Do plasma neprilysin activity and plasma neprilysin concentration predict cardiac events in chronic kidney disease patients?

Emrich, Insa E.; Vodovar, Nicolas; Feuer, Linda; Untersteller, Kathrin; Nougué, Hélène; Seiler-Mußler, Sarah; Fliser, Danilo; Launay, Jean‐Marie; Heine, Gunnar H.

doi:10.1093/ndt/gfy066

Cited by 16 publications

(13 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of a nonmembrane-associated or soluble form has also been reported in blood, urine, and cerebrospinal fluid ( 7 , 8 ). NEP in the blood stream apparently retains its catalytic activity, which is supported by several studies that reported NEP activity in plasma samples ( 7 , 8 , 9 , 10 ). Alterations of circulating NEP concentrations and NEP activity have been found to be associated with various diseases, such as metabolic syndrome, lung disease, chronic rheumatoid disease, and Alzheimer’s disease ( 11 , 12 , 13 , 14 , 15 , 16 ).…”

supporting

confidence: 64%

Heart Failure With Reduced Ejection Fraction Is Characterized by Systemic NEP Downregulation

Pávó

Kastner

et al. 2020

JACC: Basic to Translational Science

View full text Add to dashboard Cite

show abstract

supporting

confidence: 64%

Heart Failure With Reduced Ejection Fraction Is Characterized by Systemic NEP Downregulation

Pávó

Kastner

et al. 2020

JACC: Basic to Translational Science

View full text Add to dashboard Cite

show abstract

“…Vodovar et al showed that the biologically active B-type natriuretic peptide directly inhibits cNEP activity but not cNEP concentration in HF patients [ 28 ]. It is known that cNEP activity predicts future hospitalization for HF in CKD patients and that cNEP activity but not cNEP concentration is associated with HF in non-dialysis-dependent CKD patients [ 20 ]. We confirm these findings for the first time in a cohort of chronic dialysis patients.…”

Section: Discussionmentioning

confidence: 99%

“…cNEP is less impaired by decreased renal function and other comorbidities than NT-proBNP [ 19 ]. In patients with CKD stages 2–4, reduced cNEP activity but not concentration predicted future hospitalization for HF [ 20 ]. Finally, cNEP has not been studied as a diagnostic marker for HF in ESRD patients.…”

Section: Introductionmentioning

confidence: 99%

Soluble neprilysin, NT-proBNP, and growth differentiation factor-15 as biomarkers for heart failure in dialysis patients (SONGBIRD)

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background Dialysis patients are at increased risk of HF. However, diagnostic utility of NT-proBNP as a biomarker is decreased in patients on dialysis. GDF-15 and cNEP are biomarkers of distinct mechanisms that may contribute to HF pathophysiology in such cohorts. The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) and circulating neprilysin (cNEP) improve the diagnosis of congestive heart failure (HF) in patients on dialysis. Methods and results We compared circulating concentrations of NT-proBNP, GDF-15, and cNEP along with cNEP activity in patients on chronic dialysis without ( n = 80) and with HF ( n = 73), as diagnosed by clinical parameters and post-dialysis echocardiography. We used correlation, linear and logistic regression as well as receiver operating characteristic (ROC) analyses. Compared to controls, patients with HF had higher median values of NT-proBNP (16,216 [interquartile range, IQR = 27739] vs. 2883 [5866] pg/mL, p < 0.001), GDF-15 (7512 [7084] vs. 6005 [4892] pg/mL, p = 0.014), but not cNEP (315 [107] vs. 318 [124] pg/mL, p = 0.818). Median cNEP activity was significantly lower in HF vs. controls (0.189 [0.223] vs. 0.257 [0.166] nmol/mL/min, p < 0.001). In ROC analyses, a multi-marker model combining clinical covariates, NT-proBNP, GDF-15, and cNEP activity demonstrated best discrimination of HF from controls (AUC = 0.902, 95% CI 0.857–0.947, p < 0.001 vs. base model AUC = 0.785). Conclusion We present novel comparative data on physiologically distinct circulating biomarkers for HF in patients on dialysis. cNEP activity but not concentration and GDF-15 provided incremental diagnostic information over clinical covariates and NT-proBNP and may aid in diagnosing HF in dialysis patients. Graphic abstract Electronic supplementary material The online version of this article (10.1007/s00392-020-01597-x) contains supplementary material, which is available to authorized users.

show abstract

“…32 Plasma NEP concentrations were not related to activity in CKD patients either. 38 In contrast, NEP inhibition in HFrEF patients receiving ARNi therapy resulted in decreased plasma NEP activity. 21 In CKD, higher plasma NEP activity, but not concentration, was associated with a lower incidence of hospitalisation for HF or cardiovascular events.…”

Section: Non-membrane-associated Circulating Neprilysin Activitymentioning

confidence: 99%

“…21 In CKD, higher plasma NEP activity, but not concentration, was associated with a lower incidence of hospitalisation for HF or cardiovascular events. 38 Plasma NEP activity has also been implicated in other non-HF contexts. Plasma NEP activity increased with indices of metabolic syndrome, such as insulin resistance, homeostatic model assessment index and BMI, in 318 otherwise-healthy adults in a previously published study.…”

Section: Non-membrane-associated Circulating Neprilysin Activitymentioning

confidence: 99%

Neprilysin as a Biomarker: Challenges and Opportunities

et al. 2020

View full text Add to dashboard Cite

Neprilysin (NEP) inhibition is a successful novel therapeutic approach in heart failure with reduced ejection fraction. Assessing individual NEP status might be important for gathering insights into mechanisms of disease and optimising individualised patient care. NEP is a zinc-dependent multisubstrate-metabolising oligoendopeptidase localised in the plasma membrane with the catalytic site facing the extracellular space. Although NEP activity in vivo is predominantly tissue-based, NEP can be released into the circulation via ectodomain shedding and exosomes. Attempts to determine circulating NEP concentrations and activity have not yet resulted in convincingly coherent results relating NEP biomarkers to heart failure disease severity or outcomes. NEP is naturally expressed on neutrophils, opening up the possibility of measuring a membrane-associated form with integrity. Small studies have linked NEP expression on neutrophils with inflammatory state and initial data might indicate its role in heart failure with reduced ejection fraction. Future studies need to assess the regulation of systemic NEP activity, which is assumed to be tissue-based, and the relationship of NEP activation with disease state. The relationship between tissue NEP activity and easily accessible circulating NEP biomarkers and the impact of the latter remains to be established.

show abstract

Do plasma neprilysin activity and plasma neprilysin concentration predict cardiac events in chronic kidney disease patients?

Cited by 16 publications

References 27 publications

Heart Failure With Reduced Ejection Fraction Is Characterized by Systemic NEP Downregulation

Heart Failure With Reduced Ejection Fraction Is Characterized by Systemic NEP Downregulation

Soluble neprilysin, NT-proBNP, and growth differentiation factor-15 as biomarkers for heart failure in dialysis patients (SONGBIRD)

Neprilysin as a Biomarker: Challenges and Opportunities

Contact Info

Product

Resources

About