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BACKGROUND: Current techniques used to obtain lung samples have significant limitations and do not provide reproducible biomarkers of inflammation. We have developed a novel technique that allows multiple sampling methods from the same area (or multiple areas) of the lung under direct bronchoscopic vision. It allows collection of mucosal lining fluid and bronchial brushing from the same site; biopsy samples may also be taken. The novel technique takes the same time as standard procedures and can be conducted safely. METHODS: Eight healthy smokers aged 40-65 years were included in this study. An absorptive filter paper was applied to the bronchial mucosa under direct vision using standard bronchoscopic techniques. Further samples were obtained from the same site using bronchial brushings. Bronchoalveolar lavage (BAL) was obtained using standard techniques. Chemokine (C-C Motif) Ligand 20 (CCL20), CCL4, CCL5, Chemokine (C-X-C Motif) Ligand 1 (CXCL1), CXCL8, CXCL9, CXCL10, CXCL11, Interleukin 1 beta (IL-1ß), IL-6, Vascular endothelial growth factor (VEGF), Matrix metalloproteinase 8 (MMP-8) and MMP-9 were measured in exudate and BAL. mRNA was collected from the bronchial brushings for gene expression analysis. RESULTS: A greater than 10 fold concentration of all the biomarkers was detected in lung exudate in comparison to BAL. High yield of good quality RNA with RNA integrity numbers (RIN) between 7.6 and 9.3 were extracted from the bronchial brushings. The subset of genes measured were reproducible across the samples and corresponded to the inflammatory markers measured in exudate and BAL. CONCLUSIONS: The bronchoabsorption technique as described offers the ability to sample lung fluid direct from the site of interest without the dilution effects caused by BAL. Using this method we were able to successfully measure the concentrations of biomarkers present in the lungs as well as collect high yield mRNA samples for gene expression analysis from the same site. This technique demonstrates superior sensitivity to standard BAL for the measurement of biomarkers of inflammation. It could replace BAL as the method of choice for these measurements. This method provides a systems biology approach to studying the inflammatory markers of respiratory disease progression. TRIAL REGISTRATION: NHS Health Research Authority (13/LO/0256).
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Broncoscopia/métodos , Mediadores da Inflamação/análise , Pulmão/patologia , Pneumonia/patologia , Fumar/efeitos adversos , Fumar/patologia , Manejo de Espécimes/métodos , Absorção Fisico-Química , Adulto , Idoso , Biomarcadores/análise , Líquido da Lavagem Broncoalveolar/química , Broncoscopia/instrumentação , Feminino , Perfilação da Expressão Gênica , Humanos , Pulmão/química , Masculino , Pessoa de Meia-Idade , Papel , Pneumonia/genética , Pneumonia/metabolismo , RNA Mensageiro/análise , Fumar/genética , Fumar/metabolismo , Manejo de Espécimes/instrumentaçãoRESUMO
BACKGROUND: SH2-containing inositol-5'-phosphatase 1 (SHIP1) is an endogenous inhibitor of the phosphoinositide-3-kinase pathway that is involved in the activation and chemotaxis of inflammatory cells. AQX-1125 is a first-in-class, oral SHIP1 activator with a novel anti-inflammatory mode of action. OBJECTIVE: To evaluate the effects of AQX-1125 on airway responses to allergen challenge in mild-to-moderate asthmatic patients. METHODS: A randomized, double-blind, placebo-controlled, two-way crossover study was performed in 22 steroid-naïve mild-to-moderate asthmatics with a documented late-phase response to inhaled allergen (LAR). AQX-1125 (450 mg daily) or placebo was administered orally for 7 days. Allergen challenge was performed on day 6 (2 h postdose), followed by methacholine challenge (day 7), and induced sputum collection and fractional exhaled nitric oxide (FeNO). RESULTS: AQX-1125 significantly attenuated the late-phase response compared with placebo (FEV1 4-10 h: mean difference 150 mL, 20%; P = 0.027) and significantly increased the minimum FEV1 during LAR (mean difference 180 mL; P = 0.014). AQX-1125 had no effect on the early-phase response. AQX-1125 showed a trend in reduction of sputum eosinophils, neutrophils and macrophages although this did not achieve significance as there were only 11 paired samples for analysis. There was no effect on methacholine responsiveness or FeNO. Pharmacokinetic data showed AQX-1125 was rapidly absorbed with geometric mean Cmax and AUC0-24 h values of 1417 ng/mL and 16 727 h ng/mL, respectively. AQX-1125 was well tolerated, but mild GI side-effects (dyspepsia, nausea and abdominal pain) were described in 4/22 subjects on active treatment. These side-effects were mild self-limiting, required no further treatment and did not lead to discontinuation of therapy. CONCLUSION AND CLINICAL RELEVANCE: AQX-1125, a novel oral SHIP1 activator, significantly reduces the late response to allergen challenge, with a trend to reduce airway inflammation. AQX-1125 was safe and well tolerated and merits further investigation in inflammatory disorders.
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Alérgenos/imunologia , Asma/tratamento farmacológico , Asma/imunologia , Cicloexanóis/farmacologia , Cicloexanóis/uso terapêutico , Indanos/farmacologia , Indanos/uso terapêutico , Adulto , Alérgenos/administração & dosagem , Análise de Variância , Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Asma/diagnóstico , Asma/metabolismo , Testes de Provocação Brônquica , Estudos Cross-Over , Expiração , Feminino , Volume Expiratório Forçado , Humanos , Inositol Polifosfato 5-Fosfatases , Masculino , Óxido Nítrico/metabolismo , Fosfatidilinositol-3,4,5-Trifosfato 5-Fosfatases , Fosfatidilinositóis/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Fatores de Risco , Índice de Gravidade de Doença , Transdução de Sinais , Escarro , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: CRTH2 is a G-protein-coupled receptor on T helper2 cells that mediates pro-inflammatory effects of prostaglandin D2 in allergic responses. OBJECTIVE: To investigate the tolerability and pharmacokinetics of setipiprant (ACT-129968), a selective orally active CRTH2 antagonist, in allergic asthmatics and to assess the protective effects of multiple doses of this drug against allergen-induced airway responses. METHODS: In this 3-centre, double-blinded, placebo-controlled, cross-over study, 18 allergic asthmatic males were randomized to setipiprant 1000 mg or matching placebo b.i.d. for 5 consecutive days. Study periods were separated by a washout of ≥ 3 weeks. On study day 4, subjects underwent a standardized allergen challenge and airway response was recorded by FEV1 until 10 h post-allergen. Airway responsiveness to methacholine and exhaled nitric oxide (eNO) were measured pre- and post-dosing. The effects of both treatments on the allergen-induced airway responses were compared by a paired Student's t-test. RESULTS: Fifteen subjects completed the study per-protocol and were included in the analysis. Overall, setipiprant was well tolerated and no clinically relevant adverse events occurred. Trough plasma concentrations showed a high inter-subject variability. Compared with placebo, setipiprant significantly reduced the allergen-induced late asthmatic response (LAR), inhibiting the area under the response vs. time curve (AUC(3-10 h) ) by on average 25.6% (P = 0.006) and significantly protected against the allergen-induced airway hyperresponsiveness (AHR) to methacholine (P = 0.0029). There was no difference in the early asthmatic response (EAR) or in allergen-induced changes in eNO between treatments. CONCLUSION AND CLINICAL RELEVANCE: Setipiprant at multiple oral doses was well tolerated and reduced both the allergen-induced LAR and the associated AHR in allergic asthmatics. Our findings confirm that CRTH2 may be a promising target for the treatment of allergic disorders.
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Alérgenos/imunologia , Asma/tratamento farmacológico , Asma/imunologia , Indóis/farmacologia , Indóis/uso terapêutico , Naftalenos/farmacologia , Naftalenos/uso terapêutico , Receptores Imunológicos/antagonistas & inibidores , Receptores de Prostaglandina/antagonistas & inibidores , Adulto , Antiasmáticos/farmacologia , Antiasmáticos/uso terapêutico , Asma/diagnóstico , Testes de Provocação Brônquica , Expiração , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Testes de Função Respiratória , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Constipation, diminished gut blood flow, ischaemic colitis and drug therapy may be associated. AIM: To study the effect of constipating medication on, and the regulation of, gut blood flow. METHODS: 24 healthy females (mean age 30) received, in a double-blind, three-way crossover study: (i) placebo, (ii) ipratropium 40 microg by inhalation (positive control known to reduce rectal mucosal blood flow) and (iii) oral loperamide 4 mg. Mucosal blood flow was measured at the splenic flexure and rectum using laser Doppler flowmetry. Blood flow in the superior and inferior mesenteric arteries was measured by trans-abdominal Doppler ultrasound. RESULTS: Ipratropium decreased rectal mucosal blood flow by 16% (P=0.009) and splenic flexure mucosal blood flow by 8% (P=0.075). Loperamide caused no change in rectal (P=0.40) or splenic flexure mucosal blood flow (P=0.73). Neither treatment changed superior or inferior mesenteric artery blood flow. Splenic flexure mucosal blood flow showed a positive correlation with rectal mucosal blood flow (r=0.69; P<0.0001). CONCLUSIONS: Vasoactive agents may reduce gut mucosal blood flow in the absence of reduced large vessel flow. Constipating drugs do not necessarily reduce gut blood flow. Rectal mucosal blood flow correlates with splenic flexure mucosal flow, and potentially may be used as a more convenient surrogate for studying splenic flexure blood flow.
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Colo Transverso/irrigação sanguínea , Ipratrópio/farmacologia , Loperamida/farmacologia , Reto/irrigação sanguínea , Circulação Esplâncnica/efeitos dos fármacos , Administração por Inalação , Administração Oral , Adulto , Constipação Intestinal/tratamento farmacológico , Estudos Cross-Over , Método Duplo-Cego , Feminino , Humanos , Mucosa Intestinal/irrigação sanguínea , Fluxometria por Laser-Doppler , Artéria Mesentérica Inferior/efeitos dos fármacos , Artéria Mesentérica Superior/efeitos dos fármacos , Pessoa de Meia-Idade , Fluxo Sanguíneo RegionalRESUMO
Non-invasive mucosal sampling (nasosorption and nasal curettage) was used following nasal allergen challenge with grass pollen in subjects with allergic rhinitis, in order to define the molecular basis of the late allergic reaction (LAR). It was found that the nasal LAR to grass pollen involves parallel changes in pathways of type 2 inflammation (IL-4, IL-5 and IL-13), inflammasome-related (IL-1ß), and complement and circadian-associated genes. A grass pollen nasal spray was given to subjects with hay fever followed by serial sampling, in which cytokines and chemokines were measured in absorbed nasal mucosal lining fluid, and global gene expression (transcriptomics) assessed in nasal mucosal curettage samples. Twelve of 19 subjects responded with elevations in interleukin (IL)-5, IL-13, IL-1ß and MIP-1ß/CCL4 protein levels in the late phase. In addition, in these individuals whole-genome expression profiling showed upregulation of type 2 inflammation involving eosinophils and IL-4, IL-5 and IL-13; neutrophil recruitment with IL-1α and IL-1ß; the alternative pathway of complement (factor P and C5aR); and prominent effects on circadian-associated transcription regulators. Baseline IL-33 mRNA strongly correlated with these late-phase responses, whereas a single oral dose of prednisone dose-dependently reversed most nasal allergen challenge-induced cytokine and transcript responses. This study shows that the LAR to grass pollen involves a range of inflammatory pathways and suggests potential new biomarkers and therapeutic targets. Furthermore, the marked variation in mucosal inflammatory events between different patients suggests that in the future precision mucosal sampling may enable rational specific therapy.
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Proteínas do Sistema Complemento/metabolismo , Hipersensibilidade/imunologia , Inflamassomos/metabolismo , Mucosa Nasal/imunologia , Células Th2/imunologia , Adulto , Alérgenos/imunologia , Antígenos de Plantas/imunologia , Feminino , Humanos , Hipersensibilidade/dietoterapia , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade Tardia , Interleucina-13/metabolismo , Interleucina-1beta/metabolismo , Interleucina-5/metabolismo , Masculino , Pessoa de Meia-Idade , Poaceae/imunologia , Pólen/imunologia , Prednisona/uso terapêutico , Adulto JovemRESUMO
INTRODUCTION: Janus kinases (JAKs) regulate inflammatory gene expression through phosphorylation of signal transducer and activator of transcription (STAT) proteins. Expression of STAT proteins is increased in chronic obstructive pulmonary disease (COPD), and may be involved in driving chronic inflammation. Oral JAK inhibitors are effective as anti-inflammatory therapy but exhibit dose-limiting adverse effects. Development of inhaled compounds would be enhanced by robust biomarkers that directly reflect the anti-inflammatory and pharmacological activity in the lung. METHODS: A novel flow cytometry assay was developed to measure STAT1 phosphorylation in sputum inflammatory cells. The standard sputum processing method was refined to improve sputum cell viability. The flow cytometric assay was used to assess the reproducibility of the measurement of STAT1 phosphorylation and the in vitro activity of a pan JAK-inhibitor on three separate visits in patients with COPD. RESULTS: Upregulation of STAT1 phosphorylation was measured following in vitro IFNγ stimulation of sputum macrophages (stimulated/unstimulated ratio 1.57; p<0.00001). Upregulation was inhibited following in vitro preincubation with a pan JAK-inhibitor (inhibited+stimulated/unstimulated ratio 0.97). STAT1 phosphorylation activity could only be measured in macrophages. CONCLUSIONS: Sputum from patients with COPD can be used to reproducibly measure phospho-STAT expression in sputum macrophages. The flow cytometry-based method can be used to evaluate kinase inhibitors in vitro and subsequently in ex vivo studies. The assay is particularly useful for the assessment of inhaled compounds where whole blood assays may not be relevant.
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Fifteen patients with the loin pain and haematuria syndrome (LPH) were compared with 10 patients with complicated renal stone disease referred to the same tertiary centre and matched for age, sex and duration of illness. LPH patients had a history of three times more medically unexplained somatic symptoms other than loin pain (p < 0.01) and a higher proportion took analgesics regularly (p < 0.01). The onset of pain was associated with an adverse psychologically important life-event in eight of the LPH patients but in none of the controls (p < 0.02). LPH patients more frequently recalled serious parental illness and disability in childhood (p < 0.001) than controls, and a higher proportion felt responsible for causing or alleviating parental illness or distress (p < 0.05). LPH subjects scored higher in the 'paternal care' dimension of the Parental Bonding Instrument (p < 0.05). No difference was found between LPH patients and controls in terms of current depression and anxiety but both groups exhibited high rates of lifetime depression. LPH patients expressed lower levels of anger and hostility (p < 0.002) than did controls. Our observations suggest that psychological factors are of major importance in the aetiology of LPH, which may represent a type of somatoform pain disorder.
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Dor nas Costas/psicologia , Hematúria/psicologia , Transtornos Somatoformes/psicologia , Adulto , Ansiedade , Depressão , Relações Pai-Filho , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Pessoa de Meia-Idade , Relações Mãe-Filho , Estresse PsicológicoRESUMO
We examined the occurrence of crystals and casts in the urine of healthy subjects after administration of triamterene and the site of crystal formation in experimental animals. Twenty out of twenty healthy subjects had abundant triamterene crystals and casts in acid urine after receiving a single 100 mg dose. Casts were present in the urine from 2-11 hours after administration of the diuretic. Cast formation occurred in acidic urine and was prevented by alkalinization of the urine with potassium citrate. Animal studies showed that crystallization and cast formation occurred in the medullary and papillary collecting ducts of the rat kidney. These findings provide a possible explanation for the reported nephrotoxicity of triamterene, particularly when given to patients who are receiving non-steroidal anti-inflammatory agents.
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Rim/efeitos dos fármacos , Triantereno/efeitos adversos , Urina/efeitos dos fármacos , Adulto , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Cristalização , Interações Medicamentosas , Feminino , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Ratos , Triantereno/administração & dosagem , Triantereno/urinaRESUMO
We report our experience of intensive plasma exchange (PE) in the treatment of 12 females with severe diffuse proliferative lupus nephritis. All had active disease with crescentic lesions demonstrated on biopsy immediately before PE. Nine patients were also treated with high dose steroids, three patients with low dose steroids and most patients also received cytotoxic therapy. Eight of the 12 patients were biopsied immediately after a course of PE. All but one patient (low dose steroid group) showed considerable diminution of histologic activity with resolution of crescentic lesions. Plasma exchange may accelerate such resolution over conventional therapy, prevent subsequent sclerosis and preserve functional renal tissue.
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Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Nefrite/terapia , Troca Plasmática , Adolescente , Adulto , Biópsia , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Rim/patologia , Metilprednisolona/uso terapêutico , Nefrite/etiologia , Nefrite/patologia , Prednisolona/uso terapêuticoRESUMO
The accuracy of reagent strip testing for urinary tract infection (UTI) was assessed in 100 elderly patients (50 acute patients admitted to hospital and 50 attending the day hospital). Reagent strip sensitivities were: acute patients-urinary nitrite 83%, blood 67%, protein 72% and leucocytes 72%, and day hospital patients-urinary nitrite 90%, blood 65%, protein 30% and leucocytes 60%. Urinary nitrite specificities were 100% for both groups of patients. Only 28% of patients with a UTI had specific symptoms of the infection; pyrexia and a raised WBC also proved poor indicators. Urinary nitrite was thus the most accurate immediate indicator of UTI.
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Kit de Reagentes para Diagnóstico/normas , Infecções Urinárias/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Bacteriúria/diagnóstico , Feminino , Hematúria/diagnóstico , Humanos , Masculino , Nitritos/urina , Proteinúria/diagnóstico , Sensibilidade e Especificidade , Infecções Urinárias/urinaRESUMO
BACKGROUND: beta-Tryptase is a multifunctional mast cell serine protease released during mast cell degranulation and tryptase/trypsin inhibitors are a novel potential therapeutic approach for allergic inflammatory diseases. OBJECTIVES: This study was performed to assess the effects of RWJ-58643 on nasal symptoms, eosinophil influx, and cytokine and chemokine release following nasal allergen challenge (NAC). METHODS: Male patients with grass pollen allergic rhinitis (n=16) out of season received single doses of RWJ-58643 (100, 300, 600 microg) or matched placebo given 30 min before NAC in a double-blind, randomized crossover design. A single dose of 200 microg budesonide was studied in an open-label extension phase. NAC was performed with Timothy grass pollen (ALK) via a nasal device, and nasal lavage was performed at times 0 (pre-drug, pre-allergen), 0.5 (30 min post-drug, pre-NAC) 1.5, 2.5, 4.5, 6.5, 8.5, and 24 h after drug administration. Nasal lavage mediators were analysed using a sensitive multiplexed bead immunoassay system. RESULTS: Low-dose RWJ-58643 (100 microg) and budesonide (200 microg) significantly reduced symptoms, eosinophils and levels of IL-5 following NAC. However, higher doses of RWJ-58643 (300 and 600 microg) caused a late eosinophilia and preceding increases in IL-5 compared with placebo. CONCLUSIONS: This study suggests that combined beta-tryptase and trypsin inhibition has therapeutic potential in allergic inflammation, however, this property is dose responsive and higher doses are ineffective and may cause eosinophilia.
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Pirrolidinas/imunologia , Rinite Alérgica Sazonal/imunologia , Serina Endopeptidases/imunologia , Tiazóis/imunologia , Inibidores da Tripsina/imunologia , Administração Intranasal , Adulto , Alérgenos/imunologia , Benzotiazóis , Budesonida/administração & dosagem , Budesonida/imunologia , Quimiocina CCL11 , Quimiocina CCL2/análise , Quimiocinas CC/análise , Fatores Quimiotáticos de Eosinófilos/imunologia , Estudos Cross-Over , Método Duplo-Cego , Eosinófilos/imunologia , Feminino , Humanos , Mediadores da Inflamação/imunologia , Interleucina-5/análise , Interleucina-8/análise , Contagem de Leucócitos , Masculino , Mastócitos/imunologia , Pessoa de Meia-Idade , Pirrolidinas/administração & dosagem , Tiazóis/administração & dosagem , Inibidores da Tripsina/administração & dosagem , Triptases , Fator de Necrose Tumoral alfa/análiseRESUMO
BACKGROUND: Nasal lavage is a noninvasive method of obtaining inflammatory exudates following nasal allergen challenge (NAC), and permits cells and released mediators to be evaluated. OBJECTIVE: To determine the effects of a single dose of topical steroid on eosinophils and levels of chemokines and cytokines in nasal lavage fluid following NAC in patients with allergic rhinitis. METHODS: Patients with grass pollen seasonal allergic rhinitis (n = 32) out of the allergy season received either nasal budesonide (100 microg per nostril) or matched placebo before allergen challenge in a double blind two-way crossover design. A semi-automated mixed bead array system was employed to measure multiple chemokines and cytokines in small volumes (50 microl) of nasal lavage supernatants. RESULTS: Following NAC there was a rapid onset of nasal symptoms together with nasal eosinophilia, and the appearance of IL-5 and IL-13 in lavages between 4 and 8 h. Elevated levels of eotaxin, RANTES, IL-8 and MCP-1 were also detected following allergen challenge. A single dose of nasal budesonide caused a decrease in symptoms (P < 0.05) and nasal eosinophils (P < 0.05) with selective abrogation of IL-5 and IL-13 responses (P < 0.05), but a lack of effect on levels of eotaxin, RANTES, IL-8 and MCP-1. CONCLUSION: This study suggests that a single dose of nasal steroid has the capacity to selectively abolish IL-5 and IL-13 responses following NAC. This model should be convenient for testing novel anti-inflammatory and immunoregulatory agents intended for the treatment of allergic rhinitis.
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Anti-Inflamatórios/administração & dosagem , Budesonida/administração & dosagem , Interleucina-13/antagonistas & inibidores , Interleucina-5/antagonistas & inibidores , Phleum/imunologia , Pólen/imunologia , Rinite Alérgica Sazonal/tratamento farmacológico , Administração Intranasal , Adulto , Alérgenos/efeitos adversos , Alérgenos/imunologia , Anti-Inflamatórios/uso terapêutico , Budesonida/uso terapêutico , Feminino , Humanos , Interleucina-13/metabolismo , Interleucina-5/metabolismo , Masculino , Pessoa de Meia-Idade , Líquido da Lavagem Nasal/imunologia , Testes de Provocação Nasal , Phleum/efeitos adversos , Pólen/efeitos adversos , Rinite Alérgica Sazonal/etiologia , Rinite Alérgica Sazonal/metabolismo , Rinite Alérgica Sazonal/fisiopatologia , Resultado do TratamentoRESUMO
Twenty-five patients (seven male, 18 female) were diagnosed as having the loin pain and haematuria syndrome. Presenting symptoms were either loin pain alone or pain associated with macroscopic or microscopic haematuria, and were longstanding, having been present for mean of 9.3 years in males, and 10 years in females. Ten patients described symptoms of passing gravel or renal stones but these were only demonstrated radiologically in two patients. Investigation of all patients showed anatomically normal renal tracts, normal renal function, and no significant proteinuria. Phase-contrast microscopy during episodes of haematuria revealed dysmorphic red cells in all 10 patients studied. Renal biopsies were performed in 20 patients and showed no glomerular pathology, but arteriolar and arterial hyalinosis was seen in 13 of 20 (65 per cent), fibro-elastosis in larger vessels in eight of 20 (40 per cent) and red blood cells in tubules in 13 of 20 (65 per cent) patients. The histological appearance in vessels was similar to that seen in cyclosporin A nephrotoxicity and would be consistent with the hypothesis that regional vasospasm occurs in the cortical circulation. Haematological studies in 22 patients, when compared with age and sex matched controls, showed the presence of circulating platelet aggregates, elevation of plasma beta-thromboglobulin (p less than 0.001), and increased platelet aggregation in response to serotonin and ADP (p less than 0.05 and p less than 0.03, respectively). Plasma concentrations of D dimer (p less than 0.02) and C-reactive protein (p less than 0.03) were also significantly elevated in the patient group. There was no deterioration of renal function during a mean observation period of 3.7 years and no patients developed proteinuria. Treatment was largely supportive; seven patients with intractable loin pain underwent surgical denervation with the relief of pain in four.
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Hematúria/etiologia , Dor/etiologia , Veias Renais/patologia , Adulto , Constrição Patológica/fisiopatologia , Denervação , Feminino , Hematúria/patologia , Hematúria/cirurgia , Humanos , Rim/patologia , Rim/cirurgia , Masculino , Manejo da Dor , Agregação PlaquetáriaRESUMO
Haemostatic activation was measured in patients with either non-diabetic chronic renal failure (CRF) or diabetic nephropathy. We have investigated the relationship between these haemostatic markers and the rate of progression of renal failure. When compared with age- and sex-matched healthy controls, both patient groups showed significantly elevated plasma concentrations of D dimer, von Willebrand factor antigen (vWFAg), and C-reactive protein (CRP) (all P less than 0.001), as well as an increase in spontaneous platelet aggregation (P less than 0.01). Plasma concentration of platelet factor 4 was slightly but not significantly increased. Serum thromboxane was subnormal (P less than 0.01). Multiple regression analysis showed that in non-diabetic CRF proteinuria and serum TxB2 were independently related to the rate of progression of renal failure; in diabetic nephropathy proteinuria and vWFAg were independently related to the rate of progression. In both groups the relationship was stronger with proteinuria (standardised regression coefficients 0.56 and 0.45 respectively) than with serum TxB2 (0.29) or with vWFAg (0.37). We have found haemostatic activation in both non-diabetic and diabetic progressive renal failure. Proteinuria, and also in this study serum TxB2 and vWFAg, appear to be determining factors in the progression of renal failure, and their measurement may have prognostic value.