Dataset Information

Analogs of C-type natriuretic peptide as a potential new non-surgical treatment strategy in knee osteoarthritis.

ABSTRACT: Osteoarthritis (OA) is a common, chronic, progressive, and multifactorial musculoskeletal system disease affecting millions of people around the world. Despite the use of several treatment modalities, the search for a disease modifying drug continuous. Recent evidence suggest involvement of C-type natriuretic peptide (CNP) signaling in induction of chondroprotective pathways. A CNP analog (BMN 111) with an extended plasma half-life due to its neutral-endopeptidase resistance has shown to be pharmacologically active in achondroplasia enabling to hypothesize that BMN 111 may also be used as a treatment strategy in OA, in which CNP signaling has been suggested to be protective and/or reparative.

SUBMITTER: Tufan AC

PROVIDER: S-EPMC6818356 | biostudies-literature | 2019 Nov-Dec

REPOSITORIES: biostudies-literature

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Analogs of C-type natriuretic peptide as a potential new non-surgical treatment strategy in knee osteoarthritis.

Tufan Ahmet Cevik AC

Journal of orthopaedics 20190525 6

Osteoarthritis (OA) is a common, chronic, progressive, and multifactorial musculoskeletal system disease affecting millions of people around the world. Despite the use of several treatment modalities, the search for a disease modifying drug continuous. Recent evidence suggest involvement of C-type natriuretic peptide (CNP) signaling in induction of chondroprotective pathways. A CNP analog (BMN 111) with an extended plasma half-life due to its neutral-endopeptidase resistance has shown to be phar ...[more]

PMID: 31680745

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Project description:ObjectivesThis study was conducted to determine whether urinary excretion of C-type natriuretic peptide (CNP) is elevated in acute decompensated heart failure (ADHF) and whether elevated levels predict adverse outcomes.BackgroundUrinary CNP has been detected in patients with heart failure, but its clinical significance and prognostic utility, compared to established kidney injury biomarkers, in ADHF is unknown.MethodsWe measured 24-h urinary excretion and concurrent plasma concentrations of CNP22, CNP53, and NT-CNP53 in 58 ADHF patients and 20 healthy control subjects. Urinary kidney injury molecule (KIM)-1 and neutrophil gelatinase–associated lipocalin (NGAL) and plasma N-terminal pro-B type natriuretic peptide (NT-proBNP) were also measured. Mortality and all-cause rehospitalization/death were assessed over a follow-up of 1.5 ± 0.9 years.ResultsADHF patients had higher urinary excretion of all 3 CNP molecular forms than did controls. Plasma CNP22 and CNP53 were elevated in ADHF but showed limited correlation with urinary excretion, suggesting that mainly renal-derived CNP appears in urine. Plasma NT-proBNP and urinary KIM-1 were also elevated in ADHF (p < 0.0001); urinary NGAL was similar to that in controls. At 6 months, event-free survival values in ADHF patients were 86% for mortality and 59% for all-cause rehospitalization/death. On Cox regression analysis, urinary NT-CNP53 was the only predictor of mortality (hazard ratio: 1.7; 95% confidence interval: 1.1 to 2.4; p = 0.01) and all-cause rehospitalization/death (hazard ratio: 1.8; 95% confidence interval: 1.3 to 2.4; p = 0.0004), even after adjustment. Integrated discrimination analysis suggested that urinary NT-CNP53 combined with plasma NT-proBNP improved the prediction of adverse outcomes.ConclusionsThe findings from this study support the clinical utility of urinary CNP molecular forms. In ADHF, urinary NT-CNP53 correlated with prognosis, better predicted outcomes than did urinary NGAL and KIM-1, and improved the prognostic value of plasma NT-proBNP.

Dataset Information

Analogs of C-type natriuretic peptide as a potential new non-surgical treatment strategy in knee osteoarthritis.

Publications

Analogs of C-type natriuretic peptide as a potential new non-surgical treatment strategy in knee osteoarthritis.

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