The role of carnitine in maintenance dialysis therapy

Morgans, Heather A.; Chadha, Vimal; Warady, Bradley A.

doi:10.1007/s00467-021-05101-z

Cited by 8 publications

(5 citation statements)

References 34 publications

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“…There is growing interest in how the acylcarnitine/ carnitine axis may reflect mitochondrial dysfunction in CKD. 86,87 Hydroxy-CMPF and 3-carboxy-4-methyl-5pentyl-2-furanpropionate were associated with proteinuria and eGFR, respectively. These compounds are believed to be mitochondrial toxins and have been previously associated with worse neurocognitive outcomes in children with CKD.…”

Section: Discussionmentioning

confidence: 96%

“…17 Carnitine is an emerging biomarker of interest potentially related to mitochondrial dysfunction in CKD. 86,87 Another limitation is participant differences between the baseline and follow-up samples. Participants without follow-up metabolomic assessments represent a different clinical phenotype, with lower baseline eGFR and more glomerular disease.…”

Section: Discussionmentioning

confidence: 99%

“…17 Carnitine is an emerging biomarker of interest potentially related to mitochondrial dysfunction in CKD. 86,87…”

Section: Discussionmentioning

confidence: 99%

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Longitudinal Plasma Metabolome Patterns and Relation to Kidney Function and Proteinuria in Pediatric CKD

Lee,

Xu,

et al. 2024

CJASN

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Introduction Understanding plasma metabolome patterns in relation to changing kidney function in pediatric chronic kidney disease (CKD) is important for continued research for identifying novel biomarkers, characterizing biochemical pathophysiology, and developing targeted interventions. There is a limited number of studies of longitudinal metabolomics, and virtually none in pediatric CKD. Methods The Chronic Kidney Disease in Children (CKiD) study is a multi-institutional, prospective cohort that enrolled children aged six-months to 16-years with estimated glomerular filtration rate (eGFR) 30-90ml/min/1.73m2. Untargeted metabolomics profiling was performed on plasma samples from the baseline, two-, and four-year study visits. There were technologic updates in the metabolomic profiling platform used between the baseline and follow-up assays. Statistical approaches were adopted to avoid direct comparison of baseline and follow-up measurements. To identify metabolite associations with eGFR or urine protein:creatinine (UPCR) among all three timepoints, we applied linear mixed effects (LME) models. To identify metabolites associated with time, we applied LME models to the two- and four-year follow-up data. We applied linear regression analysis to examine associations between change in metabolite level over time (∆level) and change in eGFR (∆eGFR) and UPCR (∆UPCR). We reported significance based on both the False Discovery Rate (FDR) <0.05 and p<0.05. Results There were 1156 person-visits (N: baseline=626, 2-year=254, 4-year=276) included. There were 622 metabolites with standardized measurements at all three timepoints. In LME modeling, 406 and 343 metabolites associated with eGFR and UPCR at FDR<0.05 respectively. Among 530 follow-up person-visits, 158 metabolites showed differences over time at FDR<0.05. For participants with complete data at both follow-up visits (N=123), we report 35 metabolites with ∆level∼∆eGFR associations significant at FDR<0.05. There were no metabolites with significant ∆level∼∆UPCR associations at FDR<0.05. We report 16 metabolites with ∆level∼∆UPCR associations at p<0.05 and associations with UPCR in LME modeling at FDR<0.05. Conclusion We characterized longitudinal plasma metabolomic patterns associated with eGFR and UPCR in a large pediatric CKD population. Many of these metabolite signals have been associated with CKD progression, etiology, and proteinuria in previous CKD Biomarkers Consortium studies. There were also novel metabolite associations with eGFR and proteinuria detected.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

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Longitudinal Plasma Metabolome Patterns and Relation to Kidney Function and Proteinuria in Pediatric CKD

Lee,

Xu,

et al. 2024

CJASN

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“…72 Carnitine dysmetabolism has been described in children and adults on dialysis. 73 Previous studies suggest CMPF mediates neurotoxicity by inhibiting mitochondrial respiration in CKD. 74,75 By contrast, our data showed CMPF and hydroxy-CMPF to be positively associated with working memory.…”

Section: Discussionmentioning

confidence: 98%

Circulating Metabolomic Associations with Neurocognitive Outcomes in Pediatric CKD

Lee,

Xu,

Hooper

et al. 2023

CJASN

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Background: Children with chronic kidney disease (CKD) are at risk for impaired neurocognitive functioning. We investigated metabolomic associations with neurocognition in children with CKD. Methods: We leveraged data from the Chronic Kidney Disease in Children (CKiD) study and the Neurocognitive Assessment and Magnetic Resonance Imaging Analysis of Children and Young Adults with Chronic Kidney Disease (NiCK) study. CKiD is a multi-institutional cohort that enrolled children age 6 months to 16 years with estimated glomerular filtration rate (eGFR) 30-90ml/min/1.73m2 (n=569). NiCK is a single center cross-sectional study of participants aged 8-25 years with eGFR<90ml/min/1.73m2 (n=60) and matched healthy controls (n=67). Untargeted metabolomics quantification was performed on plasma (CKiD, 622 metabolites) and serum (NiCK, 825 metabolites) samples. Four neurocognitive domains were assessed (intelligence, attention regulation, working memory, and parent ratings of executive function). Repeat assessments were performed in CKiD at 2-year intervals. Linear regression and linear mixed-effects regression analyses adjusting for age, sex, delivery history, hypertension, proteinuria, CKD duration, and glomerular vs. non-glomerular diagnosis were used to identify metabolites associated with neurocognitive z-scores. Analyses were performed with and without adjustment for eGFR. Results: There were multiple metabolite associations with neurocognition observed in at least two of the analytic samples (CKiD baseline, CKiD follow-up, NiCK CKD). Most of these metabolites were significantly elevated in children with CKD compared to healthy controls in NiCK. Notable signals included associations with parental ratings of executive function: phenylacetylglutamine, indoleacetylglutamine, and trimethylamine N-oxide, - and with intelligence: gamma-glutamyl amino acids and aconitate. Conclusions: Several metabolites were associated with neurocognitive dysfunction in pediatric CKD, implicating gut microbiome-derived substances, mitochondrial dysfunction and altered energy metabolism, circulating toxins, and redox homeostasis.

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“…Chronic renal failure patients often suffer from carnitine deficiency due to dietary restrictions, renal dysfunction, and continuous loss during dialysis. Thus, oral or intravenous supplementation of L-carnitine presents a potential therapy for correcting the abnormal metabolic reprogramming in these patients [134,135]. Several clinical randomized controlled trials of L-carnitine supplementation have been conducted in patients undergoing hemodialysis or peritoneal dialysis for chronic renal failure; however, the existing results are somewhat controversial [136][137][138][139][140].…”

Section: Kidney Failure Caused By Mitochondrial Respiratory Chain Abn...mentioning

confidence: 99%

Focus on Mitochondrial Respiratory Chain: Potential Therapeutic Target for Chronic Renal Failure

Wang,

Yang,

Zhang

et al. 2024

IJMS

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The function of the respiratory chain is closely associated with kidney function, and the dysfunction of the respiratory chain is a primary pathophysiological change in chronic kidney failure. The incidence of chronic kidney failure caused by defects in respiratory-chain-related genes has frequently been overlooked. Correcting abnormal metabolic reprogramming, rescuing the “toxic respiratory chain”, and targeting the clearance of mitochondrial reactive oxygen species are potential therapies for treating chronic kidney failure. These treatments have shown promising results in slowing fibrosis and inflammation progression and improving kidney function in various animal models of chronic kidney failure and patients with chronic kidney disease (CKD). The mitochondrial respiratory chain is a key target worthy of attention in the treatment of chronic kidney failure. This review integrated research related to the mitochondrial respiratory chain and chronic kidney failure, primarily elucidating the pathological status of the mitochondrial respiratory chain in chronic kidney failure and potential therapeutic drugs. It provided new ideas for the treatment of kidney failure and promoted the development of drugs targeting the mitochondrial respiratory chain.

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The role of carnitine in maintenance dialysis therapy

Cited by 8 publications

References 34 publications

Longitudinal Plasma Metabolome Patterns and Relation to Kidney Function and Proteinuria in Pediatric CKD

Longitudinal Plasma Metabolome Patterns and Relation to Kidney Function and Proteinuria in Pediatric CKD

Circulating Metabolomic Associations with Neurocognitive Outcomes in Pediatric CKD

Focus on Mitochondrial Respiratory Chain: Potential Therapeutic Target for Chronic Renal Failure

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