Kidney Stones Predict Chronic Trouble, ESRD

By Todd Neale, Senior Staff Writer, MedPage Today

Published: August 31, 2012

Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania

Action Points

• Note that in this large registry cohort study, even a single kidney stone episode during follow-up was associated with a significant increase in the likelihood of adverse renal outcomes including ESRD.
• Point out however that the increases were small in absolute terms.

Having a kidney stone may portend poor renal function, including end-stage renal disease, researchers found.
Individuals who had at least one kidney stone event were significantly more likely to develop end-stage renal disease through 11 years of follow-up (HR 2.16, 95% CI 1.79 to 2.62), according to Marcello Tonelli, MD, of the University of Alberta in Edmonton, and colleagues.
Kidney stones also were associated with greater risks of developing stage 3b to 5 chronic kidney disease (HR 1.74, 95% CI 1.61 to 1.88) and a doubling of serum creatinine (HR 1.94, 95% CI 1.56 to 2.43) through 4 years of follow-up, the researchers reported online in BMJ.
They noted, however, that the absolute risks remained low, even among the individuals with kidney stones.
"Further research should be aimed at determining the mechanisms explaining this association and assessing the optimal way to prevent kidney stones in the general population, especially young women," who appeared to have greater risks compared with other groups, they wrote.
Tonelli and colleagues examined claims and facility utilization data from Alberta, where residents are covered by a universal healthcare system. The analysis included 3,089,194 adults who did not have end-stage renal disease or a history of pyelonephritis at baseline in April 1997; 63% had outpatient serum creatinine measurements in their records.
The main outcomes were the development of end-stage renal disease, new-onset stage 3b to 5 chronic kidney disease (an estimated glomerular filtration rate less than 45 mL/min/1.73 m²), and a sustained doubling of serum creatinine.
Overall, 0.8% of patients (23,706) had at least one kidney stone during follow-up, 0.2% (5,333) developed end-stage renal disease, 4% (68,525) developed stage 3b to 5 chronic kidney disease, and 0.3% (6,581) had a sustained doubling of serum creatinine.
After adjustment for age, sex, Aboriginal status, receipt of social assistance, rural residence, comorbidities, and prior nephrolithiasis, having at least one kidney stone was associated with developing end-stage renal disease.
And after further adjustment for baseline kidney function, kidney stones were associated with development of chronic kidney disease and a doubling of serum creatinine.
The risks appeared to be greater in women versus men -- possibly because of anatomical differences -- and in patients younger than 50 -- possibly because of the competing risk of death in older individuals, the researchers noted.
Even so, absolute risks of adverse renal outcomes remained low. The unadjusted rate of end-stage renal disease, for example, was 2.48 per million person-days in people with at least one stone during follow-up and 0.52 per million person-days in people who did not develop stones.
There are multiple possible mechanisms linking kidney stones to declines in renal function, according to the authors.
"The association between calcium kidney stones and progressive loss of kidney function may be the direct result of progressive calcification within the renal interstitium, and specifically at the tubular basement membrane and around the ducts of Bellini," they wrote. "Extension of such calcification into the tubular lumen might cause more renal damage, with potential for progressive scarring, chronic kidney disease, and ultimately end-stage renal disease."
"Alternatively," they continued, "crystallization within the tubular lumen itself may cause damage to the tubular epithelium, and/or obstruction leading to progressive scarring."
Other possible explanations include the loss of kidney function following multiple episodes of urinary tract obstruction or from the surgical or percutaneous treatment of stones.
Tonelli and colleagues acknowledged that the results may not apply to individuals who do not seek medical care for a stone episode.
Other limitations included the possibility of misclassification of the number of stone episodes, the inability to look at the composition of the stones, the possibility of residual confounding, and the lack of genetic information.

Primary source: BMJ
Source reference:
Alexander R, et al "Kidney stones and kidney function loss: a cohort study" BMJ 2012; DOI: 10.1136/bmj.e5287.

The study was supported by a team grant to the Interdisciplinary Chronic Disease Collaboration from the Alberta Heritage Foundation for Medical Research (AHFMR), by the Kidney Foundation of Canada, and by the University Hospital Foundation. Tonelli is supported by an AHFMR Population Health Scholar award and a Government of Canada Research Chair in the optimal care of people with chronic kidney disease. His co-authors reported support from a Clinician-Scientist award from the Canadian Institutes of Health Research, KRESCENT New Investigator awards, an Alberta Innovates Health Solutions Clinical Investigator Award, a Canadian Child Health Clinician Scientist Program Career Development award, and a grant from the NIH.
The authors reported that they had no conflicts of interest.