Background. Patients with IgA nephropathy (IgAN) often show aggravation of renal injury with macroscopic hematuria after mucosal infections, especially tonsillitis. We previously demonstrated the important role of mucosal Toll-like receptor 9 (TLR9) activation in the pathogenesis of murine IgAN. Moreover, a single nucleotide polymorphism (SNP) in TLR9 was significantly associated with pathological severity in human IgAN. In this study, we investigated correlations between tonsillar TLR9 messenger RNA expression, TLR9 SNP genotypes and clinical outcomes following tonsillectomy with steroid pulse therapy (SPT) in IgAN patients. Methods. Tonsillar TLR9 expression was examined in IgAN (n ¼ 49) and control (n ¼ 15) patients who had undergone tonsillectomy. The correlations between tonsillar TLR9 expression level, TLR9 SNP genotypes and clinical outcomes after tonsillectomy with SPT were examined. Results. High expression of tonsillar TLR9 was observed in ~23% of IgAN patients. These patients showed stronger and earlier remission of hematuria and proteinuria than those with low TLR9 expression. Patients with the TT genotype of TLR9 SNP (rs352140) had more severe renal damage than those with other genotypes. Patients whose serum IgA level decreased more than average after tonsillectomy (large DIgA) showed higher cumulative remission rates of proteinuria than patients with a smaller decrease in these levels (small DIgA). CT/CC genotypes were more dominant and tonsillar TLR9 expressions significantly higher in large DIgA patients than in small DIgA patients. Conclusion. In IgAN patients, expression levels of tonsillar TLR9 and TLR9 SNP were well correlated with the efficacy of tonsillectomy with SPT.

Tonsillar TLR9 expression and efficacy of tonsillectomy with steroid pulse therapy in IgA nephropathy patients

:

Aim: The effectiveness of steroid pulse therapy combined with tonsillectomy (ST) has been shown in immunoglobulin A nephropathy (IgAN) patients with moderate or severe urinary abnormalities. The present study aimed to clarify whether the effectiveness may be extrapolated to IgAN with minor urinary abnormalities, and whether the effectiveness may depend on the histological severity with minor urinary abnormalities.



Methods:  Data on 388 IgAN patients diagnosed by renal biopsies between 1987 and 2000 in Sendai Shakaihoken Hospital, who presented glomerular haematuria and minimal proteinuria (≤0.5 g/day) at baseline, were analyzed. Cox regression was used to examine associations between baseline use of ST and subsequent clinical remission (CR), defined as negative proteinuria by dipstick and urinary erythrocytes of less than 1/high-power field. The instrumental variable method was also used to overcome confounding by treatment indication.



Results:  During a median follow up of 24 months, we observed 170 CR cases. Patients receiving ST were younger and showed a better case-mix profile. Patients with ST had a significantly higher rate of CR than patients without tonsillectomy or steroid pulse in an unadjusted (hazard ratio (HR) = 5.51, 95% confidence interval (CI) = 3.33–9.12, P < 0.001) or adjusted Cox model (HR = 4.65, 95% CI = 2.43–8.88, P < 0.001). Less severe histological findings were substantially associated with higher CR rate in ST group. Adjusting for confounding by treatment indication showed an attenuated but still significant effect of ST (HR = 3.10, 95% CI = 2.02–4.77, P < 0.001).



Conclusion:  ST significantly increased the probability of CR in IgAN patients with glomerular haematuria and minimal proteinuria, and it was more effective in those with less severe histological findings.

/pdf/clinical-effectiveness-of-steroid-pulse-therapy-combined-4xmecazc82.pdf

Clinical effectiveness of steroid pulse therapy combined with tonsillectomy in patients with immunoglobulin A nephropathy presenting glomerular haematuria and minimal proteinuria

Because of the well-established annual urinalysis screening system in Japan, the duration of nephropathy (DN) can be estimated in more than half of all patients with IgA nephropathy (IgAN) Treatment using a combination of tonsillectomy and steroid pulse (TSP) therapy has been reported as an effective method for obtaining clinical remission (CR), defined as negative hematuria and proteinuria, in IgAN patients The present study aims to identify the correlation between DN and CR rate in IgAN patients treated by TSP therapy We retrospectively investigated 830 IgAN patients who were followed up for 816 months after TSP therapy DN could be estimated in 495 of the 830 patients The CR rate among patients with DN ≤36 months was 873% (295/338 patients) The CR rate among patients with DN of 37–84 months was 733% (63/86 patients), while that among patients with DN ≥85 months was 423% (30/71 patients) The CR rate among the remaining 335 patients in whom DN could not be estimated because of missing annual urinalysis results was 436% (146/335 patients) A multivariate Cox regression model using data from the former group of 495 patients showed that DN ≤36 months was a significant predictor of CR (hazard ratio 1839; 95% confidence interval 1410–2398; P < 0001) Shorter DN is associated with higher likelihood of clinical remission in IgAN patients treated by TSP therapy

Significance of the duration of nephropathy for achieving clinical remission in patients with IgA nephropathy treated by tonsillectomy and steroid pulse therapy.

Evaluation of tonsillectomy before kidney transplantation in patients with IgA nephropathy.

Background
Medical intervention for patients with IgA nephropathy and mild proteinuria (<10 g/day) is controversial, and the effectiveness of tonsillectomy plus steroid pulse therapy (TSP) for such patients remains obscure

/pdf/significance-of-tonsillectomy-combined-with-steroid-pulse-51ywgj2o6r.pdf

Significance of tonsillectomy combined with steroid pulse therapy for IgA nephropathy with mild proteinuria

Use of Corticosteroids, Other Immunosuppressive Therapies, and Tonsillectomy in the Treatment of IgA Nephropathy

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Use of Corticosteroids, Other Immunosuppressive Therapies, and Tonsillectomy in the Treatment of IgA Nephropathy