Acute Effect of High Fat Intake on Urinary Acidification Parameters

Area of Science:

• Nephrology
• Metabolic Disorders
• Urology

Background:

• Uric acid nephrolithiasis is increasingly prevalent, linked to obesity and acidic urine pH (UpH).
• Acidic UpH stems partly from reduced ammonia (NH3) buffering of H+.
• Renal ammoniagenesis in proximal tubules generates NH3, crucial for acid-base balance.

Purpose of the Study:

• To investigate if free fatty acids (FFAs) reduce renal ammoniagenesis in uric acid stone formers (UASFs) versus controls (Ctrls).
• To assess the impact of a dietary fat load as an alternative energy substrate on renal ammoniagenesis.

Main Methods:

• Seven UASFs and 8 Ctrls underwent a 4-day fixed metabolic diet.
• Fasting urine and blood samples were collected, followed by a 10-hour oral fat load with serial sampling.

Main Results:

• Both groups showed similar increases in serum FFAs.
• UASFs had a persistently lower baseline UpH (5.3) compared to Ctrls (6.6), which decreased significantly in Ctrls but not UASFs during the fat load.
• The ammonium (NH4+) to net acid excretion (NAE) ratio was lower at baseline in UASFs and decreased in both groups during the fat load.

Conclusions:

• Controls demonstrated reduced NH4+ excretion with fat load, suggesting a substrate switch.
• UASFs exhibited a chronic defect in NH4+ excretion, indicative of lipotoxic impairment of proximal tubule function.
• Dietary fat restriction alone may be insufficient for managing aciduria in UASFs.