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

Ultrastructural Aspects of Rat Renal Tubular Epithelium in Vitro: Scanning Electron Microscopy （SEM） Analyses at Various Stages of Culture

Renal tubular epithelial cells are capable of regenerating themselves after severe injury. In cellular regeneration, cell migration plays a crucial role. Previous studies have demonstrated that changes in cellular morphology, including the formation of lamellipodia, are very important in cell migration. However, the ultrastructure of a migrating cell largely remains undescribed. In the present study, we applied scanning electron microscopy techniques to cultured cells, and observed fine ultrastructural changes in cultured renal tubular epithelium during migration. We found that there were small sphere-like structures and/or microvilli on the cell surface of floating epithelia, that leaf-like structures closely resembling lamellipodia developed circumferentially in the early stages of culture, and that long and branched filopodia developed that were much larger in diameter compared to filopodia at earlier stages. To the best of our knowledge, these findings are new, and may contribute to the development of a new therapeutic strategy for severe tubular damage of the kidney

Positive renal familial history in IgA nephropathy is associated with worse renal outcomes: a single-center longitudinal study

Abstract Background IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Although most IgAN cases are sporadic, few show a familial aggregation. However, the prevalence and prognosis of IgAN individuals with positive familial history (FH) of renal disorders remains uncertain. To address these issues, we conducted a longitudinal observational study on a single-institution cohort of patients with biopsy-proven IgAN. Methods A total of 467 IgAN patients who underwent renal biopsy during 1994 to 2019 were ascertained to have positive- or negative-FH by history taking and were followed for an average of 8.9 years. We compared the clinical and pathological features of the two subgroups. The primary outcome, a composite of a hard endpoint (end-stage renal disease [ESRD]) and surrogate endpoint (a 50% or more reduction in the estimated glomerular filtration rate [eGFR] from baseline), was evaluated. To estimate the risk for progression to ESRD, a Cox proportional hazards analysis was performed for a subset of patients who underwent follow-up for > 2 years and had an eGFR > 30 mL/min/1.73 m2 at baseline (n = 389; observation, 8.7 years). Results Positive-FH subtype accounted for 11.6% (n = 54) of all IgAN patients. At baseline, there were no significant differences between the positive- and negative-FH subgroups regarding age, sex, comorbid disease, MEST-C score, observation period, and therapeutic interventions. However, the eGFR value at baselines was significantly lower in the positive-FH subgroup than in the negative-FH subgroup (P < 0.01). On multivariate analysis, positive-FH emerged an independent determinant of poorer renal outcomes (odds ratio, 2.31; 95% confidence interval, 1.10–4.85; P = 0.03), after adjusting for confounding factors. eGFR at follow-up was significantly lower in the positive-FH subgroup than in the negative-FH subgroup after adjustment for age and observation period. Conclusions Positive-FH was found in 11.6% of all IgAN patients, consistent with the incidence seen in previous literature. A significantly lower eGFR at baseline and last follow-up and unfavorable renal outcomes in the positive-FH subgroup suggest that certain genetic risk factors predisposing to renal failure may exist in a fraction of our IgAN cohort. (331 words)