IntroductionIgA nephropathy is the most common glomerulonephritis in the world. We conducted a pilot trial (NCT01103778) to test the effect of bortezomib in patients with IgA nephropathy and significant proteinuria.MethodsWe treated 8 consecutive subjects from July 2011 until March 2016 with 4 doses of bortezomib. All subjects had biopsy-proven IgA nephropathy and proteinuria of greater than 1 g per day. They were given 4 doses of bortezomib i.v. at 1.3 mg/m2 of body surface area per dose. Changes in proteinuria and renal function were followed for 1 year after enrollment. The primary endpoint was full remission defined as proteinuria of less than 300 mg per day.ResultsAll 8 subjects received and tolerated 4 doses of bortezomib over a 2-week period during enrollment. The median baseline daily proteinuria was 2.46 g (interquartile range: 2.29–3.16 g). At 1-year follow-up, 3 subjects (38%) had achieved the primary endpoint. The 3 subjects who had complete remission had Oxford classification T scores of 0 before enrollment. Of the remaining 5 subjects, 1 was lost to follow-up within 1 month of enrollment and 4 (50%) did not have any response or had progression of disease.ConclusionProteasome inhibition by bortezomib may reduce significant proteinuria in select cases of IgA nephropathy. Subjects who responded to bortezomib had Oxford classification T score of 0 and normal renal function.
Purpose To evaluate the value of multiparametric quantitative ultrasound imaging (QUI) in assessing chronic kidney disease (CKD) using kidney biopsy pathology as the reference standard. Methods We prospectively measured multiparametric QUI markers with grayscale, spectral Doppler, and acoustic radiation force impulse imaging in 25 patients with CKD prior to their kidney biopsies and in 10 healthy volunteers. Based on all pathology (glomerulosclerosis, IF/TA, arteriosclerosis, and edema) scores, the 25 CKD patients were classified into mild (no grade 3 and < 2 of grade 2) and moderate to severe (at least 2 of grade 2 or 1 of grade 3) CKD groups. Multiparametric QUI in the study included kidney length, cortical thickness, pixel-intensity, parenchymal shear wave velocity (SWV), intrarenal artery peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive index (RI). We tested the difference in QUI parameters among mild CKD, moderate to severe CKD, and healthy controls using ANOVA, analyzed correlations of QUI parameters to kidney pathology scores and to eGFR using the Pearson correlation coefficient, and examined the diagnostic performance of QUI parameters in determining moderate CKD and eGFR <60 using ROC curve analysis. Results There were significant differences in cortical thickness, pixel-intensity, PSV, and EDV among the 3 groups (all p< 0.01). Among QUI parameters, the top AUROCs of PSV and EDV for determining pathologic moderate to severe CKD were 0.88 and 0.97, and for eGFR <60 were 0.76 and 0.86, respectively. Moderate to good correlations were found for PSV, EDV, and pixel-intensity to pathology score and eGFR. Conclusion PSV, EDV, and pixel-intensity are valuable in determining moderate to severe CKD. The value of SWV in assessing CKD needs further investigation.
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