Nephrotic syndrome and renal failure after allogeneic stem cell transplantation: novel molecular diagnostic tools for a challenging differential diagnosis.
BACKGROUND
Sudden onset of nephrotic syndrome after allogeneic stem cell transplantation is rare and has been associated mostly with membranous glomerulonephritis related to chronic graft-versus-host disease (cGVHD). We report a case of nephrotic syndrome and rapidly progressive renal failure occurring in a young woman 3 years after allogeneic stem cell transplantation from her HLA-identical brother. In the renal biopsy, a diffuse mononuclear cell infiltrate was observed. Furthermore, histological analysis, immunofluorescence, and electron microscopy of the kidney specimen defined the diagnosis as minimal change disease, a T-cell-mediated glomerulopathy associated with lymphoproliferative disorders, but that has never been described as an isolated manifestation of cGVHD.


METHODS
The differential diagnosis was performed by using immunohistochemistry and laser capture microdissection combined with Taq-Man quantitative polymerase chain reaction.


RESULTS
Infiltrating mononuclear cells in renal tissue consisted of T cells expressing DNA levels of a Y chromosome-specific gene quantitatively similar to those observed in a male subject, showing that these cells derived from the transplant donor and definitely excluding leukemia relapse. However, the large number of infiltrating T cells allowed the possibility that in this patient, minimal change disease could be related to an atypical form of GVHD.


CONCLUSIONS
This is the first study to use molecular techniques to show the differential diagnosis of nephrotic syndrome after allogeneic stem cell transplantation. This novel method approach might represent a key tool to characterize kidney infiltrate after allogeneic stem cell transplantation.
Romagnani
Paola
P
Department of Clinical Pathophysiology, Center for Research, Transfer and High Education DE NOVO Therapies, University of Florence, Italy. p.romagnani@dfc.unifi.it
Lazzeri
Elena
E
Mazzinghi
Benedetta
B
Lasagni
Laura
L
Guidi
Stefano
S
Bosi
Alberto
A
Cirami
Calogero
C
Salvadori
Maurizio
M
D058186:Acute Kidney Injury / Q000175:diagnosis* / Q000209:etiology; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology / Q000637:transplantation*; D041322:Chromosomes, Human, Y / Q000235:genetics; D004247:DNA / Q000032:analysis; D003937:Diagnosis, Differential; D018450:Disease Progression; D005260:Female; D005819:Genetic Markers; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000209:etiology; D006801:Humans; D007668:Kidney / Q000473:pathology*; D017254:Leukemic Infiltration / Q000175:diagnosis; D019520:Living Donors; D008297:Male; D009402:Nephrosis, Lipoid / Q000175:diagnosis* / Q000209:etiology; D009404:Nephrotic Syndrome / Q000175:diagnosis* / Q000209:etiology; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000601:surgery; D014184:Transplantation, Homologous / Q000009:adverse effects* / Q000276:immunology
D005819:Genetic Markers; D004247:DNA