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1.
Nephrol Dial Transplant ; 37(1): 63-71, 2021 12 31.
Artículo en Inglés | MEDLINE | ID: mdl-33313875

RESUMEN

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) carries a high risk of morbidity and mortality, with outcomes modified by treatment and an incidence that may be increasing. We examined temporal changes in incidence and mortality during 2000-15 using nationwide healthcare registries. METHODS: Patients with incident AAV were identified using International Classification of Diseases Version 10 (ICD10) codes and grouped according to inclusion year (Period 1: 2000-04, Period 2: 2005-09, Period 3: 2010-15). Log link cumulative incidence regression adjusted for age, sex, renal function, cardiovascular disease, diabetes, hypertension and advanced disease severity were used to model survival. RESULTS: We identified 1631 patients (52% male), corresponding to an incidence of 18.5 persons/million/year (Period 1: 15.1, Period 2: 18.5, Period 3: 21.4). The slope of incident serologic ANCA testing was steeper than that of AAV (P = 0.002). Mean [standard deviation (SD)] age was 60.2 (16.7) years and mean (SD) follow-up was 6.8 (4.7) years. A total of 571 (35%) patients died (5-year mortality of 22.1%), with an absolute risk ratio (ARR) for Periods 2 and 3 compared with Period 1 of 0.80 [confidence interval (CI) 0.65-0.98, P = 0.031] and 0.39 (CI 0.31-0.50, P < 0.001). About 274 patients developed end-stage renal disease (ESRD) [16.8% (Period 1: 23.3%, Period 2: 17.6%, Period 3: 12.5%)], with ARR decreasing over time: Period 2 0.61 (CI 0.42-0.87, P = 0.007) and Period 3 0.57 (CI 0.39-0.83, P = 0.003). The overall risk of death associated with ESRD or chronic kidney disease was 1.74 (CI 1.29-2.37, P < 0.001) and 1.58 (CI 1.21-2.07, P < 0.001). CONCLUSIONS: Incidence of ANCA testing and AAV diagnosis increased over the test period. Falls over time in mortality and ESRD risk may relate to earlier diagnosis and changes in treatment practice.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Fallo Renal Crónico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Anticuerpos Anticitoplasma de Neutrófilos , Dinamarca/epidemiología , Femenino , Humanos , Incidencia , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
2.
BMC Nephrol ; 22(1): 307, 2021 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-34507554

RESUMEN

BACKGROUND: Patients with stage 5 chronic kidney disease (CKD5) collaborate with their clinicians when choosing their future treatment modality. Most elderly patients with CKD5 may only have two treatment options: dialysis or conservative kidney management (CKM). The objective of this systematic review was to investigate whether CKM offers a quantity or quality of life benefit compared to dialysis for some patients with CKD5. METHODS: The databases MEDLINE, EMBASE, the Cochrane Library, and CINAHL were systematically searched for studies comparing patients with CKD5 who had chosen or were treated with either CKM or dialysis. The primary outcomes were mortality and quality of life (QoL). Hospitalization, symptom burden, and place of death were secondary outcomes. For studies reporting hazard ratios, pooled values were calculated, and forest plots conducted. RESULTS: Twenty-five primary studies, all observational, were identified. All studies reported an increased mortality in patients treated with CKM (pooled hazard ratio 0.47, 95 % confidence interval 0.34-0.65). For patients aged ≥ 80 years and for elderly individuals with comorbidities, results were ambiguous. In most studies, CKM seemed advantageous for QoL and secondary outcomes. Findings were limited by the heterogeneity of studies and biased outcomes favouring dialysis. CONCLUSIONS: In general, patients with CKD5 who have chosen or are on CKM live for a shorter time than patients who have chosen or are on dialysis. In patients aged ≥ 80 years old, and in elderly individuals with comorbidities, the survival benefits of dialysis seem to be lost. Regarding QoL, symptom burden, hospitalization, and place of death, CKM may have advantages. Higher quality studies are needed to guide patients and clinicians in the decision-making process.


Asunto(s)
Tratamiento Conservador , Fallo Renal Crónico/terapia , Esperanza de Vida , Calidad de Vida , Diálisis Renal , Anciano , Anciano de 80 o más Años , Humanos , Fallo Renal Crónico/mortalidad , Factores de Tiempo
3.
Rheumatology (Oxford) ; 58(11): 1942-1949, 2019 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-30938436

RESUMEN

OBJECTIVES: This study aimed to characterize the association between HLA alleles and ANCA-associated vasculitis (AAV) in a genetically homogeneous population, and to analyse the contribution of specific HLA molecule amino acid sequences to the risk of AAV. METHODS: We included 187 Danish patients with AAV and 1070 healthy controls. All were HLA typed at two-field resolution. The association of HLA alleles to PR3- or MPO-AAV was analysed. The contribution of the dominant molecular motifs of the HLA-DPB1 molecule to the risk of AAV was investigated by association studies that included specific amino acid sequences of the hypervariable regions in exon 2. RESULTS: Ninety-four percent of patients with PR3-AAV were carriers of HLA-DPB1*04:01 while all patients with PR3-AAV were carriers of an HLA-DPB1*04 allele, and 85% were homozygous. This was significantly more than in the control group (P < 0.0001). The association was even stronger when HLA-DPB1*04:02 and -DPB1*23:01 were included. HLA-DPB1*04:01, -DPB1*04:02 and -DPB1*23:01 share amino acids in positions 8-9, 69, 76 and 84-87 within the hypervariable regions, but only positions 69 and 84-87 contributed significantly to the disease risk. HLA-DRB1*15 was associated with an increased risk of developing PR3-AAV, while HLA-DRB1*04, -DRB1*07 and -DQB1*03 were associated with a reduced risk of kidney involvement in PR3-AAV. MPO-AAV was only weakly associated with HLA class I alleles. CONCLUSION: PR3-AAV is strongly associated with the HLA-DPB1 alleles HLA-DPB1*04:01, -DPB1*04:02 and -DPB1*23:01, which share amino acid sequences crucial for the peptide-binding groove.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/genética , Predisposición Genética a la Enfermedad/genética , Antígenos HLA-DP/genética , Mieloblastina/genética , Peroxidasa/genética , Adulto , Anciano , Alelos , Secuencias de Aminoácidos/genética , Estudios de Casos y Controles , Dinamarca , Exones , Femenino , Genotipo , Cadenas HLA-DRB1/genética , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Población Blanca/genética
4.
BMC Nephrol ; 20(1): 58, 2019 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-30777023

RESUMEN

BACKGROUND: Intravenous pulse methylprednisolone (MP) is commonly included in the management of severe ANCA associated vasculitis (AAV) despite limited evidence of benefit. We aimed to evaluate outcomes in patients who had, or had not received MP, along with standard therapy for remission induction in severe AAV. METHODS: We retrospectively studied 114 consecutive patients from five centres in Europe and the United States with a new diagnosis of severe AAV (creatinine > 500 µmol/L or dialysis dependency) and that received standard therapy (plasma exchange, cyclophosphamide and high-dose oral corticosteroids) for remission induction with or without pulse MP between 2000 and 2013. We evaluated survival, renal recovery, relapses, and adverse events over the first 12 months. RESULTS: Fifty-two patients received pulse MP in addition to standard therapy compared to 62 patients that did not. There was no difference in survival, renal recovery or relapses. Treatment with MP associated with higher risk of infection during the first 3 months (hazard ratio (HR) 2.7, 95%CI [1.4-5.3], p = 0.004) and higher incidence of diabetes (HR 6.33 [1.94-20.63], p = 0.002), after adjustment for confounding factors. CONCLUSIONS: The results of this study suggest that addition of pulse intravenous MP to standard therapy for remission induction in severe AAV may not confer clinical benefit and may be associated with more episodes of infection and higher incidence of diabetes.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Diabetes Mellitus , Infecciones , Metilprednisolona , Quimioterapia por Pulso/métodos , Inducción de Remisión/métodos , Antiinflamatorios/administración & dosificación , Antiinflamatorios/efectos adversos , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/epidemiología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Diabetes Mellitus/epidemiología , Diabetes Mellitus/etiología , Femenino , Humanos , Inmunosupresores/uso terapéutico , Infecciones/epidemiología , Infecciones/etiología , Pruebas de Función Renal/métodos , Masculino , Metilprednisolona/administración & dosificación , Metilprednisolona/efectos adversos , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Intercambio Plasmático/estadística & datos numéricos , Diálisis Renal/estadística & datos numéricos , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad
6.
Clin Kidney J ; 17(1): sfad261, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38186880

RESUMEN

Background: Epidemiologic assessments of anti-glomerular basement membrane (GBM) disease have been challenging due to its rare occurrence. We examined changes in the incidence and outcomes from 1998 to 2018 using nationwide healthcare registries. Methods: All patients with incident anti-GBM disease were identified using the International Classification of Diseases, 10th Revision code DM31.0A. Controls were matched 4:1 on birthyear and sex using exposure density sampling. Log link regression adjusted for time, age and sex was applied to model survival. Results: We identified 97 patients with incident anti-GBM disease, corresponding to an incidence of 0.91 cases/million/year [standard deviation (SD) 0.6]. The incidence increased over time [1998-2004: 0.50 (SD 0.2), 2005-2011: 0.80 (SD 0.4), 2012-2018: 1.4 (SD 0.5); P = .02] and with age [0.76 (SD 0.4), 1.5 (SD 1.04) and 4.9 (SD 2.6) for patients <45, 45-75 and >75 years]. The median age was 56 years (interquartile range 46) and 51.6% were female. Dialysis was required in 58.4%, 61.9% and 62.9% of patients at day 30, 180 and 360, respectively. The 1-year kidney survival probability was 0.38 (SD 0.05) and exhibited time-dependent changes [1998-2004: 0.47 (SD 0.13), 2005-2011: 0.16 (SD 0.07), 2012-2018: 0.46 (SD 0.07); P = .035]. The 5-year mortality was 26.8% and mortality remained stable over time (P = .228). The risk of death was greater than that of the matched background population {absolute risk ratio [ARR] 5.27 [confidence interval (CI) 2.45-11.3], P < .001}, however, it was comparable to that of patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) requiring renal dialysis at presentation [ARR 0.82 (CI 0.48-1.41), P = .50]. Conclusion: The incidence of anti-GBM disease increased over time, possibly related to temporal demographic changes. Mortality remained high and was comparable with an age- and sex-matched cohort of dialysis-dependent AAV patients.

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