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The effect of renin angiotensin system genetic variants in acute pancreatitis.

ABSTRACT: OBJECTIVES:We sought association of genetic variants in the renin-angiotensin system (RAS) and vitamin D system with acute pancreatitis (AP) development and severity. BACKGROUND:The endocrine RAS is involved in circulatory homeostasis through the pressor action of angiotensin II at its AT1 receptor. However, local RAS regulate growth and inflammation in diverse cells and tissues, and their activity may be suppressed by vitamin D. Intrapancreatic angiotensin II generation has been implicated in the development of AP. METHODS:Five hundred forty-four white patients with AP from 3 countries (United Kingdom, 22; Germany, 136; and The Netherlands 386) and 8487 control subjects (United Kingdom 7833, The Netherlands 717) were genotyped for 8 polymorphisms of the RAS/vitamin D systems, chosen on the basis of likely functionality. RESULTS:The angiotensin-converting enzyme I (rather than D) allele was significantly associated with alcohol-related AP when all cohorts were combined (P = 0.03). The renin rs5707 G (rather than A) allele was associated with AP (P = 0.002), infected necrosis (P = 0.025) and mortality (P = 0.046). CONCLUSIONS:The association of 2 RAS polymorphisms with AP suggests the need for further detailed analysis of the role of RAS/vitamin D in the genesis or severity of AP, particularly given the ready potential for pharmacological manipulation of this system using existing marketed agents. However, further replication studies will be required before any such association is considered robust, particularly given the significant heterogeneity of AP causation and clinical course.

SUBMITTER: Skipworth JR

PROVIDER: S-EPMC4199936 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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The effect of renin angiotensin system genetic variants in acute pancreatitis.

Skipworth James R A JR Nijmeijer Rian M RM van Santvoort Hjalmar C HC Besselink Marc G H MG Schulz Hans-Ulrich HU Kivimaki Mika M Kumari Meena M Cooper Jackie A JA Acharya Jay J Shankar Arjun A Malago Massimo M Humphries Steve E SE Olde Damink Steven W M SW Montgomery Hugh E HE

Annals of surgery 20150101 1

<h4>Objectives</h4>We sought association of genetic variants in the renin-angiotensin system (RAS) and vitamin D system with acute pancreatitis (AP) development and severity.<h4>Background</h4>The endocrine RAS is involved in circulatory homeostasis through the pressor action of angiotensin II at its AT1 receptor. However, local RAS regulate growth and inflammation in diverse cells and tissues, and their activity may be suppressed by vitamin D. Intrapancreatic angiotensin II generation has been ...[more]

PMID: 24743610

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Project description:The purpose of this study was to assess the relationship between biomarkers of renin-angiotensin-aldosterone system (RAAS) activation and decongestion strategies, worsening renal function, and clinical outcomes.High-dose diuretic therapy in patients with acute heart failure (AHF) is thought to activate the RAAS; and alternative decongestion strategies, such as ultrafiltration (UF), have been proposed to mitigate this RAAS activation.This study analyzed 427 AHF patients enrolled in the DOSE-AHF (Diuretic Optimization Strategies in Acute Heart Failure) and CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) trials. We assessed the relationship between 2 markers of RAAS activation (plasma renin activity [PRA] and aldosterone) from baseline to 72 h and 96 h and decongestion strategy: high- versus low-dose and continuous infusion versus bolus furosemide for DOSE-AHF and UF versus stepped pharmacologic care for CARRESS-HF. We determined the relationships between RAAS biomarkers and 60-day outcomes.Patients with greater RAAS activation at baseline had lower blood pressures, lower serum sodium levels, and higher blood urea nitrogen (BUN) concentration. Continuous infusion furosemide and UF were associated with greater PRA increases (median: +1.66 vs. +0.66 ng/ml/h with continuous vs. bolus infusion, respectively, p = 0.021; +4.05 vs. +0.56 ng/ml/h with UF vs. stepped care, respectively, p = 0.014). There were no significant differences in RAAS biomarker changes with high- versus low-dose diuretic therapy (both: p > 0.5). Neither baseline log PRA nor log aldosterone was associated with increased death or HF hospitalization (hazard ratio [HR] for a doubling of 1.05; 95% confidence interval [CI]: 0.98 to 1.13; p = 0.18; and HR: 1.13; 95% CI: 0.99 to 1.28; p = 0.069, respectively). The change in RAAS biomarkers from baseline to 72 and 96 h was not associated with outcomes (both: p > 0.5).High-dose loop diuretic therapy did not result in RAAS activation greater than that with low-dose diuretic therapy. UF resulted in greater PRA increase than stepped pharmacologic care. Neither PRA nor aldosterone was significantly associated with short-term outcomes in this cohort. (Determining Optimal Dose and Duration of Diuretic Treatment in People With Acute Heart Failure [DOSE-AHF]; NCT00577135; Effectiveness of Ultrafiltration in Treating People With Acute Decompensated Heart Failure and Cardiorenal Syndrome [CARRESS]; NCT00608491).

Dataset Information

The effect of renin angiotensin system genetic variants in acute pancreatitis.

Publications

The effect of renin angiotensin system genetic variants in acute pancreatitis.

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