Demographic and Clinical Predictors of Failure to Achieve Remission Following Tonsillectomy in Japanese IgA Nephropathy: A Multi-Center Electronic Medical Record (EMR)-based Study

IgA nephropathy (IgAN) represents approximately 30% of primary glomerulonephritis and progresses to end-stage kidney disease in up to 40% of cases. In Japan, tonsillectomy combined with steroid pulse therapy is widely practiced, based on the hypothesis that the palatine tonsils are a major site of aberrant IgA1 production. Although this approach frequently induces remission of hematuria and proteinuria in many cases, approximately one-third fail to achieve clinical remission and reliable predictors remain undefined in the real-world clinical setting. This study aimed to identify clinical and demographic factors associated with failure to achieve remission following tonsillectomy.

This retrospective cohort study utilized the DATuM IDEA electronic medical record (EMR) database, covering 55 National Hospitals across Japan and approximately 1.2 million patients. Adults (≥18 years) with IgAN who underwent their first recorded tonsillectomy and had ≥3 measurements both urinary protein and occult blood were included. Patients with prior kidney transplantation, prior tonsillectomy, or insufficient observation periods (less than 6-month) were excluded. Complete clinical remission was defined according to the criteria proposed by Suzuki et al. (Clin Exp Nephrol. 2014): simultaneous remission of hematuria (urinary RBC <5/HPF or dipstick negative/trace) and proteinuria (urinary protein <0.3g/day or dipstick negative/trace) at each assessment, maintained for ≥6 months and documented by ≥2 consecutive assessments (and ≥3 assessments in total) meeting both criteria. Cox proportional hazard model was used to estimate hazard ratios (HR) for clinical remission. Covariates included demographics, baseline CKD stage, clinical laboratory parameters, comorbidities, and medications. Variables with effect sizes (HR≤ 0.80 or ≥1.25, 95% confidence interval (CI) not crossing 1) in univariate analysis with clinically relevant factors were entered into the multivariate model. 

Among 2,279 IgAN patients, 336 underwent tonsillectomy, and 139 were included the analytic cohort; 33.8% achieved complete clinical remission, the mean age was 41.2 years, and 36.7% were male. For hematuria remission, compared with no/trace (−/±), mild 1+ (HR 0.20; 95% CI 0.06–0.67), moderate 2+ (HR 0.07; 95% CI 0.02–0.20, and severe 3+/4+ (HR 0.07; 95% CI 0.02–0.22) hematuria were each associated with a lower likelihood of remission in multivariable Cox models.　For proteinuria remission: compared with no/trace (−/±), higher dipstick grades were associated with a lower likelihood of remission, including 2+ (HR 0.31;  95% CI 0.12–0.81) and 3+/4+ (HR 0.15; 95% CI 0.04–0.55); post‑index steroid pulse therapy was associated with a higher likelihood of proteinuria remission (HR 2.88, 95% CI 1.20–6.87). For complete clinical remission: severe baseline proteinuria 3+/4+ was independently associated with failure to achieve remission (HR 0.17; 95% CI 0.03–0.92).

Current research findings highlight the importance of baseline urinary severity, and adjunctive immunologic therapy in achieving for remission with tonsillectomy. Importantly, for non-remitters despite tonsillectomy, management should integrate risk stratification by baseline urinary severity and the timely consideration of immunologic therapy or alternative disease‑specific treatment intervention.