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