STONE DISEASE

Obesity, weight gain, and the risk of kidney stones
Taylor EN, Stampfer MJ, Curhan GC
Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass, USA
JAMA. 2005; 293: 455-62

• Context: Larger body size may result in increased urinary excretion of calcium, oxalate, and uric acid, thereby increasing the risk for calcium-containing kidney stones. It is unclear if obesity increases the risk of stone formation, and it is not known if weight gain influences risk.
• Objective: To determine if weight, weight gain, body mass index (BMI), and waist circumference are associated with kidney stone formation.
• Design, Setting, and Participants: A prospective study of 3 large cohorts: the Health Professionals Follow-up Study (N = 45,988 men; age range at baseline, 40-75 years), the Nurses’ Health Study I (N = 93,758 older women; age range at baseline, 34-59 years), and the Nurses’ Health Study II (N = 101,877 younger women; age range at baseline, 27-44 years).
• Main Outcome Measures: Incidence of symptomatic kidney stones.
• Results: We documented 4827 incident kidney stones over a combined 46 years of follow-up. After adjusting for age, dietary factors, fluid intake, and thiazide use, the relative risk (RR) for stone formation in men weighing more than 220 lb (100.0 kg) vs men less than 150 lb (68.2 kg) was 1.44 (95% confidence interval [CI], 1.11-1.86; P = .002 for trend). In older and younger women, RRs for these weight categories were 1.89 (95% CI, 1.52-2.36; P<.001 for trend) and 1.92 (95% CI, 1.59-2.31; P<.001 for trend), respectively. The RR in men who gained more than 35 lb (15.9 kg) since age 21 years vs men whose weight did not change was 1.39 (95% CI, 1.14-1.70; P = .001 for trend). Corresponding RRs for the same categories of weight gain since age 18 years in older and younger women were 1.70 (95% CI, 1.40-2.05; P<.001 for trend) and 1.82 (95% CI, 1.50-2.21; P<.001 for trend). Body mass index was associated with the risk of kidney stone formation: the RR for men with a BMI of 30 or greater vs those with a BMI of 21 to 22.9 was 1.33 (95% CI, 1.08-1.63; P<.001 for trend). Corresponding RRs for the same categories of BMI in older and younger women were 1.90 (95% CI, 1.61-2.25; P<.001 for trend) and 2.09 (95% CI, 1.77-2.48; P<.001 for trend). Waist circumference was also positively associated with risk in men (P = .002 for trend) and in older and younger women (P<.001 for trend for both).
• Conclusions: Obesity and weight gain increase the risk of kidney stone formation. The magnitude of the increased risk may be greater in women than in men.
  
  
• Editorial Comment
  Many urologists have long suspected that obese individuals are at increased risk of kidney stone formation, with the risk of stone disease assumed to be due to across-the-board overindulgence in substances know to be associated with stone formation, such as dairy products, animal protein and salt. Taylor and colleagues confirmed the suspicion of increased stone risk with obesity in 3 prospective cohort studies that used food frequency questionnaires and assessed the rate of incident stone formation. They determined that the relative risk (RR) of incident stone formation correlated positively with weight, weight gain and body mass index (BMI) in over 240,000 individuals comprising 3 large independent cohorts of men (Health Professional follow-up Study), younger women (Nurses’ Health Study II) and older women (Nurses’ Health Study I). Furthermore, this correlation held when adjusting for age and dietary and medication factors known to be associated with stone risk.
  The mechanism by which obesity increases stone risk is not known. Several studies have linked obesity and insulin resistance with an increased risk of uric acid stone formation as a result of a defect in renal ammoniagenesis (1). Of note, this association was found to be independent of diet. Hyperinsulinemia has also been shown to have a hypercalciuric effect that could potentially increase the risk of calcium stones (2). Other investigators found higher urinary uric acid levels in obese stone formers compared with non-obese stone formers (3). Taken together, these studies suggest both diet-dependent and diet-independent mechanisms for the increased rate of stone formation. Given the increased difficulty in surgically treating stones in obese patients, efforts should be made not only to correct underlying metabolic risk factors in these patients, but also to encourage weight control.

References
1. Abate, N, Chandalia, M, Cabo-Chan AV Jr, Moe OW, Sahkaee, K: The metabolic syndrome and uric acid nephrolithiasis: novel features of renal manifestation of insulin resistance. Kidney Int. 2004; 65: 386-92.
2. Shimamoto K, Higashiura K, Nakagawa M, Masuda A, Shiiki M, Miyazaki Y, Ise T, Fukuoka M, Hirata A, Iimura O: Effects of hyperinsulinemia under the euglycemic condition on calcium and phosphate metabolism in non-obese normotensive subjects. Tohoku J Exp Med. 1995; 177: 271-8.
3. Powell CR, Stoller ML, Schwartz BF, Kane C, Gentle DL, Bruce JE, Leslie SW: Impact of body weight on urinary electrolyes in urinary stone formers. Urology. 2000; 55: 825-30.

Dr. Margaret S. Pearle
Associate Professor of Urology
University of Texas Southwestern Med Ctr
Dallas, Texas, USA