Strategy and rationale for urine collection protocols employed in the NEPTUNE study.

Luca Manganelli, Markus Bitzer, Matthias Kretzler, Lawrence B Holzmann, Heather N Reich, Sharon G Adler, Peter J Nelson, Jeffrey B Kopp, Wenjun Ju, Marie C Hogan, Jamie L Sundsbak, Christopher J Ward, Peter C Harris, Christina M Heyer, Larysa T Wickman, Lisa L Nesbitt, Chrysta C Lienczewski, John C Lieske

Journal: BMC nephrology 2016;16():190

PMID: 26577187

Free Full Text on BioMed Central View on PubMed

Abstract

BACKGROUND

Glomerular diseases are potentially fatal, requiring aggressive interventions and close monitoring. Urine is a readily-accessible body fluid enriched in molecular signatures from the kidney and therefore particularly suited for routine clinical analysis as well as development of non-invasive biomarkers for glomerular diseases.

METHODS

The Nephrotic Syndrome Study Network (NEPTUNE; ClinicalTrials.gov Identifier NCT01209000) is a North American multicenter collaborative consortium established to develop a translational research infrastructure for nephrotic syndrome. This includes standardized urine collections across all participating centers for the purpose of discovering non-invasive biomarkers for patients with nephrotic syndrome due to minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. Here we describe the organization and methods of urine procurement and banking procedures in NEPTUNE.

RESULTS

We discuss the rationale for urine collection and storage conditions, and demonstrate the performance of three experimental analytes (neutrophil gelatinase-associated lipocalin [NGAL], retinol binding globulin, and alpha-1 microglobulin) under these conditions with and without urine preservatives (thymol, toluene, and boric acid). We also demonstrate the quality of RNA and protein collected from the urine cellular pellet and exosomes.

CONCLUSIONS

The urine collection protocol in NEPTUNE allows robust detection of a wide range of proteins and RNAs from urine supernatant and pellets collected longitudinally from each patient over 5 years. Combined with the detailed clinical and histopathologic data, this provides a unique resource for exploration and validation of new or accepted markers of glomerular diseases.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier NCT01209000.

Address: Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. [email protected].; Department of Medicine, Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA. [email protected].; Department of Internal Medicine - Nephrology, University of Michigan Health System, Ann Arbor, MI, USA. [email protected].; Cardiovascular Research, Mayo Clinic, Rochester, MN, USA. [email protected].; Pediatric Nephrology, University of Michigan, Ann Arbor, MI, USA. [email protected].; Nephrology and Hypertension Research, Mayo Clinic, Rochester, MN, USA. [email protected].; Nephrology and Hypertension Research, Mayo Clinic, Rochester, MN, USA. [email protected].; Department of Internal Medicine, Division of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, KS, USA. [email protected].; Nephrology and Hypertension Research, Mayo Clinic, Rochester, MN, USA. [email protected].; Oncology, Novartis Pharma AG, Basel, Switzerland. [email protected].; Department of Internal Medicine - Nephrology, University of Michigan Health System, Ann Arbor, MI, USA. [email protected].; Kidney Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA. [email protected].; Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, WA, USA. [email protected].; Division of Nephrology and Hypertension, Harbor-UCLA Medical Center, Torrance, CA, USA. [email protected].; Department of Medicine, University Health Network and University of Toronto, Toronto, ON, Canada. [email protected].; Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. [email protected].; Department of Internal Medicine - Nephrology, University of Michigan Health System, Ann Arbor, MI, USA. [email protected].; Department of Internal Medicine - Nephrology, University of Michigan Health System, Ann Arbor, MI, USA. [email protected].

DOI: 10.1186/s12882-015-0185-3

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MeSH Terms: Biological Specimen Banks, Biomarkers, Female, Humans, Male, Nephrotic Syndrome, Proteinuria, Reproducibility of Results, Sensitivity and Specificity, Tissue Preservation, United States, Urine Specimen Collection