tract obstruction associated with stones could contribute to
progressive loss of renal function. Finally, it is possible that
surgical or percutaneous treatment of stones (rather than the
stones themselves) accounts for the excess risk of kidney
function loss. However, since our data do not permit us to
address the mechanism linking kidney stones to adverse renal
outcomes, these speculations require confirmation in future
Our study is limited by the fact that people with kidney stones
were identified by their presentation to health services, meaning
that our findings do not apply to those who did not seek medical
care for a stone episode. Consequently we cannot comment on
the association between asymptomatic kidney stones and adverse
renal outcomes. Similarly, although we attempted to capture
discrete episodes of kidney stones, the algorithm we used
requires some assumptions, and some patients were therefore
probably misclassified with respect to their number of
presentations. Since we prospectively used claims and
hospitalisation data to assess the incidence of kidney stones
(rather than a history obtained at the time of dialysis initiation),
ascertainment bias due to more complete assessment of stones
among patients with ESRD is unlikely to have influenced our
findings. We were not able to determine the composition of the
kidney stones and thus cannot assess the specific risk associated
with different stone types. Although we adjusted for numerous
characteristics that differ by whether a participant had a kidney
stone episode (such as age, prior kidney stone, and other
comorbidity), the possibility for residual confounding remains.
Patients with stones may be more likely to have serum creatinine
concentration measured—and, therefore, we might be more
likely to detect a sustained doubling of serum creatinine or new
chronic kidney disease in this group. However, given that ESRD
is unlikely to remain undetected for long, the primary outcome
is unlikely to have been biased in this way. Finally, since the
dataset we used did not include genetic information, we cannot
assess how many of the patients in our study had a monogenic
disorder predisposing to stones. However, given the number of
ESRD events in our study, it seems unlikely that our findings
are driven by such rare conditions.
In conclusion, we found a graded association between episodes
of kidney stones and the risk of adverse renal outcomes,
including ESRD. 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.
Contributors: RTA conceived the study. RTA, NW, AB, and MT designed
the analysis plan. NW performed the statistical analyses. RTA, NW,
and MT wrote the first draft of the study. All authors contributed to the
design, interpretation of results, and critical revision of the article for
intellectually important content.
Funding: This work was supported by a team grant to the Interdisciplinary
Chronic Disease Collaboration from the Alberta Heritage Foundation
for Medical Research (AHFMR), the Kidney Foundation of Canada, and
by the University Hospital Foundation. RTA is supported by a
Clinician-Scientist award from the Canadian Institute of Health Research,
a KRESCENT New Investigator award, and an Alberta Innovates Health
Solutions Clinical Investigator Award. SS is supported by a KRESCENT
New Investigator award and a Canadian Child Health Clinician Scientist
Program Career Development award. GCC is supported by grant
DK070756 from the National Institutes of Health. MT 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
Competing interests: All authors have completed the ICMJE uniform
disclosure form at ww.icmje.org/coi_disclosure.pdf (available on request
from the corresponding author) and declare: no financial relationships
with any organisations that might have an interest in the submitted work
in the previous three years; and no other relationships or activities that
could appear to have influenced the submitted work.
Ethical approval: Our protocol was approved by the University of Alberta
Health Research Ethics Board and the University of Calgary Conjoint
Health Research Ethics Board.
Data sharing: No additional data available.
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Accepted: 25 July 2012
Cite this as: BMJ 2012;345:e5287
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BMJ 2012;345:e5287 doi: 10.1136/bmj.e5287 (Published 30 August 2012) Page 4 of 8