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Introduction and Aims: Deposition of C1q occurs in 0 to 45% of patients with IgAN. In order to identify whether mesangial C1q deposition in IgAN is a novel marker for the response to tonsillectomy plus steroid pulse therapy (TSP), we studied the association between mesangial C1q deposition in IgAN and the remission rate after TSP therapy for IgAN. Methods: We conducted a retrospective cohort study at a single Japanese center. We analyzed data on 110 patients diagnosed with IgA nephropathy who received TSP between January 2003 and December 2012. Positive C1q findings were defined as diffuse mesangial C1q deposition. The study outcome was the resolution of abnormal urinary findings and was defined as negative proteinuria and negative occult blood 1 year after steroid pulse therapy. Results: In all enrolled cases, 69 patients (62.7%) went into remission. Ten out of 24 (41.7%) C1q-positive patients experienced remission, and 59 out of 86 (68.6%) C1q-negative patients experienced remission. Multiple logistic regression model analysis showed that the absence of C1q deposition increased the odds ratio for remission (odds ratio 4.41; 95% confidence interval 1.33-15.75, p = 0.017). Conclusions: These results suggest that the absence of diffuse C1q deposition in the mesangial area of the glomerulus in patients with IgA nephropathy is a positive predictive sign for a response to TSP and is associated with the resolution of urinary abnormalities 1 year after TSP.

A common form of methicillin-resistant Staphylococcus aureus (MRSA) associated glomerulonephritis is either an endocapillary proliferative glomerulonephritis or a crescentic glomerulonephritis. This report describes the development of reversible nephrotic syndrome following MRSA infection in a patient with amyloid A amyloidosis. The patient had been diagnosed as having rheumatoid arthritis for 50 years. Suppurative arthritis due to MRSA became complicated 2 years prior to admission to our hospital. In the meantime, a nonnephrotic-range proteinuria developed. Two weeks before admission, nephrotic syndrome developed. The serum creatinine level remained unchanged throughout the course, but common features characteristic of MRSA-associated glomerulonephritis were observed in this patient, such as elevated serum IgG and IgA levels. A renal biopsy specimen showed glomerular amyloid A amyloidosis of a nodular type, infiltrated mononuclear cells in the mesangium, deposition of IgG, IgA, and C3, and swelling of glomerular endothelial cells. There were no crescentic glomeruli. Following surgical eradication of the MRSA focus in the right knee joint, nephrotic syndrome disappeared. Hence, it was highly possible that MRSA infection induced a reversible nephrotic syndrome by causing reversible injuries to glomerular endothelial cells. The description of this case serves to illustrate the range of MRSA infections that may cause various forms of glomerulonephritides.

Although most studies suggest that the hypercellularity in mesangial proliferative nephritis is due to increased cell proliferation, we hypothesized that it may also be due to increased expression of survival factors that may block their removal (apoptosis). We therefore studied the expression of apoptosis preventing/delaying the bcl-2 gene product in the glomerulus with various human glomerulonephritides. Immunohistochemistry for Bcl-2, proliferating cell associated protein (Ki-67) and α-smooth muscle actin (α-SMA) was performed on 55 biopsied kidney tissues: 6 cases of orthostatic proteinuria as a control (OP); 6 cases of diffuse proliferative lupus nephritis (WHO type IV, LN-MPGN); 24 cases of IgA nephropathy (IgA); 9 cases of minimal change nephrosis and 10 cases of idiopathic membranous nephropathy. The number of Ki-67-positive cells and the expression of α-SMA in the glomerulus were significantly higher in LN-MPGN and IgA. There was a significant positive correlation between glomerular Bcl-2 expression and glomerular cell proliferation evaluated by the number of Ki-67-positive cells (r = 0.605, p < 0.01) or glomerular α-SMA expression (r = 0.674, p < 0.01). Glomerular expression of Bcl-2 in IgA or LN-MPGN was significantly higher than that in OP (p < 0.01 and p < 0.05 vs. OP, respectively). The Bcl-2-positive cells were present in mesangial locations and demonstrated a perinuclear pattern. These results suggest that maintenance of glomerular hypercellularity in human glomerular diseases is partly due to the prevention of mesangial cell death via Bcl-2 expression.