IgA nephropathy (IgAN) features variable renal pathology and a heterogeneous clinical course. Our aim was to search noninvasive biomarkers from urinary exosomes for IgAN patients; membrane nephropathy and minimal change disease were included as other glomerulopathy controls. Transmission electron microscopy and nanoparticle tracking analysis confirmed the size and morphology characteristic of urinary exosomes. Exosome markers (Alix and CD63) as well as renal cell markers [aquaporin 2 (AQP2) and nephrin] were detected, which indicate the renal origin of urinary exosomes. Exosome excretion was increased markedly in IgAN patients compared with controls and correlated with levels of proteinuria and tubular injury. More important, urinary exosome excretion correlated with greater histologic activity (mesangial hypercellularity, crescents, and endocapillary hypercellularity). Profiling of the inflammation-related mRNA revealed that exosomal chemokine (C-C motif) ligand 2 (CCL2) was up-regulated in IgAN patients. In a validation study, CCL2 was exclusively highly expressed in IgAN patients compared with healthy controls as well as minimal change disease and membrane nephropathy patients. Also, a correlation between exosomal CCL2 and estimated glomerular filtration rate levels was found in IgAN. Exosomal CCL2 was correlated with tubulointerstitial inflammation and C3 deposition. High CCL2 levels at the time of renal biopsy were associated with subsequent deterioration in renal function. Thus, urinary exosomes and exosomal CCL2 mRNA are promising biomarkers reflecting active renal histologic injury and renal function deterioration in IgAN.

Conventional methods used for measuring regional renal blood flow, such as laser-Doppler flowmetry, are highly invasive, and each measurement is restricted to a discrete location. The aim of this study was to determine whether ultrasound imaging in conjunction with enhanced contrast agent (microbubbles; Vevo MicroMarker, VisualSonics) could provide a viable noninvasive alternative. This was achieved by determining changes in renal cortical and medullary rate of perfusion in response to a bolus injection of endothelin-1 (ET-1; 0.6, 1.0, or 2.0 nmol/kg) and comparing these responses to those observed in separate groups of mice with conventional laser-Doppler methods. Intravenous infusion of ET-1 in anesthetized male C57bl/6 mice resulted in a dose-dependent increase in mean arterial pressure and a dose-dependent decrease in total renal blood flow as measured by pulse-wave Doppler. ET-1 infusion resulted in a dose-dependent decrease in regional kidney perfusion as measured by both ultrasound with enhanced contrast agent and laser-Doppler measurements, verifying the use of ultrasound to measure regional kidney perfusion. Noted limitations of ultrasound imaging compared with laser-Doppler flowmetry included a lower degree of sensitivity to changes in tissue perfusion and the inability to assess rapid or transient changes in tissue perfusion. In conclusion, ultrasound represents an effective and noninvasive method for the measurement of relatively short-term, steady-state changes in regional blood flow in the mouse kidney.

A novel fluorinated montmorillonite (F-MT) was synthesized via exchange of cationic fluorinated surfactant to selectively adsorb perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) from water. F-MT displayed fast and high sorption for PFOS and PFOA at concentrations below 10 μg/L, and performed better than the best activated carbon and resin previously reported. The spent F-MT can be completely regenerated by methanol solution and can be reused five times without reduction in sorption capacity. Moreover, the F-MT possessed excellent selectivity for PFOS and PFOA in the presence of other organic pollutants. The coexisting phenol, pyridine, dodecylbenzenesulfonate (SDBS), and phenanthrene (PHE) exhibited no effect on PFOS and PFOA sorption. Due to the nanoscale interlayer structure and chemical nature of F-MT, macromolecular humic acid had little effect on PFOS and PFOA sorption. Also, F-MT adsorbed very little SDBS and PHE. The results of competitive sorption and density functional theory calculations verified that PFOS and PFOA were adsorbed on the C–F chain of F-MT, while PHE and SDBS sorption occurred on the hydrocarbon part of F-MT. The unique hydro-oleophobic C–F chain on the F-MT was responsible for selective sorption of perfluoroalkyl acids (PFAAs), providing a new mechanistic insight for the interactions between PFAAs and fluorinated adsorbents. In addition, F-MT offers promising potential for removal of PFOS and PFOA from contaminated water.

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