Abstract
Excessive consumption of fructose (FR) leads to obesity, metabolic syndrome (MS) and insulin resistance, which are known risk factors for kidney stones. The epidemiological study has suggested the association between fructose consumption and urolithiasis, but the precise mechanism is still not well understood. Male Wistar rats were assigned for 8 weeks to three groups with different FR content in diet: RD (n = 5)—regular diet with a FR <3%; F10 (n = 6)—regular diet with an addition of 10% Fr in drinking water; F60 (n = 5)—60% FR as a solid food. Serum concentration of FR, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (HCS), uric acid (UA), calcium (Ca), phosphate (Pi), magnesium (Mg) and sodium (Na) were measured. Based on 24 h urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (uUAEx), phosphate (uPiEx), calcium (uCaEx), magnesium (uMgEx) and sodium (uNaEx). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using hematoxylin and eosin (HE) and von Kossa stains. The rats on F10 and F60, as compared to the RD diet, showed a tendency for lower CrCl, higher HCS level and some features of MS as higher Ins and TG levels. Interestingly, F10 (fluid) versus F60 (solid) diet led to higher serum Ins levels. F10 and F60 versus RD demonstrated higher urinary excretion of MCP-1 and NAG which were suggestive for inflammatory injury of the proximal tubule. F10 and F60 as compared to RD showed significantly lower uUAEx, although there were no differences in clearance and fractional excretion of UA. F60 versus RD induced severe phosphaturia (>30×) and natriuria (4×) and mild calciuria. F10 versus RD induced calciuria (3×), phosphaturia (2×) and mild natriuria. Calcium phosphate stones within the tubules and interstitium were found only in rats on FR diet, respectively, in two rats from the F10 group and another two in the F60 group. The rats which developed stones were characterized by significantly higher serum insulin concentration and urinary excretion of calcium and magnesium. A fructose-rich diet may promote development of calcium stones due to proximal tubule injury and metabolic syndrome.
Highlights
Fructose (FR) is a monosaccharide occurring naturally in fruits and honey
In our previous study conducted on the same group of rats, we showed that F10 versus F60 stimulated higher secretion of insulin and C-peptide by the pancreatic islet cells, and lead to more pronounced insulin resistance [9]
We found that serum concentration of HCS and urinary excretion of monocyte chemoattractant protein-1 (MCP-1) and NAG increased with FR content in diet, reaching a statistical significance for the F60 group compared to the RD group (Table 2)
Summary
Its consumption has been increasing dramatically worldwide primarily due to the addition of sucrose (a disaccharide containing 50% fructose and 50% glucose) and high-fructose corn syrup (HFCS) to foods and soft drinks. It is estimated that the FR consumption has increased by 2000% in the US since HFCS introduction in 1967 [1]. A similar trend has been observed in European countries where total sugar consumption contributes to 15 to 25% of energy supply, with relatively higher intake of added sugars in children compared to adults [3]. In our previous study on a group of patients with stage 2 and 3 chronic kidney disease (CKD), the daily FR intake was 59 ± 22 g, where added sugars constituted 63% [4]
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