Patients with IgA nephropathy exhibit high systemic PDGF-DD levels.
BACKGROUND
Platelet-derived growth factor (PDGF) is a central mediator of mesangioproliferative glomerulonephritis (GN). In experimental mesangioproliferative GN, PDGF-DD serum levels, unlike PDGF-BB, increased up to 1000-fold.


METHODS
We assessed disease activity in 72 patients with GN, established a novel PDGF-D ELISA and then determined their PDGF-DD levels. In parallel, we studied renal PDGF-DD mRNA expression by RT-PCR.


RESULTS
PDGF-DD serum levels in patients with IgA nephropathy (IgAN) were significantly higher (1.67 +/- 0.45 ng/ml) and in patients with lupus nephritis significantly lower (0.66 +/- 0.86 ng/ml) compared to healthy controls (1.17 +/- 0.46 ng/ml), while patients with focal segmental glomerulosclerosis, membranous GN and ANCA-positive vasculitis did not differ from controls. The subgroup of IgAN patients with elevated PDGF-DD levels (27% of samples) did not differ in their clinical features from those with normal PDGF-DD levels. In IgAN patients with repetitive PDGF-DD determinations, most exhibited only minor fluctuations of serum levels over time. Intrarenal PDGF-DD mRNA expression did not differ between controls and patients, suggesting an extrarenal source of the elevated PDGF-DD in IgAN.


CONCLUSIONS
Serum PDGF-DD levels were specifically elevated in patients with IgAN, in particular in those with early disease, i.e. preserved renal function. Our data support the rationale for anti-PDGF-DD therapy in mesangioproliferative GN.
Boor
Peter
P
RWTH University of Aachen, Germany. boor@email.cz
Eitner
Frank
F
Cohen
Clemens D
CD
Lindenmeyer
Maja T
MT
Mertens
Peter R
PR
Ostendorf
Tammo
T
Floege
Jürgen
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood; D000077214:Becaplermin; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015432:Glomerulonephritis, Membranoproliferative / Q000097:blood / Q000628:therapy; D015433:Glomerulonephritis, Membranous / Q000097:blood; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D008181:Lupus Nephritis / Q000097:blood; D008297:Male; D008875:Middle Aged; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011507:Proteinuria / Q000097:blood; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014657:Vasculitis / Q000097:blood / Q000276:immunology; D055815:Young Adult
D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D000077214:Becaplermin