Endothelial
damage as a missing link… perhaps. Recent
study published in KI tries to link TMA as a cause of collapsing variant of
FSGS or CG. They looked at 53 patients
with renal limited TMA in a native kidney with emphasis on looking for
FSGS. 33 of the 53 had FSGS( mostly 19
being CG, 9 with NOS type, 3 with cellular and rest perihalar and tip
variant).
Some interesting findings:
1.
Prognosis
of TMA with FSGS was worse than TMA alone
2.
Most
of the patients with TMA were from HTN followed by complement disorders, drugs
and other causes. The more diffuse the TMA in the kidney in the 53 patients,
the more likely they would have systemic TMA, higher crt and higher BP
3.
At the time of the renal biopsy, there
was no significant difference between TMA without FSGS, TMA-CG, and TMA
with other FSGS variants with respect to age, sex, and ethnicity. The degree of
renal impairment also did not differ among the 3 groups. Proteinuria was
significantly higher(2.5gm) in cases with FSGS (CG and other FSGS variants) than in
cases without FSGS(1.42gm). Nevertheless, there was no difference of proteinuria
between CG and the “other FSGS” category (2.39 vs 2.72gm)
4.
The frequency of nephrotic syndrome was low in
each group (5.9%, 11.8%, and 7.7% in “no FSGS,” CG, and “other FSGS” groups,
respectively.
This is interesting as FSGS classically presents with significant proteinuria.
5.
TMA associated CG and “classical” CG (i.e., CG related
to ethnicity, viruses, or drugs, or a combination of these) differ on many
points although they are indistinguishable by light microscopy. Classic CG usually is seen in blacks, there they
saw it in whites more. The nephrotic syndrome
is more severe in classic CG compared to TMA associated CG. Third, the authors found
that dysregulation of the immunohistochemical phenotype of podocytes was
less marked in our TMA-CG cases than in “classical” CG: although we observed
podocyte dedifferentiation in one-half of the tested cases, proliferation of
podocytes was not detected. This result is in accordance with the fact that the
degree of podocyte dysregulation is less prominent in the reactive forms of CG.
6.
TMA-CG is associated with attenuated podocyte
changes relative to “classical” CG and may be insufficient to trigger a
full-blown clinical, immunohistochemical, and ultrastructural phenotype.
7.
Perhaps the TMA came first and led to HTN and
ischemia and that leads to CG( hence the less severe proteinuria). Or is one
protecting the other to keep
the VEGF balance as too little VEGF leads to TMA and too much to CG.
8.
Clearly, this is an important association and
finally something that can be seen in practice. Classically this is seen in HTN
as it can lead to both forms of endothelial injury.
9.
Similar concepts have been noticed in post
transplant CG in a prior post
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