Burden and Distribution of MSU Deposition in Patients with Hyperuricemia and Gout: A Large Cohort Chinese Population Based DECT Study

doi:10.21203/rs.3.rs-1622091/v1

Download PDF

Research Article

Burden and Distribution of MSU Deposition in Patients with Hyperuricemia and Gout: A Large Cohort Chinese Population Based DECT Study

https://doi.org/10.21203/rs.3.rs-1622091/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Objectives

To investigate the distribution and burden of monosodium urate (MSU) deposition in hyperuricemia and gout patients with dual-energy CT (DECT) and to explore whether the MSU burden can be predictive of the renal insufficiency in these subjects.

Methods

We retrospectively analyzed 4,954 DECT examinations in 642 consecutive patients (hyperuricemia group, n = 121; gout group, n = 521) with at least two anatomical locations and recorded the volume and number of MSU deposits. For each anatomical location, we recorded MSU deposition of bone cortex, soft tissue and joint cavity, respectively. MSU deposition were analyzed and compared between groups. Patients were followed up to explore whether there was a correlation between MSU deposition and renal function if appropriate.

Results

The MSU deposition in gout group was significantly higher in the foot and knee than those in the hyperuricemia group (all P < 0.05). In gout group, MSU deposition at the elbow soft tissue was significantly higher than those in bone cortex and joint cavity, while in the hyperuricemia group, MSU deposits in cortical cortex of the knee and foot/ankle were significantly higher than those in the soft tissue and joint cavity (all P ≤ 0.05). Fifty-two gout patients had a median 2 years follow up, however, MSU burden was not predictive of the renal insufficiency (P = 0.678).

Conclusions

The MSU deposition in the gout group was significantly higher than that in the hyperuricemia group, while MSU deposition was predominant in foot/ankle and knee. The MSU burden is not predictive of renal function decline in gout patients.

Monosodium urate

DECT

Renal insufficiency

Gout

Hyperuricemia

Gout, the most common form of inflammatory arthritis [1], the incidence has tripled over the recent decades, has a prevalence of 3.9% in the USA [2].Elevated levels of serum uric acid (sUA) greater than 6.8mg/dL (410 µmol/L) can cause crystallisation of monosodium urate (MSU) crystal deposits and eventually trigger gout in some patients [3–4]. While hyperuricemia is a known cause of gout, many patients with hyperuricemia do not develop gout [5]. To date, it is not fully understood why and when some patients with asymptomatic hyperuricemia (ie, hyperuricemia in the absence of gout) develop gout. Sedimentary sites may play a role, for example, the deposition around the joints may not lead to clinically significant diseases [6]. The quantity of urate crystal deposition may also affect the development of symptomatic diseases [6]. Nevertheless, the mechanism and location of MSU crystal deposition in gout have received little attention from the scientific community till now. So the main purpose of this study is to try to figure out whether distribution and burden have an effect on the progression of asymptomatic hyperuricemia to symptomatic gout, so that we can better prevent the occurrence of gout and better manage clinical hyperuricemia and gout. Moreover, we innovatively divide a single joint into distinct segments (cortical bone, soft tissue, and joint cavity). In this way, the systemic MSU deposition in gout patients will be measured more precisely, and correspondingly, the clinical treatment will be more precise, controllable and targeted.

Gout is connected with many diseases that affect longevity and well-being [7], such as metabolic syndrome [8], cardiovascular diseases [9–12] and renal diseases [13]. Gout and these comorbidities are all linked to hyperuricemia, which has been associated with impaired renal function and the development and progression of renal disease [14–16]. Chronic kidney disease was associated with a 60% increase in gout risk [17] and a six-fold increased risk of incident gout for those with renal disease has also been reported [7]. Studies have emphasized that the negative effects of gout on the cardiovascular effect is not only caused by serum uric acid [18], whether the deposition of MSU crystals also plays a role remains unclear. In patients with rheumatoid arthritis, uric acid has been proven a powerful independent predictor of renal insufficiency [19]. Thus, we speculated that MSU crystals can independently predict renal function decline in gout patients. The second purpose of this study is to explore whether the MSU burden can be predictive of the renal insufficiency.

For many decades, the gold standard for the diagnosis of gout has been the identification of MSU crystal deposits in the synovial fluid of the affected joint using polarised light microscopy [20–21]. Given the limitations of joint aspiration and use of polarised microscopy, alternative strategies for diagnosing gout have been developed, including dual-energy CT (DECT) [22]. Dual-energy CT (DECT) is a recently developed advanced imaging method that allows for specific detection and volume measurement of urate deposits in gout patients [23]. Although DECT has been proven to be useful in detecting articular MSU detection in gout patients in some studies [24–25], no study has been reported to use DECT to compare the distribution and burden of MSU deposits in patients with hyperuricemia and gout and investigate the role of DECT in predicting renal function changes in gout patients.

Therefore, we aimed to investigate the distribution and burden of MSU crystal deposition in patients with asymptomatic hyperuricemia and symptomatic gout with DECT and to explore if the extent of MSU burden measured with DECT can be predictive of the renal function decline in gout patients.

Study Population

This retrospective study was approved by the institutional review board of Jinling Hospital, Medical School of Nanjing University. Written informed consent was waived. A total of 1936 consecutive patients from January 1, 2009 to September 15, 2017 underwent DECT examinations with at least two anatomical locations including symmetrical hands/wrists, feet/ankles, knees, elbows and kidneys. Of these, 1294 patients were excluded due to other clinical diagnosis which was neither gout nor hyperuricemia (n = 1041), inappropriate location which is atypical MSU deposition site (n = 82), poor quality images (n = 105), training cases (n = 30) and duplicated data (n = 36). Finally, 642 patients (male: 94.4%; mean age: 44 ± 16 years; range 12–90 years) were included. The flowchart of this study is provided in Fig. 1. Additionally, the demographics and comorbidities from patients’ medical history were recorded from the patients’ medical record.

DECT scans

DECT examinations were performed in 59% (380/642) patients on the first-generation dual-source CT system (Somatom Definition or Definition FLASH, Siemens Healthcare), while the remaining 41% patients underwent DECT examination on a second-generation dual-source CT system (Somatom Definition or Definition FLASH, Siemens Healthcare) within 1 week of clinical diagnosis. The clinical indication to perform DECT in asymptomatic HUA patients were (1) clinical diagnosis is hyperuricemia, (2) sUA levels ≥ 261umol/L. Each patient underwent at least 2 of the 10 anatomical locations for DECT scans: hands/wrists, elbows, knees, feet/ankles and kidneys (one for each side). All scans were performed with the same imaging protocols except for scanning coverage, tube voltage (kV) and effective tube current (mAs). The scanning parameters: tube voltage of (sn)140/80–100 KVp, the effective tube currents of 40/170 mAs and 37/157 mAs in the first generation and the second generation dual-source CT for upper extremity; 55/234 mAs / 240/120 mAs for knees and 250/125 mAs for feet/ankles, 95/404 mAs/ 153/120 mAs for kidney. Technical features included slice thickness of 0.6mm, field of view 120 and slice interval of 0.3mm. Bone and soft tissue window algorithm images were obtained in the axial plane with additional sagittal and coronal reconstructed images.

Image postprocessing and image analysis

Post‑processing and image interpretation were performed with a commercial software program (Syngo.via, VB10, Siemens Healthineers) to create material-selective images to perform post-processing, where MSU depositions were color-coded as green, cortical bone were color-coded as blue and trabecular bone were color-coded as purple. Prior to the beginning of the study, 30 training cases (15 gout cases and 15 control cases) were used to familiarize observer with the Gout DECT software. These 30 training cases were excluded from the final analysis. When the observer measured the volume of MSU crystal deposition, artifacts such as nail beds, skin, submillimeter, motion, and beam hardening were removed manually because they are easy to identify [26].

For the evaluation of inter-observer agreement, two radiologists (C. X. T. and X. Y. Z. with 8 and 2 years experiences in DECT interpretation) who were blinded to all clinical features including gout status and serum urate results, recorded the sites, numbers and volume of urate deposition using the DECT software in 100 randomly selected cases independently. Then, one radiologist (X. Y. Z.) evaluated the remaining cases. Volume and numbers of MSU deposition on DECT were recorded for specific anatomical locations (hands/wrists, feet/ankles, knees, elbows and kidneys), different parts of each anatomical location (bone cortex, the surrounding soft tissues and the joint cavity). The numbers of MSU deposition were recorded, one separated MSU deposit or multiple deposits with continuous border on the DECT was regarded one, or else they were defined as two and above. The representative cases are shown in Fig. 2.

(A) Gout patient, urate volume of knees is 17.59 cm³. (B) Gout patient, urate volume of feet/ankles is 29.39 cm³. (C, D) The MPR figures of the corresponding locations of Panels A and B. (E) Hyperuricemia patient, urate volume of knees is 1.75 cm³. (F) Hyperuricemia patient, urate volume of feet/ankles is 0.42 cm³. (G, H) MPR figures of the corresponding locations of Panels E and F. Panels A-D are from the same gout patient, while Panels E-H are from the same hyperuricemia patient. Green indicates urate; blue indicates cortical bone; purple indicates trabecular bone.

Follow-up visits

The follow-up was performed after the first DECT examination if appropriate, the last clinical visit was considered at the end point. The baseline and follow-up EGFR values were recorded. It is appropriate if the interval of baseline estimated glomerular filtration rate (eGFR) and DECT examination was within one week. The endpoint of interest was renal insufficiency, defining as eGFR < 90 (mL/min/1.73m²) by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula at follow-up [27].

Statistical analysis

All statistical data were analyzed using SPSS V.23 (SPSS, Chicago, Illinois, USA) software. The Kolmogorov-Smirnov test was conducted to assess the normality of quantitative data. Quantitative variables were expressed as mean ± SD if normally distributed. Categorical variables were expressed as frequencies or percentages with differences analyzed using Chi-squared test or Fisher’s exact test, as appropriate. For normally distributed data, independent sample t-tests were used for the comparisons between two groups. The independent samples nonparametric test was used to analyze non-normally distributed data. Reliability was assessed using agreement statistics to obtain intra-class correlation coefficients. With regard to the calculation of the consistency analysis between readers, the study used kappa values to calculate the consistency of the sites, using the correlation coefficient within the group (intraclass correlation coefficient, ICC) to calculate the consistency of numbers and volumes. Differences between groups were analyzed using χ² analysis, or ANOVA tests if appropriate. The 95% confidence intervals were presented. All tests were two tailed and p < 0.05 was considered statistically significant.

Patient Characteristics

A total of 121 patients (men: 90%; mean age: 38 ± 16 years; range 13–85 years) with asymptomatic hyperuricemia and 521 patients (men: 95.4%; mean age: 47 ± 16 years; range 12–90 years) with gout were included in this study. Detailed clinical features of the participants can be seen in Table 1.

Table 1

Clinical features of the participants in this study
	Asymptomatic hyperuricemia (n = 121)		Symptomatic Gout (n = 521)	P value
Age, yrs	38 ± 16		47 ± 16	༜0.001
Sex (male), n (%)	108 (90%)		497 (95%)	0.022
Gout disease duration, yrs	NA		5 ± 5	NA
Chronic kidney disease, n (%)	5 (42%)		89 (52%)	0.488
Ischemic heart disease, n (%)	1 (14%)		9 (6%)	0.401
Heart failure, n (%)	0 (0%)		3 (2%)	0.705
Diuretic use, n (%)	1 (17%)		6 (4%)	0.176
Urate-lowering therapy, n (%)*	38 (90%)		216 (84%)	0.280
Duration of ULT, mths	0.5 ± 4.8		1.0 ± 4.0	0.326
BMI, kg/㎡	NA		23.1 ± 1.0	NA
Serum urate, µ mol/L	499.5 ± 123.8		515.6 ± 143.8	0.257
Serum creatinine, µ mol/L		83 ± 36	88 ± 45	0.005
Unless specified, data are presented as mean ± SD if normally distributed. Categorical variables were expressed as numbers (frequencies or percentages). * includes allopurinol and probenecid.
ULT = Urate-lowering therapy, BMI = body mass index.

DECT urate deposition analysis

Inter-reader agreement

The level of agreement between the two observers in measuring the sites of MSU deposition with DECT was moderate (k = 0.63). While the level of agreement between the two observers in measuring the volume and numbers of MSU deposition with DECT was high. The intraclass correlation coefficient (ICC) are 0.945 (in volume) and 0.996 (in quantity), respectively.

Comparison of MSU deposits between the gout and hyperuricemia groups

Overall, the volume and numbers of MSU deposition in the gout group was significantly higher than those in the hyperuricemia group both on a per-patient basis and on a per anatomical location basis (all P < 0.05) (Table 2). For each anatomical location, DECT urate deposition volume and numbers in gout group were observed more frequently in knees, feet and ankles than those in the asymptomatic hyperuricemia group (all P ≤ 0.050) (Table 2), but the MSU deposition at the elbows was significantly higher in the hyperuricemia group than that in the gout group (P < 0.001) (Table 2).

Table 2

Volume and number of MSU deposition in the asymptomatic hyperuricemia and symptomatic gout patient groups
Location	Asymptomatic HUA (n = 121)	Symptomatic Gout (n = 521)	P value
DECT MSU Volume, cm³
All patients	1.11 ± 5.27	2.48 ± 8.16	0.023
Male (n = 606)	1.11 ± 5.53	2.54 ± 8.33	0.028
Female (n = 36)	1.02 ± 1.55	1.05 ± 3.04	0.976
Anatomical locations
Hands/Wrists (n = 127)	0.04 ± 0.10	0.60 ± 2.32	0.366
Elbows (n = 19)	28.12 ± 39.77	3.31 ± 4.11	༜0.001
Knees (n = 225)	0.33 ± 0.66	2.01 ± 5.41	0.047
Kidneys (n = 159)	0.00 ± 0.00	0.00 ± 0.01	0.461
Feet/Ankles (n = 597)	0.56 ± 1.50	1.53 ± 5.16	0.050
Average value	0.60 ± 3.92	1.36 ± 4.65	0.013
DECT MSU Number, n All patients	10.69 ± 10.00	17.52 ± 27.19	༜0.001
Male (n = 606)	10.72 ± 9.55	17.84 ± 27.37	༜0.001
Female (n = 36)	10.42 ± 14.02	10.96 ± 22.47	0.940
Anatomical locations
Hands/Wrists (n = 127)	1.35 ± 3.46	6.54 ± 13.86	0.167
Elbows (n = 18)	NA	NA	NA
Knees (n = 224)	5.02 ± 4.93	9.81 ± 13.55	0.027
Kidneys (n = 159)	0.00 ± 0.00	0.04 ± 0.23	0.254
Feet/Ankles (n = 596)	9.54 ± 9.28	12.62 ± 14.72	0.035
Average value	5.88 ± 8.09	9.76 ± 13.98	༜0.001
HUA = hyperuricemia; MSU = monosodium urate.

The effect of sex on MSU deposition

For male patients, the same results as above-mentioned were observed (Table 2). There were no significant differences in volume (P = 0.366, P = 0.461) and numbers (P = 0.167, P = 0.254) of MSU deposition between other parts when comparing 2 groups (Table 2). For female patients, there were no significant differences in volume (P = 0.976) and numbers (P = 0.940) of MSU deposition among all the locations when comparing 2 groups (Table 2).

Distribution of MSU deposition in bone cortex, soft tissue and joint cavity

In the gout group, the MSU deposition in the soft tissue of the elbow was significantly higher than that of bone cortex and joint cavity (P = 0.005, P < 0.001) (Table 3). In the hyperuricemia group, the bone MSU deposition at both knees (P = 0.028, P = 0.007) and feet was significantly higher than those in soft tissue and joint cavity (P = 0.025, P = 0.001) (Table 3). There was no significant difference in the three parts of MSU deposition in the other parts of the two groups (all P > 0.05) (Table 3). In the gout group, MSU deposition was more likely to be deposited on the right elbow (volume significantly higher than other parts) (P < 0.05), while in the hyperuricemia group, the deposition of bilateral elbows was the heaviest (significantly higher than other parts) (all P < 0.05) (Fig. 3).

Table 3

The distribution and burden of volume (units:cm³) of MSU deposition in the symptomatic gout group and the asymptomatic hyperuricemia group
Location	Bone Cortex (n = 1582)	Soft Tissue (n = 1793)	Joint Cavity (n = 1579)	P Value
Gout Group Hands/Wrists
Left Right	0.045 ± 0.155 0.070 ± 0.415	0.216 ± 1.308 0.148 ± 0.726	0.110 ± 0.757 0.021 ± 0.122	0.337 0.147
Elbows
Left Right	0.012 ± 0.045 0.007 ± 0.023	1.254 ± 2.054 2.392 ± 2.700	0.000 ± 0.000 0.000 ± 0.000	0.005 ༜0.001
Knees
Left	0.355 ± 0.899	0.367 ± 1.368	0.275 ± 2.045	0.820
Right	0.251 ± 0.598	0.434 ± 1.464	0.349 ± 1.987	0.493
Feet/Ankles Left Right	0.292 ± 1.420 0.242 ± 0.899	0.294 ± 1.478 0.260 ± 1.303	0.185 ± 1.280 0.271 ± 1.996	0.381 0.959
HUA Group
Hands/Wrists
Left Right	0.007 ± 0.024 0.001 ± 0.003	0.012 ± 0.045 0.019 ± 0.048	0.000 ± 0.000 0.000 ± 0.000	0.558 0.132
Elbows
Left Right	0.095 ± 0.134 0.50 ± 0.071	10.36 ± 14.19 17.94 ± 25.37	0.000 ± 0.000 0.000 ± 0.000	0.467 0.466
Knees
Left	0.091 ± 0.274	0.022 ± 0.042	0.001 ± 0.005	0.028
Right	0.194 ± 0.521	0.022 ± 0.045	0.000 ± 0.000	0.007
Feet/Ankles Left Right	0.167 ± 0.578 0.204 ± 0.588	0.062 ± 0.305 0.088 ± 0.535	0.027 ± 0.234 0.015 ± 0.149	0.025 0.010
HUA = hyperuricemia; MSU = monosodium urate.

(A) Volume with urate deposition at different sites in the symptomatic gout group and asymptomatic hyperuricemia group in male patients. The MSU deposition of the elbows in hyperuricemia group is significantly higher than the gout group (P < 0.05). Within each group, the MSU deposition of the elbows is significantly higher than the hands, knees, kidneys and feet (all P < 0.05). (B) Volume with urate deposition at different sites in the asymptomatic hyperuricemia group and symptomatic gout group in the female patients. The MSU deposition of the knees in gout group is significantly higher than that in the hyperuricemia group (all P < 0.05).

Follow-up visits

A total of 59 patients (men: 84.7%; mean age: 41 ± 19 years; range 18–90 years) were followed up in a median 2-year duration, including 7 patients with hyperuricemia, all of whom had normal renal function at follow up then were excluded. The remaining 52 gout patients were divided into the renal insufficiency group (n = 15) and the normal renal function group (n = 37). Univariable analysis showed the patients’ age in renal insufficiency group was significantly older (P < 0.001) and the incidence of chronic kidney disease (CKD) (P = 0.023) was higher than those of normal kidney function group (Table 4), no significant differences were found for any other variables including BMI, diuretic use, disease characteristics and MSU volume assessed with DECT (all P > 0.05) (Table 4).

Table 4

Baseline characteristics of the gout patients with and without renal insufficiency during follow-up
Characteristics	Patients with normal RF (n = 37)	Patients with renal insufficiency (n = 15)
Demographics
Age, yrs	34.4 ± 9.2	62.7 ± 22.5	༜0.001
Sex (male), n (%)	37(100%)	13 (86.7%)	0.079
BMI, kg/m²	25.1 ± 1.6	26.1 ± 3.7	0.642
Serum Creatine, µ mol/L	90.8 ± 32.4	73.7 ± 12.3	0.054
Disease characteristics
Gout disease duration, yrs	3.3 ± 3.7	3.0 ± 3.3	0.836
ULT, n (%)*	16 (88.9%)	6 (75%)	0.563
Serum urate, µ mol/L	475.7 ± 122.5	489.7 ± 129.6	0.716
DECT MSU volume, cm³ All patients Male (n = 50) Female (n = 2)	0.80 ± 2.35 0.80 ± 2.35 NA	1.12 ± 2.94 1.29 ± 3.14 0.01 ± 0.01	0.678* 0.553* NA
Anatomical locations
Hands/Wrists (n = 12)	0.07 ± 0.22	0.03 ± 0.04	0.788*
Knees (n = 20)	0.33 ± 0.58	0.22 ± 0.48	0.722*
Kidneys (n = 18)	0.00 ± 0.00	0.00 ± 0.00	NA
Feet/Ankles (n = 47)	0.75 ± 2.36	1.02 ± 2.95	0.731*
Average value	0.45 ± 1.68	0.66 ± 2.31	0.629*
DECT = dual-energy computed tomography, MSU = monosodium urate, CKD = Chronic kidney disease, IHD = Ischemic heart disease, ULT = Urate-lowering therapy, BMI = body mass index. *means significance of the DECT MSU volume of the p value.

Significance of the p value was set at 5% are in bold.

Our study explored the burden and distribution of MSU deposition in symptomatic gout and asymptomatic hyperuricemia with DECT and compared renal function in gout patients in follow-up DECT. We observed the following important results: 1) The MSU deposition in the gout group was significantly higher than that in the hyperuricemia group except for the elbows. 2) MSU deposition in the knees and feet was significantly higher in the gout group than the hyperuricemia group. 3) In the hyperuricemia group, the MSU deposits at the cortical cortex of the knee and foot/ankle were both significantly higher than those in the soft tissue and joint cavity. 4) The extent of MSU burden measured with DECT was not predictive of the renal insufficiency in gout patients in our study.

The lower MSU deposition in hyperuricemia than gout group in this study is in line with the previous study [6], supporting the concept that urate deposition precedes clinical gout [29]. This also reminds us that DECT can be used to better monitor and manage patients with hyperuricemia in our clinical work. We should pay more attention to the burden of MSU deposition in patients with hyperuricemia, which may has certain clinical indications for predicting the development of hyperuricemia into gout. So is there a cutoff for MSU deposition between asymptomatic hyperuricemia and symptomatic gout? What is the critical value and where does it exist? These questions deserve further exploration in our future research.

While our sample size is large, supporting that the MSU deposition of symptomatic gout in the feet and knees are more frequently than asymptomatic hyperuricemia [6]. This may imply that the distribution of MSU deposits in the knee and foot is more discriminative for patients with asymptomatic hyperuricemia and those with gout. Perhaps the deposition in these parts is more clinically indicative. In normal clinical work, we should pay more attention to the follow-up and observation of the knees and feet of patients with hyperuricemia, so as to precisely prevent, diagnose and treat potential gout in time.

In the hyperuricemia group, the MSU deposits at the cortical cortex of the knee and foot/ankle were both significantly higher than those in the soft tissue and joint cavity. This means that in practice, it will be more clinically meaningful to observe the bone changes and structural functions of these key location(knees, feet and ankles) of patients with hyperuricemia. The research on bone changes in these parts should also be more in-depth, which is not only conducive to refined clinical management, but may also reveal the deeper mechanisms and reasons behind the progression of hyperuricemia to gout.

The MSU crystal deposition of the elbow in patients with hyperuricemia was much higher than that of gout patients, which is contrary to the previous observations [23, 24] and overall results of other anatomical sites. This may be due to the deviation caused by the small sample size of the elbow DECT examinations or the different MSU sedimentary distributions of different diseases. It is possible because our finding is attributed to the long-term use of urate-lowering drugs which can be reported in most gout patients in our study. In the gout group, the MSU burden on the right elbow was the severest, significantly higher than the MSU burden at all other sites, where the deposition of soft tissue was significantly higher than in the bone cortex and joint cavity. While the previous study showed that the elbow, suprapatellar bursa, and ankle collateral ligaments were among the least common of the affected sites [29]. This may be a statistical artefact of outliers due to the small sample size of the elbow and selection bias of anatomical regions.

To the best of our knowledge, this is the largest sample study to estimate the burden of MSU deposition distribution using DECT and the first study to explore whether the extent of MSU burden can be predictive of the renal insufficiency in gout. However, we observed that the extent of MSU burden measured with DECT was not predictive of the renal insufficiency in gout patients.

We have to acknowledge that our study has several limitations. The main shortfall of this study is a selection bias of anatomical regions and patients. There may be a selection bias as we included only patients with DECT. Besides, not all regions were imaged in all patients. This fact must be considered for the analysis, especially when comparing the tophus volume of different anatomical regions. Furthermore, selection bias can be present in our study because our study enrolled the patients from one single hospital.

Besides, our study is retrospective, thus many variables were missing. This resulted in a small sample size in our follow-up study which may not clarify the relationship between the MSU burden and renal function decline during the follow-up. Thus, prospective large cohort study is needed to uncover the role of DECT MSU burden in predicting renal function decline in future. Moreover, the accuracy of DECT is different for different anatomical locations, and the sample size of some anatomical locations is small. Thus, it is rational to collect more anatomical locations to observe MSU distribution. What’s more, for the first time, we divided a single joint into different parts (cortical bone, soft tissue and joint cavity), but whether DECT can fully and accurately distinguish the distribution of MSU in different components lacks corresponding clinical application, and further data support and verification are needed.

Last but not least, the short follow-up duration in this study (the mean follow-up time was 2 years) was not sufficient to verify the relationship between MSU deposition and renal insufficiency in gout patients.

In conclusion, this large cohort retrospective study showed the systemic distribution and burden of urate deposition in symptomatic gout and asymptomatic hyperuricemia with advanced DECT technique. However, our limited data indicated MSU burden measured by DECT was not predictive of renal function decline in gout patients. These findings encourage the study of MSU deposition in specific sites (knee, foot and ankle) reaching a certain threshold may have clinical implications for the progression of hyperuricemia to gout, revealing the mechanism by which asymptomatic hyperuricemia develops into symptomatic gout, so as to prevent, diagnose and treat gout in a more targeted and timely manner.

BMI

body mass index

CKD

Chronic kidney disease

DECT

dual-energy computed tomography

HUA

hyperuricemia

IHD

Ischemic heart disease

MSU

monosodium urate

ULT

Urate-lowering therapy

Ethical Approval and Consent to participate

This retrospective study was approved by the institutional review board of Jinling Hospital, Medical School of Nanjing University. Written informed consent was waived.

Consent for publication

Not applicable.

Availability of supporting data

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

This work was supported by funding from The National Key Research and Development Program of China (2017YFC0113400 for L.J.Z.).

Authors' contributions

Xin Yu Zhang, Chun Xiang Tang and Fan Zhou had equal contribution to this work.

Xin Yu Zhang, Chun Xiang Tang and Fan Zhou wrote the main manuscript text. Pin Hua Lin, Chang Qing Yin and Qin Yue Gao collected and measured the main data. Lei Lei Zhou and Chang Sheng Zhou prepared Figures 1-3. Long Jiang Zhang reviewed and revised the article. All authors reviewed the manuscript.

Acknowledgements

The authors thank Pin Hua Lin for collecting and measuring the primary data.

Authors' information

Xin Yu Zhang, Chun Xiang Tang and Fan Zhou contributed equally to this work.

Affiliations

Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China.

Xin Yu Zhang, Chun Xiang Tang, Fan Zhou, Chang Qing Yin, Qin Yue Gao, Chang Sheng Zhou, Guang Ming Lu, Long Jiang Zhang

Nanjing Brain Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210093, China.

Pin Hua Lin

Department of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, China.

Xin Yu Zhang, Lei Lei Zhou

Neogi T, Jansen TL, Dalbeth N, Fransen J, Schumacher HR, Berendsen D, Brown M, Choi H, Edwards NL, Janssens HJ, Lioté F, Naden RP, Nuki G, Ogdie A, Perez-Ruiz F, Saag K, Singh JA, Sundy JS, Tausche AK, Vazquez-Mellado J, Yarows SA, Taylor WJ. 2015 Gout Classification Criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 2015;74:1789–1798.
Zhu Y, Pandya BJ, Choi HK. Prevalence of gout and hyperuricemia in the US general population: the National Health and Nutrition Examination Survey 2007–2008. Arthritis Rheum 2011;63:3136–3141.
Khanna D, Fitzgerald JD, Khanna PP, et al. 2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis Care Res 2012;64:1431–46.
Campion EW, Glynn RJ, DeLabry LO. Asymptomatic hyperuricemia. Risks and consequences in the Normative Aging Study. Am J Med 1987;82:421–6.
Wang P, Smith SE, Garg R, et al. Identification of monosodium urate crystal deposits in patients with asymptomatic hyperuricemia using dualenergy CT. RMD Open 2018;4:e000593.
Dalbeth N, House ME, Aati O, Tan P, Franklin C, Horne A, Gamble GD, Stamp LK, Doyle AJ, McQueen FM. Urate crystal deposition in asymptomatic hyperuricaemia and symptomatic gout: a dual energy CT study. Ann Rheum Dis 2015;0:1–4.
Kuo CF, Grainge MJ, Mallen C, Zhang W, Doherty M. Comorbidities in patients with gout prior to and following diagnosis: case-control study. Ann Rheum Dis 2016;75(1):210–217.
Puig JG, Martinez MA. Hyperuricemia, gout and the metabolic syndrome. Curr Opin Rheumatol 2008;20:187–191.
Abbott RD, Brand FN, Kannel WB, Castelli WP. Gout and coronary heart disease: the Framingham Study. J Clin Epidemiol 1988;41:237–242.
De Vera MA, Rahman MM, Bhole V, Kopec JA, Choi HK. Independent impact of gout on the risk of acute myocardial infarction among elderly women: a population based study. Ann Rheum Dis 2010;69:1162–1164.
Krishnan E, Baker JF, Furst DE, Schumacher HR. Gout and the risk of acute myocardial infarction. Arthritis Rheum 2006;54:2688–2696.
Kuo CF, Yu KH, See LC, Chou IJ, Ko YS, Chang HC, Chiou MJ, Luo SF. Risk of myocardial infarction among patients with gout: a nationwide population-based study. Rheumatology (Oxford) 2013;52:111–117.
Yu KH, Kuo CF, Luo SF, See LC, Chou IJ, Chang HC, Chiou MJ. Risk of end-stage renal disease associated with gout: a nationwide population study. Arthritis Res Ther 2012; 18;14(2):R83.
Domrongkitchaiporn S, Sritara P, Kitiyakara C, Stitchantrakul W, Krittaphol V, Lolekha P, Cheepudomwit S, Yipintsoi T. Risk factors for development of decreased kidney function in a southeast Asian population: a 12-year cohort study. J Am Soc Nephrol 2005;16: 791–799.
Obermayr RP, Temml C, Knechtelsdorfer M, Gutjahr G, Kletzmayr J, Heiss S, Ponholzer A, Madersbacher S, Oberbauer R, Klauser-Braun R. Predictors of new-onset decline in kidney function in a general middle European population. Nephrol Dial Transplant 2008; 23:1265–1273.
Obermayr RP, Temml C, Gutjahr G, Knechtelsdorfer M, Oberbauer R, Klauser-Braun R. Elevated uric acid increases the risk for kidney disease. J Am Soc Nephrol 2008;19: 2407–2413.
Krishnan E. Chronic kidney disease and the risk of incident gout among middle-aged men: a seven-year prospective observational study. Arthritis Rheum 2013;65:3271–3278.
Borghi C, Rosei EA, Bardin T, Dawson J, Dominiczak A, Kielstein JT, Manolis AJ, Perez-Ruiz F, Mancia G. Serum uric acid and the risk of cardiovascular and renal disease. J Hypertens 2015;33:1729–1741.
Daoussis D, Panoulas V, Toms T, John H, Antonopoulos I, Nightingale P, Douglas KM, Klocke R, Kitas GD. Uric acid is a strong independent predictor of renal dysfunction in patients with rheumatoid arthritis. Arthritis Res Ther 2009;11(4):R116.
Annals of the Rheumatic Diseases. 2016 updated EULAR evidencebased recommendations for the management of gout. http://ard. bmj.com/content/early/2016/07/25/annrheumdis-2016-209707 (accessed 4 Aug 2017).
Swan A, Amer H, Dieppe P. The value of synovial fluid assays in the diagnosis of joint disease: a literature survey. Ann Rheum Dis 2002;61:493–8.
Newberry SJ, FitzGerald JD, Motala A, et al. Diagnosis of gout: a systematic review in support of an American College of Physicians Clinical Practice Guideline. Ann Intern Med 2017;166:27.
Choi HK, Al-Arfaj AM, Eftekhari A, Munk P L, Shojania K, Reid G, Nicolaou S. Dual energy computed tomography in tophaceous gout. Ann Rheum Dis 2009;68:1609–1612.
Choi HK, Burns LC, Shojania K, Koenig N, Reid G, Abufayyah M, Law G, Kydd AS, Ouellette H, Nicolaou S. Dual energy CT in gout: a prospective validation study. Ann Rheum Dis 2012;71:1466–1471.
Glazebrook KN, Guimarães LS, Murthy NS, Black DF, Bongartz T, Manek NJ, Leng S, Fletcher JG, McCollough CH. Identification of intraarticular and periarticular uric acid crystals with dual-energy CT: initial evaluation. Radiology 2011;261:516–524.
Mallinson PI, Coupal T, Reisinger C, Chou H, Munk PL, Nicolaou S, Ouellette H. Artifacts in dual-energy CT gout protocol: a review of 50 suspected cases with an artifact identification guide. AJR Am J Roentgenol 2014;203:W103-109.
Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150:604–612.
Pascual E, Addadi L, Andrés M, Sivera F. Mechanisms of crystal formation in gout—a structural approach. Nat Rev Rheumatol 2015;11(12):725–730.
Mallinson PI1, Reagan AC, Coupal T, Munk PL, Ouellette H, Nicolaou S. The distribution of urate deposition within the extremities in gout: a review of 148 dual-energy CT cases. Skeletal Radiol 2013;1771–1778.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Burden and Distribution of MSU Deposition in Patients with Hyperuricemia and Gout: A Large Cohort Chinese Population Based DECT Study

Status:

Version 1

Abstract

Objectives

Methods

Results

Conclusions

Figures

Introduction

Methods

Study Population

DECT scans

Image postprocessing and image analysis

Follow-up visits

Statistical analysis

Results

Patient Characteristics

DECT urate deposition analysis

Inter-reader agreement

Comparison of MSU deposits between the gout and hyperuricemia groups

The effect of sex on MSU deposition

Distribution of MSU deposition in bone cortex, soft tissue and joint cavity

Follow-up visits

Discussion

Conclusion

Abbreviations

Declarations

Affiliations

References

Additional Declarations

Status:

Version 1