Serum carnitine levels and carnitine esters of patients after kidney transplantation: Role of immunosuppression

Wanner, Christoph; Schollmeyer, P.; Hörl, Walter H.

doi:10.1016/0026-0495(88)90106-0

Cited by 13 publications

(6 citation statements)

References 17 publications

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“…The result is reduced concentration of low-molecular-weight triacylglycerols and accumulation of high-molecular-weight triacylglycerols ( Rhee et al 2010 ). Consistent with this theory, we and others find higher concentrations of long-chain fatty acids (palmitate, oleate, stearate and myristate) ( Fouque et al, 2006 , Shah et al, 2013 , Wanner et al, 1988 ) and adipate ( Rhee et al, 2010 , Toyohara et al, 2010 ) in plasma ( Table 2 ). In addition, we find significant alteration in metabolism of two of the most abundant short-chain fatty acids (SCFA; propanoate and butanoate), with marked reduction in urinary excretion of several distal propanoate metabolites (hydroxypropionate, methylcitrate, tiglyglycine, methylmalonate).…”

Section: Discussionsupporting

confidence: 89%

Metabolomics and Gene Expression Analysis Reveal Down-regulation of the Citric Acid (TCA) Cycle in Non-diabetic CKD Patients

et al. 2017

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Chronic kidney disease (CKD) is a public health problem with very high prevalence and mortality. Yet, there is a paucity of effective treatment options, partly due to insufficient knowledge of underlying pathophysiology. We combined metabolomics (GCMS) with kidney gene expression studies to identify metabolic pathways that are altered in adults with non-diabetic stage 3–4 CKD versus healthy adults. Urinary excretion rate of 27 metabolites and plasma concentration of 33 metabolites differed significantly in CKD patients versus controls (estimate range − 68% to + 113%). Pathway analysis revealed that the citric acid cycle was the most significantly affected, with urinary excretion of citrate, cis-aconitate, isocitrate, 2-oxoglutarate and succinate reduced by 40–68%. Reduction of the citric acid cycle metabolites in urine was replicated in an independent cohort. Expression of genes regulating aconitate, isocitrate, 2-oxoglutarate and succinate were significantly reduced in kidney biopsies. We observed increased urine citrate excretion (+ 74%, p = 0.00009) and plasma 2-oxoglutarate concentrations (+ 12%, p = 0.002) in CKD patients during treatment with a vitamin-D receptor agonist in a randomized trial. In conclusion, urinary excretion of citric acid cycle metabolites and renal expression of genes regulating these metabolites were reduced in non-diabetic CKD. This supports the emerging view of CKD as a state of mitochondrial dysfunction.

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Section: Discussionsupporting

confidence: 89%

Metabolomics and Gene Expression Analysis Reveal Down-regulation of the Citric Acid (TCA) Cycle in Non-diabetic CKD Patients

et al. 2017

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“…A common finding during renal insufficiency is the elevation of acylcarnitine serum content, most likely due to defective kidney excretion [28]. In the sample of patients under study, butyrylcarnitine (C4) and dodecanoylcarnitine (C12) were significantly higher in patients with worse graft function (C4: T3 = 0.60 [0.35, 0.74] vs. T1 = 0.30 [0.26, 0.42] μM, p = 0.01; C12: T3 = 0.12 [0.08, 0.15] vs. T1 = 0.10 [0.08, 0.11] μM, p<0.05; Fig 1A and 1B).…”

Section: Resultsmentioning

confidence: 99%

Metabolomic Profiling in Individuals with a Failing Kidney Allograft

et al. 2017

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BackgroundAlteration of certain metabolites may play a role in the pathophysiology of renal allograft disease.MethodsTo explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls.ResultsLC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively). The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively). In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels.ConclusionsWe report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function.

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“…Conversely, CyA treatment resulted in an increase on the hepatic concentration of LC but did not affect the LC levels in the pancreas or kidney. A study with cadaveric kidney transplant patients being administered either azathioprine (AZA) or CyA showed significantly elevated levels of total carnitine, LC, and short-chain ACs in serum when patients were treated with CyA and prednisone and compared to AZA-treated [101].…”

Section: Cyclosporinementioning

confidence: 99%

L-Carnitine and Acylcarnitines: Mitochondrial Biomarkers for Precision Medicine

et al. 2021

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Biomarker discovery and implementation are at the forefront of the precision medicine movement. Modern advances in the field of metabolomics afford the opportunity to readily identify new metabolite biomarkers across a wide array of disciplines. Many of the metabolites are derived from or directly reflective of mitochondrial metabolism. L-carnitine and acylcarnitines are established mitochondrial biomarkers used to screen neonates for a series of genetic disorders affecting fatty acid oxidation, known as the inborn errors of metabolism. However, L-carnitine and acylcarnitines are not routinely measured beyond this screening, despite the growing evidence that shows their clinical utility outside of these disorders. Measurements of the carnitine pool have been used to identify the disease and prognosticate mortality among disorders such as diabetes, sepsis, cancer, and heart failure, as well as identify subjects experiencing adverse drug reactions from various medications like valproic acid, clofazimine, zidovudine, cisplatin, propofol, and cyclosporine. The aim of this review is to collect and interpret the literature evidence supporting the clinical biomarker application of L-carnitine and acylcarnitines. Further study of these metabolites could ultimately provide mechanistic insights that guide therapeutic decisions and elucidate new pharmacologic targets.

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Serum carnitine levels and carnitine esters of patients after kidney transplantation: Role of immunosuppression

Cited by 13 publications

References 17 publications

Metabolomics and Gene Expression Analysis Reveal Down-regulation of the Citric Acid (TCA) Cycle in Non-diabetic CKD Patients

Metabolomics and Gene Expression Analysis Reveal Down-regulation of the Citric Acid (TCA) Cycle in Non-diabetic CKD Patients

Metabolomic Profiling in Individuals with a Failing Kidney Allograft

L-Carnitine and Acylcarnitines: Mitochondrial Biomarkers for Precision Medicine

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