C3 glomerulopathy (C3G) is a group of heterogeneous ultrarare kidney diseases characterized by dysregulated activation of the complement alternative pathway (AP) leading to excessive C3 cleavage. Diagnosis relies on kidney biopsy showing predominant C3 deposition in the glomerular basement membrane, with electron microscopy differentiating between dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). The main drivers of AP dysregulation in C3G are acquired rather than genetic and consist primarily of autoantibodies called nephritic factors (C3Nefs, C4Nefs and C5Nefs) that bind to and stabilize complement convertases, causing complement overactivation.
View Article and Find Full Text PDF: Early and accurate grading of renal cell carcinoma (RCC) improves patient risk stratification and has implications for clinical management and mortality. However, current diagnostic approaches using imaging and renal mass biopsy have limited specificity and may lead to undergrading. : This study explored the use of hyperpolarised [1-C]pyruvate MRI (HP C-MRI) to identify the most aggressive areas within the tumour of patients with clear cell renal cell carcinoma (ccRCC) as a method to guide biopsy targeting and to reduce undergrading.
View Article and Find Full Text PDFInvestigating venetoclax (VTX) resistance in multiple myeloma (MM) is crucial for the development of novel therapeutic strategies to tackle resistance. We conducted a multi-omic characterization of established VTX-resistant isogenic human myeloma cell lines (HMCL) and primary MM patient samples pre- and post-VTX treatment. Transcriptomic and proteomic analysis revealed that resistance was largely associated with BCL-2 family protein dysregulation, including upregulation of anti-apoptotic proteins such as MCL-1, BCL-XL, BCL-2, and downregulation of pro-apoptotic members.
View Article and Find Full Text PDFBackground: Patients with advanced chronic kidney disease requiring initiation of kidney replacement therapy (KRT) are frequently asked to enact complex management plans. Treatment burden has been defined as the effect of healthcare workload and the capacity a person has to manage this workload has on wellbeing. The aim of this review is to examine the experience of healthcare workload and the factors that affect capacity to meet that workload for people transitioning onto KRT for the first time, using a framework synthesis of published literature informed by normalisation process theory (NPT) and theory of patient capacity (TPC).
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