-6 is useful in distinguishing between upper and lower urinary tract infections. Pediatr Nephrol 2008; 23 (03) 429-433
    CrossrefPubMedGoogle Scholar
  • 26 Ching CB, Gupta S, Li B. et al. Interleukin-6/Stat3 signaling has an essential role in the host antimicrobial response to urinary tract infection. Kidney Int 2018; 93 (06) 1320-1329
    CrossrefPubMedGoogle Scholar
  • 27 Anders HJ, Banas B, Schlöndorff D. Signaling danger: toll-like receptors and their potential roles in kidney disease. J Am Soc Nephrol 2004; 15 (04) 854-867
    CrossrefPubMedGoogle Scholar
  • 28 Song J, Duncan MJ, Li G. et al. A novel TLR4-mediated signaling pathway leading to IL-6 responses in human bladder epithelial cells. PLoS Pathog 2007; 3 (04) e60
    CrossrefPubMedGoogle Scholar
  • 29 Zhang J, Dyer KD, Rosenberg HF. Human RNase 7: a new cationic ribonuclease of the RNase A superfamily. Nucleic Acids Res 2003; 31 (02) 602-607
    CrossrefPubMedGoogle Scholar
  • 30 Eichler T, Bender K, Murtha MJ. et al. Ribonuclease 7 shields the kidney and bladder from invasive uropathogenic Escherichia coli infection. J Am Soc Nephrol 2019; 30 (08) 1385-1397
    CrossrefPubMedGoogle Scholar
  • 31 Becknell B, Ching C, Spencer JD. The responses of the ribonuclease A superfamily to urinary tract infection. Front Immunol 2019; 10: 2786
    CrossrefPubMedGoogle Scholar
  • 32 Seo WH, Nam SW, Lee EH, Je BK, Yim HE, Choi BM. A rapid plasma neutrophil gelatinase-associated lipocalin assay for diagnosis of acute pyelonephritis in infants with acute febrile urinary tract infections: a preliminary study. Eur J Pediatr 2014; 173 (02) 229-232
    CrossrefPubMedGoogle Scholar
  • 33 Krzemień G, Pańczyk-Tomaszewska M, Adamczuk D, Kotuła I, Demkow U, Szmigielska A. Neutrophil gelatinase-associated lipocalin: a biomarker for early diagnosis of urinary tract infections in infants. Adv Exp Med Biol 2018; 1047: 71-80
    CrossrefPubMedGoogle Scholar
  • 34 Shaikh N, Martin JM, Hoberman A. et al. Biomarkers that differentiate false positive urinalyses from true urinary tract infection. Pediatr Nephrol 2020; 35 (02) 321-329
    CrossrefPubMedGoogle Scholar
  • 35 Forster CS, Loechtenfeldt AM, Shah SS, Goldstein S. Urine neutrophil gelatinase-associated lipocalin in girls with recurrent urinary tract infections. Pediatr Nephrol 2020; 35 (11) 2121-2128
    CrossrefPubMedGoogle Scholar
  • 36 Decavele AS, Dhondt L, De Buyzere ML, Delanghe JR. Increased urinary neutrophil gelatinase associated lipocalin in urinary tract infections and leukocyturia. Clin Chem Lab Med 2011; 49 (06) 999-1003
    CrossrefPubMedGoogle Scholar
  • 37 Kim BH, Yu N, Kim HR. et al. Evaluation of the optimal neutrophil gelatinase-associated lipocalin value as a screening biomarker for urinary tract infections in children. Ann Lab Med 2014; 34 (05) 354-359
    CrossrefPubMedGoogle Scholar
  • 38 Hill EB, Watson JR, Cohen DM, Kline D, Schwaderer AL, Spencer JD. Novel urine biomarkers to distinguish UTI from culture-negative pyuria. Pediatr Nephrol 2022; 37 (02) 385-391
    CrossrefPubMedGoogle Scholar
  • 39 Babikir IH, Abugroun EA, Bilal NE, Alghasham AA, Abdalla EE, Adam I. The impact of cathelicidin, the human antimicrobial peptide LL-37 in urinary tract infections. BMC Infect Dis 2018; 18 (01) 17
    CrossrefPubMedGoogle Scholar
  • 40 Caterino JM, Hains DS, Camargo CA, Quraishi SA, Saxena V, Schwaderer ALA. A prospective, observational pilot study of the use of urinary antimicrobial peptides in diagnosing emergency department patients with positive urine cultures. Acad Emerg Med 2015; 22 (10) 1226-1230
    CrossrefPubMedGoogle Scholar