Correspondence

Transmission of Glomerular Permeability Factor from a Mother to Her Child

N Engl J Med 2001; 344:386-387February 1, 2001

Article

To the Editor:

In the idiopathic nephrotic syndrome, including focal segmental glomerulosclerosis, a glomerular permeability factor may be responsible for the development of proteinuria and the recurrence of disease after renal transplantation.1,2 Plasma from patients with active focal segmental glomerulosclerosis can cause proteinuria in rats.3 The effect of a glomerular permeability factor after transmission from one person to another is not known. We report the transfer of an unknown glomerular permeability factor from a mother with focal segmental glomerulosclerosis to her child.

The nephrotic syndrome developed in a 35-year-old woman (gravida 5, para 3) in the 13th week of gestation during her fifth pregnancy. Laboratory studies showed proteinuria (26 g of protein per day), a serum albumin level of 1.6 g per deciliter, and a serum creatinine level of 1.2 mg per deciliter. Renal biopsy showed focal segmental glomerulosclerosis without evidence of tubulointerstitial fibrosis. The patient was treated with prednisone (90 mg per day) for eight weeks without an effect on the proteinuria. Because of the development of severe hypertension and erosive gastritis, the prednisone was tapered and finally discontinued before delivery.

At 33 weeks' gestation, a cesarean section was performed because of preeclampsia and fetal dystrophy. A girl was delivered without complications; the birth weight was 1030 g, the length 38 cm, and the head circumference 28 cm (all below the 3rd percentile). The child's blood pressure was 51/28 mm Hg. Laboratory studies showed a serum creatinine level of 0.3 mg per deciliter and a serum albumin level of 2.7 g per deciliter, with normal values for triglycerides and cholesterol. On day 1, proteinuria (935 mg per deciliter) was present. The proteinuria was highly selective (76 percent albumin, 5 percent transferrin, and 1.5 percent alpha₁-microglobulin, with no IgG). It diminished during the next several days (Figure 1Figure 1Course of Proteinuria after Birth in the Infant of a Woman with Focal Segmental Glomerulosclerosis.). The serum albumin level increased to 3.4 g per deciliter on day 5. The child had no overt edema. Immunosuppressive therapy with cyclosporine was initiated in the mother two weeks after delivery. Proteinuria was subsequently reduced to about 10 g of protein per day, and the serum albumin level increased to 2.8 g per deciliter.

Our observations provide evidence that a glomerular permeability factor can be transferred through the placenta and that it loses its proteinuric effect within a few days. In this case, in utero exposure did not cause chronic glomerular disease in the neonate. This finding suggests that the molecular size of the factor was smaller than that of IgG, which would persist in the infant's circulation for many months. A group of investigators has recently reported a glomerular permeability factor with a molecular size of 30 to 50 kd.3 The biochemical structure and properties of glomerular permeability factors require further study.

Markus J. Kemper, M.D.
University Children's Hospital, CH-8032 Zurich, Switzerland

Gunter Wolf, M.D.
Dirk E. Müller-Wiefel, M.D.
University Hospital Eppendorf, D-20246 Hamburg, Germany

3 References

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   Feld SM, Figueroa P, Savin V, et al. Plasmapheresis in the treatment of steroid-resistant focal segmental glomerulosclerosis in native kidneys. Am J Kidney Dis 1998;32:230-237
   CrossRef | Web of Science | Medline

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   Sharma M, Sharma R, McCarthy ET, Savin VJ. “The FSGS factor“: enrichment and in vivo effect of activity from focal segmental glomerulosclerosis plasma. J Am Soc Nephrol 1999;10:552-561
   Web of Science | Medline

Citing Articles (22)

Citing Articles

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   Samir M. Parikh. (2011) Circulating Mediators of Focal Segmental Glomerulosclerosis: Soluble Urokinase Plasminogen Activator Receptor in Context. American Journal of Kidney Diseases
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   Changli Wei, Shafic El Hindi, Jing Li, Alessia Fornoni, Nelson Goes, Junichiro Sageshima, Dony Maiguel, S Ananth Karumanchi, Hui-Kim Yap, Moin Saleem, Qingyin Zhang, Boris Nikolic, Abanti Chaudhuri, Pirouz Daftarian, Eduardo Salido, Armando Torres, Moro Salifu, Minnie M Sarwal, Franz Schaefer, Christian Morath, Vedat Schwenger, Martin Zeier, Vineet Gupta, David Roth, Maria Pia Rastaldi, George Burke, Phillip Ruiz, Jochen Reiser. (2011) Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nature Medicine 17:8, 952-960
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   Matjaž Kopač, Anamarija Meglič, Rina R Rus. (2011) Partial Remission of Resistant Nephrotic Syndrome After Oral Galactose Therapy. Therapeutic Apheresis and Dialysis 15:3, 269-272
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    Gian Marco Ghiggeri, Mary Artero, Michele Carraro, Giovanni Candiano, Luca Musante, Maurizio Bruschi, Cristina Zennaro, Fabrizio Ginevri, Gianluca Caridi, Luigi Faccini, Francesco Perfumo, Rosanna Gusmano. (2004) Glomerular albumin permeability as an in vitro model for characterizing the mechanism of focal glomerulosclerosis and predicting post-transplant recurrence. Pediatric Transplantation 8:4, 339-343
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    Luca Musante, Giovanni Candiano, Maurizio Bruschi, Cristina Zennaro, Michele Carraro, Mary Artero, Maria Gabriella Giuffrida, Amedeo Conti, Annalisa Santucci, Gian Marco Ghiggeri. (2002) Characterization of plasma factors that alter the permeability to albumin within isolated glomeruli. PROTEOMICS 2:2, 197-205
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