Enfermedad de Wilson en adolescente con hipertransaminasemia asintomática / Wilson's disease in adolescent with asymptomatic hypertransaminasemia

La hipertransaminasemia en la edad pediátrica es un hallazgo relativamente frecuente en niños asintomáticos; suele ser un indicador sensible de daño hepático, aunque poco específico. Se considera crónica cuando persiste más de 6 meses. En esos casos puede ser el primer indicador de enfermedades que requieren tratamiento precoz para mejorar el pronóstico. Presentamos el caso de una niña preadolescente que presenta hipertransaminasemia crónica en el contexto de un estudio inicial de dolor abdominal inespecífico, cuyo diagnóstico final fue enfermedad de Wilson

Hypertransaminasemia in the pediatric age is a relatively common finding in asymptomatic children, which is usually a sensitive indicator of liver damage, although not very specific. It is considered prolonged when hypertransaminasemia persists for more than 6 months. In those cases, it may be the first indicator of diseases that require early treatment to improve prognosis. We present the case of a preadolescent girl who presented hypertransaminasemia detected during the study of nonspecific abdominal pain, whose final diagnosis was Wilson's disease

Effect of vitamin B6 deficiency on glyoxylate metabolism in rats with or without glyoxylate overload.

We examined the effect of vitamin B6 deficiency on glyoxylate metabolism and hepatic alanine: glyoxylate aminotransferase (AGT) activity in rats with normal or high glyoxylate intake. Male rats were divided into four groups: a control group, a vitamin B6-free diet group, a glyoxylate water group, and a vitamin B6-free diet + glyoxylate water group. Each group was given special diet (control or vitamin B6-deficient diet) and drinking water (plain or 0.5% glyoxylate water) for 4 weeks, after which biochemical parameters and hepatic AGT mRNA level were measured. Compared with control rats, the urinary oxalate/creatinine ratio was higher in each of the other 3 groups. The urinary glycolate/creatinine ratio was also higher in the vitamin B6-free diet group and the vitamin B6-free diet + glyoxylate water group than the control group, while the urinary glycine/creatinine and citrate/creatinine ratio was lower in both groups. The hepatic AGT mRNA level was reduced in the vitamin B6-free diet group, but was increased in the glyoxylate water group than the control group. These results suggest that vitamin B6 is necessary for glyoxylate metabolism as a coenzyme of AGT. Especially in the presence of a high glyoxylate intake, vitamin B6 deficiency leads to severe hyperoxaluria and hypocituria.

Historical control data on urinary and renal tissue biomarkers in naive male Wistar rats.

Total proteins, angiotensin-converting enzyme, N-acetyl-beta-D-glucosaminidase, glutamine transaminase K and glutamine synthetase were determined in urine collected overnight (14 h: 6:00 p.m.-8:00 a.m.) from naive male Wistar rats; glutamine transaminase K and glutamine synthetase in the kidney 10,000 g supernatant and p-aminohippurate uptake in renal cortical slices also were measured. Urinary parameters were related both to urinary creatinine concentration and urinary flow rate; kidney parameters were related to protein concentration (enzymes) or slice/medium (S/M) ratio (p-aminohippurate uptake). The following reference ranges (1.0 and 99.0 percentiles) were obtained: urine: total urinary proteins (195 samples) 0.03-0.29 g mmol(-1) creatinine and 0.13-1.77 mg h(-1); angiotensin-converting enzyme (115 samples) 8.9-63.7 micromol mmol(-1) creatinine and 59.4-282.7 nmol h(-1); glutamine transaminase K (115 samples) 0-1.7 micromol mmol(-1) creatinine and 0-8.5 nmol h(-1); N-acetyl-beta-D-glucosaminidase (72 samples) 0.7-5.0 micromol mmol(-1) creatinine and 4.9-28.4 nmol h(-1) (naive male rats did not excrete glutamine synthetase); kidney: glutamine transaminase K (36 samples) 14.5-32.8 nmol mg(-1) protein; glutamine synthetase (22 samples) 13.9-48.6 nmol mg(-1) protein and p-aminohippurate (54 samples) 4.77-17.89 S/M. Urinary creatinine (r = -0.780), total urinary proteins (r = -0.521), angiotensin-converting enzyme (r = -0.650) and N-acetyl-beta-D-glucosaminidase (r = -0.796) but not glutamine transaminase K were well correlated with diuresis. In addition, the same parameters, but not glutamine transaminase K, were well correlated with creatinine (r = 0.604,0.701 and 0.747, respectively). Significant correlation also was observed between urinary indices adjusted to creatinine or urinary flow rate (total urinary proteins: r = 0.813; angiotensin-converting enzyme: r = 0.677; glutamine transaminase K: r = 0.939; N-acetyl-beta-D-glucosaminidase: r = 0.657). Finally, a low but significant correlation was found between total urinary proteins and angiotensin-converting enzyme (r = 0.293) and N-acetyl-beta-D-glucosaminidase (r = 0.471).

Glutamine transaminase K intranephron localization in rats determined by urinary excretion after treatment with segment-specific nephrotoxicants.

Glutamine transaminase K(GTK) excretion assessed in urine and by kidney histology was evaluated in rats after single treatment with 1.0 mg/kg i.p. of mercuric chloride, 100 mg/kg i.p. of hexachloro-1:3-butadiene (both S3, pars recta, segment-specific nephrotoxicants) and 25 mg/kg s.c. of potassium dichromate (S1-S2, pars convoluta, segment-specific nephrotoxicant). The aim was to correlate segment-specific injury and enzyme excretion in order to assess, using non-vasive methods, localization of GTK along the proximal tubule. Mercuric chloride and hexachloro-1:3-butadiene produced early focal damage in the pars recta (focal necrosis was shown 10 h after treatment, and diffuse necrosis appeared later at 34 and 24 h after treatment). Changes of the pars convoluta were occasional and delayed (72 h after treatment for both substances). On the contrary, potassium dichromate induced damage of the pars convoluta (vacuolar degeneration and focal necrosis were evident 24 h and 48 h after treatment, respectively), whereas the pars recta was affected later (focal vacuolar degeneration was observed 72 h after treatment). Increase urinary GTK excretion was early after treatment with mercuric chloride and hexachloro-1:3-butadiene (significant increase was observed within 10 h), with a peak for both substances 24 h after treatment, in agreement with the necrosis of the pars recta. Potassium dichromate induced a significant increase of enzyme excretion in urine also 24 h after injection, according to histological features showing vacuolar degeneration of the pars convoluta; the peak of excretion was reached 48 h after treatment (delay was due, probably, to s.c. administration). The results show that GTK increased in urine after treatment with S3 and S1-S2 specific nephrotoxicants; the combination of histological examination and urinary enzyme supports the evidence that the enzyme is distributed along the whole of the proximal tubule.

In vivo inhibition of kynurenine aminotransferase activity by isonicotinic acid hydrazide in rats.

It is known that the anti-tuberculosis drug, isonicotinic acid hydrazide (INH), causes pellagra, a niacin deficiency syndrome, and peripheral neuritis in humans. We investigated the effects of INH on the metabolism of tryptophan to niacin in rats fed on a niacin-free diet. The activity of kynurenine aminotransferase was significantly inhibited by feeding a diet containing INH and by an injection of INH, and the urinary excretion of xanthurenic acid, the side-reaction product of the conversion pathway of tryptophan to niacin, was below the limit of detection. The inhibition of kynurenine aminotransferase and the resulting decreased formation of xanthurenic acid generally mean a higher conversion ratio of tryptophan to niacin. However, the conversion ratio was no different between the control and INH groups.

Urinary enzyme changes in children undergoing cineangiographic evaluation using iopromid.

Nephropathy due to radiocontrast media presents with a wide spectrum of changes from reversible renal dysfunction to oliguria requiring dialysis. Nineteen patients (mean age 4.5 +/- 3.7 years) were included. Mean +/- SD values of the variables obtained before and 48 hours after angiography were the following: plasma creatinine: 0.6 +/- 0.10 and 0.6 +/- 0.16 mg/dl; endogenous creatinine clearance: 76.1 +/- 17.0 and 80.9 +/- 19.3 ml/min/1.73 m2; plasma osmolality: 279 +/- 23 and 298 +/- 39 mOsm/kg H2O; urine osmolality: 429 +/- 225 and 459 +/- 196 mOsm/kg H2O; fractional sodium excretion: 2.1 +/- 1.3% and 2.4 +/- 1.3%; plasma uric acid: 3.9 +/- 1.3 and 3.4 +/- 1.0 mg/dl; urinary AST/creatinine: 5.2 +/- 4.8 and 4.2 +/- 2.6 mU/mg; ALT/creatinine: 16.8 +/- 12.4 and 15.3 +/- 12.6 mU/mg; LDH/creatinine: 52.0 +/- 39.6 and 42.3 +/- 31.5 mU/mg; NAG/creatinine: 20.1 +/- 2.8 and 16.8 +/- 2.3 mU/mg, respectively. The changes in renal function parameters and urinary enzyme levels were insignificant statistically (p > 0.05). In conclusion, iopromid injection at maximum doses of 5 ml/kg does not result in injury to the tubular epithelium leading to increased urinary enzyme levels.

Chromium-induced early changes in renal function among ferrochromium-producing workers.

Urinary biochemical indicators of renal injury were examined in 84 male and 38 female ferrochromium-producing workers exposed to water-soluble chromium compounds [Cr(VI)]. The indicators examined included urinary chromium (U-Cr), alkaline phosphatase (ALP), gamma-glutamyl transferase (gamma-GT), glutamic-oxalacetic and glutamic-pyruvic transaminases (GOT & GPT), lactate dehydrogenase (LDH), N-acetyl-beta-D-glucosaminidase (NAG), total protein (TPr) and beta 2-microglobulin (beta 2-MG). The U-Cr levels in the exposed group were approximately 1.8 times that of the control group. Compared to controls, the activities of gamma-GT, NAG, ALP, GOT and LDH in the urine of workers were significantly increased whenever U-Cr concentration exceeded 45 microgram/g creatinine. The activities of gamma-GT, GOT and NAG were elevated in workers employed for longer than ten years. However, no clear dose-response relationships nor time-effect relationships were found. The present results suggest that long-term exposure to water-soluble chromium [Cr(VI)] produces chronic renal injury. The site of the injury appears to mainly involve the proximal tubule. U-Cr concentrations of > 15 microgram/g creatinine can be proposed as a threshold dosage for nephrotoxicity, and gamma-GT, NAG and ALP are early sensitive indicators of the most valuable for evaluating the renal injury.

[Urinary transaminase in the diagnosis of kidney disorders in liver cirrhosis]. / Harntransamidinase in der Diagnostik von Nierenstörungen bei Leberzirrhose.

In examinations of 72 patients with liver cirrhosis and chronic hepatitis the transaminase activity of the urine (T-uria) was found in 55.6% of the cases, above all in liver cirrhosis. The T-uria increases parallel to the progressing portal hypertension to the hepatocellular insufficiency and to the hepatorenal syndrome. It is reduced in positive dynamics of the hepatic process. The T-uria has an essential prognostic value. In the terminal phase of the liver cirrhosis the T-uria is perhaps connected with disturbances of the hepatic haemodynamics.