Advertisement
American Journal of Kidney Diseases

Transmission of Glomerular Permeability Factor Soluble Urokinase Plasminogen Activator Receptor (suPAR) From a Mother to Child

Published:November 22, 2012DOI:https://doi.org/10.1053/j.ajkd.2012.10.011
      To the Editor:
      In 2001, Kemper et al
      • Kemper M.J.
      • Wolf G.
      • Mueller-Wiefel D.E.
      Transmission of glomerular permeability factor from a mother to her child.
      described a case in which a mother with focal segmental glomerulosclerosis (FSGS) gave birth to a girl who was noted to have proteinuria at birth, which then lasted for several days. The newborn's proteinuria gradually decreased and eventually resolved completely.
      • Kemper M.J.
      • Wolf G.
      • Mueller-Wiefel D.E.
      Transmission of glomerular permeability factor from a mother to her child.
      At that time, the authors speculated about the transmission of a putative glomerular permeability factor from the mother to her child; blood was archived for future analysis should the circulating FSGS factor be identified.
      Recently it has been reported that soluble urokinase plasminogen activator receptor (suPAR) level is increased in a large number of patients with native and recurrent posttransplantation FSGS causing podocyte dysfunction.
      • Wei C.
      • El Hindi S.
      • Li J.
      • et al.
      Circulating urokinase receptor as a cause of focal segmental glomerular sclerosis.
      There are 3 forms of suPAR, with molecular weights ranging from 20-55 kDa, depending on the number of domains (1, 2, or 3) included. Based on reported correlations between maternal and fetal concentrations of proteins such as immunoglobulin A (150 kDa), human chorionic gonadotropin (42 kDa), and human placental lactogen (21 kDa), macromolecules are thought to diffuse passively across the placenta from mother to fetus.
      • Malek A.
      • Sager R.
      • Schneider H.
      Transport of proteins across the human placenta.
      Thus, we analyzed the original blood samples for suPAR and compared them with samples from healthy newborns. We found a mean suPAR level of 2,884 pg/mL in controls versus highly elevated levels in both the mother (4,635 pg/mL) and the newborn (5,225 pg/mL; Fig 1) at the time of the infant's reported peak proteinuria.
      • Kemper M.J.
      • Wolf G.
      • Mueller-Wiefel D.E.
      Transmission of glomerular permeability factor from a mother to her child.
      The family moved away from Northern Germany in 2002 and is not available for follow-up. However, when the infant was 12 months old, the family pediatrician tested a spot urine sample and found proteinuria to be undetectable (H. Böhm, personal communication, October 2012).
      Figure thumbnail gr1
      Figure 1Levels of soluble urokinase plasminogen activator receptor (suPAR) in the blood of a mother and her newborn. Controls comprise samples from 7 male and female apparently healthy neonates 2-5 days after birth, reported as mean ± standard deviation. suPAR concentration was determined using a human urokinase plasminogen activator receptor immunoassay kit (R&D Systems Inc).
      Taken together, this evidence suggests that suPAR was transmitted from the mother to her newborn. We hypothesize that the healthy infant, in whom there would have been no intrinsic overproduction of suPAR, rapidly eliminated suPAR in the urine, which resulted in resolution of the proteinuria within a few days. This is consistent with the observation that the infant had normal protein excretion at day 6
      • Kemper M.J.
      • Wolf G.
      • Mueller-Wiefel D.E.
      Transmission of glomerular permeability factor from a mother to her child.
      and at 12 months of age.
      This “experiment of nature” allows insights into the pathogenesis of native and recurrent FSGS,
      • Savin V.J.
      • Sharma R.
      • Sharma M.
      • et al.
      Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis.
      as well as into the resolution of proteinuria in recurrent FSGS using plasmapheresis that can decrease suPAR serum levels.
      • Wei C.
      • El Hindi S.
      • Li J.
      • et al.
      Circulating urokinase receptor as a cause of focal segmental glomerular sclerosis.
      The finding of increased suPAR level and transient proteinuria in an infant born to a mother with FSGS is consistent with a role of suPAR as circulating FSGS factor.

      Acknowledgements

      Financial Disclosure: Drs Reiser and Wei are inventors on issued (J.R.) and pending (J.R., C.W.) patents on novel mechanisms and technologies for proteinuric kidney diseases. They stand to gain royalties from the commercialization of these technologies. Dr Kemper declares that he has no relevant financial interests.

      References

        • Kemper M.J.
        • Wolf G.
        • Mueller-Wiefel D.E.
        Transmission of glomerular permeability factor from a mother to her child.
        N Engl J Med. 2001; 344: 386-387
        • Wei C.
        • El Hindi S.
        • Li J.
        • et al.
        Circulating urokinase receptor as a cause of focal segmental glomerular sclerosis.
        Nat Med. 2011; 17: 952-960
        • Malek A.
        • Sager R.
        • Schneider H.
        Transport of proteins across the human placenta.
        Am J Reprod Immunol. 1998; 40: 347-351
        • Savin V.J.
        • Sharma R.
        • Sharma M.
        • et al.
        Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis.
        N Engl J Med. 1996; 334: 878-883