scholarly journals Whole-body arginine dimethylation is associated with all-cause mortality in adult renal transplant recipients

Amino Acids ◽  
2021 ◽  
Author(s):  
Adrian Post ◽  
Alexander Bollenbach ◽  
Stephan J. L. Bakker ◽  
Dimitrios Tsikas
Keyword(s):  
Renal Transplant ◽  
Excretion Rate ◽  
Whole Body ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Kidney Donors ◽  
Body Protein ◽  
All Cause Mortality ◽  
Arginine Residues ◽  
Excretion Rates

AbstractArginine residues in proteins can be singly or doubly methylated post-translationally. Proteolysis of arginine-methylated proteins provides monomethyl arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA). ADMA and SDMA are considered cardiovascular risk factors, with the underlying mechanisms being not yet fully understood. SDMA lacks appreciable metabolism and is almost completely eliminated by the kidney, whereas ADMA is extensively metabolized to dimethylamine (DMA), with a minor ADMA fraction of about 10% being excreted unchanged in the urine. Urinary DMA and ADMA are useful measures of whole-body asymmetric arginine-dimethylation, while urinary SDMA serves as a whole-body measure of symmetric arginine-dimethylation. In renal transplant recipients (RTR), we previously found that higher plasma ADMA concentrations and lower urinary ADMA and SDMA concentrations were associated with a higher risk of all-cause mortality. Yet, in this RTR collective, no data were available for urinary DMA. For the present study, we additionally measured the excretion rate of DMA in 24-h collected urine samples of the RTR and of healthy kidney donors in the cohort, with the aim to quantitate whole-body asymmetric (ADMA, DMA) and symmetric (SDMA) arginine-dimethylation. We found that lower DMA excretion rates were associated with higher all-cause mortality, yet not with cardiovascular mortality. In the healthy donors, kidney donation was associated with considerable decreases in ADMA (by − 39%, P < 0.0001) and SDMA (by − 21%, P < 0.0001) excretion rates, yet there was no significant change in DMA (by − 9%, P = 0.226) excretion rate. Our results suggest that protein-arginine dimethylation is altered in RTR compared to healthy kidney donors and that it is pronouncedly shifted from symmetric to asymmetric arginine-dimethylation, with whole-body protein-arginine dimethylation being almost unaffected.

scholarly journals Urinary Excretion of N1-Methylnicotinamide, as a Biomarker of Niacin Status, and Mortality in Renal Transplant Recipients

2019 ◽  
Vol 8 (11) ◽  
pp. 1948 ◽  
Author(s):  
Carolien P.J. Deen ◽  
Anna van der Veen ◽  
Martijn van Faassen ◽  
Isidor Minović ◽  
António W. Gomes-Neto ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Dietary Intake ◽  
Urinary Excretion ◽  
Vitamin B6 ◽  
Renal Transplant Recipients ◽  
Healthy Controls ◽  
Transplant Recipients ◽  
Kidney Donors ◽  
Long Term Outcome ◽  
All Cause Mortality

Renal transplant recipients (RTR) commonly suffer from vitamin B6 deficiency and its functional consequences add to an association with poor long-term outcome. It is unknown whether niacin status is affected in RTR and, if so, whether this affects clinical outcomes, as vitamin B6 is a cofactor in nicotinamide biosynthesis. We compared 24-h urinary excretion of N1-methylnicotinamide (N1-MN) as a biomarker of niacin status in RTR with that in healthy controls, in relation to dietary intake of tryptophan and niacin as well as vitamin B6 status, and investigated whether niacin status is associated with the risk of premature all-cause mortality in RTR. In a prospective cohort of 660 stable RTR with a median follow-up of 5.4 (4.7–6.1) years and 275 healthy kidney donors, 24-h urinary excretion of N1-MN was measured with liquid chromatography-tandem mass spectrometry LC-MS/MS. Dietary intake was assessed by food frequency questionnaires. Prospective associations of N1-MN excretion with mortality were investigated by Cox regression analyses. Median N1-MN excretion was 22.0 (15.8–31.8) μmol/day in RTR, compared to 41.1 (31.6–57.2) μmol/day in healthy kidney donors (p < 0.001). This difference was independent of dietary intake of tryptophan (1059 ± 271 and 1089 ± 308 mg/day; p = 0.19), niacin (17.9 ± 5.2 and 19.2 ± 6.2 mg/day; p < 0.001), plasma vitamin B6 (29.0 (17.5–49.5), and 42.0 (29.8–60.3) nmol/L; p < 0.001), respectively. N1-MN excretion was inversely associated with the risk of all-cause mortality in RTR (HR 0.57; 95% CI 0.45–0.71; p < 0.001), independent of potential confounders. RTR excrete less N1-MN in 24-h urine than healthy controls, and our data suggest that this difference cannot be attributed to lower dietary intake of tryptophan and niacin, nor vitamin B6 status. Importantly, lower 24-h urinary excretion of N1-MN is independently associated with a higher risk of premature all-cause mortality in RTR.

scholarly journals Urinary excretion of amino acids and their advanced glycation end-products (AGEs) in adult kidney transplant recipients with emphasis on lysine: furosine excretion is associated with cardiovascular and all-cause mortality

Amino Acids ◽  
2021 ◽  
Author(s):  
Svetlana Baskal ◽  
Adrian Post ◽  
Daan Kremer ◽  
Alexander Bollenbach ◽  
Stephan J. L. Bakker ◽  
...  
Keyword(s):  
Amino Acids ◽  
Urinary Excretion ◽  
Excretion Rate ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
All Cause Mortality ◽  
Excretion Rates

AbstractArginine (Arg) and lysine (Lys) moieties of proteins undergo various post-translational modifications (PTM) including enzymatic NG- and Nε-methylation and non-enzymatic NG- and Nε-glycation. In a large cohort of stable kidney transplant recipients (KTR, n = 686), high plasma and low urinary concentrations of asymmetric dimethylarginine (ADMA), an abundant PTM metabolite of Arg, were associated with cardiovascular and all-cause mortality. Thus, the prediction of the same biomarker regarding mortality may depend on the biological sample. In another large cohort of stable KTR (n = 555), higher plasma concentrations of Nε-carboxymethyl-lysine (CML) and Nε-carboxyethyl-lysine (CEL), two advanced glycation end-products (AGEs) of Lys, were associated with higher cardiovascular mortality. Yet, the associations of urinary AGEs with mortality are unknown. In the present study, we measured 24 h urinary excretion of Lys, CML, and furosine in 630 KTR and 41 healthy kidney donors before and after donation. Our result indicate that lower urinary CML and lower furosine excretion rates are associated with higher mortality in KTR, thus resembling the associations of ADMA. Lower furosine excretion rates were also associated with higher cardiovascular mortality. The 24 h urinary excretion rate of amino acids and their metabolites decreased post-donation (varying as little as − 24% for CEL, and as much as − 62% for ADMA). For most amino acids, the excretion rate was lower in KTR than in donors pre-donation [except for S-(1-carboxyethyl)-l-cysteine (CEC) and NG-carboxyethylarginine (CEA)]. Simultaneous GC–MS measurement of free amino acids, their PTM metabolites and AGEs in urine is a non-invasive approach in kidney transplantation.

scholarly journals Plasma ADMA associates with all-cause mortality in renal transplant recipients

Amino Acids ◽  
2015 ◽  
Vol 47 (9) ◽  
pp. 1941-1949 ◽  
Author(s):  
Anne-Roos S. Frenay ◽  
Else van den Berg ◽  
Martin H. de Borst ◽  
Bibiana Beckmann ◽  
Dimitrios Tsikas ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Plasma Adma ◽  
All Cause Mortality

Low plasma homoarginine concentration is associated with high rates of all-cause mortality in renal transplant recipients

Amino Acids ◽  
2017 ◽  
Vol 49 (7) ◽  
pp. 1193-1202 ◽  
Author(s):  
Arslan Arinc Kayacelebi ◽  
Isidor Minović ◽  
Erik Hanff ◽  
Anne-Roos S. Frenay ◽  
Martin H. de Borst ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
All Cause Mortality

scholarly journals Urinary Excretion of N1-methyl-2-pyridone-5-carboxamide and N1-methylnicotinamide in Renal Transplant Recipients and Donors

2020 ◽  
Vol 9 (2) ◽  
pp. 437 ◽  
Author(s):  
Carolien P. J. Deen ◽  
Anna van der Veen ◽  
António W. Gomes-Neto ◽  
Johanna M. Geleijnse ◽  
Karin J. Borgonjen-van den Berg ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Nutritional Status ◽  
Urinary Excretion ◽  
Kidney Function ◽  
Density Lipoprotein ◽  
Kidney Donation ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Cross Sectional ◽  
Kidney Donors

N1-methylnicotinamide (N1-MN) and N1-methyl-2-pyridone-5-carboxamide (2Py) are successive end products of NAD+ catabolism. N1-MN excretion in 24-h urine is the established biomarker of niacin nutritional status, and recently shown to be reduced in renal transplant recipients (RTR). However, it is unclear whether 2Py excretion is increased in this population, and, if so, whether a shift in excretion of N1-MN to 2Py can be attributed to kidney function. Hence, we assessed the 24-h urinary excretion of 2Py and N1-MN in RTR and kidney donors before and after kidney donation, and investigated associations of the urinary ratio of 2Py to N1-MN (2Py/N1-MN) with kidney function, and independent determinants of urinary 2Py/N1-MN in RTR. The urinary excretion of 2Py and N1-MN was measured in a cross-sectional cohort of 660 RTR and 275 healthy kidney donors with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Linear regression analyses were used to investigate associations and determinants of urinary 2Py/N1-MN. Median 2Py excretion was 178.1 (130.3–242.8) μmol/day in RTR, compared to 155.6 (119.6–217.6) μmol/day in kidney donors (p < 0.001). In kidney donors, urinary 2Py/N1-MN increased significantly after kidney donation (4.0 ± 1.4 to 5.2 ± 1.5, respectively; p < 0.001). Smoking, alcohol consumption, diabetes, high-density lipoprotein (HDL), high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) were identified as independent determinants of urinary 2Py/N1-MN in RTR. In conclusion, the 24-h urinary excretion of 2Py is higher in RTR than in kidney donors, and urinary 2Py/N1-MN increases after kidney donation. As our data furthermore reveal strong associations of urinary 2Py/N1-MN with kidney function, interpretation of both N1-MN and 2Py excretion may be recommended for assessment of niacin nutritional status in conditions of impaired kidney function.

scholarly journals Dietary Approach to Stop Hypertension (DASH) diet and risk of renal function decline and all-cause mortality in renal transplant recipients

2018 ◽  
Vol 18 (10) ◽  
pp. 2523-2533 ◽  
Author(s):  
Maryse C. J. Osté ◽  
António W. Gomes-Neto ◽  
Eva Corpeleijn ◽  
Rijk O. B. Gans ◽  
Martin H. de Borst ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Transplant ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Dash Diet ◽  
Renal Function Decline ◽  
All Cause Mortality

Alcohol Consumption, New Onset of Diabetes After Transplantation, and All-Cause Mortality in Renal Transplant Recipients

2011 ◽  
Vol 92 (2) ◽  
pp. 203-209 ◽  
Author(s):  
Dorien M. Zelle ◽  
Pramod K. Agarwal ◽  
Jessica L. Pinto Ramirez ◽  
Jaap J. Homan van der Heide ◽  
Eva Corpeleijn ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Renal Transplant ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
All Cause Mortality ◽  
Onset Of Diabetes ◽  
New Onset

scholarly journals Sclerostin is an independent risk factor for all-cause mortality in kidney transplant recipients

2020 ◽  
Vol 24 (12) ◽  
pp. 1177-1183
Author(s):  
Shufei Zeng ◽  
Torsten Slowinski ◽  
Wolfgang Pommer ◽  
Ahmed A. Hasan ◽  
Mohamed M. S. Gaballa ◽  
...  
Keyword(s):  
Risk Factor ◽  
Renal Transplant ◽  
Kidney Transplant ◽  
Independent Risk Factor ◽  
Cox Regression ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Kaplan Meier ◽  
All Cause Mortality

Abstract Background Sclerostin is a hormone contributing to the bone-vascular wall cross talk and has been implicated in cardiovascular events and mortality in patients with chronic kidney disease (CKD). We analyzed the relationship between sclerostin and mortality in renal transplant recipients. Methods 600 stable renal transplant recipients (367men, 233 women) were followed for all-cause mortality for 3 years. Blood and urine samples for analysis and clinical data were collected at study entry. We performed Kaplan–Meier survival analysis and Cox regression models considering confounding factors such as age, eGFR, cold ischemia time, HbA1c, phosphate, calcium, and albumin. Optimal cut-off values for the Cox regression model were calculated based on ROC analysis. Results Sixty-five patients died during the observation period. Nonsurvivors (n = 65; sclerostin 57.31 ± 30.28 pmol/L) had higher plasma sclerostin levels than survivors (n = 535; sclerostin 47.52 ± 24.87 pmol/L) (p = 0.0036). Kaplan–Meier curve showed that baseline plasma sclerostin concentrations were associated with all-cause mortality in stable kidney transplant recipients (p = 0.0085, log-rank test). After multiple Cox regression analysis, plasma levels of sclerostin remained an independent predictor of all-cause mortality (hazard ratio, 1.011; 95% CI 1.002–1.020; p = 0.0137). Conclusions Baseline plasma sclerostin is an independent risk factor for all-cause mortality in patients after kidney transplantation.

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