Introduction 5 14 17 10 12 Therefore, we carried out a prospective study of routine renal Doppler ultrasound in children presenting with isolated hematuria at our Nephrology Unit. The main aim was to assess the detection rate of nutcracker syndrome by renal Doppler ultrasound as a screening examination. Methods Patients All consecutive 221 children with isolated hematuria (gross and microscopic) who visited our Nephrology Unit between 1 January 2002 and 31 December 2004 were routinely offered a renal Doppler ultrasound to detect cases of nutcracker syndrome in addition to a complete blood cell count, electrolytes, biochemistry, coagulation profile, serology for hepatitis B, antinuclear antibody, anti-streptococcal O titer, complement C3 and C4, urine culture, urinary calcium/creatinine, two-dimensional ultrasonography and excretory urography. Hematuria was defined as the presence of at least five red blood cells (RBCs) in a centrifuged specimen. A urine sample from each parent and sibling was examined for hematuria, and a family history of urolithiasis was considered positive if a sibling, parent, grandparent, or parental sibling had a history of renal-stone disease. We excluded proteinuria by urinalysis in most patients, but also collected 24-h urine collections if proteinuria was suspected by urinalysis in some patients with gross hematuria. We collected 24-h calcium and creatinine if the urinary calcium/creatinine ratio was more than 0.2. Hypercalciuria was defined when 24-h calcium excretion was more than 4 mg/kg. Children with a documented urinary tract infection (n=2), Henoch-Schoenlein purpura (n=1), and systemic lupus erythematosus (n=2) were excluded, because the causes of hematuria were evident in these patients. Therefore, 216 patients were included in this study: 176 showed microscopic hematuria on several examinations (170 through mass urinary screening and 6 through routine urinalysis during admission due to other diseases) and 40 gross hematuria. The hematuria was intermittent in 19 patients and permanent in 197. Blood pressure was normal in all patients. Also, 32 age- and sex-matched normal healthy children with no evidence of renal disease or other chronic diseases were selected for comparison. This study was approved by the institutional review board and the research ethics committee of Yonsei Severance Hospital. Renal Doppler ultrasound Renal Doppler ultrasound was performed at the first visit by one experienced radiologist, not knowing whether the subjects had hematuria or were control subjects. A HDI 5000 sonography system with 5- to 8- and 4- to 6-MHz convex transducers (Philips, Ultrasound, Bothell, Wash.) was used, and the Doppler spectrum could be successfully obtained in most cases, except in one with a retroaortic left renal vein. After the patients had fasted for 6 to 8 h, renal Doppler ultrasound was performed with the patients in the supine position. Peak velocity (PV) was measured in the transverse plane at two points in the LRV, one at the lateral portion of the LRV near the hilum (PV1) and the other where the LRV courses between the aorta and the superior mesenteric artery (aortomesenteric portion, PV2). Doppler spectra of the LRV at the hilum were obtained with the transducer placed on the middle of the upper abdomen. Doppler spectra of the LRV at the aortomesenteric angle were obtained with the transducer placed on the right or left subcostal area for keeping the Doppler angle of the LRV less than 60°. It was relatively easy to obtain the PV at the hilar portion of the LRV with the Doppler angle of less than 60°, but there were some patients in whom the measurements of the PV at or beyond the aortomesenteric portion of the LRV were somewhat difficult with the Doppler angle of 60°. The median Doppler angle was 60° (range 32–66°) at the hilar portion and 60° (range 56–70°) at the aortomesenteric portion of the LRV. Ratios of the PV of the LRV between the two portions (Aortomesenteric PV/Hilar PV, PV2/PV1) were calculated. Statistical analysis Statistical analysis was performed with Student’s t-test and chi-square test, using SPSS for Windows (version 11.0). The mean ±2 SD of PV2/PV1 ratios was calculated for normal controls and was used as the cut-off value for diagnosing nutcracker syndrome. A P value of 0.05 or less was defined as significant. Results 1 Fig. 1 a b c d a b c d  1 2 1 2 2 Table 1 Renal Doppler findings and anthropometric parameters (median values and ranges)   Gross hematuria (n=40) Microhematuria (n=176) Total hematuria (n=216) Control (n=32) P-value Doppler findings  PV at AM portion (PV2, cm/s) 72.2 (23.9–207) 76.2 (30.1–288) 75.4 (23.9–288) 60.2 (20–133.7) 0.003  PV at hilar portion (PV1, cm/s) 22.6 (11.5–40.7) 24.1 (7.3–38.4) 23.8 (7.3–40.7) 23.9 (10.7–36.8) NS  PV2/PV1 ratio 3.06 (1.18–10.34) 3.19 (1.2–16.44) 3.14 (1.18–16.44) 2.56 (1.21–3.87) 0.003  PV ratio >4.1* 9 (22.5%) 63 (35.8%) 72 (33%) 0 (0%) <0.0001 Anthropometric findings  Height (cm) 132 (72–183) 134 (88–171) 133 (72–183) 133 (109–164) NS  Weight (kg) 31.5 (13.5–71) 30 (12–74) 30 (12–74) 30 (18–56) NS 2 1.09 (0.53–1.78) 1.06 (0.54–1.86) 1.06 (0.53–1.86) 1.05 (0.74–1.6) NS 2 17.24 (12.98–27.23) 16.88 (13.13–25.97) 17.05 (12.98–27.73) 17.09 (15.15–20.82) NS *Data are number (%) PV= peak velocity, AM= aortomesenteric, BSA= body surface area, BMI= body mass index, and NS= not significant (P>0.05) There were no differences between gross and microscopic hematuria Fig. 2 The peak velocity ratios of the left renal vein in children with gross (GH) or microscopic hematuria (MH) and normal controls  Table 2 Renal Doppler findings and anthropometric parameters in 216 children with and without nutcracker syndrome   Nutcracker group (PV ratio >4.1: n=72) Non-nutcracker group (PV ratio <4.1: n=144) P-value Doppler findings  PV at AM portion, PV2 (cm/s) 129 (69.8–288)* 63.9 (23.9–113) <0.0001  PV at hilar portion, PV1 (cm/s) 20.1 (7.3–30.1) 26.3 (14.2–40.7) <0.0001  PV2/PV1 ratio 6.46 (4.1–16.44) 2.45 (1.18–4.0) <0.0001 Anthropometric findings  Height (cm) 137 (72–183) 132 (90–171) 0.031  Weight (kg) 32 (12–67) 30 (13–74) NS 2 1.1 (0.53–1.78) 1.05 (0.58–1.86) NS 2 16.12 (13.42–27.01) 17.24 (12.98–27.73) 0.006 *Median and ranges PV= peak velocity, AM= aortomesenteric, BSA= body surface area, BMI= body mass index, and NS= not significant (P>0.05) 3 Table 3 Clinical characteristics and diagnoses of 216 children with hematuria with and without nutcracker syndrome   PV ratios of the LRV Nutcracker group (PV ratio >4.1: n=72) Non-nutcracker group (PV ratio <4.1: n=144) Clinical characteristics*  Age (years) 9 (2–16) 9 (3–15)  Sex (M/F) 37:35 76:68  Gross hematuria** 9 31  Abdominal or flank pain 11 17  Familial history of urolithiasis 4 10 Clinical diagnoses†    IgA nephropathy 1 (1) 1 (1)  Thin GBM disease  5 (5)  Hereditary nephritis with deafness  2  Proliferative glomerulonephritis  1 (1)  Postinfectious glomerulonephritis  4  Familial hematuria 3 20  Cystitis  3  Trauma  1  Hypercalciuria 8 18  Hematuria unexplained 60 (3)‡ 89 (5)‡ *There were no differences between the two groups (**P=0.107) †Numbers in parenthesis indicate the number of diagnoses confirmed by renal biopsy ‡Results of renal biopsies were normal 4 Table 4 Diagnostic studies Diagnostic study Normal result (no. of patients) Abnormal result (no. of patients) Positive rate (%) Complete blood count 216 0 0 Electrolytes and biochemistry 216 0 0 Coagulation profile 216 0 0 C3 212 4 1.9 C4 214 2 0.9 Anti-streptococcal O titer 179 37 17 Antinuclear antibody 203 13 6 Hepatitis B surface antigen 215 1 0.5 Urine culture 216 0 0 Urinary calcium/creatinine 190 26 12 Renal/bladder ultrasonography 205 11 5 Excretory urography 209 7 3 Renal Doppler ultrasound 144 72 33 Discussion 14 In the present study, we could not identify the cause of hematuria in 149 (69%) of the 216 patients when renal Doppler ultrasound was not performed, but 40 percent was found to have nutcracker syndrome by renal Doppler ultrasound. Thus, nutcracker syndrome was the most common cause of isolated hematuria in children without urinary tract infection or proteinuria in our study, and we speculate that childhood nutcracker syndrome might have been underestimated in the past. 6 8 1 5 4 9 12 9 10 10 10 12 10 3 3 18 15 10 10 12 12 10 10 7 2 13 16 5 10