A recent letter to the editor in the American Journal of Kidney Diseases discusses soluble urokinase plasminogen activator receptor (suPAR) levels in newborns of mothers with suPAR-based focal segmental glomerulosclerosis (FSGS). Corresponding author Dr. Jochen Reiser (JR) discusses this interesting concept with the Dr. Kenar Jhaveri (eAJKD), blog editor.
eAJKD: Antibody titers in newborns usually mimic that of the mother . Would sUPAR follow similar patterns in affected individuals?
JR: At present, we do not know what exactly determines the amount of maternal suPAR that is transferred to an infant. From this single case, it appears that maternal and fetal suPAR blood levels are comparable.
eAJKD: Is suPAR really the cause of kidney injury? Is it a pathogenic antibody, or a surrogate of potential damage?
JR: The upstream mechanisms of increased suPAR release in FSGS are not yet understood. In a recent study in JASN, we reported that elevated serum suPAR levels in FSGS are not associated with high CRP, suggesting infection is unlikely to be the sole trigger. In fact, any suPAR measurement during active infection (for example mimicked by high CRP) could confound the measurement of suPAR. From unpublished work in the laboratory, we think that there might be pathologically derived suPAR fragments that are produced in FSGS patients capable of causing the disease. Better and more specific tests in the future will hopefully help us detect even more specifically which forms of pathological suPAR is present in FSGS patients. Mechanistically, suPAR can bind to the podoctyte alpha-v beta-3 integrin and cause a specific signal that leads to change in podocyte structure and function. This results in proteinuria and kidney disease.
eAJKD: While your study supports the existence of suPAR, how does this identify suPAR as the circulating factor?
JR: The infant had reported proteinuria for a few days that then resolved. Non-proteinuric controls had normal suPAR blood levels. It is likely that suPAR from the mother was transferred to the baby, which absent intrinsic production cleared high levels of suPAR in the urine. The case supports the role of suPAR as a circulating factor and suggests that elevated levels need to persist in order for FSGS to manifest beyond transient proteinuria.
eAJKD: Is this child at high risk for future CKD?
JR: I don’t think this child will have a risk of kidney disease. In fact, I know that the child is now 12 years of age and has no reported kidney disease. Unless, there was a genetic risk for elevated blood suPAR in this mother-child case, the child will likely not develop FSGS.
eAJKD: Can this child donate a kidney when an adult?
JR: Obviously, we do not know enough about this, but I would suggest that donation of a kidney from the child as an adult would be okay.