RESUMEN

BACKGROUND: Acute kidney injury is a frequent cause of hospital readmission in kidney transplant recipients (KTR), usually associated with infections and graft rejection. Herein, we report a case of an unusual cause of acute kidney injury in a KTR (massive histiocytes renal interstitial infiltration). CASE PRESENTATION: A 40-year-old woman was submitted to a second kidney transplant. One year after surgery, she presented asthenia, myalgia, and fever, haemoglobin 6.1 g/dL; neutrophils: 1.3 × 109/µL; platelets: 143 × 109/µL; blood creatinine 11.8 mg/dL, requiring dialysis. A kidney biopsy revealed diffuse histiocytic infiltration, which was assumed due to dysregulated immunological activation triggered by infections. The patient had multiple infections, including cytomegalovirus infection (CMV), aspergillosis, bacteraemia, and urinary tract infections, which could trigger the immune response. Haemophagocytic lymphohistiocytosis (HLH) was ruled out. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies. CONCLUSIONS: Renal histiocyte activation and infiltration may have been initiated by an immunological mechanism similar to what occurs in HLH and infectious processes. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies.

Asunto(s)

Lesión Renal Aguda , Trasplante de Riñón , Linfohistiocitosis Hemofagocítica , Femenino , Humanos , Adulto , Trasplante de Riñón/efectos adversos , Histiocitos , Diálisis Renal , Riñón/patología , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Rechazo de Injerto

RESUMEN

BACKGROUND: The introduction of tacrolimus (TAC) to clinical practice was essential to the establishment of transplantation as a therapy for patients with chronic renal disease. However, the higher interindividual variation of TAC metabolism has been an important limiting factor for its clinical use. Although the relationship between CYP3A5 polymorphisms and TAC pharmacokinetics (PK) is well established, the effects of other genetic variants on TAC metabolism, such as POR*28, still remain uncertain. OBJECTIVE: The study aimed to evaluate the impact of POR variants on TAC PK in renal transplant patients with different CYP3A5 genotypes (expressers and non-expressers). METHODS: A total of 115 patients were included in this study. Genomic DNA was isolated from peripheral blood, and the real-time PCR technique was used to analyze the polymorphism POR rs1057868; C>T. RESULTS: During the initial post-transplant period, variant allele carriers (*1/*28 and *28/*28) showed a lower TAC dose requirement than POR wild homozygotes (*1/*1). Regarding the influence of the different polymorphisms of POR within the CYP3A5 expresser and non-expresser groups, no differences were observed in any of the PK parameters analyzed during 12 months after transplantation. CONCLUSION: In the studied population, the variant allelic POR*28 was significantly associated with lower TAC dose requirements and higher Co/D ratio in the first-month post-transplant. However, the effects of this polymorphism on the CYP3A5 enzyme activity were not observed.

Asunto(s)

Sistema Enzimático del Citocromo P-450/genética , Trasplante de Riñón , Tacrolimus , Citocromo P-450 CYP3A/genética , Genotipo , Humanos , Inmunosupresores/farmacocinética , Polimorfismo de Nucleótido Simple , Tacrolimus/farmacocinética

RESUMEN

AIM: To investigate primary care physicians' knowledge of and attitudes toward care for chronic kidney disease patients. BACKGROUND: In Brazil, care for chronic kidney disease, a global public health problem, is provided by the Brazilian National Health System, which is organized around primary care. The study aimed to investigate the knowledge and attitudes of primary care physicians about the management of chronic kidney disease. METHOD: This research is based on quantitative and qualitative data. The participants were 92 physicians from 81 primary care units located in eight cities of the São Paulo/Brazil health region, who answered a self-administered questionnaire. FINDINGS: Only 59% and 58% of the physicians recognized smoking and obesity, respectively, as risk factors for chronic kidney disease. Health appointments and drug therapy predominated as disease prevention strategies and less than 30% mentioned multiprofessional care and health education groups. For early diagnosis, isolated serum creatinine was the most used test and 64.6% stated they classified the disease stages. Exclusive follow-up in primary care decreased from 79% in stage 1 to 19.5% in stage 3B and the patients' monitoring in the healthcare network varied from 8.7% in stage 1 to 70.6% in stages 4 and 5ND, suggesting early referrals and lack of referral at the necessary stages. Access to information on the referred patient was, predominantly, through the patient's report and 74% of the physicians did not have matrix support regarding chronic kidney disease. CONCLUSION: The study showed that the healthcare teams need to update their knowledge and procedures to be able to provide a comprehensive and efficient approach to treating chronic kidney disease in primary care.

Asunto(s)

Médicos de Atención Primaria , Insuficiencia Renal Crónica , Adulto , Brasil , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud , Derivación y Consulta

RESUMEN

PURPOSE: Genetic polymorphisms have been associated with variation in the metabolism of tacrolimus (TAC) in kidney transplant patients. This study is aimed at assessing the impact of allelic variants of CYP3A5 and PPARA genes on the pharmacokinetics (PK) of TAC in Brazilian kidney transplant recipients in the first-year post-transplant. METHODS: A total of 127 patients were included for genetic evaluation. Genomic DNA was isolated from peripheral blood and real-time PCR was used to analyze the main polymorphisms described for the genes CYP3A5 (rs776746; C > G) and PPARA (rs4823613; A > G and rs4253728; G > A). RESULTS: CYP3A5 expressors showed a lower Co/dose ratio than non-expressors, with the median values of this parameter <1.01 ng/mL/mg in the first group at all evaluated times. Additionally, PPARA variant homozygotes had a lower Co/D ratio than wild allele carriers in the 12-month post-transplant period, with a median value of 0.65 ng/mL/mg. In the CYP3A5 expressers, the presence of the variant homozygous genotype PPARA was associated with a lower value of Co/D compared with the other genotypic groups at month 12. CONCLUSION: In the population under study, polymorphisms on CYP3A5 and PPARA were identified as determining and independent factors associated with the reduction of Co/D of TAC. Thus, the genotyping of these genetic variants may be a useful tool for the individualized prescription of TAC in kidney transplant patients.

Asunto(s)

Citocromo P-450 CYP3A/genética , Inmunosupresores/farmacocinética , PPAR alfa/genética , Tacrolimus/farmacocinética , Receptores de Trasplantes , Adulto , Alelos , Brasil , Femenino , Humanos , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple

RESUMEN

PURPOSE: Parathyroidectomy can be subtotal or total with an autograft for the treatment of renal hyperparathyroidism. In both cases, it may be extended with bilateral thymectomy and total or partial thyroidectomy. Thymectomy may be recommended in combination with parathyroidectomy in order to prevent mediastinal recurrence. Also, the occurrence of thyroid disease observed in patients with hyperparathyroidism is poorly understood and the incidence of cancer is controversial. The aim of the present study was to report the experience of a single center in the surgical treatment of renal hyperparathyroidism and to analyse the role of thyroid and thymus surgery in association with parathyroidectomy. MATERIALS AND METHODS: We analysed parathyroid surgery data, considering patient demographics, such as age and gender, and surgical procedure data, such as type of hyperparathyroidism, associated thyroid or thymus surgery, surgical duration and mediastinal recurrence. Histopathological results of thyroid and thymus samples were also analysed. RESULTS: Medical records of 109 patients who underwent parathyroidectomy for secondary hyperparathyroidism were reviewed. On average, thymectomy did not have impact on time of parathyroidectomy (p = 0.62) even when thyroidectomy was included (p = 0.91). Intrathymic parathyroids were detected in 7.5% of the thymuses removed and papillary carcinoma was detected in 20,8% of thyroid tissue samples. Two patients showed recurrence of supernumerary intrathymic parathyroids and a single case of mediastinitis was observed. CONCLUSIONS: Parathyroidectomy with thymectomy and/or thyroidectomy has an important role in the treatment of renal hyperparathyroidism since thyroid cancer can frequently occur and require surgery. Thymectomy should be considered to avoid recurrence and a risky re-operation.

Asunto(s)

Hiperparatiroidismo Secundario/cirugía , Paratiroidectomía , Insuficiencia Renal Crónica/complicaciones , Timectomía , Tiroidectomía , Adulto , Femenino , Humanos , Hiperparatiroidismo Secundario/etiología , Masculino , Persona de Mediana Edad , Selección de Paciente , Estudios Retrospectivos , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/cirugía , Resultado del Tratamiento

RESUMEN

Overweight, obese and chronic kidney disease patients have an altered and negative body composition being its assessment important. Bioelectrical impedance analysis is an easy-to-operate and low-cost method for this purpose. This study aimed to compare and correlate data from single- and multi-frequency bioelectrical impedance spectroscopy applied in subjects with different body sizes, adiposity, and hydration status. It was a cross-sectional study with 386 non-chronic kidney disease volunteers (body mass index from 17 to 40 kg/m2), 30 patients in peritoneal dialysis, and 95 in hemodialysis. Bioelectrical impedance, body composition, and body water data were assessed with single- and multi-frequency bioelectrical impedance spectroscopy. Differences (95% confidence interval) and agreements (Bland-Atman analyze) between devices were evaluated. The intraclass correlation coefficient was used to measure the strength of agreement and Pearson's correlation to measure the association. Regression analyze was performed to test the association between device difference with body mass index and overhydration. The limits of agreement between devices were very large. Fat mass showed the greatest difference and the lowest intraclass and Pearson's correlation coefficients. Pearson's correlation varied from moderate to strong and the intraclass correlation coefficient from weak to substantial. The difference between devices were greater as body mass index increased and was worse in the extremes of water imbalance. In conclusion, data obtained with single- and multi-frequency bioelectrical impedance spectroscopy were highly correlated with poor agreement; the devices cannot be used interchangeably and the agreement between the devices was worse as body mass index and fat mass increased and in the extremes of overhydration.

RESUMEN

We present a case of ocular syphilis after a renal transplantation involving progressive vision loss without clinically identifiable ocular disease. Electroretinography showed signs of ischemia, especially in the internal retina. A serological test was positive for syphilis. Lumbar puncture revealed lymphocytic meningitis and a positive serologic test for syphilis in the cerebrospinal fluid. The patient was treated with penicillin, and had a quick vision improvement. In the case of transplant recipients, clinicians should always consider the diagnosis of ocular syphilis in cases with unexplained visual acuity decrement, as this condition may cause serious complications if not treated.

Asunto(s)

Infecciones Bacterianas del Ojo/etiología , Trasplante de Riñón/efectos adversos , Sífilis/etiología , Adulto , Infecciones Bacterianas del Ojo/diagnóstico , Humanos , Masculino , Sífilis/diagnóstico , Agudeza Visual

RESUMEN

AIMS: Tacrolimus (TAC) is one of the most successful immunosuppressive drugs in transplantation. Its pharmacokinetics (PK) and pharmacogenetics (PG) have been extensively studied, with many studies showing the influence of CYP3A5 on TAC metabolism and bioavailability. However, data concerning the functional significance of ABCB1 polymorphisms are uncertain due to inconsistent results. We evaluated the association between ABCB1 diplotypes, CYP3A5 polymorphisms and TAC disposition in a cohort of Brazilian transplant recipients. METHODS: Individuals were genotyped for the CYP3A5*3 allele and ABCB1 polymorphisms (2677G>A/T, 1236C>T, 3435C/T) using a TaqMan® PCR technique. Diplotypes were analyzed for correlation with the TAC dose-normalized ratio (Co : dose). RESULTS: We genotyped 108 Brazilian kidney recipients for CYP3A5 (11% CYP3A5*1/*1; 31% CYP3A5*1/*3 and 58% CYP3A5*3/*3) and ABCB1 haplotypes (42% CGC/CGC; 41% GCG/TTT and 17% TTT/TTT). Homozygous subjects for the CYP3A5*3 allele or carriers of the ABCB1 TTT/TTT diplotype showed a higher Co : dose ratio compared with wild type subjects [median (interquartile range) 130.2 (97.5-175.4) vs. 71.3 (45.6-109.0), P < 0.0001 and 151.8 (112.1-205.6) vs. 109.6 (58.1-132.9), P = 0.01, respectively]. When stratified for the CYP3A5*3 group, ABCB1 TTT/TTT individuals showed a higher Co : dose ratio compared with non-TTT/TTT individuals [167.8 (130.4-218.0) vs. 119.4 (100.2-166.3), P = 0.04]. Multivariate linear regression analysis showed that the effects of CYP3A5 polymorphisms and ABCB1 diplotypes remained significant after correction for confounding factors. CONCLUSIONS: CYP3A5 is the major enzyme responsible for the marked interindividual variability in TAC PK, but it cannot be considered alone when predicting dose adjustment because ABCB1 diplotypes also affect TAC disposition, showing independent and additive effects on the TAC dose-normalized concentration.

Asunto(s)

Inhibidores de la Calcineurina/farmacocinética , Citocromo P-450 CYP3A/genética , Rechazo de Injerto/prevención & control , Trasplante de Riñón , Tacrolimus/farmacocinética , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Adulto , Brasil , Inhibidores de la Calcineurina/administración & dosificación , Inhibidores de la Calcineurina/uso terapéutico , Femenino , Frecuencia de los Genes , Haplotipos , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Estudios Retrospectivos , Tacrolimus/administración & dosificación , Tacrolimus/uso terapéutico , Distribución Tisular

RESUMEN

Glomerulonephritis may complicate the course of a wide variety of malignant diseases. However, there are relatively few reports of membranous glomerulonephritis (MGN) in patients with non-Hodgkin lymphoma (NHL). We describe for the first time a case of MGN associated with splenic marginal zone lymphoma with extreme plasmacytic differentiation and bone marrow infiltration mimicking multiple myeloma. We also reviewed the literature and summarize the clinical-pathological findings and the mechanisms involved in NHL-induced MGN. Our current case highlights the importance of a quick and correct diagnosis of the underlying disease and the value of a thorough physical examination. Clinicians should be aware of the possibility of an underlying hematologic malignancy in such cases, particularly in elderly patients with renal biopsy that shows the presence of atypical histology.

Asunto(s)

Glomerulonefritis Membranosa/patología , Linfoma de Células B de la Zona Marginal/patología , Neoplasias del Bazo/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Diagnóstico Diferencial , Estudios de Seguimiento , Glomerulonefritis Membranosa/complicaciones , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/tratamiento farmacológico , Humanos , Linfoma de Células B de la Zona Marginal/complicaciones , Linfoma de Células B de la Zona Marginal/diagnóstico , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Masculino , Mieloma Múltiple/diagnóstico , Neoplasias del Bazo/complicaciones , Neoplasias del Bazo/diagnóstico , Neoplasias del Bazo/tratamiento farmacológico , Resultado del Tratamiento

RESUMEN

Fabry disease is an X-linked inborn error of metabolism, which is caused by the deficiency of α-galactosidase A, leading to progressive accumulation of neutral glycosphingolipids and a-galactosyl breakdown products in most body fluids and several tissues, resulting in the clinical manifestations. The onset of Fabry disease symptoms in females is not observed as early as in males. We report a novel presentation of Fabry disease in a female patient with medical history of relapsing strokes and brain magnetic resonance angiography showing signs of microangiopathy and multiple lacunar strokes that were first diagnosed as Moyamoya disease (a chronic progressive cerebrovascular disease). The patient subsequently displayed increased levels of serum creatinine and proteinuria. Diagnosis of Fabry disease was made by a renal biopsy and was confirmed by molecular studies showing a missense mutation: c1066C > T (het) [R356W]. The diagnosis was delayed by 21 years with respect to her first symptom (stroke), probably because her initial clinical presentation was neurological and diagnosed as Moyamoya disease. Other factors that contributed to the delay of the diagnosis were the lack of acute or chronic pain (neuropathic pain) and angiokeratomas. Some similarities in the pathogenic aspects of the patient's vascular lesions lead us to speculate that this patient has Fabry disease, with a phenotype that had not yet been described. It is necessary to be aware of this possibility to avoid misdiagnosis of Fabry disease as Moyamoya disease.

Asunto(s)

Errores Diagnósticos , Enfermedad de Fabry/diagnóstico , Enfermedades Renales/diagnóstico , Enfermedad de Moyamoya/diagnóstico , Accidente Cerebrovascular/diagnóstico , Adulto , Biomarcadores/sangre , Biopsia , Angiografía Cerebral , Creatinina/sangre , Análisis Mutacional de ADN , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/etiología , Enfermedades Renales/genética , Angiografía por Resonancia Magnética , Fenotipo , Valor Predictivo de las Pruebas , Proteinuria/etiología , Recurrencia , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/genética , alfa-Galactosidasa/genética

RESUMEN

A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents.

Asunto(s)

Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Nefrosis Lipoidea/etiología , Síndrome Nefrótico/etiología , Síndrome Nefrótico/patología , Anciano , Biopsia , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/patología , Femenino , Humanos , Riñón/patología , Microscopía Electrónica , Nefrosis Lipoidea/tratamiento farmacológico , Nefrosis Lipoidea/patología , Esteroides/uso terapéutico , Adulto Joven

RESUMEN

A 19-year-old female with type 1 diabetes for four years, and a 73-year-old female with type 2 diabetes for twenty years developed sudden-onset nephrotic syndrome. Examination by light microscopy, immunofluorescence, and electron microscopy (in one case) identified minimal change disease (MCD) in both cases. There was a potential causative drug (meloxicam) for the 73-year-old patient. Both patients were treated with prednisone and responded with complete remission. The patient with type 1 diabetes showed complete remission without relapse, and the patient with type 2 diabetes had two relapses; complete remission was sustained after associated treatment with cyclophosphamide and prednisone. Both patients had two years of follow-up evaluation after remission. We discuss the outcomes of both patients and emphasize the role of kidney biopsy in diabetic patients with an atypical proteinuric clinical course, because patients with MCD clearly respond to corticotherapy alone or in conjunction with other immunosuppressive agents.

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Uma paciente de 19 anos de idade com diabetes tipo 1 durante quatro anos e uma paciente de 73 anos de idade com diabetes tipo 2 durante vinte anos desenvolveram quadro súbito de síndrome nefrótica. O exame histológico à microscopia de luz, imunofluorescência e microscopia eletrônica (em um caso) diagnosticou glomerulopatia de lesões mínimas (GLM) em ambos os casos. Na paciente de 73 anos de idade, houve uma associação com o uso de meloxicam. As duas pacientes foram tratadas com corticosteroides e responderam com remissão completa do quadro. A paciente de 19 anos com diabetes tipo 1 apresentou remissão completa sem recidivas, e a paciente de 73 anos com diabetes tipo 2 apresentou dois episódios de recidiva; a remissão completa foi conseguida após associação ao tratamento com ciclofosfamida. As duas pacientes foram seguidas dois anos após a remissão completa. Os casos descritos enfatizam o papel da biópsia renal em pacientes diabéticos com evolução atípica do aparecimento de proteinúria, pois pacientes com GLM respondem bem à corticoterapia como único tratamento ou associado a outro agente imunossupressor.

Asunto(s)

Anciano , Femenino , Humanos , Adulto Joven , Diabetes Mellitus Tipo 1/complicaciones , /complicaciones , Nefrosis Lipoidea/etiología , Síndrome Nefrótico/etiología , Síndrome Nefrótico/patología , Biopsia , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/patología , /tratamiento farmacológico , /patología , Riñón/patología , Microscopía Electrónica , Nefrosis Lipoidea/tratamiento farmacológico , Nefrosis Lipoidea/patología , Esteroides/uso terapéutico

RESUMEN

Some patients with systemic lupus erythematosus (SLE) present with nephrotic syndrome due to minimal change disease (MCD). Histopathological diagnosis of patients with SLE and nephrotic-range proteinuria has shown that these patients present with diffuse proliferative glomerulonephritis and membranous glomerulonephritis, World Health Organization (WHO) classes IV and V, respectively, more frequently than the other classes. In the present study, we reported a case of nephrotic syndrome and renal biopsy-proven MCD associated with SLE. A complete remission occurred after steroid treatment, which was followed by a relapse 15 months later with a concomitant reactivation of SLE. A second biopsy showed WHO class IIb lupus nephritis. Prednisone treatment was restarted, and the patient went into complete remission again. The association of MCD and SLE may not be a coincidence, and MCD should be considered as an associated SLE nephropathy.