Krieger JN, Kronmal RA, Coxon V, Wortley P, THompson L,
Dietary and behavioral risk factors for urolithiasis:
potential implications for prevention
Am J Kidney Dis
(Aug) 28:195-201 1996
Much data exist suggesting that diet is an important risk factor for
stone formation (1). More affluent members of industrialized
societies consume diets containing greater amounts of animal protein
and purines are at increased risk, as are those who ingest greater
amounts of sodium and oxalates (2). Fluid intake appears to be an
important determinant of stone risk, perhaps explaining the increased
incidence of stone formation in "stone belts" like the southern
United States and the Middle East (1). Controlled trials in which
these variables are manipulated prospectively though have very rarely
been done. We rely therefore on retrospective data to study risk
factors for nephrolithiasis.
The authors of the current study have proceeded in this tradition by
performing a prospective case-control study of risk factors for stone
formation in a large managed care organization in Seattle. They
legitimately claim that their data have special merit since they
arise from a "primary care" setting and not the usual referred
population seen in stone centers. The cases were all men between 25
and 55 experiencing their first episode of stone formation. The
self-contained nature of managed care organizations makes it credible
that case-finding was complete. Patients with previous episodes of
stones were excluded. Controls, men matched for age, without history
of stone formation, were difficult to obtain, and the authors are
forthcoming about this problem. In the end they had 240 cases and 392
controls (only 22% of those eligible). They then performed telephone
interviews collecting demographic variables, and dietary and
medication variables possibly related to stone formation.
Reduced risk for stone disease was associated with postsecondary
education, low-fat or weight loss diet, and antacid use. Beer
drinking was protective, associated with a relative risk for stones
of 0.44, with greater amounts of beer ingested not giving further
protection. Other drinks (coffee, tea or soda) were not associated
with altered risk. Logistic regression confirmed low-fat or weight
reduction diet, beer drinking and antacid use as being protective.
African-American ethnicity, postsecondary education, and a warm work
place were also protective. A positive family history of stones and
diuretic use both conferred a doubling of risk for stones. These
associations all appear to be statistically significant, with
impressive p values, and reasonable confidence intervals.
Comment: The first issue in case-control studies is the
selection of the controls. There is always the chance that the
controls are a self-selected group that somehow differ from the
general population. In this case, other than the relatively low
percentage of controls successfully recruited, one has no clear basis
for finding that the controls are not appropriately selected.
The larger problem here is the biologic plausibility: why should
these variables be important and influence stone formation in the
direction they do? The authors can offer hypotheses for their
findings, but do so in a rather post-hoc fashion. This is
particularly suggested by the authors' statement that the data were
collected as part of an investigation of a correlation between
vasectomy and stone formation. This detracts from the prospective
nature of the trial. The data therefore may represent true
determinations of risk factors, and may serve as the basis for
further research, but there is also always the danger of asking too
many questions and producing Type I errors. Without prospective
delineation of the details of the variables studied and found to vary
from cases to controls, our understanding of the relevant
pathophysiology is not necessarily advanced.
In the case of beer drinking, the authors' finding would not
ordinarily be expected since beer is often cited as a beverage with
relatively high oxalate content. Its protective effect however has
been demonstrated in a previous study (showing relative risk of 0.36-
0.58)(3), adding credibility to the present finding. Drinking more
beer added no further protection, and drinking other liquids was not
protective, so no ready explanation is at hand. Perhaps oral oxalate
reduces calciuria. Though this may seem counter-intuitive, oral
ingestion of oxalate in hypercalciuric rats reduced urinary calcium
oxalate supersaturation (4).
It is reassuring that a family history conferred a higher risk,
but disturbing that diuretic use increased risk as well. These
presumably relatively healthy, relatively young men, should not be
taking much furosemide, a drug that increases calciuria. Instead, one
would expect them to be taking thiazides for hypertension, a class of
drugs definitively shown to reduce stone formation (5). As the
authors point out, thiazides may cause hypocitraturia (via
hypokalemia) and triamterene has low solubility and can cause stones
itself. But the authors did not ascertain the nature of the diuretic
use, and the number of patients taking them was obviously small.
Similarly the authors must have prospectively believed that a warm
work place would increase risk; yet it reduced risk. This is
unexpected and varies from previous data.
The authors attribute the improved risk of low-fat or weight loss
diet to reduction in protein intake, but that this is what
occurred is not documented. (The trendy weight loss diet in New York
in the '90s is HIGH protein). The benefits of antacids may be
due to increased urinary pH, oxalate binding, or magnesium
supplementation (though most trials of magnesium supplements have not
demonstrated efficacy) (5). But the type of antacid and the
indication for them was not determined.
In summary, the authors have demonstrated one advantage of
studying the self- contained managed care environment, by determining
several risk factors in a primary care population. The questions
raised, but not answered, about pathophysiologic mechanisms are
important and should lead to fruitful research. Two studies have now
shown a protective effect of beer: it should now be struck from the
list of forbidden liquids where it occasionally appears. That
Seattle is at the forefront of the American trend favoring microbrews
makes this group's finding particularly apropos. Zalman Agus said at
the ASN this past year that a beer and acetazolamide at bedtime was
an excellent therapy for uric acid stones. As a homebrewer, and
stone-former, I am tremendously gladdened by the transformation of
beer into a therapeutic libation. Cheers!
David S. Goldfarb, M.D. Co-Director, Kidney Stone Prevention and
Treatment Program, New York University School of Medicine
1. Asplin, J., Chandhoke, P.S. The stone-forming patient, in Kidney
Stones. Medical and Surgical Management, Coe, F.L., Favus, M.J.,
Pak, C.Y.C, Parks, J.H., Preminger, G.M., eds., Lippincott-Raven, New
2. Goldfarb, S. Dietary factors in the pathogenesis and prophylaxis of
calcium nephrolithiasis. Kidney Int 34:544-555 (88).
3. Shuster, J., Finlayson, B., Scheaffer, R.L., Sierakowski, R.,
Zoltek, J., Dzegede, S. Primary liquid intake and urinary stone
disease. J Chron Dis 39: 907-914 (85).
4. Bushinsky, D., ... Coe, F.L. J Am Soc Nephrol (95).
5. Ettinger, B., Citron, J.T., Livermore, B., Dolman, L.I.
Chlorthalidone reduces calcium oxalate calculous recurrence but
magnesium hydroxide does not. J Urol 139:679-684 (88).