IgA nephropathy is the most common form of glomerulonephritis in many parts of the world and remains an important cause of end-stage renal disease. Current evidence suggests that IgA nephropathy is not due to a single pathogenic insult, but rather the result of multiple sequential pathogenic “hits”. An abnormally increased level of circulating poorly O-galactosylated IgA1 and the production of O-glycan-specific antibodies leads to the formation of IgA1-containing immune complexes, and their subsequent mesangial deposition results in inflammation and glomerular injury. While this general framework has formed the foundation of our current understanding of the pathogenesis of IgA nephropathy, much work is ongoing to try to precisely define the genetic, epigenetic, immunological, and molecular basis of IgA nephropathy. In particular, the precise origin of poorly O-galactosylated IgA1 and the inciting factors for the production of O-glycan-specific antibodies continue to be intensely evaluated. The mechanisms responsible for mesangial IgA1 deposition and subsequent renal injury also remain incompletely understood. In this review, we summarize the current understanding of the key steps involved in the pathogenesis of IgA nephropathy. It is hoped that further advances in our understanding of this common glomerulonephritis will lead to novel diagnostic and prognostic biomarkers, and targeted therapies to ameliorate disease progression.
<b><i>Introduction:</i></b> Acute kidney injury (AKI) in coronavirus infection disease (COVID-19) is associated with disease severity. We aimed to evaluate risk factors associated with AKI beyond COVID-19 severity. <b><i>Methods:</i></b> A retrospective observational study of COVID-19 patients admitted to a tertiary hospital in Singapore. Logistic regression was used to evaluate associations between risk factors and AKI (based on Kidney Disease Improving Global Outcomes criteria). Dominance analysis was performed to evaluate the relative importance of individual factors. <b><i>Results:</i></b> Seven hundred seven patients were included. Median age was 46 years (interquartile range [IQR]: 29–57) and 57% were male with few comorbidities (93%, Charlson Comorbidity Index [CCI] <1). AKI occurred in 57 patients (8.1%); 39 were in AKI stage 1 (68%), 9 in stage 2 (16%), and 9 in stage 3 (16%). Older age (adjusted odds ratio [aOR] 1.04; 95% confidence interval [CI]: 1.01–1.07), baseline use of angiotensin-converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) (aOR 2.86; 95% CI: 1.20–6.83), exposure to vancomycin (aOR 5.84; 95% CI: 2.10–16.19), use of nonsteroidal anti-inflammatory drugs (NSAIDs) (aOR 3.04; 95% CI: 1.15–8.05), and severe COVID-19 with hypoxia (aOR 13.94; 95% CI: 6.07–31.98) were associated with AKI in the multivariable logistic regression model. The 3 highest ranked predictors were severe COVID-19 with hypoxia, vancomycin exposure, and age, accounting for 79.6% of the predicted variance (41.6, 23.1, and 14.9%, respectively) on dominance analysis. <b><i>Conclusion:</i></b> Severe COVID-19 is independently associated with increased risk of AKI beyond premorbid conditions and age. Appropriate avoidance of vancomycin and NSAIDs are potentially modifiable means to prevent AKI in patients with COVID-19.
Immunoglobulin A nephropathy (IgAN) is one of the commonest global patterns of primary glomerulonephritis and remains a leading cause of chronic kidney disease and end‐stage renal disease. The sole diagnostic criterion of IgAN remains the presence of dominant mesangial immunoglobulin A deposits on kidney biopsy. Beyond this defining feature, there is significant heterogeneity in the epidemiology, clinical presentation, renal progression and long‐term outcomes of IgAN in different ethnic populations. Mirroring this heterogeneity in clinical phenotypes, there is also marked ethnic variation in the extent of histopathological lesions observed on kidney biopsy, which may partly explain the well‐documented differences in response to immunomodulatory agents reported in different regions of the world. In parallel, disparities have been identified in genetic association studies and key pathogenic pathways in different ethnic populations. Understanding the basis for these differences in IgAN has important implications for both clinical care and future research. In this review, we will examine the impact of ethnicity on the epidemiology, clinical presentation and outcomes, pathogenesis and genetic associations in IgAN.
With the exponential surge in patients with coronavirus disease 2019 (COVID-19) worldwide, the resources needed to provide continuous kidney replacement therapy (CKRT) for patients with acute kidney injury or kidney failure may be threatened. This article summarizes subsisting strategies that can be implemented immediately. Pre-emptive weekly multicenter projections of CKRT demand based on evolving COVID-19 epidemiology and routine workload should be made. Corresponding consumables should be quantified and acquired, with diversification of sources from multiple vendors. Supply procurement should be stepped up accordingly so that a several-week stock is amassed, with administrative oversight to prevent disproportionate hoarding by institutions. Consumption of CKRT resources can be made more efficient by optimizing circuit anticoagulation to preserve filters, extending use of each vascular access, lowering blood flows to reduce citrate consumption, moderating the CKRT intensity to conserve fluids, or running accelerated KRT at higher clearance to treat more patients per machine. If logistically feasible, earlier transition to intermittent hemodialysis with online-generated dialysate, or urgent peritoneal dialysis in selected patients, may help reduce CKRT dependency. These measures, coupled to multicenter collaboration and a corresponding increase in trained medical and nursing staffing levels, may avoid downstream rationing of care and save lives during the peak of the pandemic. Complete author and article information provided before references.
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