Identification of Serum Metabolites for Predicting Chronic Kidney Disease Progression according to Chronic Kidney Disease Cause

Kang, Eunjeong; Li, Yufei; Kim, Bora; Huh, Ki Young; Ahn, Jung Ja; Sung, Hye Youn; Park, Yong Seek; Lee, Seung Eun; Lee, Sangjun; Park, Sue Kyung; Cho, Joo Youn; Oh, Kook Hwan

doi:10.3390/metabo12111125

Cited by 5 publications

(4 citation statements)

References 52 publications

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“…In summary, each of the reviewed metabolomic studies among ADPKD patients proposed different metabolites for predicting rapid ADPKD progression, and those are: urinary lactate/ pyruvate ratio (101), urinary alanine/citrate ratio (102), urinary myoinositol/citrate ratio (103), urinary methyladenosine, ornithine and kynurenate levels (104,105) and a prognostic model incorporating hexadecenoylcarnitine, pimelylcarnitine, creatinine, acyl-alkyl-phosphatidylcholin and five different diacylphosphatidylcholines (106). Since metabolic profiling seems to be a promising strategy for predicting disease progression in ADPKD patients by reflecting the underlying dysregulated metabolism with increased glycolytic flux, all of the suggested metabolites should be verified as ADPKD prognostic biomarkers in additional prospective clinical studies.…”

Section: Metabolomic Biomarkersmentioning

confidence: 99%

Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers

Sorić Hosman,

Cvitković Roić,

Fištrek Prlić

et al. 2023

Front. Pediatr.

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Autosomal dominant polycystic kidney disease (ADPKD) is one of the leading causes of end-stage renal disease. In spite of the recent tremendous progress in the understanding of ADPKD pathogenesis, the molecular mechanisms of the disease remain incompletely understood. Considering emerging new targeted therapies for ADPKD, it has become crucial to disclose easily measurable and widely available biomarkers for identifying patients with future rapid disease progression. This review encompasses all the research with a shared goal of identifying promising serum or urine biomarkers for predicting ADPKD progression or response to therapy. The rate of the ADPKD progress varies significantly between patients. The phenotypic variability is only partly explained by the underlying genetic lesion diversity. Considering significant decline in kidney function in ADPKD is not usually evident until at least 50% of the parenchyma has been destroyed, conventional kidney function measures, such as glomerular filtration rate (GFR), are not suitable for monitoring disease progression in ADPKD, particularly in its early stages. Since polycystic kidney enlargement usually precedes the decline in GFR, height-adjusted total kidney volume (ht-TKV) has been accepted as an early biomarker for assessing disease severity in ADPKD patients. However, since measuring ht-TKV is time-consuming and observer-dependent, the identification of a sensitive and quickly measurable biomarker is of a great interest for everyday clinical practice. Throughout the last decade, due to development of proteomic and metabolomic techniques and the enlightenment of multiple molecular pathways involved in the ADPKD pathogenesis, a number of urine and serum protein biomarkers have been investigated in ADPKD patients, some of which seem worth of further exploring. These include copeptin, angiotensinogen, monocyte chemoattractant protein 1, kidney injury molecule-1 and urine-to-plasma urea ratio among many others. The aim of the current review is to provide an overview of all of the published evidence on potentially clinically valuable serum and urine biomarkers that could be used for predicting disease progression or response to therapy in patients with ADPKD. Hopefully, this review will encourage future longitudinal prospective clinical studies evaluating proposed biomarkers as prognostic tools to improve management and outcome of ADPKD patients in everyday clinical practice.

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Section: Metabolomic Biomarkersmentioning

confidence: 99%

Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers

Sorić Hosman,

Cvitković Roić,

Fištrek Prlić

et al. 2023

Front. Pediatr.

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“…Interestingly, the kidney has an important role in glomerular uptake, tubular secretion, and catabolism of the majority of metabolites. Several longitudinal studies have been applied for metabolomic profiling in CKD patients [ 9 , 10 ]. For example, a Korean study that followed up 1741 subjects for 8 years showed a positive correlation between kynurenine and kynurenine/tryptophane ratio and new-onset CKD.…”

Section: Introductionmentioning

confidence: 99%

Untargeted Metabolomics by Ultra-High-Performance Liquid Chromatography Coupled with Electrospray Ionization-Quadrupole-Time of Flight-Mass Spectrometry Analysis Identifies a Specific Metabolomic Profile in Patients with Early Chronic Kidney Disease

Glavan

Socaciu

et al. 2023

Biomedicines

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Chronic kidney disease (CKD) has emerged as one of the most progressive diseases with increased mortality and morbidity. Metabolomics offers new insights into CKD pathogenesis and the discovery of new biomarkers for the early diagnosis of CKD. The aim of this cross-sectional study was to assess metabolomic profiling of serum and urine samples obtained from CKD patients. Untargeted metabolomics followed by multivariate and univariate analysis of blood and urine samples from 88 patients with CKD, staged by estimated glomerular filtration rate (eGFR), and 20 healthy control subjects was performed using ultra-high-performance liquid chromatography coupled with electrospray ionization-quadrupole-time of flight-mass spectrometry. Serum levels of Oleoyl glycine, alpha-lipoic acid, Propylthiouracil, and L-cysteine correlated directly with eGFR. Negative correlations were observed between serum 5-Hydroxyindoleacetic acid, Phenylalanine, Pyridoxamine, Cysteinyl glycine, Propenoylcarnitine, Uridine, and All-trans retinoic acid levels and eGFR. In urine samples, the majority of molecules were increased in patients with advanced CKD as compared with early CKD patients and controls. Amino acids, antioxidants, uremic toxins, acylcarnitines, and tryptophane metabolites were found in all CKD stages. Their dual variations in serum and urine may explain their impact on both glomerular and tubular structures, even in the early stages of CKD. Patients with CKD display a specific metabolomic profile. Since this paper represents a pilot study, future research is needed to confirm our findings that metabolites can serve as indicators of early CKD.

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“…The decline in insulin sensitivity is the main reason for the development of hyperglycemia. This is the basis and the main cause of the microangiopathies which lead to ocular, kidney and neural pathology, and atherosclerosis, which results in cardiovascular complications [31][32][33][34]. What is more, insulin resistance has an influence on lipids metabolism and protein synthesis.…”

Section: Introductionmentioning

confidence: 99%

Inflammation and Oxidative Stress in Frailty and Metabolic Syndromes—Two Sides of the Same Coin

Dzięgielewska-Gęsiak

Muc-Wierzgoń

2023

Metabolites

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In developed countries, aging is often seen as typical, but it is made complicated by many disorders and co-morbidities. Insulin resistance seems to be an underlying pathomechanism in frailty and metabolic syndromes. The decline in insulin sensitivity leads to changes in the oxidant–antioxidant balance and an accelerated inflammatory response, especially by adipocytes and macrophages in adipose tissue, as well as muscle mass density. Thus, in the pathophysiology of syndemic disorders—the metabolic syndrome and frailty syndrome—an extremely important role may be played by increased oxidative stress and pro-inflammatory state. Papers included in this review explored available full texts and the reference lists of relevant studies from the last 20 years, before the end of 2022; we also investigated the PubMed and Google Scholar electronic databases. The online resources describing an elderly population (≥65 years old) published as full texts were searched for the following terms: “oxidative stress and/or inflammation”, “frailty and/or metabolic syndrome”. Then, all resources were analyzed and narratively described in the context of oxidative stress and/or inflammation markers which underlie pathomechanisms of frailty and/or metabolic syndromes in elderly patients. So far, different metabolic pathways discussed in this review show that a similar pathogenesis underlies the development of the metabolic as well as frailty syndromes in the context of increased oxidative stress and acceleration of inflammation. Thus, we argue that the syndemia of the syndromes represents two sides of the same coin.

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Identification of Serum Metabolites for Predicting Chronic Kidney Disease Progression according to Chronic Kidney Disease Cause

Cited by 5 publications

References 52 publications

Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers

Predicting autosomal dominant polycystic kidney disease progression: review of promising Serum and urine biomarkers

Untargeted Metabolomics by Ultra-High-Performance Liquid Chromatography Coupled with Electrospray Ionization-Quadrupole-Time of Flight-Mass Spectrometry Analysis Identifies a Specific Metabolomic Profile in Patients with Early Chronic Kidney Disease

Inflammation and Oxidative Stress in Frailty and Metabolic Syndromes—Two Sides of the Same Coin

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