Sodium-sensitive variability of the antiproteinuric efficacy of RAS inhibitors in outpatients with IgA nephropathy

Inhibition of the renin-angiotensin system (RAS) decreases proteinuria in IgA nephropathy and often retards disease progression. However, its antiproteinuric efficacy varies considerably among patients or different stages in a single patient. We sought for the factor(s) underlying the variation in urinary protein excretion in RAS inhibitor-treated outpatients with IgA nephropathy.

43 patients with biopsy-proven IgA nephropathy, moderate proteinuria (0.5 - 3.5 g/day), normal to moderately-low estimated GFR (eGFR) (28.6 - 114.2 ml/min/1.73 m2) and normal blood pressure, prehypertension or mild hypertension (systolic/diastolic blood pressures < 160/100 mmHg) were placed on RAS inhibitors following diagnosis.

Excretion of urinary protein (UprV) and sodium (UNaV), estimated protein intake (EPI) and the mean blood pressure (MBP) were determined on 12 consecutive visits for an average duration of 17.6 months. Analyses were performed to determine which factor(s) influenced the variation in UprV.

14 patients (32.6%) showed a significant correlation between UprV and UNaV, whereas UprV correlated significantly with EPI or MBP in 7 (16.3%) and 3 patients (7.0%), respectively. The 14 patients were characterized by lower eGFR and more extensive glomerulosclerosis and tubulointerstitial damage at baseline than the other 29 patients. The UprV-UNaV correlation was significant in 8 of 12 patients (66.7%) with eGFR < 60 ml/min/1.73 m2 and in 6 of 29 patients (19.4%) with eGFR >= 60 ml/min/1.73 m2 (p < 0.05). The UprV/UNaV regression lines were significantly steeper with more extensive glomerulosclerosis (p < 0.05) and tubulointerstitial damage (p < 0.05) at baseline. The lines also tended to be steeper with lower baseline eGFR (p = 0.062).

These results showed that the antiproteinuric effect of RAS inhibitors becomes susceptible to an increase in urinary sodium excretion as renal function and functioning nephron mass decline with the progression of renal histological damage. Stringent dietary sodium restriction is required to maximize the antiproteinuric effect of RAS inhibitors in outpatients with IgA nephropathy.