Enzymuria as a marker of renal injury and disease: studies of N-acetyl-beta-glucosaminidase in the general population and in patients with renal disease.

Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) was shown to be reproducible in random urine specimens when expressed as the ratio of NAG to milligrams of urinary creatinine. The enzyme/creatinine ratio in 815 healthy people was relatively constant throughout childhood and adult life except for the first two years after birth and in individuals 56 years or greater. High ratios in the young children may be explained by low urinary creatinine excretion probably related to small body mass and reduced glomerular filtration rate at this age. The ratio was increased in adult uremic patients and children and adults with a variety of neurologic and obstructive lesions of the voiding mechanism. The presence of bacteriuria did not appear to increase the ratio. Significant enzymuria (greater than 2 SD above the mean for age and sex) was detected in 38 of 81 children with well-characterized renal disease. Among patients with predominantly glomerular disorders there was a close relationship between activity of the disease and enzymuria. In patients with tubulointerstitial disease enzymuria was frequent even in the absence of proteinuria. One of the highest enzyme/creatinine ratios was observed in a child with cystinosis. These studies indicate that NAG enzymuria is a sensitive indicator of activity of renal disease and may prove to be a suitable screening test for significant renal disease or injury in childhood.     

Salivary IgA antigliadin antibody as a marker for coeliac disease.

In recent years, serum antibodies to gliadin (AGA) have been reported to be useful markers of coeliac disease. IgA AGA have also been found in intestinal secretions and saliva in coeliac disease and may offer a convenient, non-invasive screening test. In order to test this hypothesis, salivary and serum AGA were measured in children with coeliac disease proved by biopsy and compared with several control groups. Measurement of salivary IgA AGA provided excellent discrimination between those children with coeliac disease and the control groups, and our study suggests that it may provide a rapid, non-invasive method of screening for this disease before intestinal biopsy.     

Procalcitonin as a diagnostic marker of meningococcal disease in children presenting with fever and a rash.

BACKGROUND: Procalcitonin (PCT), a precursor of calcitonin, is a recognised marker of bacterial sepsis, and high concentrations correlate with the severity of sepsis. PCT has been proposed as an earlier and better diagnostic marker than C reactive protein (CRP) and white cell count (WCC). This comparison has never been reported in the differentiation of meningococcal disease (MCD) in children presenting with a fever and rash. AIM: To determine if PCT might be a useful marker of MCD in children presenting with fever and rash. METHODS: PCT, CRP, and WCC were measured on admission in 108 children. Patients were classified into two groups: group I, children with a microbiologically confirmed clinical diagnosis of MCD (n = 64); group II, children with a self limiting illness (n = 44). Median ages were 3.57 (0.07-15.9) versus 1.75 (0.19-14.22) years respectively. Severity of disease in patients with MCD was assessed using the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS). RESULTS: PCT and CRP values were significantly higher in group I than in group II (median 38.85 v 0.27 ng/ml and 68.35 v 9.25 mg/l; p < 0.0005), but there was no difference in WCC between groups. Sensitivity, specificity, and positive and negative predictive values were higher for PCT than CRP and WCC. In group I, procalcitonin was significantly higher in those with severe disease (GMSPS >/=8). CONCLUSIONS: PCT is a more sensitive and specific predictor of MCD than CRP and WCC in children presenting with fever and a rash.     

Soluble interleukin-2 receptor as a marker of lymphocyte activation in childhood Crohn's disease.

Serum concentrations of the soluble form of the interleukin-2 receptor (sIL-2R) were determined by an enzyme-linked immunosorbent assay in a group of 39 pediatric and adolescent patients with Crohn's disease and in age-matched ulcerative colitis patients and controls. sIL-2R levels were found to be elevated in patients with Crohn's disease (p less than 0.001), and increased sIL-2R levels were detected in patients with clinically more severe disease. sIL-2R levels correlated more closely with other laboratory markers of disease activity than with a disease activity score. A progressive increase in sIL-2R levels was noted to correlate with endoscopic measurement of disease extent, while sIL-2R levels did not correlate with other markers of systemic lymphocyte activation, suggesting possible local mucosal production. Sequential determinations in individual patients revealed a good correlation between sIL-2R and clinical course. More important, elevated levels of sIL-2R preceded clinical relapse of asymptomatic patients. We conclude that sIL-2R measurement may be a useful adjunct to clinical assessment and routine laboratory testing in pediatric and adolescent patients with Crohn's disease and that serial levels may be predictive of clinical course and the response to therapy.     

Estimation of pro-renin as a prognostic marker for renal function in PUV patients

ObjectiveTo estimate serum pro-renin, and its clinical significance, as a marker of chronic renal disease in posterior urethral valve (PUV) patients.Patients and methodsForty patients with a PUV that were admitted to the hospital between 2010 and 2012 were reviewed. Twenty age-matched patients who were admitted for other non-urological diseases were selected for control. Clinical parameters, serum creatinine, urea, eGFR (estimated glomerular filtration rate) and serum pro-renin were analysed before and after valve ablation.ResultsForty patients with PUV were included in the study. Three groups were formed according to age: <1 year, 1–3 years, >3 years. Pro-renin was measured using an ELISA (enzyme linked immunosorbent assay) kit and ‘Graph Pad Prism’ Software. The Spearman's rho test was used for correlation. Serum pro-renin had a negative correlation with the age group (correlation coefficient −0.395, P-value 0.012), eGFR (correlation coefficient −0.850, P-value < 0.001) and follow-up eGFR (correlation coefficient −0.471, P-value 0.002). The pro-renin level correlated positively with serum creatinine at presentation (correlation coefficient 0.671, P-value < 0.001), blood urea at initial presentation (correlation coefficient 0.684, P-value < 0.001), serum creatinine at follow-up (correlation coefficient 0.546, P-value < 0.001) and blood urea at follow-up (correlation 0.603, P-value < 0.001).ConclusionPro-renin measured before PUV repair is associated with renal function three months after surgery.     

Serum neutrophil gelatinase-associated lipocalin as a marker of acute kidney injury in asphyxiated neonates

Objective

To determine the clinical utility of serum neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in asphyxiated neonates with hypoxic ischemic encephalopathy (HIE).

Design

Cohort study.

Settings

National Intensive Care Unit of Maternity Hospital, Ain Shams University, Cairo, Egypt.

Patients

The study included 30 term asphyxiated neonates (8 with mild, 13 with moderate and 9 with severe HIE) and 20 control neonates.

Intervention

Serum NGAL level was measured within 6 hours after birth using an enzyme linked immunosorbent assay.

Main outcome measures

Patients were subsequently discriminated into AKI (n=12) and no-AKI (n=18) groups.

Results

The median (Interquartile range) serum NGAL concentration was 95.0 (70.75–180.00) ng/mL in asphyxiated neonates, and 39.75 (6.0–48.0) ng/mL in control neonates; (P<0.001). Serum NGAL correlated with HIE severity: mean (SD) was 65.50 (3.77) ng/mL in infants with mild HIE, 115.07 (45.83) ng/mL in infants with moderate HIE and 229.66 (79.50) ng/mL in infants with severe HIE; (P<0.01). The median (Interquartiles) serum NGAL level was 182.50 (166.25–301.75) ng/mL in patients with AKI, 74.00 (66.00–78.75) ng/mL in those without AKI; (P<0.001). A cutoff value 157 ng/mL for serum NGAL could detect AKI in asphyxiated neonates with a sensitivity of 83.3% and a specificity of 94.4%.

Conclusion

Elevated serum NGAL measured within 6 hours after birth reliably indicates acute kidney injury in asphyxiated neonates.     

Elevated lactate as an early marker of brain injury in inflicted traumatic brain injury

Background: Traumatic brain injury is a major cause of disability and death in the pediatric population. The metabolic and neurochemical abnormalities that underlie traumatic brain injury remain poorly understood, but hypoxia-ischemic injury might play an important role. Objective: This study evaluated children with inflicted traumatic brain injury using magnetic resonance spectroscopy (MRS). We postulated that children with hypoxic-ischemic injury indicated by elevated lactate in the acute phase of injury will have worse early neurological status and short-term clinical outcomes than those without lactate upon MRS. Materials and methods: This prospective study employed proton MRS to sample bilaterally the frontal lobes and the parasagittal cortex within the parietal and occipital lobes of 11 patients with inflicted traumatic brain injury who were undergoing a clinical MRI examination. Patients measured clinical course while hospitalized included initial neurological evaluation, presence of seizure activity, need for admission to the pediatric intensive care unit (PICU), number of days hospitalized, presence of retinal hemorrhages and presence of bone fractures. Measurement of outcome was determined using the Pediatric Overall Performance Category Scale (POPCS; 1 = good performance; 6 = death). Results: Four children demonstrated elevated lactate and diminished N-acetyl aspartate (a neuronal marker) within several regions, indicating global ischemic injury (lactate-positive global group). These four children all had seizure activity and abnormal initial neurological examinations and required admission to the PICU. The mean POPCS for this group was 3.25. In four other children, lactate was detected within at least one region, indicating a focal ischemic injury (lactate-positive focal group); two of these children had seizure activity, and two had an abnormal initial neurological examination. The mean POPCS score was 1.5 for this group. The remaining three children had no evidence of lactate upon MRS (lactate-negative group). These children did not have seizure activity, did not require admission to the PICU, nor did they have initial abnormal neurological examinations. The mean POPCS score was 1.3 for this group. Summary: Patients with inflicted traumatic brain injury and evidence of hypoxic-ischemic injury as indicated by elevated lactate on MRS tend to have worse early neurological status and early outcome scores. Lactate levels as sampled by MRS might predict early clinical outcome in inflicted traumatic brain injury.     

Procalcitonin as a diagnostic marker of meningococcal disease in children presenting with fever and a rash

Background: Procalcitonin (PCT), a precursor of calcitonin, is a recognised marker of bacterial sepsis, and high concentrations correlate with the severity of sepsis. PCT has been proposed as an earlier and better diagnostic marker than C reactive protein (CRP) and white cell count (WCC). This comparison has never been reported in the differentiation of meningococcal disease (MCD) in children presenting with a fever and rash. Aim: To determine if PCT might be a useful marker of MCD in children presenting with fever and rash. Methods: PCT, CRP, and WCC were measured on admission in 108 children. Patients were classified into two groups: group I, children with a microbiologically confirmed clinical diagnosis of MCD (n = 64); group II, children with a self limiting illness (n = 44). Median ages were 3.57 (0.07–15.9) versus 1.75 (0.19–14.22) years respectively. Severity of disease in patients with MCD was assessed using the Glasgow Meningococcal Septicaemia Prognostic Score (GMSPS). Results: PCT and CRP values were significantly higher in group I than in group II (median 38.85 v 0.27 ng/ml and 68.35 v 9.25 mg/l; p < 0.0005), but there was no difference in WCC between groups. Sensitivity, specificity, and positive and negative predictive values were higher for PCT than CRP and WCC. In group I, procalcitonin was significantly higher in those with severe disease (GMSPS ≥8). Conclusions: PCT is a more sensitive and specific predictor of MCD than CRP and WCC in children presenting with fever and a rash.     

Calprotectin as a marker of inflammation in cystic fibrosis.

Calprotectin is an abundant neutrophil cytosolic protein released during neutrophil activation or death. The use of plasma calprotectin concentration as a marker of pulmonary inflammation was tested in 31 children with cystic fibrosis, none of whom was acutely unwell or pyrexic. Twenty three were receiving antibiotics, 21 had positive sputum cultures, but none of the traditional tests clearly diagnosed ongoing infection. Plasma calprotectin was significantly higher in the cystic fibrosis group than in matched controls. Sixteen children with cystic fibrosis had values above the control range (320-1570 micrograms/l). Their chest radiograph Northern score, an index of accumulated pulmonary involvement, and their plasma copper, an index of acute phase response, both correlated with plasma calprotectin. Plasma gamma-glutamyltransferase also correlated weakly with plasma calprotectin: thus, hepatic pathology may be a confounding variable. However, the data still suggested that plasma calprotectin is a better index of inflammation than the traditional indices in general use.     

Neopterin as a marker of C hepatitis in thalassaemia major.

The authors studied serum neopterin in 106 patients with beta thalassaemia major. A good correlation was found between neopterin values and glutamic pyruvic transaminase (GPT) mean values of the last 6 months, whereas no correlation was found between neopterin values and some siderosis indexes (iron/body weight, total accumulated iron). A statistically significant correlation was found between neopterin values (greater than 10 nM/L vs. less than 10 nM/L) and histological liver findings (chronic hepatitis vs. siderosis). Neopterin values were also statistically different between splenectomized and not splenectomized patients. Moreover serum neopterin was higher in HCV-Ab positive than in HCV-Ab negative patients, and 91.6% of the HCV-Ab positive group also showed histological signs of chronic hepatitis. These data suggest that increased serum neopterin might help to identify chronic C hepatitis in thalassaemic patients.     

Drug-induced lupus as a cause of relapsing inflammatory disease after renal transplantation

We discuss the case of an 18-year-old-boy presenting with relapsing fever, arthralgia, myalgia and renal failure, 7 yr after renal transplantation. A thorough diagnostic work-up for infectious and inflammatory diseases revealed a mastoiditis and atypical mycobacteria, but symptoms persisted after treatment. Persistent antinuclear antibodies in combination with cardiolipin and myeloperoxidase antibodies, despite negative dsDNA antibodies, suggested a drug induced lupus-like syndrome. Six months after withdrawal of dihydralazine, all symptoms had disappeared. Drug-induced lupus should be considered as an important differential diagnosis in transplanted patients with recurrent inflammatory disease in conjunction with lupus-like symptoms and negative dsDNA antibodies. It may prevent a potentially hazardous reduction of immunosuppression in persistent inflammation.     

Diffuse axonal injury in periventricular leukomalacia as determined by apoptotic marker fractin

Periventricular leukomalacia (PVL), the major substrate of neurologic deficits in premature infants, is associated with reduced white matter volume. Using immunomarkers of axonal pathology [beta-amyloid precursor protein (beta-APP) and apoptotic marker fractin], we tested the hypothesis that widespread (diffuse) axonal injury occurs in the gliotic white matter beyond the foci of necrosis in PVL, thus contributing to the white matter volume reduction. In a cohort of 17 control cases and 13 PVL cases with lesions of different chronological ages, diffuse axonal damage in PVL was detected by fractin in white matter sites surrounding and distant from acute and organizing foci of necrosis. Using beta-APP, axonal spheroids were detected within necrotic foci in the acute and organizing (subacute) stages, a finding consistent with others. Interestingly, GAP-43 expression was also detected in spheroids in the necrotic foci, suggesting attempts at axonal regeneration. Thirty-one percent of the PVL cases had thalamic damage and 15% neuronal injury in the cerebral cortex overlying PVL. We conclude that diffuse axonal injury, as determined by apoptotic marker fractin, occurs in PVL and that its cause likely includes primary ischemia and trophic degeneration secondary to corticothalamic neuronal damage.     

Type 1 procollagen as a biochemical marker of growth in children with inflammatory bowel disease

Using radioimmunoassay, we measured the levels of the C-terminal propeptide of type I procollagen (pColl-I-C) in sera from 69 children with functional bowel disease (control population), 18 children with ulcerative colitis, and 35 children with Crohn disease. Sexually mature fully grown adolescents from all three patient groups had mean pColl-I-C concentrations (12.0 +/- 0.8 micrograms/dl) similar to those previously reported for adults (5 to 17 micrograms/dl). Children with functional bowel disease and normal growth had significantly higher concentrations (32.8 +/- 1.7 micrograms/dl) (P less than 0.001) than did the fully grown adolescents. In patients with inflammatory bowel disease a significant relationship between growth velocity and pColl-I-C concentrations was noted (P less than .001). Lower pColl-I-C concentrations were found in patients receiving daily prednisone therapy compared with those receiving alternate-day therapy (P less than 0.01) or those not taking the drug (P less than 0.01). These data suggest that pColl-I-C concentrations reflect growth activity in children. Repeated determinations may allow rapid assessment of the effects of various therapeutic modalities on growth in children with inflammatory bowel disease.     

Procalcitonin is a marker of severity of renal lesions in pyelonephritis

OBJECTIVE: In an attempt to differentiate acute pyelonephritis from lower urinary tract infection (UTI), we measured serum procalcitonin levels, a recently described marker of infection. We compared it with other commonly used inflammatory markers and evaluated its ability to predict renal involvement as assessed by dimercaptosuccinic acid (DMSA) scintigraphy. METHODS: Serum C-reactive protein, leukocyte counts, and procalcitonin levels were measured in 80 children, 1 month to 16 years of age, admitted for suspected pyelonephritis. Renal involvement was assessed by 99mTe-DMSA scintigraphy in the first 5 days after admission. The examination was repeated at least 3 months later if the first result was abnormal. RESULTS: In lower UTI, the mean procalcitonin (PCT) was 0.38 micrograms/L +/- 0.19 compared with 5.37 micrograms/L +/- 1.9 in pyelonephritis. In these two groups, respectively, leukocyte counts were 10939/mm3 +/- 834 and 17429/mm3 +/- 994, and C-reactive protein (CRP) levels were 30.3 mg/L +/- 7.6 and 120.8 mg/L +/- 8.9. When inflammatory markers were correlated to the severity of the renal lesion as ranked by DMSA scintigraphy, we found a highly significant correlation with plasma levels of PCT, but borderline significance with CRP and none with leukocyte counts. Patients without vesicoureteral reflux had a mean PCT of 5.16 micrograms/L +/- 2.33, which was not significantly different from that in patients with reflux who had a mean PCT of 5.76 micrograms/L +/- 3.49. For the prediction of renal lesions at admission, CRP had a sensitivity of 100% and a specificity of 26.1%. The sensitivity and specificity of PCT were 70.3% and 82.6%, respectively. CONCLUSION: We conclude that serum PCT levels were increased significantly in children with febrile UTI when renal parenchymal involvement (assessed by DMSA scintigraphy) was present and allowed for prediction of patients at risk of severe renal lesions.