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Plasma metabolites and lipids associate with kidney function and kidney volume in hypertensive ADPKD patients early in the disease course.

ABSTRACT: BACKGROUND:Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and is characterized by gradual cyst growth and expansion, increase in kidney volume with an ultimate decline in kidney function leading to end stage renal disease (ESRD). Given the decades long period of stable kidney function while cyst growth occurs, it is important to identify those patients who will progress to ESRD. Recent data from our and other laboratories have demonstrated that metabolic reprogramming may play a key role in cystic epithelial proliferation resulting in cyst growth in ADPKD. Height corrected total kidney volume (ht-TKV) accurately reflects cyst burden and predicts future loss of kidney function. We hypothesize that specific plasma metabolites will correlate with eGFR and ht-TKV early in ADPKD, both predictors of disease progression, potentially indicative of early physiologic derangements of renal disease severity. METHODS:To investigate the predictive role of plasma metabolites on eGFR and/or ht-TKV, we used a non-targeted GC-TOF/MS-based metabolomics approach on hypertensive ADPKD patients in the early course of their disease. Patient data was obtained from the HALT-A randomized clinical trial at baseline including estimated glomerular filtration rate (eGFR) and measured ht-TKV. To identify individual metabolites whose intensities are significantly correlated with eGFR and ht-TKV, association analyses were performed using linear regression with each metabolite signal level as the primary predictor variable and baseline eGFR and ht-TKV as the continuous outcomes of interest, while adjusting for covariates. Significance was determined by Storey's false discovery rate (FDR) q-values to correct for multiple testing. RESULTS:Twelve metabolites significantly correlated with eGFR and two triglycerides significantly correlated with baseline ht-TKV at FDR q-value

SUBMITTER: Kim K

PROVIDER: S-EPMC6388487 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Plasma metabolites and lipids associate with kidney function and kidney volume in hypertensive ADPKD patients early in the disease course.

Kim Kyoungmi K Trott Josephine F JF Gao Guimin G Chapman Arlene A Weiss Robert H RH

BMC nephrology 20190225 1

<h4>Background</h4>Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and is characterized by gradual cyst growth and expansion, increase in kidney volume with an ultimate decline in kidney function leading to end stage renal disease (ESRD). Given the decades long period of stable kidney function while cyst growth occurs, it is important to identify those patients who will progress to ESRD. Recent data from our and other laboratories have demonstrat ...[more]

PMID: 30803434

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Project description:Unbiased global metabolomic profiling has not been used to identify distinct subclasses in patients with early sepsis and sepsis-associated acute respiratory distress syndrome. In this study, we examined whether the plasma metabolome reflects systemic illness in early sepsis and in acute respiratory distress syndrome.DesignPlasma metabolites were measured in subjects with early sepsis.SettingPatients were admitted from the emergency department to the ICU in a plasma sample collected within 24 hours of ICU admission. Metabolic profiling of 970 metabolites was performed by Metabolon (Durham, NC). Hierarchical clustering and partial least squares discriminant clustering were used to identify distinct clusters among patients with early sepsis and sepsis-associated acute respiratory distress syndrome.InterventionsNone.Measurements and main resultsAmong critically ill patients with early sepsis (n = 197), three metabolically distinct subgroups were identified, with metabolic subtype driven by plasma lipids. Group 1, with 45 subjects (23% of cohort), had increased 60-day mortality (odds ratio, 2; 95% CI, 0.99-4.0; p = 0.04 for group 1 vs all others). This group also had higher rates of vasopressor-dependent shock, acute kidney injury, and met Berlin acute respiratory distress syndrome criteria more often (all p < 0.05). Conversely, metabolic group 3, with 76 subjects (39% of cohort), had the lowest risk of 60-day mortality (odds ratio, 0.44; 95% CI, 0.22-0.86; p = 0.01) and lower rates of organ dysfunction as reflected in a lower Simplified Acute Physiology Score II (p < 0.001). In contrast, global metabolomic profiling did not separate patient with early sepsis with moderate-to-severe acute respiratory distress syndrome (n = 78) from those with sepsis without acute respiratory distress syndrome (n = 75).ConclusionsPlasma metabolomic profiling in patients with early sepsis identified three metabolically distinct groups that were characterized by different plasma lipid profiles, distinct clinical phenotypes, and 60-day mortality. Plasma metabolites did not distinguish patients with early sepsis who developed acute respiratory distress syndrome from those who did not.

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Plasma metabolites and lipids associate with kidney function and kidney volume in hypertensive ADPKD patients early in the disease course.

Publications

Plasma metabolites and lipids associate with kidney function and kidney volume in hypertensive ADPKD patients early in the disease course.

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