Heard a case this morning regarding an elderly white patient who presented with nephrotic syndrome and minimal hematuria. After going through the extensive differential diagnosis, focusing largely on the likely candidates (membranous nephropathy and minimal change disease), the biopsy ultimately showed IgA Nephropathy. Though nephrotic syndrome is an uncommon presentation of IgA Nephropathy, the fact that IgA Nephropathy is relatively common means that IgA Nephropathy actually accounts for about 14% of cases of nephrotic syndrome (in whites--IgA Nephropathy is pretty uncommon in blacks). There are a lot of different ways IgA Nephropathy can present. Here are some of them:
1. Asymptomatic hematuria: a lot of cases are picked up with routine urinalyses. Often these cases have little to no progression of renal disease over several decades.
2. Synpharyngitic hematuria: the "classic" presentation of IgA Nephropathy occurs within 1-3 days of a mucosal infection such as a URI.
3. Acute kidney injury: occasionally, IgA Nephropathy will first manifest as AKI. This can take 2 basic forms, and distinguishing between the two of them is critical:
A) The ATN Form: patients may become oliguric as a result of an acute worsening of hematuria, which can result in tubular toxicity, but will almost always recover renal full renal function afterwards.
B) The crescentic Form: patients with crescents on the background of mesangial IgA deposits on renal biopsy have a very poor prognosis and will often progress to permanent renal damage even despite aggressive therapy.
4. Nephrotic Syndrome: as mentioned above, IgA Nephropathy accounts for about 14% of all nephrotic syndrome in whites. This can also take two different forms:
A) "Minimal Change Disease" superimposed on IgA Nephropathy, which tends to be very steroid responsive.
B) "Structural Damage"--severe, prolonged damage to mesangial cells can result in secondary podocyte injury that is generally not reversible and can be thought of as a secondary nephrotic syndrome.
Always keep IgA Nephropathy in mind in formulating a differential diagnosis! It is relatively common compared to a lot of the other glomerular diseases we may invoke.
Agreed. I was similarly fooled very recently. There was minimal hematuria (few RBCs, 0-5 /hpf) and nearly 5 grams proteinuria in a 60 yo WM with serum creatinine about 2mg/dL. I think it is good advice to keep IgAN in the DDx pre-biopsy.
ReplyDeleteI also noticed you listed Membranous and Minimal Change Disease (MCD) in your initial DDx. I would always include FSGS as well. Furthermore, I always am concerned about adults diagnosed with MCD that may have unsampled FSGS... one should always have a healthy skepticism about each biopsy and look it over with the pathologist.
You are doing a great job with your blog... keep up the good work
SP
A fellow and I presented an abstract at NKF a few years ago about a nephrotic syndrome IgA. The guy went from 9g of proteinuria to 0 after about 6 hours of steroids. I never saw anything like it.
ReplyDeleteThe light microscopy looked like MCD but the immuno lit up IgA. 6 months later the kid developed Hodgkins, so in my mind the whole thing looked and felt much more like MCD.
I had never heard the stat that 16% of NS was due to IgA, the stat I keep in my mind is that 20% of IgA present as NS.
And I agree, great blog.
Thanks so much for the comments!
ReplyDeleteGood point about keeping FSGS in the DDx for nephrotic syndrome, that's one of the Big Three and not sure why I didn't mention it.
The statistic on IgA causing 14% of nephrotic syndrome (from whites only) was taken from this 1997 AJKD paper from Haas et al: Changing Etiologies of Unexplained Adult Nephrotic Syndrome: A comparison of Renal Biopsy Findings From 1976-1979 and 1995-1997. 30(5): 621-631.