Urinary metabolomic markers of aminoglycoside nephrotoxicity in newborn rats.

BACKGROUND: Aminoglycoside exposure is a common cause of acute kidney injury (AKI). Delay in the diagnosis of AKI using conventional biomarkers has been one of the important obstacles in applying early effective interventions. We tested the hypothesis that urinary metabolomics could identify novel early biomarkers for toxic renal injury. METHODS: Three-day-old rats were divided into three groups; they received a single daily injection of vehicle (0.9% NaCl solution) or gentamicin at a dose of 10 or 20 mg/kg/d for 7 d. Urine and blood were collected after 3 and 7 d of injections. Urinary metabolites were evaluated using high-performance liquid chromatography and gas chromatography/mass spectrometry. RESULTS: A distinct urinary metabolic profile characterized by glucosuria, phosphaturia, and aminoaciduria was identified preceding changes in serum creatinine. At both the gentamicin doses, urinary tryptophan was significantly (P < 0.05) increased (fold change: 1.91 and 2.31 after 3 d; 1.81 and 1.93 after 7 d). Similarly, kynurenic acid, a tryptophan metabolite, showed a significant (P < 0.05) decrease (fold change: 0.26 and 0.24 after 3 d; 0.21 and 0.52 after 7 d), suggesting an interruption of the normal tryptophan metabolism pathway. CONCLUSION: We conclude that urinary metabolomic profiling provides a robust approach for identifying early and novel markers of gentamicin-induced AKI.

Antioxidant status of children with idiopathic nephrotic syndrome.

The production of free radicals can cause renal injury and play an important role in the pathogenesis of idiopathic nephrotic syndrome. Markers of reactive oxygen species (ROS) were evaluated in 48 patients with active nephrotic syndrome (ANS) and 30 age- and gender-matched healthy children. Plasma malondialdehyde (MDA), protein carbonyl, nitrite, copper, zinc, selenium, ascorbic acid, and superoxide dismutase (SOD) levels were estimated in patients with ANS and controls. Measurements were repeated in 39 cases after achievement of remission, and in 10 other children who were in remission of >6 months' duration. Plasma MDA and nitrite levels were significantly higher and selenium was lower in ANS patients compared with controls. Plasma protein carbonyl, copper ascorbic acid, zinc, and superoxide dismutase levels were comparable in ANS patients and controls. Plasma copper level was significantly higher in active cases than in the remission and long-term remission groups. Selenium value showed a rise and then normalized in long-term remission. Among different sub-groups of ANS, no significant differences were found in the levels of various parameters, except plasma selenium, which was significantly lower in first-attack nephrotic syndrome (FANS) in comparison to infrequently relapsing nephrotic syndrome (IRNS) and frequently relapsing nephrotic syndrome (FRNS) patients. Thus, we observed evidence of oxidative stress and impaired antioxidant defense during acute nephrotic syndrome. Antioxidant status recovered completely only during long-term remission.

Dialysis-associated peritonitis in children.

Peritonitis remains a frequent complication of peritoneal dialysis in children and is the most common reason for technique failure. The microbiology is characterized by a predominance of Gram-positive organisms, with fungi responsible for less than 5% of episodes. Data collected by the International Pediatric Peritonitis Registry have revealed a worldwide variation in the bacterial etiology of peritonitis, as well as in the rate of culture-negative peritonitis. Risk factors for infection include young age, the absence of prophylactic antibiotics at catheter placement, spiking of dialysis bags, and the presence of a catheter exit-site or tunnel infection. Clinical symptoms at presentation are somewhat organism specific and can be objectively assessed with a Disease Severity Score. Whereas recommendations for empiric antibiotic therapy in children have been published by the International Society of Peritoneal Dialysis, epidemiologic data and antibiotic susceptibility data suggest that it may be desirable to take the patient- and center-specific history of microorganisms and their sensitivity patterns into account when prescribing initial therapy. The vast majority of patients are treated successfully and continue peritoneal dialysis, with the poorest outcome noted in patients with peritonitis secondary to Gram-negative organisms or fungi and in those with a relapsing infection.