Asymmetric dimethylarginine may mediate increased heat pain threshold in experimental chronic kidney disease

Kielstein, Jan T.; Suntharalingam, Mayuren; Perthel, Ronny; Rong, Song; Martens‐Lobenhoffer, Jens; Jäger, Kristin; Bode‐Böger, Stefanie M.; Nave, Heike

doi:10.1093/ndt/gfr629

Cited by 9 publications

(4 citation statements)

References 21 publications

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“…A recent study reported that ADMA might affect nociception in CKD [29]. As mentioned above, our results show that serum ADMA levels increased in FD.…”

Section: Discussionsupporting

confidence: 84%

Effect of enzyme replacement therapy on serum asymmetric dimethylarginine levels, coronary flow reserve and left ventricular hypertrophy in patients with Fabry disease

Fujii

Kono

Yamamoto

et al. 2012

Clinical Kidney Journal

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BackgroundFabry disease (FD) is a rare disorder and one of the causes of progressive renal and cardiac dysfunction. FD results from an X-linked recessive lysosomal storage disorder caused by a defect in the gene encoding lysosomal α-galactosidase A. Although accumulation of globotriaosylceramide leads to renal and cardiac manifestations, the precise mechanisms remain unclear. Coronary microvascular dysfunction may be one of the causes of cardiac complications in FD. We aimed to assess coronary flow reserve (CFR) and the effect of enzyme replacement therapy (ERT) on coronary microvascular dysfunction.MethodsFour FD patients who had never received ERT were included. The serum asymmetric dimethylarginine (ADMA) level, as a marker of endothelial dysfunction, was measured. Two-dimensional guided M-mode echocardiography was performed to measure left ventricular wall mass. Adenosine-triphosphate stress transthoracic Doppler echocardiography was used to measure CFR before starting ERT and at 3, 6 and 12 months.ResultsAll the patients tolerated ERT without any side effects. At the baseline, two patients had impaired CFR, increased left ventricular mass index (LVMI) and elevated serum ADMA levels. Twelve months after starting ERT, CFR was increased in all patients, and LVMI and serum ADMA levels decreased in two patients. Furthermore, serum ADMA levels significantly correlated with CFR (r = −0.576, P < 0.05) and LVMI (r = 0.874, P < 0.0001).ConclusionsThe results suggest that ERT prevented the progression of cardiac abnormalities, possibly by improving coronary microvascular dysfunction. ADMA may be a useful surrogate marker in FD.

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“…A recent study reported that ADMA might affect nociception in CKD [29]. As mentioned above, our results show that serum ADMA levels increased in FD.…”

Section: Discussionsupporting

confidence: 84%

Effect of enzyme replacement therapy on serum asymmetric dimethylarginine levels, coronary flow reserve and left ventricular hypertrophy in patients with Fabry disease

Fujii

Kono

Yamamoto

et al. 2012

Clinical Kidney Journal

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“…69 In clinical studies, ADMA levels are increased in diabetic polyneuropathy. 70 High ADMA levels in CKD patients also are related to high-frequency hearing loss.…”

Section: Experimental and Clinical Data On Admamentioning

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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“… 86 Interestingly, in an animal model of renal failure, infusion of ADMA in healthy rats or in those with nephrectomy (inducing renal failure) resulted in increase of thermal pain threshold. 87 ADMA levels are also increased in SCD 49 and will impact arginine bioavailability. It is unknown what role, if any, ADMA has on pain in SCD, but it will be evaluated in future studies.…”

Section: Arginine In Painmentioning

confidence: 99%

The role of the arginine metabolome in pain: implications for sickle cell disease

Bakshi¹,

Morris²

2016

JPR

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Sickle cell disease (SCD) is the most common hemoglobinopathy in the US, affecting approximately 100,000 individuals in the US and millions worldwide. Pain is the hallmark of SCD, and a subset of patients experience pain virtually all of the time. Of interest, the arginine metabolome is associated with several pain mechanisms highlighted in this review. Since SCD is an arginine deficiency syndrome, the contribution of the arginine metabolome to acute and chronic pain in SCD is a topic in need of further attention. Normal arginine metabolism is impaired in SCD through various mechanisms that contribute to endothelial dysfunction, vaso-occlusion, pulmonary complications, risk of leg ulcers, and early mortality. Arginine is a semiessential amino acid that serves as a substrate for protein synthesis and is the precursor to nitric oxide (NO), polyamines, proline, glutamate, creatine, and agmatine. Since arginine is involved in multiple metabolic processes, a deficiency of this amino acid has the potential to disrupt many cellular and organ functions. NO is a potent vasodilator that is depleted in SCD and may contribute to vaso-occlusive pain. As the obligate substrate for NO production, arginine also plays a mechanistic role in SCD-related pain, although its contribution to pain pathways likely extends beyond NO. Low global arginine bioavailability is associated with pain severity in both adults and children with SCD as well as other non-SCD pain syndromes. Preliminary clinical studies of arginine therapy in SCD demonstrate efficacy in treating acute vaso-occlusive pain, as well as leg ulcers and pulmonary hypertension. Restoration of arginine bioavailability through exogenous supplementation of arginine is, therefore, a promising therapeutic target. Phase II clinical trials of arginine therapy for sickle-related pain are underway and a Phase III randomized controlled trial is anticipated in the near future.

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Asymmetric dimethylarginine may mediate increased heat pain threshold in experimental chronic kidney disease

Cited by 9 publications

References 21 publications

Effect of enzyme replacement therapy on serum asymmetric dimethylarginine levels, coronary flow reserve and left ventricular hypertrophy in patients with Fabry disease

Effect of enzyme replacement therapy on serum asymmetric dimethylarginine levels, coronary flow reserve and left ventricular hypertrophy in patients with Fabry disease

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

The role of the arginine metabolome in pain: implications for sickle cell disease

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