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  3. SAH and SAM/SAH ratio associate with acute kidney injury in critically ill patients: A case-control study

SAH and SAM/SAH ratio associate with acute kidney injury in critically ill patients: A case-control study

  • Clin Chim Acta. 2023 Dec 16:117726. doi: 10.1016/j.cca.2023.117726.
Zhini Liu 1,  Xiaona Li 2,  Tiehua Wang 3,  Hua Zhang 4,  Xiaoxiao Li 5,  Jiamin Xu 6,  Yuanyuan Zhang 6,  Zhiling Zhao 3,  Ping Yang 6,  Congya Zhou 6,  Qinggang Ge 7,  Libo Zhao 8
Affiliations

Affiliations

  • 1 Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China; School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu Province 211198, China; Therapeutic Drug Monitoring and Clinical Toxicology Center of Peking University, Beijing 100191, China.
  • 2 Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China; Therapeutic Drug Monitoring and Clinical Toxicology Center of Peking University, Beijing 100191, China; NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Beijing 100191, China. Electronic address: [email protected].
  • 3 Department of Intensive Care Unit, Peking University Third Hospital, Beijing, China.
  • 4 Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, China.
  • 5 Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China.
  • 6 Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China; Therapeutic Drug Monitoring and Clinical Toxicology Center of Peking University, Beijing 100191, China; NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Beijing 100191, China.
  • 7 Department of Intensive Care Unit, Peking University Third Hospital, Beijing, China. Electronic address: [email protected].
  • 8 Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China; Therapeutic Drug Monitoring and Clinical Toxicology Center of Peking University, Beijing 100191, China; NMPA Key Laboratory for Research and Evaluation of Generic Drugs, Beijing 100191, China. Electronic address: [email protected].
PMID: 38110027 DOI: 10.1016/j.cca.2023.117726
Abstract

Background: Acute kidney injury (AKI) is a serious clinical emergency with an acute onset, rapid progression and poor prognosis, which has high morbidity and mortality in hospitalized patients. DNA methylation plays an important role in the occurrence and progression of kidney disease, and aberrant methylation and certain altered methylation-related metabolites have been reported in AKI patients. However, the specific alterations of methylation-related metabolites in the AKI patients were not investigated clearly.

Method: In this study, 61 AKI and 61 matched non-AKI inpatients were recruited after propensity score matching the age and hypertension. And 11 methylation-related metabolites in the plasma and urine of the two groups were quantified by using UHPLC-MS/MS method.

Results: Certain methylation-relate intermediates were up-regulated in the plasma (choline, trimethylamine N-oxide (TMAO), trimethyl lysine (TML), S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)) and down-regulated in the urine of AKI inpatients (choline, betaine, TMAO, dimethylglycine (DMG), SAM and taurine). The correlation analysis revealed a relatively strong correlation between plasma SAH, SAM/SAH ratio and renal function index (serum creatinine (SCr) and estimated glomerular filtration rate (EGFR), r = 0.523-0.616), and the correlation of urinary intermediates with renal function index was weaker than that in the plasma. Furthermore, receiver operating characteristic curve (ROC) analysis showed that plasma SAH and urinary SAM/SAH ratio represented the best distinguishing efficiency with AUC 0.844 and 0.794, respectively. Moreover, the findings of binary regression analysis demonstrated plasma choline, TMAO, TML, SAM and SAH were the risk markers of AKI (up-regulation in plasma, OR > 1), urinary choline, betaine, TMAO, DMG and SAM were protective markers of AKI (down-regulation in urine, OR < 1), and SAM/SAH ratio was a protective marker in plasma and urine (down-regulation in both two biofluids, OR = 0.510, 0.383-0.678 in plasma, OR = 0.904, 0.854-0.968 in urine), indicating the increased risk of AKI when combined with the alteration of plasma and urinary levels.

Conclusion: The comprehensive analysis of plasma and urine samples from AKI inpatients offers a more extensive assessment of methylated metabolic alterations, suggesting that a close relationship between AKI stress and altered methylation ability. The plasma level of SAH and SAM/SAH ratio and urinary SAM/SAH ratio both showed a strong correlation with renal function (SCr and EGFR) and good accuracy for distinguishing AKI in the two biomatrices, which exhibit promising prospects in predicting renal function decline and providing further information for the pathogenesis of AKI.

Keywords

Acute kidney injury (AKI); Methylation; S-adenosylhomocysteine (SAH); S-adenosylmethionine/ S-adenosylhomocysteine ratio (SAM/SAH ratio).

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