Urinary Amino-Terminal Pro-C-Type Natriuretic Peptide: A Novel Marker of Chronic Kidney Disease in Diabetes.

Abstract

BACKGROUND:

Chronic renal inflammation and fibrosis are common sequelae in diabetes mellitus (DM) and are major causes of premature mortality. Although upregulation of NPPC expression occurs in response to renal inflammation in experimental animals, nothing is known of the molecular forms of C-type natriuretic peptide (CNP) products in urine of people with DM or links with renal function.

METHODS:

ProCNP products in urine were characterized with HPLC and a range of antisera directed to specific epitopes of amino-terminal proCNP (NTproCNP). The 5-kDa intact peptide was quantified in spot urine samples from healthy adults and 202 participants with DM selected to provide a broad range of renal function.

RESULTS:

The predominant products of proCNP in urine were consistent with the 2-kDa fragment (proCNP 3-20) and a smaller peak of intact (5-kDa) fragment (proCNP 1-50, NTproCNP). No peaks consistent with bioactive forms (proCNP 82-103, 50-103) were identified. The urine NTproCNP to creatinine ratio (NCR) was more reproducible than the albumin to creatinine ratio (ACR) and strongly associated with the presence of chronic kidney disease. In models predicting independence, among 10 variables associated with renal function in DM, including plasma NTproCNP, only 3 (sex, ACR, and plasma creatinine) contributed to NCR.

CONCLUSIONS:

Characterization of the products of proCNP in urine confirmed the presence of NTproCNP. In spot random urine from study participants with DM, NCR is inversely associated with estimated glomerular filtration rate. In contrast to ACR, NCR reflects nonvascular factors that likely include renal inflammation and fibrosis.

• Authors: Timothy C R Prickett, Helen Lunt, Julie Warwick, Helen F Heenan, Eric A Espiner
• Journal: Clinical chemistry (Clin Chem) Vol. 65 Issue 10 Pg. 1248-1257 (10 2019) ISSN: 1530-8561 [Electronic] England
• PMID: 31431448 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 American Association for Clinical Chemistry.

Chemical References

• Biomarkers
• amino-terminal pro-C-type natriuretic peptide, human
• Natriuretic Peptide, C-Type
• Creatinine

Topics

• Adult
• Aged
• Albuminuria (urine)
• Biomarkers (urine)
• Case-Control Studies
• Chromatography, High Pressure Liquid
• Creatinine (urine)
• Diabetes Complications (urine)
• Diabetes Mellitus, Type 1 (complications, urine)
• Diabetes Mellitus, Type 2 (complications, urine)
• Female
• Glomerular Filtration Rate
• Humans
• Male
• Middle Aged
• Natriuretic Peptide, C-Type (urine)
• Renal Insufficiency, Chronic (etiology, urine)