TY - JOUR
T1 - Identification of urinary metabolites that distinguish membranous lupus nephritis from proliferative lupus nephritis and focal segmental glomerulosclerosis
AU - Romick-Rosendale, Lindsey E.
AU - Brunner, Hermine I.
AU - Bennett, Michael R.
AU - Mina, Rina
AU - Nelson, Shannen
AU - Petri, Michelle
AU - Kiani, Adnan
AU - Devarajan, Prasad
AU - Kennedy, Michael A.
N1 - Funding Information:
We would like to acknowledge Dr. David Witte for the interpretation of the kidney biopsies and Drs. Lena Das and Michiko Suzuki for their participation in sample selection. We appreciate the support of the NIAMS Tissue Bank, directed by Dr. Susan Thompson. We would like to thank Mr. Pendl, Mrs. Tsoras, and Mrs. Lurick for the collection and management of the urine samples. This work was supported in part by the Department of Defense (W81XWH-07-1-0322). Dr. Brunner is supported by NIH/NIAMS U01AR059509 and P60AR47784. Sample storage was supported by P30AR047363. Drs. Petri and Kiani are supported by Hopkins Lupus Cohort (NIH AR 43727) and by Grant Number UL1 RR 025005 from the National Center for Research Resources (NCRR). This work was supported in part by the Department of Defense (W81XWH-07-1-0322). Dr. Kennedy is supported by a grant from the NIH/NCI (1R15CA152985). Dr. Kennedy would like to acknowledge support of Miami University and the Ohio Board of Regents for funding to establish the Ohio Eminent Scholar Laboratory where the metabonomics work was performed.
PY - 2011/12/7
Y1 - 2011/12/7
N2 - Introduction: Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease, and kidney involvement with SLE, a.k.a. lupus nephritis (LN), is a frequent and severe complication of SLE that increases patient morbidity and mortality. About 50% of patients with SLE encounter renal abnormalities which, if left untreated, can lead to end-stage renal disease. Kidney biopsy is considered the criterion standard for diagnosis and staging of LN using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, which was developed to help predict renal outcomes and assist with medical decision-making. However, kidney biopsy-based classification of LN is highly invasive and impractical for real-time monitoring of LN status. Here, nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling was used to identify urinary metabolites that discriminated between proliferative and pure membranous LN as defined by the ISN/RPS classification, and between LN and primary focal segmental glomerulosclerosis (FSGS).Methods: Metabolic profiling was conducted using urine samples of patients with proliferative LN without membranous features (Class III/IV; n = 7) or pure membranous LN (Class V; n = 7). Patients with primary FSGS and proteinuria (n = 10) served as disease controls. For each patient, demographic information and clinical data was obtained and a random urine sample collected to measure NMR spectra. Data and sample collection for patients with LN occurred around the time of kidney biopsy. Metabolic profiling analysis was done by visual inspection and principal component analysis.Results: Urinary citrate levels were 8-fold lower in Class V LN compared to Class III/IV patients, who had normal levels of urinary citrate (P < 0.05). Class III/IV LN patients had > 10-fold lower levels of urinary taurine compared to Class V patients, who had mostly normal levels (P < 0.01). Class V LN patients had normal urinary hippurate levels compared to FSGS patients, who completely lacked urinary hippurate (P < 0.001).Conclusions: This pilot study indicated differences in urinary metabolites between proliferative LN and pure membranous LN patients, and between LN and FSGS patients. If confirmed in larger studies, these urine metabolites may serve as biomarkers to help discriminate between different classes of LN, and between LN and FSGS.
AB - Introduction: Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease, and kidney involvement with SLE, a.k.a. lupus nephritis (LN), is a frequent and severe complication of SLE that increases patient morbidity and mortality. About 50% of patients with SLE encounter renal abnormalities which, if left untreated, can lead to end-stage renal disease. Kidney biopsy is considered the criterion standard for diagnosis and staging of LN using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, which was developed to help predict renal outcomes and assist with medical decision-making. However, kidney biopsy-based classification of LN is highly invasive and impractical for real-time monitoring of LN status. Here, nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling was used to identify urinary metabolites that discriminated between proliferative and pure membranous LN as defined by the ISN/RPS classification, and between LN and primary focal segmental glomerulosclerosis (FSGS).Methods: Metabolic profiling was conducted using urine samples of patients with proliferative LN without membranous features (Class III/IV; n = 7) or pure membranous LN (Class V; n = 7). Patients with primary FSGS and proteinuria (n = 10) served as disease controls. For each patient, demographic information and clinical data was obtained and a random urine sample collected to measure NMR spectra. Data and sample collection for patients with LN occurred around the time of kidney biopsy. Metabolic profiling analysis was done by visual inspection and principal component analysis.Results: Urinary citrate levels were 8-fold lower in Class V LN compared to Class III/IV patients, who had normal levels of urinary citrate (P < 0.05). Class III/IV LN patients had > 10-fold lower levels of urinary taurine compared to Class V patients, who had mostly normal levels (P < 0.01). Class V LN patients had normal urinary hippurate levels compared to FSGS patients, who completely lacked urinary hippurate (P < 0.001).Conclusions: This pilot study indicated differences in urinary metabolites between proliferative LN and pure membranous LN patients, and between LN and FSGS patients. If confirmed in larger studies, these urine metabolites may serve as biomarkers to help discriminate between different classes of LN, and between LN and FSGS.
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U2 - 10.1186/ar3530
DO - 10.1186/ar3530
M3 - Article
C2 - 22152586
AN - SCOPUS:82755167807
SN - 1478-6354
VL - 13
JO - Arthritis Research and Therapy
JF - Arthritis Research and Therapy
IS - 6
M1 - R199
ER -