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AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.
There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Natalizumab/uso terapêutico , Cloridrato de Fingolimode/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Análise de Custo-Efetividade , Análise Custo-Benefício , Medicina Estatal , Reino UnidoRESUMO
This article reviews the literature on equine atypical myopathy (AM), an acute, severe rhabdomyolysis that occurs in horses at pasture. The prevalence, mortality, clinical signs, pathology, potential aetiology, typical aspects, diagnosis, treatment, and prognosis are described. Horse management, characteristic weather conditions, and possible preventive measures are also discussed. In addition, the characteristics of 54 highly probable or confirmed cases of equine AM occurring between autumn 2009 (27 cases) and spring 2010 (27 cases) in the Netherlands are described. Of the 54 affected horses, nineteen were mares, eleven geldings, and eight stallions; the sex of the other sixteen horses was not recorded. The mortality rate (74.5%) was in the same range as that reported in earlier studies. Many cases were reported at about the same time. Thirty-five horses had been pastured near maple trees, and in fifteen cases the maple trees were known to be infected with the fungus Rhytisma acerinum.
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Criação de Animais Domésticos/métodos , Surtos de Doenças/veterinária , Doenças dos Cavalos/epidemiologia , Doenças Musculares/veterinária , Rabdomiólise/veterinária , Animais , Feminino , Doenças dos Cavalos/diagnóstico , Doenças dos Cavalos/prevenção & controle , Cavalos , Masculino , Doenças Musculares/diagnóstico , Doenças Musculares/epidemiologia , Doenças Musculares/prevenção & controle , Países Baixos/epidemiologia , Rabdomiólise/diagnóstico , Rabdomiólise/epidemiologia , Rabdomiólise/prevenção & controle , Estações do AnoRESUMO
BACKGROUND: Periocular contact dermatitis may appear as contact conjunctivitis, contact allergic and/or irritative eyelid and periorbital dermatitis, or a combination of these symptoms. The clinical symptoms may be induced by several environmental and therapeutic contact allergens. OBJECTIVES: The aim of the present study was to map the eliciting contact allergens in 401 patients with periocular dermatitis (PD) by patch testing with environmental and ophthalmic contact allergens. METHODS: Following the methodics of international requirements, 401 patients were tested with contact allergens of the standard environmental series, 133 of 401 patients with the Brial ophthalmic basic and supplementary series as well. RESULTS: Contact hypersensitivity was detected in 34.4% of the patients. Highest prevalence was seen in cases of PD without other symptoms (51.18%), in patients of PD associated with ophthalmic complaints (OC; 30.4%), and PD associated with atopic dermatitis (AD; 27.9%). In the subgroup of PD associated with seborrhoea (S) and rosacea (R), contact hypersensitivity was confirmed in 17.6%. Most frequent sensitisers were nickel sulphate (in 8.9% of the tested 401 patients), fragrance mix I (4.5%), balsam of Peru (4.0%), paraphenylendiamine (PPD) (3.7%), and thiomersal (3.5%). By testing ophthalmic allergens, contact hypersensitivity was observed in nine patients (6.7% of the tested 133 patients). The most common confirmed ophthalmic allergens were cocamidopropyl betaine, idoxuridine, phenylephrine hydrochloride, Na chromoglycinate, and papaine. LIMITATIONS: Patients with symptoms of PD were tested from 1996 to 2006. CONCLUSIONS: The occurence of contact hypersensitivity in PD patients was in present study 34.4%. A relatively high occurrence was seen in cases of PD without other symptoms, in PD + OC and in PD + AD patients. The predominance of environmental contact allergens was remarkable: most frequent sensitizers were nickel sulphate, fragrance mix I, balsam of Peru, thiomersal, and PPD. The prevalence of contact hypersensitivity to ophthalmic allergens did not exceed l.5%.
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Dermatite de Contato/diagnóstico , Dermatite Perioral/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alérgenos/efeitos adversos , Criança , Cosméticos/efeitos adversos , Dermatite de Contato/etiologia , Dermatite Perioral/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes do EmplastroRESUMO
The central nervous system (CNS) is known to be an immunologically privileged organ in the body largely because the blood brain barrier (BBB) prevents the flow of large molecules, proteins, and cells from crossing into the CNS from the periphery. These restrictive properties of the BBB have made it difficult to treat CNS diseases. In this study, mice were infected intracranially (i.c.) with Sindbis virus (SV) and then treated either i.c. or intraperitoneally (i.p.) with neutralizing antibodies against interferon alpha (IFNalpha). SV infected control mice received i.p. saline. Antibodies against mouse IFNalpha were detected in the brain tissue of mice that received i.p. and i.c. injections of the antibody. ELISA analysis showed that both i.c. and i.p. antibody treated mice had significantly decreased levels of IFNalpha in the brain tissue. Also, mice that received IFNalpha neutralizing antibodies showed decreased presence of protein kinase R (PKR) measured by immunohistochemical densitometry, indicating the antibody successfully inhibited IFNalpha. The data shows that antibodies are capable of crossing the BBB and inhibiting IFNalpha, indicating that it is possible to target molecules of interest in the CNS with peripheral antibody treatment.
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Anticorpos/imunologia , Barreira Hematoencefálica , Interferon-alfa/imunologia , Animais , Encéfalo/metabolismo , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Injeções Intraperitoneais , Interferon-alfa/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Testes de NeutralizaçãoRESUMO
BACKGROUND: Atopic dermatitis (AD) is a clinically well-defined, chronic-intermittant, genetically predisposed skin disease. The increasing number of adult cases observed in the last years has turned the attention to ascertaining factors eliciting skin symptoms. Studies have revealed numerous environmental components (e.g. contact and aeroallergens) that may play an important role in sustaining the symptoms. The aim of the study was to search for contact allergens and aeroallergens triggering the skin disease in adult AD patients. METHODS: Patients over 18 years from our Atopy Outpatient Department were included in the study. Diagnosis of AD was based on the clinical criteria of Hanifin and Rajka. The distribution of skin symptoms was characteristic for adult AD: hands, shoulders, neck, flexures, face and eyelids. The extremities and the trunk were less involved. The potentially provoking contact and aeroallergens were examined in symptom and drug-free period with atopy patch and epicutaneous tests (APT, ET), which were supplemented by in vitro allergy and Prick tests. The relevance of sensibilization was evaluated by the comparison of in vivo and in vitro test results, medical history and skin symptoms. RESULTS: A total number of 34 cases of adult AD (23 women and 11 men) were studied. Four of them were classified into the intrinsic group (IG; 12%), and 30 were classified into the extrinsic group (EG; 88%). The incidence of contact sensitization to environmental allergens was remarkable: 13 of the EG, 1 of the IG (14 of 34, 41%). In the IG, a late thiomersal positivity was detected without clinical relevance. In the EG, epicutaneous standard series late positivity was seen in 13 patients, in four of them with multiple sensitivity. The allergens causing positivity were nickel (6 of 13), thiomersal (3 of 13), mercury-amidochlorate (3 of 13), mercury-chloride (2 of 13), iodine chlorhyrdoxyquin (1 of 13), lanalcolum (1 of 13) and fragrance mix (1 of 13). Among the detected allergens, the following were relevant: lanalcolum (1 of 13: cosmetics), fragrance mix (1 of 13: cosmetics), nickel (1 of 13: metal objects), thiomersal (1 of 13: eyedrops). No immediate response was seen with APT. Relevant late positivity was shown with APT test in one patient in the IG (1 of 4) to Dermatophagoides pteronyssinus. We observed late positivity in 18 patients in the EG (18 of 30). Among the detected allergens, the following were clinically relevant: D. pteronyssinus and/or Dermatophagoides farinae (15 of 18), cat epithel (4 of 18), timothy pollen (1 of 18) and dog epithel (1 of 18). Furthermore, we examined the relevance of APT, specific immunoglobulin E (IgE) tests and Prick tests. We observed multiplex positivity by specific IgE tests, APT and Prick tests in 14 patients in EG. Sensitization to D. pteronyssinus and/or D. farinae (11 of 14) cat epithel (4 of 14), dog epithel (1 of 14) and timothy pollen (1 of 14) proved to be clinically relevant with the atopic skin symptoms and medical history. CONCLUSION: The proportion of contact sensitization to environmental allergens in the 34 adult atopic patients was remarkable (14 of 34, 41%). Out of the verified contact allergens, nickel, fragrance mix, thiomersal and lanalcolum proved to be relevant. House dust mite and cat epithel proved to be the most common relevant aeroallergens. D. pteronyssinus and D. farinae sensibilization was high, particularly in patients with severe skin symptoms on the face, eyelids and hands. Pollens should be considered in patients with seasonal relapse of AD. Sensitization to animal epithel was usually indicated by the flare-up of skin symptoms upon contact with animals. The relevance of the eliciting effects of sensitization could easily be supported in most cases by the medical history and the distribution of skin symptoms. In some adult AD patients with long-lasting AD, the relevance of triggering factors is hard to determine.
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Alérgenos/imunologia , Dermatite Atópica/imunologia , Adolescente , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes CutâneosRESUMO
INTRODUCTION: Hypertension is prevalent in most patients after renal transplantation, and it is the main factor contributing to cardiovascular diseases that cause death of a significant number of these patients. Up to 95% of patients after transplantation have hypertension, and among them are patients with refractory hypertension. Elevated blood pressure is one of the causes of deterioration of transplant function and may accelerate transplant loss. CASE REPORT: We present the first case in the world of a patient (who was 61 years old) in whom denervation of native renal arteries was performed after renal transplantation (2004). The patient was suffering from uncontrolled refractory hypertension. Antihypertensive therapy was used but the effect was not satisfactory. The patient received amlodipine, bisoprolol, clonidine, furosemide, and doxazosin in high doses. Clinical assessments with ambulatory blood pressure monitoring revealed a predominant blood pressure 149/96 with incidents of hypertensive crises. High blood pressure is a cardiovascular risk factor and it also has a significant influence on transplant failure, which was the reason for performing the denervation. The procedure was carried out through the femoral artery with the use of a 6F guiding catheter. During a 3-year observation, significant decreases in ambulatory blood pressure monitoring systolic and diastolic blood pressures were observed after the procedure (149/96 mm Hg vs 134/91 mm Hg before and after the denervation, respectively). There was a significant regression of left ventricle mass (577 g before denervation vs 470 g after 3 years). The functioning of the renal transplant became stable after 3 years of observation (38 mL/min before denervation and 38 mL/min after 3 years). CONCLUSIONS: The first case in the world of a renal transplant patient who had denervation of native renal arteries has demonstrated a positive effect in controlling blood pressure over a 3-year observation. Three years after denervation, a reduction of heart hypertrophy and stabilization of renal function were noted. The presented case shows that denervation of native renal arteries denervation may be successful and safe in kidney transplant recipients.
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Denervação/métodos , Hipertensão/cirurgia , Transplante de Rim/efeitos adversos , Artéria Renal/inervação , Artéria Renal/cirurgia , Humanos , Hipertensão/etiologia , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The occurrence of anti-angiotensin II type 1 receptor (AT1R) antibodies is thought to be a risk factor for transplant injury, but the relationship of AT1R to graft loss in renal transplantation has not been assessed. The aim of our study was to evaluate the expression of AT1R and its relationship with graft loss in patients who had a renal transplant biopsy for cause. METHODS: AT1R immunoreactivity was analyzed in 170 renal transplant biopsies. Immunohistochemical evaluation of AT1R expression was performed on 4 µm-thick paraffin sections mounted on silanized slides. AT1R expression was analyzed in 5 compartments: 1. glomeruli, 2. renal blood vessels (small and intermediate arteries), 3. peritubular capillaries, 4. tubular epithelium, and 5. interstitium based on a 3-step scale. RESULTS: Initially we checked 170 consecutive samples of biopsies for the immunoreactivity of the AT1R. The study finally included 118 renal transplant patients in 1-year observation after the biopsy. The renal allograft biopsy was performed between 6 days and 24 years after transplantation and the diagnosis was based on Banff criteria. We observed positive immunostaining of AT1R in tubular epithelium in 26.3% (42/118) of patients. A total of 7 patients had staining assessed as 2 and 35 as 1. One year post-biopsy graft loss in the AT1R (+) patients was 35.7 % (15/42) compared to 14.5% (11/76) in the AT1R (-) group (P = .008). CONCLUSIONS: The expression of AT1R in tubular epithelium of the biopsy for cause was associated with significantly higher graft loss. The relevance of AT1R should be considered for better transplant immunological risk assessment.
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Transplante de Rim , Rim/metabolismo , Receptor Tipo 1 de Angiotensina/biossíntese , Adulto , Biópsia , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Humanos , Rim/imunologia , Rim/patologia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina/imunologia , Fatores de Risco , Transplante HomólogoRESUMO
Rupture of Achilles tendon is a common accident affecting professional and recreational athletes. Acute and chronic pain are symptoms commonly observed in patients with rupture. However, few studies have investigated whether Achilles tendon rupture is able to promote disorders in the central nervous system (CNS). Therefore, the current study aimed to evaluate nociceptive alterations and inflammatory response in the L5 lumbar segment of Balb/c mice spinal cord after Achilles tendon rupture. We found increased algesia in the paw of the ruptured group on the 7th and 14th days post-tenotomy compared with the control group. This phenomenon was accompanied by overexpression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase-2 (NOS-2) as well as hyperactivation of astrocytes and microglia in nociceptive areas of L5 spinal cord as evidenced by intense GFAP and IBA-1 immunostaining, respectively. Biochemical studies also demonstrated increased levels of nitrite in the L5 spinal cord of tenotomized animals compared with the control group. Thus, we have demonstrated for the first time that total rupture of the Achilles tendon induced inflammatory response and nitrergic and glial activation in the CNS in the L5 spinal cord region.
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Stimulus-induced rhythmic EEG discharges (SIRDs) is a recently reported phenomenon in critically ill patients and little is known about their evolution. We found SIRDs in three patients with encephalopathy and followed them with serial EEGs. SIRDs appeared between 4 and 13 days after the onset of illness and persisted for 2-3 days. The discharges were elicited by tactile or nociceptive stimuli and lasted for 20-120 s. They were detected in 2/6, 1/3 and 2/11 EEGs performed between 9 and 32, 2 and 4 and 3 and 15 days, respectively, after the onset of illness. Their morphology varied: blunt triphasic waves, rhythmic delta activity and rhythmic sharp wave complexes. The background EEG activity was slowed or suppressed in all. One patient had acute disseminated encephalomyelitis (ADEM) with good recovery and the other two had fatal hypoxic ischemic encephalopathy. SIRDs appear to be a transient phenomena occurring in patients with encephalopathy, appearing hours to few days after the onset of illness. This is the first report of SIRDs in ADEM. Serial EEGs and repeated testing of EEG response to tactile and nociceptive stimuli is required for their detection. Larger number of patients with SIRDs need to be studied to assess their prognostic significance.
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Encefalopatias/fisiopatologia , Eletroencefalografia , Epilepsia/fisiopatologia , Adulto , Encefalopatias/classificação , Edema Encefálico/fisiopatologia , Infarto Encefálico/fisiopatologia , Encefalomielite Aguda Disseminada/fisiopatologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-IdadeRESUMO
ABSTRACT: Equine coital exanthema is a venereal infectious disease poorly reported in horses in Brazil and was never described in the northeastern region of the country. This work aims to describe the clinical and pathological aspects of an outbreak of equine coital exanthema caused by equid alphaherpesvirus 3, occurred in a herd of horses at the semiarid region of the State of Rio Grande do Norte. Main clinical signs consisted of anorexia, hiporexia, fibrinous or purulent secretion in the penis mucosa and vagina. Two mares presented mild to minimal lesions that consisted of scars in the mucosa of the vagina and in the perivulvar region. In a stallion the disease consisted of severe, multifocal, umbilicated-exanthematous ulcers of approximately 1cm in diameter on the penis mucosa. Other areas where ulcers and crusts were focally observed included the skin of the scrotum and on the lips and mucocutaneous junctions of the oral cavity. Histologically, the main lesion consisted of multifocal severe ulcerative and fibrinous necrotizing balanoposthitis and mild multifocal necrotizing, lymphocytic dermatitis in the lips and scrotum. The equide alphaherpesvirus 3 DNA was amplified in blood samples and penis mucosa using the PCR technique. This is the first report of molecular diagnosis of equine coital exanthema affecting horses in northeastern Brazil. Further studies should be carried out in order to investigate the epidemiology and the importance of this herpetic disease in the country.
RESUMO: O exantema coital equino é uma doença infecciosa venérea pouco relatada em equinos no Brasil e nunca descrita na região Nordeste do país. Este trabalho tem como objetivo descrever os aspectos clínicos e patológicos de um surto de exantema coital equino causado pelo alphaherpesvirus equídeo 3, que ocorreu em um haras na região semiárida do Estado do Rio Grande do Norte. Os principais sinais clínicos consistiram em anorexia, hiporexia, secreção fibrinosa ou purulenta na mucosa do pênis e vagina. Duas éguas apresentavam lesões discretas que consistiam em cicatrizes na mucosa da vagina e na região perivulvar. Em um garanhão, a doença consistia em úlceras umbilicadas-exantematosas severas, multifocais, de aproximadamente 1 cm de diâmetro na mucosa do pênis. Outras áreas onde úlceras e crostas foram observadas focalmente incluíram a pele do escroto, lábios e junções mucocutâneas da cavidade oral. Histologicamente, as principais lesões consistiam em balanopostite multifocal ulcerativa e necrosante fibrinosa grave e dermatite linfocítica necrosante multifocal leve nos lábios e escroto. O DNA do alphaherpesvirus equídeo tipo 3 foi amplificado em amostras de sangue e mucosa do pênis pela técnica de PCR. Este é o primeiro relato de diagnóstico molecular de exantema coital equino afetando cavalos no nordeste do Brasil. Novos estudos devem ser realizados a fim de investigar a epidemiologia e a importância dessa doença herpética no país.
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A 24-year-old woman of Somali origin delivered at term after an uncomplicated pregnancy. Post-partum haemorrhage resulted in hypovolaemic shock which was treated by hysterectomy. Five days later she became comatose due to unrecognised hypoglycaemia which caused severe irreversible brain damage and status epilepticus. Treatment in the intensive care unit with artificial respiration, prednisolone, desmopressin, inotropic support, barbiturates and an anaesthetic under EEG guidance was unsuccessful. The patient died 28 days post-partum. The hypoglycaemia was due to a combination of (a) inadequate glucose intake and (b) lack of counter-regulatory mechanisms due to a deficiency of steroids and growth hormone as a result of loss of pituitary function (Sheehan syndrome) together with adrenocortical insufficiency. The combination of Sheehan syndrome and primary adrenocortical insufficiency has not been described previously in the literature.
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Insuficiência Adrenal/complicações , Coma/etiologia , Hipoglicemia/complicações , Hipopituitarismo/complicações , Hemorragia Pós-Parto/cirurgia , Insuficiência Adrenal/tratamento farmacológico , Adulto , Glicemia/metabolismo , Evolução Fatal , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hipoglicemia/tratamento farmacológico , Hipopituitarismo/tratamento farmacológico , Histerectomia , Hemorragia Pós-Parto/complicações , Hemorragia Pós-Parto/etiologia , Prednisona/uso terapêutico , Gravidez , Choque/etiologia , Choque/cirurgiaRESUMO
INTRODUCTION: Non-HLA antibodies specific for angiotensin II type 1 receptor (anti-AT1R) and endothelin-1 type A receptor (anti-ETAR) of vascular cells activate signaling pathways leading to cell proliferation and vascular injury. The aim of this study was to evaluate the impact of non-HLA antibodies on kidney allograft morphology and function in patients who underwent a kidney biopsy due to renal function impairment. PATIENTS AND METHODS: The study included 65 consecutive renal transplant patients who were evaluated for the presence of non-HLA and anti-HLA antibodies at the time of transplant biopsy. Results of pre-transplant CDC cross-match were negative. A kidney allograft biopsy was performed between 6 days and 13 years (42 ± 49 months) after transplantation, and the diagnosis was made on the basis of the Banff criteria. The level >9 U/L of anti-AT1R and anti-ETAR antibodies was considered high. RESULTS: A high level of non-HLA antibodies (anti-AT1R and/or anti-ETAR) was found in 7 (10.7%) of 65 patients at the time of biopsy. Graft loss in the non-HLA-positive patients was significantly higher (71% in non-HLA-positive cases after 7.8 ± 2.6 months vs 11% after 6 months in non-HLA-negative cases [P = .00099]). In these non-HLA-positive patients, the mean anti-AT1R level was 15.3 ± 9.4 U/L and the mean anti-ETAR level was 13.8 ± 8.6 U/L. In only 2 of these patients were anti-HLA antibodies additionally detected: anti-class I in 1 and anti-class II in both patients. The mean serum creatinine level was 2.34 ± 0.6 mg/dL at the time of biopsy. Results of an early biopsy revealed acute vascular rejection (Banff grade IIB). Chronic allograft injury was found (grading cg1-3, cv1-2, ci1-2, ct1-2) in the remaining 6 patients. C4d was present in 3 of 7 patients. CONCLUSIONS: High levels of anti-AT1R and/or anti-ETAR antibodies were associated with morphological and functional allograft injury and graft loss in these study patients. Non-HLA antibodies can be helpful in assessing the risk of graft failure.