Is arterial calcification in children and adolescents with end-stage renal disease a rare finding?

AIM: To investigate if calcification and intimal media thickness (IMT) of arteries are present in children and adolescents with end-stage renal disease and to describe the risk factors associated with these alterations. METHODS: In an observational, cross-sectional prospective study, 68 patients were evaluated at the time of renal transplantation. A fragment of the inferior epigastric artery was removed during surgery for histopathological analysis to verify the presence or not of arterial calcification. Two outcomes were considered: the presence of calcium deposition and the measurement of the IMT of the artery. The potential exposure variables were: age, chronic kidney disease aetiology, diagnosis time, systolic blood pressure (SBP), use of oral active vitamin D, homocysteine and C-reactive protein. RESULTS: No arterial calcification was observed in the studied sample. The median value of the IMT of the inferior epigastric artery was 166 µm (interquartile range = 130-208). SBP standard deviation score and age were the only factors associated with this outcome. There was no statistical interaction between SBP and age with the IMT (P = 0.280). CONCLUSION: Arterial calcification is rare in children and adolescents with end-stage renal disease. The factors associated with IMT were age and SBP.

Expression of cytokines and chemokines and microvasculature alterations of the tongue from patients with chronic Chagas' disease.

Chagas' disease is caused by the protozoan Trypanosoma cruzi and continues to be a significant public health problem, since 10 million people are still infected in Latin America. The purpose of this study was to analyze the microvasculature alterations as well the expression of cytokines and chemokines in the tongues from patients with chronic Chagas' disease (CC; n = 18), comparatively with a non-chagasic group (NC; n = 22). We observed several vascular alterations in the tongue of CC such as a greater vascular diameter, increased vascular wall area, high density of the blood vessels, and increased thickening of the capillary basement membrane. The expression of cytokines interferon gamma and tumor necrosis factor alpha and chemokine macrophage inflammatory protein 1alpha were significantly down-regulated in the tongue of CC group. These results demonstrated that, in the tongue of chagasic patients, a microvascular abnormality and immunological impairment occurs, probably due to chronic inflammation evoked by T. cruzi antigens.

A role for regulatory T cells in renal acute kidney injury.

Ischemia reperfusion injury (IRI) is a potential contributor for the development of chronic allograft nephropathy. T cells are important mediators of injury, even in the absence of alloantigens. We performed a depletion of TCD4(+)CTLA4(+)Foxp3(+) cells with anti-CD25(PC61), a treatment with anti-GITR (DTA-1) and rat-IgG, followed by 45 min of ischemia and 24/72 h of reperfusion, and then analyzed blood urea, kidney histopathology and gene expression in kidneys by QReal Time PCR. After 24 h of reperfusion, depletion of TCD4(+)CTLA4(+)Foxp3(+) cells reached 30.3%(spleen) and 67.8%(lymph nodes). 72 h after reperfusion depletion reached 43.1%(spleen) and 90.22%(lymph nodes) and depleted animals presented with significantly poorer renal function, while DTA-1(anti-GITR)-treated ones showed a significant protection, all compared to serum urea from control group (IgG: 150.10+/-50.04; PC61: 187.23+/-31.38; DTA-1: 64.53+/-25.65, mg/dL, p<0.05). These data were corroborated by histopathology. We observed an increase of HO-1 expression in animals treated with DTA-1 at 72 h of reperfusion with significant differences. Thus, our results suggest that PC61(anti-CD25) mAb treatment is deleterious, while DTA-1(anti-GITR) mAb treatment presents a protective role in the renal IRI, indicating that some regulatory populations of T cells might have a role in IRI.

Critical involvement of Th1-related cytokines in renal injuries induced by ischemia and reperfusion.

Renal ischemia and reperfusion injury (IRI) is considered an inflammatory syndrome. To move forward in its pathogenesis, we exploited the role of several cytokines on renal damages triggered by IRI. Specifically to evaluate the role of Th1 immune profile in this system, IL-12, IFN-gamma, and IFN-gamma/IL-12 deficient (KO) mice on C57BL/6 background and their controls were subjected to IRI. In each group, blood and kidney samples were harvested. Renal function was evaluated by serum creatinine and renal morphometric analyses. Gene expression of IL-6 and HO-1 were also investigated by Q-PCR. IFN-gamma KO animals presented the highest impairment in renal function compared to controls. Conversely, IL-12 KO animals were absolutely protected and, in a lesser extent, IFN-gamma/IL-12 KO double knockout was also protected from IRI. Gene expression analyses showed higher expression of HO-1, a cytoprotective gene, and IL-6, a pro-inflammatory cytokine, in IFN-gamma deficient animals subjected to IRI. Our results confirm that Th1 related cytokines such as IL-12 and IFN-gamma are critically involved in renal ischemia and reperfusion injury.

Inhibition of COX 1 and 2 prior to renal ischemia/reperfusion injury decreases the development of fibrosis.

Ischemia and reperfusion injury (IRI) contributes to the development of chronic interstitial fibrosis/tubular atrophy in renal allograft patients. Cyclooxygenase (COX) 1 and 2 actively participate in acute ischemic injury by activating endothelial cells and inducing oxidative stress. Furthermore, blockade of COX 1 and 2 has been associated with organ improvement after ischemic damage. The aim of this study was to evaluate the role of COX 1 and 2 in the development of fibrosis by performing a COX 1 and 2 blockade immediately before IRI. We subjected C57Bl/6 male mice to 60 min of unilateral renal pedicle occlusion. Prior to surgery mice were either treated with indomethacin (IMT) at days -1 and 0 or were untreated. Blood and kidney samples were collected 6 wks after IRI. Kidney samples were analyzed by real-time reverse transcription-polymerase chain reaction for expression of transforming growth factor beta (TGF-beta), monocyte chemoattractant protein 1 (MCP-1), osteopontin (OPN), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1 beta, IL-10, heme oxygenase 1 (HO-1), vimentin, connective-tissue growth factor (CTGF), collagen I, and bone morphogenic protein 7 (BMP-7). To assess tissue fibrosis we performed morphometric analyses and Sirius red staining. We also performed immunohistochemical analysis of anti-actin smooth muscle. Renal function did not significantly differ between groups. Animals pretreated with IMT showed significantly less interstitial fibrosis than nontreated animals. Gene transcript analyses showed decreased expression of TGF-beta, MCP-1, TNF-alpha, IL-1-beta, vimentin, collagen I, CTGF, and IL-10 mRNA (all P < 0.05). Moreover, HO-1 mRNA was increased in animals pretreated with IMT (P < 0.05). Conversely, IMT treatment decreased osteopontin expression and enhanced BMP-7 expression, although these levels did not reach statistical significance when compared with control expression levels. The blockade of COX 1 and 2 resulted in less tissue fibrosis, which was associated with a decrease in proinflammatory cytokines and enhancement of the protective cellular response.

[Developmental characteristics of Cysticercus cellulosae in the human brain and heart]. / Características evolutivas do Cysticercus cellulosae no encéfalo e no coração humanos.

The present study aimed to evaluate the prevalence of cysticercosis, to classify the developmental phases of cysticerci found in human brains and hearts, and differentiate these according to the macro and microscopic aspects of the general pathological processes, and to compare the process found in the brains and hearts. Protocols from autopsies performed at the Hospital of the School of Medicine of the Triângulo Mineiro, Uberaba, MG, Brazil, in the period from 1970 to 2000 were reviewed. The prevalence of cysticercosis was verified in 71 cases, of which 53 (74.6%) were encephalic cysticercosis and 18 (25.3%) cardiac cysticercosis. Nineteen cysticerci were analyzed, from 9 brains and 10 hearts. The cysticerci were classified according to their developmental stage: vesicular, colloidal vesicular, granular nodular and calcified nodular, with similarities between the macroscopic and microscopic diagnoses. Among the pathological processes found beta-fibrilosis and endocardial fibroelastosis are underscored. In addition, it was demonstrated that this classification may be applied both to encephalic and cardiac cysticercosis.