A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy

Abstract

Background: The study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN).

Methods: Patients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria.

Results: During 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01-8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission.

Conclusions: The results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified.

Keywords: clinical remission; estimated glomerular filtration rate; hematuria; proteinuria.

FIGURE 1:

Trial profile.

FIGURE 2:

Urinary protein excretion during the trial period. Mean values and standard errors are presented. The rate of decrease in urinary protein excretion was significantly higher in Group A than in Group B using a mixed effect model. The numbers of patients analyzed at each time point are shown below the figure for each group.

FIGURE 3:

Patient distribution of the severity of proteinuria during the trial period. The severity of proteinuria was divided into the four grades shown below the figure according to the level of urinary protein (UP) in g/g creatinine (Cr). The patient distribution in the four grades is shown as a percentage. *The rate of the disappearance of proteinuria (UP level of <0.3 g/g Cr) was significantly higher in Group A than in Group B (Pearson's chi-square test).

FIGURE 4:

Patient distribution of the severity of hematuria during the trial period. The severity of hematuria was divided into the five grades according to the number of red blood cells per high power field (HPF). The patient distribution in the five grades is shown as a percentage. The rate of the disappearance of hematuria, defined as the number of red blood cells <5/HPF, was not different between both groups at any time point (Pearson's chi-square test).

FIGURE 5:

Frequency of clinical remission during the trial period. The frequency of patients with clinical remission (i.e. the disappearance of both proteinuria and hematuria) is shown for each time point. The frequency was not significantly higher in Group A than Group B at any time point (Pearson's chi-square test).

FIGURE 6:

Renal function during the trial period. Mean values and standard errors of the estimated glomerular filtration rate (eGFR) are shown. The value of eGFR remained stable in both groups.