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Abstract: SA-PO302

Distinguishing Uric Acid Stone Formers from Type 2 Diabetics with Low Urine pH: The Role of Impaired Buffering

Session Information

Category: Bone and Mineral Metabolism

  • 502 Bone and Mineral Metabolism: Clinical

Authors

  • Zomorodian, Seyed Alireza, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Poindexter, John, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Sakhaee, Khashayar, The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Maalouf, Naim M., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Moe, Orson W., The University of Texas Southwestern Medical Center, Dallas, Texas, United States
Background

The prevalence of uric acid (UA) nephrolithiasis has increased in the past decades, particularly among patients with metabolic syndrome, and this lithogenicity is driven by acidic urine pH. Previous studies in these patients on random diets showed that this lower urine pH results from higher acid excretion and insufficient urinary buffering by ammonia. However, intrinsic vs. extrinsic contributors are hard to discern because diet was not controlled. In addition, patients with type 2 diabetes mellitus (T2DM) often exhibit an acidic urine, but only a minority develop UA stones. Here, we provide a comprehensive report of acid-base and stone risk parameters in UA stone formers (UASF) and non-stone forming controls with and without T2DM who were equilibrated and studied under a fixed metabolic diet.

Methods

A total of 74 UASF, 13 T2DM patients without a history of kidney stones, and 51 normal subjects without stones or diabetes (Ctrl) were studied. All participants were equilibrated on metabolic diet for at least 5 days. Blood and urine samples were collected for analysis of acid-base and stone risk parameters. Statistical analyses were performed to compare the stone risk profiles among the three groups.

Results

Participants were comparable with respect to demographic characteristics, with age range of 48-60 years (aligning with peak incidence of UA stones). UASF had slightly higher and Ctrl exhibited a lower body mass index. Under a fixed diet, UASF and T2DM exhibited lower urinary pH, higher net acid excretion (NAE), and lower levels of citrate and bicarbonate compared to Ctrl. The proportion of NAE excreted as ammonium (ammonium/NAE) was significantly lower in UASF [0.50 (95% confidence intervals: 0.46-0.54)] compared to T2DM [0.64 (0.53-0.76)] and Ctrl [0.74 (0.68-0.81)].

Conclusion

This study has the largest number of subjects evaluated on a controlled metabolic diet to date. We found a similarly high NAE in UASF and T2DM non-stone formers; the parameter that sets aside UASF was the significantly lower ammonium/NAE in UASF. An increased acid load to the kidney is an important contributing factor in the development of UA nephrolithiasis but it is not sufficient, and a defect in urinary buffering is necessary for its full pathogenesis.

Funding

  • NIDDK Support