T cells play a key role in immune-mediated glomerulonephritis, but how cytotoxic T cells interact with podocytes remains unclear. To address this, we injected EGFP-specific CD8+ T cells from just EGFP death inducing (Jedi) mice into transgenic mice with podocyte-specific expression of EGFP. In healthy mice, Jedi T cells could not access EGFP+ podocytes. Conversely, when we induced nephrotoxic serum nephritis (NTSN) and injected Jedi T cells, EGFP+ podocyte transgenic mice showed enhanced proteinuria and higher blood urea levels. Morphometric analysis showed greater loss of EGFP+ podocytes, which was associated with severe crescentic and necrotizing glomerulonephritis. Notably, only glomeruli with disrupted Bowman's capsule displayed massive CD8+ T cell infiltrates that were in direct contact with EGFP+ podocytes, causing their apoptosis. Thus, under control conditions with intact Bowman's capsule, podocytes are not accessible to CD8+ T cells. However, breaches in Bowman's capsule, as also noted in human crescentic glomerulonephritis, allow access of CD8+ T cells to the glomerular tuft and podocytes, resulting in their destruction. Through these mechanisms, a potentially reversible glomerulonephritis undergoes an augmentation process to a rapidly progressive glomerulonephritis, leading to end-stage kidney disease. Translating these mechanistic insights to human crescentic nephritis should direct future therapeutic interventions at blocking CD8+ T cells, especially in progressive stages of rapidly progressive glomerulonephritis.

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High prevalence of total VC in Chinese CKD patients will supplement current knowledge, which is mostly limited, contributing in creating awareness and optimizing VC management.

The apoptosis of tubular epithelial cells in diabetic nephropathy (DN) is commonly observed in human renal biopsies. Inflammation plays a key role in DN, and pentosan polysulfate (PPS) has been shown to largely attenuate the inflammation of nephropathy in aging diabetic mice. p38 mitogen-activated protein kinase (p38 MAPK) plays a crucial role in tissue inflammation and cell apoptosis, and it is activated by hyperglycemia. In the present study, high glucose (HG)-treated human renal proximal tubular epithelial cells (HK-2) were used to examine the protective effects of PPS against HG-stimulated apoptosis and inflammation. The results of the study revealed that PPS markedly suppressed the HG-induced reduction in cell viability. Incubation of HK-2 cells with HG activated the p38 MAPK pathway and, subsequently, as confirmed by western blot analysis and flow cytometry, increased cell apoptosis, which was blocked by PPS. In addition, PPS treatment significantly inhibited HG-stimulated p38 MAPK and nuclear factor-κB activation, and reduced the production of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β and IL-6. In conclusion, PPS ameliorates p38 MAPK-mediated renal cell apoptosis and inflammation. The anti-apoptotic actions and anti-inflammatory effects of PPS prompt further investigation of this compound as a promising therapeutic agent against DN.

This systematic review and meta-analysis aimed to assess the predictive value of diabetic retinopathy (DR) on further diabetic nephropathy (DN) risk in patients with type 2 diabetes (T2D) based on the prospective cohort studies. PubMed, Embase, and the Cochrane Library were systematically searched for eligible prospective cohort studies through March 2020. The predictive value of DR was assessed using sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC) through the bivariate generalized linear mixed model and the random-effects model. Ten prospective cohort studies recruited 635 patients with T2D. The pooled sensitivity and specificity of DR for predicted DN were noted to be 0.64 (95% CI, 0.54–0.73) and 0.77 (95% CI, 0.60–0.88), respectively. The pooled PLR and NLR of DR for predicted DN were 2.72 (95% CI, 1.42–5.19) and 0.47 (95% CI, 0.33–0.67), respectively. The summary DOR for the relationship between DR and subsequent DN for T2D patients was 5.53 (95% CI, 2.00–15.30), and the AUC of DR for predicted DN was 0.73 (95% CI, 0.69–0.77). This study found significant associations between DR and subsequent DN risk for patients with T2D. Moreover, the predictive value of DR on subsequent DN risk was relatively lower.