Glomerular Disease Clinical Case Review

In this video, Craig Gordon, MD, nephrologist at Tufts Medical Center and associate professor of medicine at Tufts University School of Medicine, presents the baseline characteristics in this case of IgA nephropathy:

Editor’s note: The following is an automatically generated transcript of the above video.

"So this is a 46-year-old male recently referred for hematuria, proteinuria, and decreased GFR. His blood pressure was 138 over 84, millimeters of mercury, and his BMI was 27.4. His exam was entirely normal. His urinalysis revealed 3+ blood and 3+ protein, and quantification of the proteinuria revealed 2.9 grams per gram. His EGFR was 58 at the time of the visit, and there was evidence over the years of a decline from more normal values. So he was initially started on an ARB to manage the hypertension and proteinuria, and a kidney biopsy was recommended, and he eventually agreed to do this, and the biopsy showed changes consistent with IgA neuropathy. I don't have the images here to show, but the Oxford classification or MEST-C scores were as follows, M1, E0, S1, T0, C0. Essentially, there was evidence of mesangial hypercellularity, that's the M, and segmental sclerosis, that's the S. These were present. But endocapillary hypercellularity, and tubular atrophy, and interstitial fibrosis were largely absent.

And so this led to a series of discussions with a very intelligent patient to consider next steps as far as additional therapies. So before we get to the specific therapies, let's take a step back to understand the pathogenesis. So our current thought process regarding IGA is that it's a four hit phenomenon as far as its pathogenesis. The first hit is an increase in the production as well as circulation of galactose-deficient IgA1, represented here in red in panel A. The second hit are production of auto-antibodies targeting the galactose-deficient IgA1 here in panel B. Hit three is development of immune complexes between the galactose-deficient IgA1 and the autoantibodies. And in the final hit or hit four in panel D here is deposition of the circulating immune complexes in the mesangium at the glomerulus. Presented somewhat differently in a slide that looks at therapeutic options are shown here from a recent review."