Tonsillectomy Associated with Outcomes in Patients with Immunoglobin A Nephropathy

Worldwide, immunoglobulin A nephropathy (IgAN) is the most prevalent primary chronic glomerulonephritis and a major cause of end-stage renal disease (ESRD). IgAN is the cause of ESRD in up to 40% of affected patients. Among patients with IgAN who reach ESRD, the mortality rate increases 5-fold; cardiovascular events account for 45% of all deaths.

The genetic risk for IgAN increases with the eastward distance from Africa. There are wide variations in the relative frequency of IgAN in all primary glomerulonephritis cases, ranging from 50% in China and Japan to 10% to 35% across Europe, decreasing to 5% in the Middle East.

Methods of medical management, including the use of renin-angiotensin system inhibitors (RASI) and corticosteroids, are unproven in clinical trials. In two previous randomized clinical trials in Japan in 2014 and China in 2016, results demonstrated that tonsillectomy with corticosteroid treatment improved proteinuria. However, there are few data demonstrating the association between tonsillectomy and long-term renal outcomes.

Keita Hirano, MD, and colleagues recently conducted a retrospective multicenter cohort study in Japan. The researchers aimed to examine the possible association between tonsillectomy and outcomes in patients with IgAN. Results were reported online in JAMA Network Open

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The primary outcome of interest was the first occurrence of a 1.5-fold increase in serum creatinine level from baseline or initiation of dialysis. Secondary outcomes were (1) additional therapy with RASI or corticosteroids initiated 1 year following renal biopsy and (2) adverse events.

Participants were recruited from the Japanese Nationwide Retrospective Cohort Study in IgAN. The final study cohort included 1065 patients with IgAN. The enrollment period was 2002 to 2004. Patients were divided into two groups: those who underwent tonsillectomy within 1 year after renal biopsy (23.7%, n=252) and those who did not (76.3%, n=813).

Of the total cohort, 49.8% were women, median age was 35 years, mean estimated glomerular filtration rate (eGFR) was 76.6 mL/min/1.73 m2, and median proteinuria was 0.68 g per day. Median follow-up was 5.8 years. During that time, 12.1% (n=129) of patients among the overall population reached the primary outcome. An additional 14.4% (n=153) received additional therapy 1 year after the renal biopsy with RASI and/or corticosteroid therapy.

Results of a matched analysis demonstrated an association between tonsillectomy and a lower risk of the primary outcome. To account for between group differences, a 1:1 propensity score matching was  performed; matching resulted in 153 matched pairs. The Kaplan-Meier survival curve and Cox regression models revealed significantly better renal survival in patients in the tonsillectomy group compared with patients in the non-tonsillectomy group (hazard ratio [HR], 0.34; 95% confidence interval [CI], 0.13-0.77; P=.009).

The independent association between tonsillectomy and lower risk of the primary outcome was consistently confirmed in an inverse probability of treatment weighted model and in the entire cohort, using two increased sampling sizes from the entire cohort. There were no interaction effects between baseline characteristics, including eGFR, proteinuria, hematuria extent, and RASI use.

One year after renal biopsy, there was an association between tonsillectomy and fewer additional requirements, in addition to the favorable renal outcome, in the 1:1 matched cohort (HR, 0.36; 95% CI, 0.17-0.71; P=.003) and in the entire cohort (HR, 0.37; 95% CI, 0.20-0.63; P<.001).

During the follow-up period, six patients in the non-tonsillectomy group died, including two patients with lung cancer, two with gastric cancer, one with chronic obstructive pulmonary disease and pneumonia, and one with a ruptured abdominal aortic aneurysm. There were no observed deaths in the tonsillectomy group. In the entire cohort, there were 90 adverse events from 59 patients, including infectious disease, diabetes, malignant neoplasms, cardiovascular disease, cerebral infarction, peptic ulcer, psychogenic disorder, and transient tonsillectomy-related complications. There was no increase in the risk of adverse events with tonsillectomy with the exception of transient tonsillectomy-related complications, including postoperative hemorrhage or infection.

Limitations to the study cited by the authors included studying patients who received additional treatment during the follow-up period, leading to uncertainty regarding the association between the primary outcome and additional treatments; not including the covariates of urinalysis findings and renal function during the follow-up, making the exact effect of IgAN recurrence unknown; only including Japanese patients, making the generalizability of the findings to other populations unknown; not including pediatric patients ≤18 years of age; and the possibility of bias due to unidentified confounding factors.

In conclusion, the researchers said, “This nationwide retrospective cohort study in Japan found that tonsillectomy is associated with improved renal survival rates in patients with IgAN. Further data from prospective studies, including the ongoing prospective Japan IgA Nephropathy Cohort Study, will provide additional evidence on longer-term outcomes following initial treatment with tonsillectomy in the coming years.”

Takeaway Points

  1. Researchers in Japan conducted a retrospective cohort study designed to examine the possible association between tonsillectomy and renal outcomes in patients with immunoglobulin A nephropathy (IgAN).
  2. The primary outcome of the first occurrence of a 1.5-fold increase in serum creatinine level from baseline or dialysis initiation was reached by 129 study participants during a median follow-up of 5.8 years.
  3. In matched analysis, there was an association between tonsillectomy and the primary outcome reduction; the benefit was not modified by baseline characteristic differences in subgroup analyses.