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


METHODS
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Suzuki
T
T
Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Nishishinbashi, Minato-ku, Tokyo, Japan.
Miyazaki
Y
Y
Shimizu
A
A
Ito
Y
Y
Okonogi
H
H
Ogura
M
M
Utsunomiya
Y
Y
Kawamura
T
T
Hosoya
T
T
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D011507:Proteinuria / Q000188:drug therapy*; D012044:Regression Analysis; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012189:Retrospective Studies; D012964:Sodium / Q000652:urine*; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D012964:Sodium