Bowman's capsule rupture and the Oxford MEST-C score in adult patients with Immunoglobulin a vasculitis nephritis: a single center experience.

OBJECTIVE: Bowman's capsule rupture (BCR) is a glomerular pathological change, but it is still not well recognized in immunoglobulin A vasculitis nephritis (IgAV-N). The Oxford MEST-C score is a classification for IgA nephropathy; however, its clinical correlation and prognostic value in adult patients with IgAV-N are unclear. METHODS: A retrospective study of 145 adult patients with IgAV-N diagnosed by renal biopsy was conducted. Clinical manifestations, pathological changes and the prognosis of IgAV-N patients were compared depending on the presence or absence of BCR, International Study of Kidney Disease in Children (ISKDC) classification and MEST-C score. The primary endpoint events were end-stage renal disease, renal replacement therapy and all-cause death. RESULTS: In total, 51 of 145 (35.17%) patients with IgAV-N presented with BCR. Patients with BCR had more proteinuria, lower serum albumin, and more crescents. Compared with IgAV-N patients with crescents only, 51/100 patients with crescents combined with BCR had a higher proportion of crescents in all glomeruli (15.79% vs. 9.09%; p = 0.003). Patients with higher ISKDC grades had more severe clinical presentation, but it did not reflect the prognosis. However, the MEST-C score not only reflected clinical manifestations but also predicted prognosis (p < 0.05). BCR contributed to the effectiveness of the MEST-C score in predicting the prognosis of IgAV-N (C-index: 0.845 to 0.855). CONCLUSIONS: BCR is associated with clinical manifestations and pathological changes in patients with IgAV-N. The ISKDC classification and MEST-C score are related to the patient's condition, but only the MEST-C score is correlated with the prognosis of patients with IgAV-N, while BCR can improve its predictive ability.

BCR was associated with clinical manifestations and pathological changes in patients with IgAV-N, particularly crescents.The ISKDC classification was related to clinical manifestations of patients with IgAV-N, but it wasn't associated with prognosis.The Oxford MEST-C score was correlated to clinical presentations and prognosis of patients with IgAV-N, while BCR can improve its predictive ability.

Crescents, an Independent Risk Factor for the Progression of Type 2 Diabetic Kidney Disease.

CONTEXT: Crescents have been noticed in pathologic changes in patients with diabetic kidney disease (DKD). However, the clinical significance of crescents is still not well recognized. OBJECTIVE: The main objective was to investigate the association between crescents and the prognoses of type 2 DKD (T2DKD) patients, and, secondly, to analyze the relationship between crescents and clinicopathologic features. METHODS: A retrospective cohort study of 155 patients with T2DKD diagnosed by renal biopsy was carried out in a single center. Clinicopathologic features of patients with or without crescents were analyzed. Cox regression models and meta-analysis were used to determine the prognostic values of crescents for T2DKD. A nomogram was constructed to provide a simple estimation method of 1, 3, and 5-year renal survival for patients with T2DKD. RESULTS: Compared with T2DKD patients without crescents, patients with crescents had higher 24-hour proteinuria and serum creatinine levels, as well as more severe Kimmelstiel-Wilson (K-W) nodules, segmental sclerosis (SS), and mesangiolysis (all P < .05). Furthermore, the crescents were positively correlated with serum creatinine, 24-hour proteinuria, K-W nodules, SS, mesangiolysis, and complement 3 deposition. Multivariate Cox models showed that crescents were an independent prognostic risk factor for renal survival (hazard ratio [HR] 2.68, 95% CI 1.27-5.64). The meta-analyzed results of 4 studies on crescents in T2DKD confirmed that patients with crescents had a significantly higher HR for renal progression. CONCLUSION: Patients with crescents in T2DKD have more severe clinicopathologic changes and worse prognoses. The crescent can serve as an independent risk factor for T2DKD progression.

Digital Spatial Profiling of Individual Glomeruli From Patients With Anti-Neutrophil Cytoplasmic Autoantibody-Associated Glomerulonephritis.

We previously showed that the rupture of Bowman's capsule (BC) promotes the progression of crescentic glomerulonephritis by enhancing the entry of CD8+ T cells into the glomeruli. In the present study, we utilized digital spatial profiling to simultaneously profile the altered abundances of the messenger RNA (mRNA) transcripts and proteins in the glomerular and periglomerular areas of four biopsy samples of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis (ANCA-GN) and two biopsy specimens of minimal change disease (MCD) controls. The paraffin-embedded biopsy samples were stained with collagen IV, CD45, and SYTO 13 to distinguish the glomeruli with periglomerular infiltration but intact BC, with focal BC rupture, and with extensive rupture of BC and glomeruli without crescent formation and leukocytic infiltration in ANCA-GN. By assessing multiple discrete glomerular areas, we found that the transcript expression levels of the secreted phosphoprotein-1 and its receptor CD44 were upregulated significantly in the glomeruli with more severe ruptures of BC, and their expression levels correlated positively with the fibrotic markers. We also found that both alternative and classic complement pathways were activated in the glomeruli from patients with ANCA-GN. Furthermore, M1 macrophages were involved mostly in the early stage of BC rupture, while M2 macrophages were involved in the late stage and may contribute to the fibrosis process of the crescents. Finally, loss of glomerular cells in ANCA-GN was likely mediated by apoptosis. Our results show that digital spatial profiling allows the comparative analysis of the mRNA and protein profiles in individual glomeruli affected differently by the disease process and the identification of potential novel mechanisms in ANCA-GN.