Oral sodium bicarbonate reduces proximal renal tubular peptide catabolism, ammoniogenesis, and tubular damage in renal patients

Abstract

Oral sodium bicarbonate (NaHCO3) is widely used to treat acidosis in patients with renal failure. However, no data are available in man on the effects on proximal renal tubular protein catabolism or markers of tubular injury. We have developed methods to allow such studies, and both increased tubular catabolism of 99mTc-labelled aprotinin (Apr*), as well as tubular damage were found in association with increased ammonia (NH3) excretion in patients with nephrotic range proteinuria. We now examine the effects of reducing renal ammoniogenesis, without altering proteinuria, using oral NaHCO3 in 11 patients with mild/moderate renal impairment and proteinuria. Renal tubular catabolism of Apr* was measured before and after NaHCO3 by renal imaging (Kidney uptake, K% of dose) and urinary excretion of free 99mTcO4- (metabolism, Met% of dose/h) over 26 h. Fractional degradation (Frac) was calculated from Met/K (/h). Fresh urine was also analyzed for NH3 excretion every fortnight from 6/52 before treatment. Total urinary N-acetyl-beta-D-glucose-aminidase (NAG) and the more tubulo-specific NAG "A2" were measured. 51CrEDTA clearance and 99mTc-MAG 3 TER were also assessed. After NaHCO3 Met over 26 h was significantly reduced (from 1.3 +/- 0.2% of dose/h to 0.9 +/- 0.1% dose/hr, p < 0.005), as was Frac of Apr* (from 0.06 +/- .006/h to 0.04 +/- 0.005/hr, p < 0.003). NH3 excretion also fell significantly (from 0.9 +/- 0.2 mmol/h to 0.2 +/- 0.05 mmol/h, p < 0.007), as did both total urinary NAG (from 169 mumol/24 h, 74-642 mumol/24 h to 79 mumol/ 24 h, 37-393 mumol/24 h, p < 0.01), and the NAG 'A2' isoenzyme (from 81.5 mumol/24 h, 20-472 mumol/24 h to 35.0 mumol/24 h, 6-388 mumol/24 h, p < 0.001). Proteinuria remained unaltered, and there was no change in blood pressure nor in glomerular haemodynamics. Oral NaHCO3 may thus pro-tect the proximal renal tubule and help delay renal disease progression.