The metabolic syndrome and uric acid nephrolithiasis: novel features of renal manifestation of insulin resistance.
BACKGROUND
Uric acid nephrolithiasis primarily results from low urinary pH, which increases the concentration of the insoluble undissociated uric acid, causing formation of both uric acid and mixed uric acid/calcium oxalate stones. These patients have recently been described as exhibiting features of insulin resistance. This study was designed to evaluate if insulin resistance is associated with excessively low urinary pH in overtly healthy volunteers (non-stone formers) and if insulin resistance may explain the excessively low urinary pH in patients with uric acid nephrolithiasis.


METHODS
Fifty-five healthy volunteers (non stone-formers) with a large range of body mass index and 13 patients with recurrent uric acid nephrolithiasis underwent hyperinsulinemic euglycemic clamp, 24-hour urinary studies, and anthropometric measurements of adiposity. A subgroup of 35 non-stone formers had 2-hour timed urinary collection before and during the hyperinsulinemic phase of the clamp studies.


RESULTS
For the non-stone former population, low insulin sensitivity measured as glucose disposal rate significantly correlated with low 24-hour urinary pH (r= 0. 35; P= 0.01). In addition to the previously described acidic urine pH and hypouricosuria, patients with recurrent uric acid nephrolithiasis were found to be severely insulin resistant (glucose disposal rate: uric acid stone-formers vs. normals; 4.1 +/- 1.3 vs. 6.9 +/- 2.1 mg/min/kg of lean body mass, P= 0.008). Acute hyperinsulinemia was associated with higher urinary pH (6.1 +/- 0.7 at baseline to 6.8 +/- 0.7 during hyperinsulinemia; P < 0.0001), urinary ammonia excretion (2.7 +/- 1.6 mEq/2 hr at baseline and 4.0 +/- 2.6 mEq/2 hr P= 0.002) and urinary citrate excretion (48 +/- 33 mg/2 hr at baseline and 113 +/- 68 mg/2 hr P < 0.0001).


CONCLUSIONS
We conclude that one renal manifestation of insulin resistance may be low urinary ammonium and pH. This defect can result in increased risk of uric acid precipitation despite normouricosuria.
Abate
Nicola
N
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9169, USA. Nicola.Abate@UTSouthwestern.edu
Chandalia
Manisha
M
Cabo-Chan
Alberto V
AV
Moe
Orson W
OW
Sakhaee
Khashayar
K
D000143:Acids / Q000652:urine; D000328:Adult; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006946:Hyperinsulinism / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D007669:Kidney Calculi / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D000644:Quaternary Ammonium Compounds / Q000652:urine; D014527:Uric Acid / Q000378:metabolism
D000143:Acids; D000644:Quaternary Ammonium Compounds; D014527:Uric Acid