Febrile urinary tract infection (UTI) is common in children, especially those under two years old who are immunocompromised hosts or have severe congenital urinary tract anomalies. Febrile UTI is considered as upper UTI or pyelonephritis. However, according to data from acute dimercaptosuccinic acid (DMSA) scans routinely performed in children with febrile UTI regardless of how urine samples were collected before the year of 2011, only less than 30% of them had positive DMSA renal scan results [1].

Children with febrile UTI but with negative DMSA results have pyelitis or lower UTI with other fever focus and manifesting only fever initially. Only pyelonephritis can produce acquired renal scarring, and only recurrent pyelonephritis can lead to chronic renal insufficiency. Therefore, among children with febrile UTI, determining the presence of pyelonephritis is very important. However, positive urine culture results, which is currently the gold standard in the diagnosis of acute pyelonephritis, cannot predict the presence of cortical defects on DMSA scan in children with febrile UTI, although urine sampling was appropriately collected. Furthermore, urine culture results cannot contribute to making treatment decisions during clinical visits. Nevertheless, performing DMSA renal scans in all children with febrile UTI is not acceptable because of its invasiveness.

Due to these reasons, trying to find simple, cheap, prompt, and more accurate diagnostic methods than serum C-reactive protein (CRP), white blood cell (WBC) count, or urine culture for determining the presence of pyelonephritis among children with febrile UTI is challenging to pediatricians.

Authors previously reported that mean hemoglobin (Hgb) level was significantly lowered in children with positive DMSA results than in those with negative DMSA results [2].

In the present study, we investigated whether WBC to Hgb ratio could be helpful for determining the presence of cortical defects on DMSA scan in children with febrile UTI.

Among 124 consecutive children admitted to our hospital with their first episode of febrile UTI from July 2013 to June 2015, 95 children with completed data sheets were included in this study. Twenty-two children who did not undergo a DMSA renal scan at the time of acute infection and seven children with missing data were excluded. Febrile UTI was defined as follows: high fever ≥38℃, abnormal urinalysis (pyuria [>5 WBC counts/high-power field] and positive leukocyte esterase results), positive CRP results (>0.3 mg/dL), and lack of other fever focus. Urine was sampled by collecting a midstream urine specimen in toddlers or in older children and using the clean catch bag method in non-toilet trained children. Significant bacteriuria (BU) was defined as the presence of ≥10⁵ colonyforming units/high-power field of a single-strain isolate. All the enrolled children with febrile UTI underwent a DMSA renal scan upon admission. In addition, blood (C-reactive protein [CRP], white blood cell [WBC] count, hemoglobin [Hgb]) tests were performed at their admission.

DMSA scans were performed using the planar technique with a dual-headed Symbia E gamma camera (Siemens, Erlangen, Germany) equipped with low-energy high-resolution collimator (140 KeV, 20% symmetric window) and were interpreted by two nuclear medicine consultants. A positive DMSA result (indicative of cortical defects) was defined as reduced or absent tracer localization and indistinct margins that did not deform the renal contour.

Written informed consent was obtained from the parents of all febrile UTI children prior to DMSA scans. The CHA University Institutional Review Board approved this study, including the consent procedure (CHA IRB No.2018-06-057).

All data were collected retrospectively and were compared between the children with the positive and negative DMSA results. The correlation was analyzed between WBC to Hgb ratio and the presence of cortical defects on DMSA scan and between WBC to Hgb ratio and CRP.

There are many possible advantages if the exact prediction of cortical defects through acute DMSA scans in children with febrile UTI. First, admission is not necessary in children with pyelitis or lower UTI with other fever foci even if they are less than 12 months old. Second, performing imaging studies according to UTI guidelines is not necessary if UTI is not recurrent. To some extent, the possibility of recurrent febrile UTI or developing acquired renal scars in the future can be individually predicted. Total medical expenses at the national level can be reduced.

There are disadvantages in urine culture results being considered as a gold standard for a diagnosis of pyelonephritis: if all children with positive urine culture results among children with febrile UTI might have cortical defects on acute DMSA scans, which might result in false positive findings of urine culture are high (71%) even though urine sampling is appropriately collected [3]. Most of them include children with pyelitis or lower UTI associated with other fever foci. False negative results (15%) of urine culture are not low even though urine sampling is appropriately collected [4]. The discrimination of children with pyelonephritis from children with lower UTI and other fever foci accompanying asymptomatic bacteriuria is impossible. Urine culture is not helpful when a prompt diagnosis of pyelonephritis is needed at clinics.

Therefore, many clinicians depend on other helpful parameters correlated with pyelonephritis, such as serum CRP, WBC or procalcitonin etc. when pyelonephritis is considered as a diagnosis in children with abnormal urinalysis. Serum WBC level is a known factor helpful for predicting the presence of cortical defects on acute DMSA scans [4,5]. Authors reported that Hgb level was significantly lower in children with positive DMSA results than in those with negative DMSA results [2]. Thus, authors hypothesized that the combination of these two factors could be more helpful for predicting positive DMSA results in children with febrile UTI. If the cut-off value of WBC count would be 14,000/mm3, sensitivity, specificity, positive predictive value, and negative predictive value of WBC count for predicting positive DMSA results would be 80.9% [95% CI (confidence interval), 66.7–90.9%], 56.1% (95% CI, 43.3–68.3%), 56.7% (95% CI, 49.1–64.0%) and 80.4% (95% CI, 68.8–88.5%). If the cut-off value of WBC/Hgb ratio be 1200, sensitivity, specificity, positive predictive value, and negative predictive value of WBC/Hgb ratio for predicting positive DMSA results would be 84.6% [95% CI, 69.5–94.1%], 57.1% (95% CI, 43.2–70.3%), 57.79% (95% CI, 49.7–65.7%) and 84.2% (95% CI, 71.2–92.0%). The sensitivity and negative predictive value of WBC/Hgb ratio is slightly increased compared to that of WBC count alone. Although the predicting power of WBC/Hbg ratio is not comparable to that of serum CRP, it can be used as a complementary tool for evaluation.

The reason why Hgb level decreases in children with positive DMSA results is unknown. However, authors thought that their decreased Hgb level could be due to dilutional effect resulting from the activation of intrarenal renin-angiotensin-aldosterone system in the pathogenesis of acute pyelonephritis [2].

The limitations of this study are as follows: WBC/Hgb ratio is not better compared to other factors by a large margin. Other factors influencing Hgb levels like nutrition, nutritional supplements, socioeconomic status, or previous Hgb levels were not considered. The reason for decreased Hgb level in children with the positive DMSA results is currently unclear. Follow-up of their Hgb levels is needed.

In conclusion, WBC/Hgb ratio may help predict the presence of cortical defects on acute DMSA scans in children with febrile UTI.