Dual-Source CT in Predicting and Treating Uric Acid Stones: A Retrospective and Prospective Study

doi:10.21203/rs.3.rs-4817159/v1

Download PDF

Research Article

Dual-Source CT in Predicting and Treating Uric Acid Stones: A Retrospective and Prospective Study

https://doi.org/10.21203/rs.3.rs-4817159/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Purpose

To evaluate the clinical application of dual-source CT in analyzing and treating urinary tract stone components.

Methods

A retrospective study of 204 patients with upper urinary tract stones who underwent preoperative dual-source CT and postoperative infrared spectroscopic stone analysis. Preoperative CT parameters were compared to assess diagnostic efficacy. A prospective study selected 60 patients predicted to have uric acid stones by dual-source stone energy spectrum CT, divided into experimental and control groups. The control group received diet and exercise therapy, while the experimental group received additional sodium potassium hydroxy citrate to dissolve the stones.

Results

Retrospective study: 204 patients (159 males, 45 females, mean age 50.7 ± 14.3 years). Stone length diameter (13.4 ± 5.1) mm. Significant differences in CT values for different stone types, with uric acid stones having lower CT values. ROC curves indicated high accuracy for dual-source CT, particularly at 100 kV. Prospective study: 60 patients (32 males, 28 females, mean age 61.2 ± 11.8 years), 38 renal stones, 22 ureteral stones. Experimental group showed higher complete dissolution rate (80% vs. 20%), lower non-response rate (3.3% vs. 33.3%), and lower surgical treatment rate (3.3% vs. 30%) at three-month follow-up. Urine pH improved in the trial group, with no significant change in uric acid levels. Incidence of renal colic was slightly lower in the trial group. Dual-source CT accuracy for predicting uric acid stones was 96.7%.

Conclusion

Dual-source CT accurately predicts uric acid stones to guide treatment choices, improving patient outcomes and reducing surgery need.

Dual-source CT

Urolithiasis

Uric acid calculi

Stone dissolving drugs

Urinary stones, as one of the most common urological disorders, especially in the upper urinary tract, have a wide range of global prevalence between 2 and 20 percent ^[1] The prevalence of stones in the upper urinary tract ranges from 2–20% worldwide. The formation of stones is influenced by several factors, including lifestyle habits, dietary habits, genetic factors, and metabolic abnormalities in the body. Currently, treatment strategies for stones include pharmacological and surgical treatments, the choice of which depends on the size, location, and composition of the stones. These include uric acid output, urinary pH, urine output, genetic predisposition, and metabolic syndrome.^[2] The following are some of the factors that may contribute to the development of stones.

Uric acid stones, which account for 10–15 per cent of all urinary tract stones. About 79% of these uric acid stones occur in men, with the majority occurring between 60 and 65 years of age ^[3]. Persistent aciduria, hyperuricosuria and insufficient urine output are the main factors causing uric acid stone formation ^[4]. Currently, medication is still the treatment of choice for uric acid stones, and alkalinisation of the urine has a success rate of 70–80%.^[5]. For non-uric acid stones, surgical intervention is usually required due to their hardness. However, current analyses of the composition of urinary stones require the stone to be isolated before they can be performed, which limits the choice of treatment options to some extent. Compared with conventional CT, dual-source dual-energy CT (DSDECT, hereafter referred to as dual-source CT), as an emerging imaging technology, not only has a lower radiation dose, but also provides more detailed information on stone composition, especially in identifying uric acid stones and non-uric acid stones with higher accuracy. ^{[6, 7]} The results of this study have been very favourable. However, prospective studies of dual-source CT in predicting the composition of urinary stones and guiding treatment are extremely limited, and most of them are still retrospective.

Therefore, the aim of this study was to investigate in depth the ability of dual-source CT in predicting uric acid stones and providing precise guidance for individualised treatment options through a comprehensive study design, integrating retrospective and prospective study methods. By filling the current lack of prospective studies, we expect to provide more practical and effective options for the diagnosis and treatment strategies of urinary stones.

2.1 Research design

We combined retrospective study analysis and prospective validation study. In the first part, a retrospective study evaluated the accuracy and sensitivity of dual-source CT for examining urinary tract stone components by collecting CT image data and clinical information from stone patients. Based on these results, a prospective study validated the diagnostic efficacy of dual-source CT and its role in guiding stone treatment.

2.2 Retrospective study

A total of 760 isolated specimens from patients with urinary stones admitted to the Department of Urology of our hospital from January 2017 to January 2022 were collected. Inclusion criteria: (1) patients who underwent preoperative dual-source stone energy spectrum CT and IRS analysis after surgical stone removal; (2) patients with stone diameters of 1.0-2.5 cm, meeting surgical indications; (3) those who were aware of the experiment and voluntarily participated. Exclusion criteria: (1) those with serious cardiopulmonary diseases; (2) pregnant and menstruating women.

Patients were scanned with Siemens’s dual-source CT with the following parameters: bulb voltage of 100 kV and 150 kV, tube current of 250 mAs and 120 mAs, pitch of 0.6 mm, scanning layer thickness of 5 mm, reconstruction layer thickness of 0.6 mm, and layer spacing of 0.6 mm. Data were analyzed by a professional radiologist, recording the stone’s length, diameter, location, and CT values at two voltages. Stone composition was judged according to the dual-energy ratio (Ratio = CT value at 100 kV / CT value at 150 kV), with specific ranges for uric acid stones (≤ 1.15), cystine stones (1.16–1.35), calcium oxalate stones (1.36–1.55), and hydroxyapatite stones (> 1.55).

All patients underwent surgical removal of stones, including percutaneous nephrolithotomy and ureteroscopic lithotripsy. Stone specimens were analyzed for composition by infrared spectroscopy. Simple stones with > 95% volume of the main components, including non-uric acid stones such as calcium oxalate stones, transkisapatite, and cystine stones, were included. The predictive efficacy of dual-source CT was evaluated by comparing the postoperative isolated stone composition with the stone composition predicted by preoperative CT.

2.3 Prospective validation studies

Based on the retrospective study results, 60 patients diagnosed with uric acid stones by dual-source CT from July 2022 to November 2023 were included. Inclusion criteria: (1) age 18–60 years, (2) uric acid stones predicted by dual-source CT, (3) stone diameter below 2 cm, (4) no urinary tract obstruction distal to the stone, (5) informed consent. Exclusion criteria: uncontrolled urinary tract infection, pregnant women, renal insufficiency, and poor general condition.

The study protocol was approved by the Ethics Committee of the Shanghai Sixth People's Hospital. Each participant provided informed consent.

Sixty patients meeting the criteria were randomly divided into experimental and control groups and underwent comprehensive examinations including abdominal ultrasound, dual-source CT, electrolytes, blood, urine, renal, and coagulation functions at the first clinic visit. Randomization was done using a computerized randomization table. Both groups received dietary and lifestyle instructions: (1) high fluid intake to ensure daily urine output of ≥ 2,000 ml; (2) purine-restricted diet; (3) oral allopurinol for patients with hyperuricemia. The experimental group received potassium sodium hydrogen citrate (Youlite, JX20160180, 97.1/100g bottle), 4 standard measuring spoons daily (10g granules total), taken in three divided doses after meals. Urine pH was monitored and adjusted to maintain an ideal range of 6.8–7.2. The treatment period was 3 months.

The primary observation was stone clearance rate (SFR), with CT examination within 3 months post-treatment. Categories included complete remission (no residual stones), no response (stones unchanged or increased), and partial remission (stones decreased). Secondary observations included complications such as renal colic and need for adjuvant surgery. These observations were recorded and analyzed to assess the treatment regimen’s safety and efficacy.

2.4 Data analysis

The data were processed by SPSS 26.0 statistical software. Measurement data that met the normal distribution were expressed as x ± s, and the comparison between groups was made by independent samples t-test; measurement data that did not meet the normal distribution were expressed as M(O0,), and the comparison between groups was made by Mann-Whitney U-test. The difference was considered statistically significant at P < 0.05. The full procedure is described in Fig. 1 for reference.

3.1 A retrospective study

3.1.1 Parametric features of dual-source CT scanning

The results of postoperative infrared spectroscopic analysis of 760 cases in this study showed that there were 664 cases of non-uric acid stones, including 481 cases of calcium oxalate stones,174 cases of hydroxyapatite,96 cases of uric acid stones and 9 cases of cystine stones. The dual-source CT scan data of stones of different compositions are shown in Table 1. Under the same tube voltage, the CT values of uric acid stones were smaller than those of the other three types of stones, and the differences were statistically significant(P < 0.01);the Ratio values of uric acid stones were lower than those of the other three types of stones, and the differences were statistically significant(P < 0.01). The results are presented in Table 1.

Table 1
Stone composition	number of examples	CT value/(HU)		Ratio	t	p
Stone composition	number of examples	100kV	150kV	Ratio	t	p
calcium oxalate	481	1358.37 ± 298.38	897.63 ± 205.27	1.52 ± 0.09	49.24	<0.01
hydroxy-apatite (phosphatic lime deposited in bone)	174	1114.06 ± 241.87	711.38 ± 186.72	1.59 ± 0.16	35.80	<0.01
Uric acid stones	96	558.58 ± 77.07	521.12 ± 83.54	1.08 ± 0.06	6.97	<0.01
cystine calculi	9	684.5 ± 67.18	573.5 ± 67.10	1.19 ± 0.02	-	<0.01
p	-	<0.01	<0.01	<0.01
Note: Ratio value = CT value at 100kV divided by CT value at 150kV

3.1.2 Efficacy of dual-source CT for the diagnosis of uric acid stones

Of the 760 patients, preoperative dual-source CT predicted uric acid stones in 102 cases: non-uric acid stones in 658 cases, including calcium oxalate stones in 523 cases, basal apatite in 121 cases, and cystine stones in 14 cases. Postoperative infrared spectroscopic analysis showed 6 false-positive and no false-negative uric acid stones when compared with preoperative CT results. The ROC curve of dual-source CT for the prediction of uric acid stones was calculated, and it was found that the sensitivity of the CT value at 100 kV for the prediction of uric acid stones was 96.2%, the specificity was 99.5%, and the area under the curve was 0.995, with the optimal prediction value of 620.0 HU; and the sensitivity of the CT value at 150 kV for the prediction of uric acid stones was 96.2% and the specificity was 99.5%, with the best prediction value of 620.0 HU. The sensitivity of CT value at 150 kV for predicting uric acid stones was 96.2%, the specificity was 85.5%, the AUC was 0.916, and the best prediction value was 597.5 HU; the sensitivity of Ratio value for predicting uric acid stones was 100.0%, the specificity was 97.9%, the AUC was 0.996, and the best prediction value was 1.14.

3.2 Prospective validation studies

Of the 60 patients, 32 were male and 28 were female. Age (61.2 ± 11.8) years. There were 38 cases of renal stones and 22 cases of ureteral stones. The differences between the two groups of patients in terms of age, gender, creatinine, uric acid, urine pH, stone length and number of stones were not significant (P > 0.05). In addition, no significant differences were demonstrated in the radiological findings in terms of CT value (100Kv), CT value (150Kv) and Ratio value (P > 0.05). Regarding the incidence of hydronephrosis (mild), it was slightly higher in the test group compared to the control group, but the difference was not significant (P = 0.17). Also, in terms of hypertension, diabetes mellitus and hyperuricemia, the prevalence was slightly higher in the test group than in the control group, but these differences also did not reach significant levels (P > 0.05).

According to the follow-up results, there was a significant difference between the trial and control groups in the treatment of uric acid stones. At the first month follow-up, although the difference in complete dissolution rate was not significant (P = 0.18), the complete dissolution rate was slightly higher in the trial group than in the control group (13.3% vs 3.3%). However, the trial group showed a significantly lower proportion of non-response than the control group (50% vs 76.7%, P = 0.02) and showed a lower rate of surgical treatment (0% vs 6.7%, P = 0.16). At the second month follow-up, the complete dissolution rate increased significantly to 43.3% in the test group compared to 10% in the control group (P = 0.005). The surgical treatment rate also remained low in the test group (0% vs 13.3%, P = 0.04). At the third month follow-up, the complete dissolution rate further improved to 80% in the trial group compared with only 20% in the control group (P < 0.01). In addition, the proportion of non-response and partial dissolution was significantly lower in the test group than in the control group (non-response: 3.3% vs. 33.3%, P = 0.005; partial dissolution: 13.3% vs. 46.7%, P = 0.005), whereas the rate of surgical treatment remained at a low level (3.3% vs. 30%, P = 0.009). The results are presented in Table 2.

Table 2
Norm	Test group	Control group	P-value
Patient characteristics
Age (years)	61.0 ± 11.2	61.5 ± 12.6	0.86
Distinguishing between the sexes
Males	23	24	0.18
females	7	6	0.17
Creatinine (umol/L)	93.2 ± 17.9	98.1 ± 17.2	0.27
Creatinine (umol/L)	332.8 ± 74.4	348.1 ± 76.1	0.44
Urine pH	5.7 ± 0.6	5.8 ± 0.6	0.38
Radiological findings
Stone length and diameter (cm)	1.27 ± 0.31	1.32 ± 0.33	0.60
Number of stones
an odd one	25(83.3%)	23(76.7%)	0.87
Multiple (≥ 2)	5(16.7%)	7(23.3%)	0.32
CT value (100Kv)(U)	517.7 ± 94.0	538.1 ± 97.5	0.39
CT value (150Kv)(U)	509.4 ± 123.3	515.2 ± 107.6	0.84
Ratio value	1.03 ± 0.09	1.05 ± 0.09	0.40
Complication (medicine)
Hydronephrosis (mild)	6(20.0%)	8(26.7%)	0.17
Hypertensive	7(23.3%)	5(16.7%)	0.16
Diabetes	5(16.7%)	4(13.3%)	0.25
Hyperuricemia	3(10.0%)	4(13.3%)	0.13

In terms of urine pH, the test group showed a significant improvement at the third month follow-up (6.97 ± 0.56) compared to 5.83 ± 0.66 in the control group (P < 0.01). In terms of complications, neither group showed any correlation in terms of hematuria, but 10% cases of renal colic were seen in the control group, and this difference did not reach a significant level compared to the test group (P = 0.08). The results are presented in Table 3.

Table 3
Therapeutic effect	Test group	Control group	P-value
First month follow-up
1. Completely dissolved	4(13.3%)	1(3.3%)	0.18
2. Partial dissolution	11(36.7%)	6(20.0%)	0.09
3. No response	15(50%)	23(76.7%)	0.02
4. Surgical treatment	0(0%)	2(6.7%)	0.16
Second month follow-up
1. Completely dissolved	13(43.3%)	3(10.0%)	0.005
2. Partial dissolution	8(26.7%)	11(36.7%)	0.44
3. No response	9(30.0%)	16(53.3%)	0.11
4. Surgical treatment	0(0%)	4(13.3%)	0.04
Third month follow-up
1. Completely dissolved	24(80.0%)	6(20.0%)	<0.01
2. Partial dissolution	4(13.3%)	14(46.7%)	0.005
3. No response	1(3.3%)	10(33.3%)	0.005
4. Surgical treatment	1(3.3%)	9(30.0%)	0.009
Uric acid (umol/L) at third month follow-up	335.3 ± 63.7	341.4 ± 62.4	0.69
Urine pH	6.97 ± 0.56	5.83 ± 0.66	<0.01
complications (undesired side-effect of medical procedure)
hematuria	0(0%)	0(0%)	/
renal colic	0(0%)	3(10%)	0.08

Urological stones, as a common and highly treatable disease with a high risk of recurrence, have a global prevalence of approximately 5% and a recurrence rate of up to 50% within ten years of treatment. ^[3] The pathogenesis of this disease is complex and involves several mechanisms. The pathogenesis of this disease is complex and involves multiple factors such as genetics, metabolic abnormalities, diet, and lifestyle. Therefore, accurate diagnosis and personalized treatment are essential to improve treatment outcomes and reduce recurrence rates.

Uric acid stones account for 10–15% of the incidence of all urinary tract stones ^[8]. For uric acid stones that are in the kidneys and do not have significant obstruction or infection, drug therapy is usually the preferred option. The success rate of this treatment is high and can reach 70–80 per cent. Treatment is mainly based on alkalinisation with citrate or sodium bicarbonate to control the urine pH at 7.0-7.2 ^[9–11]. Since uric acid stones do not show up in conventional X-rays, CT plain scanning improves the sensitivity of detection of non-calcific stones and at the same time is able to clearly visualize complex anatomical structures. However, the most important limitation of conventional CT plain scanning is its inability to predict stone composition, making it difficult to accurately individualize treatment ^{[12, 13]} The most important limitation of conventional CT scanning is its inability to predict stone composition, making it difficult to accurately individualize treatment.

Dual source CT technology has high sensitivity and specificity in the diagnosis of uric acid stones and is able to accurately differentiate between uric acid stones and other types of stones, such as calcium oxalate and calcium phosphate. Compared with conventional CT and MRI, dual-source CT has obvious advantages in diagnosing uric acid stones. By providing information on the energy spectrum of stones, dual source CT improves the specificity of diagnosis of uric acid stones ^[14–16]. Nestler's team^[17] s study found that dual-source CT had a positive predictive value of 100% and a negative predictive value of 98.5% for uric acid stones, and that the new generation of dual-source stone energy-spectrum CT is less damaging to patients. In addition, Zhang et al. ^[18] prospectively evaluated the diagnostic accuracy of dual-source dual-energy CT (DSDECT) in predicting the major components of urinary tract stones. The study population consisted of 81 patients with urinary tract stones assessed by DSDECT, with postoperative extracorporeal Fourier transform infrared spectroscopy (FT-IR) analysis as a reference standard. The results showed that DSDECT was able to accurately predict the major components of all pure stones and 36 mixed stones.

The diagnostic guidance of dual-source CT plays a crucial role in the strategy of treating urinary tract stones. Accurate diagnosis by dual-source CT allows physicians to develop more effective treatment plans for stones of different compositions. Habashy et al.^[19] 's study found that dual-source CT prospectively predicted the composition of urinary stones, and patients with predicted uric acid stones were treated with oral medications to dissolve the stones, and 12 of them had successful stone evacuation, avoiding surgical treatment. Pharmacological treatments, such as potassium hydrogen citrate sodium, are commonly used to dissolve uric acid stones. Dietary modifications and exercise therapy are indicated for all types of urinary stones. In terms of treatment outcomes, dual-source CT diagnostic-guided pharmacological therapy demonstrated high results in terms of stone dissolution rate and surgical avoidance rate.

In conclusion, dual-source CT has important clinical applications in the diagnosis and treatment of urinary tract stones. Its high sensitivity and specificity, as well as its ability to recognize different stone components, provide clinicians with precise diagnostic and therapeutic guidance ^{[20, 21]}. Despite the limitations of this study, the results provide strong support for further research and the application of dual-source CT in clinical practice.

Author Contribution

Wang Li and Yanduo Lin completed the data analysis, wrote the main manuscript text and prepared figure 1 and tables 1-3.Hong Xie, Rong Chen, Kun Zheng performed the operations.Luyi Yang and Ranxing Yang were responsible for the planning the subject and collecting data.Wang Li, Hong Xie and Yanduo Lin have contributed equally to this work.All authors reviewed the manuscript.

Zeng G, Mai Z, Xia S et al (2017) Prevalence of kidney stones in China: an ultrasonography based cross-sectional study. BJU Int 120(1):109–116
Siener R (2021) Nutrition and Kidney Stone Disease. nutrients. 13(6)
Ma Q, Fang L, Su R et al (2018) Uric acid stones, clinical manifestations and therapeutic considerations. Postgrad Med J 94(1114):458–462
Ngo TC, Assimos DG (2007) Uric acid nephrolithiasis: recent progress and future directions. Rev Urol 9(1):17–27
Khan SR, Pearle MS, Robertson WG et al (2016) Kidney stones. nature reviews. disease primers. 2(16008
Graser A, Johnson TR, Bader M et al (2008) Dual energy CT characterization of urinary calculi: initial in vitro and clinical experience. Invest Radiol 43(2):112–119
Wisenbaugh ES, Paden RG, Silva AC et al (2014) Dual-energy vs conventional computed tomography in determining stone composition. urology 83(6):1243–1247
Hall PM (2009) Nephrolithiasis: treatment, causes, and prevention. Cleve Clin J Med 76(10):583–591
Ferraro PM, Bargagli M, Trinchieri A et al (2020) Risk of Kidney Stones: Influence of Dietary Factors, Dietary Patterns, and Vegetarian-Vegan Nutrients. 12(3)
Barghouthy Y, Corrales M, Somani B (2021) The Relationship between Modern Fad Diets and Kidney Stone Disease: a Systematic Review of Literature. nutrients. 13(12)
Goldfarb DS, Modersitzki F, Asplin JR et al (2023) Effect of a high-citrate beverage on urine chemistry in patients with calcium kidney stones. Urolithiasis 51(1):96
Jepperson MA, Cernigliaro JG, Sella D et al (2013) Dual-energy CT for the evaluation of urinary calculi: image interpretation, pitfalls and stone mimics. Clin Radiol 68(12):e707–714
Mansouri M, Aran S, Singh A et al (2015) Dual-Energy Computed Tomography Characterisation of Urinary Calculi: Basic Principles, Applications and Concerns. Curr Probl Diagn Radiol 44(6):496–500
Kordbacheh H, Baliyan V, Uppot RN et al (2019) Dual-Source Dual-Energy CT in Detection and Characterisation of Urinary Stones in Patients with Large Body Habitus: Observations in a Large Cohort. AJR Am J Roentgenol 212(4):796–801
Matlaga BR, Kawamoto S, Fishman E (2008) Dual source computed tomography: a novel technique to determine stone composition. urology 72(5):1164–1168
Fung GS, Kawamoto S, Matlaga BR et al (2012) Differentiation of kidney stones using dual-energy CT with and without a tin filter. AJR Am J Roentgenol 198(6):1380–1386
Nestler T, Nestler K, Neisius A et al (2019) Diagnostic accuracy of third-generation dual-source dual-energy CT: a prospective trial and protocol for clinical implementation. World J Urol 37(4):735–741
Zhang XZ, Lei XX, Jiang YL et al (2023) Application of metabolomics in urolithiasis: the discovery and usage of succinate. signal Transduct Signal Transduct Target therapy 8(1):41
Habashy D, Xia R, Ridley W et al (2016) Impact of dual energy characterization of urinary calculus on management. J Med Imaging Radiat Oncol 60(5):624–631
Wortman JR, Shyu JY, Dileo J et al (2020) Dual-energy CT for routine imaging of the abdomen and pelvis: radiation dose and image quality. Emerg Radiol 27(1):45–50
Garcia LI, Azorin JF, Almansa JF (2016) A new method to measure electron density and effective atomic number using dual-energy CT images. Phys Med Biol 61(1):265–279

No competing interests reported.

Download PDF

Editorial decision: Revision requested
18 Aug, 2024
Reviews received at journal
14 Aug, 2024
Reviewers agreed at journal
14 Aug, 2024
Reviews received at journal
10 Aug, 2024
Reviewers agreed at journal
07 Aug, 2024
Reviewers invited by journal
05 Aug, 2024
Editor assigned by journal
31 Jul, 2024
Submission checks completed at journal
31 Jul, 2024
First submitted to journal
28 Jul, 2024

You are reading this latest preprint version

Dual-Source CT in Predicting and Treating Uric Acid Stones: A Retrospective and Prospective Study

Status:

Version 1

Abstract

Purpose

Methods

Results

Conclusion

Figures

1. Introduction

2. Patients and Methods

2.1 Research design

2.2 Retrospective study

2.3 Prospective validation studies

2.4 Data analysis

3. Results

3.1 A retrospective study

3.1.1 Parametric features of dual-source CT scanning

3.1.2 Efficacy of dual-source CT for the diagnosis of uric acid stones

3.2 Prospective validation studies

4. Discussion

Declarations

Author Contribution

References

Additional Declarations

Status:

Version 1