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Polymorphisms in the myeloperoxidase gene locus are associated with acute kidney injury-related outcomes.

ABSTRACT: Myeloperoxidase (MPO) is a lysosomal enzyme that may be involved in oxidative stress-mediated kidney injury. Using a two-step approach, we measured the association of four polymorphisms across the length of the MPO gene with systemic markers of oxidative stress: plasma MPO and urinary 15-F(2t)-isoprostane levels. Adverse outcomes were measured in a primary cohort of 262 adults hospitalized with acute kidney injury, and a secondary cohort of 277 adults undergoing cardiac surgery with cardiopulmonary bypass and at risk for postoperative acute kidney injury. Dominant and haplotype multivariable logistic regression analyses found a genotype-phenotype association in the primary cohort between rs2243828, rs7208693, rs2071409, and rs2759 MPO polymorphisms and both markers of oxidative stress. In adjusted analyses, all four polymorphic allele groups had 2-3-fold higher odds for composite outcomes of dialysis or in-hospital death or a composite of dialysis, assisted mechanical ventilation, or in-hospital death. The MPO T-G-A-T haplotype copy-number was associated with lower plasma MPO levels and lower adjusted odds for the composite outcomes. Significant but less consistent associations were found in the secondary cohort. In summary, our two-step genetic association study identified several polymorphisms spanning the entire MPO gene locus and a common haplotype marker for patients at risk for acute kidney injury.

SUBMITTER: Perianayagam MC

PROVIDER: S-EPMC3461107 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Polymorphisms in the myeloperoxidase gene locus are associated with acute kidney injury-related outcomes.

Perianayagam Mary C MC Tighiouart Hocine H Liangos Orfeas O Kouznetsov Diana D Wald Ron R Rao Fangwen F O'Connor Daniel T DT Jaber Bertrand L BL

Kidney international 20120627 8

Myeloperoxidase (MPO) is a lysosomal enzyme that may be involved in oxidative stress-mediated kidney injury. Using a two-step approach, we measured the association of four polymorphisms across the length of the MPO gene with systemic markers of oxidative stress: plasma MPO and urinary 15-F(2t)-isoprostane levels. Adverse outcomes were measured in a primary cohort of 262 adults hospitalized with acute kidney injury, and a secondary cohort of 277 adults undergoing cardiac surgery with cardiopulmon ...[more]

PMID: 22739978

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Project description:It has been suggested that fluid accumulation may delay recognition of acute kidney injury. We sought to determine the impact of fluid balance on the incidence of nondialysis requiring acute kidney injury in patients with acute lung injury and to describe associated outcomes, including mortality.Analysis of the Fluid and Catheter Treatment Trial, a factorial randomized clinical trial of conservative vs. liberal fluid management and of management guided by a central venous vs. pulmonary artery catheter.Acute Respiratory Distress Syndrome Network hospitals.One thousand patients.None.The incidence of acute kidney injury, defined as an absolute rise in creatinine of ?0.3 mg/dL or a relative change of >50% over 48 hrs, was examined before and after adjustment of serum creatinine for fluid balance. The incidence of acute kidney injury before adjustment for fluid balance was greater in those managed with the conservative fluid protocol (57% vs. 51%, p = .04). After adjustment for fluid balance, the incidence of acute kidney injury was greater in those managed with the liberal fluid protocol (66% vs. 58%, p = .007). Patients who met acute kidney injury criteria after adjustment of creatinine for fluid balance (but not before) had a mortality rate that was significantly greater than those who did not meet acute kidney injury criteria both before and after adjustment for fluid balance (31% vs. 12%, p < .001) and those who had acute kidney injury before but not after adjustment for fluid balance (31% vs. 11%, p = .005). The mortality of those patients meeting acute kidney injury criteria after but not before adjustment for fluid balance was similar to patients with acute kidney injury both before and after adjustment for fluid balance (31% vs. 38%, p = .18).Fluid management influences serum creatinine and therefore the diagnosis of acute kidney injury using creatinine-based definitions. Patients with "unrecognized" acute kidney injury that is identified after adjusting for positive fluid balance have higher mortality rates, and patients who have acute kidney injury before but not after adjusting for fluid balance have lower mortality rates. Future studies of acute kidney injury should consider potential differences in serum creatinine caused by changes in fluid balance and the impact of these differences on diagnosis and prognosis.

Project description:BackgroundAKI is a significant complication of coronavirus disease 2019 (COVID-19), with no effective therapy. Niacinamide, a vitamin B3 analogue, has some evidence of efficacy in non-COVID-19-related AKI. The objective of this study is to evaluate the association between niacinamide therapy and outcomes in patients with COVID-19-related AKI.MethodsWe implemented a quasi-experimental design with nonrandom, prospective allocation of niacinamide in 201 hospitalized adult patients, excluding those with baseline eGFR <15 ml/min per 1.73 m2 on or off dialysis, with COVID-19-related AKI by Kidney Disease Improving Global Outcomes (KDIGO) criteria, in two hospitals with identical COVID-19 care algorithms, one of which additionally implemented treatment with niacinamide for COVID-19-related AKI. Patients on the niacinamide protocol (B3 patients) were compared against patients at the same institution before protocol commencement and contemporaneous patients at the non-niacinamide hospital (collectively, non-B3 patients). The primary outcome was a composite of death or RRT.ResultsA total of 38 out of 90 B3 patients and 62 out of 111 non-B3 patients died or received RRT. Using multivariable Cox proportional hazard modeling, niacinamide was associated with a lower risk of RRT or death (HR, 0.64; 95% CI, 0.40 to 1.00; P=0.05), an association driven by patients with KDIGO stage-2/3 AKI (HR, 0.29; 95% CI, 0.13 to 0.65; P=0.03; P interaction with KDIGO stage=0.03). Total mortality also followed this pattern (HR, 0.17; 95% CI, 0.05 to 0.52; in patients with KDIGO stage-2/3 AKI, P=0.002). Serum creatinine after AKI increased by 0.20 (SEM, 0.08) mg/dl per day among non-B3 patients with KDIGO stage-2/3 AKI, but was stable among comparable B3 patients (+0.01 [SEM, 0.06] mg/dl per day; P interaction=0.03).ConclusionsNiacinamide was associated with lower risk of RRT/death and improved creatinine trajectory among patients with severe COVID-19-related AKI. Larger randomized studies are necessary to establish a causal relationship.

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Project description:BACKGROUND:Acute kidney injury (AKI) during pregnancy is a public health problem and is associated with maternal and fetal morbidity and mortality. Clinical outcomes and health care utilization in pregnancy-related AKI, especially in women with diabetes, are not well studied. METHODS:Using data from the 2006 to 2015 Nationwide Inpatient Sample, we identified 42,190,790 pregnancy-related hospitalizations in women aged 15-49 years. We determined factors associated with AKI, including race/ethnicity, and associations between AKI and inpatient mortality, and between AKI and cardiovascular (CV) events, during pregnancy-related hospitalizations. We calculated health care expenditures from pregnancy-related AKI hospitalizations. RESULTS:Overall, the rate of AKI during pregnancy-related hospitalizations was 0.08%. In the adjusted regression analysis, a higher likelihood of AKI during pregnancy-related hospitalizations was seen in 2015 (OR 2.20; 95% CI 1.89-2.55) than in 2006; in older women aged 36-40 years (OR 1.49; 95% CI 1.36-1.64) and 41-49 years (OR 2.12; 95% CI 1.84-2.45) than in women aged 20-25 years; in blacks (OR 1.52; 95% CI 1.40-1.65) and Native Americans (OR 1.45; 95% CI 1.10-1.91) than in whites, and in diabetic women (OR 4.43; 95% CI 4.04-4.86) than in those without diabetes. Pregnancy-related hospitalizations with AKI were associated with a higher likelihood of inpatient mortality (OR 13.50; 95% CI 10.47-17.42) and CV events (OR 9.74; 95% CI 9.08-10.46) than were hospitalizations with no AKI. The median cost was higher for a delivery hospitalization with AKI than without AKI (USD 18,072 vs. 4,447). CONCLUSION:The rates of pregnancy-related AKI hospitalizations have increased during the last decade. Factors associated with a higher likelihood of AKI during pregnancy included older age, black and Native American race/ethnicity, and diabetes. Hospitalizations with pregnancy-related AKI have an increased risk of inpatient mortality and CV events, and a higher health care utilization than do those without AKI.

Dataset Information

Polymorphisms in the myeloperoxidase gene locus are associated with acute kidney injury-related outcomes.

Publications

Polymorphisms in the myeloperoxidase gene locus are associated with acute kidney injury-related outcomes.

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