Evaluation of renal damage biomarkers in an experimental Pyelonephritis model ınduced by uropathogenic Escherichia coli

Abstract

This study aims to determine the levels of biomarkers in rats on different days of the disease by creating a pyelonephritis model using Uropathogenic Escherichia coli (UPEC). Forty rats were used in the study; 10 were designated as the control group and the remaining 30 rats were intrarenally administered UPEC to create a pyelonephritis model. Blood and urine samples were collected on days 1, 4 and 7 of the experiment. Histopathologically, it was determined that pyelonephritis occurred in all experimental groups. In serum samples, significant changes were observed in the groups’ clusterin, L-FABP and clusterin/Cr levels. In urine samples: while no significant changes were detected in Cr, clusterin, NGAL/Cr and clusterin/Cr levels, significant alterations were identified in NGAL, L-FABP, KIM-1, cystatin C, KIM-1/Cr, cystatin C/Cr and L-FABP/Cr levels. In the scope of the study, changes in the identified biomarkers in the serum and urine samples of rats with induced pyelonephritis were particularly evident. In evaluations conducted on different days of the disease, it was observed that urine NGAL, L-FABP, KIM-1 and cystatin C levels increased up to the 4th day compared to the control group. These findings suggest that urine biomarkers, in particular, may play a significant role in diagnosing pyelonephritis.

Downloads

Download data is not yet available.

References

Gupta K, Donnola SB, Sadeghi Z, Lu L, Erokwu BO, Kavran M, Hijaz A, Flask CA. Intrarenal Injection of Escherichia coli in a Rat Model of Pyelonephritis. J. Vis. Exp. [Internet]. 2017; 2017(125):e54649. doi: https://doi.org/ph5v

Ramakrishnan K, Scheid DC. Diagnosis and management of acute pyelonephritis in adults. Am. Fam. Physician. [Internet]. 2005 [cited Feb.26 2025]; 71(5):933-942. Available in: https://goo.su/lcGqP

Piccoli GB, Consiglio V, Deagostini MC, Serra M, BiolcatiM, Ragni F, Biglino A, De Pascale A, Frascisco MF, Veltri A, Porpiglia F. The clinical and imaging presentation of acute “non complicated” pyelonephritis: a new profile for an ancient disease. BMC Nephrol. [Internet]. 2011; 12:68. doi: https://doi.org/dx9nzz

Sobel JD, Kaye D. Urinary Tract Infections. In: BennettJE, Dolin R, Blaser MJ, editors. Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases. 8th ed. Philadelphia: Elsevier Saunders; 2015. p. 886-913.

Whalan EJ. A Toxicologist’s Guide to Clinical Pathology inAnimals: Hematology, Clinical Chemistry; Urinalysis. 1st ed. Switzerland: Springer International Publishing; 2015.

Cooper KL, Badalato GM, Rutman MP. Infections of the rinary Tract. In: Partin AW, Dmochowski RR, Kavoussi LR, Peters CA, editors. Campbell-Walsh-Wein Urology. 12th ed. Philadelphia, PA: Elsevier; 2021. p.1129-1201.

Löfberg H, Grubb AO. Quantitation of gamma-trace in human biological fluids: indications for production in the central nervous system. Scand. J. Clin. Lab. Invest. [Internet]. 1979 ;39(7):619-626. doi: https://doi.org/cqx7rk

Adingwupu OM, Barbosa ER, Palevsky PM, Vassalotti JA, Levey AS, Inker LA. Cystatin C as a GFR Estimation Marker in Acute and Chronic Illness: A Systematic Review. Kidney Med. [Internet]. 2023; 5(12):100727. doi: https://doi.org/ph6t

Munavalli V, Dhumale AJ, Kothiwale V A. Serum Cystatin C concentration levels as a marker of acute Kidney injury in critically ill Patients -A cross sectional study. APIK J. Int. Med. [Internet]. 2016; 4(3):9-14. doi: https://doi.rg/ph6v

Satapathy S, Wilson MR. The Dual Roles of Clusterin in Extracellular and Intracellular Proteostasis. Trends Biochem. Sci. [Internet]. 2021; 46(8):652-660. doi: https://doi.org/gqj3rt

Itakura E, Chiba M, Murata T, Matsuura A. Heparan sulfate is a clearance receptor for aberrant extracellular proteins. J. Cell Biol. [Internet]. 2020; 219(3):e201911126. doi: https://doi.org/ghswdt

Dieterle F, Perentes E, Cordier A, Roth DR, Verdes P, Grenet O, Pantano S, Moulin P, Wahl D, Mahl A, End P, Staedtler F, Legay F, Carl K, Laurie D, Chibout SD, Vonderscher J, Maurer G. Urinary clusterin, cystatin C, beta2-microglobulin and total protein as markers to detect drug-induced kidney injury. Nat. Biotechnol. [Internet]. 2010; 28(5):463-469. doi: https://doi.org/b6p92f

Udupa V, Prakash V. Gentamicin induced acute renal damage and its evaluation using urinary biomarkers in rats. Toxicol. Rep. [Internet]. 2019;6:91-99. doi: https://doi.org/ph6x

Crescenzi E, Leonardi A, Pacifico F. NGAL as a Potential Target in Tumor Microenvironment. Int. J. Mol. Sci. [Internet]. 2021; 22(22):12333. doi: https://doi.org/gpw8wz

Defauw P, Schoeman JP, Leisewitz AL, Goddard A, Duchateau L, Aresu L, Meyer E, Daminet S. Evaluation of acute kidney injury in dogs with complicated or uncomplicated Babesia rossi infection. Ticks Tick Borne Dis. [Internet]. 2020; 11(3):101406. doi: https://doi.org/ph62

Monari E, Troìa R, Magna L, Gruarin M, Grisetti C, Fernandez M, Balboni A, Giunti M, Dondi F. Urine neutrophil gelatinase-associated lipocalin to diagnoseand characterize acute kidney injury in dogs. J. Vet. Intern. Med. [Internet]. 2020; 34(1):176-185. doi: https://doi.org/ph63

Li B, Hao J, Zeng J, Sauter ER. SnapShot: FABP Functions. Cell. [Internet]. 2020; 182(4):1066-1066.e1. doi: https://doi.org/gp8k68

Xu Y, Xie Y, Shao X, Ni Z, Mou S. L-FABP: A novel biomarker of kidney disease. Clin. Chim. Acta. [Internet]. 2015; 445:85-90. doi: https://doi.org/f7c9kd

Yokoyama T, Kamijo-Ikemori A, Sugaya T, Hoshino S, Yasuda T, Kimura K. Urinary excretion of liver type fatty acid binding protein accurately reflects the degree of tubulointerstitial damage. Am. J. Pathol. [Internet]. 2009; 174(6):2096-2106. doi: https://doi.org/bkrntq

Kamijo-Ikemori A, Kimura K. Clinical utility of tubular markers in kidney disease: a narrative review. J. Lab. Precis. Med. [Internet]. 2022;7:27. doi: https://doi.org/ph64

Medic B, Rovcanin B, Basta Jovanovic G, RadojevicŠkodric S, Prostran M. Kidney Injury Molecule-1 and Cardiovascular Diseases: From Basic Science to Clinical Practice. Biomed. Res. Int. [Internet]. 2015; 2015:854070. doi: https://doi.org/f84jnb

Bland SK, Clark ME, Côté O, Bienzle D. A specific immunoassay for detection of feline kidney injury molecule 1. J. Feline Med. Surg. [Internet]. 2019; 21(12):1069-1079. doi: https://doi.org/gfns9x

Jiang Y, Xiong Z, Huang J, Yan F, Yao G, Lai B. Effective E. coli inactivation of core-shell ZnO@ZIF-8 photocatalysis under visible light synergize with peroxymonosulfate: Efficiency and mechanism. Chin. Chem. Lett. [Internet]. 2022; 33(1):415–423. doi: https://doi.org/ph65

Kasap B, Soylu A, Ertoy Baydar D, Kiray M, Tugyan K, Kavukçu S. Protective effects of bilirubin in an experimental rat model of pyelonephritis. Urology. [Internet]. 2012; 80(6):1389.e17-1389.e22. doi: https://doi.org/f2fj5j

Sabetkish N, Sabetkish S, Mohseni MJ, Kajbafzadeh AM. Prevention of Renal Scarring in Acute Pyelonephritis by Probiotic Therapy: an Experimental Study. Probiotics Antimicrob. Proteins. [Internet]. 2019; 11(1):158-164. doi: https://doi.org/ph66

Suckow MA, Danneman P, Brayton C. The Laboratory Mouse. Boca Raton, London, Newyork, Washington DC: CRC Press LLC; 2001. Available in: https://goo.su/Hgcq

Waynforth HB, Flecknell PA. Experimental and Surgical Technique In the Rat. 2nd ed. Amsterdam, Boston, Heidelberg, London, Newyork, Oxford, Paris, San Diego, Sanfrancisco, Singapore, Sydney, Tokyo: Academic Press; 1995. Available in: https://goo.su/vXYDhK8

Culling CFA, Allison RT, Barr WT. Cellular Pathology Technique. 4th ed. London; Boston: Butterworths. 1985.

Poswiatowska-Kaszczyszyn I. Usefulness of serum cystatin C measurement for assessing renal function in cats. Bull Vet. Inst. Pulawy. [Internet]. 2012; 56(2):235–239. doi: https://doi.org/ph67

Miyagawa Y, Takemura N, Hirose H. Evaluation of the measurement of serum cystatin C by an enzyme-linked immunosorbent assay for humans as a marker of the glomerular filtration rate in dogs. J. Vet. Med. Sci. [Internet]. 2009; 71(9):1169-1176. doi: https://doi.org/ft65qf

Yan Y, Liu Y, Guo Y, Li B, Li Y, Wang X. Early diagnostic model of pyonephrosis with calculi based on radiomic features combined with clinical variables. Biomed. Eng. [Internet]. 2024; 23(1):97. doi: https://doi.org/ph69

Zhang L, Li Y, Wang Z, Jiang J, Jin S, Zhu L, Lu Q, Chen J. The relationship between pathogenic bacteria distribution and the expression of serum YKL-40 and IL-8 in patients with acute pyelonephritis. Chin. J. Microecol. [Internet]. 2022; 34(10):1186-1190. doi: https://doi.org/ph7b

Yim HE, Yim H, Bae ES, Woo SU, Yoo KH. Predictive value of urinary and serum biomarkers in young children with febrile urinary tract infections. Pediatr. Nephrol. [Internet]. 2014; 29(11):2181-2189. doi: https://doi.org/f6jg2x

Lezhenko HO, Zakharchenko NA. The role of nitric oxide synthase and cystatin C in the mechanisms of antimicrobial protection in children with urinary tract infections considering the etiological factor. Zaporozhye Med. J. [Internet]. 2022; 24(4):459-463. doi: https://doi.org/ph7c

Islekel H, Soylu A, Altun Z, Yis U, Turkmen M, Kavukcu S. Serum and urine cystatin C levels in children with postpyelonephritic renal scarring: a pilot study. Int. Urol. Nephrol. [Internet]. 2007; 39(4):1241-1250. doi: https://doi.org/bc38t6

Sansanwal P, Li L, Sarwal MM. Inhibition of intracellular clusterin attenuates cell death in nephropathic cystinosis. J. Am. Soc. Nephrol. [Internet]. 2015; 26(3):612-625. doi: https://doi.org/f64bqz

Steblaj B, Kutter APN, Stirn M, Daminet S, Major A, Zini E. Endotoxic kidney injury in Beagle dogs assessed by serum creatinine and symmetric dimethylarginine, and urinary neutrophil gelatinase-associated lipocalin and clusterin. Res. Vet. Sci. [Internet]. 2023;162:104966. doi: https://doi.org/gs3q9x

Zhou X, Ma B, Lin Z, Qu Z, Huo Y, Wang J, Li B. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs. Toxicol. Appl. Pharmacol. [Internet]. 2014; 280(1):30-35. doi: https://doi.org/f6h7z6

Palm CA, Segev G, Cowgill LD, LeRoy BE, Kowalkowski KL, Kanakubo K, Westropp JL. Urinary Neutrophil Gelatinaseassociated Lipocalin as a Marker for Identification of Acute Kidney Injury and Recovery in Dogs with Gentamicininduced Nephrotoxicity. J. Vet. Intern. Med. [Internet]. 2016; 30(1):200-205. doi: https://doi.org/ph7d

Mizutani M, Hasegawa S, Matsushige T, Ohta N, Kittaka S, Hoshide M, Kusuda T, Takahashi K, Ichihara K, Ohga S. Distinctive inflammatory profile between acute focal bacterial nephritis and acute pyelonephritis in children. Cytokine. [Internet]. 2017; 99:24-29. doi: https://doi.org/ph7f

Rafiei A, Abedi Arzefuni F, Mohammadjafari H, Yazdani-Charati J. The Urinary Level of Liver-type Fatty Acid Binding Protein in Children with Febrile UTI. Iran J. Kidney Dis. [Internet]. 2020 [cited Feb.26 2025]; 14(3):191-197. Available in: https://goo.su/P6qzNQ6

Ni AN, Shumatova TA, Sergeeva EV, Prikhodchenko NG, Zernova ES, Bykova OG. Endogenous Proteins in Infants and Toddlers with Urinary Tract Infections. Doctor Ru Magazine. [Internet]. 2021; 20(10):44–47. doi: https://doi.org/ph7g

Sergeeva EV, Nee A, Shumatova TA, Bykova OG, Prikhodchenko NG, Zernova ES. The role of increased intestinal permeability markers in developing urinary tract infection in children of the first three years of life. Russ. J. Infect. Immun. [Internet]. 2022; 12(2):339-346. https://doi.org/ph7h

Krzemien G, Turczyn A, Panczyk-Tomaszewska M, Kotula I, Demkow U, Szmigielska A. Prognostic value of serum and urine kidney injury molecule-1 in infants with urinary tract infection. Cent. Eur. J. Immunol. [Internet]. 2019; 44(3):262-268. doi: https://doi.org/ph7j

Urbschat A, Obermüller N, Paulus P, Reissig M, Hadji P, Hofmann R, Geiger H, Gauer S. Upper and lower urinary tract infections can be detected early but not be discriminated by urinary NGAL in adults. Int. Urol. Nephrol. [Internet]. 2014; 46(12):2243-2249. doi: https://doi.org/f6sgv7

Lee HE, Lee SH, Baek M, Choi H, Park K. Urinary Measurement of Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 Helps Diagnose Acute Pyelonephritis in a Preclinical Model. J. Biomark. [Internet]. 2013; 2013:413853. doi: https://doi.org/gb6935

Rius-Gordillo N, Ferré N, González JD, Ibars Z, Parada-Ricart E, Escribano J, DEXCAR Study Group. Role of dexamethasone in controlling the proinflammatory cytokine cascade in the first episode of paediatric acute pyelonephritis. Acta Paediatr. [Internet]. 2024; 113(3):564-572. doi: https://doi.org/ph7k

Skowron B, Baranowska A, Dobrek L, Ciesielczyk K, Kaszuba-Zwoinska J, Wiecek G, Malska-Wozniak A, Strus M, Gil K. Urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, uromodulin, and cystatin C concentrations in an experimental rat model of ascending acute kidney injury induced by pyelonephritis. J. Physiol. Pharmacol. [Internet]. 2018; 69(4):625-637 doi: https://doi.org/ph7m

Anandkumar DG, Dheerendra PC, Vellakampadi D, Ramanathan G. Kidney injury molecule-1; is it a predictive marker for renal diseases? J. Nephropharmacol. [Internet]. 2023; 12(2):e10572. doi: https://doi.org/ph7n

Published
2025-04-25
How to Cite
1.
Canlar-Akar D, Kiral F. Evaluation of renal damage biomarkers in an experimental Pyelonephritis model ınduced by uropathogenic Escherichia coli. Rev. Cient. FCV-LUZ [Internet]. 2025Apr.25 [cited 2025Jul.29];35(2):7. Available from: https://produccioncientifica.luz.edu.ve/index.php/cientifica/article/view/43812
Section
Veterinary Medicine