Fructose: A New Variable to Consider in SIADH and the Hyponatremia Associated With Long-Distance Running?

Fructose has recently been proposed to stimulate vasopressin secretion in humans. Fructose-induced vasopressin secretion is not only postulated to result from ingestion of fructose-containing drinks but may also occur from endogenous fructose production via activation of the polyol pathway. This raises the question of whether fructose might be involved in some cases of vasopressin-induced hyponatremia, especially in situations where the cause is not fully known such as in the syndrome of inappropriate secretion of diuretic hormone (SIADH) and exercise-associated hyponatremia, which has been observed in marathon runners. Here we discuss the new science of fructose and vasopressin, and how it may play a role in some of these conditions, as well as in the complications associated with rapid treatment (such as the osmotic demyelination syndrome). Studies to test the role of fructose could provide new pathophysiologic insights as well as novel potential treatment strategies for these common conditions.

Hyponatremia with Persistent Elevated Urinary Fractional Uric Acid Excretion: Evidence for Proximal Tubular Injury?

BACKGROUND/AIMS: Hyponatremia associated with high urinary fractional excretion of uric acid which persists after serum sodium is corrected is the cardinal feature of salt losing nephropathy (SLN). We hypothesize that low grade proximal tubular injury is present in SLN because the proximal tubule is the main site of uric acid and sodium transport. METHODS: Five subjects with SLN were compared to four subjects with recurrent hyponatremia and three healthy individuals. Urinary NGAL (neutrophil gelatinase associated lipocalin, a marker of tubular injury) and fasting urinary fructose levels (a marker of proximal tubular injury) were measured. RESULTS: Subjects with SLN (n=5) showed elevated fractional uric acid excretion (22 ± 6 vs 4 ± 2 percent, p<0.0001), elevated urinary NGAL levels (62 ± 37 vs 9 ± 7 ng/mg creatinine, p=0.001) and fasting urinary fructose levels compared with the 7 controls (383 ± 465 vs 60 ± 34µmole/µg creatinine, p <0.001). A strong correlation between urinary NGAL levels and urinary fructose levels was observed (r =0.87, p<0.001). CONCLUSION: High urinary fractional excretion of uric acid in SLN is associated with elevated NGAL and fasting urinary fructose levels suggesting that SLN may involve tubular injury.

Low serum uric acid level is a risk factor for death in incident hemodialysis patients.

BACKGROUND: A reverse epidemiology of classic cardiovascular risk factors was observed in hemodialysis patients with a high comorbidity burden. We hypothesized that uric acid, a novel cardiovascular risk factor, also has an altered association with survival in these patients. METHODS: A retrospective study was conducted on 168 consecutive outpatient hemodialysis patients over a 6-year period. Serum uric acid, albumin levels and relevant laboratory information were recorded monthly. The disease severity was assessed using Comorbidity Index (CoI) scores. Patients were stratified into 3 groups according to their serum uric acid concentrations: group I was the lowest quintile, group II was the middle 3 quintiles and group III was the highest quintile. The risks of death were calculated utilizing a Cox regression model. RESULTS: Using group II as a reference group, the hazard ratio of group I was 2.23 [95% confidence interval (CI) 1.21-4.11, p = 0.01] and group III was 0.89 (95% CI 0.47-1.71, p = 0.74). The serum uric acid levels correlated inversely with CoI scores (r = -0.31, 95% CI -0.44 to -0.17, p < 0.0001) and positively with serum albumin levels (r = 0.35, 95% CI 0.21-0.48, p < 0.0001). CONCLUSION: Low serum uric acid is a mortality risk factor in incident hemodialysis patients with a high comorbidity burden and hypoalbuminemia.