Akihiro Fukuda1, Yuji Sato1, Takashi Iwakiri1, Hiroyuki Komatsu1, Masao Kikuchi1, Kazuo Kitamura1, Roger C Wiggins2, Shouichi Fujimoto3. 1. First Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan. 2. Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. 3. First Department of Internal Medicine, University of Miyazaki, Miyazaki, Japan Department of Hemovascular Medicine and Artificial Organs, University of Miyazaki, Miyazaki, Japan.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: From 2009 to 2013, early morning voided urine samples and kidney biopsies from IgANpatients (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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Kathryn E White; Rudolf W Bilous; Sally M Marshall; Meguid El Nahas; Giuseppe Remuzzi; Giampiero Piras; Salvatore De Cosmo; GianCarlo Viberti Journal: Diabetes Date: 2002-10 Impact factor: 9.461
Authors: Madhusudan Venkatareddy; Su Wang; Yan Yang; Sanjeevkumar Patel; Larysa Wickman; Ryuzoh Nishizono; Mahboob Chowdhury; Jeffrey Hodgin; Paul A Wiggins; Roger C Wiggins Journal: J Am Soc Nephrol Date: 2013-12-19 Impact factor: 10.121
Authors: Kevin V Lemley; Richard A Lafayette; Massy Safai; Geraldine Derby; Kristina Blouch; Addy Squarer; Bryan D Myers Journal: Kidney Int Date: 2002-04 Impact factor: 10.612
Authors: Abhijit S Naik; Jawad Aqeel; Su Q Wang; Mahboob Chowdhury; Kevin He; Roger C Wiggins Journal: Clin Transplant Date: 2021-11-02 Impact factor: 2.863
Authors: Kathryn E Haley; Nils M Kronenberg; Philipp Liehm; Mustafa Elshani; Cameron Bell; David J Harrison; Malte C Gather; Paul A Reynolds Journal: Sci Adv Date: 2018-06-27 Impact factor: 14.136