R. Rustom et al., ORAL SODIUM-BICARBONATE REDUCES PROXIMAL RENAL TUBULAR PEPTIDE CATABOLISM, AMMONIOGENESIS, AND TUBULAR DAMAGE IN RENAL PATIENTS, Renal failure, 20(2), 1998, pp. 371-382
Oral sodium bicarbonate (NaHCO3) is widely used to treat acidosis in p
atients with renal failure. However, no data are available in man on t
he effects on proximal renal tubular protein catabolism or markers of
tubular injury. We have developed methods to allow such studies, and b
oth increased tubular catabolism of Tc-99m-labelled aprotinin (Apr),
as well as tubular damage were found in association with increased amm
onia (NH3) excretion in patients with nephrotic range proteinuria. We
now examine the effects of reducing renal ammoniogenesis, without alte
ring proteinuria, using oral NaHCO3 in II 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 (TcO4-)-Tc-99m (metabolism, Met
% of dose/h) over 26 h. Fractional degradation (Fmc) was calculated f
rom Met/K (/h). Fresh urine was also analyzed for NH3 excretion every
fortnight from 6/52 before treatment. Total urinary N-acetyl-beta-D-gl
ucoseaminidase (NAG) and the more tubulo-specific NAG ''A2'' were meas
ured. (51)CrEDTA clearance and Tc-99m-MAG 3 TER were also assessed. Af
ter 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 mu mol/24 h, 74
-642 mu mol/24 h to 79 mu mol/24 h, 37-393 mu mol/24 h, p < 0.01), and
the NAG 'A2' isoenzyme (from 81.5 mu mol/24 h, 20-472 mu mol/24 h to
35.0 mu mol/24 h, 6-388 mu mol/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.