Na osnovi kliničke slike nije moguće procijeniti mjesto, intenzitet i tijek infekcije mokraćnog sustava u dječjoj dobi. Cilj istraživanja je odrediti mogu li vrijednosti serumskih parametara upale (sedimentacija, prokalcitonin, C-reaktivni protein, fibrinogen, leukociti u perifernoj krvi, interleukin-6) doprinijeti u procjeni lokalizacije, intenziteta i tijeka infekcije mokraćnog sustava te nastanka ožiljčenja bubrežnog parenhima, kao i procjeni postojanja vezikoureteralnog refluksa. Cilj je odrediti senzitivnost i specifičnost ispitivanih serumskih biomarkera. U istraživanje je uključeno 80 djece oboljele od infekcije mokraćnog sustava oba spola, do sedme godine života. Učinjene su: kemijska pretraga urina, mikrobiološka pretraga urina te su određene vrijednosti serumskih parametara upale u perifernoj krvi, ultrazvučna pretraga urotrakta, mikcijska cistouretrografija i statička scintigrafija bubrega. Od svih ispitanika 70,0% je imalo uredan scintigrafski nalaz. Kod 26,3% ispitanika nađena je blaga lezija bubrežnoga tkiva, dok kod 3,8% umjereno teška lezija. Svi ispitivani biomarkeri bili su statistički značajni za predikciju akutnog pijelonefritisa. Statistikom određena pripadnost skupini, kao i osjetljivost i specifičnost, pokazala je prokalcitonin kao najznačajniji biomarker za akutni pijelonefritis. Kod 58,33% ispitanika s pozitivnim scintigrafskim nalazom, ponovljena statička scintigrafija bubrega pokazala je ožiljčenje nakon šest mjeseci. Ovi ispitanici imali su statistički značajno više vrijednosti C-reaktivnog proteina i fibrinogena te prokalcitonina tijekom infekcije mokraćnog sustava. Kod 36,25% ispitanika nađen je vezikoureteralni refluks različitoga stupnja. Sedimentacija iznad 59 mm/h povećava mogućnost za pripadnost skupini s refluksom za 4,48 puta. Za razlikovanje stupnjeva refluksa statistički su značajne leukocitoza i visoke vrijednosti prokalcitonina. Procjenom vrijednosti serumskih parametara upale može se izbjeći izlaganje djece invazivnim i neugodnim radiološkim pretragama.
|Abstract (english)|| |
Introduction: Acute pyelonephritis is an inflammation of the kidneys and the renal parenchyma channel system. Unrecognized and inadequately treated in childhood, it can cause renal scarring, permanent damage to the renal parenchyma and permanent damage to kidney function. Renal scarring leads to the occurrence of late complications such as hypertension, preeclampsia, and chronic renal disease. Based on the clinical picture, it is not always possible to estimate a clear position, intensity and course of urinary tract infection and the possible risk of renal scarring. Therefore, it is important to distinguish between acute pyelonephritis from lower urinary tract infection. This difference affects the selection of the type of treatment and the decision to further nephrology treatment and monitoring of patients. Objective: The objective of this study was to determine whether the value of some serum parameters of inflammation (sedimentation rate, procalcitonin, C-reactive protein, fibrinogen, the number of leukocytes in peripheral blood, interleukin -6) can contribute to the assessment of the localization (acute pyelonephritis or infection of the lower urinary tract), intensity and course of urinary tract infections among children. In addition, the aim of the research was to examine whether the value of the tested serum parameters of inflammation contribute to the assessment of occurrence of renal scarring of the renal parenchyma, as well as whether the value of these biomarkers contributes to the assessment of the vesicoureteral reflux (VUR). Besides that, the aim was to determine the sensitivity and specificity of test serum biomarkers of inflammation. Such an assessment would help the clinician in deciding on appropriate therapy implementation, conducting further nephrology processing which includes scintigraphy and invasive radiological examination, such as voiding cystouretherography (VCUG). Assessing the value of some serum parameters of inflammation, the clinician would avoid unnecessary and potentially harmful exposure of children to invasive radiological examinations. Only clearly defined target groups of children would be the only to further undergo radiological processing. Patients and methods: The prospective study included 80 children with urinary tract infections of both genders, aged one month to seven years, with a body temperature of more than 38ºC, leukocyturia (more than 10 white blood cells per field of view) and the finding of a positive urine culture (≥105 cfu / ml urine sample taken with sterile urine collector or catheter). In each patient besides routine laboratory tests, chemical urine tests and
microbiological urine analysis were performed and values of test serum parameters of inflammation in the peripheral blood were determined. In 15 cases IL-6 was determined in the serum. Ultrasound urinary tract research was performed with all patients, and potential damage to the renal tissues was examined by scintigraphy with 99mTc-dimercaptosuccinic acid scan in the first week of illness. On the fourth and tenth day of treatment, laboratory blood control, urine tests and microbiological urine testing were performed with all patients. Patients showing moderate and severe renal scintigraphic lesions were examined using the same treatment six months after they had recovered from the disease. Throughout the following month, after a urinary tract infection, all examinees underwent voiding cystouretherography. The data obtained during the test were statistically analyzed. The analysis used statistical support for IBM SPSS Statistics, version 21.0. Data are presented in tables and graphs. Differences between quantitative values were obtained by Kruskal - Wallis test. Differences in categorical variables were analyzed by Χ² - test. The analysis of the sensitivity curve determined the limit of certain biochemical markers in the prediction of acute pyelonephritis, renal scarring, sonographic findings of hydronephrosis and VUR. Significant limits were used in the binary regression model predicting individual disorders to determine the importance of each biochemical marker. All P values less than 0.05 were considered statistically significant. Results: From a total of 80 subjects, over two-thirds consisted of girls. All 80 patients had a fever higher than 38 ° C, leukocyturia and positive urine culture finding. With regards to scintigraphy, the patients were divided into those with an infection of the lower urinary tract and those with AP. Of all patients, 70.0% had normal 99mTc-DMSA scintigraphy. In 26.3% of the patients, mild lesions of the renal tissue were found, while in 3.8% moderately severe lesions were found. Subjects with AP were significantly older, had significantly higher values of ESR, CRP, PCT, fibrinogen and leukocytes in serum (p <0.05). All tested serum biomarkers were statistically significant in predicting acute pyelonephritis (p <0.05), except for IL-6. Given the statistics of affiliation to the group, as well as sensitivity and specificity, the most important serum biomarker for acute pyelonephritis was PCT. In 14 patients (58.33%) out of 24 with a positive scintigraphy, repeated static scintigraphy showed renal scarring after six months of illness. These patients had significantly higher values of CRP and fibrinogen and PCT during a urinary tract infection, p <0.05. All patients underwent ultrasound examination of the urinary system, and in 41 patients (51.25%) ultrasound showed the expansion of canal systems (hydronephrosis) of varying degrees. Ultrasound changes in terms of hydronephrosis stastically were significantly more
frequent among boys in our group of patients, (p <0.05). From a total of 80 patients suffering from urinary tract infection, in 36.25% of the patients vesicoureteral reflux of varying degrees was found. ESR is a statistically significant predictor of being member of the VUR. ESR above 59 mm / h increases the possibility of belonging to a group with VUR by 4.48 times, p <0.05. Patients with higher VUR (third and fourth degree) had significantly higher values of leukocytes and serum PCT as compared to patients with lower VUR degree (first and second degree), p <0.05. In comparing the group of patients with acute pyelonephritis and lower urinary tract infection statistically significant differences were not found between the two groups with regard to the existence of VUR, p> 0.05. IL-6 in our study did not show statistically significant prognostic value in any examined trait. The most common isolated cause of urinary tract infections was E. coli, isolated in 92.5% of patients. Conclusions: Our study showed that all the examined serum parameters of inflammation, except IL-6, are statistically significant confirmation of acute pyelonephritis in children, and the PCT proved to be the most important among them. In renal scarring, our results highlight CRP as the most important predictive factor for renal scarring, while statistically significant proved to be fibrinogen and PCT. The serum biomarker of inflammation which demonstrated statistically significant predictive value in the existence of all degrees of VUR in children with urinary tract infection was ESR. To distinguish the degrees of VUR (first and second in relation to the third and fourth) elevated leukocyte levels and the high value of the PCT showed as being statistically significant biomarkers. Therefore, patients with urinary tract infections and high value of ESR, PCT and white blood cells in serum, need additional patient treatment with VCUG.