Collapsing GN is an interesting entity that is now thought to be related to proliferative epithelial cells in the kidney rather than a form of FSGS. ApolipoproteinL1(APOL1) gene mutation has been linked with this entity as well.
Individuals with genetic variants in the ApolipoproteinL1 gene have greatly increased risk of kidney disease. The high-risk genotypes are associated with elevated risk (7–29 fold) of hypertension-associated end-stage renal disease (H-ESRD), focal segmental glomerulosclerosis (FSGS), and HIV-associated nephropathy.
Nichols et al did an interesting study that sheds light on what might be upregulating these certain genetic foci. We are aware of interferon associated collapsing GN . This finding raised the possibility that interferons and the molecular pattern recognition receptors that stimulate interferon production may contribute to APOL1-associated kidney disease. In cell culture, interferons and toll-like receptor agonists increased APOL1 expression by up to 200-fold, in some cases with the appearance of transcripts not detected under basal conditions. PolyI:C, a double-stranded RNA TLR3 agonist, increased APOL1 expression by upregulating interferons directly or through an interferon-independent, IRF-3 dependent pathway.
The authors showed that inflammatory factors can induce APOL1 expression, and extended them to include interferon subclasses, multiple cell types, and the appearance of new APOL1 transcript variants. What produces interferons?—viruses such as HIV, HTLV, CMV, H pylori infection and cancers and autoimmune diseases such as SLE( their presence in the kidney is marked by TRI- as I had proposed is a TRI associated nephropathy)
So an APOL1 gene variant patient is doing fine till this second hit happens that increases inflammatory factors and lead to FSGS. In SLE patients as well, APOL1 G1/G2 alleles strongly impacted the risk of LN-ESRD in African Americans, as well as the time to progression to ESRD. How many of these had the FSGS lesions, few of the patients did but there was proliferative GN as well in many of the cases.
It basically supports the notion that “ high interferon state” + APOL1 Gene mutation == bad renal outcomes!”