Diagnostic value of biomarkers for paediatric urinary tract infections in primary care: systematic review and meta-analysis

Abstract

Background Accurate diagnosis of urinary tract infection is essential as children left untreated may suffer permanent renal injury. Aim To compare the diagnostic values of biomarkers or clinical prediction rules for urinary tract infections in children presenting to ambulatory care. Design and setting Systematic review and meta-analysis of ambulatory care studies. Methods Medline, Embase, WOS, CINAHL, Cochrane library, HTA and DARE were searched until 21 May 2021. We included diagnostic studies on urine or blood biomarkers for cystitis or pyelonephritis in children below 18 years of age. We calculated sensitivity, specificity and likelihood ratios. Data were pooled using a bivariate random effects model and a Hierarchical Summary Receiver Operating Characteristic analysis. Results Seventy-five moderate to high quality studies were included in this review and 54 articles in the meta-analyses. The area under the receiver-operating-characteristics curve to diagnose cystitis was 0.75 (95%CI 0.62 to 0.83, n = 9) for C-reactive protein, 0.71 (95% CI 0.62 to 0.80, n = 4) for procalcitonin, 0.93 (95% CI 0.91 to 0.96, n = 22) for the dipstick test (nitrite or leukocyte esterase ≥trace), 0.94 (95% CI 0.58 to 0.98, n = 9) for urine white blood cells and 0.98 (95% CI 0.92 to 0.99, n = 12) for Gram-stained bacteria. For pyelonephritis, C-reactive protein < 20 mg/l had LR- of 0.10 (95%CI 0.04–0.30) to 0.22 (95%CI 0.09–0.54) in children with signs suggestive of urinary tract infection. Conclusions Clinical prediction rules including the dipstick test biomarkers can support family physicians while awaiting urine culture results. CRP and PCT have low accuracy for cystitis, but might be useful for pyelonephritis.

Accuracy of the IDEXX SediVue Dx analyzer for quantifying RBC and WBC indices in the urine sediments of cats and dogs compared with manual microscopic evaluations

“…21,22 However, in veterinary medicine, this cutoff has no established predictive value for identifying different disease states, such as urinary tract infection, nor does it account for the method of collection (eg, RBC contamination when cystocentesis is performed), urine concentration, or methodology of urine sediment preparation as has been evaluated in human medicine. 23 Though not within the scope of this study (as To the authors' knowledge, there are currently no studies that establish acceptable limits of agreement for bias between two methods of urine sediment preparation and examination in veterinary medicine. The survey of internists and clinical pathologists that was prepared and used in this study was intended as an informal representation of clinically-tolerable bias (limits of agreement).…”

“…While clinically relevant differences are not well defined for urine sediments, a standard of >5 RBC/HPF and >5 WBC/HPF is clinically accepted to define hematuria and pyuria, respectively 21,22 . However, in veterinary medicine, this cutoff has no established predictive value for identifying different disease states, such as urinary tract infection, nor does it account for the method of collection (eg, RBC contamination when cystocentesis is performed), urine concentration, or methodology of urine sediment preparation as has been evaluated in human medicine 23 . Though not within the scope of this study (as patient clinical information was not coupled with the urine sediment analysis), investigation of potential predictive values of different urine cell counts for various disease states may be a focus for future studies as the profession moves toward standardized benchtop analytical capabilities.…”

What is the Diagnostic Accuracy of Novel Urine Biomarkers for Urinary Tract Infection?

“…We excluded studies of leucocyte esterase and nitrites, as they have been thoroughly studied, have modest test accuracy, 1 , 13 , 14 and are insufficient for making a final diagnosis in clinical practice. 14 , 15 , 20 …”

“…We excluded studies of leucocyte esterase and nitrites, as they have been thoroughly studied, have modest test accuracy, 1,13,14 and are insufficient for making a final diagnosis in clinical practice. 14,15,20 Reference standard: We included studies with microscopy and/or culture as a reference standard and we did not specify a threshold for infection after culture as our aim was to offer a wide perspective on the available evidence for novel biomarkers. There is not one agreed threshold level of bacteria for diagnosing all UTIs 21,22 and microscopy only can be useful for ruling out bacteriuria.…”

Asymptomatic Bacteriuria or Urinary Tract Infection? New and Old Biomarkers

“…Such peculiarities provide prognostic information in patients with infections, suggesting the management of bacterial infection, especially in septic disease [7]. On the other hand, two recent meta-analyses in children disputed this promising ability in UTI diagnosis, showing little accuracy for cystitis (AUC around 0.71 in ROC curve) [8,9], and limited evidence supports its utility in pyelonephritis diagnosis [10]. Consequently, PCT could not be recommended in clinical practice as a predictive marker of cystitis or pyelonephritis in children.…”