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 ◽  
...  

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.

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 ◽  
...  

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.


Amino Acids ◽  
2021 ◽  
Author(s):  
Adrian Post ◽  
Alexander Bollenbach ◽  
Stephan J. L. Bakker ◽  
Dimitrios Tsikas

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.


2012 ◽  
Vol 94 (10S) ◽  
pp. 1166
Author(s):  
S. Kesiraju ◽  
P. Paritala ◽  
C. Uma Maheswara Rao ◽  
A. S. Murthy ◽  
V. S. Reddy ◽  
...  

2012 ◽  
Vol 44 (6) ◽  
pp. 1871-1876 ◽  
Author(s):  
Samra Abouchacra ◽  
Ahmed Chaaban ◽  
Raafat Hakim ◽  
Nicole Gebran ◽  
Hanan El-Jack ◽  
...  

2019 ◽  
Vol 122 (12) ◽  
pp. 1386-1397 ◽  
Author(s):  
Ana Paula Medeiros Menna Barreto ◽  
Maria Inês Barreto Silva ◽  
Karine Scanci da Silva Pontes ◽  
Mariana Silva da Costa ◽  
Kelli Trindade de Carvalho Rosina ◽  
...  

AbstractSarcopenia is a progressive and generalised skeletal muscle disorder associated with adverse outcomes. Ageing causes primary sarcopenia, while secondary causes include chronic kidney disease (CKD), long-term use of glucocorticoids and obesity. The aim of the present study was to evaluate the prevalence of sarcopenia using guidelines recommended by the European Working Group on Sarcopenia in Older People (EWGSOP, 2010; EWGSOP2, 2018) and the Foundation of the National Institutes of Health (FNIH) and analyse the relationship between sarcopenia and body adiposity in adult renal transplant recipients (RTR). This was a cross-sectional study of adult RTR (BMI ≥ 18·5 kg/m2). Body composition was evaluated by dual-energy X-ray absorptiometry (DXA) and anthropometry. Glomerular filtration rate was estimated (eGFR) by CKD-Epidemiology Collaboration equation. The prevalence of sarcopenia in adult RTR (n 185; 57 % men, 50 (se 0·82) years and eGFR 55·80 (se 1·52) ml/min) was 7 % (FNIH), 11 % (EWGSOP2) and 17 % (EWGSOP). Low muscle mass, muscle function and physical performance affected, respectively, up to 28, 46 and 10 % of the participants. According to EWGSOP and EWGSOP2, body adiposity evaluated by anthropometry and DXA (percentage trunk fat) was lower in participants with sarcopenia. Conversely, according to the FNIH criteria, RTR with sarcopenia presented higher waist:height ratio. The present study suggests that adult RTR sarcopenia prevalence varies according to the diagnostic criteria; low muscle mass, low muscle function and low physical performance are common conditions; the association of body adiposity and sarcopenia depends on the criteria used to define this syndrome; and the FNIH criteria detected higher adiposity in individuals with sarcopenia.


2012 ◽  
Vol 94 (10S) ◽  
pp. 585
Author(s):  
E. Tutal ◽  
S. Sezer ◽  
M. Erkmen Uyar ◽  
Z. Bal ◽  
B. Gürlek Demirci ◽  
...  

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