Anomalous kinetics of galactose-deficient IgA incurring nephropathy revealed by cross-scale optical imaging

IgA nephropathy (IgAN) is the most common glomerulonephritis, characterized by the presence of predominant IgA deposits in the mesangium. Deposition of pathogenic IgA in kidney tissue is a fundamental initiating process that has not been fully studied. Here, we employed optical imaging to directly visualize kidney deposition of IgA with optimized spatial and temporal resolution in BALB/c nude mice. Real-time fluorescence imaging revealed that IgA isolated from patients with IgAN preferentially accumulated in the kidneys, compared with IgA purified from healthy individuals. There was no difference in the distribution of either IgA preparation by the liver. Photoacoustic computed tomography dynamically demonstrated and quantified the enhanced retention of pathological IgA in the kidney cortex. Photoacoustic microscopy tracked IgA deposition in the glomeruli with a resolution down to three microns in a mouse model. Notably, longitudinal fluorescent imaging revealed that galactose-deficient IgA (Gd-IgA), which was elevated in the circulation of patients with IgAN, persisted in the kidney for longer than two weeks, and stable deposition of Gd-IgA induced kidney impairment, including albuminuria and mesangial proliferation. Thus, our study highlights that the aberrant kidney depositional kinetics of Gd-IgA is involved in the pathogenesis of IgAN. Hence, cross-scale optical imaging has potential applications in assessing immune-mediated kidney diseases and uncovering underlying mechanisms of disease. IgA nephropathy (IgAN) is the most common glomerulonephritis, characterized by the presence of predominant IgA deposits in the mesangium. Deposition of pathogenic IgA in kidney tissue is a fundamental initiating process that has not been fully studied. Here, we employed optical imaging to directly visualize kidney deposition of IgA with optimized spatial and temporal resolution in BALB/c nude mice. Real-time fluorescence imaging revealed that IgA isolated from patients with IgAN preferentially accumulated in the kidneys, compared with IgA purified from healthy individuals. There was no difference in the distribution of either IgA preparation by the liver. Photoacoustic computed tomography dynamically demonstrated and quantified the enhanced retention of pathological IgA in the kidney cortex. Photoacoustic microscopy tracked IgA deposition in the glomeruli with a resolution down to three microns in a mouse model. Notably, longitudinal fluorescent imaging revealed that galactose-deficient IgA (Gd-IgA), which was elevated in the circulation of patients with IgAN, persisted in the kidney for longer than two weeks, and stable deposition of Gd-IgA induced kidney impairment, including albuminuria and mesangial proliferation. Thus, our study highlights that the aberrant kidney depositional kinetics of Gd-IgA is involved in the pathogenesis of IgAN. Hence, cross-scale optical imaging has potential applications in assessing immune-mediated kidney diseases and uncovering underlying mechanisms of disease. in this issueKidney InternationalVol. 103Issue 2PreviewAspirin (ASA) has been postulated to improve cardiovascular outcomes in at-risk individuals, although the extent of protection remains controversial. The effect of ASA on cardiovascular outcomes in patients with chronic kidney disease (CKD) was examined in The International Polycap Study-3 (TIPS-3). Patients were treated with low-dose ASA (75 mg/d) or placebo and stratified by estimated glomerular filtration rate (eGFR). The investigators looked at a composite outcome of nonfatal myocardial infarction, nonfatal stroke, and cardiac death. Full-Text PDF