RESUMEN
A French (Caucasian) woman with a history of nonobstructive hypertrophic cardiopathy, type 1 diabetes mellitus, cataract, and ante-hypophysary insufficiency had undergone multiple magnetic resonance imaging (MRI) studies. She had developed end-stage renal disease (ESRD) and had undergone hemodialysis for 10 years before receiving a kidney-pancreas allotransplantation at the age of 48 years. She received antithymocyte globulins as induction immunosuppression and steroids (5 mg/d), mycophenolate mofetil (2 g/d), and tacrolimus (5 mg/d) as maintenance immunosuppression. Following transplantation, she underwent a cerebral MRI with injection of a gadolinium-based contrast agent (GBCA) in the work-up for Schwartz-Bartter syndrome. Shortly thereafter, she progressively developed cutaneous infiltration, sclerosis, and hyperpigmentation on her extremities and back (Figure 1), firm nodules on the thighs and the right hand, and confluent papules on the back, all of which were asymptomatic. She had no facial involvement, sclerodactyly, periungual telangiectasias, Raynaud syndrome, or arthralgias. Histologic examination showed mild epidermal hyperplasia and a thickened dermis containing several fibroblasts and some histiocytes (Figure 2a). The alcian blue stain revealed increased dermal mucin deposits (Figure 3b). Remarkably, several round-to-ovoid, well-limited yellowish collagenous structures containing basophilic (elastic) fibers were seen in the dermis (Figures 2b, 2c, 3a, and 4a). These "elasto-collagenous balls" stained blue with Masson's trichrome stain (Figure 4c); the orcein stain confirmed the presence of elastic fibers within them (Figure 4b). Some orange-yellow elasto-collagenous balls contained osteocytes, indicative of osseous metaplasia (Figure 5); these were von Kossa stain-positive, highlighting calcium deposition (Figure 4d). Immunohistochemically, the dermal fibroblasts were variably CD34-positive. Factor XIIIa+ dermal dendrocytes and histiocytic, occasionally multinucleated, CD68+ cells were also seen. (SKINmed. 2022;20:145-148).
Asunto(s)
Calcinosis , Dermopatía Fibrosante Nefrogénica , Trasplante de Páncreas , Enfermedades de la Piel , Femenino , Humanos , Riñón/patología , Metaplasia/patología , Persona de Mediana Edad , Dermopatía Fibrosante Nefrogénica/etiología , Dermopatía Fibrosante Nefrogénica/patología , Trasplante de Páncreas/efectos adversos , Enfermedades de la Piel/etiología , Enfermedades de la Piel/patologíaRESUMEN
Localized scleroderma (LS) is a rare fibrosing disorder of skin and underlying tissues. Although it can affect all races, it has a higher prevalence in whites. Deep LS is the least common among seven LS variants, representing less than 5% of cases, and typically affects areas of pressure such as the hips and waist. We report a unique clinical case of bilateral lower extremity deep LS in a 51-year-old Puerto Rican woman with chronic kidney disease (CKD). In patients with CKD, it is important to distinguish LS from nephrogenic systemic fibrosis (NSF). Both can present with skin fibrosis and contractures over joints yet have significantly differing treatment approaches and prognosis. Our case report is unique due to the patient's Puerto Rican ethnicity, CKD history, and isolated anterior lower extremity involvement. In this report, we highlight key clinical and histopathological findings of LS, and how they differ from that of NSF.
Asunto(s)
Dermopatía Fibrosante Nefrogénica , Insuficiencia Renal Crónica , Esclerodermia Localizada , Enfermedades de la Piel , Medios de Contraste , Progresión de la Enfermedad , Femenino , Gadolinio , Humanos , Masculino , Persona de Mediana Edad , Dermopatía Fibrosante Nefrogénica/etiología , Dermopatía Fibrosante Nefrogénica/patología , Dermopatía Fibrosante Nefrogénica/terapia , Insuficiencia Renal Crónica/complicaciones , Esclerodermia Localizada/complicacionesRESUMEN
Gadolinium-based contrast agents (GBCAs) have transformed magnetic resonance imaging (MRI) by facilitating the use of contrast-enhanced MRI to allow vital clinical diagnosis in a plethora of disease that would otherwise remain undetected. Although over 500 million doses have been administered worldwide, scientific research has documented the retention of gadolinium in tissues, long after exposure, and the discovery of a GBCA-associated disease termed nephrogenic systemic fibrosis, found in patients with impaired renal function. An understanding of the pharmacokinetics in humans and animals alike are pivotal to the understanding of the distribution and excretion of gadolinium and GBCAs, and ultimately their potential retention. This has been well studied in humans and more so in animals, and recently there has been a particular focus on potential toxicities associated with multiple GBCA administration. The purpose of this review is to highlight what is currently known in the literature regarding the pharmacokinetics of gadolinium in humans and animals, and any toxicity associated with GBCA use.
Asunto(s)
Medios de Contraste/administración & dosificación , Gadolinio/administración & dosificación , Imagen por Resonancia Magnética/métodos , Animales , Medios de Contraste/farmacocinética , Medios de Contraste/toxicidad , Gadolinio/farmacocinética , Gadolinio/toxicidad , Humanos , Dermopatía Fibrosante Nefrogénica/etiología , Insuficiencia Renal/complicacionesRESUMEN
Although neutrophil elastase (NE) may play a role in lung fibrosis and liver fibrosis, NE involvement in the development of nephrogenic systemic fibrosis has been unclear. We investigated the involvement of NE in the development of nephrogenic systemic fibrosis-like skin lesions post-injections of linear gadolinium-based contrast agents in renal failure mouse models. Renal failure mouse models were randomly divided into three groups: control group (saline), gadodiamide group, and gadopentetate group. Each solution was intravenously administered three times per week for three weeks. The mice were observed daily for skin lesions. Quantification of skin lesions, infiltrating inflammatory cells, and profibrotic cytokines in the affected skin was performed by immunostaining and reverse-transcription polymerase chain reaction (RT-PCR). Blood samples were collected from the facial vein to quantify NE enzymatic activity. The 158Gd concentrations in each sample were quantified using inductively coupled plasma mass spectrometry (ICP-MS). In the gadodiamide group, the mRNA expression of fibrotic markers was increased in the skin lesions compared to the control group. In the gadopentetate group, only collagen 1α and TGF-ß mRNA expression were higher than in the control group. The expression of CD3+, CD68+, NE cells and the NE activity in the blood serum were significantly higher in the gadodiamide and gadopentetate groups compared to the control group. Gadolinium concentration in the skin of the gadodiamide group was significantly higher than the gadopentetate group, while almost no traces of gadolinium were found in the control group. Although gadopentetate and gadodiamide affected the fibrotic markers in the skin differently, NE may be involved in the development of fibrosis linked to the GBCAs injections in renal failure mouse models.
Asunto(s)
Medios de Contraste/toxicidad , Gadolinio/toxicidad , Elastasa de Leucocito/metabolismo , Dermopatía Fibrosante Nefrogénica/etiología , Insuficiencia Renal/complicaciones , Piel/efectos de los fármacos , Animales , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/genética , Antígenos de Diferenciación Mielomonocítica/metabolismo , Complejo CD3/genética , Complejo CD3/metabolismo , Citocinas/genética , Citocinas/metabolismo , Femenino , Ratones , Piel/metabolismo , Piel/patología , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
Nephrogenic systemic fibrosis (NSF) is a progressive systemic fibrosing disease that may occur after gadolinium contrast exposure. It can lead to severe complications and even death. NSF is highly prevalent among patients with advanced chronic kidney disease (CKD). In this report, however, we describe the case of a patient with NSF that occurred during early CKD. A 65-year-old man with stage 3a CKD was transferred to our hospital because of lower extremity edema. The medical history revealed that he was exposed to gadolinium 185 days earlier, and the result of his tibial skin biopsy was consistent with NSF. The patient underwent a combined therapy with ultraviolet-A1 phototherapy and methotrexate and steroid therapy for 6 months. The combined therapy stopped the systemic progression of NSF.
Asunto(s)
Dermopatía Fibrosante Nefrogénica/diagnóstico , Insuficiencia Renal Crónica/patología , Anciano , Medios de Contraste/efectos adversos , Medios de Contraste/química , Fármacos Dermatológicos/uso terapéutico , Progresión de la Enfermedad , Gadolinio/química , Tasa de Filtración Glomerular , Humanos , Imagen por Resonancia Magnética , Masculino , Metotrexato/uso terapéutico , Dermopatía Fibrosante Nefrogénica/etiología , Dermopatía Fibrosante Nefrogénica/terapia , Índice de Severidad de la Enfermedad , Piel/patología , Terapia UltravioletaRESUMEN
Gadolinium-based contrast agents (GBCAs) have an excellent safety profile. However, over the last 2 decades, two specific concerns have surfaced. GBCAs are associated with nephrogenic systemic fibrosis (NSF) and tissue retention of gadolinium. NSF is a rare fibrosing disorder with a poor prognosis, which is characterized by skin and subcutaneous thickening as well as systemic manifestations. The disease has been reported exclusively in patients with advanced renal disease, and it is associated with higher doses and specific types of GBCAs. The number of new cases of NSF has fallen over the past decade, presumably because of adherence by health care providers to regulatory guidelines, which continue to evolve. While gadolinium retention has been known to occur in the liver and bones, the relatively recent findings of deposition and retention in the brain have reignited the debate concerning the safety profile of GBCAs. Despite these concerns, there have been no proven health effects related to gadolinium deposition and retention other than NSF. The authors review the different categories of GBCAs available for commercial use, discuss NSF and gadolinium retention in the brain, and provide updates on the latest U.S. and European regulatory guidelines regarding use of these agents. Given the frequency with which GBCAs are used in clinical practice, it is imperative for all radiologists to learn the current guidelines to provide the safest and highest quality of patient care. ©RSNA, 2019.
Asunto(s)
Medios de Contraste/efectos adversos , Medios de Contraste/farmacocinética , Gadolinio/efectos adversos , Gadolinio/farmacocinética , Dermopatía Fibrosante Nefrogénica/etiología , Europa (Continente) , Humanos , Estados UnidosRESUMEN
Gadolinium-based contrast agents (GBCAs) are widely used for T1-weighted magnetic resonance imaging (MRI) in clinic diagnosis. However, a major drawback of GBCAs is that they can increase the toxicological risk of nephrogenic systemic fibrosis (NSF) in patients with advanced renal dysfunction. Hence, safer alternatives to GBCAs are currently in demand, especially for patients with renal diseases. Here we investigated the potential of polyethylene glycol (PEG)-stabilized iron oxide nanoclusters (IONCs) as biocompatible T1MRI contrast agents and systematically evaluated their NSF-related risk in rats with renal failure. We profiled the distribution, excretion, histopathological alterations, and fibrotic gene expressions after administration of IONCs and GBCAs. Our results showed that, compared with GBCAs, IONCs exhibited dramatically improved biosafety and a much lower risk of causing NSF, suggesting the feasibility of substituting GBCAs with IONCs in clinical MRI diagnosis of patients with renal diseases.
Asunto(s)
Medios de Contraste/toxicidad , Compuestos Férricos/química , Gadolinio/química , Nanoestructuras/química , Insuficiencia Renal/diagnóstico por imagen , Animales , Medios de Contraste/química , Medios de Contraste/farmacocinética , Células HEK293 , Humanos , Imagen por Resonancia Magnética/efectos adversos , Imagen por Resonancia Magnética/métodos , Ratones , Dermopatía Fibrosante Nefrogénica/etiología , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley , Distribución TisularAsunto(s)
Calcifilaxia/tratamiento farmacológico , Quelantes/administración & dosificación , Fallo Renal Crónico/complicaciones , Dermopatía Fibrosante Nefrogénica/tratamiento farmacológico , Úlcera Cutánea/tratamiento farmacológico , Tiosulfatos/administración & dosificación , Anciano , Calcifilaxia/diagnóstico , Calcifilaxia/etiología , Humanos , Fallo Renal Crónico/terapia , Masculino , Microscopía Electrónica , Dermopatía Fibrosante Nefrogénica/diagnóstico , Dermopatía Fibrosante Nefrogénica/etiología , Diálisis Renal , Piel/patología , Piel/ultraestructura , Úlcera Cutánea/diagnóstico , Úlcera Cutánea/etiología , Resultado del TratamientoAsunto(s)
Gadolinio/efectos adversos , Terapia por Láser/métodos , Espectrometría de Masas/métodos , Dermopatía Fibrosante Nefrogénica/patología , Biopsia con Aguja , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Fallo Renal Crónico/diagnóstico por imagen , Fallo Renal Crónico/fisiopatología , Persona de Mediana Edad , Dermopatía Fibrosante Nefrogénica/diagnóstico por imagen , Dermopatía Fibrosante Nefrogénica/etiología , Dermopatía Fibrosante Nefrogénica/cirugía , Fotomicrografía , Medición de Riesgo , Resultado del TratamientoRESUMEN
Iodinated and gadolinium-based contrast materials have excellent safety profiles for use in pediatric computed tomography and MR imaging. The rate of acute adverse reactions and contrast-induced nephropathy is lower than in adults. The relationship between nephrogenic systemic fibrosis and gadolinium administration is well established and only a small number of children suffer from this debilitating disorder. The recent finding of gadolinium deposition in the brain of patients with normal renal function has renewed concerns regarding its long-term toxicity. The necessity of gadolinium-based contrast agent use in children should be considered carefully for each examination, and more stable macrocyclic agents should be the primary choice.
Asunto(s)
Medios de Contraste/efectos adversos , Gadolinio/efectos adversos , Imagen por Resonancia Magnética , Dermopatía Fibrosante Nefrogénica/etiología , Insuficiencia Renal Crónica/etiología , Tomografía Computarizada por Rayos X , Niño , HumanosRESUMEN
No discussion of challenges for chemistry in molecular imaging would be complete without addressing the elephant in the room-which is that the purest of chemical compounds needs to interact with a biological system in a manner that does not perturb normal biology while still providing efficacious feedback to assist in diagnosis of disease. In the past decade, magnetic resonance imaging (MRI) agents long considered inert have produced adverse effects in certain patient populations under certain treatment regimens. More recently, inert blood pool agents have been found to deposit in the brain. Release of free metal is often suspected as the culprit but that hypothesis has yet to be validated. In addition, even innocuous agents can cause painful side effects during injection in some patients. In this brief review, we summarize known biological effects for gadolinium- and iron-based MRI contrast agents, and discuss some of the potential mechanisms for the observed biological effects, including the potential role of phosphorus imbalance, related to kidney disease or cancer, in destabilizing gadolinium-based chelates and precipitating free gadolinium.This article is part of the themed issue 'Challenges for chemistry in molecular imaging'.
Asunto(s)
Medios de Contraste/efectos adversos , Gadolinio/efectos adversos , Imagen por Resonancia Magnética/efectos adversos , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Medios de Contraste/química , Medios de Contraste/farmacocinética , Gadolinio/química , Gadolinio/farmacocinética , Humanos , Modelos Biológicos , Imagen Molecular/efectos adversos , Dermopatía Fibrosante Nefrogénica/etiología , Fósforo/metabolismo , Insuficiencia Renal/diagnóstico por imagen , Insuficiencia Renal/metabolismoRESUMEN
BACKGROUND: Despite multiple therapeutic approaches for nephrogenic systemic fibrosis (NSF), no single treatment has convincingly shown consistent benefit. The most successful outcomes have been associated with recovery of renal function, although evidence remains limited and past studies have been inconclusive. OBJECTIVE: We sought to investigate whether improvement of renal function via successful transplantation or via return of renal function after acute kidney injury correlates with improvement of NSF, and to further characterize the clinical features and progression of NSF. METHODS: A retrospective medical chart review led to the identification of patients (n = 8) diagnosed with NSF who presented to a single academic tertiary referral center over a 15-year period. These 8 patients were contacted by phone to obtain information related to treatment and clinical course of their NSF and renal function. Statistical analysis was performed using Fisher's exact test. RESULTS: There is a significant correlation (P = .0286) of improved renal function with improvement of NSF. All 4 patients who had improvement of renal function also had improvement of NSF. Two of these patients had end-stage renal disease and a successful kidney transplant, and two had acute kidney injury that resolved. No improvement in NSF was observed without kidney function resolution. LIMITATIONS: Our study is limited by a small sample size (n = 8) and a retrospective study design, which increased its potential for selection and recall bias. CONCLUSION: Improvement of renal function through either transplantation or resolution of acute kidney injury with medical management is significantly associated with improvement of NSF.
Asunto(s)
Lesión Renal Aguda/fisiopatología , Fallo Renal Crónico/fisiopatología , Dermopatía Fibrosante Nefrogénica/etiología , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/terapia , Adulto , Anciano , Medios de Contraste , Femenino , Estudios de Seguimiento , Gadolinio , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Centros de Atención Terciaria , Factores de TiempoRESUMEN
OBJECTIVE: The aim of this study was to assess the potential risk of gadobutrol-enhanced magnetic resonance imaging (MRI) in patients with moderate to severe renal impairment for the development of nephrogenic systemic fibrosis (NSF). MATERIALS AND METHODS: We performed a prospective, international, multicenter, open-label study in 55 centers. Patients with moderate to severe renal impairment scheduled for any gadobutrol-enhanced MRI were included. All patients received a single intravenous bolus injection of gadobutrol at a dose of 0.1 mmol/kg body weight. The primary target variable was the number of patients who develop NSF within a 2-year follow-up period. RESULTS: A total of 908 patients were enrolled, including 586 with moderate and 284 with severe renal impairment who are at highest risk for developing NSF. The mean time since renal disease diagnosis was 1.83 and 5.49 years in the moderate and severe renal impairment cohort, respectively. Overall, 184 patients (20.3%) underwent further contrast-enhanced MRI with other gadolinium-based contrast agents within the 2-year follow-up. No patient developed symptoms conclusive of NSF. CONCLUSIONS: No safety concerns with gadobutrol in patients with moderate to severe renal impairment were identified. There were no NSF cases.
Asunto(s)
Dermopatía Fibrosante Nefrogénica/diagnóstico por imagen , Compuestos Organometálicos/administración & dosificación , Insuficiencia Renal/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste/administración & dosificación , Medios de Contraste/efectos adversos , Femenino , Humanos , Inyecciones Intravenosas , Imagen por Resonancia Magnética/efectos adversos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Dermopatía Fibrosante Nefrogénica/etiología , Compuestos Organometálicos/efectos adversos , Estudios Prospectivos , Insuficiencia Renal/complicaciones , Adulto JovenRESUMEN
Gadolinium-based contrast agents have greatly expanded the capability of magnetic resonance imaging and have been used extensively in neuroradiology over the past 30 years. When initially developed they were thought to be relatively harmless; it was later discovered they are associated with nephrogenic systemic fibrosis and should be used with caution in certain patient groups, especially those with renal failure. Lately it has been found that the use of these contrast agents may result in deposition of gadolinium in the brain even in patients with an intact blood-brain barrier. While this has not been shown to be associated with any clinical effects, a precautionary approach has been advised by the regulatory authorities. Here we review the development of the gadolinium contrast agents, their use and the advice related to this new information.
Asunto(s)
Encéfalo/efectos de los fármacos , Medios de Contraste/efectos adversos , Gadolinio/efectos adversos , Imagen por Resonancia Magnética/efectos adversos , Dermopatía Fibrosante Nefrogénica/etiología , Insuficiencia Renal/complicaciones , Barrera Hematoencefálica , Encéfalo/metabolismo , Gadolinio/metabolismo , Humanos , Factores de RiesgoRESUMEN
In addition to general skin changes like pallor or dryness and the frequent, often excruciating nephrogenic pruritus, specific diseases in patients with renal failure may occur. Acquired perforating dermatoses are usually also highly pruritic. Calciphylaxis is a severe disease with poor prognosis. Nonhealing wounds with superinfection and progression to sepsis are characteristic. Bullous lesions can be caused by disturbances in porphyrin metabolism. Nephrogenic systemic fibrosis is a disease which was first described in 2000. Its incidence is already on the decline. Furthermore, this article provides an overview of systemic diseases which have both skin symptoms and kidney changes. These include connective tissue diseases, vasculitis or sarcoidosis and amyloidosis. After a kidney transplantation, particular attention must be paid to the development of skin tumors and infections. The last part of this article is dedicated to genodermatoses with skin and renal involvement, where numerous causative mutations have already been characterized. Knowing the correlations of characteristic skin symptoms and specific, potentially life-threatening kidney disease is important in order to initiate further investigations and steps such as referral to nephrologists at an early stage.
Asunto(s)
Dermatitis/etiología , Enfermedades Renales/complicaciones , Trasplante de Riñón/efectos adversos , Dermopatía Fibrosante Nefrogénica/diagnóstico , Neoplasias Cutáneas/etiología , Dermatitis/diagnóstico , Diagnóstico Diferencial , Medicina Basada en la Evidencia , Humanos , Dermopatía Fibrosante Nefrogénica/etiología , Prurito/diagnóstico , Prurito/etiología , Neoplasias Cutáneas/diagnóstico , Evaluación de Síntomas/métodosAsunto(s)
Contractura/etiología , Medios de Contraste/efectos adversos , Gadolinio/efectos adversos , Imagen por Resonancia Magnética/efectos adversos , Dermopatía Fibrosante Nefrogénica/etiología , Insuficiencia Renal/complicaciones , Articulación del Codo/efectos de los fármacos , Articulación del Codo/patología , Fibrosis , Gadolinio/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Piel/efectos de los fármacos , Piel/patologíaRESUMEN
End-stage renal disease (ESRD) is a rapidly growing global health problem within the past decades due to increased life expectancy, diabetes mellitus, hypertension, and vascular diseases. Since ESRD is not curable definitively, patients suffering from ESRD have a very low quality of life; therefore, symptomatic management is the cornerstone of medical treatment. Uremia affects almost all body organs, such as skin, through different mechanisms including biochemical, vascular, neurologic, immunologic, hematologic, endocrine, and electrolyte and volume balance disturbances. Some of these conditions are associated with significant morbidity, and patients with ESRD commonly present with a spectrum of dermatologic disorders. Each one has its own unique presentation and treatment approaches. In this review article, we discuss the clinical presentation, pathophysiology, and treatment of the most common skin disorders associated with ESRD.