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Surfactant protein D (SP-D) gene polymorphism rs721917 is an independent predictor of acute kidney injury development in sepsis patients: a prospective cohort study.

ABSTRACT: BACKGROUND:Currently, there are no reliable predictors of risk of development and severity of acute kidney injury (AKI) in septic patients. The surfactant protein D (SP-D) polymorphism rs721917C/T is associated with a greater susceptibility to AKI in the Chinese population. Our aim was to evaluate the value of SP-D polymorphisms rs721917C/T and of plasma SP-D levels to predict the risk of development of AKI (defined with KDIGO criterion) in septic patients. METHODS:The study enrolled septic patients admitted to the Critical Care Department of two tertiary care hospitals. SP-D rs721917C/T polymorphisms were determined using the PCR-SSP method. Plasma SP-D and urine NGAL contents were measured using commercially available ELISA kits. RESULTS:330 septic patients were included. Their SOFA scores were 12?±?3. Patients with AKI (n?=?156) had higher plasma SP-D levels (median: 153 ng/mL, range 111-198 ng/mL) and urinary NGAL levels (median: 575 ng/mL, range 423-727 ng/mL) than those without AKI (SP-D median: 124 ng/mL, range 81-159 ng/mL, P?=?0.001; NGAL median: 484 ng/mL, range 429-573 ng/mL). Plasma SP-D levels of AKI patients were correlated with urinary NGAL contents (r?=?0.853). In 32 patients receiving continuous renal replacement therapy (CRRT), plasma SP-D levels correlated with duration of CRRT (r?=?0.448). The area under the receiver operating characteristic curve for plasma SP-D levels to predict AKI was 0.84. Patients with AKI had a higher rate of rs721917 CC genotype (AKI: 35% vs. non-AKI: 20%; P?=?0.012), but a significantly lower rate of TT genotype (AKI: 19% vs. non-AKI: 26%; P?=?0.005). SP-D rs721917 CC genotype was an independent predictor of AKI (P?=?0.044) and mortality (P?=?0.014). CONCLUSION:Our study showed that increased plasma SP-D level is associated with a higher risk of AKI in patients with sepsis. The SP-D rs721917CC genotype is an independent and significant predictor of AKI development and mortality of septic patients. The SP-D rs721917C/T polymorphisms should be further studied as diagnostic and prognostic biomarkers to facilitate early recognition of AKI.

SUBMITTER: Liu J

PROVIDER: S-EPMC6957590 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Surfactant protein D (SP-D) gene polymorphism rs721917 is an independent predictor of acute kidney injury development in sepsis patients: a prospective cohort study.

Liu Jiao J Yao Jianying J Zhang Lidi L Chen Yizhu Y Du Hangxiang H Wen Zhenliang Z Chen Dechang D

Annals of intensive care 20200113 1

<h4>Background</h4>Currently, there are no reliable predictors of risk of development and severity of acute kidney injury (AKI) in septic patients. The surfactant protein D (SP-D) polymorphism rs721917C/T is associated with a greater susceptibility to AKI in the Chinese population. Our aim was to evaluate the value of SP-D polymorphisms rs721917C/T and of plasma SP-D levels to predict the risk of development of AKI (defined with KDIGO criterion) in septic patients.<h4>Methods</h4>The study enrol ...[more]

PMID: 31933054

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Project description:AbstractTo investigate the relationship between thrombomodulin (THBD) gene single nucleotide polymorphisms (SNPs) and susceptibility to sepsis and the occurrence and prognosis of acute kidney injury (AKI) in sepsis patients.The genotypes of THBD gene rs1962, rs3176123, and rs1042580 in 178 sepsis patients with AKI, 243 sepsis patients without AKI (No AKI), and 103 healthy controls were analyzed by direct sequencing. Enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma THBD protein levels. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of plasma THBD levels in sepsis, AKI, and death of sepsis patients.The C allele carriers of THBD gene rs1962 were more likely to develop AKI and sepsis than the T allele carriers (OR = 1.61, 95% CI: 1.18-2.19, P < .01; OR = 2.16, 95% CI: 1.42-3.29, P < .01). The rs3176123 G allele was associated with an increased risk of AKI in sepsis patients (OR = 1.41, 95% CI: 1.06-1.88, P = .02), the G allele had a significant association with a higher risk of sepsis susceptibility (OR = 1.91, 95% CI: 1.33-2.75, P < .01). Sepsis patients of rs1042580 C allele had a lower risk of AKI than those of T allele (OR = 0.58, 95% CI: 0.37-0.91, P = .02), the C allele was related to a reduced risk of sepsis susceptibility (OR = 0.38, 95% CI: 0.26-0.55, P < .01). The THBD gene rs1962, rs3176123, and rs1042580 TGT haplotype was linked to higher risk of AKI in patients with sepsis (OR = 1.96, 95%CI: 1.14-3.38, P = .02). Sepsis patients with the THBD gene rs1962 TC + CC genotype had a higher risk of death than those with TT genotype (OR = 10.93, 95%CI: 5.05-26.96, P < .01), but there was no significant difference in the risk of death in sepsis patients with different genotypes at rs3176123 and rs1042580 (P > .05).The THBD gene rs1962, rs3176123, and rs1042580 SNPs are significantly associated with sepsis susceptibility and the risk of AKI. The rs1962 SNP is related to the risk of death in sepsis patients.

Project description:BackgroundVenous thromboembolism is a leading cause of morbidity after trauma. Endothelial cells are essential regulators of coagulation. Although endothelial cell dysregulation is widely reported after trauma, the link between endothelial injury and venous thromboembolism has not been reported.MethodsWe conducted a secondary analysis of the Pragmatic Randomized Optimal Platelets and Plasma Ratios study. Deaths from hemorrhage or within 24 hours were excluded. Venous thromboembolism was diagnosed by duplex ultrasound or chest computed tomography. Endothelial markers soluble endothelial protein c receptor, thrombomodulin, and syndecan-1 were measured in plasma by enzyme-linked immunosorbent assay and compared over the first 72 hours from admission using the Mann-Whitney test. Multivariable logistic regression assessed the adjusted effects of endothelial markers on venous thromboembolism risk.ResultsOf 575 patients enrolled, 86 developed venous thromboembolism (15%). The median time to venous thromboembolism was 6 days ([Q1, Q3], [4, 13]). No differences were identified in demographics or injury severity. Soluble endothelial protein c receptor, thrombomodulin, and syndecan-1 showed significant increases over time among patients who developed venous thromboembolism compared to those who did not. Using the last available values, patients were stratified into high and low-soluble endothelial protein c receptor, thrombomodulin, and syndecan-1 groups. Multivariable analyses revealed an independent association between elevated soluble endothelial protein c receptor and venous thromboembolism risk (odds ratio 1.63; 95% confidence interval 1.01, 2.63; P = .04). Cox proportional hazards modeling demonstrated a strong yet nonsignificant trend between elevated soluble endothelial protein c receptor and time to venous thromboembolism.ConclusionPlasma markers of endothelial injury, particularly soluble endothelial protein c receptor, are strongly associated with trauma-related venous thromboembolism. Therapeutics targeting endothelial function could mitigate the incidence of venous thromboembolism after trauma.

Project description:Pulmonary surfactant protein B (SP-B) is an essential protein for lowering surface tension in the alveoli. SP-B(1-25), a peptide comprised of the N-terminal 25 amino-acid residues of SP-B, is known to retain much of the biological activity of SP-B. Circular dichroism has shown that when SP-B(1-25) interacts with negatively charged lipid vesicles, it contains significant helical structure for the lipid compositions and peptide/lipid ratios studied here. The effect of SP-B(1-25) on lipid organization and polymorphisms was investigated via DSC, dynamic light scattering, transmission electron microscopy, and solid-state NMR spectroscopy. At 1-3 mol% peptide and physiologic temperature, SP-B(1-25) partitions at the interface of negatively charged PC/PG lipid bilayers. In lipid mixtures containing 1-5 mol% peptide, the structure of SP-B(1-25) remains constant, but (2)H and (31)P NMR spectra show the presence of an isotropic lipid phase in exchange with the lamellar phase below the T(m) of the lipids. This behavior is observed for both DPPC/POPG and POPC/POPG lipid mixtures as well as for both the PC and PG components of the mixtures. For 1-3 mol% SP-B(1-25), a return to a single lamellar phase above the lipid mixture T(m) is observed, but for 5 mol% SP-B(1-25) a significant isotropic component is observed at physiologic temperatures for DPPC and exchange broadening is observed in (2)H and (31)P NMR spectra of the other lipid components in the two mixtures. DLS and TEM rule out the formation of micellar structures and suggest that SP-B(1-25) promotes the formation of a fluid isotropic phase. The ability of SP-B(1-25) to fuse lipid lamellae via this mechanism, particularly those enriched in DPPC, suggests a specific role for the highly conserved N-terminus of SP-B in the packing of lipid lamellae into surfactant lamellar bodies or in stabilizing multilayer structures at the air-liquid interface. Importantly, this behavior has not been seen for the other SP-B fragments of SP-B(8-25) and SP-B(59-80), indicating a critical role for the proline rich first seven amino acids in this protein.

Project description:BACKGROUND:Acute kidney injury (AKI) complicates shock. Diagnosis is based on rising creatinine, a late phenomenon. Intrarenal vasoconstriction occurs earlier. Measuring flow resistance in the renal circulation, Renal Resistive Index (RRI), could become part of vital organ function assessment using Doppler ultrasound. Our aim was to determine whether RRI on ICU admission is an early predictor and discriminator of AKI developed within the first week. METHODS:In this prospective cohort of mixed ICU patients with and without shock, RRI was measured <24-h of admission. Besides routine variables, sublingual microcirculation and bioelectrical impedance were measured. AKI was defined by the Kidney Disease Improving Global Outcomes criteria. Uni- and multivariate regression and Receiver Operating Characteristics curve analyses were performed. RESULTS:Ninety-nine patients were included, median age 67 years (IQR 59-75), APACHE III score 67 (IQR 53-89). Forty-nine patients (49%) developed AKI within the first week. AKI patients had a higher RRI on admission than those without: 0.71 (0.69-0.73) vs. 0.65 (0.63-0.68), p = 0.001. The difference was significant for AKI stage 2: RRI = 0.72 (0.65-0.80) and 3: RRI = 0.74 (0.67-0.81), but not for AKI stage 1: RRI = 0.67 (0.61-0.74). On univariate analysis, RRI significantly predicted AKI 2-3: OR 1.012 (1.006-1.019); Area Under the Curve (AUC) of RRI for AKI 2-3 was 0.72 (0.61-0.83), optimal cut-off 0.74, sensitivity 53% and specificity 87%. On multivariate analysis, RRI remained significant, independent of APACHE III and fluid balance; adjusted OR: 1.008 (1.000-1.016). CONCLUSIONS:High RRI on ICU admission was a significant predictor for development of AKI stage 2-3 during the first week. High RRI can be used as an early warning signal RRI, because of its high specificity. A combined score including RRI, APACHE III and fluid balance improved AKI prediction, suggesting that vasoconstriction or poor vascular compliance, severity of disease and positive fluid balance independently contribute to AKI development. TRIAL REGISTRATION:ClinicalTrials.gov NCT02558166.

Dataset Information

Surfactant protein D (SP-D) gene polymorphism rs721917 is an independent predictor of acute kidney injury development in sepsis patients: a prospective cohort study.

Publications

Surfactant protein D (SP-D) gene polymorphism rs721917 is an independent predictor of acute kidney injury development in sepsis patients: a prospective cohort study.

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