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.

Association Between Cardiac Natriuretic Peptides and Lipid Profile: a Systematic Review and Meta-Analysis

“…Although not taken into account in our work, recent evidence is emerging on the CV and metabolic role of C-type NP. Very recently, C-type NP has been identified as a good early marker of renal damage in diabetic patients, probably reflecting renal inflammation and fibrosis 82 . Moreover, an important role on blood pressure, through its anti-fibrotic and vasodilatory effect 83 and on lipid metabolism has been found in transgenic mice, in which the overexpression of C-type-NP led to increase in fatty acid β-oxidation and lipolysis and decrease in insulin-resistance and fat weight 84,85 .…”

Vitamin C Status in People with Types 1 and 2 Diabetes Mellitus and Varying Degrees of Renal Dysfunction: Relationship to Body Weight

“…This study was a retrospective analysis of blood samples collected for a study on markers of chronic kidney disease in patients with either T1DM or T2DM [ 23 ]. The participants were recruited from a single outpatient diabetes clinic at Christchurch Hospital, New Zealand (between June 2017 and June 2018).…”

“…Diabetes diagnosis (T1DM versus T2DM) was made by the attending diabetes specialist based on clinical phenotype, plus additional laboratory tests as required. The patients were recruited to ensure that a broad range of renal function (as determined by estimated glomerular filtration rate; eGFR, and albuminuria, i.e., albumin-to-creatinine ratio; ACR) were equivalently represented in both T1DM and T2DM groups [ 23 ]. eGFR was calculated using the CKD-EPI creatinine equation [ 24 ].…”

“…Standard renal function parameters (i.e., plasma cystatin C, serum and urine creatinine, urine albumin, ACR, eGFR) and metabolic health markers (i.e., triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol, urate and HbA1c) were measured at Canterbury Health Laboratories, an International Accreditation New Zealand (IANZ) laboratory as part of the original study [ 23 ].…”

Value of Urine Peptides in Assessing Kidney and Cardiovascular Disease

“…[ 29 ] Pricket and colleagues investigated urinary Amino‐Terminal Pro‐C‐Type Natriuretic Peptide (NTproCNP) in the context of DKD. [ 46 ] In a cohort of 202 type 1 and type 2 diabetic patients, the urinary NTproCNP/creatinine ratio was significantly inversely associated with eGFR. In another study, urinary epidermal growth factor (uEGF) and MCP‐1 were investigated in 83 diabetic patients.…”