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Ultrasound measured renal length versus low dose CT volume in predicting single kidney glomerular filtration rate

Departments of ¹ Radiology and ³ Nephrology, North Staffordshire NHS, Stoke-on-Trent ST4 7LN and ² Department of Mathematics, University of Keele, Stoke-on-Trent, UK

Correspondence: Dr J W Oxtoby, Department of Radiology, Royal Infirmary, North Staffordshire NHS, Stoke-on-Trent ST4 7LN, UK

	Abstract

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Ultrasound measured renal length and CT measured renal volume are potential surrogate markers for single kidney glomerular filtration rate (SKGFR). The aims of this study are to determine: (1) the repeatability of ultrasound measured length and low radiation dose spiral CT measured volume; (2) the relationship between renal length and volume; and (3) whether length and/or volume is a predictor of SKGFR. 69 patients with suspected renal artery stenosis underwent ultrasound renal length measurement, CT evaluation of renal volume and assessment of SKGFR. 40 patients had ultrasound measurement of length and CT evaluation of volume performed twice on two separate visits. 25 patients also had ultrasound measured renal parenchymal thickness and area. The region of interest was drawn around the kidneys and a threshold set to subtract renal peripelvic fat and renal pelvis. The volume from each slice was summed to obtain the total volume for each kidney. The limits of agreement for ultrasound measured renal length were –1.6 cm to 1.52 cm and that for CT renal volume were –33 ml to 32 ml. There was significant correlation between ultrasound measured length and CT volume (r=0.74, p<0.01). Volume was a better predictor of SKGFR (r²=0.57) than length (r²=0.48). The combined parameters of ultrasound measured length, area and parenchymal thickness were a better predictor of volume (r²=0.81) and SKGFR (r²=0.58) than ultrasound measured length on its own. The low dose CT technique was reasonably reproducible and renal volume measurements correlate better with SKGFR than length. Ultrasound predictions of renal volume and SKGFR can be improved by incorporating cross-sectional area and parenchymal thickness. Further investigation is required to refine our low dose CT technique.

	Introduction

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Renal artery atherosclerosis (RAS) is an important and treatable cause of hypertension. The prevalence of atherosclerotic renal artery disease is unknown, although extrapolation from necropsy series suggested 40% of individuals aged over 75 years have occult anatomical renal artery stenosis [1]. RAS occurs in up to 22% of patients with aortic aneurysm and up to 45% of patients with peripheral vascular disease [2]. Atherosclerotic renal artery stenosis is increasingly recognized as an important cause of progressive chronic renal failure, and currently accounts for more than 14% of patients entering dialysis programmes in the UK [3]. Although the natural history is not clearly established, atherosclerotic RAS is likely to progress to occlusion if left untreated. The likelihood of progression to occlusion is greatest in patients with the most severe degree of stenosis [4–6]. This has led to increasing numbers of renal angioplasties and stenting being performed in an attempt to arrest or retard the progression towards dialysis dependency. Outcomes of the intervention have been gauged by control of blood pressure and prevention of deterioration of renal function.

Renal function is conventionally assessed by serum creatinine levels which rise in progressive renal failure or more specifically by measuring creatinine clearance by radioisotopic serum dilution technique [7]. Serum creatinine level provides a measure of overall combined renal function and may remain normal even in the presence of severe unilateral renal artery disease giving rise to severe damage to the kidney distally. Moreover serum creatinine levels are influenced by the muscle mass and nutritional status of the individual; these limitations severely restrict the value of creatinine measurements alone in assessing unilateral renal function. Unilateral renal function can be assessed by isotope studies of chromium edentate clearance combined with renographic assessment of divided renal function. However, this is cumbersome and expensive.

Renal artery stenosis has been associated with decreasing kidney size [4, 8]. In renal artery stenosis where disease progresses by sequential loss of nephrons, it is anticipated that there should be good correlation between renal size and function. Pathologically, there is glomerular crowding with progressive loss of renal cortical mass culminating in the small shrunken kidney seen in patients with proximal renal artery occlusion [9]. In this group of patients, renal size could be applicable as a surrogate for renal function and measures of renal size such as ultrasound measured length and CT measured volume could be used to chart the progress of the disease. This however will only apply in patients free from other renal pathology such as diabetic glomerulosclerosis.

Traditionally, ultrasound measured renal length has been used to estimate renal size. However, renal length is not a good predictor of renal volume. Renal volume best correlates with body surface area whereas renal length correlates with body height [10] and the kidney becomes shorter, and thicker with age [10]. Moreover, ultrasound measured renal length is prone to interobserver variability and poor repeatability [11–13]. Renal volume can be assessed directly by ultrasound using the ellipsoid formula. However, this has resulted in underestimation of renal volume [14, 15].

Contiguous CT slices to evaluate renal volume have been shown to be a reliable, objective and reproducible method of assessing renal volume [16–18]. One potential limitation of the use of CT is the radiation dose involved, particularly if these studies are repeated on a regular basis. We have developed a low radiation dose spiral CT protocol for measuring renal volume. Preliminary studies using a cadaveric pig model showed that the minimally acceptable parameters which allowed adequate discrimination of kidneys from surrounding fat were 120 kV, 50 mAs, 3 mm collimation, pitch of five and index of 3 mm. With this technique, the calculated volumes were within 4–8% of the actual renal volume and the estimated radiation dose was 0.5 mSv [19]. This dose is only a fraction of the effective dose of a standard CT abdomen, which is 10 mSv [20]. This study investigated whether this CT protocol could be used to measure renal volume in humans with suspected renal artery disease and compared the reproducibility of volume measured by this technique with ultrasound measured length. We also attempted to use these measures to predict single kidney function.

The specific aims of this study are to determine: (1) the repeatability of ultrasound measured renal length and CT measured renal volume; (2) the relationship between renal length and volume; and (3) whether length and/or volume is a predictor of single kidney renal function.

	Materials and method

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Patient population
Those patients who were investigated for possible renal artery stenosis by spiral CT renal angiography were recruited into the study. Patients undergoing spiral CT angiography for renal artery assessment and for abdominal aortic aneurysm with abnormal renal function (serum creatinine >150 µmol l^–1) were included in the study since the latter group of patients also have a high incidence of RAS. Women of child bearing age, children under the age of 18 years, patients with iodine sensitivity and patients with acute renal failure or diabetes were excluded from the study. Patients with angiotensin converting enzyme inhibitor drug induced renal impairment were included only after renal function had recovered and had been stable for a 4 week period. Informed consent was obtained from all the patients, in keeping with the guidelines of the hospital ethics committee who also approved the study design.

78 patients were recruited. The data were incomplete in two patients and one patient had horse-shoe kidney and was therefore considered ineligible. These patients were excluded from the study. Of the remaining 75 patients, 6 further patients were excluded from the analysis due to motion artefacts on the CT images, which made it difficult to delineate the renal outlines. There were 69 patients, 47 males and 22 females, included in the final analysis, mean age 68.4 years (range 41–80 years).

The first 40 patients underwent CT evaluation of renal volume and ultrasound assessment of renal length on two separate visits (mode 7 days, interquartile range 7–14 days) in order to assess the repeatability of the techniques. A radionuclide study to obtain single kidney function was carried out at the time of the first visit. The spiral CT angiography to evaluate for the presence of renal artery stenosis or abdominal aortic aneurysm was performed at the second visit. CT renal volume and ultrasound measured renal length were carried out on both visits. This timing was to ensure there was no effect on renal function due to contrast nephrotoxicity.

Assessment of single kidney renal function
The results from chrominium-51 ethyl enediamine tetraacetic acid (⁵¹Cr-EDTA) glomerular filtration rate (GFR) measurement and differential renal function assessment from DMSA radionuclide imaging were combined to calculate the absolute function of each individual kidney. Differential renal function was assessed by intravenous injection of 74 MBq of ⁹⁹Tc^m dimercaptosuccinic acid (DMSA). 3 h later, anterior and posterior images were obtained using an ADAC/Philips Vertex Plus gamma-camera (CA, USA) with low energy general purpose collimator. Regions of interest were drawn on the anterior and posterior images for both kidneys and the geometric mean of anterior and posterior counts of each kidney was used in order to calculate differential renal function.

To assess total glomerular filtration rate (GFR) 3 MBq of ⁵¹Cr-EDTA was administered intravenously and venous blood samples obtained at 3 h, 4 h and 5 h post administration. These plasma samples together with a standard were counted. Total GFR (ml min^–1) was calculated from these sequential measurements.

Assessment of renal length
Ultrasound was performed on ATL HDI 3000 (Philips, DA Best, Netherlands) with 2–4 MHz frequency probe by a consultant radiologist (JO). During each visit, two to three measurements of individual renal length were obtained, and the largest measurement was used. The presence, size and number of renal cysts and the presence and degree of pelvicalyceal dilatation were noted as these affect the relationship between renal volume, renal length and renal function. During the study it became apparent that other ultrasound parameters such as renal parenchymal thickness and cross sectional area may be of interest as predictors of renal volume. Therefore in 25 patients, the renal parenchymal thickness and cross sectional area were also assessed on the transverse section at the interpolar region of the kidney.

Assessment of spiral CT renal volume
Spiral CT was performed with a Toshiba Xpress GX CT scanner (Toshiba Medical Systems, Tokyo, Japan). No contrast or preparation was required. The kidneys were first localized with a scannogram. The patient was then instructed to breath-hold. The scanning parameters were 120 kVp, 50 mAs, collimation of 3 mm, pitch of 5 and index of 10 mm. Scanning was performed in a single breath hold with total scan duration of approximately 10 s. The region of interest was drawn around the kidneys and an attenuation threshold was set to subtract peripelvic fat and renal pelvis from the images. Renal cysts were excluded visually from the region of interest. The volume from each slice was summed to obtain the total volume for each kidney.

Statistical analysis
The repeatability of renal length and volume measurements was calculated using Bland and Altman [21] measures of agreement. Pearson's correlation coefficient was used to evaluate the relationship between renal length and volume. To predict single kidney renal function from renal length and volume, regression analysis was utilized.

	Results

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Reproducibility of length and volume
40 patients had ultrasound assessment of the renal length and CT study of the renal volume repeated within a period of 3 weeks. The Bland and Altman measure of agreement of renal length and volume is shown in Table 1. The limits of agreement of the renal length were –1.6 cm to 1.52 cm (mean renal length 9.91 cm). The limits of agreement of the renal volume were –33.1 ml to 31.6 ml (mean renal volume 121 ml).

Relationship between length and volume
The renal length (n=138 kidneys) as measured by ultrasound was significantly correlated with renal volume (r=0.86, p<0.01). There was also significant correlation between the square and cube length against the volume (r=0.85, p<0.01; r=0.85, p<0.01, respectively), but this was no better than renal length on its own. The relationship of ultrasound measured length and CT measured renal volume is demonstrated in Figure 1. Renal volume was best predicted from the following equation: Volume=–183.2+30.7 length. The combined ultrasound parameters of length, cross-sectional area and parenchymal thickness (n=50 kidneys) were a better predictor of CT measured renal volume in the smaller number of patients who underwent these additional measurements (r²=0.81) than length (n=138) on its own (r²=0.73).

View larger version (18K): [in this window] [in a new window]   Figure 1. Relationship of ultrasound measured renal length and CT measured renal volume.

View larger version (18K): [in this window] [in a new window]   Figure 2. CT measured renal volume in predicting single kidney glomerular filtration rate (SKGFR).

View larger version (18K): [in this window] [in a new window]   Figure 3. Ultrasound measured renal length in predicting single kidney glomerular filtration rate (SKGFR).

	Discussion

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Ultrasound measured renal length has been used as an indicator to evaluate the need for intervention [26, 27] and also to assess the natural progression of renal artery stenosis [6]. Since therapeutic decisions are frequently based on the size of the kidney, it is important that renal length measurements are consistent, both for replicate measurements by a single ultrasonographer and by different ultrasonographers. Ablett et al [11] have shown that the limits of agreement of renal length in normal subjects for each ultrasonographer were similar and did not exceed ±1.45 cm. The limits of agreement for each pair of ultrasonographers did not exceed ±1.85 cm. Similar results for interobserver and intraobserver variability were obtained by Schlesinger et al [13]. In diseased kidneys, the identification of the renal poles is more difficult and therefore the interobserver and intraobserver variability would be expected to be greater. In our study, although both normal size and small diseased kidneys were evaluated, our results for the reproducibility of renal length were very similar to previous studies.

In contrast to renal length, renal volume has received little attention in the literature as a parameter for clinical follow up, and is rarely included as an indication for intervention. This is due to the difficulty in measuring renal volume. Renal volume has been shown to be a more sensitive means of detecting renal abnormality than any single linear measurement and correlated better with renal mass [28]. In autopsy studies, kidney volume has been shown to correlate well, although indirectly, with the number of functioning nephrons [29, 30]. Ultrasound has been used as a modality to predict renal volume, using either the stepped section or the ellipsoid method. The stepped section method [31] is labour-intensive and technically difficult. The ellipsoid method is associated with unacceptably wide limits of agreement [10, 12, 14], ranging from –82 ml to 51 ml and resulted in up to 25% systematic underestimation of the renal volume [14, 15].

A preliminary in vitro study utilizing pig kidneys has demonstrated that CT is potentially a highly accurate technique for evaluating renal volume [19]. When this is extrapolated to humans in this current study the results were not as good. The discrepancy in results could be due to various factors, including respiratory movement artefact, the presence of cysts in this older population and irregularity of kidneys due to disease. In the post-mortem assessment of pig kidneys, there is no respiratory motion and the kidneys were stationary and free from disease. Partial volume effects in the upper and lower poles of the kidneys is another potential source of error. In this study, which comprised patients with suspected renal vascular disease, both diseased shrunken and normal sized kidneys were assessed. Partial volume effects are likely to be greater in smaller kidneys due to the greater difficulty in defining the poles of the kidneys on axial images.

Various methods of evaluating CT renal volume have been described in the literature [17, 18, 32]. Unlike our study, intravenous iodine containing contrast agent was used in many of these investigations. Avoidance of iodine contrast agent is preferable, especially in patients whose renal function has deteriorated. Although D'Souza et al [33] did not use an intravenous iodine based contrast agent, their patient cohort received oral contrast. This was given because unopacified loops of bowel abutting the kidney were otherwise difficult to separate from renal tissue both visually and with the processing software. We have not found this issue to be problematic when delineating the region of interest around the kidneys. Moreover, by omitting oral contrast we have avoided the problem of streak artefacts produced over the kidneys by the gas and contrast interface in the adjacent bowel. In contrast to the technique used by D'Souza et al [33], we have used a lower dose of ionizing radiation, which gives an effective dose of 0.5 mSv. This is about one sixth of the effective dose in their study.

Bakker et al [14] found renal length to be weakly correlated with renal volume (r=0.36) whereas we have found a significantly higher level of correlation (r=0.86). The reason for this discrepancy remains unclear. In our study the prediction of renal volume was further improved by including ultrasound measured cross-sectional area and parenchymal thickness. Emamian et al [10] have found that renal length is a poorer indicator of the amount of renal parenchyma than is renal volume, and therefore, it is a poorer parameter for the diagnosis of renal disease. Our results are in agreement with Emamian et al [12], in that CT measured renal volume is a better predictor of SKGFR than ultrasound measured renal length. D'Souza et al [33] have also shown CT measured renal parenchymal volume to be highly correlated with SKGFR (r=0.86). This is significantly higher than we achieved in our study (r=0.57) and this may be a reflection of the low radiation dose protocol and lack of vascular contrast in our study, giving rise to less accurate measurement of volume. Although the combined ultrasound parameters of cortical thickness, area and length improved our prediction of single kidney renal function and appear almost as good as the CT measured renal volume, the results are not directly comparable as the analysis was done on a smaller number of kidneys. However, our results suggest that when these ultrasound parameters are combined, they improved the prediction of renal function compared with length alone.

Renal volume has also been assessed using MR imaging with the voxel-count method in vitro [15]. The repeatability of renal volumetry with the voxel-count method with MR imaging was excellent, with intraobserver limits of agreement ranging from –12 ml to 16 ml [14]. These data are encouraging and these limits of agreement are superior to those achieved by our CT technique.

Our technique for measuring renal volume by CT has advantages over previously described CT techniques because of its lower dose requirement and the lack of iodinated contrast agents. However, unfortunately our technique is somewhat less accurate (±31 ml versus ±22 ml) [33]. It is also less accurate than MR assessment of renal volume. The clinical significance of these differences remains uncertain but they may be important in assessing minor sequential changes in renal volume as RAS progresses. Currently the processing time in measuring CT renal volume is a significant impediment to the use of CT but this limitation will be readily addressed with newer measurement software incorporated in semi-automated volume measurement.

Renal volume as measured by our CT technique clearly does correlate better with SKGFR than does length measured by the ultrasound technique. SKGFR is, as outlined previously, a difficult parameter to measure directly and is also a key indicator of the effects of renovascular disease on a kidney. Therefore, the measurement of renal volume with its greater predictivity of single kidney function should be a more relevant measure in these cases than ultrasound renal length.

In the clinical setting the increased validity of this measure will have to be weighed against the more invasive and time consuming nature of the CT procedure. It may be that an ultrasound method involving the additional parameters of parenchymal thickness and area may represent a workable compromise whilst providing a slightly less accurate measure than CT renal volume.

	Conclusion

Top Abstract Introduction Materials and method Results Discussion Conclusion References

 
Our study has evaluated a simple low dose technique for measurement of CT renal volume. We have found that the technique is reasonably reproducible and that renal volume measurements calculated by this technique correlate significantly better with single kidney renal function than ultrasound length measurements in the same kidney. Our technique however, appears less reproducible than some other CT and MR techniques. Further investigation is required to refine our low dose CT technique and to assess the clinical significance of improvements in the assessment of renal size and function as compared with the ultrasound technique. Indeed, our study also suggests that ultrasound can approach CT in prediction of SKGFR if other parameters in addition to length are incorporated.

	Footnotes

 
Funding body: West Midlands R&D (LORS) Project Grant.

Received for publication December 18, 2003. Accepted for publication April 15, 2004.

	References

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This Article Abstract Figures Only Full Text (PDF) Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Widjaja, E Articles by McCall, I W Search for Related Content PubMed PubMed Citation Articles by Widjaja, E Articles by McCall, I W