Effects of chronic SDMA infusion on glomerular filtration rate, blood pressure, myocardial function and renal histology in C57BL6/J mice

Veldink, Hendrik; Faulhaber-Walter, Robert; Park, Joon-Keun; Martens‐Lobenhoffer, Jens; Bode‐Böger, Stefanie M.; Schuett, Harald; Haghikia, Arash; Hilfiker‐Kleiner, Denise; Kielstein, Jan T.

doi:10.1093/ndt/gfs554

Cited by 30 publications

(25 citation statements)

References 24 publications

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“…In one animal study, chronic SDMA infusion did not have any effect on blood pressure, fibrosis or NO production, which suggests that perhaps SDMA may not be associated with toxicity. (49)…”

Section: Discussionmentioning

confidence: 99%

Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in Hemodialysis Patients

Shafi

Hostetter

Meyer

et al. 2017

American Journal of Kidney Diseases

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Background Asymmetric and symmetric dimethylarginines (ADMA and SDMA) are putative uremic toxins that may exert toxicity by a number of mechanisms including impaired nitric oxide synthesis and generation of reactive oxygen species. The study goal was to determine the association between these metabolites and cardiovascular outcomes in hemodialysis patients. Study Design Post hoc analysis of the Hemodialysis (HEMO) Study. Setting & Participants 1,276 prevalent hemodialysis patients with available samples 3–6 months after randomization. Predictor ADMA and SDMA measured in stored specimens. Outcomes Cardiac death, sudden cardiac death, first cardiovascular event, and any-cause death. Association with predictors analyzed using Cox regression adjusted for potential confounders (including demographics, clinical characteristics, comorbidities, albumin, and residual kidney function). Results Mean age of patients was 57 ±14 (SD) years, 63% were Black and 57% were female. Mean ADMA (0.9 ± 0.2 µM) and SDMA (4.3 ± 1.4 µM) were moderately correlated (r=0.418). Higher dialysis dose or longer session length were not associated with lower predialysis concentrations of ADMA or SDMA. In fully adjusted models, each doubling of ADMA was associated with higher risk (HR per 2-fold higher concentration; 95% CI) of cardiac death (1.83; 1.29–2.58), sudden cardiac death (1.79; 1.19–2.69), first cardiovascular event (1.50; 1.20–1.87), and any-cause death (1.44; 1.13–1.83). Compared to the lowest ADMA quintile (≤0.745 µM), the highest ADMA quintile (≥1.07 µM) was associated with higher risk (HR; 95% CI) of cardiac death (2.10; 1.44–3.05), sudden cardiac death (2.06; 1.46–2.90), first cardiovascular event (1.75; 1.35–2.27), and any-cause death (1.56; 1.21–2.00). SDMA was associated with higher risk of cardiac death (1.40; 1.03–1.92) but this was no longer statistically significant after adjusting for ADMA (1.20; 0.86–1.68). Limitations Single time-point measurement of ADMA and SDMA. Conclusions ADMA and, to a lesser extent SDMA are associated with cardiovascular outcomes in hemodialysis patients.

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“…In one animal study, chronic SDMA infusion did not have any effect on blood pressure, fibrosis or NO production, which suggests that perhaps SDMA may not be associated with toxicity. (49)…”

Section: Discussionmentioning

confidence: 99%

Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in Hemodialysis Patients

Shafi

Hostetter

Meyer

et al. 2017

American Journal of Kidney Diseases

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“…However, the sole increase of SDMA by exogenous infusion in otherwise healthy mice affected neither renal function nor blood pressure or cardiac function. 44 …”

Section: Origin and Removal Of Adma And Sdmamentioning

confidence: 99%

Dimethylarginines ADMA and SDMA: The Real Water-Soluble Small Toxins?

Schepers

Speer

Bode‐Böger

et al. 2014

Seminars in Nephrology

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“…Increased SDMA also has been associated with both all‐cause and cardiovascular mortality in people . Although SDMA has been implicated as an inflammatory mediator in CKD, any specific biological role of SDMA, and in particular, any influence of SDMA on myocardial or renal function, is still ill‐defined …”

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confidence: 99%

“…8 Although SDMA has been implicated as an inflammatory mediator in CKD, 9 any specific biological role of SDMA, and in particular, any influence of SDMA on myocardial or renal function, is still ill-defined. 3,10 Recent studies determined that SDMA correlates strongly with GFR in cats with and without evidence of decreased renal function. [11][12][13] Importantly, SDMA consistently increased months to years earlier than sCr in cats with naturally occurring CKD.…”

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confidence: 99%

Symmetric Dimethylarginine Assay Validation, Stability, and Evaluation as a Marker for the Early Detection of Chronic Kidney Disease in Dogs

Nabity

Lees

Boggess

et al. 2015

Veterinary Internal Medicne

179

236

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BackgroundSymmetric dimethylarginine (SDMA) is a small molecule formed by methylation of arginine, and released into blood during protein degradation. SDMA is primarily eliminated by renal excretion and is a promising endogenous marker of glomerular filtration rate (GFR).ObjectivesTo validate an assay for SDMA measurement, determine stability of SDMA in blood, and compare SDMA with serum creatinine concentration (sCr) and GFR for early detection of decreasing kidney function in dogs with chronic kidney disease (CKD).AnimalsEight male dogs affected with X‐linked hereditary nephropathy and 4 unaffected male littermates.MethodsProspective study validating SDMA measurement using liquid chromatography‐mass spectrometry, assessing stability of SDMA in serum and plasma, and serially determining sCr, SDMA, and GFR (using iohexol clearance) in dogs during progression from preclinical disease to end‐stage renal failure. Correlations were determined using linear regression. Timepoints at which sCr, SDMA, and GFR identified decreased renal function were compared using defined cutoffs, trending in an individual dog, and comparison with unaffected littermates.ResultsSymmetric dimethylarginine was highly stable in serum and plasma, and the assay demonstrated excellent analytical performance. In unaffected dogs, SDMA remained unchanged whereas in affected dogs, SDMA increased during disease progression, correlating strongly with an increase in sCr (r = 0.95) and decrease in GFR (r = −0.95). Although trending improved sCr's sensitivity, SDMA identified, on average, <20% decrease in GFR, which was earlier than sCr using any comparison method.Conclusions and Clinical ImportanceSymmetric dimethylarginine is useful for both early identification and monitoring of decreased renal function in dogs with CKD.

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Effects of chronic SDMA infusion on glomerular filtration rate, blood pressure, myocardial function and renal histology in C57BL6/J mice

Abstract: Based on our experiments, it seems unlikely that chronically elevated SDMA alone has an effect on renal and cardiac function in otherwise healthy mice. Future studies have to clarify the potential pathophysiological role of SDMA in cardiovascular disease.

Cited by 30 publications

References 24 publications

Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in Hemodialysis Patients

Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in Hemodialysis Patients

Dimethylarginines ADMA and SDMA: The Real Water-Soluble Small Toxins?

Symmetric Dimethylarginine Assay Validation, Stability, and Evaluation as a Marker for the Early Detection of Chronic Kidney Disease in Dogs

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