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1.
Kidney Int ; 105(1): 177-188, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37923132

RESUMEN

Activation of the alternative pathway (AP) of complement is involved in the pathogenesis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), although the underlying molecular mechanisms are unclear. To gain insight into the role of the AP, common gene variants in CFH/CFHR1-5, CFB, C3 and MCP, and longitudinal determinations of plasma C3, C4, FH, FHR-1, FHR-2, FHR-5, FB, properdin and sC5b-9 levels were analyzed in a Spanish AAV cohort consisting of 102 patients; 54 with active AAV (active cohort) and 48 in remission not receiving immunosuppressants or dialysis therapy (remission cohort). The validation cohort consisted of 100 patients with ANCA-associated glomerulonephritis. Here, we demonstrated that common genetic variants in complement components of the AP are associated with disease susceptibility (CFB32Q/W) or severity of kidney damage in AAV (CFH-H1, CFH1H2 and ΔCFHR3/1). Plasma levels of complement components were significantly different between active and remission cohorts. In longitudinal observations, a high degree of AP activation at diagnosis was associated with worse disease outcome, while high basal FHR-1 levels and lower FH/FHR-1 ratios determined severe forms of kidney associated AAV. These genetic and plasmatic findings were confirmed in the validation cohort. Additionally, autoantibodies against FH and C3 convertase were identified in one and five active patients, respectively. Thus, our study identified key genetic and plasma components of the AP that determine disease susceptibility, prognosis, and severity in AAV. Our data also suggests that balance between FH and FHR-1 is critical and supports FHR-1 as a novel AP-specific therapeutic target in AAV.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Anticuerpos Anticitoplasma de Neutrófilos , Humanos , Susceptibilidad a Enfermedades , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/genética , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Factores Inmunológicos , Properdina/genética
2.
Am J Kidney Dis ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38866126

RESUMEN

Monkeypox (mpox) is an orthopoxviral zoonotic disease with a similar but less severe clinical presentation as smallpox. However, immunocompromised patients such as solid organ transplant recipients are at higher risk of developing severe forms of the disease. Herein, we describe the case of a 43-year-old female kidney transplant recipient that manifested severe skin ulcers alongside nodular lung opacities and pleural effusion attributed directly to the monkeypox virus. Notwithstanding the initiation of early treatment with tecovirimat, a satisfactory response was not achieved until a reduction in immunosuppression to everolimus monotherapy, coupled with the transition to cidofovir for antiviral treatment. In conclusion, mpox has the potential to produce a severe form of systemic infection in individuals who have undergone solid organ transplantation, demanding a meticulous approach involving sequential antiviral treatment and modifications to immunosuppressive regimens in order to achieve complete healing.

3.
Clin Transplant ; 38(9): e15443, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39207183

RESUMEN

BACKGROUND: Thrombotic microangiopathy (TMA) is a rare complication after lung transplantation (LT) that has seldom been characterized in detail. Recent evidence has linked TMA other than primary atypical hemolytic uremic syndrome (aHUS) with hyperactivation of the complement alternative pathway. The focus of this investigation was to analyze the treatment response with eculizumab in TMA after LT. METHODS: Case series where we have studied 11 patients with TMA after LT from 2 Spanish tertiary healthcare centers. Clinical data and response rates to eculizumab are provided. RESULTS: The main indication for lung transplant was chronic obstructive pulmonary disease (COPD) (36%) and most cases (82%) received bilateral LT. The median time to TMA diagnosis was 11.6 months (4.7-28.9) and the TMA trigger in the majority of cases (73%) was immunosuppressive drugs. Platelet and hemoglobin nadir were 58 × 103/µL (24-108) and 7.7 g/dL (7.1-7.9), respectively. All cases presented acute kidney injury (AKI) with a median creatinine of 4 mg/dL (3.2-4.8) and 54.5% required acute dialysis. Eculizumab was started after a median time of 8 days (6-14) with a median duration of 3 weeks (2-8). Complete TMA response was observed in 7 (63.6%) cases and hematologic response in 10 (90.9%). The time to hematologic and renal response was 23 days (13-29) and 28 days (14-46), respectively. CONCLUSIONS: TMA after LT is infrequent but potentially devastating. Our findings suggest that short cycles of eculizumab may be effective for severe TMA after LT.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Inactivadores del Complemento , Trasplante de Pulmón , Terapia Recuperativa , Microangiopatías Trombóticas , Humanos , Femenino , Masculino , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/tratamiento farmacológico , Trasplante de Pulmón/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Persona de Mediana Edad , Estudios de Seguimiento , Pronóstico , Adulto , Inactivadores del Complemento/uso terapéutico , Anciano , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de Riesgo , Rechazo de Injerto/etiología , Rechazo de Injerto/tratamiento farmacológico , Pruebas de Función Renal , Supervivencia de Injerto/efectos de los fármacos
4.
Nephrol Dial Transplant ; 38(5): 1217-1226, 2023 05 04.
Artículo en Inglés | MEDLINE | ID: mdl-36002030

RESUMEN

BACKGROUND: Thrombotic microangiopathy (TMA) is a complication of malignant hypertension (mHTN) attributed to high blood pressure (BP). However, no studies have investigated in patients with mHTN of different aetiologies whether the presence of TMA is associated with specific causes of mHTN. METHODS: We investigated the presence of TMA (microangiopathic haemolytic anaemia and thrombocytopenia) in a large and well-characterized cohort of 199 patients with mHTN of different aetiologies [primary HTN 44%, glomerular diseases 16.6%, primary atypical haemolytic uraemic syndrome (aHUS) 13.1%, renovascular HTN 9.5%, drug-related HTN 7%, systemic diseases 5.5%, endocrine diseases 4.5%]. Outcomes of the study were kidney recovery and kidney failure. RESULTS: Patients with TMA [40 cases (20.1%)] were younger, were more likely female and had lower BP levels and worse kidney function at presentation. Their underlying diseases were primary aHUS (60%), drug-related mHTN (15%), glomerular diseases [all of them immunoglobulin A nephropathy (IgAN); 10%], systemic diseases (10%) and primary HTN (5%). The presence of TMA was 92.3% in primary aHUS, 42.9% in drug-related HTN, 36.4% in systemic diseases, 12.1% in glomerular diseases and 2.3% in primary HTN. No patient with renovascular HTN or mHTN caused by endocrine diseases developed TMA, despite BP levels as high as patients with TMA. A higher proportion of TMA patients developed kidney failure as compared with patients without TMA (56.4% versus 38.9%, respectively). CONCLUSIONS: The presence of TMA in patients with mHTN should guide the diagnosis towards primary aHUS, drug-related mHTN, some systemic diseases and IgAN, while it is exceptional in other causes of mHTN.


Asunto(s)
Síndrome Hemolítico Urémico Atípico , Hipertensión Maligna , Hipertensión , Enfermedades Renales , Púrpura Trombocitopénica Trombótica , Insuficiencia Renal , Microangiopatías Trombóticas , Humanos , Femenino , Hipertensión Maligna/complicaciones , Microangiopatías Trombóticas/complicaciones , Púrpura Trombocitopénica Trombótica/complicaciones , Púrpura Trombocitopénica Trombótica/diagnóstico , Riñón , Síndrome Hemolítico Urémico Atípico/diagnóstico , Enfermedades Renales/complicaciones , Insuficiencia Renal/complicaciones , Hipertensión/complicaciones
5.
Nephrol Dial Transplant ; 37(11): 2128-2137, 2022 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-34677610

RESUMEN

BACKGROUND: C3 glomerulopathy associated with monoclonal gammopathy (C3G-MIg) is a rare entity. Herein we analysed the clinical and histologic features of a cohort of C3G-MIg patients. METHODS: We conducted a retrospective, multicentre, observational study. Patients diagnosed with C3G-MIg between 1995 and 2021 were enrolled. All had genetic studies of the alternative complement pathway. The degree of disease activity and chronicity were analysed using the C3G histologic index. Descriptive statistics and propensity score matching (PSM) analysis were used to evaluate the main outcome of the study [kidney failure (KF)]. RESULTS: The study group included 23 patients with a median age 63 of years [interquartile range (IQR) 48-70], and 57% were males. Immunoglobulin G kappa was the most frequent MIg (65%). The diagnosis of C3G-MIg was made in transplanted kidneys in seven patients (30%). Five (22%) patients had C3 nephritic factor and five (22%) had anti-factor H antibodies. One patient carried a pathogenic variant in the CFH gene. During a follow-up of 40 months (IQR 14-69), nine patients (39%) reached KF and these patients had a significantly higher total chronicity score on kidney biopsy. Patients who received clone-targeted therapy had a significantly higher survival compared with other management. Those who achieved haematological response had a significantly higher kidney survival. Outcome was remarkably poor in kidney transplant recipients, with five of them (71%) reaching KF. By PSM (adjusting for age, kidney function, proteinuria and chronicity score), no significant differences were observed in kidney survival between C3G patients with/without MIg. CONCLUSIONS: The C3G histologic index can be used in patients with C3G-MIg to predict kidney prognosis, with higher chronicity scores being associated with worse outcomes. Clone-targeted therapies and the development of a haematological response are associated with better kidney prognosis.


Asunto(s)
Glomerulonefritis Membranoproliferativa , Enfermedades Renales , Gammopatía Monoclonal de Relevancia Indeterminada , Paraproteinemias , Humanos , Masculino , Persona de Mediana Edad , Femenino , Factor Nefrítico del Complemento 3 , Complemento C3 , Estudios Retrospectivos , Paraproteinemias/complicaciones , Paraproteinemias/patología , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/etiología , Inmunoglobulina G , Células Clonales/química , Células Clonales/patología , Glomerulonefritis Membranoproliferativa/patología
6.
Kidney Int ; 96(4): 995-1004, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31420192

RESUMEN

Malignant hypertension is listed among the causes of secondary thrombotic microangiopathy, but pathogenic mutations in complement genes have been reported in patients with hypertension-induced thrombotic microangiopathy. Here we investigated the frequency and severity of hypertension in 55 patients with primary atypical hemolytic uremic syndrome (aHUS). A genetic analysis was performed in all patients, and funduscopic examination was performed in all the patients with Grades 2 and 3 hypertension. A cohort of 110 patients with malignant hypertension caused by diseases other than aHUS served as control. Thirty-six patients with aHUS presented Grade 2 or Grade 3 hypertension and funduscopic examination showed malignant hypertension in 19. Genetic abnormalities in complement were found in 19 patients (37% among patients with malignant hypertension). Plasmapheresis was performed in 46 patients and 26 received eculizumab. Renal and hematological responses were significantly lower after plasmapheresis (24%) than after eculizumab (81%). Renal survival was significantly higher in patients treated with eculizumab (85% at one, three and five years) compared to patients who did not receive this treatment (54%, 46% and 41%), respectively. Response to eculizumab was independent of hypertension severity and the presence of complement genetic abnormalities. Among patients with malignant hypertension caused by other diseases the prevalence of thrombotic microangiopathy was very low (5%). Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, thrombotic microangiopathy is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS.


Asunto(s)
Síndrome Hemolítico Urémico Atípico/complicaciones , Proteínas del Sistema Complemento/genética , Hipertensión Maligna/epidemiología , Índice de Severidad de la Enfermedad , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Hemolítico Urémico Atípico/genética , Síndrome Hemolítico Urémico Atípico/terapia , Inactivadores del Complemento/uso terapéutico , Femenino , Humanos , Hipertensión Maligna/diagnóstico , Hipertensión Maligna/genética , Hipertensión Maligna/terapia , Incidencia , Masculino , Persona de Mediana Edad , Plasmaféresis , Estudios Retrospectivos , Adulto Joven
7.
Am J Transplant ; 19(2): 434-447, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-29947163

RESUMEN

Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplant (KT) with short-term outcomes similar to those obtained from donation after brain death (DBD) donors. However, heterogeneous results in the long term have been reported. We compared 10-year outcomes between 237 KT recipients from uDCD donors maintained by normothermic extracorporeal membrane oxygenation (nECMO) and 237 patients undergoing KT from standard criteria DBD donors during the same period at our institution. We further analyzed risk factors for death-censored graft survival in the uDCD group. Delayed graft function (DGF) was more common in the uDCD group (73.4% vs 46.4%; P < .01), although glomerular filtration rates at the end of follow-up were similar in the 2 groups. uDCD and DBD groups had similar rates for 10-year death-censored graft (82.1% vs 80.4%; P = .623) and recipient survival (86.2% vs 87.6%; P = .454). Donor age >50 years was associated with graft loss in the uDCD group (hazard ratio: 1.91; P = .058), whereas the occurrence of DGF showed no significant effect. uDCD KT under nECMO support resulted in similar graft function and long-term outcomes compared with KT from standard criteria DBD donors. Increased donor age could negatively affect graft survival after uDCD donation.


Asunto(s)
Muerte Encefálica , Funcionamiento Retardado del Injerto/fisiopatología , Oxigenación por Membrana Extracorpórea/métodos , Supervivencia de Injerto , Trasplante de Riñón/mortalidad , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/métodos , Adulto , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Preservación de Órganos/métodos , Pronóstico , Factores de Riesgo , Tasa de Supervivencia
8.
Kidney Int ; 93(2): 450-459, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28911789

RESUMEN

Pregnancy-associated atypical hemolytic uremic syndrome (aHUS) refers to the thrombotic microangiopathy resulting from uncontrolled complement activation during pregnancy or the postpartum period. Pregnancy-associated aHUS is a devastating disease for which there is a limited clinical understanding and treatment experience. Here we report a retrospective study to analyze the clinical and prognostic data of 22 cases of pregnancy-associated aHUS from the Spanish aHUS Registry under different treatments. Sixteen patients presented during the first pregnancy and as many as nine patients required hemodialysis at diagnosis. Identification of inherited complement abnormalities explained nine of the 22 cases, with CFH mutations and CFH to CFHR1 gene conversion events being the most prevalent genetic alterations associated with this disorder (66%). In thirteen of the cases, pregnancy complications were sufficient to trigger a thrombotic microangiopathy in the absence of genetic or acquired complement alterations. The postpartum period was the time with highest risk to develop the disease and the group shows an association of cesarean section with pregnancy-associated aHUS. Seventeen patients underwent plasma treatments with a positive renal response in only three cases. In contrast, ten patients received eculizumab with an excellent renal response in all, independent of carrying or not inherited complement abnormalities. Although the cohort is relatively small, the data suggest that pregnancy-associated aHUS is not different from other types of aHUS and suggest the efficacy of eculizumab treatment over plasma therapies. This study may be useful to improve prognosis in this group of aHUS patients.


Asunto(s)
Síndrome Hemolítico Urémico Atípico , Complicaciones del Embarazo , Microangiopatías Trombóticas , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Hemolítico Urémico Atípico/epidemiología , Síndrome Hemolítico Urémico Atípico/genética , Síndrome Hemolítico Urémico Atípico/inmunología , Síndrome Hemolítico Urémico Atípico/terapia , Cesárea , Activación de Complemento , Proteínas Inactivadoras del Complemento C3b/genética , Factor H de Complemento/genética , Femenino , Conversión Génica , Humanos , Inmunosupresores/uso terapéutico , Mutación , Paridad , Intercambio Plasmático , Periodo Posparto , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/genética , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/terapia , Sistema de Registros , Diálisis Renal , Estudios Retrospectivos , Factores de Riesgo , España/epidemiología , Microangiopatías Trombóticas/epidemiología , Microangiopatías Trombóticas/genética , Microangiopatías Trombóticas/inmunología , Microangiopatías Trombóticas/terapia , Resultado del Tratamiento
10.
J Am Soc Nephrol ; 28(10): 3089-3099, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28592423

RESUMEN

Hematuria is a cardinal symptom in IgA nephropathy, but its influence on the risk of disease progression has been scarcely investigated. We followed a cohort of 112 patients with IgA nephropathy for a mean±SEM period of 14±10.2 years, during which clinical and analytic risk factors (including urine sediment examination) were regularly recorded. According to the magnitude of time-averaged hematuria, we classified patients as those with persistent hematuria and those with negative or minimal hematuria. We also classified patients according to the magnitude of time-averaged proteinuria (>0.75 or ≤0.75 g/d). The proportion of patients reaching ESRD or a 50% reduction of renal function was significantly greater among patients with persistent hematuria than patients with minimal or negative hematuria (30.4% and 37.0% versus 10.6% and 15.2%, respectively; P=0.01). Multivariable analysis revealed time-averaged hematuria, time-averaged proteinuria, renal function at baseline, and the presence of tubulointerstitial fibrosis on renal biopsy as independent predictors of ESRD. After hematuria disappearance, which occurred in 46% of the patients, the rate of renal function decline changed from -6.45±14.66 to -0.18±2.56 ml/min per 1.73 m2 per year (P=0.001). Patients with time-averaged proteinuria >0.75 g/d had significantly poorer renal survival than those with time-averaged proteinuria ≤0.75 g/d. However, on further classification by time-averaged hematuria, only those patients with time-averaged proteinuria >0.75 g/d and persistent hematuria had significantly worse renal survival than those in the other three groups. In conclusion, remission of hematuria may have a significant favorable effect on IgA nephropathy outcomes.


Asunto(s)
Glomerulonefritis por IGA/orina , Hematuria/etiología , Riñón/fisiopatología , Adulto , Estudios de Cohortes , Progresión de la Enfermedad , Femenino , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis por IGA/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Proteinuria/etiología , Remisión Espontánea , Factores de Riesgo , Adulto Joven
11.
Nephrol Dial Transplant ; 32(3): 466-474, 2017 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-28339660

RESUMEN

Background: Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab. Methods: We identified 29 patients with so-called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 × 10 9 /L) and haemoglobin, disappearance of all the markers of microangiopathic haemolytic anaemia (MAHA), and improvement of renal function, with a ≥25% reduction of serum creatinine from the onset of eculizumab administration. Results: Twenty-nine patients with secondary aHUS (15 drug-induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer-related, 1 associated with acute humoral rejection and 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a ≥50% serum creatinine reduction at the last follow-up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses. Conclusion: Short treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA-inducing condition.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Inactivadores del Complemento/uso terapéutico , Adulto , Síndrome Hemolítico Urémico Atípico/etiología , Síndrome Hemolítico Urémico Atípico/metabolismo , Síndrome de Churg-Strauss/complicaciones , Creatinina/metabolismo , Femenino , Humanos , Inmunosupresores/efectos adversos , Pruebas de Función Renal , Lupus Eritematoso Sistémico/complicaciones , Masculino , Persona de Mediana Edad , Plasmaféresis , Recuento de Plaquetas , Recurrencia , Insuficiencia Renal/etiología , Insuficiencia Renal/metabolismo , Esclerodermia Sistémica/complicaciones , Microangiopatías Trombóticas/tratamiento farmacológico , Microangiopatías Trombóticas/metabolismo
12.
Rheumatol Int ; 37(6): 1035-1041, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28289874

RESUMEN

Renal failure secondary to ANCA-associated vasculitis represents a clinical and therapeutic challenge. In this study, we aimed to assess the treatment response rates and long-term outcomes of vasculitis patients presenting with renal failure. This retrospective study included 151 patients with renal vasculitis from three hospitals who underwent a renal biopsy between 1997 and 2014. Patients with renal failure which required dialysis at the onset were compared to those presenting with more preserved renal function. The primary end point was treatment response and patient surivival. Patients with severe renal involvement had a lower response to treatment compared to those having preserved renal function (26.6 versus 93.4%; p < 0.001). Dialysis-dependent patients who received plasmapheresis in addition to immune suppressants associated a higher rate of renal recovery (41.6 versus 12.5%; p = 0.05). A higher incidence of severe infections was observed among patients with severe renal involvement (38.4 versus 18.1%, p = 0.01). The mortality rate was significantly higher among vasculitis patients presenting with renal failure (53.8 versus 22.2%, p = 0.001). Global survival at 1 and 5 years was 60 and 47% in patients requiring dialysis compared with 90 and 80% among those with more preserved renal function (p < 0.001). After multivariate adjustment, the need for dialysis remained as an independent predictor of death (HR 2.5; 95% CI 1.1-5.7; p = 0.03). The presence of severe renal dysfunction represents an independent risk factor for patient survival in renal vasculitis. Patients requiring dialysis associate a lower response rate to immunosuppressive therapy and a higher incidence of severe infections.


Asunto(s)
Lesión Renal Aguda/terapia , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/terapia , Inmunosupresores/uso terapéutico , Riñón/fisiopatología , Plasmaféresis , Diálisis Renal , Insuficiencia Renal/terapia , Lesión Renal Aguda/inmunología , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/fisiopatología , Adulto , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/inmunología , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/mortalidad , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/fisiopatología , Biopsia , Causas de Muerte , Enfermedades Transmisibles/mortalidad , Enfermedades Transmisibles/terapia , Progresión de la Enfermedad , Femenino , Humanos , Inmunosupresores/efectos adversos , Estimación de Kaplan-Meier , Riñón/inmunología , Riñón/patología , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Plasmaféresis/efectos adversos , Plasmaféresis/mortalidad , Modelos de Riesgos Proporcionales , Diálisis Renal/efectos adversos , Diálisis Renal/mortalidad , Insuficiencia Renal/inmunología , Insuficiencia Renal/mortalidad , Insuficiencia Renal/fisiopatología , Estudios Retrospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , España , Factores de Tiempo , Resultado del Tratamiento
13.
Enferm Infecc Microbiol Clin ; 35(6): 367-376, 2017.
Artículo en Inglés, Español | MEDLINE | ID: mdl-28238506

RESUMEN

Rapid diagnostic techniques are valuable tools in the diagnosis of gastrointestinal infections, especially for the detection of some microorganisms and in certain groups of patients. While antigen detection techniques are widely used in Clinical Microbiology laboratories, for the diagnosis of viruses, some parasites and some bacteria, molecular techniques are routinely used only for some pathogens (such as Clostridium difficile). However, molecular techniques are constantly evolving, and they allow a rapid diagnosis for an increasing number of pathogens, with high sensitivity and specificity. In addition, they are also able to detect virulence factors or resistance mechanisms. Syndromic surveillance systems, which detect different pathogens simultaneously, are very promising because they enable the most frequent pathogens to be diagnosed in a few hours and they can be very useful in certain patients. For the diagnosis of Helicobacter pylori infection, molecular techniques are able to detect bacteria and its resistance to clarithromycin and levofloxacin, allowing the most appropriate treatment to be selected for each patient when bacterial culture is not possible.


Asunto(s)
Técnicas de Diagnóstico del Sistema Digestivo , Enfermedades Gastrointestinales/diagnóstico , Técnicas Bacteriológicas , Enfermedades Gastrointestinales/microbiología , Enfermedades Gastrointestinales/parasitología , Enfermedades Gastrointestinales/virología , Humanos , Técnicas Inmunológicas , Técnicas de Diagnóstico Molecular , Parasitología/métodos , Factores de Tiempo , Virología/métodos , Compuestos Orgánicos Volátiles/análisis
14.
Enferm Infecc Microbiol Clin ; 34(3): 184-7, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26139304

RESUMEN

BACKGROUND: Achromobacter xylosoxidans is an emerging pathogen in cystic fibrosis (CF). Although the rate of colonization by this microorganism is variable, prevalence is increasing in CF units. METHODS: A microbiological/clinical study was conducted on of adult CF patients harboring A. xylosoxidans. Identification and susceptibility testing were performed using MicroScan (Siemens). Decline in lung function was assessed using the variable, annual percentage loss of FEV1 (forced expiratory volume in 1s). RESULTS: A. xylosoxidans was isolated in 18 (19.8%) of 91 patients over a 14-year period. Mean age was 26.6 years (18-39 years). Nine patients (9.8%) were chronically colonized. Piperacillin/tazobactam and imipenem were the most active antibiotics. Mean annual decline in lung function in chronically colonized patients was 2.49%. CONCLUSIONS: A. xylosoxidans is a major pathogen in CF. A decreased lung function was observed among patients who were chronically colonized by A. xylosoxidans. Antibiotic therapy should be started early in order to prevent chronic colonization by this microorganism.


Asunto(s)
Achromobacter denitrificans/aislamiento & purificación , Fibrosis Quística/microbiología , Infecciones por Bacterias Gramnegativas/complicaciones , Adolescente , Adulto , Antibacterianos/uso terapéutico , Fibrosis Quística/tratamiento farmacológico , Femenino , Volumen Espiratorio Forzado , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos , Masculino , Estudios Retrospectivos , Adulto Joven
15.
Kidney Int ; 88(5): 1153-60, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26221755

RESUMEN

C3 glomerulonephritis is a clinicopathologic entity defined by the presence of isolated or dominant deposits of C3 on immunofluorescence. To explore the effect of immunosuppression on C3 glomerulonephritis, we studied a series of 60 patients in whom a complete registry of treatments was available over a median follow-up of 47 months. Twenty patients had not received immunosuppressive treatments. In the remaining 40 patients, 22 had been treated with corticosteroids plus mycophenolate mofetil while 18 were treated with other immunosuppressive regimens (corticosteroids alone or corticosteroids plus cyclophosphamide). The number of patients developing end-stage renal disease was significantly lower among treated compared with untreated patients (3 vs. 7 patients, respectively). No patient in the corticosteroids plus mycophenolate mofetil group doubled serum creatinine nor developed end-stage renal disease, as compared with 7 (significant) and 3 (not significant), respectively, in patients treated with other immunosuppressive regimens. Renal survival (100, 80, and 72% at 5 years) and the number of patients achieving clinical remission (86, 50, and 25%) were significantly higher in patients treated with corticosteroids plus mycophenolate mofetil as compared with patients treated with other immunosuppressive regimens and untreated patients, respectively. Thus, immunosuppressive treatments, particularly corticosteroids plus mycophenolate mofetil, can be beneficial in C3 glomerulonephritis.


Asunto(s)
Complemento C3 , Glomerulonefritis/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Ácido Micofenólico/análogos & derivados , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Antiinflamatorios/uso terapéutico , Creatinina/sangre , Ciclofosfamida/uso terapéutico , Progresión de la Enfermedad , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Glomerulonefritis/complicaciones , Glomerulonefritis/inmunología , Humanos , Fallo Renal Crónico/etiología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Estudios Retrospectivos , Tasa de Supervivencia , Adulto Joven
17.
Kidney Int Rep ; 9(6): 1742-1751, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38899166

RESUMEN

Introduction: Persistent chronic hypotension affects 5-10% of dialysis patients. It seems to be reversible after receiving a functioning graft, but data regarding its influence on transplant outcomes are scarce. We analyze the evolution of patients with chronic hypotension in dialysis who undergo kidney transplantation at our center. Methods: A retrospective observational study was conducted. Sixty-six patients with chronic hypotension (defined as systolic blood pressure ≤ 100 mm Hg at the time of transplantation) were identified. A control group of 66 non-hypotensive patients was assigned. The evolution of both groups was compared. Results: Hypotensive patients had higher rates of primary non-function (18.2% vs. 6.1%; P = 0.03) mainly due to venous thrombosis of the allograft, worse renal function at the end of follow-up (eGFR of 35 mL/min/1.73 m2 vs 48 mL/min/1.73 m2, P = 0.001) but there was no statistical difference in graft survival after censoring for primary non-function. After multivariable adjustment, chronic hypotension remained an independent predictor factor for graft failure (adjusted HR of 2.85; 95% CI: 1.24-6.57; P = 0.014). Use of vasoactive drugs and anticoagulation in hypotensive patients was associated with 7.1% of venous graft thrombosis compared to 17.3% in those with no intervention (P = 0.68). Receiving a functioning graft implied blood pressure normalization in patients with chronic hypotension. Conclusion: Chronic hypotension in dialysis has a negative impact on short-term kidney transplant outcomes but a lower impact on long-term results. It is reversible after receiving a functioning graft. Identifying this subgroup of patients seems crucial to implement measures aimed at improving transplant results.

19.
Front Immunol ; 14: 1310469, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38274833

RESUMEN

Background: Secondary atypical hemolytic uremic syndrome (secondary aHUS) is a heterogeneous group of thrombotic microangiopathies (TMA) associated with various underlying conditions. Unlike primary aHUS, there is still no hard evidence on the efficacy of complement blockade in secondary aHUS, since the two main series that investigated this subject showed discrepant results. Our work aims to reassess the efficacy of eculizumab in treating secondary aHUS. Methods: Observational, retrospective, single-center study, in which we analyzed the hematological and renal evolution of 23 patients diagnosed with secondary aHUS who received treatment with eculizumab and compared them with a control cohort of 14 patients. Complete renal response was defined as the recovery of renal function before the event, partial renal response as a recovery of 50% of lost glomerular filtration rate, and hematological response as normalization of hemoglobin and platelets. Results: We found no statistically significant differences in baseline characteristics or disease severity between both groups. After a median of 5 doses of eculizumab, the group of patients who received complement blockade presented a significant difference in renal response (complete in 52.3% of patients and partial in 23.8%) compared to the control cohort (complete response 14.3% and partial of 14.3%). Rates of hematological remission were similar in both groups (90.9% in the eculizumab cohort and 85.7% in the control cohort). Conclusion: Early and short-term use of eculizumab in patients with secondary aHUS could be an effective and safe therapeutic option, assuring better renal recovery compared to patients who do not receive complement blockade.


Asunto(s)
Síndrome Hemolítico Urémico Atípico , Humanos , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Estudios Retrospectivos , Riñón , Anticuerpos Monoclonales Humanizados/uso terapéutico , Proteínas del Sistema Complemento/uso terapéutico
20.
Front Nephrol ; 3: 1114486, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37675351

RESUMEN

Background: The current definition of chronic kidney disease applied to patients over the age of 80 has increased the number of referrals to Nephrology. However not all of these patients may benefit from its assessment. This study aims to analyze the evolution of ≥80 years old patients referred to Nephrology. Methods: Single-center study including patients ≥80 years old with eGFR <60 mL/min/1,73m2 who were referred to Nephrology consultation for the first time. Clinical and analytical parameters were collected retrospectively 12 months before the visit, and prospectively at baseline, and 12 and 24 months after the initial visit. We divided patients into two groups based on annual eGFR loss: progressors (>5 mL/min/1.73m2) and non-progressors (≤5 mL/min/1,73m2). Results: A total of 318 patients were included, mean age was 84,9 ± 4 (80-97) years. Baseline serum creatinine was 1,65 ± 0,62 mg/dL, eGRF 35 (28-42) mL/min/1,73, and albumin/creatinine ratio 36 (7-229) mg/g. 55,7% of the patients met the definition of progressor at baseline (initial-progressors), 26,3% were progressors after a 12-month follow-up and 13,4% after 24 months. 21,2% and 11,4% of initial-progressors met this definition at 12 and 24 month follow up. The main risk factor for progression was albuminuria. No relationship was found between the nephrologist intervention and the evolution of renal function among initial non-progressors. Conclusion: Elderly patients who have stable renal function at the time of referral will continue to have stable renal function over the subsequent 24 months and thus may not need to be referred to a nephrologist.

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