Predictors of Stone-Related Events in Asymptomatic Untreated Intrarenal Calculi

Abstract

Purpose:

There is a lack of data on the natural history of asymptomatic intrarenal calculi. In this study, we investigate stone-related events (SREs) in patients with untreated intrarenal calculi. We also investigate predictive factors for SREs.

Methods:

All patients found with an asymptomatic intrarenal calculus on CT kidney, ureter, bladder managed conservatively with interval imaging for ≥6 months were included. Patients were evaluated for any SRE. The rate of event according to calculus size, location, and number of calculi was also analyzed. Multivariate logistic regression analysis was performed to determine significant predictors for SREs.

Results:

In total, 266 renal units from 177 patients met inclusion criteria. The mean stone size was 4.44 mm (range 1–25 mm). Duration of follow-up was 43.78 ± 26.86 months (range 6–106 months). The overall rate of SREs, including intervention (n = 80) and spontaneous stone passage after ureteral colic (n = 40), was 45.1% (n = 120/266). Stones >5 mm were more likely to lead to an event compared with stones ≤5 mm (odds ratio [OR]: 2.94; p = 0.01). Interpolar stones and stones located in multiple calices were more likely to cause a SRE than lower pole stones (OR: 2.05; p = 0.05 and OR: 2.29; p = 0.03, respectively).

Conclusion:

In this large series of patients with asymptomatic intrarenal calculi, the incidence of a spontaneous SRE was 45.1% after 41 months. Stone size and stone location were significant predictors for a SRE. Information from this study will enable urologists to accurately risk stratify patients with asymptomatic renal stones.

Introduction

Urinary tract calculi is a common urologic condition with an incidence ranging from 4% to 20% in economically developed countries.^1,2 The variable incidence is caused by environmental, socioeconomic, and patient factors. The prevalence of asymptomatic renal stones in the general population is ∼3%³; however, there are no consensus guidelines on the management or follow-up of asymptomatic renal stones diagnosed incidentally on imaging, or detected concurrently when diagnosing symptomatic stones.⁴ Management options include active surveillance, extracorporeal shockwave lithotripsy (SWL), ureteroscopy, and percutaneous nephrolithotomy.⁵ Outcomes are variable for patients with asymptomatic urinary tract calculi undergoing surveillance, particularly in regard to key outcomes such as development of symptoms, stone growth, and rate of surgical intervention.^6
–8 The aim of this study is to evaluate the natural history of asymptomatic renal calculi managed with active surveillance by assessing stone-related events (SREs) and rates of intervention.

Methods

Study design

We retrospectively reviewed clinical notes and radiologic imaging for a period of 36 months between January 2014 and December 2016 in a single institution. The inclusion criteria were patients with nonobstructing asymptomatic renal caliceal stone(s) diagnosed on CT with ≥6 months of follow-up. All CT renal stone protocol reports within the study period to identify patients with renal stones. This was cross-checked with patients' clinical notes to identify patients who were asymptomatic and suitable for inclusion. When possible, we reviewed the earliest possible radiologic imaging of asymptomatic renal stones, which in some cases detected asymptomatic stones diagnosed before the study period. Exclusion criteria were patient preference for treatment over surveillance, nonattendance of follow-up, solitary kidney, and urinary tract abnormalities.

Stone-related events

All patients who opted for surveillance were followed up with interval imaging. This involved an annual kidney, ureter, bladder radiograph (KUB) at baseline with additional CT or ultrasonography as clinically indicated. We examined the natural history of asymptomatic renal stones managed with active surveillance. We investigated the rate of SREs that were defined as spontaneous stone passage, stone migration to ureter requiring intervention, and noncolic-related symptoms leading to intervention.

Measured parameters

We examined each renal unit separately in cases with bilateral stones undergoing surveillance. We collected data on stone characteristics (size [mm], location, and date of first and latest observation on radiologic imaging) and patient characteristics (age and gender) and SREs. We also evaluated the impact of gender, age, stone size (≤5 mm; 6–10 mm; >10 mm), laterality (unilateral/bilateral), stone position and stone burden, number of stones (single or multiple [>1 stone]), and laterality on the rate of SRE.

Statistical analysis

Numerical data are presented as mean ± standard deviation. Categorical data are given as numbers and percentages. Multivariate logistic regression analysis was performed to control for covariates and produce odds ratios (ORs) with confidence interval at 95% and significance values p ≤ 0.05 (SPSS 25.0 for Mac).

Results

Patient characteristics

All CT KUB protocols were reviewed from January 2014 to December 2016. In total, 424 renal units with intrarenal stones were identified. One hundred fifty-nine patients were excluded as the per the exclusion criteria (i.e., <6 months follow-up) and 266 renal units from 183 patients were included in the study. The patient characteristics are detailed in Table 1. The median age was 44 (range 19–84) years. The mean stone size was 4.44 mm (range of 1–25 mm). Stones were located in the lower pole in 32.7%, in the interpolar region in 22.9%, in the upper pole in 12.8%, renal pelvis in 3%, and in multiple intrarenal locations in 22.2%. In 6.4% of cases the stone location was not documented. Duration of follow-up was 43.78 ± 25.86 months (range 6–106 months).

Table 1.

Baseline Demographics of Patients with Asymptomatic Renal Calculi Managed with Active Surveillance

Variable	Value
Renal units	266
Age in years (range)	44.2 ± 13.8 (19–84)
Initial stone diameter in mm (range)	4.44 ± 3.6 (1–25)
Follow-up in months (range)	43.78 ± 25.86 (6–106)
Gender	N (%)
Male	179 (67)
Female	87 (33)
Age in years	N (%)
≤50	180 (67.7)
>50	86 (32.3)
Stone size	N (%)
0–5 mm	199 (74.8)
>5–10 mm	45 (16.9)
>10 mm	17 (6.4)
Unknown	5 (1.9)
Anatomical location	N (%)
Lower pole	87 (32.7)
Interpolar	61 (22.9)
Upper pole	34 (12.8)
Renal pelvis	8 (3.0)
Multiple	59 (22.2)
Unknown	17 (6.4)
No. of stones	N (%)
Single	115 (43.2)
Multiple	151 (56.8)
Laterality	N (%)
Left	140 (52.6)
Right	126 (47.4)
Unilateral/bilateral	N (%)
Unilateral	100 (37.6)
Bilateral	166 (62.4)

Stone-related events

The overall rate of SREs, including intervention (n = 80) and spontaneous stone passage after ureteral colic (n = 40), was 45.1% (n = 120/266). All patients with spontaneous stone passage had associated renal colic symptoms. When spontaneous stone passage was suspected by the resolution of renal colic symptoms, confirmation was performed with early follow-up imaging and outpatient review.

Of the intervention group, 82.5% (n = 66) were for ureteral colic, 15% (n = 12) were for asymptomatic stone growth, and 2.5% (n = 2) were attributable to patient preference in the absence of other indications. The methods of intervention were ureteroscopy in 83.75% (n = 67), SWL in 10% (n = 8), and a combination of ureteroscopy+SWL in 6.25% (n = 5). The median duration from diagnosis to intervention was 26.5 (range 1–103) months. For those in whom intervention was required, 31% (n = 25) had intervention ≤12 months after diagnosis. The median duration to a SRE in the nonintervention group was 29 (17–59 [IQR]) months.

Risk factors for SREs

Table 2 summarizes the identified significant risk factors for a SRE. Stones >5 mm were more likely to lead to a SRE compared with stones ≤5 mm (OR: 2.94; p = 0.01). The OR increased to 3.42 when stones >10 mm were compared with stones ≤5 mm (p = 0.03). Stone location was also associated with a SRE rate. Stones in the interpolar region and in multiple locations (i.e., multiple calices) were more likely than lower pole stones to lead to a SRE (OR: 2.05; p = 0.05 and OR: 2.29; p = 0.03, respectively). Table 3 summarized the rate of SRE according to stone location.

Table 2.

Risk Factors for Stone-Related Events Among Patients with Asymptomatic Renal Calculi Managed with Active Surveillance

Variable	Stone-related event
Gender	OR (95% CI)	p
Female	1^a
Male	0.99 (0.56–1.73)	0.97
Age in years
≤50	1 (Reference^a)
>50	0.66 (0.36–1.20)	0.17
Size of stones
1–5 mm	1 (Reference^a)
>5–10 mm	2.94 (1.38–6.27)	0.01
>10 mm	3.42 (1.13–10.31)	0.03
Unilateral/bilateral
Unilateral	1 (Reference^a)
Bilateral	1.76 (0.95–9.28)	0.07
Location
Lower	1 (Reference^a)
Interpolar	2.05 (1.01–4.16)	0.05
Upper	1.26 (0.53–3.03)	0.60
Pelvis	3.12 (0.50–19.60)	0.23
Multiple	2.29 (1.067–4.93)	0.03
No. of stones
Single	1 (Reference^a)
Multiple	1.03 (0.55–1.93)	0.93
Side
Left	1 (Reference^a)
Right	0.90 (0.51–1.59)	0.71

Statistically significant.

Corresponds to reference group for calculation of ORs.

CI = confidence interval; ORs = odds ratio.

Table 3.

Rate of Stone-Related Event According to Stone Location

Variable	Stone-related event
Location	N ^a (%)
Lower	30/87 (34.5%)
Interpolar	31/61 (50.08%)
Upper	12/34 (35.3%)
Pelvis	4/8 (50%)
Multiple	43/59 (72.9%)

Stone location was unknown in 17 patients (Table 1) leading to an analysis of n = 249 patients for stone-related event according to stone location.

Discussion

In one of the largest retrospective studies to date, we investigated the natural history of asymptomatic renal stones. We evaluated the effects of stone burden and distribution of asymptomatic renal stones on the rates of SREs. Our study found that asymptomatic renal stones managed with active surveillance have a significant rate of SREs (45.1%). We have also identified several risk factors for SREs. Patients with larger stones >5 mm, interpolar stones, and multicaliceal stone burden have a significantly higher rate of SREs. These findings are relevant as they will enable urologists to accurately risk stratify and counsel patients with asymptomatic renal stones when considering management with surveillance.

One early study by Glowacki et al. assessed 107 patients with asymptomatic renal stones and found that 31.8% developed symptoms. Of the 31.8% that developed stone-related symptoms, 16.8% required intervention after a mean follow-up of 31.6 months.⁹ Burgher et al. also investigated the outcomes of asymptomatic renal stones under observation.⁷ Their study, on 300 patients with asymptomatic renal stones, found a SRE rate of 77% and an intervention rate of 26% with a mean follow-up of 3.26 years.⁷ More recently, the natural history of asymptomatic renal stones was investigated by Dropkin et al. in 110 patients with 160 stones.⁶ In this cohort, mean stone size was 7.0 ± 4.2 mm and mean follow-up was 41 ± 19 months. In total, 72% of patients remained asymptomatic and 17% required surgical intervention for symptomatic renal colic or symptomatic obstruction.⁶

Predictive factors for SRE enable clinicians to accurately counsel patients when considering management of asymptomatic renal stones. Our findings of stone location and stone size being predictive for a SRE follow from previous trends. In a smaller study, Koh et al.¹⁰ evaluated the outcomes of asymptomatic renal stones in a cohort of 50 patients. The authors measured the rates of stone growth, stone passage, and surgical intervention at 45.9%, 20%, and 7.9%, respectively.¹⁰ The association between stone location and size, and the need for intervention was also investigated, and a nonsignificant trend for interpolar stones and larger stones toward surgical intervention was noted. Both findings are consistent with the results described herein.

Kanno et al. investigated the effect of stone size (i.e., ≤5 mm and >5 mm) on the natural history of asymptomatic renal stones in 207 patients and also found a trend for higher intervention rates in larger stones.¹¹ Dropkin et al. found that stone size and stone growth were not predictors for a SRE. However, lower pole location was associated with a lower rate of symptom development and intervention⁶ in keeping with our findings. Darrad and associates also recently investigated asymptomatic renal stones in 238 patients with 301 stone containing renal units. Patient factors predictive for a low risk of intervention were age <50 years and no stone growth on follow-up. In contrast to our findings stone location and size did not predict an SRE in their study.¹²

It is frequently questioned whether asymptomatic renal stones should be followed up and/or treated.^13,14 We would advocate elective urologic intervention in patients with predictive risk factors. Three early retrospective studies also demonstrated similar findings where expectant management of asymptomatic renal stones was associated with development of symptoms (32%, 68%, and 53.6%, respectively), and necessity for intervention (16.8%, 40%, and 24.5%, respectively).^9,15,16 There is also no consensus on an appropriate follow-up schedule for asymptomatic renal stones.¹³ CT KUB is undoubtedly the most sensitive imaging modality for characterizing stone burden; however, clinicians need to be practical in terms of its usage and risk of radiation exposure. We believe that plain film KUB and/or ultrasonography have a strong follow-up role as they are effective for monitoring larger intrarenal stones that are more likely to result in a SRE.¹⁷

There are some limitations to our study, including its retrospective nature. The study was performed in a single center and included a relatively small geographical region. In addition, 154 patients were excluded because of ≤6 months follow-up. These patients may have sought treatment elsewhere or remained asymptomatic, which may have led to a selection bias toward the SRE group. The statistical analysis used assessed the impact of individual factors on the rate of SRE while controlling for possible confounding variables. These do not calculate the cumulative risk when multiple risk factors are present in the same patient. However, in our study comprehensive follow-up of all patients who underwent surveillance of an asymptomatic renal calculus was maintained for a prolonged period and no included patients were lost to follow-up.

Conclusion

Active surveillance is a commonly used management strategy for asymptomatic renal stones. We demonstrate that patients with asymptomatic renal stones have a high rate of SREs and intervention (45% and 30%, respectively); with 21% of patients having a SRE within 12 months of surveillance. Stone size and stone location can be used to risk stratify patients on the likelihood of a SRE with stone size >5 mm, interpolar location, and multicaliceal stone burden predicting a higher rate of event. These results will enable informed clinical decision-making for the management of asymptomatic renal stones.

Footnotes

Authors' Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by K.D., M.H., and M.L. The first draft of the article was written by K.D. and all authors commented on previous versions of the article. All authors read and approved the final article. Project development, data collection, and article writing by K.D. and M.H. Data analysis and article writing by M.L. and E.M. Project development and article writing by M.R.Q. and N.F.D. Article writing by M.T.W. and A.S.

Availability of Data and Material

Stored on institutional network for patient data protection.

Ethical Approval

Institutional review board approval granted.

Consent to Participate

Not applicable, retrospective review.

Consent for Publication

Not applicable, retrospective review.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

Abbreviations Used

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