Clinical Epidemiology

Symptomatic and Radiographic Manifestations of Kidney Stone Recurrence and Their Prediction by Risk Factors: A Prospective Cohort Study

Matthew R. D’Costa, William E. Haley, Kristin C. Mara, Felicity T. Enders, Terri J. Vrtiska, Vernon M. Pais, Steven J. Jacobsen, Cynthia H. McCollough, John C. Lieske and Andrew D. Rule
JASN July 2019, 30 (7) 1251-1260; DOI: https://doi.org/10.1681/ASN.2018121241

Significance Statement

Kidney stone recurrence can manifest with symptoms from stone passage or with asymptomatic changes in kidney stone burden revealed by radiography. In a multicenter, prospective cohort study, the authors demonstrate that substantially more asymptomatic and self-managed symptomatic kidney stone recurrence occur in stone formers than has been appreciated, as many studies consider only symptomatic recurrence that results in clinical care. Among first-time symptomatic stone formers, 54% had an asymptomatic kidney stone; half of those with such a stone passed it within 5 years (but only half who did so experienced symptoms). The findings also show that when a more comprehensive definition of recurrence that includes all symptomatic and radiological manifestations is used, risk factors better predict kidney stone recurrence, thus supporting a comprehensive assessment of recurrence in clinical trials.

Abstract

Background Meaningful interpretation of changes in radiographic kidney stone burden requires understanding how radiographic recurrence relates to symptomatic recurrence and how established risk factors predict these different manifestations of recurrence.

Methods We recruited first-time symptomatic stone formers from the general community in Minnesota and Florida. Baseline and 5-year follow-up study visits included computed tomography scans, surveys, and medical record review. We noted symptomatic recurrence detected by clinical care (through chart review) or self-report, and radiographic recurrence of any new stone, stone growth, or stone passage (comparing baseline and follow-up scans). To assess the prediction of different manifestations of recurrence, we used the Recurrence of Kidney Stone (ROKS) score, which sums multiple baseline risk factors.

Results Among 175 stone formers, 19% had symptomatic recurrence detected by clinical care and 25% detected by self-report; radiographic recurrence manifested as a new stone in 35%, stone growth in 24%, and stone passage in 27%. Among those with a baseline asymptomatic stone (54%), at 5 years, 51% had radiographic evidence of stone passage (accompanied by symptoms in only 52%). Imaging evidence of a new stone or stone passage more strongly associated with symptomatic recurrence detected by clinical care than by self-report. The ROKS score weakly predicted one manifestation—symptomatic recurrence resulting in clinical care (c-statistic, 0.63; 95% confidence interval, 0.52 to 0.73)—but strongly predicted any manifestation of symptomatic or radiographic recurrence (5-year rate, 67%; c-statistic, 0.79; 95% confidence interval, 0.72 to 0.86).

Conclusions Recurrence after the first stone episode is both more common and more predictable when all manifestations of recurrence (symptomatic and radiographic) are considered.

Available strategies to prevent the recurrence of symptomatic kidney stones include dietary and medical interventions designed to decrease the urinary supersaturation of crystals that contribute to stone formation and growth. The formation and growth of a kidney stone occurs silently without symptoms, detectable only by serial imaging, until a previously asymptomatic stone migrates toward or into the ureter where symptomatic renal colic can occur from ureteral obstruction. This can result in a patient presenting for clinical care, particularly if the pain is severe. Patients may also develop symptomatic recurrence that is self-managed. Furthermore, kidney stones can form, grow, and even pass without symptoms. Figure 1 shows the relationship between different manifestations of recurrence.

Figure 1.
Figure 1.

The relationship between different symptomatic and radiographic manifestations of recurrence.

Clinical trials on the prevention of kidney stone recurrence often combine symptomatic and radiographic recurrence as a composite end point.1 However, the validity and agreement of different manifestations of recurrence is poorly understood, and the definition of recurrence varies widely in the literature.2 Symptomatic recurrence detected by clinical care may miss self-managed recurrent episodes, whereas symptomatic recurrence detected by self-report on a survey may incorrectly attribute pain from other causes to stone passage. Radiographic recurrence detected as a new stone, stone growth, or stone passage over time between imaging studies is difficult to interpret when clinically ordered studies are used because radiographic recurrence on the basis of usual clinical care is prone to selection bias (more severe stone disease often leads to more frequent follow-up imaging) and detection bias (imaging more likely to be done when patient is symptomatic). Mixed imaging modalities with different resolutions to detect stones are also often used.3,4 A prospective population-based cohort study of first-time symptomatic kidney stone formers using “gold-standard” computed tomography (CT) imaging to detect stones may help clarify the rate and relationship between different manifestations of recurrence.

To this end, we enrolled first-time symptomatic stone formers for a baseline visit and a 5-year follow-up visit with goals of comparing symptomatic recurrences by clinical care and self-report, determining how symptomatic recurrence associates with radiographic recurrence, and determining how established risk factors predict different manifestations of recurrence.

Methods

Study Population

Under institutional review board approval, clinical databases were continuously surveyed for kidney stone diagnostic codes or the term “kidney stone” (or synonym) in electronic medical records to identify and recruit first-time adult stone formers from the general community in Minnesota and Florida. The medical records of identified patients were reviewed to validate a confirmed symptomatic kidney stone episode (pain or gross hematuria with a ureter obstructing stone seen on imaging or with a voided stone seen after passage). Stone formers recruited at the Minnesota site had to live in Olmsted County or an adjacent county and were identified using the resources of the Rochester Epidemiology Project.5 Thus these stone formers received their medical care from an Olmsted County provider. Stone formers recruited at the Florida site had to live within 100 miles of Mayo Clinic in Florida and receive their medical care there. All participants were adults (age ≥18 years) with a signed informed consent. Stone formers were recruited from January 1, 2009 to March 15, 2013 for their baseline study visit, and from July 1, 2014 to December 31, 2017 for their 5-year follow-up study visit.

Study Design

Figure 2 shows the study design. The baseline CT scan of the kidneys was obtained as part of clinical care during the first symptomatic stone episode. The baseline study visit occurred after the first episode had resolved (stone surgically removed or resolution of symptoms) and included serum chemistries, 24-hour urine chemistries, and body mass index. The 5-year follow-up study visit included an administered survey that queried for symptomatic recurrence and a CT scan of the kidneys as part of the study protocol. Medical records of study participants were reviewed for any symptomatic recurrence that occurred between the first symptomatic stone episode and the 5-year follow-up study visit.

Figure 2.
Figure 2.

Prospective cohort study design.

Symptomatic Recurrence

Symptomatic recurrence by clinical care had to be confirmed (seen stone). Suspected symptomatic recurrence (pain or gross hematuria attributed by a clinician to a kidney stone but no obstructing or voided stone seen) was also identified. Symptomatic recurrence by self-report was determined by the survey response at the follow-up study visit. This included the questions “Have you ever had a second kidney stone episode?”, with queries for the month and year if “yes.” To avoid misclassifying the first symptomatic stone episode as more than one episode, we required all symptomatic recurrence by clinical care or self-report to be >60 days after the first symptomatic stone episode.

Radiographic Recurrence

Radiographic recurrence was defined by any new stone, any stone growth, or any stone passage at the 5-year follow-up CT scan compared with the baseline CT scan. A variety of clinical scanners were used for the baseline CT scan, but none used low-resolution imaging protocols.6 The 5-year follow-up CT scan was performed using a dual-energy CT scanner (Somatom Force; Siemens Healthcare, Forchheim, Germany) without intravenous contrast and with imaging limited to the kidneys. A computer-controlled automatic exposure control system (Care Dose 4D) was used to obtain the lowest patient-tailored radiation dose as well as maintaining diagnostic image quality. Parallel images from the baseline and follow-up CT scans were compared side-by-side by a single designated radiologist (T.J.V.) masked to any symptomatic recurrence. The manual measurement of the longest dimensions in the axial and coronal plane was recorded on all kidney stones at baseline and at follow-up. Each manifestation of radiographic recurrence was assessed: new kidney stone (only seen on follow-up CT scan), kidney stone growth (stone >1 mm larger in any dimension at follow-up than at baseline), or stone passage (seen only on baseline CT scan). Medical records were reviewed to ensure that all stone passage events were not owing to surgical removal of an asymptomatic kidney stone (including any surgery to treat the first symptomatic kidney stone episode).

Risk Factors for Recurrence

Risk factors for symptomatic recurrence resulting in clinical care were previously identified from the same region in Minnesota (Olmsted County), using a much larger retrospective cohort study design.7,8 These risk factors allowed generation of a Recurrence of Kidney Stone (ROKS) score, as published in 20147 and revised in 2018 (Figure 3).8 These risk factors include baseline demographics, stone symptoms, stone composition, and radiographic stone burden as listed in Table 1. Stone composition was classified into mutually exclusive groups as previously described.9 Each risk factor was assigned points and summed to calculate the ROKS score, which can be used to estimate the probability of symptomatic recurrence requiring clinical care. The ROKS score was then used as a predictor for each of the five recurrence outcomes. Participants underwent a fasting blood draw for serum chemistries and a 24-hour urine collection for urine chemistries at the baseline study visit (Table 1). Supersaturations for uric acid, calcium oxalate, brushite, sodium urate, and hydroxyapatite crystals were calculated using EQUIL2.10

Figure 3.
Figure 3.

The ROKS tool can be used to predict symptomatic recurrence after the first symptomatic stone episode.8 First, determine the total points on the basis of the sum of 13 predictors. Second, risk of symptomatic recurrence requiring clinical care at 5 years equals 1 – 0.820(−1.84089+ points ×0.01019).

View this table:
Table 1.

Baseline characteristics of incident symptomatic kidney stone formers

Statistical Analyses

The 5-year incidence rate of each manifestation of recurrence was reported. We assessed agreement (Cohen κ) between symptomatic recurrence at 5 years by clinical care versus by self-report. The association between each manifestation of symptomatic recurrence with each manifestation of radiographic recurrence was reported using odds ratios (ORs). The prediction of each manifestation of recurrence at 5 years by baseline ROKS score (per SD) was reported with both ORs (strength of association) and c-statistics (discriminatory power). Analyses were repeated after stratifying for the presence or absence of any asymptomatic kidney stone (not surgically removed) on the baseline CT scan. Analyses were also repeated using the earlier (2014) version of the ROKS score. Each 24 hour urine (after adjustment for age, sex, and urine creatinine) and serum chemistry (after adjustment for age and sex) measurement was assessed as a predictor of recurrence.

Results

Study Sample

Between January 1, 2009 and December 31, 2017 there were 334 study participants with a baseline study visit and at least 5 years of follow-up. The analysis was limited to the 175 study participants who participated in the 5-year follow-up study visit (148 from Minnesota and 27 from Florida) (Supplemental Figure 1). Compared with the historical cohort used to develop the ROKS tool,8 participants in this prospective cohort study had characteristics associated with both lower recurrence risk (older and less male) and higher recurrence risk (more obese, more family history of stones, and more severe stone burden)8 (Supplemental Table 1). Participants completed their baseline visit at a median 99 days after the first symptomatic stone episode, and their follow-up visit at a median 4.9 years after the first symptomatic stone episode. Baseline characteristics of this cohort are presented in Table 1. At the first symptomatic stone episode, 79 out of 175 (45%) participants underwent surgery for their kidney stone, 139 (79%) received fluid intake/dietary advice for stone prevention, and none were started on a stone prevention medications. The first symptomatic stone composition was known in 104 out of 175 (59%) participants. Stones with majority calcium oxalate occurred in 85 out of 104 (82%) participants, majority hydroxyapatite in 11 out of 104 (11%), any uric acid in seven out of 104 (6.7%), and any brushite in one out of 104 (1%); none were monogenic stone formers. There were 97 participants who had at least one asymptomatic kidney stone on their baseline CT scan, but three of these patients were excluded because all asymptomatic kidney stones were surgically removed. Thus, this cohort could be divided into those with at least one baseline asymptomatic kidney stone (94/175, 54%) and those with no baseline asymptomatic kidney stone (81/175, 46%). There were no significant differences in the nonimaging risk factors between these two subgroups (P>0.05 for all).

Symptomatic Recurrence

During the 5-year follow-up, symptomatic recurrence detected by clinical care occurred in 34 out of 175 (19%) participants and by self-report in 43 out of 175 (25%), with recurrence by either clinical care or self-report in 53 out of 175 (30%). Among participants with a self-reported symptomatic episode during the 5-year follow-up, 24 out of 43 (56%) participants also had a clinical care episode. Among the participants who did not self-report symptomatic recurrence over the 5-year follow-up, 122 out of 132 (92%) participants also lacked a clinical care episode. There was modest agreement between a self-reported episode and a clinical care episode (κ=0.519; 95% confidence interval [95% CI], 0.37 to 0.67). However, seven participants with a self-reported symptomatic recurrence also had clinical care for a stone that was only suspected. If clinical care for a suspected recurrence was also included, agreement improved (κ=0.637; 95% CI, 0.50 to 0.77).

Radiographic Recurrence

During the 5-year follow-up, radiographic recurrence by new stone formation occurred in 61 out of 175 (35%) participants, by stone growth in 42 out of 175 (24%), by stone passage in 46 out of 175 (26%), and by any form of radiographic recurrence in 103 out of 175 (59%). Presence of a new asymptomatic kidney stone on the 5-year follow-up imaging study visit was higher among those with a baseline asymptomatic kidney stone compared with those without (45% versus 23%; P=0.003). Among those with a baseline asymptomatic kidney stone, stone growth occurred in 42 out of 94 (43%) participants and stone passage occurred in 44 out of 94 (47%) during the 5-year follow-up. If stone growth occurred, stone passage was less likely to occur (OR, 0.36; 95% CI, 0.16 to 0.83); only possible when more than one asymptomatic kidney stone was present at baseline. Among those with a baseline asymptomatic kidney stone, new stone formation during follow-up did not associate with stone growth (OR, 1.27; 95% CI, 0.56 to 2.84) or with stone passage (OR, 0.79; 95% CI, 0.35 to 1.77) during the 5-year follow-up.

Symptomatic Recurrence with Radiographic Recurrence

Table 2 shows the association between symptomatic recurrence and radiographic recurrence during the same 5-year follow-up period. Symptomatic recurrence associated with new stone formation and stone passage but not stone growth. Symptomatic recurrence by clinical care compared with by self-report was more strongly associated with these manifestations of radiographic recurrence. Among those with a baseline asymptomatic kidney stone, stone passage during follow-up occurred in 48 out of 94 (51%) participants. Of those with stone passage during follow-up, 25 out of 48 (52%) participants had concurrent symptomatic recurrence by either clinical care or self-report. The mean diameter of the largest baseline asymptomatic kidney stone for those with versus without stone passage was 3.4 mm (range 2–9 mm) versus 3.1 mm (range 1–9 mm) (P=0.42). For those that passed a stone, the mean baseline diameter of the largest passed stone for those with symptomatic recurrence was 3.3 mm (range 1–9 mm) versus 2.7 mm (range 1–4 mm) for those without symptomatic recurrence (P=0.11). The mean diameter of the largest new stone at the 5-year follow-up was 3.3 mm (range 1–15 mm).

View this table:
Table 2.

Association between symptomatic recurrence and radiographic recurrence over the same 5-year period

Symptomatic Recurrence without Radiographic Recurrence

Symptomatic recurrence also occurred from de novo stones not present at baseline. Overall, 19 out of 72 (26%) participants had symptomatic recurrence in the absence of any manifestation of radiographic recurrence over the same 5-year period. Among the stone formers who had one or more baseline asymptomatic kidney stone with none passing and no new stone on follow-up CT scan, five out of 25 (20%) had symptomatic recurrence by clinical care or self-report during the 5-year follow-up period (due to a stone forming and passing in between). Among the stone formers who had no baseline asymptomatic kidney stone and no new stone on follow-up CT scan, 12 out of 62 (19%) had symptomatic recurrence by clinical care or self-report.

Prediction of Recurrence by Risk Factors

In the overall cohort, the estimated symptomatic recurrence rate by clinical care with the ROKS tool was 19% at 5 years compared with the actual recurrence rate of 19% (34/175; 95% CI, 14% to 25%). The c-statistic was 0.63 (95% CI, 0.52 to 0.73). The ROKS score was then used to predict other manifestations of recurrence (Table 3). For any symptomatic recurrence (clinical care or self-reported), the 5-year recurrence rate increased to 53 out of 175 (30%) participants, and the c-statistic for prediction by the ROKS score increased to 0.69 (95% CI, 0.60 to 0.78). For any symptomatic or radiographic recurrence, the 5-year recurrence rate increased to 117 out of 175 (67%) participants and the c-statistic for prediction by the ROKS score increased to 0.79 (95% CI, 0.72 to 0.86).

View this table:
Table 3.

Predicting symptomatic and radiographic recurrence over 5 yr with the ROKS score in the full cohort and the subset with or without a baseline asymptomatic kidney stone

This analysis was also stratified by presence or absence of a baseline asymptomatic kidney stone (Table 3). The risk of each manifestation of recurrence was about twice as high in those with a baseline asymptomatic kidney stone versus those without. However, the prediction of symptomatic recurrence by the ROKS score was similar between those with versus without a baseline asymptomatic kidney stone. Prediction of a new stone on follow-up CT imaging was attenuated after stratifying on presence or absence of a baseline asymptomatic kidney stone.

Repeating the analysis using the earlier (2014) version of the ROKS score7 showed a similar pattern, although the strength of associations were generally weaker (Supplemental Table 2). Urine and/or serum chemistries failed to predict any manifestation of recurrence (Supplemental Table 3).

Comparison between Minnesota and Florida

There was some evidence of higher symptomatic recurrence but not higher radiographic recurrence in Florida compared with Minnesota (Supplemental Table 4).

Discussion

This study clarifies the relationship between different manifestations of symptomatic and radiographic kidney stone recurrence and their prediction by risk factors. The most clinically relevant and definitive manifestation of recurrence is a seen symptomatic stone that results in clinical care. This only occurs in 19% by 5 years and is weakly predictable by baseline risk factors (c-statistic=0.63). However, some symptomatic recurrence does not result in clinical care with a confirmed (seen) stone. Patients may void a small stone without ever seeing it or self-manage a stone episode. This study also found that kidney stones can form, grow, and pass without causing a discernable symptomatic episode. With a more comprehensive definition of recurrence that also included self-reported symptomatic episodes and asymptomatic radiographic changes, 67% had recurrence by 5 years, and this recurrence was more strongly predicted by risk factors (c-statistic=0.79). Thus, there appears to be a tradeoff between clinically significant recurrence that is less common and difficult to predict versus a comprehensive biologic recurrence that is more common and easier to predict.

Relatively few studies have assessed kidney stone recurrence in first-time stone formers. Retrospective studies involving nephrology- or urology-based practices have reported combined symptomatic and radiographic recurrence rates that result in clinical care of approximately 50% at 10 years after the first stone episode.11–13 These studies defined recurrence as any new spontaneously passed symptomatic stone, any stone procedure to remove a new symptomatic stone and any new stone seen on follow-up imaging (if obtained). However, in these studies passage of a stone known to be present at baseline was not considered recurrence. Population-based retrospective studies of first-time stone formers in the community have reported symptomatic recurrence that results in clinical care to be about 20% at 5 years and 30% at 10 years,7,8,14 consistent with our finding of 19% symptomatic recurrence by clinical care at 5 years. Prospective cohort data are also available for comparison. In a clinical trial of first-time stone formers, 27% of those in the control arm developed symptomatic or radiographic new stone formation during 5 years of follow-up.15 In another study of first-time stone formers followed in a stone clinic, 27% developed symptomatic recurrence by survey and an additional 28% had a new stone on ultrasound during a mean follow-up of 14 years.16 Finally, a systematic review of clinical trials determined that the average recurrence rate among first time kidney stone formers was 6 per 100-person years (approximately 30% in 5 years).17 These recurrence rates are lower than the combined symptomatic and radiographic recurrence of 67% in 5 years in this study, likely owing to a less comprehensive assessment of recurrence and the use of less-sensitive imaging modalities.

Our study found moderate agreement between symptomatic recurrences by clinical care versus self-report. Because of recall bias, stone formers may not recall symptomatic recurrence that led to clinical care. Some self-reported symptomatic stone episodes that did not lead to clinical care were likely valid self-managed stone passage episodes; others may have been pain mistaken for stone passage. Comparison of radiographic recurrence to each manifestation of symptomatic recurrence supports some validity for both symptomatic manifestations. A concurrent new stone or stone passage on CT imaging was more strongly associated with symptomatic recurrence by clinical care, whereas risk factors (ROKS score) associated more strongly with symptomatic recurrence by self-report. Detecting symptomatic recurrence by both medical record review and by survey is the most comprehensive approach to capture all symptomatic recurrence (few false negatives), although there are likely false positives with self-reported episodes. Clinically, providing patients with a urine strainer may help them determine whether their symptoms are from stone passage.

CT is considered the most accurate method of imaging for detecting kidney stones.18–21 Serial CT images can be used to detect the formation of new stones and growth of previously identified stones; both are suggestive of “metabolically active” disease.18 Radiographic recurrence by new stone, stone growth, or stone passage between serial imaging has been used as a composite outcome in clinical trials and prospective cohort studies.17,22–24 However, potential drawbacks of using radiographic recurrence as an outcome include missed stones with non-CT imaging (roentgenography or ultrasound), variable follow-up periods, and detection bias when imaging is performed for symptoms. In the current study, high-resolution CT imaging occurred at a standardized 5-year follow-up study visit not dependent on patient symptoms. This allowed a more accurate assessment of how radiographic recurrence relates to symptomatic recurrence.

This study also identified a new “rule of halves”: half of first-time symptomatic stone formers present with a baseline asymptomatic kidney stone, half of these will pass the stone over the next 5 years, and half of these will have symptoms (pain or gross hematuria) with stone passage. In referral populations, about 71% of kidney stones that spontaneously pass result in symptoms.24 The baseline asymptomatic kidney stones in our cohort were an average 3 mm in diameter by CT, a size often missed by roentgenography or ultrasound.25 Baseline stone size did not predict whether symptoms would occur with stone passage, suggesting stone growth and other patient factors may contribute to whether a stone becomes symptomatic with attempted passage. Regardless, presence of these small baseline asymptomatic kidney stones was associated with about two-fold higher risk of symptomatic recurrence or new stone formation.

This study also validated the previously-developed ROKS tool that predicts symptomatic recurrence requiring clinical care.7,8 As expected, the model discrimination in this independent cohort (c-statistic=0.63) was lower than in the development cohort (c-statistic=0.68).8 Calibration of the ROKS tool was good, with an actual and expected 5-year recurrence rate both being 19%. The ROKS score used in the tool performed much better when predicting all symptomatic and radiographic manifestations of recurrence (c-statistic=0.79). Thus, improvements in predicting kidney stone recurrence can be made by a more comprehensive assessment of recurrence beyond symptomatic episodes that result in clinical care.

There were several potential limitations to this study. The stone formers who participated in this study were older, more female, and had more severe stone disease. However, the 5-year symptomatic recurrence rate resulting in clinical care of 19% among study participants is similar to the 20% rate among all first-time stone formers in Olmsted County, as detected by medical record review.7,8 Although no stone formers were started on stone prevention medications, most received diet and water intake recommendations that may have affected the natural history of kidney stone recurrence. Surgical interventions to remove asymptomatic kidney stones will affect the natural history of kidney stone recurrence, and larger kidney stones, in particular, are often removed. Thus, the recurrence findings seen in this study are most applicable to those with small (approximately 3 mm) asymptomatic stones at baseline. Symptomatic recurrence in the first 2 months after the first episode would be missed by our study design, but we wanted to avoid the patient attributing intermittent symptoms or passage of surgical stone fragments to a symptomatic recurrence. Any new stone that formed and passed without symptoms in the 5-year period between CT scans would have been missed. This study had inadequate power to assess individual predictors. Because of this, the ROKS score was used, which summed individual predictors. Because most participants were from Minnesota, external validation to determine if regional differences in recurrence requires further study. The study population was predominantly white, and findings may differ in other ethnic groups. Finally, further study is needed to determine if radiographic changes in stone burden predict future (rather than concurrent) symptomatic recurrence.

In conclusion, most efforts to improve the management of kidney stone formers have focused on prevention of recurrence. Some manifestations of recurrence, such as asymptomatic passage of kidney stones, are both common and more desirable. Clinical trials assessing the prevention of kidney stone recurrence should comprehensively assess all symptomatic and radiographic manifestations of recurrence to better capture the full spectrum of the disease.

Disclosures

Dr. Lieske reports grants from Alnylam, grants from Dicerna, grants from Retrophin, grants from Oxthera, grants from Siemens, other from Orfan, outside the submitted work. Dr. Rule reports grants from National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, during the conduct of the study. Dr. McCollough reports grants from Siemens AG, outside the submitted work. All of the remaining authors have nothing to disclose.

Supplemental Material

This article contains the following supplemental material online at http://jasn.asnjournals.org/lookup/suppl/doi:10.1681/ASN.2018121241/-/DCSupplemental.

Supplemental Figure 1. Recruitment of the prospective cohort of incident symptomatic stone formers.

Supplemental Table 1. Baseline characteristics of incident symptomatic kidney stone formers in the prospective cohort compared with those in the previously published historical cohort used to develop the ROKS tool.

Supplemental Table 2. Predicting symptomatic and radiographic recurrence over 5 years with the ROKS 2014 score in the full cohort and the subset with or without a baseline asymptomatic kidney stone.

Supplemental Table 3. Prediction of different manifestations of kidney stone recurrence over 5 years by 24-hour urine chemistries (after adjustment for age, sex, and urine creatinine) and by serum chemistries (after adjustment for age and sex).

Supplemental Table 4. Comparison of 5-year recurrence rate between the Minnesota and Florida sites.

Acknowledgments

Dr. Rule, Dr. Haley, and Dr. Lieske supervised the study. Dr. Rule, Dr. D’Costa, Dr. Lieske, and Dr. Enders designed the study. Dr. Mara and Dr. D’Costa performed the analysis. Dr. D’Costa and Dr. Rule drafted the manuscript, all authors contributed to data interpretation and editing the final manuscript.

This project was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (Mayo Clinic O’Brien Urology Research Center, DK100227 and DK83007) and made possible by the Rochester Epidemiology Project (AG034676) and the National Center for Advancing Translational Sciences (UL1 TR002377) from the National Institutes of Health, US Public Health Service.

Footnotes

  • Published online ahead of print. Publication date available at www.jasn.org.

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Symptomatic and Radiographic Manifestations of Kidney Stone Recurrence and Their Prediction by Risk Factors: A Prospective Cohort Study
Matthew R. D’Costa, William E. Haley, Kristin C. Mara, Felicity T. Enders, Terri J. Vrtiska, Vernon M. Pais, Steven J. Jacobsen, Cynthia H. McCollough, John C. Lieske, Andrew D. Rule
JASN Jul 2019, 30 (7) 1251-1260; DOI: 10.1681/ASN.2018121241
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