Urinary angiotensinogen levels in relation to renal involvement of Henoch-Schonlein purpura in children.

AIM: To investigate whether urinary angiotensinogen (UAGT) levels are correlated with renal involvement of Henoch-Schonlein purpura (HSP) in children, and to explore whether UAGT has any relation to the severity of HSP. METHODS: The study sample consisted of 107 patients (50 boys and 57 girls, 6.68±2.41 years) with clinical diagnosis of HSP. A 24 h urine sample was collected before treatment. UAGT levels were measured in patients with HSP in the acute and convalescent phases by enzyme linked immunosorbent assay. RESULTS: Urinary angiotensinogen/urinary concentration of creatinine levels were significantly higher in proteinuric HSP in the acute phase and the convalescent phase (32.02±3.95 and 25.31±4.11 µg/g) compared with those with HSP without renal involvement (17.26±2.60 and 15.14±3.81 µg/g) and those with hematuric HSP (19.70±2.21 and 17.28±3.62 µg/g) (P<0.0001 and P<0.01, respectively). Using matched urine samples from the same patients, UAGT/urinary concentration of creatinine (UCr) levels of proteinuric HSP patients were significantly lower in the convalescent phase (25.31 ± 4.11 µg/g, P<0.01) than in the acute phase (32.02±3.95 µg/g). UAGT/UCr levels showed positive correlation with 24 h urine protein or serum creatinine in both hematuric HSP and proteinuric HSP groups during the acute phase (P<0.05). CONCLUSIONS: Urinary angiotensinogen levels were remarkably high in the acute phase in the patients with proteinuric HSP, suggesting increased UAGT may indicate a series of functional changes in the kidney and it may be used as a potential biomarker of severity of HSP to monitor the progression of HSP with renal involvement.

Long-term persistance of the pathophysiologic response to severe burn injury.

BACKGROUND: Main contributors to adverse outcomes in severely burned pediatric patients are profound and complex metabolic changes in response to the initial injury. It is currently unknown how long these conditions persist beyond the acute phase post-injury. The aim of the present study was to examine the persistence of abnormalities of various clinical parameters commonly utilized to assess the degree hypermetabolic and inflammatory alterations in severely burned children for up to three years post-burn to identify patient specific therapeutic needs and interventions. PATIENTS: Nine-hundred seventy-seven severely burned pediatric patients with burns over 30% of the total body surface admitted to our institution between 1998 and 2008 were enrolled in this study and compared to a cohort non-burned, non-injured children. Demographics and clinical outcomes, hypermetabolism, body composition, organ function, inflammatory and acute phase responses were determined at admission and subsequent regular intervals for up to 36 months post-burn. Statistical analysis was performed using One-way ANOVA, Student's t-test with Bonferroni correction where appropriate with significance accepted at p<0.05. Resting energy expenditure, body composition, metabolic markers, cardiac and organ function clearly demonstrated that burn caused profound alterations for up to three years post-burn demonstrating marked and prolonged hypermetabolism, p<0.05. Along with increased hypermetabolism, significant elevation of cortisol, catecholamines, cytokines, and acute phase proteins indicate that burn patients are in a hyperinflammatory state for up to three years post-burn p<0.05. CONCLUSIONS: Severe burn injury leads to a much more profound and prolonged hypermetabolic and hyperinflammatory response than previously shown. Given the tremendous adverse events associated with the hypermetabolic and hyperinflamamtory responses, we now identified treatment needs for severely burned patients for a much more prolonged time.

Inhibitors of the hyaluronidases.

The inhibitors of hyaluronidase present in mammalian sera, first described half a century ago, have remained uncharacterized. Because of increased interest in hyaluronidases and their hyaluronan substrate, a study of these inhibitors was undertaken recently. The predominant serum inhibitor is magnesium-dependent and is eliminated by protease or chondroitinase digestion, and by heat. Kinetics of inhibition are similar against hyaluronidases from testis, snake and bee venom. The inhibitor has no effect on Streptomyces hyaluronidase; indicating inhibition is not through protection of the hyaluronan substrate. Circulating inhibition levels are increased in mice following carbon tetrachloride or interleukin-1 injection, inducers of the acute-phase response. Reverse hyaluronan gel zymography reveals a predominant band of 120 kDa relative molecular size. Additional studies indicate that the inhibitor resembles a member of the Kunitz type inter-alpha-inhibitor family. Inhibition of hyaluronidase activity is observed using purified inter-alpha-inhibitor and is reversed by antibodies specific for inter-alpha-inhibitor. This molecule, found in the hyaluronan-rich cumulus mass surrounding mammalian ova and the pericellular coat of fibroblasts and mesothelial cells, may function to stabilize such matrices by protecting against hyaluronidase degradation. Turnover of circulating hyaluronan is extraordinarily rapid, with a half-life of two to five min. Prompt increases in levels of serum hyaluronan occur in patients with shock, septicemia or massive burns, increases that may be partly attributed to suppression by these acute phase reactants of the constant and rapid rates of hyaluronan degradation by hyaluronidase. A literature survey of other hyaluronidase inhibitors is also presented.

Urinary gonadotropin peptide as acute phase reactant: transient elevation after operation for digestive diseases.

OBJECTIVE: In order to characterize urinary gonadotropin peptide (UGP) as an acute phase reactant, we focused on the UGP levels after surgical operation. DESIGN: Fifty cases of gastrointestinal cancer, 4 cases of cancers of other organs and 13 cases of benign digestive diseases were enrolled into this study. METHODS: UGP levels were measured using an enzyme immunoassay before and after surgery. RESULTS: Fifty-four (80.6%) of the 67 cases studied showed transient elevations of UGP. Both urinary interleukin (IL)-6 and LH levels were also increased transiently in 49 cases (73.1%). All of these three factors were increased in 38 cases (56.7%), and in 32 (84.2%) of these 38 cases, the order of peak appearance was as follows: IL-6, LH, and UGP. The UGP levels in the group of total gastrectomy were significantly higher than those in the group of partial gastrectomy. CONCLUSIONS: These results suggest that UGP shows a transient peak after surgery, correlating with levels of cytokines such as IL-6. UGP may be an acute phase reactant, and its levels are correlated with the grade of surgical stress.

Effects of inflammation-associated acute-phase response on hepatic and renal indices in the horse.

OBJECTIVES: To determine the effect of an acute soft tissue inflammatory response on biochemical and haematological indices of hepatic and renal function in the Thoroughbred horse. PROCEDURE: Soft tissue inflammation was induced in four Thoroughbred horses by intramuscular injections of Freund's complete adjuvant. The horses were clinically examined and blood and urine samples were collected before and after the adjuvant injections. Biochemical and haematological indices were measured in samples collected and used to determine the onset of the acute-phase response and to assess hepatic and renal function at this time. RESULTS: After adjuvant injection, significant increases (P < 0.01) in total white (13.1 +/- 1.4 x 10(9)/L) and neutrophil (10.2 +/- 1.2 x 109/L) cell counts, rectal temperature (39.7 +/- 0.5 degrees C) and various plasma protein concentrations, including fibrinogen (6.6 +/- 1.2 g/L), haptoglobin (1.3 +/- 0.1 g/L) and total protein (88.1 +/- 2.7 g/L), indicated the induction of an acute-phase response. This corresponded with significant reductions (P < 0.01) in the plasma elimination half-lives (t1/2 beta) sodium bromosulphthalein (3.13 +/- 0.05 to 2.82 +/- 0.07 min) and sodium sulphanilate (38.29 +/- 4.04 to 19.60 +/- 5.68 min) and reductions in the plasma activities of aspartate aminotransferase, glutamate dehydrogenase, creatine kinase, alkaline phosphatase, gamma glutamyl transferase; the urinary creatinine clearance ratios of sodium, chloride and potassium; and the urinary gamma glutamyl transferase-to-creatinine clearance ratios. (All values mean +/- SD.) CONCLUSIONS: The effects of the acute-phase response on indices of hepatic and renal function in the horse suggest that the disposition of pharmacological agents administered at this time may be altered and that indices of acute inflammation should be interpreted cautiously.

Ethnic differences in correlates of microalbuminuria in NIDDM. The role of the acute-phase response.

OBJECTIVE: To investigate whether microalbuminuria is associated with markers of the acute-phase response in NIDDM and whether there are ethnic differences in this association among the three main racial groups in Malaysia. RESEARCH DESIGN AND METHODS: NIDDM patients of Chinese, Indian, and Malay origin attending a diabetic clinic in Kuala Lumpur, Malaysia, were matched for age, sex, diabetes duration, and glycemic control (n = 34 in each group). Urinary albumin-to-creatinine ratio was measured in an early morning urine sample. Biochemical measurements included markers of the acute-phase response: serum sialic acid, triglyceride, and (lowered) HDL cholesterol. RESULTS: The frequency of microalbuminuria did not differ among the Chinese, Indian, and Malay patients (44, 41, and 47%, respectively). In Chinese patients, those with microalbuminuria had evidence of an augmented acute-phase response, with higher serum sialic acid and triglyceride and lower HDL cholesterol levels; and urinary albumin-to-creatinine ratio was correlated with serum sialic acid and triglyceride. The acute-phase response markers were not different in Indians, with microalbuminuria being high in even the normoalbuminuric Indians; only the mean arterial blood pressure was correlated with urinary albumin-to-creatinine ratio in the Indians. Malay NIDDM subjects had an association of microalbuminuria with acute-phase markers, but this was weaker than in the Chinese subjects. CONCLUSIONS: Microalbuminuria is associated with an acute-phase response in Chinese NIDDM patients in Malaysia, as previously found in Caucasian NIDDM subjects. Elevated urinary albumin excretion has different correlates in other racial groups, such as those originating from the Indian subcontinent. The acute-phase response may have an etiological role in microalbuminuria.

Acute phase proteins and peritoneal dialysate albumin loss are the main determinants of serum albumin in peritoneal dialysis patients.

Hypoalbuminemia predicts mortality in dialysis patients. It has been postulated that hypoalbuminemia in the dialysis population is a consequence of poor protein intake resulting from inadequate dialysis. To establish the cause of hypoalbuminemia in a group of 27 patients on peritoneal dialysis (PD), we determined the relationship between serum albumin concentration and a group of parameters including dialysis dose delivered (Kt/V), normalized protein catabolic rate (PCRn), transperitoneal and urinary albumin losses, and the serum concentration of two acute-phase proteins, C-reactive protein (CRP), and serum amyloid A (SAA). Serum albumin concentration could be predicted by a combination of transperitoneal albumin loss and either the serum concentration of CRP or of SAA. There was no relationship between weekly Kt/V or PCRn and serum albumin concentration. CRP and SAA significantly correlated with one another, but neither correlated with transperitoneal albumin losses. Hypoalbuminemia in PD patients is a consequence of transperitoneal albumin losses and of the acute phase response.

Urinary zinc excretion and acute phase response in cancer patients.

We investigated urinary zinc and serum levels of C-reactive protein, alpha-1 acid glycoprotein, haptoglobin, transferrin and prealbumin in 55 patients with solid tumors and 20 controls. Urinary zinc, serum C-reactive protein, alpha-1 acid glycoprotein and haptoglobin were significantly higher, and serum prealbumin was significantly lower in cancer patients. A significant positive correlation between urinary zinc and C-reactive protein, alpha-1 acid glycoprotein and haptoglobin, as well as a negative correlation with transferrin and prealbumin were observed. Hyperzincuria in cancer patients appears to be linked to the acute phase response. Our data provide further evidence implicating systemic inflammatory response in increased urinary zinc excretion.

Urinary zinc excretion in patients with different disorders: the acute phase response in the kidney.

While depressed circulating zinc levels constitute a well-characterized part of the acute phase response, relatively little attention has been paid to the changes in urinary zinc excretion, although urine zinc output has been reported to be elevated in various disorders, mainly those known to be accompanied by inflammatory phenomena. In order to assess the significance of urinary zinc loss and its relationship with the acute phase response, zinc concentration was determined by atomic absorption spectrophotometry together with creatinine in urine samples of patients with different disorders. Plasma zinc, C-reactive protein, alpha-1 acid glycoprotein, haptoglobin, prealbumin, transferrin, and iron have also been determined in some patients. In accordance with the results of previous studies, we report an increase in urinary zinc, notably in solid tumors, hematologic malignancies, autoimmune rheumatic disorders, bacterial infections, diabetes mellitus and nephropathy. We also found a significant positive correlation between urinary zinc and acute phase proteins alpha-1 acid glycoprotein (rs = 0.4649, P < 0.005), haptoglobin (rs = 0.4688, P < 0.005) and C-reactive protein (rs = 0.3636, P < 0.025), as well as a negative correlation with plasma zinc (rs = 0.3640, P < 0.025). As the role of lipid peroxidation in renal tubular cell injury has been proposed, the increased urinary levels of zinc, which has antioxidant properties, may be an important protecting mechanism, representing a part of the acute phase response in the kidney.

Assessment of the clinical value of urinary trypsin inhibitory activity in elderly people.

To assess the clinical value of urinary trypsin inhibitory activity (UTIA) in elderly people, a prospective study was carried out over 4 months in our internal medicine department. Two hundred and forty-three patients of more than 60 years of age were included. A positive correlation was observed between UTIA and serum creatinine (p < 10(-3)). In the population with serum creatinine of less than 133 mumol/l (200 patients), UTIA was independent of age, sex and serum creatinine. UTIA was compared with seven serum inflammatory proteins titrated on patient admission. The principal interest of UTIA determination appeared in bacterial infections. UTIA was significantly increased in this group (p < 10(-4)). However, a positive correlation was proved only with C-reactive protein (CRP) (p = 9 x 10(-4)). Nevertheless, CRP appeared to be the best marker of bacterial infectious diseases after receiver operating characteristic curves analysis.

Automated measurement of trypsin inhibitor in urine with a centrifugal analyzer: comparison with other acute phase reactants.

Automated measurement of trypsin inhibitor in urine was performed with good precision using the COBAS FARA. Elevated levels of both trypsin inhibitor in urine and acute phase proteins in serum were shown in most cases of major abdominal surgery. We suggest that the automated assay of urinary trypsin inhibitor might be useful for the clinical diagnosis of acute phase response.

The acute-phase response of the brain-injured patient.

The acute response to injury and infection is manifested by increased synthesis of acute-phase proteins by the liver, an increased white blood cell count, fever, a negative nitrogen balance, and altered serum mineral levels (zinc, iron, and copper). This response is thought to be partially mediated by cytokines such as interleukin-1, but has not been well studied in head-injured patients. In this study, 25 patients were studied for evidence of the acute-phase response extending from hospital admission up to 21 days postinjury. The patients were divided into two groups to determine if severity of injury influenced the response. Group 1 consisted of nine patients with admission peak 24-hour Glasgow Coma Scale (GCS) scores of 4 or less; Group 2 consisted of 16 patients with admission peak 24-hour GCS scores of 8 or greater. All patients demonstrated some evidence of the acute-phase response. Serum alpha-1 acid glycoprotein, ceruloplasmin, and C-reactive protein levels were elevated on admission and throughout the study. Serum albumin and zinc levels were depressed on admission; zinc levels gradually normalized by Day 21 in both groups, but hypoalbuminemia was observed throughout the study period. Serum copper levels were normal on admission but increased to above normal in both groups by Day 11 postinjury. Urinary urea nitrogen excretion was elevated in both groups and peaked on Day 7 for Group 1 and Day 11 for Group 2 patients. The patients with admission GCS scores equal to or less than 4 had overall higher temperatures than were seen in those with GCS scores greater than or equal to 8 (p = 0.009). All patients but one had an elevated white blood cell count on admission. It is concluded that brain-injured patients with admission GCS scores of 3 to 4 and 8 to 14 demonstrate an acute-phase response which lasts for at least 3 weeks postinjury. It is speculated that this response is at least partially mediated by increased intraventricular interleukin-1 activity.