Relationship Between Serum Carnitine, Acylcarnitines, and Renal Function in Patients With Chronic Renal Disease

Fouque, Denis; Holt, Shannon C.; Guebre-Egziabher, Fitsum; Nakamura, Kazunori; Vianey‐Saban, Christine; Hadj‐Aïssa, Aoumeur; Hoppel, Charles L.; Kopple, Joel D.

doi:10.1053/j.jrn.2006.01.004

Cited by 62 publications

(29 citation statements)

References 26 publications

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“…The accumulation of various acylcarnitines in the plasma likely depicts impaired clearance due to chronic kidney dysfunction, which is consistent with recent observations [47]. Besides its function in fatty acid beta oxidation, L-carnitine modulates acyl-CoA levels through esterification to acylcarnitines, thus preventing the accumulation of acyl-CoAs generated in excess in renal failure [48], [49].…”

Section: Discussionsupporting

confidence: 88%

Assessment of Metabolomic and Proteomic Biomarkers in Detection and Prognosis of Progression of Renal Function in Chronic Kidney Disease

Nkuipou‐Kenfack

Duranton²,

Gayrard³

et al. 2014

PLoS ONE

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Chronic kidney disease (CKD) is part of a number of systemic and renal diseases and may reach epidemic proportions over the next decade. Efforts have been made to improve diagnosis and management of CKD. We hypothesised that combining metabolomic and proteomic approaches could generate a more systemic and complete view of the disease mechanisms. To test this approach, we examined samples from a cohort of 49 patients representing different stages of CKD. Urine samples were analysed for proteomic changes using capillary electrophoresis-mass spectrometry and urine and plasma samples for metabolomic changes using different mass spectrometry-based techniques. The training set included 20 CKD patients selected according to their estimated glomerular filtration rate (eGFR) at mild (59.9±16.5 mL/min/1.73 m2; n = 10) or advanced (8.9±4.5 mL/min/1.73 m2; n = 10) CKD and the remaining 29 patients left for the test set. We identified a panel of 76 statistically significant metabolites and peptides that correlated with CKD in the training set. We combined these biomarkers in different classifiers and then performed correlation analyses with eGFR at baseline and follow-up after 2.8±0.8 years in the test set. A solely plasma metabolite biomarker-based classifier significantly correlated with the loss of kidney function in the test set at baseline and follow-up (ρ = −0.8031; p<0.0001 and ρ = −0.6009; p = 0.0019, respectively). Similarly, a urinary metabolite biomarker-based classifier did reveal significant association to kidney function (ρ = −0.6557; p = 0.0001 and ρ = −0.6574; p = 0.0005). A classifier utilising 46 identified urinary peptide biomarkers performed statistically equivalent to the urinary and plasma metabolite classifier (ρ = −0.7752; p<0.0001 and ρ = −0.8400; p<0.0001). The combination of both urinary proteomic and urinary and plasma metabolic biomarkers did not improve the correlation with eGFR. In conclusion, we found excellent association of plasma and urinary metabolites and urinary peptides with kidney function, and disease progression, but no added value in combining the different biomarkers data.

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Section: Discussionsupporting

confidence: 88%

Assessment of Metabolomic and Proteomic Biomarkers in Detection and Prognosis of Progression of Renal Function in Chronic Kidney Disease

Nkuipou‐Kenfack

Duranton²,

Gayrard³

et al. 2014

PLoS ONE

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“…Serum free carnitine, as a small molecular, high polarity solute, is lost to a significant degree in the dialysate after hemodialysis [33]. In the present study, the concentration of serum free carnitine in HD patients (D/CT ratio = 1.524, FDR = 0.526) was almost equal to that of the healthy subjects, which may be due to intravenous supplementation after hemodialysis.…”

Section: Serum Metabolic Profile Of Hd Patients Differs Significantlymentioning

confidence: 42%

“…In contrast, acetylcarnitine was increased markedly in HD patients. Renal failure and low hemodialysis clearance contribute to its elevation in serum [33]. Similar to carnitine, choline can also be removed from the circulation to dialysate during hemodialysis [34]; however, the concentration of serum free choline was elevated in HD patients before dialysis.…”

Section: Serum Metabolic Profile Of Hd Patients Differs Significantlymentioning

confidence: 99%

Metabolite Profiling of Feces and Serum in Hemodialysis Patients and the Effect of Medicinal Charcoal Tablets

Liu

Liang

Liu

et al. 2018

Kidney Blood Press Res

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Background/Aims: Recently, the colon has been recognized as an important source of various uremic toxins in patients with end stage renal disease. Medicinal charcoal tablets are an oral adsorbent that are widely used in patients with chronic kidney disease in China to remove creatinine and urea from the colon. A parallel fecal and serum metabolomics study was performed to determine comprehensive metabolic profiles of patients receiving hemodialysis (HD). The effects of medicinal charcoal tablets on the fecal and serum metabolomes of HD patients were also investigated. Methods: Ultra-performance liquid chromatography/mass spectrometry was used to investigate the fecal and serum metabolic profiles of 20 healthy controls and 31 HD patients before and after taking medicinal charcoal tablets for 3 months. Results: There were distinct metabolic variations between the HD patients and healthy controls both in the feces and serum according to multivariate data analysis. Metabolic disturbances of alanine, aspartate and glutamate metabolism, arginine and proline metabolism figured prominently in the serum. However, in the feces, alterations of tryptophan metabolism, lysine degradation and beta-alanine metabolism were pronounced, and the levels of several amino acids (leucine, phenylalanine, lysine, histidine, methionine, tyrosine, and tryptophan) were increased dramatically. Nineteen fecal metabolites and 21 serum metabolites were also identified as biomarkers that contributed to the metabolic differences. Additionally, medicinal charcoal treatment generally enabled the serum and fecal metabolomes of the HD patients to draw close to those of the control subjects, especially the serum metabolic profile. Conclusion: Parallel fecal and serum metabolomics uncovered the systematic metabolic variations of HD patients, especially disturbances in amino acid metabolism in the colon. Medicinal charcoal tablets had an impact on the serum and fecal metabolomes of HD patients, but their exact effects still need to be studied further.

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“…Acylcarnitines are filtered through the kidney and about 75% are excreted into urine. (73) Serum acylcarnitines deriving from lipid and amino acids are inversely correlated with GFR in individuals with normal as well as with impaired renal function. (18, 74, 75) Acylcarnitines transport is regulated by organic carnitine transporters in the kidney.…”

Section: Discussionmentioning

confidence: 99%

Uremic solutes and risk of end-stage renal disease in type 2 diabetes: metabolomic study

Niewczas

Sirich

Mathew

et al. 2014

Kidney International

197

172

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Here we studied plasma metabolomic profiles as determinants of progression to ESRD in patients with Type 2 diabetes (T2D). This nested case-control study evaluated 40 cases who progressed to ESRD during 8-12 years of follow-up and 40 controls who remained alive without ESRD from the Joslin Kidney Study cohort. Controls were matched with cases for baseline clinical characteristics; although controls had slightly higher eGFR and lower levels of urinary albumin excretion than T2D cases. Plasma metabolites at baseline were measured by mass spectrometry-based global metabolomic profiling. Of the named metabolites in the library, 262 were detected in at least 80% of the study patients. The metabolomic platform recognized 78 metabolites previously reported to be elevated in ESRD (uremic solutes). Sixteen were already elevated in the baseline plasma of our cases years before ESRD developed. Other uremic solutes were either not different or not commonly detectable. Essential amino acids and their derivatives were significantly depleted in the cases, whereas certain amino acid-derived acylcarnitines were increased. All findings remained statistically significant after adjustment for differences between study groups in albumin excretion rate, eGFR or HbA1c. Uremic solute differences were confirmed by quantitative measurements. Thus, abnormal plasma concentrations of putative uremic solutes and essential amino acids either contribute to progression to ESRD or are a manifestation of an early stage(s) of the disease process that leads to ESRD in T2D.

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Relationship Between Serum Carnitine, Acylcarnitines, and Renal Function in Patients With Chronic Renal Disease

Cited by 62 publications

References 26 publications

Assessment of Metabolomic and Proteomic Biomarkers in Detection and Prognosis of Progression of Renal Function in Chronic Kidney Disease

Assessment of Metabolomic and Proteomic Biomarkers in Detection and Prognosis of Progression of Renal Function in Chronic Kidney Disease

Metabolite Profiling of Feces and Serum in Hemodialysis Patients and the Effect of Medicinal Charcoal Tablets

Uremic solutes and risk of end-stage renal disease in type 2 diabetes: metabolomic study

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