Acute Effects of Acetaminophen on Renal Function and Urinary Excretion of Some Proteins and Enzymes in Patients with Kidney Disease

Mitić-Zlatković, Marina; Stefanović, Vladisav

doi:10.3109/08860229909045192

Cited by 13 publications

(13 citation statements)

References 15 publications

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“…Paracetamol must be considered as a safe alternative to NSAIDs for the relief of mildto-moderate pain in elderly patients, in patients with kidney disease (144), hypertension (56,93,104,110,166,184,185,225), congestive heart failure (81,85,98,139,157). In such patients, NSAIDs, for their mechanism of action, may worsen the renal and cardiovascular function, besides causing gastrointestinal damage (23,85,227,228,229).…”

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confidence: 99%

Paracetamol: New Vistas of an Old Drug

et al. 2006

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Paracetamol (acetaminophen) is one of the most popular and widely used drugs for the treatment of pain and fever. It occupies a unique position among analgesic drugs. Unlike NSAIDs it is almost unanimously considered to have no antiinflammatory activity and does not produce gastrointestinal damage or untoward cardiorenal effects. Unlike opiates it is almost ineffective in intense pain and has no depressant effect on respiration. Although paracetamol has been used clinically for more than a century, its mode of action has been a mystery until about one year ago, when two independent groups (Zygmunt and colleagues and Bertolini and colleagues) produced experimental data unequivocally demonstrating that the analgesic effect of paracetamol is due to the indirect activation of cannabinoid CB 1 receptors. In brain and spinal cord, paracetamol, following deacetylation to its primary amine (p-aminophenol), is conjugated with arachidonic acid to form N-arachidonoylphenolamine, a compound already known (AM404) as an endogenous cannabinoid. The involved enzyme is fatty acid amide hydrolase. N-arachidonoylphenolamine is an agonist at TRPV1 receptors and an inhibitor of cellular anandamide uptake, which leads to increased levels of endogenous cannabinoids; moreover, it inhibits cyclooxygenases in the brain, albeit at concentrations that are probably not attainable with analgesic doses of paracetamol. CB 1 receptor antagonist, at a dose level that completely prevents the analgesic activity of a selective CB 1 receptor agonist, completely prevents the analgesic ac- 250CNS Drug Reviews Vol. 12, No. 3-4, pp. 250-275 © 2006 tivity of paracetamol. Thus, paracetamol acts as a pro-drug, the active one being a cannabinoid. These findings finally explain the mechanism of action of paracetamol and the peculiarity of its effects, including the behavioral ones. Curiously, just when the first CB 1 agonists are being introduced for pain treatment, it comes out that an indirect cannabinomimetic had been extensively used (and sometimes overused) for more than a century.

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confidence: 99%

Paracetamol: New Vistas of an Old Drug

et al. 2006

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“…Our aim was to investigate whether ACE gene polymorphism influences urinary excretion of NAG, a urinary enzyme which was described to be enhanced in the early phase of EN [18,19,20,65,66]. Although sensitivity of urinary NAG is high [20], increased urinary NAG excretion is not specific for EN, while it was observed in different forms of primary glomerulonephritis, diabetic nephropathy and in patients with hypertension [66,67,68,70].…”

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confidence: 99%

Angiotensin-Converting Enzyme Gene Polymorphism and N-Acetyl-β-<i>D</i>-Glucosaminidase Excretion in Endemic Nephropathy

et al. 2011

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Background: Tubular proteinuria and enzymuria are hallmarks of endemic nephropathy (EN). The role of I/D angiotensin convertase (ACE) gene polymorphism has not yet been elucidated in this peculiar chronic tubulointerstitial nephritis, and our aim was to investigate the role of this polymorphism in EN focusing on the urinary N-acetyl-β-D-glucosaminidase (NAG) excretion, a biomarker of proximal tubular damage. Methods:ACE genotype and allele frequencies were determined in 229 farmers (147 women and 82 men) from an endemic Croatian village. The farmers were stratified according to the WHO criteria into the following subgroups: those ‘at risk’ for EN (n = 37), ‘suspected of having EN’ (n = 57), and ‘others’ (n = 135). Results: There were 74 (32.3%) subjects homozygous for the D allele, 99 (43.2%) heterozygous (ID genotype) and 56 (24.4%) homozygous for the I allele. No differences in allele frequency were found between the established WHO subgroups (p > 0.05). In the whole group, DD subjects had significantly higher values of diastolic blood pressure (p = 0.003) and urinary NAG than subjects with ID and II genotype (5.5 ± 1.2 vs. 4.0 ± 3.0 vs. 3.8 ± 4.2, respectively; p = 0.023). The highest values of serum creatinine (p = 0.02), proteinuria (p = 0.03) and urinary NAG (6.0 ± 3.7 vs. 3.7 ± 2.1 vs. 3.0 ± 1.6, respectively; p = 0.008) were observed in those suspected of having EN group with the DD genotype. Conclusion:ACE gene polymorphism is not a risk factor for EN. However, it might influence the clinical course of EN, and increased excretion of NAG might be a prognostic marker of this chronic tubulointerstitial nephritis.

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“…Urinary N-acetyl-β-D-glucosaminidase (NAGA) excretion was found higher in BEN patients than in healthy controls. [35] …”

Section: Urinementioning

confidence: 99%

Diagnostic Criteria for Balkan Endemic Nephropathy: Proposal by an International Panel

Stefanović¹,

Jelaković²,

Čukuranović³

et al. 2007

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Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression to terminal renal failure. Diagnostic criteria for BEN have been described more than 40 years ago. Research groups on BEN use one of at least three described lists of criteria. Comparison of studies using such criteria is difficult, and a recent meeting of investigators (Zagreb, October 2006) has suggested that unified criteria have to be elaborated. In this paper, an International Panel of BEN Investigators agreed on criteria appropriate to epidemiologic studies and clinical investigations of BEN. A screening procedure of BEN in endemic settlements is proposed.

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Acute Effects of Acetaminophen on Renal Function and Urinary Excretion of Some Proteins and Enzymes in Patients with Kidney Disease

Cited by 13 publications

References 15 publications

Paracetamol: New Vistas of an Old Drug

Paracetamol: New Vistas of an Old Drug

Angiotensin-Converting Enzyme Gene Polymorphism and N-Acetyl-β-<i>D</i>-Glucosaminidase Excretion in Endemic Nephropathy

Diagnostic Criteria for Balkan Endemic Nephropathy: Proposal by an International Panel

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