Urinary peptidome may predict renal function decline in type 1 diabetes and microalbuminuria.
One third of patients with type 1 diabetes and microalbuminuria experience an early, progressive decline in renal function that leads to advanced stages of chronic kidney disease and ESRD. We hypothesized that the urinary proteome may distinguish between stable renal function and early renal function decline among patients with type 1 diabetes and microalbuminuria. We followed patients with normal renal function and microalbuminuria for 10 to 12 yr and classified them into case patients (n = 21) with progressive early renal function decline and control subjects (n = 40) with stable renal function. Using liquid chromatography matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we identified three peptides that decreased in the urine of patients with early renal function decline [fragments of alpha1(IV) and alpha1(V) collagens and tenascin-X] and three peptides that increased (fragments of inositol pentakisphosphate 2-kinase, zona occludens 3, and FAT tumor suppressor 2). In renal biopsies from patients with early nephropathy from type 1 diabetes, we observed increased expression of inositol pentakisphosphate 2-kinase, which was present in granule-like cytoplasmic structures, and zona occludens 3. These results indicate that urinary peptide fragments reflect changes in expression of intact protein in the kidney, suggesting new potential mediators of diabetic nephropathy and candidate biomarkers for progressive renal function decline.
Merchant
Michael L
ML
University of Louisville, Louisville, Kentucky, USA.
Perkins
Bruce A
BA
Boratyn
Grzegorz M
GM
Ficociello
Linda H
LH
Wilkey
Daniel W
DW
Barati
Michelle T
MT
Bertram
Clinton C
CC
Page
Grier P
GP
Rovin
Brad H
BH
Warram
James H
JH
Krolewski
Andrzej S
AS
Klein
Jon B
JB
D000328:Adult; D000419:Albuminuria / Q000473:pathology / Q000503:physiopathology / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D001706:Biopsy; D015820:Cadherins / Q000652:urine; D002352:Carrier Proteins / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology / Q000652:urine*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology / Q000652:urine*; D018450:Disease Progression; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000652:urine; D010455:Peptides / Q000652:urine*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000652:urine; D039102:Poly(A)-Binding Proteins / Q000378:metabolism; D011237:Predictive Value of Tests; D015398:Signal Transduction / Q000502:physiology; D000074019:T-Cell Intracellular Antigen-1; D055815:Young Adult; D062825:Zonula Occludens Proteins
D015415:Biomarkers; D015820:Cadherins; D002352:Carrier Proteins; C502404:FAT2 protein, human; D008565:Membrane Proteins; D010455:Peptides; D039102:Poly(A)-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C111873:TJP3 protein, human; D062825:Zonula Occludens Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C502806:inositol 1,3,4,5,6-pentakisphosphate 2-kinase