Symmetric Dimethylarginine as Predictor of Graft loss and All-Cause Mortality in Renal Transplant Recipients

Pihlstrøm, Hege; Mjøen, Geir; Dahle, Dag Olav; Pilz, Stefan; Midtvedt, Karsten; März, Winfried; Abedini, Sadollah; Holme, Ingar; Fellström, Bengt; Jardine, Alan G.; Holdaas, Hallvard

doi:10.1097/tp.0000000000000205

Cited by 10 publications

(8 citation statements)

References 51 publications

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“…However, SDMA level showed little correlation with levels of SCr, eGFR, BUN and UA in both HV and NB groups. Similar correlation coefficients were also uncovered by many reports, including meta-analysis and metabolomics studies 29 – 32 . Additionally, SDMA was reported to be independently associated with graft loss and mortality after adjusting for eGFR in human as well as in rodents 26 , 33 .…”

Section: Discussionsupporting

confidence: 82%

Diagnostic value of plasma tryptophan and symmetric dimethylarginine levels for acute kidney injury among tacrolimus-treated kidney transplant patients by targeted metabolomics analysis

Zhang

Wang

Xia

et al. 2018

Sci Rep

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Few literatures have evaluated the exact role of metabolomics in the identification process of potential biomarkers for acute kidney injury among the patients receiving renal transplantation. On top of this, the success of metabolomics in biomarker translation seems to lie in the robust quantitative method. As such, a single-center retrospective observational study was conducted enrolling 42 patients underwent renal transplantation with/without acute kidney injury, as well as 24 healthy volunteers, in Shanghai Changzheng Hospital. Plasma amino acid metabolic patterns for the participants were investigated by targeted UHPLC-MS/MS metabolic profiling. The most significant changes of the explored metabolites were related to the disturbance of tryptophan metabolism and arginine metabolism. Abnormal circulating tryptophan and symmetric dimethylarginine were identified to be potential biomarkers of acute kidney injury, combination of which showed a higher area under receiver-operator curve value (AUC = 0.901), improved sensitivity (0.889) and specificity (0.831) compared with creatinine only. Overall, these results revealed that targeted metabolomics analysis would be a potent and promising strategy for identification and pre-validation of biomarkers of acute kidney injury in renal transplantation patients.

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Section: Discussionsupporting

confidence: 82%

Diagnostic value of plasma tryptophan and symmetric dimethylarginine levels for acute kidney injury among tacrolimus-treated kidney transplant patients by targeted metabolomics analysis

Zhang

Wang

Xia

et al. 2018

Sci Rep

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“…[12] With respect to SDMA, initial studies did not find an association with adverse outcomes,[7, 13, 14] but some more recent studies reported positive associations with all-cause mortality or CVD. [11, 15, 16] Overall, prior studies on ADMA/SDMA and CVD or all-cause mortality were derived from many different study populations (general population,[15, 17, 18] patients with CVD,[9, 11, 19, 20] renal diseases,[7, 13, 21–24] diabetes,[25, 26] or critically ill patients from intensive care unit,[27–29] respectively), differed in their methodological approaches (e.g. using types of samples (plasma vs. serum) or methods to determine the biomarker levels (HPLC vs. tandem mass spectroscopy vs. ELISA), or considered different confounders in their analysis.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric and Symmetric Dimethylarginine as Risk Markers for Total Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Studies

et al. 2016

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BackgroundA growing number of studies linked elevated concentrations of circulating asymmetric (ADMA) and symmetric (SDMA) dimethylarginine to mortality and cardiovascular disease (CVD) events. To summarize the evidence, we conducted a systematic review and quantified associations of ADMA and SDMA with the risks of all-cause mortality and incident CVD in meta-analyses accounting for different populations and methodological approaches of the studies.MethodsRelevant studies were identified in PubMed until February 2015. We used random effect models to obtain summary relative risks (RR) and 95% confidence intervals (95%CIs), comparing top versus bottom tertiles. Dose-response relations were assessed by restricted cubic spline regression models and potential non-linearity was evaluated using a likelihood ratio test. Heterogeneity between subgroups was assessed by meta-regression analysis.ResultsFor ADMA, 34 studies (total n = 32,428) investigating associations with all-cause mortality (events = 5,035) and 30 studies (total n = 30,624) investigating the association with incident CVD (events = 3,396) were included. The summary RRs (95%CI) for all-cause mortality were 1.52 (1.37–1.68) and for CVD 1.33 (1.22–1.45), comparing high versus low ADMA concentrations. Slight differences were observed across study populations and methodological approaches, with the strongest association of ADMA being reported with all-cause mortality in critically ill patients. For SDMA, 17 studies (total n = 18,163) were included for all-cause mortality (events = 2,903), and 13 studies (total n = 16,807) for CVD (events = 1,534). High vs. low levels of SDMA, were associated with increased risk of all-cause mortality [summary RR (95%CI): 1.31 (1.18–1.46)] and CVD [summary RR (95%CI): 1.36 (1.10–1.68) Strongest associations were observed in general population samples.ConclusionsThe dimethylarginines ADMA and SDMA are independent risk markers for all-cause mortality and CVD across different populations and methodological approaches.

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“…More novel markers such as asymmetric dimethylarginine, which is associated with endothelial dysfunction, are also associated with higher risk of mortality (HR = 2.18) and developing CVD (HR = 2.59) in ESRD [140] . Poorer graft outcomes are predicted by IL-6 [136,141] and elevated symmetric dimethylarginine [142] (HR = 5.51). TroponinT, usually used in the diagnosis of ACS, is a strong independent predictor of allcause mortality in stable RTRs [143] .…”

Section: Inflammationmentioning

confidence: 99%

Cardiovascular risk factors following renal transplant

Neale

Smith

2015

WJT

117

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Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Nontraditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population. Core tip: Cardiovascular disease (CVD) is the leading cause of death and disability in patients following a renal transplant. Identification of risk factors for CVD and strategies for their improvement are required in order to prevent graft failure in this complex patient

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Symmetric Dimethylarginine as Predictor of Graft loss and All-Cause Mortality in Renal Transplant Recipients

Abstract: Supplemental digital content is available in the text.

Cited by 10 publications

References 51 publications

Diagnostic value of plasma tryptophan and symmetric dimethylarginine levels for acute kidney injury among tacrolimus-treated kidney transplant patients by targeted metabolomics analysis

Diagnostic value of plasma tryptophan and symmetric dimethylarginine levels for acute kidney injury among tacrolimus-treated kidney transplant patients by targeted metabolomics analysis

Asymmetric and Symmetric Dimethylarginine as Risk Markers for Total Mortality and Cardiovascular Outcomes: A Systematic Review and Meta-Analysis of Prospective Studies

Cardiovascular risk factors following renal transplant

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