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Background: Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Corona Virus 2 has generated significant impact on global health worldwide. COVID-19 can cause pneumonia and organ injury. Chronic kidney disease (CKD) has been associated with increased mortality in previous epidemics, but there is a paucity of data regarding actual risks for non-dialysis CKD patients with COVID-19. Methods: Multicenter, observational cohort study including 136 non-dialysis CKD patients and 136 age- and sex-matched controls that required hospitalization due to COVID-19. Patients with end-stage renal disease, a kidney transplant or without registered baseline glomerular filtration rate prior to COVID-19 infection were excluded. CKD and acute kidney injury (AKI) were defined according to KDIGO criteria. Results: CKD patients had higher white blood cell count and D-dimer and lower lymphocyte percentage. No differences were found regarding symptoms on admission. CKD was associated with higher rate of AKI (61 vs. 24.3%) and mortality (40.4 vs. 24.3%). Patients with AKI had the highest hazard for death (AKI/non-CKD HR:7.04, 95% CI:2.87-17.29; AKI/CKD HR:5.25, 95% CI: 2.29-12.02), followed by CKD subjects without AKI (HR:3.39, 95% CI:1.36-8.46). CKD status did not condition ICU admission or length of in-hospital stay. Conclusions: CKD patients that require hospitalization due to COVID-19 are exposed to higher risk of death and AKI.
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BACKGROUND: Spain has dramatically increased the number of controlled circulatory death donors (cDCD). The initial selection criteria for considering cDCD for kidney transplantation (KT) have been expanded progressively, with practically no limits in donor age during the last years. We aimed to analyze the early clinical outcomes using expanded (> 65 years) cDCD in comparison with standard ones. METHODS: Observational multicenter study including 19 transplant centers in Spain. We performed a systematic inclusion in a central database of every KT from expanded cDCD at each participant unit from January-2012 to January-2017. Surgical procedures and immunosuppressive protocols were based on local practices. Data was analyzed in the central office using logistic and Cox regression or competitive-risk models for multivariate analysis. Median time of follow-up was 18.1 months. RESULTS: 561 KT were performed with kidneys from cDCD, 135 from donors older than 65 years. As expected, recipients from older cDCD were also older (65.8 (SD 8.8) vs 53.7 (SD 11.4) years; p < 0.001) and with higher comorbidity. At 1 year, no differences were found amongst older and younger cDCD KT recipients in terms of serum creatinine (1.6 (SD 0.7) vs 1.5 (SD 0.8) mg/dl; p = 0.29). Non-death censored graft survival was inferior, but death-censored graft survival was not different (95.5 vs 98.2% respectively; p = 0.481). They also presented a trend towards higher delayed graft function (55.4 vs 46.7%; p = 0.09) but a similar rate of primary non-function (3.7 vs 3.1%; p = 0.71), and acute rejection (3.0 vs 6.3%; p = 0.135). In the multivariate analysis, in short follow-up, donor age was not related with worse survival or poor kidney function (eGFR < 30 ml/min). CONCLUSIONS: The use of kidneys from expanded cDCD is increasing for older and comorbid patients. Short-term graft outcomes are similar for expanded and standard cDCD, so they constitute a good-enough source of kidneys to improve the options of KT wait-listed patients.
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Selección de Donante/métodos , Supervivencia de Injerto/fisiología , Trasplante de Riñón/mortalidad , Choque/mortalidad , Donantes de Tejidos , Factores de Edad , Anciano , Selección de Donante/tendencias , Femenino , Humanos , Trasplante de Riñón/tendencias , Masculino , Persona de Mediana Edad , Sistema de Registros , Choque/diagnóstico , España/epidemiología , Tasa de Supervivencia/tendencias , Resultado del TratamientoRESUMEN
INTRODUCTION: Many European countries have transplant programmes with controlled donors after cardiac death (cDCD). Twenty-two centres are part of GEODAS group. We analysed clinical results from a nephrological perspective. METHODS: Observational, retrospective and multicentre study with systematic inclusion of all kidney transplant recipients from cDCD, following local protocols regarding extraction and immunosuppression. RESULTS: A total of 335 cDCD donors (mean age 57.2 years) whose deaths were mainly due to cardiovascular events were included. Finally, 566 recipients (mean age 56.5 years; 91.9% first kidney transplant) were analysed with a median of follow-up of 1.9 years. Induction therapy was almost universal (thymoglobulin 67.4%; simulect 32.8%) with maintenance with prednisone-MMF-tacrolimus (91.3%) or combinations with mTOR (6.5%). Mean cold ischaemia time (CIT) was 12.3h. Approximately 3.4% (n=19) of recipients experienced primary non-function, essentially associated with CIT (only CIT ≥ 14 h was associated with primary non-function). Delayed graft function (DGF) was 48.8%. DGF risk factors were CIT ≥ 14 h OR 1.6, previous haemodialysis (vs. peritoneal dialysis) OR 2.1 and donor age OR 1.01 (per year). Twenty-one patients (3.7%) died with a functioning graft, with a recipient and death-censored graft survival at 2-years of 95% and 95.1%, respectively. The estimated glomerular filtration rate at one year of follow-up was 60.9 ml/min. CONCLUSIONS: CIT is a modifiable factor for improving the incidence of primary non-function in kidney transplant arising from cDCD. cDCD kidney transplant recipients have higher delayed graft function rate, but the same patient and graft survival compared to brain-dead donation in historical references. These results are convincing enough to continue fostering this type of donation.
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Paro Cardíaco , Trasplante de Riñón , Donantes de Tejidos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Causas de Muerte , Niño , Preescolar , Isquemia Fría/efectos adversos , Isquemia Fría/estadística & datos numéricos , Funcionamiento Retardado del Injerto/epidemiología , Funcionamiento Retardado del Injerto/etiología , Femenino , Tasa de Filtración Glomerular , Supervivencia de Injerto , Paro Cardíaco/mortalidad , Humanos , Estimación de Kaplan-Meier , Trasplante de Riñón/mortalidad , Trasplante de Riñón/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Preservación de Órganos/métodos , Estudios Retrospectivos , España , Factores de Tiempo , Donantes de Tejidos/estadística & datos numéricos , Receptores de Trasplantes/estadística & datos numéricos , Resultado del Tratamiento , Adulto JovenRESUMEN
Post-transplantation lymphoproliferative disorder (PTLD) is a well-know complication after organ transplantation. We report a case of a patient who developed an extramedullary plasmacytoma-like PTLD around his transplanted kidney treated with standard multiple myeloma chemotherapy. Three years after benefiting of a deceased donor kidney transplant for an end stage kidney disease secondary to nephroangiosclerosis, our patient developed an extra-medullary plasmacytoma confined to the transplant compartment. The transplant function was unaltered, and due to the absence of reduction of the lesion after immunosuppression reduction, a chemotherapy by bortezomib-cyclophosphamide-dexamethasone (VCD) known to be efficient in multiple myeloma was initiated. After 6 cycles, positron emission tomography (PET) scan showed complete metabolic remission confirming the biological exams. This case report suggests that a chemotherapy such as VCD can efficiently treat plasmacytoma-like PTLD allowing graft survival. Therefore, transplant removal may not be mandatory as the best second line treatment after unsuccessfulness reduction of immunosuppression.
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Neoplasias Renales/patología , Trasplante de Riñón/efectos adversos , Trastornos Linfoproliferativos/diagnóstico , Plasmacitoma/diagnóstico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Terapia de Inmunosupresión/efectos adversos , Neoplasias Renales/tratamiento farmacológico , Trastornos Linfoproliferativos/tratamiento farmacológico , Trastornos Linfoproliferativos/etiología , Masculino , Plasmacitoma/tratamiento farmacológico , Plasmacitoma/etiología , Tomografía de Emisión de Positrones , Trasplante HomólogoRESUMEN
BACKGROUND AND OBJECTIVES: The relationship between mineral metabolism disorders, bone fractures and vascular calcifications in kidney transplant recipients has not been established. METHOD: We performed a cross-sectional study in 727 stable recipients from 28 Spanish transplant clinics. Mineral metabolism parameters, the semi-quantification of vertebral fractures and abdominal aortic calcifications were determined centrally. RESULTS: Vitamin D deficiency (25OHD3<15ng/ml) was more common in female recipients at CKD-T stages I-III (29.6% vs 44.4%; p=0.003). The inverse and significant correlation between 25OHD3 and PTH was gender-specific and women exhibited a steeper slope than men (p=0.01). Vertebral fractures (VFx) with deformity grade ≥2 were observed in 15% of recipients. Factors related to VFx differed by gender; in males, age (OR 1.04; 95% CI 1.01-1.06) and CsA treatment (OR: 3.2; 95% CI: 1.6-6.3); in females, age (OR 1.07; 95% CI: 1.03-1.12) and PTH levels (OR per 100pg/ml increase: 1.27; 95% CI: 1.043-1.542). Abdominal aortic calcifications were common (67.2%) and related to classical risk factors but not to mineral metabolism parameters. CONCLUSIONS: Vitamin D deficiency is more common among female kidney transplant recipients at earlier CKD-T stages, and it contributes to secondary hyperparathyroidism. Prevalent vertebral fractures are only related to high serum PTH levels in female recipients.
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Enfermedades de la Aorta/metabolismo , Calcinosis/metabolismo , Trasplante de Riñón , Minerales/metabolismo , Complicaciones Posoperatorias/metabolismo , Factores Sexuales , Fracturas de la Columna Vertebral/metabolismo , Anciano , Albuminuria/etiología , Aorta Abdominal , Enfermedades de la Aorta/etiología , Calcinosis/etiología , Estudios Transversales , Ciclosporina/efectos adversos , Femenino , Humanos , Hiperparatiroidismo Secundario/etiología , Hiperparatiroidismo Secundario/metabolismo , Inmunosupresores/efectos adversos , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Factores de Riesgo , Fracturas de la Columna Vertebral/etiología , Tacrolimus/efectos adversos , Deficiencia de Vitamina D/complicacionesRESUMEN
BACKGROUND: Cysteamine has improved survival and prognosis in cystinosis. Increasing numbers of patients reach adulthood and face new challenges such as compliance that wanes over time. The aim of this study was to evaluate adherence to cysteamine treatment in a group of cystinotic patients in Spain in an attempt to identify potential therapy pitfalls and improve the overall care of affected individuals. Despite the impact of cysteamine on prognosis, there is a paucity of data regarding adherence. METHOD: Thirty-four cystinotic patients (21 male) 38% ≥18 years were enrolled in a voluntary, anonymous survey. Replies were obtained from patients (15/34), mothers (11/34), fathers (4/34) and both parents (4/34). RESULTS: Patient age (median and interquartile range) at diagnosis was 1 year (0.57-1), and patient age at Cystagon® initiation was also 1 year (0.8-1.8). Sixteen (47%) were kidney transplant (KTx) recipients; six were retransplanted. Age at first KTx 10 years (8.7-13.7). Patient understanding of multiorgan involvement in cystinosis: 4.1 organs reported; eye 97% and kidney 91%. Cysteamine was given by mother (100%) and father (83%) in <11 year olds, or self-administered (94%) in ≥11 year olds. Four daily doses in 89% versus 56% in <11 year olds or ≥11 year olds, with fixed schedule in 94% versus 50% in <11 or ≥11 year olds and progressive loss of reminders over time. Furthermore, 44% complained of unpleasant smell. Motivation for treatment compliance was 100% versus 40% in <11 versus ≥11 year olds, respectively. Disease impact in patients <18 years is as follows: school (29%), social (14%), 'feeling different' (10%); in patients ≥18 years: 'feeling different' (62%), professional (39%) and job absenteeism (31%). Referring physician: paediatric nephrologist (94%) and nephrologist (63%) in <11 versus ≥11 year olds. Ophthalmological follow-up: 83% versus 38% in <11 versus ≥11 year olds. Patient opinion of physician expertise: paediatric nephrologist (94%) and nephrologist (44%). New treatment options (65%) and better information (42%) were demanded to improve adherence. CONCLUSION: Treatment with Cystagon is effective in young patients. However, adherence diminishes over time in adolescents and adults despite disease impact. Strategies such as better information on the disease, patient self-care promotion and facilitated transition to adult healthcare services are required to improve compliance and the clinical management of cystinosis.
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Cisteamina/uso terapéutico , Depletores de Cistina/uso terapéutico , Cistinosis/tratamiento farmacológico , Conocimientos, Actitudes y Práctica en Salud , Cumplimiento de la Medicación , Autocuidado , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Pronóstico , España , Adulto JovenRESUMEN
INTRODUCTION: Continuous erythropoietin receptor activator (C.E.R.A.) effectively enables anemia control in patients with chronic kidney disease, but little information is available in renal transplant recipients. The authors aimed to evaluate the effect of C.E.R.A. under clinical practice conditions on anemia control in renal transplant recipients. METHODS: This was a multicenter, retrospective, observational study carried out in adult renal transplant patients in the immediate posttransplant period and at late posttransplant period receiving C.E.R.A. in clinical practice. Patients' data were retrieved from their medical charts at baseline and months 1, 3, and 6. RESULTS: A total of 318 evaluable patients were enrolled into the study: 32 in the immediate posttransplant period and 286 at late posttransplant period (erythropoiesis-stimulating agent [ESA]-naïve, n = 44; converting from other ESAs, n = 242). Patients in the immediate posttransplant period experienced a significant increase in hemoglobin (Hb) levels from baseline to month 1 (9.9±1.5 g/dL vs. 11.5±1.4 g/dL; P< 0.001). ESA-naïve patients showed increasing mean Hb levels from baseline to month 6 (10.1±0.7 g/dL vs. 11.7±1.0 g/dL; P < 0.001) and 94.7% achieved Hb ≥11 g/dL during the study. In patients converted from other ESAs, the percentage of patients with Hb between 11-13 g/dL was maintained from baseline to month 6 with no significant differences (61.0% vs. 62.4%). Mean monthly doses of C.E.R.A. at baseline were 134.4±56.4 µg, 81.3±28.1 µg, and 93.0±44.2 µg in immediate posttransplant, ESA-naïve, and converted patients, respectively. C.E.R.A. was well tolerated. CONCLUSION: C.E.R.A. enables anemia control in renal transplant recipients, allowing target Hb levels to be achieved and maintained with doses even below those described in the Summary of Product Characteristics.
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Anemia/tratamiento farmacológico , Anemia/etiología , Eritropoyetina/administración & dosificación , Hemoglobinas/efectos de los fármacos , Trasplante de Riñón/efectos adversos , Polietilenglicoles/administración & dosificación , Adulto , Anemia/fisiopatología , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Eritropoyetina/efectos adversos , Femenino , Estudios de Seguimiento , Hemoglobinas/análisis , Humanos , Inyecciones Subcutáneas , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Masculino , Persona de Mediana Edad , Polietilenglicoles/efectos adversos , Cuidados Posoperatorios/métodos , Estudios Retrospectivos , Medición de Riesgo , Administración de la Seguridad , Índice de Severidad de la Enfermedad , España , Factores de Tiempo , Resultado del TratamientoRESUMEN
UNLABELLED: Lung cancer is a malignant disease with increasing mortality rates. Cytokines play a role in normal cell growth regulation and differentiation and are also implicated in malignant disease. Among these cytokines, Transforming Growth Factor ß type 1 (TGF-ß1) acts as a tumor promoter in malignant cells. Several clinical studies have found high levels of TGF-ß1 in various cancer types. The aim of this study was to establish a TGF-ß1 cut-off point as a complementary diagnostic tool in lung cancer detection. Therefore, 72 clinically well-characterized individuals were studied, 41 lung cancer patients and 31 healthy subjects. Serum TGF-ß1 concentration was measured by an enzyme-linked immunosorbent assay (ELISA). We compared statistically the serum TGF-ß1 concentration between both groups with analysis of variance, linear regression and receiver operating curve analysis. We observed that lung cancer patients produced higher TGF-ß1 levels than healthy individuals (37,225±9,436 vs. 28,416±9,324 pg/ml, P<0.001). The cut-point diagnostic value was 30,500 pg/ml with 80.5% sensitivity, 64.5% specificity and odds ratio: 7.5, 95% CI: 2.6-21.8. CONCLUSIONS: We found significantly higher TGF-ß1 levels in lung cancer patients than in healthy individuals. We propose the measurement of serum TGF-ß1 levels as a complementary diagnostic test in lung cancer detection.
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Biomarcadores de Tumor/sangre , Neoplasias Pulmonares/sangre , Factor de Crecimiento Transformador beta1/sangre , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Curva ROCRESUMEN
PURPOSE: Paragangliomas of the head and neck are neuroendocrine tumors and are associated with germ line mutations of the tricarboxylic acid cycle-related genes SDHB, SDHC, SDHD, and SDHAF2. Hypoxia is important in most solid tumors, and was directly implicated in tumorigenesis over 40 years ago when it was shown that dwelling at high altitudes increases the incidence of carotid body hyperplasia and paragangliomas. Although recent research has now elucidated several pathways of hypoxia in paragangliomas, nothing is currently known of the genetics or of gene-environment interactions in high-altitude paraganglioma. We postulated that SDH mutations might play a role in these tumors. EXPERIMENTAL DESIGN: Patients from a Mexican family, originating and resident in Guadalajara, were tested for mutations of SDHD, and subsequently, for mutations of SDHB followed by immunohistochemical confirmation of SDHB loss. RESULTS: Two patients, born and resident at altitudes of between 1,560 and 2,240 m, were found to have head and neck paragangliomas, including a remarkably aggressive recurrent tumor. Mutation analysis identified a pathogenic missense mutation in exon 7 of SDHB, c.689G>A, p.Arg230His, and loss of the SDHB protein was confirmed by immunohistochemistry. CONCLUSIONS: This is the first report of a SDH gene mutation in paraganglioma at high altitude. A rapidly recurrent head and neck paraganglioma is a very rare finding in an SDH mutation carrier, suggesting a gene-environment interaction. Neither patient showed evidence of sympathetic paraganglioma.
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Altitud , Tumor del Cuerpo Carotídeo/genética , Hipoxia de la Célula/genética , Succinato Deshidrogenasa/genética , Anciano , Tumor del Cuerpo Carotídeo/etiología , Tumor del Cuerpo Carotídeo/patología , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Neoplasias de Cabeza y Cuello/etiología , Neoplasias de Cabeza y Cuello/genética , Humanos , Inmunohistoquímica , Masculino , Mutación , Neoplasias Primarias Múltiples/patología , Neoplasias Ováricas/patología , Linaje , Reacción en Cadena de la PolimerasaRESUMEN
BACKGROUND: Nosocomial transmission of hepatitis C virus (HCV) in hemodialysis (HD) units is well established. In units with a high prevalence of HCV infection, the implementation of universal precautionary measures may not suffice in order to decrease the incidence and prevalence of HCV. In this setting strict isolation practices can be useful in order to achieve this goal. METHODS: The incidence and prevalence of HCV infection amongst all HD and peritoneal dialysis (PD) patients from the province of Albacete, Spain, have been studied from 1992 to 2003.Through the 1993-1995 period chronic HD patients were treated either in a room exclusively for HCV- patients or in a room shared by HCV+ and HCV- patients. Complete separation of HCV+ and HCV- patients was implemented in 1995. Acute patients have been separated since 1992. The implementation of universal precautions was applied throughout the period. RESULTS: There has not been a single seroconversion in the rooms where only HCV- patients were dialyzed during the 11 years of follow-up. There were two seroconversions in the rooms shared for 3 years by both HCV+ and HCV- patients. In 1995 the prevalence of HCV+ cases in HD and PD was 21.6 and 23.2%, respectively. Since then it has decreased steadily and in parallel for both therapies, and the current prevalence is 6.8% in HD and 5.7% in PD. CONCLUSIONS: In HD units with a high prevalence of HCV+ patients, strict isolation in combination with implementation of universal prevention measures can eliminate nosocomial transmission and obtain a long-term reduction in prevalence.
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Infección Hospitalaria/epidemiología , Hepatitis C/epidemiología , Aislamiento de Pacientes/estadística & datos numéricos , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , Enfermedad Aguda , Infección Hospitalaria/etiología , Infección Hospitalaria/prevención & control , Unidades de Hemodiálisis en Hospital , Hepatitis C/etiología , Hepatitis C/prevención & control , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Trasplante de Riñón/estadística & datos numéricos , Prevalencia , Precauciones UniversalesRESUMEN
Development of tuberculosis infection in a renal transplant patient is infrequent in Spain, although the prevalence is higher than in the general population. These patients usually receive calcineurin inhibitors as the main component of their immunosuppressive treatment. The metabolism of these drugs, whether cyclosporine or tacrolimus, involves cytochrome P-450 3A. Rifampin, a widely used agent in the treatment of tuberculosis, is also an important inducer of cytochrome P-450 3A metabolism and has the capacity to decrease serum levels of the calcineurin inhibitors. This metabolic interaction makes pharmacologic management of tuberculosis-infected transplant patients more complex and can result in a higher risk of acute rejection caused by decreased levels of the immunosuppressant in the blood. The authors present a case of a renal transplant patient with a soft tissue infection caused by Mycobacterium tuberculosis who was treated with rifabutin instead of rifampin, with excellent results in terms of graft survival and overall survival. The use of rifabutin allowed the authors to achieve better control of circulating immunosuppressant levels and a lower probability of acute graft rejection.