Urine podocyte mRNAs mark disease activity in IgA nephropathy

• Published in: Nephrology, dialysis, transplantation dialysis, transplantation, 2015-07, Vol.30 (7), p.1140-1150
• Main Authors: Fukuda, Akihiro, Sato, Yuji, Iwakiri, Takashi, Komatsu, Hiroyuki, Kikuchi, Masao, Kitamura, Kazuo, Wiggins, Roger C, Fujimoto, Shouichi
• Format: Article
• Language: English
• Subjects: Adult; Biomarkers - urine; Cells, Cultured; CLINICAL SCIENCE; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA - diagnosis; Glomerulonephritis, IGA - genetics; Glomerulonephritis, IGA - urine; Humans; Kidney Glomerulus - metabolism; Kidney Glomerulus - pathology; Male; Podocytes - metabolism; Podocytes - pathology; Prognosis; Proteinuria; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - urine
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfv104

Podocyte depletion is a major mechanism driving glomerulosclerosis. We and others have previously projected from model systems that podocyte-specific mRNAs in the urine pellet might serve as glomerular disease markers. We evaluated IgA nephropathy (IgAN) to test this concept. From 2009 to 2013, early morning voided urine samples and kidney biopsies from IgAN patients (n = 67) were evaluated in comparison with urine samples from healthy age-matched volunteers (n = 28). Urine podocyte (podocin) mRNA expressed in relation to either urine creatinine concentration or a kidney tubular marker (aquaporin 2) was tested as markers. Urine podocyte mRNAs were correlated with the severity of active glomerular lesions (segmental glomerulosclerosis and acute extracapillary proliferation), but not with non-glomerular lesions (tubular atrophy/interstitial fibrosis) or with clinical parameters of kidney injury (serum creatinine and estimated glomerular filtration rate), or with degree of accumulated podocyte loss at the time of biopsy. In contrast, proteinuria correlated with all histological and clinical markers. Glomerular tuft podocyte nuclear density (a measure of cumulative podocyte loss) correlated with tubular atrophy/interstitial fibrosis, estimated-glomerular filtration rate and proteinuria, but not with urine podocyte markers. In a subset of the IgA cohort (n = 19, median follow-up period = 37 months), urine podocyte mRNAs were significantly decreased after treatment, in contrast to proteinuria which was not significantly changed. Urine podocyte mRNAs reflect active glomerular injury at a given point in time, and therefore provide both different and additional clinical information that can complement proteinuria in the IgAN decision-making paradigm.