DIAGNOSTIC VALUE OF URINARY BIOMARKERS IN CHRONIC KIDNEY DISEASES AT CHILDREN
Abstract
Chronic kidney disease(CKD) typically develops as a consequence of gradually advancing kidney ailments, and it rarely sees complete reversibility. The aim of the study is to evaluate the value of urinary biomarkers in children with progression of chronic kidney disease. The is a retrospective-prospective study in which includes 95 pediatric patients with clinical signs, symptoms, laboratory analyses, and imaging studies for CKD. The patients are aged 0 to 14 years who came to the University Clinic for Children's Diseases-Skopje at the nephrology department and the subspecialist nephrology outpatient clinic, in period from January 2019 to June 2022. The study group is divided into three groups, study group 1, which includes 41/95 pediatric patients(43.16%)with congenital anomalies of the kidneys and urinary tract, study group 2, which includes 34/95 pediatric patients(35.79%)with tubulopathies and metabolic disorders with renal affection and study group three which includes20/95(21.05%)pediatric patients with other nephrological-urological diseases. In our study, CKD is more prevalent in males 64 (67.37%) while 31 (32.63%) are females, according to age, patients aged 5-14 years (57.3 %). The average values of urine NGAL(ng/ml), β2-Microglobulin and albuminirua showed that there is a significant difference in relation to this parameter in three groups of pediatric patients at the first examination (p<0.05). As the landscape of CKD continues to reveal novel insights into its intricate mechanisms, urine biomarkers will continue to assume a pivotal role in furthering our comprehension of the disease and shaping the trajectory of personalized medicine for CKD children.
Keywords: chronic kidney disease (CKD), urine biomarkers, NGAL (Neutrophil Gelatinase Associated Lipocalin.
References
2. Baum M: Overview of chronic kidney disease in children. Curr Opin Pediatr 2010;22:158-160.
3. Wong CJ, et al: CKiD (CKD in children) prospective cohort study: a review of current findings. Am J Kidney Dis 2012;60:1002-1011.
4. Chan JC, Williams DM, Roth KS. Kidney failure in infants and children. Pediatr Rev. 2002;23(2):47-60. doi:10.1542/pir.23-2-47.
5. Schwartz G.J.Muñoz A.Schneider M.F.et al.New equations to estimate GFR in children with CKD.J Am Soc Nephrol. 2009; 20: 629-637.
6. Schwartz GJ, Furth SL. Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatr Nephrol 2007; 22: 1839-48.
7. Coresh J, Laterza OF, Price CP, Scott MG. Cystatin C: An improved estimator of glomerular filtration rate? Clin Chem. 2002;48:699–707.
8. Kidney Disease: Improving Global Outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3: 1–150.
9. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Suppl 2012; 2: 139–274
10. Harambat J, et al: Epidemiology of chronic kidney disease in children. Pediatr Nephrol 2012;27:363-373.
11. Esbjörner E, Berg U, Hansson S. Epidemiology of chronic renal failure in children: a report from Sweden 1986–1994. Swedish Pediatric Nephrology Association. Pediatr Nephrol 1997; 11: 438.
12. Atkinson MA, Martz K, Warady BA, et al. Risk for anemia in pediatric chronic kidney disease patients: a report of NAPRTCS. Pediatr Nephrol 2010; 25: 1699-706.
13. Seikaly MG, Waber P, Warady BA, et al. The effect of rhGH on height velocity and BMI in children with CKD: a report of the NAPRTCS registry. Pediatr Nephrol 2009; 24: 1711-7.
14. Seikaly MG, Salhab N, Warady BA, et al. Use of rhGH in children with chronic kidney disease: lessons from NAPRTCS. Pediatr Nephrol 2007; 22: 1195-204.
15. Furth SL, Cole SR, Moxey-Mims M, et al. Design and methods of the Chronic Kidney Disease in Children (CKiD) prospective cohort study. Clin J Am Soc Nephrol 2006; 1:1006-15.
16. Tasic, V.; Janchevska, A.; Emini, N.; Sahpazova, E.; Gucev, Z.; Polenakovic, M. Chronic kidney disease—Pediatric risk factors. Prilozi 2016, 37, 9–13. [Google Scholar] [CrossRef][Green Version]
17. Warady BA, Bakkaloglu S, Newland J, et al. Consensus guidelines for the prevention and treatment of catheter-related infections and peritonitis in pediatric patients receiving peritoneal dialysis: 2012 update. Perit Dial Int 2012; 32(Suppl 2): S32-86.
18. Siddique K, Leonard D, Borders L, et al. Validation of the CKiD formulae to estimate GFR in children post renal transplant. Pediatr Nephrol 2014; 29: 445-51.
19. Schwartz GJ, Haycock GB, Edelmann CM, et al. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976; 58: 259-63.
20. Schaefer B, Wuhl E. Educational paper: Progression in chronic kidney disease and prevention strategies. Eur J Pediatr 2012; 171: 1579-88.
21. Wong CS, Pierce CB, Cole SR, et al. Association of proteinuria with race, cause of chronic kidney disease, and glomerular filtration rate in the chronic kidney disease in children study. Clin J Am Soc Nephrol 2009; 4: 812-9.
22. Hattori S, Yosioka K, Honda M et al. The 1998 report of the Japanese National Registry data on pediatric end-stage renal disease patients. Pediatr Nephrol 2002; 17: 456–461.
23. Traynor J, Mactier R, Geddes CC, Fox JG. How to measure renal function in clinical practice. BMJ. 2006;333:733–737. [PMC free article] [PubMed] [Google Scholar].
24. Levey AS. Measurement of renal function in chronic renal disease. Kidney Int. 1990;38:167–184. [PubMed] [Google Scholar].
25. Coresh J, Heerspink HJL, Sang Y, et al. Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level Consortium meta-analysis of observational studies. Lancet Diabetes Endocrinol 2019;7:115–27
26. Bolignano D, Lacquaniti A, Coppolino G, Donato V, Campo S, Fazio MR, Nicocia G, Buemi M. Neutrophil gelatinase-associated lipocalin (NGAL) and progression of chronic kidney disease. Clin J Am Soc Nephrol. 2009;4:337–344. [PMC free article] [PubMed] [Google Scholar].
27. Jeloka T, Mathur G, Kaur R, Kohli R, Singh NP and Rizvi SN. (2010): β2 Microglobulin in chronic renal failure and effect of different dialyzer membrane on its clearance. Indian J Nephrol., 11:160-4.
28. Francesca Becherucci, Rosa Maria Roperto, Marco Materassi, and Paola Romagnani.Chronic kidney disease in children.Clin Kidney J. 2016 Aug; 9(4): 583–591.
29. Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007;298(17):2038–2047. doi: 10.1001/jama.298.17.2038 [PubMed] [CrossRef] [Google Scholar].
30. Hsu CY, Vittinghoff E, Lin F, Shlipak MG. The incidence of end-stage renal disease is increasing faster than the prevalence of chronic renal insufficiency. Ann Intern Med. 2004;141(2):95–101. doi: 10.7326/0003-4819-141-2-200407200-00007 [PubMed] [CrossRef] [Google Scholar].
31. Plantinga LC, Boulware LE, Coresh J, et al. Patient awareness of chronic kidney disease: trends and predictors. Arch Intern Med. 2008;168(20): 2268–2275. doi: 10.1001/archinte.168.20.2268 [PMC free article] [PubMed] [CrossRef] [Google Scholar].
32. Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382(9888):260–272. doi: 10.1016/S0140-6736(13)60687-X [PubMed] [CrossRef] [Google Scholar].
33. Vaidya VS, Niewczas MA, Ficociello LH, Johnson AC, Collings FB, Warram JH, Krolewski AS, Bonventre JV. Regression of microalbuminuria in type 1 diabetes is associated with lower levels of urinary tubular injury biomarkers, kidney injury molecule-1, and N-acetyl-β-D-glucosaminidase. Kidney Int. 2011;79:464–470. [PMC free article] [PubMed] [Google Scholar].
34. Krolewski AS, Niewczas MA, Skupien J, Gohda T, Smiles A, Eckfeldt JH, Doria A, Warram JH. Early progressive renal decline precedes the onset of microalbuminuria and its progression to macroalbuminuria. Diabetes Care. 2014;37:226–234. [PMC free article] [PubMed] [Google Scholar].
35. Goetz DH, Holmes MA, Borregaard N, Bluhm ME, Raymond KN, Strong RK. The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. Mol Cell. 2002;10:1033–1043. [PubMed] [Google Scholar].
36. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P. Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol. 2003;14:2534–2543. [PubMed] [Google Scholar].
37. Viau A, El Karoui K, Laouari D, Burtin M, Nguyen C, Mori K, Pillebout E, Berger T, Mak TW, Knebelmann B, et al. Lipocalin 2 is essential for chronic kidney disease progression in mice and humans. J Clin Invest. 2010;120:4065–4076. [PMC free article] [PubMed] [Google Scholar].
38. Shen SJ, Hu ZX, Li QH, Wang SM, Song CJ, Wu DD, He JL, Guan JC, Shan JP. Implications of the changes in serum neutrophil gelatinase-associated lipocalin and cystatin C in patients with chronic kidney disease. Nephrology (Carlton) 2014;19:129–135. [PubMed] [Google Scholar].
39. Ding H, He Y, Li K, Yang J, Li X, Lu R, Gao W. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for renal tubulointerstitial injury in IgA nephropathy. Clin Immunol. 2007;123:227–234. [PubMed] [Google Scholar].
40. Argyropoulos CP, Chen SS, Ng YH, et al. Rediscovering beta-2 microglobulin as a biomarker across the spectrum of kidney diseases. Front Med. 2017;4. doi: 10.3389/fmed.2017.00073 [PMC free article] [PubMed] [CrossRef] [Google Scholar].