The metabolic syndrome and uric acid nephrolithiasis: Novel features of renal manifestation of insulin resistance

Nicola Abate, Manisha Chandalia, Alberto V. Cabo-Chan, Orson W. Moe, Khashayar Sakhaee

Research output: Contribution to journalArticle

358 Citations (Scopus)

Abstract

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). Conclusion. 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.

Original languageEnglish (US)
Pages (from-to)386-392
Number of pages7
JournalKidney International
Volume65
Issue number2
DOIs
StatePublished - Feb 2004
Externally publishedYes

Fingerprint

Nephrolithiasis
Uric Acid
Insulin Resistance
Kidney
Hyperinsulinism
Healthy Volunteers
Glucose
Calcium Oxalate
Glucose Clamp Technique
Adiposity
Ammonium Compounds
Ammonia
Citric Acid
Body Mass Index
Urine
Insulin

Keywords

  • Insulin resistance
  • Metabolic syndrome
  • Nephrolithiasis
  • Renal acidification
  • Uric acid stones

ASJC Scopus subject areas

  • Nephrology

Cite this

The metabolic syndrome and uric acid nephrolithiasis : Novel features of renal manifestation of insulin resistance. / Abate, Nicola; Chandalia, Manisha; Cabo-Chan, Alberto V.; Moe, Orson W.; Sakhaee, Khashayar.

In: Kidney International, Vol. 65, No. 2, 02.2004, p. 386-392.

Research output: Contribution to journalArticle

Abate, Nicola ; Chandalia, Manisha ; Cabo-Chan, Alberto V. ; Moe, Orson W. ; Sakhaee, Khashayar. / The metabolic syndrome and uric acid nephrolithiasis : Novel features of renal manifestation of insulin resistance. In: Kidney International. 2004 ; Vol. 65, No. 2. pp. 386-392.
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