Abstract
BackgroundTaurine depletion occurs in patients with end-stage chronic kidney disease (CKD). In contrast, in the absence of CKD, plasma taurine is reported to increase following dietary L-glutamine supplementation. This study tested the hypothesis that taurine biosynthesis decreases in a rat CKD model, but is rectified by L-glutamine supplementation.MethodsCKD was induced by partial nephrectomy in male Sprague-Dawley rats, followed 2 weeks later by 2 weeks of 12% w/w L-glutamine supplemented diet (designated NxT) or control diet (NxC). Sham-operated control rats (S) received control diet.ResultsTaurine concentration in plasma, liver and skeletal muscle was not depleted, but steady-state urinary taurine excretion (a measure of whole-body taurine biosynthesis) was strongly suppressed (28.3 ± 8.7 in NxC rats versus 78.5 ± 7.6 μmol/24 h in S, P < 0.05), accompanied by reduced taurine clearance (NxC 0.14 ± 0.05 versus 0.70 ± 0.11 ml/min/Kg body weight in S, P < 0.05). Hepatic expression of mRNAs encoding key enzymes of taurine biosynthesis (cysteine sulphinic acid decarboxylase (CSAD) and cysteine dioxygenase (CDO)) showed no statistically significant response to CKD (mean relative expression of CSAD and CDO in NxC versus S was 0.91 ± 0.18 and 0.87 ± 0.14 respectively). Expression of CDO protein was also unaffected. However, CSAD protein decreased strongly in NxC livers (45.0 ± 16.8% of that in S livers, P < 0.005). L-glutamine supplementation failed to rectify taurine biosynthesis or CSAD protein expression, but worsened CKD (proteinuria in NxT 12.5 ± 1.2 versus 6.7 ± 1.5 mg/24 h in NxC, P < 0.05).ConclusionIn CKD, hepatic CSAD is depleted and taurine biosynthesis impaired. This is important in view of taurine’s reported protective effect against cardio-vascular disease - the leading cause of death in human CKD.
Highlights
Taurine depletion occurs in patients with end-stage chronic kidney disease (CKD)
There is considerable evidence that both acute kidney injury and chronic kidney disease (CKD) lead in humans and in animal models to secondary defects in distant organs [1] including the liver [1,2,3]. The mechanism of this coupling between kidney and liver is poorly understood, but the chronic systemic inflammation that occurs in CKD may exert effects on liver [3], and the stressactivated MAP kinase P38 MAPK has been shown to mediate inflammatory effects, and promote further release of inflammatory cytokines, in several models of inflammatory liver injury [4,5,6,7,8,9]. It has been proposed [10, 11] that the hepatic metabolic pathways that are affected during CKD include the catabolism pathways of the sulphur amino acids L-methionine and L-cysteine, which normally culminate in generation of sulphurous and sulphuric acid, and the sulphur amino acid taurine [12,13,14]
It has been speculated that this arises from insufficiency of the enzyme cysteine sulphinic acid decarboxylase (CSAD) which plays a role in taurine biosynthesis by catalysing the conversion of cysteine sulphinic acid (CSA) to hypotaurine which is the immediate precursor of taurine [13]
Summary
Taurine depletion occurs in patients with end-stage chronic kidney disease (CKD). In contrast, in the absence of CKD, plasma taurine is reported to increase following dietary L-glutamine supplementation. There is considerable evidence that both acute kidney injury and chronic kidney disease (CKD) lead in humans and in animal models to secondary defects in distant organs [1] including the liver [1,2,3] The mechanism of this coupling between kidney and liver is poorly understood, but the chronic systemic inflammation that occurs in CKD may exert effects on liver [3], and the stressactivated MAP kinase P38 MAPK has been shown to mediate inflammatory effects, and promote further release of inflammatory cytokines, in several models of inflammatory liver injury [4,5,6,7,8,9]. An alternative pathway through the enzyme cysteamine (2-aminoethanethiol) dioxygenase exists, but is regarded as a minor contributor to taurine biosynthesis [15]
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