Development of initial idiopathic nephrotic syndrome and post-transplantation recurrence: evidence of the same biological entity.

Abstract

BACKGROUND:

Buffalo/Mna rats spontaneously develop a nephrotic syndrome (NS). We have demonstrated that this rat nephropathy recurs after renal transplantation. We studied this recurrence by kinetic analysis of graft lesions, infiltrating cells and cytokines.

METHODS:

Kidneys from LEW.1 W rats were grafted into proteinuric Buff/Mna or healthy Wistar Furth recipients. Kidney samples were harvested before, during and after the occurrence of proteinuria and analysed for renal histology, cell populations and cytokine transcripts. Results were compared with the evolution of the initial disease studied previously.

RESULTS:

Both groups showed normal graft histology at Day 7 and an increasing podocyte swelling at Day 45 was seen only in the Buff/Mna recipients. At Day 80, glomerular atrophy with podocytosis and focal segmental glomerular sclerosis lesions, accompanied by tubular dilatation, appeared in the Buff/Mna group. At Day 122, the intensity of the tubular and glomerular lesions increased in Buff/Mna recipients but not in the control group. An analysis of desmin and Kim-1 (early markers of glomerular and tubular damage, respectively) transcripts expression showed that glomerular lesions precede tubular injury in this model. A monocyte infiltration associated with an increase in TNFα, IL1 and IL12 transcripts appeared before the recurrence. An early increase in Cbeta TCR transcripts with a predominant Th2 profile was observed, highlighting a Th2 polarization in the Buff/Mna recurrence.

CONCLUSIONS:

The comparison of profiles of recurrence and initial disease highlighted the same mediators for both events. We propose that initial Buff/Mna idiopathic nephrotic syndrome (INS) and post-transplantation recurrence represent the same entity and a valuable tool for the study of recurring INS.

• Authors: Ludmilla Le Berre, Sarah Bruneau, Karine Renaudin, Jeanne Naulet, Claire Usal, Helga Smit, Jean-Paul Soulillou, Jacques Dantal
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 26 Issue 5 Pg. 1523-32 (May 2011) ISSN: 1460-2385 [Electronic] England
• PMID: 20935016 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Transforming Growth Factor beta
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Kidney Transplantation (adverse effects)
• Nephrotic Syndrome (pathology, surgery)
• Postoperative Complications
• RNA, Messenger (genetics, metabolism)
• Rats
• Recurrence
• Reverse Transcriptase Polymerase Chain Reaction
• Transforming Growth Factor beta (genetics, metabolism)
• Tumor Necrosis Factor-alpha (genetics, metabolism)