Use of renin and aldosterone levels as diagnostic and mortality biomarkers in patients with septic shock in the emergency department

Project no. 32494 · Status: Kapanmış (Yayın bekleniyor) · 2024

Summary

<p class="ql-align-justify"><span style="color: black;">Sepsis&nbsp;and&nbsp;septic&nbsp;shock&nbsp;are&nbsp;life-threatening&nbsp;clinical&nbsp;conditions&nbsp;characterized&nbsp;by&nbsp;dysregulated&nbsp;host&nbsp;responses&nbsp;to&nbsp;infection,&nbsp;leading&nbsp;to&nbsp;tissue&nbsp;hypoperfusion,&nbsp;multiple&nbsp;organ&nbsp;dysfunction,&nbsp;and&nbsp;high&nbsp;mortality.&nbsp;Early&nbsp;diagnosis&nbsp;and&nbsp;timely&nbsp;initiation&nbsp;of&nbsp;treatment&nbsp;are&nbsp;crucial;&nbsp;however,&nbsp;the&nbsp;lack&nbsp;of&nbsp;sepsis-specific&nbsp;prognostic&nbsp;biomarkers&nbsp;highlights&nbsp;the&nbsp;need&nbsp;for&nbsp;novel&nbsp;indicators.&nbsp;The&nbsp;aim&nbsp;of&nbsp;this&nbsp;study&nbsp;was&nbsp;to&nbsp;investigate&nbsp;the&nbsp;association&nbsp;between&nbsp;mortality&nbsp;and&nbsp;the&nbsp;Renin–Angiotensin–Aldosterone&nbsp;System&nbsp;(RAAS)&nbsp;biomarkers&nbsp;renin&nbsp;and&nbsp;aldosterone&nbsp;in&nbsp;patients&nbsp;with&nbsp;septic&nbsp;shock,&nbsp;and&nbsp;to&nbsp;evaluate&nbsp;their&nbsp;prognostic&nbsp;value&nbsp;in&nbsp;comparison&nbsp;with&nbsp;established&nbsp;clinical&nbsp;and&nbsp;biochemical&nbsp;parameters.</span></p><p class="ql-align-justify"><span style="color: black;">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;This&nbsp;prospective&nbsp;cohort&nbsp;study&nbsp;was&nbsp;conducted&nbsp;in&nbsp;the&nbsp;Emergency&nbsp;Department&nbsp;of&nbsp;Ege&nbsp;University&nbsp;Faculty&nbsp;of&nbsp;Medicine.&nbsp;A&nbsp;total&nbsp;of&nbsp;156&nbsp;adult&nbsp;patients&nbsp;(≥18&nbsp;years)&nbsp;who&nbsp;were&nbsp;diagnosed&nbsp;with&nbsp;septic&nbsp;shock&nbsp;by&nbsp;the&nbsp;attending&nbsp;physician&nbsp;and&nbsp;initiated&nbsp;on&nbsp;inotropic&nbsp;therapy&nbsp;were&nbsp;included.&nbsp;Pregnant&nbsp;patients,&nbsp;those&nbsp;under&nbsp;18&nbsp;years&nbsp;of&nbsp;age,&nbsp;and&nbsp;patients&nbsp;presenting&nbsp;with&nbsp;cardiac&nbsp;arrest&nbsp;were&nbsp;excluded.&nbsp;Demographic&nbsp;characteristics,&nbsp;comorbidities,&nbsp;vital&nbsp;signs,&nbsp;laboratory&nbsp;parameters,&nbsp;Sequential&nbsp;Organ&nbsp;Failure&nbsp;Assessment&nbsp;(SOFA)&nbsp;scores,&nbsp;and&nbsp;Glasgow&nbsp;Coma&nbsp;Scale&nbsp;(GCS)&nbsp;scores&nbsp;were&nbsp;recorded.&nbsp;In&nbsp;addition&nbsp;to&nbsp;routine&nbsp;tests,&nbsp;serum&nbsp;renin&nbsp;and&nbsp;aldosterone&nbsp;levels&nbsp;were&nbsp;measured.&nbsp;Thirty-day&nbsp;mortality&nbsp;was&nbsp;defined&nbsp;as&nbsp;the&nbsp;primary&nbsp;outcome.&nbsp;Continuous&nbsp;variables&nbsp;were&nbsp;analyzed&nbsp;using&nbsp;the&nbsp;independent&nbsp;samples&nbsp;t-test&nbsp;or&nbsp;Mann–Whitney&nbsp;U&nbsp;test&nbsp;according&nbsp;to&nbsp;data&nbsp;distribution,&nbsp;and&nbsp;categorical&nbsp;variables&nbsp;were&nbsp;analyzed&nbsp;using&nbsp;the&nbsp;chi-square&nbsp;test.&nbsp;Independent&nbsp;predictors&nbsp;of&nbsp;mortality&nbsp;were&nbsp;assessed&nbsp;by&nbsp;multivariate&nbsp;logistic&nbsp;regression&nbsp;analysis,&nbsp;and&nbsp;the&nbsp;discriminative&nbsp;ability&nbsp;of&nbsp;each&nbsp;parameter&nbsp;was&nbsp;evaluated&nbsp;using&nbsp;Receiver&nbsp;Operating&nbsp;Characteristic&nbsp;(ROC)&nbsp;curve&nbsp;analysis.</span></p><p class="ql-align-justify"><span style="color: black;">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;The&nbsp;mean&nbsp;age&nbsp;of&nbsp;the&nbsp;study&nbsp;population&nbsp;was&nbsp;71.7&nbsp;±&nbsp;14.6&nbsp;years,&nbsp;and&nbsp;55.8%&nbsp;were&nbsp;male.&nbsp;The&nbsp;most&nbsp;common&nbsp;source&nbsp;of&nbsp;infection&nbsp;was&nbsp;the&nbsp;respiratory&nbsp;system&nbsp;(42.3%).&nbsp;The&nbsp;30-day&nbsp;mortality&nbsp;rate&nbsp;was&nbsp;72.4%.&nbsp;In&nbsp;univariate&nbsp;analyses,&nbsp;GCS&nbsp;(p&lt;0.001),&nbsp;SOFA&nbsp;score&nbsp;(p&lt;0.001),&nbsp;leukocyte&nbsp;count&nbsp;(p=0.007),&nbsp;pH&nbsp;(p=0.007),&nbsp;PaO₂&nbsp;(p=0.015),&nbsp;lactate&nbsp;(p=0.047),&nbsp;and&nbsp;aldosterone&nbsp;levels&nbsp;(p=0.002)&nbsp;were&nbsp;significantly&nbsp;different&nbsp;in&nbsp;the&nbsp;non-survivor&nbsp;group.&nbsp;Among&nbsp;categorical&nbsp;variables,&nbsp;endotracheal&nbsp;intubation&nbsp;(70.8%&nbsp;vs.&nbsp;8.6%),&nbsp;history&nbsp;of&nbsp;cardiac&nbsp;arrest&nbsp;(33.6%&nbsp;vs.&nbsp;0.0%),&nbsp;and&nbsp;inotropic&nbsp;use&nbsp;(43.4%&nbsp;vs.&nbsp;7.0%)&nbsp;were&nbsp;strongly&nbsp;associated&nbsp;with&nbsp;mortality&nbsp;(p&lt;0.001).&nbsp;In&nbsp;multivariate&nbsp;logistic&nbsp;regression&nbsp;analysis,&nbsp;endotracheal&nbsp;intubation&nbsp;(OR:&nbsp;4.82,&nbsp;95%&nbsp;CI:&nbsp;1.71–13.55,&nbsp;p=0.003)&nbsp;and&nbsp;inotropic&nbsp;use&nbsp;(OR:&nbsp;9.87,&nbsp;95%&nbsp;CI:&nbsp;1.71–56.49,&nbsp;p=0.010)&nbsp;were&nbsp;identified&nbsp;as&nbsp;independent&nbsp;predictors&nbsp;of&nbsp;mortality.&nbsp;ROC&nbsp;curve&nbsp;analysis&nbsp;demonstrated&nbsp;an&nbsp;AUC&nbsp;of&nbsp;0.683&nbsp;for&nbsp;SOFA&nbsp;score,&nbsp;0.675&nbsp;for&nbsp;aldosterone,&nbsp;0.632&nbsp;for&nbsp;leukocyte&nbsp;count,&nbsp;and&nbsp;0.587&nbsp;for&nbsp;lactate.</span></p><p class="ql-align-justify"><span style="color: black;">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;This&nbsp;study&nbsp;demonstrates&nbsp;that&nbsp;aldosterone&nbsp;levels&nbsp;measured&nbsp;at&nbsp;the&nbsp;time&nbsp;of&nbsp;diagnosis&nbsp;in&nbsp;the&nbsp;emergency&nbsp;department&nbsp;are&nbsp;significantly&nbsp;associated&nbsp;with&nbsp;30-day&nbsp;mortality&nbsp;in&nbsp;patients&nbsp;with&nbsp;septic&nbsp;shock.&nbsp;Although&nbsp;no&nbsp;direct&nbsp;association&nbsp;was&nbsp;found&nbsp;between&nbsp;renin&nbsp;levels&nbsp;and&nbsp;mortality,&nbsp;renin&nbsp;concentrations&nbsp;were&nbsp;significantly&nbsp;higher&nbsp;in&nbsp;patients&nbsp;requiring&nbsp;high-dose&nbsp;inotropic&nbsp;support&nbsp;compared&nbsp;with&nbsp;those&nbsp;receiving&nbsp;low-dose&nbsp;inotropes,&nbsp;suggesting&nbsp;a&nbsp;relationship&nbsp;between&nbsp;renin&nbsp;levels&nbsp;and&nbsp;hemodynamic&nbsp;support&nbsp;requirements.&nbsp;In&nbsp;multivariate&nbsp;analysis,&nbsp;aldosterone&nbsp;did&nbsp;not&nbsp;remain&nbsp;an&nbsp;independent&nbsp;prognostic&nbsp;factor&nbsp;when&nbsp;strong&nbsp;indicators&nbsp;of&nbsp;life-support&nbsp;needs,&nbsp;such&nbsp;as&nbsp;mechanical&nbsp;ventilation&nbsp;and&nbsp;inotropic&nbsp;therapy,&nbsp;were&nbsp;included.&nbsp;These&nbsp;findings&nbsp;indicate&nbsp;that&nbsp;the&nbsp;need&nbsp;for&nbsp;life-support&nbsp;interventions&nbsp;represents&nbsp;the&nbsp;strongest&nbsp;predictor&nbsp;of&nbsp;mortality&nbsp;in&nbsp;septic&nbsp;shock.&nbsp;While&nbsp;aldosterone&nbsp;showed&nbsp;moderate&nbsp;discriminative&nbsp;ability&nbsp;(AUC=0.675),&nbsp;it&nbsp;may&nbsp;provide&nbsp;additional&nbsp;prognostic&nbsp;value&nbsp;when&nbsp;interpreted&nbsp;alongside&nbsp;established&nbsp;clinical&nbsp;and&nbsp;laboratory&nbsp;parameters.&nbsp;Despite&nbsp;the&nbsp;lack&nbsp;of&nbsp;a&nbsp;significant&nbsp;association&nbsp;between&nbsp;renin&nbsp;levels&nbsp;and&nbsp;30-day&nbsp;mortality,&nbsp;elevated&nbsp;renin&nbsp;concentrations&nbsp;in&nbsp;the&nbsp;early&nbsp;phase&nbsp;of&nbsp;septic&nbsp;shock&nbsp;suggest&nbsp;that&nbsp;selected&nbsp;patients&nbsp;may&nbsp;potentially&nbsp;benefit&nbsp;from&nbsp;RAAS-targeted&nbsp;therapeutic&nbsp;strategies.&nbsp;Larger,&nbsp;multicenter,&nbsp;prospective&nbsp;studies&nbsp;are&nbsp;warranted&nbsp;to&nbsp;further&nbsp;clarify&nbsp;the&nbsp;role&nbsp;of&nbsp;neurohormonal&nbsp;biomarkers&nbsp;in&nbsp;the&nbsp;management&nbsp;of&nbsp;septic&nbsp;shock.</span></p><p class="ql-align-justify"><strong style="color: black;">Keywords:</strong><span style="color: black;">&nbsp;Sepsis,&nbsp;Septic&nbsp;Shock,&nbsp;Renin,&nbsp;Aldosterone,&nbsp;Mortality,&nbsp;Prognosis,&nbsp;RAAS,&nbsp;Emergency&nbsp;Department</span></p>

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