Prominent IgM Deposition in Glomerulus Is Associated with Severe Proteinuria and Reduced after Combined Treatment of Tonsillectomy with Steroid Pulse Therapy in Patients with IgA Nephropathy

IgA nephropathy (IgAN) is characterized by mesangial deposition of IgA, C3, and often IgM. We examined the relationship among IgM deposition, clinical features, and renal outcome in IgAN patients who underwent combined treatment of tonsillectomy with steroid pulse therapy (Tx-SP). We retrospectively reviewed 73 IgAN patients treated with Tx-SP from March 2006 to March 2014. The patients were divided into those with moderate (2+) to severe (3+) mesangial IgM deposition (Prominent IgM-positive patients, P-Group) and those with negative (−) to faint (1+) deposition (the “Other” patients, O-Group). Using propensity scores to minimize confounding factors, 11 propensity score-matched patients with O-Group (mO-Group) were compared to 11 P-Group patients. The study outcome was defined as urinary protein grade by urine test strip before Tx-SP and one year after Tx-SP. P-Group patients exhibited an increased severity of proteinuria compared to O-Group (p=0.018) and mO-Group patients (p=0.009) before Tx-SP. After Tx-SP, proteinuria was significantly ameliorated in the P-Group, reaching the same severity recorded in the O-Group (p=0.007) and mO-Group (p=0.021). No significant differences were noted between P-Group and mO-Group in microhematuria, serum creatinine level, and histological severity. Prominent IgM deposition is associated with severe proteinuria in IgAN. However, Tx-SP induces a sufficient reduction in the severity of proteinuria in IgM-positive IgAN

Comparison of administration of single- and triple-course steroid pulse therapy combined with tonsillectomy for immunoglobulin A nephropathy

Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis that can cause end-stage renal disease. Recently, tonsillectomy combined with corticosteroid pulse (TSP) has been shown to be effective for achieving clinical remission and favorable renal outcome in patients with IgAN. However, the standard regimen of corticosteroid use in TSP has not been established. Herein, we compared the effect of single- or triple-course steroid pulse therapy combined with tonsillectomy in patients with IgAN. This retrospective, observational cohort study included 122 patients with IgAN enrolled from January 2004 to December 2018 at 2 independent institutions. We divided the patients into 2 groups; single-course (TSP1: n = 70) and triple-course (TSP3: n = 52) of corticosteroid pulse therapy (1 course comprised 3 consecutive days' infusion of 0.5 g methylprednisolone) combined with tonsillectomy. The primary outcome for renal survival was defined as the first occurrence of >= 30% decrease in estimated glomerular filtration rate from baseline. Secondary outcomes included the incidence of clinical remission and recurrence of the disease. Regarding clinical parameters and findings at baseline, there were no significant differences between the 2 groups. The 8-years renal survival in the 2 groups was not significantly different according to Kaplan-Meier curves (TSP1; 82.5% vs TSP3; 69.2%, log-rank test P = .39). The cumulative incidence rates of remission of hematuria (94.4% vs 85.4%, P = .56) and clinical remission (85.0% vs 64.8%, P = .07) were comparable in both groups, while those of proteinuria showed higher rates in TSP1 than TSP3 (88.4% vs 65.4%, P = .02). The cumulative incidence of relapse of hematuria (5.6% vs 2.3%, P = .42) and proteinuria (7.1% vs 3.3%, P = .41) showed no significant differences in the 2 groups. Cox regression analyses showed that the number of courses of corticosteroid pulse therapy was not significantly associated with renal outcome (TSP1 vs TSP3; Hazard ratios 0.69, 95% confidence intervals 0.29-1.64, P = .39). The effect of single-course corticosteroid pulse therapy is not statistically, significantly different from triple-course in TSP protocol for improving renal outcome and preventing relapse in patients with IgAN. Single-course corticosteroid pulse therapy may become a treatment option for patients with IgAN

Soluble Interleukin-2 Receptor Predicts Treatment Outcome in Patients With Autoimmune Tubulointerstitial Nephritis. A Preliminary Study

BackgroundAutoimmune tubulointerstitial nephritis (TIN) is characterized by immune-mediated tubular injury and requires immunosuppressive therapy. However, diagnosing TIN and assessing therapeutic response are challenging for clinicians due to the lack of useful biomarkers. Pathologically, CD4(+) T cells infiltrate to renal tubulointerstitium, and soluble interleukin-2 receptor (sIL-2R) has been widely known as a serological marker of activated T cell. Here, we explored the usefulness of serum sIL-2R to predict the treatment outcome in patients with autoimmune TIN. MethodsStudy Design: Single-center retrospective observational study. Participants62 patients were diagnosed of TIN from 2005 to April 2018 at Hokkaido University Hospital. Among them, 30 patients were diagnosed with autoimmune TIN and treated with corticosteroids. We analyzed the association between baseline characteristics including sIL-2R and the change of estimated glomerular filtration rate (eGFR) after initiation of corticosteroids. ResultsThe serum sIL-2R level in patients with autoimmune TIN was significantly higher than that in chronic kidney disease patients with other causes. Mean eGFR in autoimmune TIN patients treated with corticosteroids increased from 43.3 +/- 20.4 mL/min/1.73 m(2) (baseline) to 50.7 +/- 19.9 mL/min/1.73 m(2) (3 months) (Delta eGFR; 22.8 +/- 26.0%). Multivariate analysis revealed that higher sIL-2R (per 100 U/mL, beta = 1.102, P < 0.001) level was independently associated with the renal recovery. In ROC analysis, sIL-2R had the best area under the curve value (0.805) and the cutoff point was 1182 U/mL (sensitivity = 0.90, 1-specificity = 0.45). ConclusionsOur study showed that elevated serum sIL-2R levels might become a potential predictive marker for therapeutic response in autoimmune TIN