Pam Harrison

November 05, 2017

NEW ORLEANS — Risk for end-stage renal disease and all-cause mortality can be elevated in people who develop certain stones, according to a longitudinal cohort study presented here at Kidney Week 2017.

"Recurrent stone formers are at much higher risk for end-stage renal disease than control subjects, whereas incident (first time) symptomatic stone formers are not," said Tsering Dhondup, MD, a resident at the Mayo Clinic in Rochester, Minnesota.

Surprisingly, asymptomatic stone formers are also at higher risk for renal disease, "even after adjustment for things like chronic kidney disease, high blood pressure, diabetes, high cholesterol, gout, and obesity — all of which can increase the risk for kidney failure and end-stage renal disease," he reported.

As part of the Rochester Epidemiology Project, Dr Dhondup and his colleagues compared 7008 people who developed stones with about 28,000 control subjects in Olmsted County from 1984 to 2012.

"We wanted to look at the effect the category of stone had on risk of end-stage renal disease and mortality," Dr Dhondup told Medscape Medical News.

Table 1. Classification of Patients at Study Recruitment

Stone Type Definition
Incident symptomatic kidney No previous stone episode
Recurrent A previous episode of kidney stones
Asymptomatic Kidney stones discovered on unrelated imaging
Bladder Bladder but no kidney stones
Miscoded Initial diagnosis of kidney stones not confirmed on subsequent imaging


The relative risk for renal disease and all-cause mortality was higher in people with certain types of stones than in age- and sex-matched control subjects.

Table 2. Relative Risk by Type of Stone

Stone type Risk for End-Stage Renal Disease Risk for All-Cause Mortality
Incident symptomatic kidney 1.40 1.05
Recurrent 3.31 1.18
Asymptomatic 3.76 1.40
Bladder 1.28 1.35
Miscoded 6.52 1.07


Other Conditions

The elevation seen in patients with asymptomatic stones and in those with miscoded stones was likely related to the conditions that triggered the imaging request. These other conditions, possibly even kidney cancer, were responsible for the heightened end-stage renal disease risk, not kidney stones per se, Dr Dhondup explained.

In recurrent stone formers, the elevation in risk for both renal disease and all-cause mortality was likely the result of the repeated, transient reductions in kidney function that accompany each episode of kidney stone formation.

"Usually the kidneys are resilient and function comes back," he pointed out. "But once a patient has repeated episodes, we believe that ongoing cumulative damage to kidneys causes end-stage renal disease."

Patients who develop even a second episode of kidney stones should be seen by a nephrologist, Dr Dhondup stressed.

"The urine really needs to be checked," he elaborated, "and physicians need to find out what's happening in this particular patient that is increasing their risk of kidney stones."

Prediction Tool

In a separate study of the same Olmsted County cohort, another team of researchers developed a revised kidney stone prediction tool for first-time and recurrent stone formers.

The Recurrence of Kidney Stone (ROKS) nomogram helps physicians determine which patients are at high risk for recurrence after a first stone episode, as reported by Medscape Medical News. It also helps identify patients who would benefit from medication or diet restrictions to prevent long-term complications from recurrent kidney stones, such as end-stage renal disease.

The researchers wanted to expand the tool so it would be useful for patients with more than one previous stone episode, and searched for predictors of symptomatic recurrence.

The ROKS2 prediction tool uses many of the same risk factors as the initial ROKS nomogram, Lisa Vaughan, a statistician at the Mayo Clinic, explained.

For example, younger patients are significantly more likely to develop kidney stones than older patients, and males are more likely than females, she told Medscape Medical News. In addition, a family history of stones and a higher body mass index also increase risk.

However, the team also found that women who were pregnant during a previous stone episode were 82% more likely to have a recurrent episode than women who were not pregnant (P = .005). This elevated risk for stone recurrence might be caused by the hypercalciuria that can occur during pregnancy, Vaughan speculated.

"The more stones you have, the more at risk you are for recurrence," she added.

For example, estimated 5-year recurrence rates were 17% for those who had a first episode, 32% for those who had a second episode, 47% for those who had a third episode, and 60% for those who had a fourth episode.

"We were also able to look at imaging characteristics for this prediction tool," Vaughan noted. And, as expected, the more kidney stones seen on imaging, even if they are not symptomatic, the more predisposed a patient is to form more."

The diameter of the kidney stone is also related to risk for a recurrent episode. Stones larger than 6 mm in diameter are associated with less risk for recurrence, probably because patients who have large stones are more likely to have them removed surgically, Vaughan explained. However, stones 3 mm to 6 mm are 25% more likely to be associated with another stone episode than stones smaller than 3 mm.

Consistent Findings

These data on the association between kidney stone disease and recurrent kidney stone disease are very consistent with findings from other studies, said Gregory Tasian, MD, for the University of Pennsylvania Perelman School of Medicine in Philadelphia.

However, he said he was surprised by the magnitude of risk for end-stage renal disease in both the miscoded and asymptomatic kidney stone groups. Perhaps a lot of unmeasured confounders, with respect to other diseases, explain some of this risk, he said.

The medical community needs to move away from the idea that kidney stones are a crisis that bring patients to the emergency department because they're in pain, to the understanding that kidney stones truly are, in fact, a disorder of mineral metabolism, Dr Tasian suggested.

"It's very important for patients to understand that kidney stones are a disease, not just an event," he said.

"And in patients who do have recurring kidney stones, you have to be aggressive about reducing the risk of a future stone. Even though we still don't know if you prevent a future stone, you reduce the risk of a decrease in kidney function in the future," he added.

These studies were funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institutes of Health. Dr Dhondup and Ms Vaughan has disclosed no relevant financial relationships. Dr Tasian is on the medical advisory board for Allena Pharmaceuticals.

Kidney Week 2017: American Society of Nephrology Annual Meeting. Abstracts TH-PO1082 and TH-PO1081. Presented November 2, 2017.

Follow Medscape on Twitter @Medscape


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.