Pediatr Nephrol (2008) 23:99–105 DOI 10.1007/s00467-007-0637-5
ORIGINAL ARTICLE
Renal length discrepancy by ultrasound is a reliable predictor of an abnormal DMSA scan in children Mahmood R. Khazaei & Fiona Mackie & Andrew R. Rosenberg & Gad Kainer
Received: 6 June 2007 / Revised: 16 August 2007 / Accepted: 20 August 2007 / Published online: 26 October 2007 # IPNA 2007
Abstract A renal length discrepancy (RLD) of more than 10 mm by ultrasound (US) is accepted as a potential indicator of an underlying renal pathology; however, there are few supporting data for this in children. Our objective was to determine a cutoff at which RLD on US is a reliable predictor of dimercaptosuccinate acid (DMSA) scan abnormality. We present data from 90 patients who had both renal US and a DMSA scan, as well as DMSA scan results compared with bipolar RLD by US. Positive (PPV) and negative (NPV) predictive values were calculated for renal RLD from 6 to >10 mm. The left kidney was longer in 56%, whereas the right kidney was longer in 37%; their lengths were equal in 8%. For children at all ages, a left kidney longer than the right by ≥10 mm or a right kidney longer than the left by ≥7 mm gave a PPV for DMSA abnormality of 79% and 100%, respectively. In children older than 4 years, if the right kidney was longer by ≥7 mm or if the left kidney was longer by ≥10 mm, the PPVs for DMSA abnormality were 100% and 63%, respectively. In children younger than 4 years, when the right kidney was longer by ≥6 mm or the left was kidney longer by ≥10 mm, the PPV were 86% and
M. R. Khazaei Pediatrics, Mashad Azad University, 22 Bahman Hospital, Pediatrics, Mashad, Iran F. Mackie : A. R. Rosenberg : G. Kainer (*) Department of Nephrology, 4th Floor Emergency Wing, Sydney Children’s Hospital, High Street, Randwick, NSW 2031, Australia e-mail:
[email protected] F. Mackie : A. R. Rosenberg University of New South Wales, Sydney, NSW, Australia
100%, respectively. Thus, children with a right kidney longer than the left by even <10 mm is a reliable predictor of an abnormal DMSA scan. Keywords Kidney size . Renal length . Ultrasonography DMSA . Child . Length discrepancy . Prediction
Introduction Renal tract imaging by ultrasonography (US) is an integral component in the evaluation of children with kidney disease. The safety and noninvasive nature of US make it the imaging modality of first choice in congenital and acquired renal diseases. Renal tract evaluation with US should include assessment of the length and shape of the kidneys, the thickness and echogenicity of the cortex and the presence of corticomedullary differentiation. The appearance of the renal pelves, ureters and bladder should be reported. Measurement of renal size should be compared with data from published charts [1–3]. In general, normal renal size and echotexture is suggestive of a normal kidney. Renal length has been shown to correlate well with renal volume [4] and glomerular filtration rate (GFR) [5]. Similarly, maximum parenchymal surface area has also been shown to correlate with functioning renal mass by radionuclide scintigraphy [6]. Unfortunately, these methods are too complex for routine clinical use. In clinical practice, ultrasound determination of maximum bipolar renal length is generally used as a measure of kidney size and growth. A difference of more than 10 mm in the length between the kidneys is found in less than 6% of children [7]. However, “acceptable” renal length differences may be smaller in the younger child. There are no published data
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that correlate renal length discrepancy (RLD) with objective evidence of renal function or dysfunction to confirm the utility of a 10-mm RLD cutoff in children. Available data in children of different ages, height and sex that compare renal length by US with functioning renal mass do not assist in answering the clinical question as to what constitutes a “significant” RLD. Uptake of radionuclidelabelled dimercaptosuccinate acid (Tc99m-DMSA) is a reliable, noninvasive method for assessing differential renal function and is currently the most sensitive way of detecting renal scars [8]. The aims of this study were to (1) determine whether in children an RLD of 10 mm or more by US correlates with an abnormal DMSA scan and (2) determine whether there is an RLD cutoff by US that is a reliable predictor for DMSA scan abnormality, and if so, what that cutoff is at different ages. Additionally, we wondered whether the significance of RLD varies depending on whether the right or left kidney is smaller.
Methods In this retrospective study, we evaluated the results from 167 children at Sydney Children’s Hospital who had both renal US and DMSA scan from January 2000 to June 2003. For each child, the US report in closest chronological proximity to the DMSA scan was chosen, with a mean interval between tests (± SD) 69 (55.5) days. The US report was used to extract data on maximum longitudinal renal length, pelvicalyceal system dilatation and existence of cysts, masses or abscesses for each kidney. From the nuclear medicine department report of the DMSA scan, differential renal function, existence or absence of kidney scars and the reasons for referral were obtained. All DMSA scans were performed at least 3 months following urinary tract infection (UTI) [8]. Patients’ gender, age, weight and height at time of US and also their principal diagnoses were extracted from their hospital medical files. Body surface area (BSA) was calculated using the formula BSA ¼ p ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi ffi HtðcmÞ WtðkgÞ=3600. Exclusion and inclusion criteria Patients were excluded if they had a solitary or horseshoe kidney; renal cyst ≥10 mm, mass or abscess; or when pelvicalyceal dilation (maximal anteroposterior midpelvic diameter) was ≥10 mm or defined by terms in the radiologist’s report describing pelvicalyceal dilatation as marked, severe, significant or prominent dilatation. From the initial 167 children, 26 patients were excluded because the interval between DMSA scanning and US was more than 6 months. A further 51 patients were excluded due to:
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severe hydronephrosis (15), single kidney (seven), kidney transplantation (five), cyst or abscess (four), horseshoe kidney (one) and incomplete data (19). A total of 90 patients met the inclusion criteria: 51 girls and 39 boys, age range 1 week to 212 months. Body weight ranged from 3.0 to 74.25 kg, height from 48 to 177 cm and BSA from 0.2 to 1.84 m2. In 62 (69%) patients, a history of UTI was the main reason for the DMSA scan. Other reasons for referral were antenatal hydronephrosis in eight (9%), hypertension in five (6%), ureteral reflux in four (5%), renal infarction and renal vein thrombosis in four (5%), renal failure in three (3%), haemoglobinuria and/or proteinuria in two (2%), urinary tract anomaly in one (1%) and kidney hypoplasia in one (1%). No patient was referred to DMSA scanning primarily because of RLD, but it was noted on the request form in eight patients. Patient categorisation In order to determine whether a RLD of ≥10 mm was predictive of DMSA abnormality in children, the 90 patients were divided into various groups either according to RLD (G1a,b) or by age (G2a,b), or by the larger kidney (see Fig. 1). We evaluated results for those with ≥10 mm RLD (G1a) and those with <10 mm RLD (G1b) . Based on age, younger (G2a) or older (G2b) than 48 months, we determined the optimal predictive cutoff for RLD. Finally, we determined whether the cutoff varied depending on whether the right or left kidney was longer by US (Fig. 1). Kidneys with differential kidney function in the range of 50% ± 5% and absence of scarring by DMSA were considered to be normal. Differential renal function below 45% and/or an unequivocal scar by DMSA scan was considered abnormal. Based on the above criteria for DMSA findings, groups with normal and abnormal DMSA findings were assigned for statistical analysis. Statistical analysis Normality of distribution of demographic parameters was examined by Shapiro-Wilk test. χ2 and unpaired Student’s t test were used to compare DMSA finding between groups G1a and G1b with <10 mm or ≥10 mm RLD. Linear regression analysis was used to examine the correlations between RLD and demographic parameters. Pearson’s correlation coefficients were determined for nonlinear data. Receiver operating characteristic (ROC) curves were used [9, 10] to determine the RLD that best predicted an abnormality by DMSA scan. Positive predictive values (PPV) were calculated for 6-mm through 11-mm RLDs as candidate cutoffs for all kidneys and for right or left longer kidneys. PPVs were also calculated for 6- to 11-mm RLD for the two age groups (younger or older than 4 years) and
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Fig. 1 Patient categorisation
PATIENTS CATEGORIZATION Grouped by RLD
G1a RLD* < 10 mm = 68
G1b RLD* ≥10 mm = 22
All patients
Grouped by age
G2a¶ Age ≤ 48 m = 52
Left longer kidney = 29
Right longer kidney = 21
G2b¶ Age > 48 m = 38
Left longer kidney = 21
Right longer kidney = 12
* RLD: Renal length discrepancy; m months ¶: Seven patients had equal length for left and right kidney, 2 belong to G2a and 5 to G2b
their related subgroups. P values <0.05 were considered significant. Analyse-It® statistical software package was used for statistical analysis.
Results Renal length discrepancy The left kidney was longer by US in 50/90 (56%) children and the right in 33/90 (37%). They were of equal length in 7/90 (8%). DMSA abnormalities ranged from discrete scars to global reduction in differential function. Because the main question we wanted to answer was whether <10-mm or ≥10-mm renal size discrepancy correlated with abnormal DMSA findings, all patients with DMSA abnormalities (scars
or abnormal differential function) were analysed as a group. Abnormal DMSA findings were noted in 82% (18/22) of patients with US RLD ≥10 mm and in 32% (22/68) of patients with renal discrepancy <10 mm (χ2; p<0.0005). Forty patients (22 males) had abnormal DMSA. These were noted in 40% of patients with longer left kidneys and 60% with longer right kidneys (Table 1). Children with kidneys of equal length had normal DMSA scans. Of those with a normal DMSA scan, 17 were boys. Analysis of data from all 90 children showed that RLD by US for kidneys with abnormal DMSA scans was significantly larger than for kidneys with normal DMSA scans (mean ± SD) 12.4±9.7 mm vs 3.9±3.9 mm (unpaired t test; p<0.0001). When data were analysed by DMSA abnormality in children younger than 48 months (G2a) and older than 48 months (G2b), the difference in RLD is also significant (Table 2). RLD by US
Table 1 Comparison of renal length discrepancy (RLD) in millimetres in children with normal or abnormal dimercaptosuccinate acid (DMSA) scan
All kidneys (90)a Left kidney longer (50) Right kidney longer (33)
Abnormal DMSA n (%)
Abnormal DMSA mean RLD ± SD
Normal DMSA mean RLD ± SD
P value
40 (44%) 20 (40%) 20 (60%)
12.4±9.7 13.3±8.2 11.5±11.1
3.9±3.9 5.2±4.3 3.1±1.9
<0.0001 <0.0001 0.0121
SD standard deviation Includes 7 children who had kidneys of equal size b Comparison between mean RLD in normal and abnormal DMSA scan
a
b
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Table 2 Comparison by age groups of mean renal length discrepancy (RLD) in children with abnormal and normal dimercaptosuccinate acid (DMSA) scans Abnormal DMSA
Normal DMSA
Age Group (n)
Mean RLD ± SD
Mean RLD± SD
<48 months (52) >48 months (38)
10.9±8.9 14.4±10.5
3.6±2.9 4.4±4.8
sensitivity and specificity data are presented in Table 3, and the data for the ‘cutoffs’ at the two age groups and their related subgroups are presented in Tables 4, 5 and 6, 7.
P value
Discussion The relationship between kidney length and age is biphasic. There is rapid growth during the first year of life and a more gradual enlargement thereafter up to 12–18 years of age [1, 2]. Kidney length in adult men is larger than that in women, but in children up to the age of 16 years, renal length does not vary between the sexes after correction for height [3, 4, 11– 14]. The maximum bipolar renal length by US has become the standard parameter measured because it is simple to obtain [11] and correlates well with renal volume [4]. Although renal volume correlates well with renal length [4], renal mass [6] and glomerular filtration rate [5], determination of renal volume needs a renal longitudinal measurement and at least two renal transverse dimensions. Calculation of volume is not clinically practical [11] and is prone to
0.0001 0.0005
SD standard deviation
did not correlate significantly with age, height and BSA. Correlation coefficients (r2) for age, height, weight and BSA were 0.03, 0.01, 0.02 and 0.02 (not significant), respectively. ROC curves for all kidneys and for longer right or left kidneys revealed an area under the ROC curve of >0.8 [10], suggesting that RLD is a useful measurement in predicting renal abnormality on DMSA scan (Fig. 2). The RLDs that resulted in the best PPVs were ≥10 for longer left and ≥6 mm for longer right kidneys. The predictive values,
Fig. 2 Receiver operating characteristic (ROC) curves for all (a), longer left (b) and longer right (c) kidneys
1 0.9
a
Sensitivity (true positives)
0.8 0.7 0.6 0.5
Area: 0.82 P value<0.0001
0.4 0.3 0.2
No discrimination
0.1
L - R DIS - R1
0 0
0.2
0.4
0.6
0.8
1
1 - Specificity (false positives)
1
1
0.9
b
0.8
c
0.8 Sensitivity (true positives)
Sensitivity (true positives)
0.9
0.7 0.6 0.5
Area: 0.81 P value<0.0001
0.4 0.3
0.7 0.6 0.5
Area: 0.80 P value<0.0001
0.4 0.3 0.2
0.2 No discrimination 0.1
No discrimination
0.1
L-R DIS
L-R DIS
0
0 0
0.2
0.4 0.6 0.8 1 - Specificity (false positives)
1
0
0.2
0.4
0.6
0.8
1 - Specificity (false positives)
1
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Table 3 Renal length discrepancy at any age and an abnormal dimercaptosuccinate acid (DMSA) scana Numberb
Kidneys
L>R
50
R>L
33
Cutoff
>12 mm >11 mm >10 mm >9 mm >10 mm >9 mm >8 mm >7 mm >6 mm >5 mm
Sensitivity
Specificity
(95% CI)
(95% CI)
50% 55% 55% 55% 40% 45% 45% 45% 45% 60%
97% (83–100) 93% (78–99) 90% (74–98) 80% (61–92) 100% (75–100) 100% (75–100) 100% (75–100) 100% (75–100) 100% (75–100) 85% (55–98)
(27–72) (32–77) (32–77) (32–77) (19–64) (23–69) (23–69) (23–69) (23–67) (36–81)
PPV
NPV
91% 85% 79% 65% 100% 100% 100% 100% 100% 86%
74% 76% 75% 73% 52% 54% 54% 54% 54% 56%
a
With <45% differential function and/or a scar b Number of patients; 7 had kidney with identical lengths PPV Positive predictive value, NPV Negative predictive value
significant inaccuracy because the errors in each measurement are compounded [13, 15]. Determining whether the length of a kidney is abnormal by US requires knowledge of the expected length for age and sex of the patient and of potential variations in size and shape of normal kidneys. Normal renal length averages 11 cm in adults of average height [11], and a range of 10–12 cm is considered normal [16]. Miletic et al. concluded that in adults, an RLD is likely to be abnormal if the longitudinal measurement of the right kidney is greater than that of the left by >4 mm; however, the left can be up to 9 mm longer [17]. Difference between left and right kidney length has previously been described in children; the left kidney is usually longer and larger in volume than the right [2–4, 7, 13, 14, 16–21] and on postmortem examination is longer [22]. Postulated explanations for this may be simply the availability of a larger space for growth because of the relatively smaller size of the spleen compared with the liver, or perhaps increased blood supply for left kidney from the short and straight left renal artery [11]. The variation in the length of
the left kidney by US may be exaggerated, as the spleen does not provide as good an acoustic window as does the liver, making it technically more difficult to measure the left kidney accurately [23]. Some have argued for a standardisation of methods for evaluating the length of both kidneys by US; however, others contend that this may introduce a different set of measurement errors [24]. Our results in 90 children referred to a renal clinic revealed that the left kidney was longer by US in 56%, whereas the right kidney was longer in 37% and equal in length in 8%. Although the patients were referred for evaluation of potential renal disease, our study confirms previous data that show that normally, the left kidney is longer than the right [2–4, 7, 11– 14, 16–21]. Hence, when the right kidney is longer, a smaller RLD could be significant. A ≥10-mm RLD is considered an acceptable cutoff for further investigation in adults. This magnitude of RLD was noted as a significant discrepancy in the US report of only eight of our patients and was not the stated reason for referral to the nuclear medicine department. Most children were
Table 4 Analysis of renal length discrepancy (RLD) by cutoff as a predictor for dimercaptosuccinate acid (DMSA) abnormality in children younger than 4 years when the left kidney is longer than the right (n=29)
Table 5 Analysis of renal length discrepancy (RLD) by cutoff as a predictor for dimercaptosuccinate acid (DMSA) abnormality in children younger than 4 years when the right kidney is longer than the left (n=23)
RLD (mm)
Sensitivity % (CI)
Specificity % (CI)
Positive predictive value %
Negative predictive value %
RLD (mm)
Sensitivity % (CI)
Specificity % (CI)
Positive predictive value %
Negative predictive value %
11 10 9 8 7 6
50 50 50 50 50 50
100 (81–100) 94 (71–100) 82 (57–96) 82 (57–96) 82 (57–96) 77 (50–93)
100 86 67 67 67 60
74 73 70 70 70 68
11 10 9 8 7 6
18 27 36 36 36 36
100 100 100 100 100 100
100 100 100 100 100 100
57 60 63 63 63 63
(21–79) (21–79) (21–79) (21–79) (21–79) (21–79)
(2–52) (6–61) (11–69) (11–69) (11–69) (11–69)
(74–100) (74–100) (74–100) (74–100) (74–100) (74–100)
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referred for DMSA scans because they had a history of UTIs and/or high-grade vesicoureteric reflux. We showed that an RLD cutoff of 10 mm for longer left kidneys and as low as 6 mm for longer right kidneys predicts abnormality on DMSA scan. We confirmed the clinical impression that in children, a smaller difference in kidney length by US is predictive of abnormality on DMSA scan, especially if the right kidney is longer. However, our data cannot rule out the possibility that a lower cutoff could be used, especially in younger children, as the number of children in the study was too small. There was no clear correlation between RLD and age, BSA, height and weight. We chose 48 months of age for group assignment because renal growth slows after that age. It is likely that predictive accuracy would increase with larger studies. Our study suffers from the disadvantages inherent in retrospective data analysis and the relatively small study population. Although our imaging department routinely performs renal tract US in children, errors in measurement of renal length may occur. Our report reflects findings in a clinical setting rather than a controlled experimental protocol. In our hospital, we delay DMSA scans for at least 3 months from an identified UTI. It may be argued that some changes found in a DMSA scan 3 months after a UTI may resolve if scanning is delayed beyond 6–12 months. Characteristically, most DMSA scan abnormalities of acute pyelonephritis are unlikely to persist beyond 3 months, but resolution of minor residual changes may occur [8, 25, 26]. The time interval between renal US and DMSA scan in our study was up to 6 months. A shorter interval is unlikely to have greatly affected the interpretation, as RLD is more likely to increase with time due to hypertrophy of the less affected kidney. Thus, if RLD by US was smaller, this could have resulted in a reduced rather than an increased correlation with DMSA abnormalities.
Table 6 Analysis of renal length discrepancy (RLD) as a predictor for dimercaptosuccinate acid (DMSA) abnormality in children older than 4 years when the left kidney is longer than the right (n=26) RLD (mm)
Sensitivity % (CI)
Specificity % (CI)
Positive predictive value %
Negative predicitve value %
11 10 9 8 7 6
63 (25–92) 63 (25–92) 63 (25–92) 75 (34–97) 88 (47–100) 100 (63–100)
89 83 83 78 72 72
71 63 63 60 58 61
84 83 83 88 93 100
(65–99) (59–96) (59–96) (52–94) (47–90) (47–90)
Table 7 Analysis of renal length discrepancy (RLD) as a predictor for dimercaptosuccinate acid (DMSA) abnormality in children older than 4 years when the right kidney is longer than the left (n=12) RLD
Sensitivity % (CI)
Specificity % (CI)
Positive predictive value %
Negative predictive value %
11 10 9 8 7 6
44 44 44 44 44 56
100 (29–100) 100 (29–100) 100 (29–100) 100 (29–100) 100 (29–100) 67 (9–99)
100 100 100 100 100 83
38 38 38 38 38 33
(14–79) (14–79) (14–79) (14–79) (14–79) (21–86)
Our findings agree with those of Klare et al. [7] who used intravenous urography measurements to show that RLD is not as large in children as in adults and that acceptable RLDs increase with age. In the older children (>48 months), we found that the cutoff for RLD was not different from adults, but for younger children, (≤48 months) the cutoff was as low as 6 mm. In our study, especially in younger children, we demonstrated the importance of using different cutoffs according to whether the left or right kidney was longer.
Conclusion RLD is a useful measurement for making decisions regarding further investigations including a DMSA scan, but what constitutes an abnormal discrepancy in renal length must be defined further in prospective studies. Our data revealed that a different RLD cutoff for age and for the left or right kidney correlates well with and is predictive of abnormal DMSA scans, the gold standard for parenchymal damage. Overall, in children and adults, an RLD (>10 mm) alone is sufficient for further investigation, but a smaller size discrepancy of only ≥6 mm may be significant in children, especially when the right kidney is longer than left. Our study shows that RLD increases with age. An “acceptable” renal discrepancy in children younger than 4 years is up to 6 mm. In older children, RLD of 10 mm or larger is sufficient reason to refer for further evaluation, but importantly, this cutoff falls to ≥6 mm if the right kidney is longer. Acknowledgements We thank the staff of the departments of medical imaging and Prof. M. A. Rossleigh and staff of the nuclear medicine department for the excellent performance and reporting of renal ultrasounds and nuclear scans.
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