Dynamic soluble changes in sVEGFR1, HGF, and VEGF promote chemotherapy and bevacizumab resistance: A prospective translational study in the BECOX (GEMCAD 09-01) trial.

Despite initial responsiveness, acquired resistance to both bevacizumab and chemotherapy in metastatic colorectal cancer is universal. We have recently published that in vitro, chronically oxaliplatin resistance upregulates soluble vascular endothelial growth factor receptor 1, downregulates vascular endothelial growth factor, and also promotes c-MET, b-catenin/transcription factor 4, and AKT activation. We tested whether variation in three serum biomarkers such as the natural c-MET ligand (hepatocyte growth factor), soluble vascular endothelial growth factor receptor 1, and vascular endothelial growth factor-A was associated with efficacy in metastatic colorectal cancer patients treated in the prospective BECOX study. Serum levels of vascular endothelial growth factor-A165, soluble vascular endothelial growth factor receptor 1, and hepatocyte growth factor were assessed by enzyme-linked immunosorbent assay method basally and every 3 cycles (at the time of computed tomography evaluation) in a preplanned translational study in the first-line BECOX trial in metastatic colorectal cancer patients treated with CAPOX plus bevacizumab. Response was evaluated by routine contrast-enhanced computed tomography by RECIST 1.1 by investigator assessment and by three blinded independent radiologists. Ratios between soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A and hepatocyte growth factor/vascular endothelial growth factor-A were established and variations through time were related to RECIST 1.1 by investigator assessment and independent radiologist. The BECOX trial included 68 patients, and 27 patients were analyzed in the translational trial. A total of 80 RECIST 1.1 evaluations were done by investigator assessment and 56 by independent radiologist. We found that a 3.22-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by investigator assessment and a 3.06-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by independent radiologist from previous determination were associated with responses compared with 1.38-fold increase by investigator assessment and 1.59 by independent radiologist in non-responders (p = 0.0009 and p = 0.03, respectively). Responders had a 3.36-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A from previous determination by investigator assessment and 3.66-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A by independent radiologist compared with 1.43-fold increase by investigator assessment and 1.53 by independent radiologist for non-responders (p = 0.002 and 0.003, respectively). In conclusion, a decrease in vascular endothelial growth factor-A and an increase in soluble vascular endothelial growth factor receptor 1 during chemotherapy and bevacizumab exposure can contribute to both chemotherapy (due to c-MET/b-catenin activation) and bevacizumab (due to low vascular endothelial growth factor requirements) resistance. Because hepatocyte growth factor levels decrease also during acquired resistance, alternative strategies to hepatocyte growth factor-ligand inhibition should be investigated.

Variance sum rule for entropy production.

Entropy production is the hallmark of nonequilibrium physics, quantifying irreversibility, dissipation, and the efficiency of energy transduction processes. Despite many efforts, its measurement at the nanoscale remains challenging. We introduce a variance sum rule (VSR) for displacement and force variances that permits us to measure the entropy production rate σ in nonequilibrium steady states. We first illustrate it for directly measurable forces, such as an active Brownian particle in an optical trap. We then apply the VSR to flickering experiments in human red blood cells. We find that σ is spatially heterogeneous with a finite correlation length, and its average value agrees with calorimetry measurements. The VSR paves the way to derive σ using force spectroscopy and time-resolved imaging in living and active matter.

Toll-like receptor 2 is critical for induction of Reg3 beta expression and intestinal clearance of Yersinia pseudotuberculosis.

OBJECTIVE: Yersinia pseudotuberculosis causes ileitis and mesenteric lymphadenitis by mainly invading the Peyer's patches that are positioned in the terminal ileum. Whereas toll-like-receptor 2 (TLR2) controls mucosal inflammation by detecting certain microbiota-derived signals, its exact role in protecting Peyer's patches against bacterial invasion has not been defined. DESIGN: Wild-type, Tlr2-, Nod2- and MyD88-deficient animals were challenged by Y pseudotuberculosis via the oral or systemic route. The role of microbiota in conditioning Peyer's patches against Yersinia through TLR2 was assessed by delivering, ad libitum, exogenous TLR2 agonists in drinking water to germ-free and streptomycin-treated animals. Bacterial eradication from Peyer's patches was measured by using a colony-forming unit assay. Expression of cryptdins and the c-type lectin Reg3 beta was quantified by quantitative reverse transcriptase polymerase chain reaction analysis. RESULTS: Our data demonstrated that Tlr2-deficient mice failed to limit Yersinia dissemination from the Peyer's patches and succumbed to sepsis independently of nucleotide-binding and oligomerisation domain 2 (NOD2). Recognition of both microbiota-derived and myeloid differentiation factor 88 (MyD88)-mediated elicitors was found to be critically involved in gut protection against Yersinia-induced lethality, while TLR2 was dispensable to systemic Yersinia infection. Gene expression analyses revealed that optimal epithelial transcript level of the anti-infective Reg3 beta requires TLR2 activation. Consistently, Yersinia infection triggered TLR2-dependent Reg3 beta expression in Peyer's patches. Importantly, oral treatment with exogenous TLR2 agonists in germ-free animals was able to further enhance Yersinia-induced expression of Reg3 beta and to restore intestinal resistance to Yersinia. Lastly, genetic ablation of Reg3 beta resulted in impaired clearance of the bacterial load in Peyer's patches. CONCLUSIONS: TLR2/REG3 beta is thus an essential component in conditioning epithelial defence signalling pathways against bacterial invasion.

Acute pancreatitis promotes the generation of two different exosome populations.

Exosomes are small extracellular vesicles that act as intercellular messengers. Previous studies revealed that, during acute pancreatitis, circulating exosomes could reach the alveolar compartment and activate macrophages. However, proteomic analysis suggested that the most likely origin of these exosomes could be the liver instead of the pancreas. The present study aimed to characterize the exosomes released by pancreas to pancreatitis-associated ascitic fluid (PAAF) as well as those circulating in plasma in an experimental model of taurocholate-induced acute pancreatitis in rats. We provide evidence that during acute pancreatitis two different populations of exosomes are generated with relevant differences in cell distribution, protein and microRNA content as well as different implications in their physiological effects. During pancreatitis plasma exosomes, but not PAAF exosomes, are enriched in the inflammatory miR-155 and show low levels of miR-21 and miR-122. Mass spectrometry-based proteomic analysis showed that PAAF exosomes contains 10-30 fold higher loading of histones and ribosomal proteins compared to plasma exosomes. Finally, plasma exosomes have higher pro-inflammatory activity on macrophages than PAAF exosomes. These results confirm the generation of two different populations of exosomes during acute pancreatitis. Deep understanding of their specific functions will be necessary to use them as therapeutic targets at different stages of the disease.

Prognostic value of antigen expression in multiple myeloma: a PETHEMA/GEM study on 1265 patients enrolled in four consecutive clinical trials.

Persistence of minimal residual disease (MRD) after treatment for myeloma predicts inferior outcomes, but within MRD-positive patients there is great heterogeneity with both early and very late relapses. Among different MRD techniques, flow cytometry provides additional information about antigen expression on tumor cells, which could potentially contribute to stratify MRD-positive patients. We investigated the prognostic value of those antigens required to monitor MRD in 1265 newly diagnosed patients enrolled in the GEM2000, GEM2005MENOS65, GEM2005MAS65 and GEM2010MAS65 protocols. Overall, CD19pos, CD27neg, CD38lo, CD45pos, CD81pos, CD117neg and CD138lo expression predicted inferior outcomes. Through principal component analysis, we found that simultaneous CD38lowCD81posCD117neg expression emerged as the most powerful combination with independent prognostic value for progression-free survival (HR:1.69; P=0.002). This unique phenotypic profile retained prognostic value among MRD-positive patients. We then used next-generation flow to determine antigen stability throughout the course of the disease, and found that the expression of antigens required to monitor MRD is mostly stable from diagnosis to MRD stages, except for CD81 whose expression progressively increased from baseline to chemoresistant tumor cells (14 vs 28%). Altogether, we showed that the phenotypic profile of tumor cells provides additional prognostic information, and could be used to further predict risk of relapse among MRD-positive patients.

Development and psychometric validation of a brief comprehensive health status assessment scale in older patients with hematological malignancies: The GAH Scale.

OBJECTIVES: The purpose of this study was to develop a new brief, comprehensive geriatric assessment scale for older patients diagnosed with different hematological malignancies, the Geriatric Assessment in Hematology (GAH scale), and to determine its psychometric properties. MATERIALS AND METHODS: The 30-item GAH scale was designed through a multi-step process to cover 8 relevant dimensions. This is an observational study conducted in 363 patients aged≥65years, newly diagnosed with different hematological malignancies (myelodysplasic syndrome/acute myeloblastic leukemia, multiple myeloma, or chronic lymphocytic leukemia), and treatment-naïve. The scale psychometric validation process included the analyses of feasibility, floor and ceiling effect, validity and reliability criteria. RESULTS: Mean time taken to complete the GAH scale was 11.9±4.7min that improved through a learning-curve effect. Almost 90% of patients completed all items, and no floor or ceiling effects were identified. Criterion validity was supported by reasonable correlations between the GAH scale dimensions and three contrast variables (global health visual analogue scale, ECOG and Karnofsky), except for comorbidities. Factor analysis (supported by the scree plot) revealed nine factors that explained almost 60% of the total variance. Moderate internal consistency reliability was found (Cronbach's α: 0.610), and test-retest was excellent (ICC coefficients, 0.695-0.928). CONCLUSION: Our study suggests that the GAH scale is a valid, internally reliable and a consistent tool to assess health status in older patients with different hematological malignancies. Future large studies should confirm whether the GAH scale may be a tool to improve clinical decision-making in older patients with hematological malignancies.

Insulin-like growth factor binding protein-1 induces insulin release in the rat.

Injections of human insulin-like growth factor binding protein (hIGFBP-1) are reported to induce hyperglycemia in the rat, suggesting that IGFBP-1 acutely regulates glucose homeostasis. We now report the effects on glucose and insulin levels of administering recombinant (r) hIGFBP-1. In a series of studies, normal and streptozotocin (STZ) diabetic male Wistar rats (180-210 g), fasted for 6 or 16 h, were injected with rhIGFBP-1 (i.v., 80-500 microg/rat). rhIGFBP-1 did not affect blood glucose acutely but did stimulate insulin release in normal rats (5 min post injection; PBS, 103.5 +/- 8.5; rhIGFBP-1 (500 microg), 166.8 +/- 15.7; rhIGFBP-1 (100 microg); 151.4 +/- 14.1% initial). rhIGFBP-1 pretreatment, in normal and diabetic rats, reduced the hypoglycemic response to rhIGF-I (diabetic rats after 20 min: PBS, 103.4 +/- 11.4; BP-1 (500 microg) +/- rhIGF-I (50 microg), 97.6 +/- 3.6; rhIGF-I, 48.2 +/- 4.3% initial) but did not affect the hypoglycemic response to des(1-3)IGF-I or insulin (0.5 U/kg). These studies show that rhIGFBP-1 causes insulin release, has a minimal effect on blood glucose, and inhibits the hypoglycemic effect of rhIGF-I. These data suggest that endogenous IGF-I tonically suppresses insulin secretion and imply that aberrant IGFBP levels or reduced IGF-I bioactivity may lead to chronic hyperinsulinemia.

Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease.

BACKGROUND AND AIMS: Increased pancreatitis associated protein (PAP) mRNA has been reported in active inflammatory bowel disease (IBD). The aims of the current study were to characterise PAP production in IBD and the effects of PAP on inflammation. PATIENTS AND METHODS: Serum PAP levels were determined in healthy controls (n = 29), inflammatory controls (n = 14), and IBD patients (n = 171). Ex vivo PAP secretion in intestinal tissue was measured in 56 IBD patients and 13 healthy controls. Cellular origin of PAP was determined by immunohistochemistry. The effects of exogenous PAP on nuclear factor kappaB (NFkappaB) activation, proinflammatory cytokine production, and endothelial adhesion molecule expression were also analysed ex vivo. RESULTS: Patients with active IBD had increased serum PAP levels compared with controls, and these levels correlated with clinical and endoscopic disease severity. Ex vivo intestinal PAP synthesis was increased in active IBD and correlated with endoscopic and histological severity of inflammatory lesions. PAP localised to colonic Paneth cells. Incubation of mucosa from active Crohn's disease with PAP dose dependently reduced proinflammatory cytokines secretion. PAP prevented TNF-alpha induced NFkappaB activation in monocytic, epithelial, and endothelial cells and reduced proinflammatory cytokine mRNA levels and adhesion molecule expression. CONCLUSIONS: PAP is synthesised by Paneth cells and is overexpressed in colonic tissue of active IBD. PAP inhibits NFkappaB activation and downregulates cytokine production and adhesion molecule expression in inflamed tissue. It may represent an anti-inflammatory mechanism and new therapeutic strategy in IBD.

Heparin mobilizes xanthine oxidase and induces lung inflammation in acute pancreatitis.

OBJECTIVE: To evaluate the effect of low molecular weight heparin on plasma xanthine oxidase concentrations and lung inflammatory response during acute pancreatitis. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Acute pancreatitis was induced by intraductal administration of 5% sodium taurocholate. Low molecular weight heparin (0, 30, 90, or 300 units/kg) was administered immediately after induction of pancreatitis. MEASUREMENTS AND MAIN RESULTS: Lipase and xanthine oxidase plasma concentrations were measured 3 hrs after pancreatitis induction. Expression of P-selectin messenger RNA and myeloperoxidase activity as a marker of neutrophil infiltration were determined in the lung. An increase in xanthine oxidase plasma concentrations was observed during pancreatitis. Administration of heparin also increased plasma xanthine oxidase activity in both control and pancreatitis animals. Measures of xanthine oxidase present in the endothelial surface indicate that during pancreatitis, the enzyme is released from the gastrointestinal endothelium. By contrast, heparin mobilizes xanthine oxidase from almost all organs evaluated. Neutrophil infiltration was increased in the lung during pancreatitis. Heparin administration further increased, in a dose-dependent manner, myeloperoxidase activity and P-selectin expression in the lung in animals with pancreatitis. By contrast, in control animals, heparin had no effect on myeloperoxidase activity and did not induce P-selectin up-regulation. CONCLUSION: During acute pancreatitis, heparin administration might mobilize xanthine oxidase attached to endothelial cells, originating a free radical-generating system in the circulation that would trigger an inflammatory response in the lung.

[Prune-belly syndrome in a female]. / Síndrome de "prune-belly", femenino.

Authors describe a case of newborn whose malformations of genitourinary tract of abdominal muscles deficiency and renal dysplasia make it very compatible with Prune-Belly Syndrome. The case it is exceptionally interesting because it is a female subject; and on the other hand because of its' associated malformations. The so debated pathogenic of the Syndrome is commented.

[Eosinophilic cystitis]. / Cistitis eosinofílica.

We report two cases of eosinophilic cystitis in children of 11 months and 11 and a half year of age respectively. The presenting symptoms were the emision of mucosanguinolent filaments in the urine in one case and with lower urinary tract symptoms and macroscopic hematuria in the other. Physical examination revealed in one of them a round, tough and painful mass in the hypogastric area. In one case we found peripheral blood eosinophilia. They both showed in the Urinalysis albuminuria, pyuria and hematuria, with the presence of eosinophils in one of them. Macroscopic examination presented in the two cases a tumoral, mamelonne mass in the wall of the bladded. The diagnosis was anatomopathologic due to the demonstration of an inflammatory infiltration, primarily of eosinophils. The clinical course was unfavourable in the case an hemicystectomy was practicated and self-limited in the one only symptomatic treatment was used.

VCAM-1, but not ICAM-1 or MAdCAM-1, immunoblockade ameliorates DSS-induced colitis in mice.

Adhesion molecule immunoneutralization is envisioned as a promising therapy for inflammatory bowel disease, but the relative value of selective blockade of different adhesion molecules has not been established. The aims of this study were to measure expression and functional relevance of endothelial intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in leukocyte recruitment in experimental colitis and to compare the therapeutic effectiveness of their selective blockade. For this purpose, cell adhesion molecule expression was measured by the dual radiolabeled antibody technique in mice with dextran sulfate sodium-induced colitis and controls. Leukocyte-endothelial cell interactions were determined in colonic venules by fluorescence intravital microscopy. Therapeutic effects of chronic treatment with anti-ICAM-1, anti-VCAM-1, or anti-MAdCAM-1 antibodies were also assessed. Whereas colonic endothelial ICAM-1 was constitutively expressed and had a mild up-regulation in colitic animals, constitutive expression of VCAM-1 and MAdCAM-1 was low, but markedly increased after induction of colitis. Leukocyte adhesion was abrogated by immunoneutralization of VCAM-1 or MAdCAM-1 but not by treatment with an anti-ICAM-1 antibody. Chronic administration of anti-VCAM-1 antibody, but not anti-ICAM-1 or anti-MAdCAM-1, resulted in significant attenuation of colitis in terms of disease activity index, colon length, ratio of colon weight to length, and myeloperoxidase activity. In conclusion, VCAM-1 plays a central role in leukocyte recruitment in colitis and blockade of this adhesion molecule has higher therapeutic effect than immunoneutralization of ICAM-1 or MAdCAM-1 in this experimental model.

Role of P-selectin in radiation-induced intestinal inflammatory damage.

The aims of our study were to characterize the dose- and time-dependent changes in endothelial P-selectin expression and the role of this adhesion molecule as a mediator of radiation-induced inflammation. For that purpose, endothelial P-selectin expression was measured by the radiolabeled antibody technique in control and irradiated mice at 2, 6, and 24 hr following abdominal irradiation with 4 or 10 Gy; leukocyte endothelial cell interactions were assessed using intravital microscopy in intestinal venules following irradiation at the aforementioned doses and times in C57BL/6 and P-selectin-deficient mice. In wild-type mice, radiation induced a time- and dose-dependent up-regulation of P-selectin and a significant increase in the flux of rolling leukocytes 2 hr after irradiation. Irradiation induced a significant increase in leukocyte adhesion that was dose-dependent. Following irradiation, P-selectin-deficient mice did not show any increase in leukocyte rolling but did demonstrate a response in leukocyte adhesion similar to that of the wild-type mice. Radiation-induced dose-dependent histological inflammatory damage that did not differ between P-selectin-deficient and wild-type mice. We conclude that P-selectin is up-regulated following irradiation and is a key molecular determinant of leukocyte rolling but not leukocyte adhesion in this inflammatory condition. Therefore, isolated neutralization of this adhesion molecule is not an effective means for preventing radiation-induced inflammation.

Differential role of selectins in experimental colitis.

BACKGROUND AND AIMS: The role of selectins in experimental colitis remains unknown. The aims of this study were to characterize the time-course expression of selectins in trinitrobenzene sulfonic acid (TNBS)-induced colitis, the functional role of selectins in colonic leukocyte-endothelial cell interactions, and the therapeutic usefulness of selectin blockade in this model. METHODS: Control and TNBS-induced colitic rats were studied. Expression of P- and E-selectin was assessed by the radiolabeled antibody technique, and L-selectin by flow cytometry. Leukocyte-endothelial cell interactions were studied in colonic venules by using intravital microscopy under basal conditions and after P-, E-, or L-selectin immunoblockade. Additional groups of animals were treated with anti-P-selectin antibody, a nonbinding antibody, or dexamethasone, for 7 days. RESULTS: P-selectin and E-selectin expression were markedly up-regulated in colitic rats. Increased leukocyte rolling was abrogated by anti-P-selectin, but only attenuated by anti-E- or anti-L-selectin antibodies. Only pretreatment with anti-P- selectin decreased leukocyte adhesion. Animals chronically treated with dexamethasone, but not with anti- P-selectin, had significantly lower macroscopic and histologic damage scores, colon weight, and myeloperoxidase (MPO) activity than those treated with nonbinding antibody. CONCLUSIONS: P-selectin plays a key role on leukocyte rolling and its blockade attenuates leukocyte adhesion in TNBS-induced colitis. However, treatment with an anti-P-selectin antibody does not significantly improve colitis.

[Chronic renal insufficiency secondary to infectious mononucleosis]. / Insuficiencia renal crónica secundaria a mononucleosis infecciosa.

This report describes the first pediatric case of chronic renal failure as a complication of infectious mononucleosis in a 3 1/2 year old girl. The clinical features were marked at onset by proteinuria and later by nephrotic syndrome. The evolution to chronic renal failure took about two years. In the renal biopsy, lesions characteristic of interstitial nephritis were observed, associated with focal and segmental glomeruloesclerosis and deposits of C3 in granular and discontinued form. Renal participation in infectious mononucleosis is not unusual and fundamentally it is manifested by proteinuria and abnormalities of urinary sediment, with interstitial nephritis as a characteristic lesion in the renal biopsy.

P-selectin upregulation in bleomycin induced lung injury in rats: effect of N-acetyl-L-cysteine.

BACKGROUND: A number of adhesion molecules are involved in the process of neutrophil infiltration into the lung. P-selectin is one of these neutrophil-endothelial cell adhesion molecules. A study was undertaken to examine the involvement of P-selectin in the development of bleomycin induced inflammation and the ability of N-acetyl-L-cysteine to reduce the potential expression of this selectin in rats. METHODS: N-acetyl-L-cysteine (3 mmol/kg po) was administered daily for seven days prior to bleomycin administration (2.5 U/kg). The kinetics of P-selectin expression and the effect of N-acetyl-L-cysteine after bleomycin treatment were measured using radiolabelled antibodies. P-selectin localisation was evaluated by immunohistochemistry and neutrophil infiltration was assessed by myeloperoxidase activity. RESULTS: Bleomycin administration resulted in an upregulation of P-selectin at 1 hour, returning to baseline at 3 hours. Myeloperoxidase activity showed a significant increase at 6 hours after bleomycin administration that lasted for 3 days. N-acetyl-L-cysteine treatment completely prevented these increases. CONCLUSION: Upregulation of P-selectin in the lung is associated with neutrophil recruitment in response to bleomycin. The beneficial effect of N-acetyl-L-cysteine on bleomycin induced lung injury may be explained in part by the prevention of neutrophil recruitment in the inflammatory stage of the disease.

[Xanthine lithiasis in a case of Lesch-Nyhan syndrome treated with allopurinol]. / Litiasis xantínica en un caso de síndrome de Lesch-Nyham tratado con allopurinol.

Classically it is considered that vital prognosis of Lesch-Nyhan syndrome depends on renal affectation secondary to uric nephropathy. A case of Lesch-Nyhan syndrome treated with Allopurinol is described which presented multiple and bilateral renal stones by precipitation of xanthine. Treatment with Allopurinol inhibits the formation of uric acid and qualitatively renal excretion of oxypurines modifies. In special circumstances (disminution of urinary output and pH), they can precipitate and originate a radiotransparent lithiasis with uric lithiasis. Interest of this case, lies in being alert to possible xanthine stone formation in patients with a large excretion of purinics metabolites, who are treated with Allopurinol.

[Ambulatory monitoring of arterial pressure in a group of children with reflux nephropathy of different degrees]. / Monitorización ambulatoria de la presión arterial en un grupo de niños con nefropatía por reflujo de diferente grado.

OBJECTIVE: The purpose of this study was to search for risk factors for the evolution reflux nephropathy by comparing the results of the ambulatory blood pressures in a group of children with reflux nephropathy of different degrees. PATIENTS AND METHODS: Out-patient blood pressure monitoring was performed in 31 children (15 males and 15 females) affected to different degrees by reflux nephropathy. This was done during a 24-hour period on a normal schoolday by using a Spacelabs 90207 oscilometric monitor. An appropriately sized armband was chosen for each case with the readings being programmed for every 20 minutes between 8:00 a.m. and 23:00 p.m. and every 30 minutes for the remaining readings. The mean blood pressure, blood pressure load and hyperbaric index over the 24 hour period (on all the readings obtained), activity period (0800 to 2200 hours) and the resting period (midnight to 6:00 a.m.) were calculated. The circadian variability (difference and ratio between the mean values of active and resting periods and the nocturnal fall in blood pressure as a percentage of the daytime mean value) was also determined. The children were classified into subgroups according to their degree of reflux nephropathy: Group 1) Degrees A and B of unilateral reflux nephropathy. Group 2) Degrees C and D of unilateral reflux nephropathy and Group 3) Bilateral nephropathy. Those monitorings with a percentage of erroneous readings over 30% were excluded. RESULTS: Two children were excluded because of a high percentage of erroneous readings. We could not find any significant difference among the three groups in casual blood pressure. We observed significant differences between the group formed by children with unilateral reflux nephropathy and children with bilateral reflux nephropathy in the blood pressure during the resting period. No significant differences were found among the three groups in the tensional load, hyperbaric index or the variables that determine the nightly descent in blood pressure. CONCLUSIONS: Ambulatory blood pressure monitoring allow the detection of risk factors for the evolution of reflux nephropathy; i.e., higher risk of blood pressure elevation, especially during the resting period and mainly for bilateral reflux nephropathy.