STONE DISEASE

Association of urinary pH with body weight in nephrolithiasis
Maalouf NM, Sakhaee K, Parks JH, Coe FL, Adams-Huet B, Pak CY
Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
Kidney Int. 2004; 65: 1422-5

• Background: The prevalence of kidney stone disease in the United States is progressively increasing, paralleling the growing rate of obesity. Uric acid nephrolithiasis, a condition associated with a low urinary pH, has been linked to obesity and insulin resistance. Based on these observations, we hypothesized that urinary pH may be inversely associated to body weight in nephrolithiasis.
• Methods: Data were retrieved from 4883 patients with nephrolithiasis who underwent ambulatory evaluation at two established stone clinics in Dallas and Chicago. The patients collected 24-hour urine samples on an outpatient basis, while avoiding any drug that could alter urinary pH. Patients were divided in increasing sextiles of body weight, and urinary pH was adjusted for urinary creatinine and for age.
• Results: Urinary pH had a strong, graded inverse association with body weight. Urinary creatinine and age were both found to be significant covariates of urinary pH, while gender was not a significant independent variable after adjustment for urinary creatinine. Mean 24-hour urinary pH, adjusted for age and urinary creatinine, were 6.09, 6.04, 6.01, 5.99, 5.97, and 5.91 for sextiles of body weight in increasing order from Dallas (P for linear trend < 0.0001), and 6.18, 6.10, 6.04, 6.02, 5.97, and 5.88 for the sextiles from Chicago (P for linear trend < 0.0001).
• Conclusion: We conclude that urinary pH is inversely related to body weight among patients with stones. The results confirm the previously proposed scheme that obesity may sometimes cause uric acid nephrolithiasis by producing excessively acid urine due to insulin resistance.
  
  
• Editorial Comment
  For those of us who treat a lot of stones and have a large referral practice for obese stone-forming patients, the observation that many of these patients have uric acid stones is no surprise. On the surface many of us have assumed that the high incidence of uric acid stone disease was due to overindulgence in salt, meat and dairy leading to low urine pH and high urinary uric acid. However, the group from Dallas has postulated a novel pathophysiologic mechanism for uric acid stone formation (1). By their theory, the acidic urine seen in obese uric acid stone formers is attributed to insulin resistance in the kidney, which leads to decreased renal ammonia excretion and subsequent reduced urinary buffering capacity, thereby causing an acidic urine.
  In the current study, patient databases from 2 of the largest metabolic stone clinics in the country were searched to establish the relationship between urine pH and body weight in a large group of stone patients. A strong, inverse association was found between urine pH and body weight, a relationship which held even after adjustment for a variety of potential confounding factors. Interestingly, after adjustment for urinary sulfate, a marker for animal protein intake, the strong inverse association persisted, suggesting that that the mechanism is independent of diet and not simply a result of dietary indiscretion. Indeed in their seminal work, the investigators confirmed low urine pH in obese uric acid stone patients maintained on a controlled metabolic diet.
  These findings support the insulin resistance-mediated mechanism of increased urinary acidity in obese patients. Therefore, it is hoped that with weight loss (and dietary modification), insulin-resistance may be reversible and urinary acidity can be returned to normal, thereby reducing the risk of stone formation.
  

Reference
1. Sakhaee K, Adams-Huet B, Moe OW, Pak CY: Pathophysiologic basis for normouricosuric uric acid nephrolithiasis. Kidney Int. 2002; 62: 971-9

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