Assessment of uremic toxins in advanced chronic kidney disease patients on maintenance hemodialysis by LC-ESI-MS/MS

Ragi, Nagarjunachary; Pallerla, Pavankumar; Gari, Aravind Reddy Babi Reddy; Lingampelly, Sai Sachin; Ketavarapu, Vijayasarathy; Addipilli, Ramunaidu; Chirra, Nagaraju; Kantevari, Srinivas; Yadla, Manjusha; Prabhakar, S.

doi:10.1007/s11306-023-01978-z

Cited by 13 publications

(13 citation statements)

References 43 publications

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“…As anticipated, increased levels of all evaluated PBUTs, including HA, IxS, pCS, IAA, pCG, and CMPF, were observed in our patients on hemodialysis compared with the healthy controls, a finding apparently attributed to their compromised removal by dialysis membranes [14,15]. A recent study has described immunosenescent and immunoexhaustion phenotypic changes in the presence of KF [13].…”

Section: Discussionsupporting

confidence: 81%

Immunosenescence and Immune Exhaustion Are Associated with Levels of Protein-Bound Uremic Toxins in Patients on Hemodialysis

Tourountzis,

Lioulios,

Van Laecke

et al. 2023

Biomedicines

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Background: The accumulation of protein-bound uremic toxins (PBUTs) in chronic kidney disease may affect patients’ immune status. The aim of the study was to evaluate their potential impacts on lymphocyte alterations in patients on hemodialysis (HD). Methods: The plasma levels of PBUTs were assessed in 54 patients on HD and 31 healthy individuals, using ultra-performance liquid chromatography. The results correlated with the senescent and exhausted status of lymphocytes, based on certain surface molecules, analyzed by flow cytometry. Results: The plasma levels of PBUTs were significantly increased in the patients on HD compared with the healthy controls. The patients with residual kidney function had reduced hippuric acid (HA) levels, total (p = 0.03) and free (p = 0.04), and free IxS levels (p = 0.02). The total and free HA levels correlated negatively with less differentiated subpopulations, CD4+CD45RA+CD31+ (p = 0.037 and p = 0.027), CD8+CD28+CD57− (p = 0.01, p = 0.01), and naïve B cells (CD19+IgD+CD27−) (p = 0.04, p = 0.03). Both the total and the free pCS levels correlated positively with exhausted CD4 cells, p = 0.02 and p = 0.01, respectively. A multivariate analysis showed that IxS and age were the main independent parameters implicated in the reduction intotal CD4 and B lymphocytes and their naïve and early differentiated subsets. Conclusions: Increased PBUTs levels are associated with immune disturbances of patients on HD, HA, and IxS in the immunosenescent and pCS in the immunoexhaustion alterations.

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Section: Discussionsupporting

confidence: 81%

Immunosenescence and Immune Exhaustion Are Associated with Levels of Protein-Bound Uremic Toxins in Patients on Hemodialysis

Tourountzis,

Lioulios,

Van Laecke

et al. 2023

Biomedicines

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“…This might be due to the C≡N group in ACN, which is a stronger nucleophile compared to the OH group, thereby minimizing the required contact time. On the other hand, some assays used a longer vortex time in place of having a separate incubation period, but it is not apparent whether this approach affects the extraction efficiency or sensitivity [ 37 , 49 , 52 ]. Likewise, the impact of ultrasonication is not clear since it was used only in one assay [ 50 ].…”

Section: Resultsmentioning

confidence: 99%

“…However, ACN was used as the organic phase in more assays ( Table 1 ), including a few assays that had used methanol in their sample extraction process [ 31 , 32 , 38 ]. Additionally, ACN was employed as the organic phase in assays with relatively shorter run times (i.e., <6 min) quantifying a mixture of IxS and p CS [ 29 , 37 , 39 , 44 , 45 ], compared to the run time (i.e., 6–22 min) achieved by assays utilizing methanol as the organic phase [ 40 , 42 , 43 , 49 , 52 , 53 ]. This is likely due to the potentially stronger interaction between ACN and IxS or p CS, as already discussed above.…”

Section: Resultsmentioning

confidence: 99%

“…According to Ma et al, the ineffective hemodialysis removal of these PBUTs is due to their high protein binding ratio and high affinity toward serum albumin [46]. Consistently, Ragi et al [52] illustrated that IxS and pCS plasma concentrations pre-and post-hemodialysis were 3.5 ± 1.5 µg/mL to 2.34 ± 0.6 µg/mL and 16.68 ± 8.8 µg/mL to 12.59 ± 7.1 µg/mL, respectively [52]. Etinger et al [81] hypothesized that dialysate pH affects the clearance of PBUTs and tested two conditions: isohydric dialysis with reduced bicarbonate buffer concentration for the first 90 min vs. standard dialysis with normal dialysate bicarbonate concentration for the full dialysis run [81] (Table 2).…”

Section: Dialysismentioning

confidence: 87%

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Liquid Chromatography-Mass Spectrometry Analytical Methods for the Quantitation of p-Cresol Sulfate and Indoxyl Sulfate in Human Matrices: Biological Applications and Diagnostic Potentials

Al-Dajani,

Hou,

Kiang

2024

Pharmaceutics

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Indoxyl sulfate (IxS) and p-cresyl sulfate (pCS) are toxic uremic compounds with documented pathological outcomes. This review critically and comprehensively analyzes the available liquid chromatography-mass spectrometry methods quantifying IxS and pCS in human matrices and the biological applications of these validated assays. Embase, Medline, PubMed, Scopus, and Web of Science were searched until December 2023 to identify assays with complete analytical and validation data (N = 23). Subsequently, citation analysis with PubMed and Scopus was utilized to identify the biological applications for these assays (N = 45). The extraction methods, mobile phase compositions, chromatography, and ionization methods were evaluated with respect to overall assay performance (e.g., sensitivity, separation, interference). Most of the assays focused on human serum/plasma, utilizing acetonitrile or methanol (with ammonium acetate/formate or formic/acetic acid), liquid–liquid extraction, reverse phase (e.g., C18) chromatography, and gradient elution for analyte separation. Mass spectrometry conditions were also consistent in the identified papers, with negative electrospray ionization, select multiple reaction monitoring transitions and deuterated internal standards being the most common approaches. The validated biological applications indicated IxS and/or pCS were correlated with renal disease progression and cardiovascular outcomes, with limited data on central nervous system disorders. Methods for reducing IxS and/or pCS concentrations were also identified (e.g., drugs, natural products, diet, dialysis, transplantation) where inconsistent findings have been reported. The clinical monitoring of IxS and pCS is gaining significant interest, and this review will serve as a useful compendium for scientists and clinicians.

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“…While indoxyl sulfate is a well-known uremic toxin that exhibits cytotoxic effects in the case of chronic kidney diseases, , its effects on colon cancer cells have been less studied. In a previous study, an indole derivative, indole-3-cabinol (I3C), has been well studied using HT-29, HCT-116, and DLD1 cell lines and found decrease in cell viability and accelerated apoptosis as an AHR agonist .…”

Section: Discussionmentioning

confidence: 99%

Gut Metabolite Indoxyl Sulfate Has Selective Deleterious and Anticancer Effect on Colon Cancer Cells

Dalal,

Makharia,

Dalal

et al. 2023

J. Med. Chem.

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Assessment of uremic toxins in advanced chronic kidney disease patients on maintenance hemodialysis by LC-ESI-MS/MS

Cited by 13 publications

References 43 publications

Immunosenescence and Immune Exhaustion Are Associated with Levels of Protein-Bound Uremic Toxins in Patients on Hemodialysis

Immunosenescence and Immune Exhaustion Are Associated with Levels of Protein-Bound Uremic Toxins in Patients on Hemodialysis

Liquid Chromatography-Mass Spectrometry Analytical Methods for the Quantitation of p-Cresol Sulfate and Indoxyl Sulfate in Human Matrices: Biological Applications and Diagnostic Potentials

Gut Metabolite Indoxyl Sulfate Has Selective Deleterious and Anticancer Effect on Colon Cancer Cells

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