RESUMEN
Lifelong immunosuppression is required for allograft survival after kidney transplantation but may not ultimately prevent allograft loss resulting from chronic rejection. We developed an approach that attempts to abrogate immune rejection and the need for post-transplantation immunosuppression in three patients with Schimke immuno-osseous dysplasia who had both T-cell immunodeficiency and renal failure. Each patient received sequential transplants of αß T-cell-depleted and CD19 B-cell-depleted haploidentical hematopoietic stem cells and a kidney from the same donor. Full donor hematopoietic chimerism and functional ex vivo T-cell tolerance was achieved, and the patients continued to have normal renal function without immunosuppression at 22 to 34 months after kidney transplantation. (Funded by the Kruzn for a Kure Foundation.).
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Síndromes de Inmunodeficiencia , Trasplante de Riñón , Síndrome Nefrótico , Osteocondrodisplasias , Enfermedades de Inmunodeficiencia Primaria , Arteriosclerosis/genética , Arteriosclerosis/terapia , Rechazo de Injerto/prevención & control , Humanos , Síndromes de Inmunodeficiencia/terapia , Riñón/fisiología , Trasplante de Riñón/efectos adversos , Síndrome Nefrótico/genética , Síndrome Nefrótico/terapia , Osteocondrodisplasias/genética , Osteocondrodisplasias/terapia , Enfermedades de Inmunodeficiencia Primaria/genética , Enfermedades de Inmunodeficiencia Primaria/terapia , Embolia Pulmonar/genética , Embolia Pulmonar/terapia , Acondicionamiento Pretrasplante/métodosRESUMEN
Antibody-mediated rejection is a common cause of early kidney allograft loss but the specifics of antibody measurement, therapies and endpoints have not been universally defined. In this retrospective study, we assessed the performance of risk stratification using systematic donor-specific antibody (DSA) monitoring. Included in the study were children who underwent kidney transplantation between January 1, 2010 and March 1, 2018 at Stanford, with at least 12-months follow-up. A total of 233 patients were included with a mean follow-up time of 45 (range, 9-108) months. Median age at transplant was 12.3 years, 46.8% were female, and 76% had a deceased donor transplant. Fifty-two (22%) formed C1q-binding de novo donor-specific antibodies (C1q-dnDSA). After a standardized augmented immunosuppressive protocol was implemented, C1q-dnDSA disappeared in 31 (58.5%). Graft failure occurred in 16 patients at a median of 54 (range, 5-83) months, of whom 14 formed dnDSA. The 14 patients who lost their graft due to rejection, all had persistent C1q-dnDSA. C1q-binding status improved the individual risk assessment, with persistent; C1q binding yielding the strongest independent association of graft failure (hazard ratio, 45.5; 95% confidence interval, 11.7-177.4). C1q-dnDSA is more useful than standard dnDSA as a noninvasive biomarker for identifying patients at the highest risk of graft failure.
Asunto(s)
Complemento C1q , Trasplante de Riñón , Anticuerpos , Suero Antilinfocítico , Biomarcadores , Niño , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Antígenos HLA , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Estudios Retrospectivos , Medición de RiesgoRESUMEN
BACKGROUND: Currently, there is no consensus among pediatric kidney transplant centers regarding the use and regimen for immunosuppressive induction therapy. METHODS: In this single center, retrospective cohort study, pediatric kidney transplant recipients transplanted between 1 May 2013 and 1 May 2018 with rabbit antithymocyte globulin (rATG) induction were included. We stratified patients based on immunological risk, with high risk defined as those with repeat transplant, preformed donor specific antibody, current panel-reactive antibodies > 20%, 0 antigen match and/or African-American heritage. Outcome of interest was the incidence of biopsy proven acute rejection by 1 year. RESULTS: A total of 166 patients met inclusion criteria. Age of patients was 12 years (11 mo-21 y), (median, range), 21.5% received a living donor transplant and 50.6% were female. Low-immunologic-risk patients were divided into 2 groups, those who received the lower cumulative rATG dose of ≤ 3.5 mg/kg (n = 52) versus the higher cumulative dose of > 3.5 mg/kg (n = 47). The median total dose in the lower dose group was 3.1 (IQR 0.3) and 4.4 (IQR 0.8) in the higher dose group, P < 0.001. Rejection rate did not differ significantly between the 2 treatment groups (7/52 vs. 6/47). None in the lower dose group developed BK nephropathy versus 3 in the higher dose group. Graft loss due to BK nephropathy occurred in 1 patient in the higher dose group. Graft loss in the whole cohort at 12 months was a rare event (n = 1) with 99.5% graft survival and 100% patient survival. CONCLUSIONS: Reduced rATG dosing (≤ 3.5 mg/kg) when compared to higher dosing (> 3.5 mg/kg) is safe and effective in low-risk pediatric kidney transplant recipients without increasing risk of rejection. A higher resolution version of the Graphical abstract is available as Supplementary information.
Asunto(s)
Trasplante de Riñón , Suero Antilinfocítico/efectos adversos , Femenino , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/epidemiología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Masculino , Estudios RetrospectivosRESUMEN
INTRODUCTION: Urinary diversion in pediatric renal transplant candidates with bladders not amenable to primary reconstruction can be achieved by pre-transplant ileal conduit creation. We performed cutaneous ureterostomies to limit pre-transplant surgery, protect the peritoneum for dialysis, transplant patients sooner, and preserve ureter length for future surgical reconstruction. METHODS: We compared four pediatric transplant recipients with ureterostomies to four recipients with ileal conduits from 2009 to 2017. RESULTS: All patients with ileal conduits developed at least one urinary tract infection (UTI) within 1 year of transplant and three of four patients had recurrent UTIs within the first year. Two patients required ileal conduit revisions for redundant conduits and recurrent UTIs. Of the four ureterostomy patients, two patients had UTIs within one year of transplant. Two patients developed ureterostomy strictures requiring revision at the fascial level; one was associated with a UTI. CONCLUSION: In our small case series, ureterostomy allowed for a single operative intervention with preservation of ureter length for later reconstruction. Ureterostomy is safe and recurrent UTI may be lower in the ureterostomy group. Long-term evaluation of ureterostomy for urinary diversion in pediatric kidney transplant is warranted.
Asunto(s)
Trasplante de Riñón , Uréter , Derivación Urinaria , Niño , Humanos , Uréter/cirugía , UreterostomíaRESUMEN
BACKGROUND: During kidney transplantation, the transplanted kidney undergoes ischemia reperfusion injury, with adenosine being a major mediator. This study aimed to assess whether aminophylline, an adenosine receptor antagonist, improves early graft function and reduces incidence of delayed graft function (DGF) and slow graft function (SGF). METHODS: Single center, double-blinded, placebo-controlled randomized clinical trial. Pediatric patients admitted for renal transplantation from donation after brain death donors were randomized into a treatment arm receiving aminophylline and a placebo arm receiving normal saline infusions. Primary outcome was estimated glomerular filtration rate (eGFR) at 5 days post-transplant. Secondary outcomes were rates of DGF/SGF and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels. RESULTS: Twenty-three patients were randomized to aminophylline and 27 to placebo. There was no difference in day 5 eGFR, rate of DGF/SGF, or urine NGAL/Creatinine level between aminophylline vs. placebo arm (eGFR 67.39 ± 38.9 ml/min/1.73m2 vs. 80.48 ± 52.1 ml/min/1.73m2p = 0.32; DGF/SGF 5/23 (21.7%) vs. 3/27 (11.1%) p = 0.31; urine NGAL/creatinine 300.5 ng/mg IQR 105.5-1464.5 ng/mg vs. 425.4 ng/mg IQR 140.3-1126.2 ng/mg, p = 0.95; respectively). At 12 months, there was 100% patient survival and 98% graft survival. eGFR at 12 months was similar between the two arms. CONCLUSIONS: There was no benefit in peri-transplant aminophylline administration. Our results are limited by small sample size, since sample calculations were based on primary outcome of day 5 eGFR and low rate of DGF/SGF, which may have precluded us from demonstrating efficacy. Further clinical studies are necessary to determine any benefit of aminophylline in kidney transplant recipients, particularly from high-risk donors.
Asunto(s)
Aminofilina/administración & dosificación , Tasa de Filtración Glomerular/efectos de los fármacos , Trasplante de Riñón/métodos , Antagonistas de Receptores Purinérgicos P1/administración & dosificación , Adolescente , Niño , Creatinina/orina , Funcionamiento Retardado del Injerto/prevención & control , Método Doble Ciego , Femenino , Humanos , MasculinoRESUMEN
Bilateral renal agenesis is associated with severe oligohydramnios and was considered incompatible with postnatal life due to severe pulmonary hypoplasia. The use of renal replacement therapy was limited by significant morbidity and mortality associated with dialysis in very young infants with major pulmonary pathology. In the United States, there is a tremendous controversy about whether or not the use of prenatal amniotic fluid infusions provides a benefit to fetuses with bilateral renal agenesis. One of the critical issues identified is that there are, as yet, no children reported who had achieved long-term survival. Previous reports all indicated these children died shortly after birth or after unsuccessful peritoneal dialysis. We present two infants with a prenatal diagnosis of bilateral renal agenesis whose mothers elected to undergo prenatal amnioinfusions. One was born at 28 weeks with a birthweight of 1230 g and the other born at 34 weeks with a birthweight of 1940 g. We present the details of both cases, with initial management on chronic peritoneal dialysis, which started shortly after birth, as a bridge to living related kidney transplants.
Asunto(s)
Anomalías Congénitas/cirugía , Enfermedades Renales/congénito , Trasplante de Riñón , Riñón/anomalías , Diálisis Peritoneal , Preescolar , Femenino , Humanos , Terapia de Inmunosupresión , Lactante , Recien Nacido Extremadamente Prematuro , Recién Nacido , Recien Nacido Prematuro , Riñón/cirugía , Enfermedades Renales/cirugía , Terapia de Reemplazo Renal , Estados UnidosRESUMEN
PURPOSE: The treatment of VUR in children with UTI has changed significantly, due to studies showing that antibiotic prophylaxis does not decrease renal scarring. As children with kidney transplants are at higher risk for UTI, we investigated if select patients with renal transplant VUR could be managed without surgery. MATERIALS AND METHODS: A total of 18 patients with VUR into their renal grafts were identified, and 319 patients underwent transplantation from 2006 to 2016. The cause for the detection of the VUR, treatment, and graft function was reviewed. RESULTS: Six boys and 12 girls were identified, 13 of whom had grade 3 or 4 VUR into the renal graft. Nine patients presented with hydronephrosis or abnormal renal biopsy: eight were successfully managed with antibiotic prophylaxis and bladder training, one developed UTI and underwent Dx/HA subureteric injection. Nine patients presented with recurrent febrile UTI, only one was successfully managed without surgery. Only 2 of 9 (22%) patients who underwent Dx/HA injection had resolution of their reflux. Of the remaining seven, five required open ureteral reimplantation (two for obstruction), one lost the graft due to rejection, and one had significant hydronephrosis. eGFR was similar between the hydronephrosis, UTI, and abnormal renal biopsy groups at all times. CONCLUSION: Patients with transplant VUR and recurrent febrile UTI are more likely to require surgical therapy, but the complication and failure rate for Dx/HA injection is significant. Patients with transplant VUR without febrile UTI can be successfully managed with bladder training and temporary antibiotic prophylaxis.
Asunto(s)
Trasplante de Riñón/efectos adversos , Infecciones Urinarias/terapia , Reflujo Vesicoureteral/terapia , Adolescente , Profilaxis Antibiótica , Biopsia , Niño , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Ácido Hialurónico/administración & dosificación , Hidronefrosis/complicaciones , Lactante , Riñón/patología , Masculino , Riesgo , Resultado del Tratamiento , Uréter , Infecciones Urinarias/etiología , Reflujo Vesicoureteral/complicacionesRESUMEN
Pediatric renal transplant recipient survival continues to improve, but ABMR remains a significant contributor to graft loss. ABMR prognostic factors to guide treatment are lacking. C4d staining on biopsies, diagnostic of ABMR, is associated with graft failure. Persistent C4d+ on follow-up biopsies has unknown significance, but could be associated with worse outcomes. We evaluated a retrospective cohort of 17 pediatric renal transplant patients diagnosed with ABMR. Primary outcome at 12 months was a composite of ≥50% reduction in eGFR, transplant glomerulopathy, or graft failure. Secondary outcome was the UPCR at 12 months. We used logistic and linear regression modeling to determine whether persistent C4d+ on follow-up biopsy was associated with the outcomes. Forty-one percent reached the primary outcome at 12 months. Persistent C4d+ on follow-up biopsy occurred in 41% and was not significantly associated with the primary outcome, but was significantly associated with the secondary outcome (estimate 0.22, 95% CI 0.19-0.25, P < .001), after controlling for confounding factors. Persistent C4d+ on follow-up biopsies was associated with a higher UPCR at 12 months. Patients who remain C4d+ on follow-up biopsy may benefit from more aggressive or prolonged ABMR treatment.
Asunto(s)
Complemento C4b/inmunología , Rechazo de Injerto/inmunología , Trasplante de Riñón , Riñón/inmunología , Fragmentos de Péptidos/inmunología , Adolescente , Biomarcadores/metabolismo , Biopsia , Niño , Preescolar , Complemento C4b/metabolismo , Femenino , Estudios de Seguimiento , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/patología , Humanos , Lactante , Riñón/metabolismo , Riñón/patología , Modelos Lineales , Modelos Logísticos , Masculino , Evaluación de Resultado en la Atención de Salud , Fragmentos de Péptidos/metabolismo , Pronóstico , Estudios RetrospectivosRESUMEN
Nephropathic cystinosis is a rare disorder causing the accumulation of intracellular cystine crystals in tissues. The damage to the proximal tubules of the kidneys results in Fanconi syndrome, and patients with cystinosis experience the progression of chronic kidney disease, resulting in the need for kidney transplantation. Treatment of cystinosis with cysteamine has proven to be effective; however, it has many gastrointestinal side effects that are concerning for transplant specialists during the immediate post-transplant period. Transplant specialists routinely discontinue cysteamine therapy for up to six weeks to ensure proper immunosuppressant absorption. This practice is worrisome because it communicates the acceptability of lapses of cysteamine treatment to patients. It may be better to re-initiate cysteamine therapy shortly after transplantation while the patient is followed more closely by the transplant team. This report presents two pediatric patients with nephropathic cystinosis who successfully restarted cysteamine therapy in the immediate post-transplant period without issue in regard to immunosuppression absorption or gastrointestinal side effects. These cases challenge current practice of discontinuing cysteamine therapy during kidney transplantation, and immediate re-initiation of cysteamine therapy in cystinosis patients post-transplant should be considered.
Asunto(s)
Cisteamina/uso terapéutico , Cistinosis/tratamiento farmacológico , Trasplante de Riñón , Insuficiencia Renal/cirugía , Adolescente , Niño , Enfermedades de la Córnea/complicaciones , Cistinosis/complicaciones , Cistinosis/cirugía , Esquema de Medicación , Síndrome de Fanconi/complicaciones , Femenino , Humanos , Terapia de Inmunosupresión/métodos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Pacientes Internos , Masculino , Periodo Posoperatorio , Insuficiencia Renal/complicaciones , Tacrolimus/administración & dosificación , Resultado del TratamientoRESUMEN
Identifying and monitoring donor-directed anti-human leukocyte antigen antibodies are a rapidly evolving area of solid organ transplantation. Donor-specific antibodies dictate pre-transplant donor choice and donor-recipient matching and underlie much acute and chronic allograft rejection and loss. The evolution of available technology has driven this progress. Early, labor-intensive, whole-cell assays based on complement-dependent cytotoxicity suffered from poor sensitivity and specificity, technical challenges and lack of precision. Sequential improvement in assay performance included anti-human immunoglobulin-enhanced, complement-dependent cytotoxicity techniques followed by cell-based flow cytometry. However, variable specificity and sensitivity inherent in cell-based testing continued to limit flow cytometry. The introduction of solid-phase assays led to a second revolution in histocompatibility testing with the use of purified antigens bound to artificial surfaces rather than whole cells. These techniques augmented sensitivity and specificity to detect even low-titer antibodies to previously undetected antigens. Identification of complement-activating antibodies is being introduced, but current technology is in the developmental stage. While the detection of alloantibodies has improved dramatically, our comprehension of their importance remains imperfect. Variability in methodology and a lack of standardization limits the clinical application of these tests. In spite of the hurdles that remain, antibody-mediated rejection has become a key target to improve graft survival.
Asunto(s)
Pruebas Inmunológicas de Citotoxicidad/métodos , Selección de Donante/métodos , Rechazo de Injerto/diagnóstico , Antígenos HLA/inmunología , Prueba de Histocompatibilidad/métodos , Isoanticuerpos/análisis , Trasplante de Riñón , Trasplantes/inmunología , Complemento C1q/inmunología , Vía Clásica del Complemento/inmunología , Citometría de Flujo , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Antígenos HLA/análisis , Humanos , Isoanticuerpos/inmunología , Sensibilidad y Especificidad , Donantes de TejidosRESUMEN
OBJECTIVES: Acute kidney injury occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of acute kidney injury in certain populations. This study sought to determine whether postoperative administration of aminophylline attenuates acute kidney injury in children undergoing congenital cardiac surgery with cardiopulmonary bypass. DESIGN: Single-center, double-blinded, placebo-controlled, randomized clinical trial. SETTING: Tertiary center, pediatric cardiovascular ICU. PATIENTS: A total of 144 children after congenital heart surgery with cardiopulmonary bypass. INTERVENTIONS: Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every 6 hours for 72 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome variable was the development of any acute kidney injury, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes. Secondary outcomes included the development of severe acute kidney injury, time between cardiovascular ICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase-associated lipocalin. The unadjusted rate and severity of acute kidney injury were not different between groups; 43 of 72 (60%) of the treatment group and 36 of 72 (50%) of the placebo group developed acute kidney injury (p = 0.32). Stage 2/3 acute kidney injury occurred in 23 of 72 (32%) of the treatment group and 15 of 72 (21%) of the placebo group (p = 0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group vs 18% in the placebo group; p = 0.30). CONCLUSIONS: In this placebo-controlled randomized clinical trial, we found no effect of aminophylline to prevent acute kidney injury in children recovering from cardiac surgery performed with cardiopulmonary bypass. Future study of preoperative aminophylline administration to prevent acute kidney injury may be warranted.
Asunto(s)
Lesión Renal Aguda/prevención & control , Aminofilina/uso terapéutico , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Puente Cardiopulmonar/efectos adversos , Cardiopatías Congénitas/cirugía , Inhibidores de Fosfodiesterasa/uso terapéutico , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Preescolar , Método Doble Ciego , Femenino , Humanos , Lactante , Unidades de Cuidado Intensivo Pediátrico , MasculinoRESUMEN
BK virus (BKV) infection causing end-organ disease remains a formidable challenge to the hematopoietic cell transplant (HCT) and kidney transplant fields. As BKV-specific treatments are limited, immunologic-based therapies may be a promising and novel therapeutic option for transplant recipients with persistent BKV infection. Here, we describe a whole-genome, deep-sequencing methodology and bioinformatics pipeline that identify BKV variants across the genome and at BKV-specific HLA-A2-, HLA-B0702-, and HLA-B08-restricted CD8 T-cell epitopes. BKV whole genomes were amplified using long-range PCR with four inverse primer sets, and fragmentation libraries were sequenced on the Ion Torrent Personal Genome Machine (PGM). An error model and variant-calling algorithm were developed to accurately identify rare variants. A total of 65 samples from 18 pediatric HCT and kidney recipients with quantifiable BKV DNAemia underwent whole-genome sequencing. Limited genetic variation was observed. The median number of amino acid variants identified per sample was 8 (range, 2 to 37; interquartile range, 10), with the majority of variants (77%) detected at a frequency of <5%. When normalized for length, there was no statistical difference in the median number of variants across all genes. Similarly, the predominant virus population within samples harbored T-cell epitopes similar to the reference BKV strain that was matched for the BKV genotype. Despite the conservation of epitopes, low-level variants in T-cell epitopes were detected in 77.7% (14/18) of patients. Understanding epitope variation across the whole genome provides insight into the virus-immune interface and may help guide the development of protocols for novel immunologic-based therapies.
Asunto(s)
Virus BK/genética , Virus BK/inmunología , Epítopos de Linfocito T/genética , Epítopos de Linfocito T/inmunología , Variación Genética , Adolescente , Virus BK/aislamiento & purificación , Niño , Preescolar , Secuencia Conservada , ADN Viral/química , ADN Viral/genética , Femenino , Genoma Viral , Humanos , Masculino , Análisis de Secuencia de ADN , Adulto JovenRESUMEN
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) evolves into end-stage renal failure in nearly half of affected patients and is associated with defective regulation of the alternative complement pathway. Patients with a complement factor H (CFH) mutation have a 30-100% risk of graft loss due to aHUS recurrence or graft thrombosis. Since CFH is produced predominantly by the liver, combined liver-kidney transplant is a curative treatment option. One major unexpected risk includes liver failure secondary to uncontrolled complement activation. We report a successful combined liver-kidney transplantation with perioperative plasma exchange and use of the humanized anti-C5 monoclonal antibody eculizumab. CASE DIAGNOSIS/TREATMENT: An 11-month-old female presented with oliguric renal failure after 3 weeks of flu-like symptoms in the absence of diarrhea. Following the identification of Escherichia coli 0157:H7 in her stool, she was discharged home on peritoneal dialysis with a diagnosis of Shiga toxin-associated HUS. Three months later, she developed severe anemia, thrombocytopenia, and neurological involvement. aHUS was diagnosed and confirmed, and genetic testing revealed a mutation in CFH SCR20. Once donor organs became available, she received preoperative plasma exchange followed by eculizumab infusion with intra-operative fresh frozen plasma prior to combined liver-kidney transplant. At 19 months post-transplant, she continues to have excellent allograft and liver function without signs of disease recurrence. CONCLUSION: Perioperative use of eculizumab in conjunction with plasma exchange during simultaneous liver-kidney transplant can be used to inhibit terminal complement activity, thereby optimizing successful transplantation by reducing the risk of graft thrombosis.
Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Factor H de Complemento/deficiencia , Síndrome Hemolítico-Urémico/cirugía , Inmunosupresores/uso terapéutico , Enfermedades Renales/complicaciones , Trasplante de Riñón , Trasplante de Hígado , Mutación , Intercambio Plasmático , Síndrome Hemolítico Urémico Atípico , Factor H de Complemento/genética , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Síndrome Hemolítico-Urémico/diagnóstico , Síndrome Hemolítico-Urémico/etiología , Enfermedades por Deficiencia de Complemento Hereditario , Humanos , Lactante , Enfermedades Renales/diagnóstico , Enfermedades Renales/genética , Fenotipo , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine if aminophylline administration is associated with improved creatinine clearance and greater urine output in children with acute kidney injury in the cardiovascular ICU. DESIGN: Single-center retrospective cohort study. SETTING: Pediatric cardiovascular ICU, university-affiliated children's hospital. PATIENTS: Children with congenital or acquired heart disease in the cardiovascular ICU who received aminophylline to treat oliguric acute kidney injury and fluid overload. INTERVENTIONS: Patients received aminophylline after consultation with a pediatric nephrologist. Data were collected retrospectively over 7 days to assess if aminophylline was associated with improvement in creatinine clearance, urine output, and fluid overload. MEASUREMENTS AND MAIN RESULTS: Thirty-one patients received 52 aminophylline courses. Over the 7-day study period, serum creatinine decreased from a mean of 1.13 ± 0.91 to 0.87 ± 0.83 mg/dL (-0.05 mg/dL/d, p < 0.001). A concomitant increase was seen in estimated glomerular filtration rate from a mean of 50.0 ± 30.0 to 70.6 ± 58.1 mL/min/1.73 m (+3.66 mL/min/1.73 m/d, p < 0.001). Average daily urine output increased by 0.22 mL/kg/hr (p < 0.001), and fluid overload decreased on average by 0.42% per day in the 7-day study period (p = 0.005). Although mean furosemide dose increased slightly (0.12 mg/kg/d, p = 0.01), hydrochlorothiazide dosing did not significantly change over the study period. There were no complications related to aminophylline administration. CONCLUSIONS: Our study suggests that aminophylline therapy may be associated with significantly improved renal excretory function and may augment urine output in children who experience oliguric acute kidney injury in the cardiovascular ICU. Additionally, we did not identify any aminophylline-related side effects in this high-risk cardiac population. Future prospective studies are necessary to confirm the safety profile and to ensure that the beneficial effects are independent of other clinical interventions.
Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/fisiopatología , Aminofilina/administración & dosificación , Inhibidores de Fosfodiesterasa/administración & dosificación , Lesión Renal Aguda/orina , Aminofilina/efectos adversos , Niño , Preescolar , Creatinina/sangre , Creatinina/orina , Diuréticos/uso terapéutico , Femenino , Furosemida/uso terapéutico , Tasa de Filtración Glomerular , Cardiopatías/complicaciones , Cardiopatías/terapia , Humanos , Hidroclorotiazida/uso terapéutico , Lactante , Recién Nacido , Unidades de Cuidado Intensivo Pediátrico , Masculino , Oliguria/tratamiento farmacológico , Oliguria/etiología , Inhibidores de Fosfodiesterasa/efectos adversos , Estudios RetrospectivosRESUMEN
Infants with congenital bilateral renal agenesis are at significant risk for morbidity and mortality, despite substantial and continuing advances in fetal and neonatal therapeutics. Infants with bilateral renal agenesis may episodically develop severe hypotension that can be refractory to traditional vasopressors. Synthetic angiotensin-II has been successfully used in adult and a few pediatric patients with refractory hypotension but has not been extensively studied in infants. We describe the use of angiotensin-II in treating refractory hypotension in a premature infant with congenital bilateral renal agenesis admitted to the NICU. Within 48 hours, he no longer required other vasopressors. Subsequently, angiotensin-II was gradually weaned and discontinued over 10 days and the patient was ultimately discharged from the hospital. This case demonstrates that angiotensin-II may be a helpful agent to treat refractory hypotension in infants with bilateral renal agenesis.
Asunto(s)
Angiotensina II , Hipotensión , Enfermedades Renales , Vasoconstrictores , Hipotensión/tratamiento farmacológico , Anomalías Congénitas/tratamiento farmacológico , Riñón/anomalías , Enfermedades Renales/congénito , Enfermedades Renales/tratamiento farmacológico , Angiotensina II/administración & dosificación , Vasoconstrictores/administración & dosificación , Humanos , Recién Nacido , LactanteRESUMEN
BK polyomavirus (BKV) is an emerging pathogen in immunocompromised individuals. BKV subtype III is rarely identified and has not previously been associated with disease. Here we provide the whole-genome sequence of a subtype III BKV from a pediatric kidney transplant patient with polyomavirus-associated nephropathy.
Asunto(s)
Virus BK/aislamiento & purificación , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/diagnóstico , Trasplante , Adolescente , Secuencia de Aminoácidos , Virus BK/clasificación , Virus BK/genética , Análisis por Conglomerados , ADN Viral/química , ADN Viral/genética , Genoma Viral , Histocitoquímica , Humanos , Inmunohistoquímica , Riñón/patología , Masculino , Microscopía , Datos de Secuencia Molecular , Filogenia , Infecciones por Polyomavirus/patología , Alineación de Secuencia , Análisis de Secuencia de ADNRESUMEN
Interstitial fibrosis is an outcome measure of increasing importance in clinical trials of both renal transplantation and native disease, but data on the comparative advantages of fibrosis measurement methods are limited. We compared four morphometric techniques and contrasted these with two visual fibrosis-scoring methods on trichrome-stained slides. Two morphometric methods included whole-slide digital images: collagen III immunohistochemistry and a new technique using trichrome and periodic acid-Schiff subtraction morphometry; the other two methods included Sirius Red with and without polarization on multiple digital fields. We evaluated 10 serial sections from 15 renal biopsies with a range of fibrosis extent and diagnoses on duplicate sections with each method on separate days. Three pathologists performed visual scoring on whole-slide images. Visual and morphometric techniques had good to excellent interassay reproducibility (R(2) = 0.62 to 0.96) and interobserver reproducibility (R(2) = 0.75 to 0.99, all P < 0.001). Morphometry showed less variation between observers than visual assessment (mean of 1% to 5% versus 11% to 13%). Collagen III, Sirius Red unpolarized, and visual scores had the strongest correlations (R(2) = 0.78 to 0.89), the greatest dynamic range, and the best correlation with estimated GFR (R(2) = 0.38 to 0.50, P < 0.01 to 0.001). Considering efficiency, reproducibility, and functional correlation, two current techniques stand out as potentially the best for clinical trials: collagen III morphometry and visual assessment of trichrome-stained slides.
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Histocitoquímica/métodos , Inmunohistoquímica/métodos , Riñón/patología , Adolescente , Adulto , Compuestos Azo , Biopsia , Niño , Preescolar , Colágeno Tipo III/metabolismo , Eosina Amarillenta-(YS) , Fibrosis , Humanos , Riñón/metabolismo , Verde de Metilo , Persona de Mediana Edad , Reacción del Ácido Peryódico de Schiff , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: High tacrolimus intrapatient variability has been associated with inferior graft outcomes in patients with kidney transplants. We studied baseline patterns of tacrolimus intrapatient variability in pediatric patients with kidney transplants and examined these patterns in relation to C1q-binding de novo donor-specific antibodies. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All tacrolimus levels in participants who underwent kidney-only transplantation at a single pediatric center from 2004 to 2018 (with at least 12-month follow-up, followed until 2019) were analyzed to determine baseline variability. Intrapatient variability was defined using the coefficient of variation (SD/mean ×100%) of all samples in a 6-month moving window. Routine de novo donor-specific antibody measurements were available for a subgroup of patients transplanted in 2010-2018. Cox proportional hazards models using tacrolimus intrapatient variability as a time-varying variable were used to examine the association between intrapatient variability and graft outcomes. The primary outcome of interest was C1q-binding de novo donor-specific antibody formation. RESULTS: Tacrolimus intrapatient variability developed a steady-state baseline of 30% at 10 months post-transplant in 426 patients with a combined 31,125 tacrolimus levels. Included in the outcomes study were 220 patients, of whom 51 developed C1q-binding de novo donor-specific antibodies. De novo donor-specific antibody formers had higher intrapatient variability, with a median of 38% (interquartile range, 28%-48%) compared with 28% (interquartile range, 20%-38%) for nondonor-specific antibody formers (P<0.001). Patients with high tacrolimus intrapatient variability (coefficient of variation >30%) had higher risk of de novo donor-specific antibody formation (hazard ratio, 5.35; 95% confidence interval, 2.45 to 11.68). Patients in the top quartile of tacrolimus intrapatient variability (coefficient of variation >41%) had the strongest association with C1q-binding de novo donor-specific antibody formation (hazard ratio, 11.81; 95% confidence interval, 4.76 to 29.27). CONCLUSIONS: High tacrolimus intrapatient variability was strongly associated with de novo donor-specific antibody formation.