RESUMEN
BACKGROUND: Cyst infection may occur in autosomal dominant polycystic kidney disease (ADPKD) and autosomal dominant polycystic liver disease (ADPLD). Antimicrobial agents often fail to control infection, leading to invasive action. We aimed to identify factors predicting escalation of care. METHODS: ADPKD and ADPLD patients were identified from local/national databases (2001-2013). Records were screened for patients meeting criteria for cyst infection (positive cyst aspirate and/or clinical findings). Factors that predict escalated care were identified with multivariate modified Poisson regression. RESULTS: We screened 1773 patients. A total of 77 patients with cyst infection (4.3%) were included for analysis (hepatic 36%; male 49%; age 54 ±; 13 years; ADPKD 95%; dialysis 9%, diabetes 18%, renal transplant 56%, eGFR [IQR 24-78] ml/min/1.73 m2 (excluding patients with a history of renal transplant or receiving dialysis)). A pathogen was identified in 71% of cases. Escherichia coli was the most common pathogen and accounted for 69% of cases. Initial treatment was limited to antibiotics in 87% of patients (n = 67), 40% included a fluoroquinolone. Ultimately, 48% of patients underwent some form of invasive action (escalation of care). Increasing white blood cell count (WBC) (RR 1.04 95%-CI 1.01-1.07, p = 0.008) was associated with escalating care, whereas an increase in time between transplant and infection (RR 0.92 95% CI 0.86-0.97, p = 0.005) and E. coli isolation (RR 0.55 95% CI 0.34-0.89, p = 0.02) were protective. CONCLUSION: High serum WBC, isolation of atypical pathogens and early infection after transplantation are factors that increase the risk of escalation of care in hepatic and renal cyst infection patients.
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Antibacterianos/uso terapéutico , Quistes/complicaciones , Infecciones por Escherichia coli/tratamiento farmacológico , Hepatopatías/complicaciones , Riñón Poliquístico Autosómico Dominante/complicaciones , Anciano , Quistes/genética , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/sangre , Infecciones por Escherichia coli/cirugía , Femenino , Humanos , Trasplante de Riñón , Recuento de Leucocitos , Hepatopatías/genética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Hepatic cyst infection is a potentially severe complication in cystic disease. Treatment demands effective antibiotic concentrations within the infected cyst. OBJECTIVES: The aim of this study was to use elective hepatic cyst drainage as a unique pharmacokinetic model to investigate whether cefazolin, a first-generation cephalosporin, is able to penetrate hepatic cysts. PATIENTS AND METHODS: Patients scheduled to undergo percutaneous aspiration sclerotherapy of a symptomatic non-infected, non-neoplastic hepatic cyst were eligible for this study. All participants received a single perioperative prophylactic dose of cefazolin (1000 mg, intravenously). We collected blood and cyst fluid samples to determine total and unbound cefazolin concentrations using HPLC. The primary outcome was hepatic cyst penetration, expressed as the ratio (%) of unbound concentration of cefazolin in cyst fluid to plasma (both in mg/L). RESULTS: We included eight patients [maleâ=â25%, median ageâ=â60 years (IQR 54-75), median estimated glomerular filtration rateâ=â97 mL/min/1.73 m(2) (IQR 67-102) and median serum albuminâ=â40 g/L (IQR 37-40)]. We detected low concentrations of unbound cefazolin in cyst fluid (≤1.0 mg/L). The median plasma unbound cefazolin peak level (immediately after cefazolin administration) was 36.6 mg/L (IQR 23.7-54.1) and the level at the time of cyst fluid aspiration was 16.1 mg/L (IQR 13.0-20.1). In total, the hepatic cyst penetration of free cefazolin was only 2.2% (IQR 0.7-5.2). CONCLUSIONS: We developed a study model to investigate the penetration of antibiotics into hepatic cysts. Cefazolin did not reach adequate intracystic concentrations. Future studies should explore alternatives.
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Antibacterianos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Cefazolina/farmacocinética , Quistes/complicaciones , Hepatopatías/complicaciones , Escleroterapia , Anciano , Antibacterianos/administración & dosificación , Aspiraciones Psicológicas , Secreciones Corporales/química , Cefazolina/administración & dosificación , Cromatografía Líquida de Alta Presión , Quistes/cirugía , Femenino , Humanos , Hepatopatías/cirugía , Masculino , Persona de Mediana Edad , Plasma/químicaRESUMEN
BACKGROUND: For decades, high-dose intravenous cyclophosphamide (ivCY) given for 24-30 months was regarded as the standard therapy for proliferative lupus nephritis, despite serious side effects. Our aim was to evaluate the effect of induction therapy with short-term high-dose ivCY followed by mycophenolate mofetil (MMF) on disease parameters, mortality and health-related quality of life (HRQoL) in patients with proliferative lupus nephritis. METHODS: Between January 2003 and November 2006, 71 patients with biopsy-proven proliferative lupus nephritis were included in the second Dutch Lupus Nephritis Study. All patients were treated with ivCY (750 mg÷m2, six monthly pulses) plus oral prednisone, followed by MMF (2000 mg÷day) plus oral prednisone for 18 months, and then azathioprine (2 mg÷kg÷day) plus oral prednisone. Study endpoints included the occurrence of renal relapse, end-stage renal disease (ESRD) and mortality. RESULTS: After a median follow-up of 3.8 years (range 0.1-4.5), four (5.6%) of the 71 patients had a renal relapse, one (1.4%) failed treatment, one (1.4%) reached ESRD, and two (2.8%) died. Systemic lupus erythematosus (SLE) Disease Activity Index, serum creatinine, proteinuria and antibodies against anti-dsDNA decreased significantly during treatment and serum levels of complement factor 3 and 4 increased significantly. Furthermore, six of eight domains of the Short Form-36 as well as the number of symptoms and total distress level according to the SLE Symptom Checklist improved significantly over time. CONCLUSIONS: This open-label study shows that induction therapy with short-term (six monthly pulses) high-dose ivCY followed by MMF is effective in preventing renal relapses, ESRD and mortality and improving HRQoL in patients with proliferative lupus nephritis.
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Ciclofosfamida/administración & dosificación , Inmunosupresores/administración & dosificación , Quimioterapia de Inducción/métodos , Nefritis Lúpica/tratamiento farmacológico , Ácido Micofenólico/análogos & derivados , Administración Intravenosa , Adulto , Antiinflamatorios/uso terapéutico , Azatioprina/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Fallo Renal Crónico/etiología , Nefritis Lúpica/complicaciones , Masculino , Persona de Mediana Edad , Ácido Micofenólico/administración & dosificación , Prednisona/uso terapéutico , Calidad de Vida , Recurrencia , Tasa de Supervivencia , Adulto JovenRESUMEN
Proliferative lupus nephritis is a strong predictor of morbidity and mortality in patients with systemic lupus erythematosus. Despite improvements in the management of lupus nephritis, a significant number of the patients do not respond to immunosuppressive therapy and progress to end-stage renal failure. In order to optimise the diagnostic strategy and treatment of patients with proliferative lupus nephritis, guidelines are needed. In this review, the Dutch Working Party on Systemic Lupus Erythematosus provides recommendations regarding four important areas in patients with proliferative lupus nephritis: I) indications for a first renal biopsy, II ) definitions of treatment response, III ) selection of treatment options, and IV) indications for a repeat biopsy.
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Nefritis Lúpica/tratamiento farmacológico , Guías de Práctica Clínica como Asunto , Antirreumáticos/uso terapéutico , Azatioprina/uso terapéutico , Biopsia , Ciclofosfamida/uso terapéutico , Progresión de la Enfermedad , Humanos , Inmunosupresores/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/patología , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/patología , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Países Bajos , Pronóstico , Resultado del TratamientoRESUMEN
OBJECTIVE: Interaction of advanced glycation end products (AGEs) with their receptors (RAGE) plays an important role in inflammation in auto-immune diseases. Several functional polymorphisms of RAGE have been described. In this study we analysed the role of RAGE polymorphisms in disease susceptibility for systemic lupus erythematosus (SLE). In addition, we investigated whether these polymorphisms in SLE are associated with serum levels of soluble RAGE (sRAGE), renal involvement (lupus nephritis (LN)) and its outcome. METHODS: For this cross-sectional study DNA samples of 97 SLE patients, 114 LN patients and 429 healthy controls (HC) were genotyped for four RAGE polymorphisms: -429 T/C, -374 T/A, 2184 A/G and Gly82Ser. Differences in genotype frequencies and allele frequencies were tested between patients and HCs. In SLE patients, sRAGE was measured by enzyme-linked immunosorbent assay (ELISA). In addition, association of genotypes with sRAGE and disease severity in LN was analysed. RESULTS: The C allele of -429 T/C, the T allele of -374 T/A and the G allele of 2184 A/G were significantly more prevalent in SLE and LN compared with HC. In LN, the C allele of RAGE -429 T/C, the A allele of -374 T/A and the G allele of RAGE 2184 A/G polymorphism were significantly associated with more proteinuria and worse renal function during the first two years of treatment. No association of genotype with sRAGE was found. CONCLUSION: RAGE polymorphisms are associated with susceptibility to SLE and LN. In addition, some of these polymorphisms are likely to be associated with disease severity and initial response to treatment in LN.
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Lupus Eritematoso Sistémico/genética , Nefritis Lúpica/genética , Polimorfismo Genético , Receptores Inmunológicos/genética , Adulto , Anciano , Estudios Transversales , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Receptor para Productos Finales de Glicación AvanzadaRESUMEN
Encapsulating peritoneal sclerosis (EPS) represents a rare complication of long-term peritoneal dialysis (PD). It is characterised by diffuse peritoneal membrane fibrosis, progressive intestinal encapsulation and the clinical spectrum of intestinal obstruction. The pathogenesis is as yet not well understood but includes inflammation, angiogenesis and fibrosis. The current diagnosis of EPS lacks specificity and relies on clinical, radiographic or macroscopic evaluation. There is no general agreement on managing EPS although accumulating clinical data suggest drug treatment (steroids, tamoxifen), surgery (enterolysis) or a combination of both. Here, we provide a short overview on the current knowledge of EPS, with a focus on treatment. Moreover, we present a diagnostic and a therapeutic algorithm for EPS based on the best available published data and our combined experience.
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Diálisis Peritoneal/efectos adversos , Fibrosis Peritoneal/etiología , Fibrosis Peritoneal/terapia , Terapia Combinada , Humanos , Fibrosis Peritoneal/diagnósticoRESUMEN
Encapsulating peritoneal sclerosis (EPS) is an uncommon but one of the most serious complications in patients on long-term peritoneal dialysis. EPS is characterised by a diffuse thickening and/or sclerosis of the peritoneal membrane which leads to a decreased ultrafiltration and ultimately to bowel obstruction. We present four cases of EPS and discuss the clinical manifestations, multifactorial aetiology, diagnosis, treatment, prognosis, and prevention. We end with a proposal for the development of an EPS prevention guideline.
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Diálisis Peritoneal/efectos adversos , Enfermedades Peritoneales/etiología , Peritoneo/patología , Adulto , Biopsia , Diagnóstico Diferencial , Resultado Fatal , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Enfermedades Peritoneales/patología , Esclerosis/diagnóstico , Esclerosis/etiología , Tomografía Computarizada por Rayos XRESUMEN
Although the definitions of renal dysfunction vary, loss of renal function is a common complication following cardiac surgery using cardiopulmonary bypass (CPB). When postoperative dialysis is required, mortality is approximately 50%. CPB-accompanied hemodilution is a major contributing factor to renal damage as it notably reduces oxygen delivery by reducing the oxygen transport capacity of the blood as well as disturbing the microcirculation. To minimize hypoxemic damage during CPB, lowering of body temperature is applied to reduce the patient's metabolic rate. At present, however, temperature management during elective adult cardiac surgery is shifting from moderate hypothermia to normothermia. To determine whether the currently accepted levels of hemodilution during CPB can suffice the normothermic patient's high oxygen demand, we focused this study on renal physiology and postoperative renal function. Hemodilution reduces the capillary density through a diminished capillary viscosity, thereby, redistributing blood from the renal medulla to the renal cortex. As the physiology of the renal medulla makes it a hypoxic environment, this part of the kidney appears to be especially at risk for hypoxic damage caused by a hemodilution-induced lowered oxygen transport and oxygen delivery. In addition, hemodilution is also likely to disturb the hormonal systems regulating renal blood distribution. Clinical studies, mostly of retrospective or observational nature, show that perioperative nadir hematocrit levels lower than approximately 24% are associated with an increased risk to develop postoperative renal failure. A better comprehension of the cause-and-effect relation between low perioperative hematocrits and loss of postoperative renal function may enable more effective renal protective strategies.
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Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Hemodilución , Riñón/fisiología , Temperatura Corporal , HumanosRESUMEN
The use of more intensive immunosuppressive regimens and the increasing number of patients that are exposed to immunosuppressive strategies in transplantation medicine have changed the spectrum of infections that is encountered by the clinician. We describe a 62-year-old female renal transplant recipient receiving immunosuppressive therapy who developed complaints of weight loss, diarrhoea, cough, and fever. Increased C-reactive protein and pancytopenia were found. The presence of Mycobacterium gordonae, a non-tuberculous mycobacterium, was eventually demonstrated in bronchoalveolar lavage fluid, bone marrow, spleen, and liver. Determination of the pathogen was accelerated using a Line Probe Assay, a reverse hybridisation technique using an RNA fragment specific for different mycobacterium species. Treatment was initiated using a combination of clarithromycin, ethambutol, and rifampicin. The initial response to treatment was good, but splenectomy and change of immunosuppressive and antimycobacterial therapy were necessary for long-term control of the infection. Problems in the diagnosis and treatment of this uncommon pathogen are discussed.
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Trasplante de Riñón/efectos adversos , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Micobacterias no Tuberculosas/aislamiento & purificación , Médula Ósea/microbiología , Líquido del Lavado Bronquioalveolar/microbiología , Femenino , Humanos , Hígado/microbiología , Persona de Mediana Edad , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas/genética , Bazo/microbiologíaRESUMEN
INTRODUCTION: After renal transplantation, the incidence of premalignant and malignant skin lesions is high. Treatment with acitretin improves the number and aspect of actinic keratoses and appears to reduce the incidence of squamous cell carcinomas, but treatment is hampered by frequent side effects. No optimal long-term dosing advice is available. METHODS: A total of 26 long-term renal transplant recipients were randomized to 1-year treatment with acitretin, either 0.4 mg/kg/d throughout the whole year or 0.4 mg/kg/d during the first 3 months followed by 0.2 mg/kg/d for the remaining 9 months. At 9 different time points, the number of actinic keratoses and tumors was counted, and erythema and thickness of the lesions, and severity of side effects were scored. Patient's judgment was recorded using visual analog scores. RESULTS: In both groups, the number of actinic keratoses decreased by nearly 50%, but the number of new malignant tumors during the study year was similar to the number of tumors in the year before the study. Thickness of the keratoses decreased significantly in both groups. Acitretin dose had to be reduced in most patients because of the frequent occurrence of mucocutaneous side effects, such as cheilitis, excessive peeling of the skin, and hair disorders. In the 14 patients randomized to continuous treatment with a dose of 0.4 mg/kg/d, this dose could be maintained in 3 of 14 patients only. Temporary interruption of acitretin therapy was necessary in 7 of 26 patients. Patients' contentment about the aspect of their skin increased significantly, with no differences between groups. CONCLUSIONS: Acitretin therapy decreased the number of actinic keratoses in renal transplant recipients at a low maintenance dose of 0.2 mg/kg/d and significantly decreased the degree of thickness of the lesions. However, the incidence of new skin malignancies remained unchanged. Despite the high incidence of mucocutaneous side effects, patient's contentment with the aspect of their skin increased significantly.
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Acitretina/administración & dosificación , Trasplante de Riñón , Lesiones Precancerosas/tratamiento farmacológico , Lesiones Precancerosas/patología , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Adulto , Anciano , Análisis de Varianza , Biopsia con Aguja , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Queratolíticos/administración & dosificación , Cuidados a Largo Plazo , Masculino , Persona de Mediana Edad , Probabilidad , Valores de Referencia , Medición de Riesgo , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
Scedosporium apiospermum is a mold that is increasingly being recognized as an opportunistic pathogen in immunocompromised patients, and treatment is complicated by intrinsic resistance to several antifungal agents. In our hospital, two cases of S. apiospermum infection occurring within 2 weeks were successfully treated with voriconazole. Since both patients were infected with an uncommon pathogen, a search for a common nosocomial source was performed. As environmental cultures yielded no S. apiospermum, and random amplified polymorphic DNA (RAPD) fingerprinting showed that the patients' strains were genotypically unrelated, we considered a common nosocomial source of S. apiospermum to be unlikely.