RESUMEN
An 11-month-old girl presented with a history of failure to thrive, vomiting, polydipsia, polyuria and visual inattention. She was found to have malignant hypertension due to unilateral renal artery stenosis. This was successfully treated with percutaneous transluminal balloon angioplasty. Nearly 10 years following this initial presentation, she remains normotensive on no anti-hypertensive medications.
Asunto(s)
Angioplastia de Balón , Insuficiencia de Crecimiento/tratamiento farmacológico , Insuficiencia de Crecimiento/etiología , Hipertensión Maligna/tratamiento farmacológico , Hipertensión Maligna/etiología , Obstrucción de la Arteria Renal/complicaciones , Obstrucción de la Arteria Renal/terapia , Antihipertensivos/uso terapéutico , Femenino , Humanos , LactanteRESUMEN
BACKGROUND AND OBJECTIVES: Heart disease is a major cause of death in young adults with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) is common and is associated with hypertension. The aims of this study were to evaluate whether there is a relationship between LVH and BP in children with CKD and whether current targets for BP control are appropriate. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this single-center cross-sectional study, 49 nonhypertensive children, (12.6 ± 3.0 years, mean GFR 26.1 ± 12.9 ml/min per 1.73 m²) underwent echocardiographic evaluation and clinic and 24-hour ambulatory BP monitoring. LVH was defined using age-specific reference intervals for left ventricular mass index (LVMI). Biochemical data and clinic BP for 18 months preceding study entry were also analyzed. RESULTS: The mean LVMI was 37.8 ± 9.1 g/m²·7, with 24 children (49%) exhibiting LVH. Clinic BP values were stable over the 18 months preceding echocardiography. Patients with LVH had consistently higher BP values than those without, although none were overtly hypertensive (> 95th percentile). Multiple linear regression demonstrated a strong relationship between systolic BP and LVMI. Clinic systolic BP showed a stronger relationship than ambulatory measures. Of the confounders evaluated, only elemental calcium intake yielded a consistent, positive relationship with LVMI. CONCLUSIONS: LVMI was associated with systolic BP in the absence of overt hypertension, suggesting that current targets for BP control should be re-evaluated. The association of LVMI with elemental calcium intake questions the appropriateness of calcium-based phosphate binders in this population.
Asunto(s)
Presión Sanguínea , Hipertensión/etiología , Hipertrofia Ventricular Izquierda/etiología , Enfermedades Renales/complicaciones , Adolescente , Monitoreo Ambulatorio de la Presión Arterial , Calcio/efectos adversos , Distribución de Chi-Cuadrado , Niño , Enfermedad Crónica , Estudios Transversales , Suplementos Dietéticos/efectos adversos , Ecocardiografía Doppler , Femenino , Tasa de Filtración Glomerular , Humanos , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Enfermedades Renales/diagnóstico por imagen , Enfermedades Renales/fisiopatología , Modelos Lineales , Londres , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
Serological evidence of drug-induced lupus (DIL) and antiphospholipid syndrome (APS) were detected in a paediatric patient with nephropathic cystinosis during work-up for live related renal transplantation. Cysteamine was considered the most likely cause. Antinuclear (ANA) and antihistone antibodies disappeared after stopping cysteamine. ANA became positive after reintroduction of cysteamine. The patient's post-transplant course was complicated by severe thrombosis, with histological findings in her native nephrectomy consistent with APS. This is the first reported case of DIL and APS secondary to cysteamine therapy. Clinicians should exclude autoimmune abnormalities in patients with cystinosis, especially if patients report non-specific, unusual or unexplained symptoms.
Asunto(s)
Síndrome Antifosfolípido/inducido químicamente , Cisteamina/efectos adversos , Nefritis Lúpica/inducido químicamente , Adolescente , Anticuerpos Antinucleares/sangre , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/patología , Sedimentación Sanguínea/efectos de los fármacos , Cistinosis/tratamiento farmacológico , Femenino , Humanos , Trasplante de Riñón , Nefritis Lúpica/inmunología , Nefritis Lúpica/patologíaRESUMEN
We present a patient with steroid-sensitive but high-dose steroid-dependent nephrotic syndrome who was treated with rituximab. For 9 months following therapy she had undetectable CD19 cells in the peripheral circulation. She remained in remission during this period even though therapy was reduced to low-dose, alternate day prednisolone only. After 9 months, CD19 cells were once again detectable. Shortly after CD19 cells became detectable again she relapsed. We conclude that B-lymphocytes play a central role in the pathogenesis of idiopathic minimal change nephrotic syndrome (MCNS) and that rituximab may have a useful role in the management of steroid-dependent patients.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Nefrosis Lipoidea/tratamiento farmacológico , Síndrome Nefrótico/tratamiento farmacológico , Prednisona/uso terapéutico , Esteroides/química , Anticuerpos Monoclonales de Origen Murino , Femenino , Humanos , Lactante , RituximabRESUMEN
Peritoneal dialysis is the treatment of choice in children with end-stage renal failure who are awaiting renal transplantation. Traditionally patients requiring bilateral nephrectomy spent time on haemodialysis prior to being converted to peritoneal dialysis during a separate operation. Bilateral synchronous retroperitoneoscopic nephrectomy with the initiation of or return to peritoneal dialysis in the immediate postoperative period was performed on three patients with end-stage renal failure in our unit. The indications for bilateral nephrectomy were persistent heavy proteinuria in two children and difficult to control hypertension in the third. Bilateral laparoscopic nephrectomy was performed with the patients in the prone position. Two of the children were then placed in a supine position and a tunneled peritoneal dialysis catheter was inserted in the standard open fashion. The postoperative complications included a peritoneal catheter line breach requiring intraperitoneal antibiotics and a fever that was culture negative and settled spontaneously. This technique allows for immediate peritoneal dialysis, with the added benefit of reduced postoperative pain and improved cosmetic appearance.
Asunto(s)
Fallo Renal Crónico/terapia , Laparoscopía , Nefrectomía/métodos , Diálisis Peritoneal , Adolescente , Niño , Terapia Combinada , Femenino , Humanos , MasculinoRESUMEN
The hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by mutations of the dual zinc finger transcription factor, GATA3. The C-terminal zinc finger (ZnF2) binds DNA, whereas the N-terminal finger (ZnF1) stabilizes this DNA binding and interacts with other zinc finger proteins, such as the Friends of GATA (FOG). We have investigated seven HDR probands and their families for GATA3 abnormalities and have identified two nonsense mutations (Glu-228 --> Stop and Arg-367 --> Stop); two intragenic deletions that result in frameshifts from codons 201 and 355 with premature terminations at codons 205 and 370, respectively; one acceptor splice site mutation that leads to a frameshift from codon 351 and a premature termination at codon 367; and two missense mutations (Cys-318 --> Arg and Asn-320 --> Lys). The functional effects of these mutations, together with a previously reported GATA3 ZnF1 mutation and seven other engineered ZnF1 mutations, were assessed by electrophoretic mobility shift, dissociation, yeast two-hybrid and glutathione S-transferase pull-down assays. Mutations involving GATA3 ZnF2 or adjacent basic amino acids resulted in a loss of DNA binding, but those of ZnF1 either lead to a loss of interaction with specific FOG2 ZnFs or altered DNA-binding affinity. These findings are consistent with the proposed three-dimensional model of ZnF1, which has separate DNA and protein binding surfaces. Thus, our results, which expand the spectrum of HDR-associated GATA3 mutations and report the first acceptor splice site mutation, help to elucidate the molecular mechanisms that alter the function of this zinc finger transcription factor and its role in causing this developmental anomaly.
Asunto(s)
Proteínas de Unión al ADN/genética , Sordera/genética , Hipoparatiroidismo/genética , Enfermedades Renales/patología , Transactivadores/genética , Adolescente , Adulto , Secuencia de Aminoácidos , Animales , Sitios de Unión , Núcleo Celular/metabolismo , Niño , Preescolar , Codón , Codón sin Sentido , ADN/química , Exones , Salud de la Familia , Femenino , Mutación del Sistema de Lectura , Factor de Transcripción GATA3 , Eliminación de Gen , Genes Dominantes , Glutatión Transferasa/metabolismo , Proteínas Fluorescentes Verdes , Humanos , Proteínas Luminiscentes/metabolismo , Masculino , Ratones , Persona de Mediana Edad , Modelos Genéticos , Datos de Secuencia Molecular , Mutación , Mutación Missense , Linaje , Unión Proteica , Conformación Proteica , Estructura Terciaria de Proteína , Empalme del ARN , ARN Mensajero/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Programas Informáticos , Relación Estructura-Actividad , Técnicas del Sistema de Dos Híbridos , Zinc/química , Dedos de ZincRESUMEN
Benign intracranial hypertension (BIH) is a condition characterized by headache, papilledema, and a raised cerebrospinal fluid pressure with normal cranial imaging. It is uncommon in childhood. Previously, there have been reports that children with chronic impairment of renal function may be at greater risk of developing BIH. This study involved retrospective case note analysis of children undergoing renal transplantation over the last 11 years at our institution. Nine children developed BIH after renal transplantation. The prevalence of the condition in our series was 4.4%. Several etiologically relevant risk factors were identified, including medication (nitrofurantoin, minocycline) and excess weight gain. Our results suggest that BIH may be a more frequent complication of the post-operative care of pediatric renal transplant recipients than previously thought. We hope to alert pediatric nephrologists that examination of the fundus for papilledema in all renal transplant patients complaining of headache is essential. If the diagnosis of BIH is delayed, irretrievable visual loss may not be avoided.
Asunto(s)
Trasplante de Riñón/efectos adversos , Seudotumor Cerebral/etiología , Adolescente , Presión del Líquido Cefalorraquídeo/fisiología , Niño , Femenino , Cefalea/etiología , Humanos , Masculino , Papiledema/diagnóstico , Papiledema/etiología , Complicaciones Posoperatorias/epidemiología , Seudotumor Cerebral/complicaciones , Seudotumor Cerebral/epidemiología , Estudios Retrospectivos , Trastornos de la Visión/etiología , Aumento de PesoAsunto(s)
Encefalitis/etiología , Terapia de Inmunosupresión/efectos adversos , Trasplante de Riñón , Sarampión/complicaciones , Formación de Anticuerpos/inmunología , Preescolar , Encefalitis/virología , Humanos , Trasplante de Riñón/inmunología , Sarampión/virología , Virus del Sarampión/aislamiento & purificación , Vacuna contra el Sarampión-Parotiditis-Rubéola/inmunologíaRESUMEN
We reviewed the medical records of seven children with congenital nephrotic syndrome (CNS) treated by unilateral nephrectomy, captopril, and indomethacin since 1990. Clinical response to the treatment was analyzed using the Students' t-test. After a median period of 54 months (range 36-88 months) follow-up, five patients were alive at a median age of 74 (range 43-88) months. Median (range) plasma albumin rose from 11 (6-17) g/l at the start of treatment to 18 (15-22) g/l and 21 (18-25) g/l after 6 and 12 months treatment, respectively ( P=0.001 and P=0.0006). Albumin infusions per patient per month decreased from 7 (0-18) to 0 (0-30) in the 6 months post treatment ( P=0.017). The median (range) height standard deviation scores at 12 months and 30 months from onset of treatment were -1.56 (-2.96 to 0.41) and -1.43 (-2.40 to 0.90), respectively. In conclusion, management of CNS with captopril and indomethacin therapy in combination with unilateral nephrectomy achieves significant improvements in plasma albumin and reduces the need for albumin infusions and time in hospital, while growth is maintained. Second nephrectomy, dialysis, and transplantation can be delayed until the 3rd year of life or longer.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Captopril/administración & dosificación , Enfermedades del Recién Nacido/tratamiento farmacológico , Enfermedades del Recién Nacido/cirugía , Síndrome Nefrótico/tratamiento farmacológico , Síndrome Nefrótico/cirugía , Antiinflamatorios no Esteroideos/administración & dosificación , Terapia Combinada , Quimioterapia Combinada , Femenino , Humanos , Indometacina/administración & dosificación , Recién Nacido , Masculino , Nefrectomía , Síndrome Nefrótico/congénito , Resultado del TratamientoRESUMEN
An analysis of all pediatric cadaveric renal transplant recipients in the UK and Eire was undertaken to review the outcomes of pediatric cadaveric renal transplantation and to consider the implications for organ allocation procedures for pediatric recipients. Factors influencing the outcome of 1,252 pediatric cadaveric renal transplants in the UK and Eire in the 10-yr period from 1 January 1986 to 31 December 1995 were analyzed by Cox proportional hazards regression, including analysis of four distinct post-transplant epochs (0-3 months, 3-12 months, 12-36 months, and beyond 36 months). At the time of analysis (December 2000), 113 (11%) recipients had died and 47% of grafts had failed. In the multi-factorial modelling, the factors significantly affecting transplant outcome were cold ischaemia time, donor and recipient age and human leucocyte antigen (HLA) matching. Epoch analysis demonstrated that these factors operated at different times post-transplant. Cold ischaemia time had a strong influence on outcome at 3 months. A highly significant increased risk of graft failure was associated with donors under 5 yr of age. Young recipients had an increased risk of failure in the short term, but beyond 1 yr post-transplant there were few failures in young recipients while a steady rate of graft loss persisted in the older children. In terms of HLA matching, the worst outcome was observed for two HLA-DR mismatched grafts, while 000 and favorably matched kidneys (100, 010, 110 HLA-A, -B, -DR mismatches) survived longest. Hence, a policy of exchanging organs on the basis of HLA matching is justified for 000 mismatched and favorably matched kidneys. The poor outcome associated with very young donors should discourage pediatric units from transplanting kidneys from such young donors. The reasons for late losses in older recipients need investigation.