RESUMEN
This study was conducted in order to investigate the mechanical effects of high density polyethylene screw hole inserts in 4.5 mm Dynamic Compression Plate (DCP)--synthetic bone constructs. A mid-shaft 'osteotomy' was created in synthetic bone cylinders. The bisecting 'osteotomy' was reduced using six-hole broad DCPs and 4.5 mm cortical bone screws. The screws adjacent to the 'osteotomy' were placed using a load-guide. The remaining screws were placed in neutral position. High density polyethylene DCP screw hole inserts were incorporated with each screw in neutral position, in the experimental group. The bone plate constructs were tested in four point cyclical bending with the plates loaded at 2,000 Newtons, for a total of 6,000 cycles. Osteotomy gap was measured at 3,000 and 6,000 cycles. Screw head deflection adjacent to the osteotomy was measured. Kruskal-Wallis non-parametric testing was used for statistical comparisons. There was significantly less gapping at the osteotomy site in the treatment group after 3,000 cycles (0.49 +/- 0.18 mm [control] vs. 0.06 +/- 0.14 mm [treated], P=0.02) and 6,000 cycles (0.6 +/- 0.18 mm [control] vs. 0.1 +/- 0.22 mm [treated], P=0.02). The screws adjacent to the gap were significantly more deformed in the control group than those in the treated constructs (3.63 +/- 1.81 [control] vs. 1.06 +/- 1.55 [treated], P=0.0002). The polyethylene inserts improved the interface between bone plate and screw head, resulting in decreased relative movement of the implant and bone. The polyethylene inserts also resulted in less bending of the loaded screws.
Asunto(s)
Placas Óseas/veterinaria , Tornillos Óseos/veterinaria , Ensayo de Materiales/veterinaria , Animales , Fuerza Compresiva , Ensayo de Materiales/métodos , Osteotomía/métodos , Osteotomía/veterinaria , Polietileno , Estadísticas no ParamétricasRESUMEN
PURPOSE: This 9-month study compared the intraocular pressure (IOP)-lowering efficacy and safety of once-daily travoprost ophthalmic solutions (0.0015% and 0.004%) with twice-daily timolol 0.5%. PATIENTS AND METHODS: This study was conducted using a double-masked, randomized, parallel-group design; adult patients with open-angle glaucoma or ocular hypertension (IOP between 24 and 36 mm Hg, inclusive at 9 am and between 21 and 36 mm Hg, inclusive, at 11 am and 4 pm on two eligibility visits after an appropriate washout of previous treatments). In both eyes, the travoprost vehicle (placebo) was instilled at 9 am and travoprost (0.0015% or 0.004%) was instilled at 9 pm, or timolol 0.5% was instilled at both times. The primary efficacy variable was mean IOP measured at 9 am, 11 am, and 4 pm at baseline and follow-up visits. RESULTS: Five hundred seventy-three patients were randomized to the study treatments. Mean IOP, which was combined across study visits, was lower with travoprost 0.004% than with timolol 0.5% at 9 am (P = 0.0246), 11 am (P = 0.0039), and 4 pm (P = 0.0004). Intraocular pressure was lower with travoprost 0.004% than with travoprost 0.0015% at 11 am (P = 0.0314), the time of peak drug activity. Mean IOP was consistently lower with travoprost 0.0015% than with timolol 0.5%. Mean IOP reductions from baseline were significantly (P less than equal 0.0001) greater with travoprost 0.004% (8.0-8.9 mm Hg) than with timolol 0.5% (6.3-7.9 mm Hg). The most frequent related adverse events were hyperemia, pruritus, discomfort, pain, and iris pigmentation changes. The local tolerance was better in the timolol group compared with patients receiving travoprost. There were no serious unexpected treatment-related adverse events in any group. CONCLUSIONS: Travoprost 0.004% reduced diurnal mean intraocular pressure significantly more than timolol 0.5%. Both concentrations of travoprost were well tolerated and safe for use in patients with open-angle glaucoma or ocular hypertension.
Asunto(s)
Antihipertensivos/administración & dosificación , Cloprostenol/análogos & derivados , Cloprostenol/administración & dosificación , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Presión Intraocular/efectos de los fármacos , Timolol/administración & dosificación , Administración Tópica , Anciano , Antihipertensivos/efectos adversos , Cloprostenol/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hipertensión Ocular/tratamiento farmacológico , Soluciones Oftálmicas , Seguridad , Timolol/efectos adversos , Travoprost , Resultado del TratamientoRESUMEN
PURPOSE: This study evaluated the safety and intraocular pressure-lowering efficacy of two concentrations of travoprost (0.0015% and 0.004%) compared with latanoprost 0.005% and timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. METHODS: Eight hundred one patients with open-angle glaucoma or ocular hypertension were randomly assigned to travoprost 0.0015%, travoprost 0.004%, latanoprost 0.005%, or timolol 0.5%. The efficacy and safety of travoprost (0.0015% and 0.004%) daily was compared with latanoprost daily and timolol twice daily for a period of 12 months. RESULTS: Travoprost was equal or superior to latanoprost and superior to timolol with mean intraocular pressure over visits and time of day ranging from 17.9 to 19.1 mm Hg (travoprost 0.0015%), 17.7 to 19.1 mm Hg (travoprost 0.004%), 18.5 to 19.2 mm Hg (latanoprost), and 19.4 to 20.3 mm Hg (timolol). For all visits pooled, the mean intraocular pressure at 4 PM for travoprost was 0.7 mm Hg (0.0015%, P =.0502) and 0.8 mm Hg (0.004%, P =.0191) lower than for latanoprost. Travoprost 0.004% was more effective than latanoprost and timolol in reducing intraocular pressure in black patients by up to 2.4 mm Hg (versus latanoprost) and 4.6 mm Hg (versus timolol). Based on a criterion of 30% or greater intraocular pressure reduction from diurnal baseline or intraocular pressure 17 mm Hg or less, travoprost 0.0015% and 0.004% had an overall response to treatment of 49.3% and 54.7%, respectively, compared with 49.6% for latanoprost and 39.0% for timolol. Iris pigmentation change was observed in 10 of 201 of patients (5.0%) receiving travoprost 0.0015%, six of 196 of patients (3.1%) receiving travoprost 0.004%, 10 of 194 of patients (5.2%) receiving latanoprost, and none of the patients receiving timolol (0 of 196). The average ocular hyperemia score was less than 1 on a scale of 0 to 3, indicating that on average patients experienced between none/trace and mild for all treatment groups. There were no serious, unexpected, related adverse events reported for any therapy. CONCLUSIONS: Travoprost (0.0015% and 0.004%), a highly selective, potent prostaglandin F (FP) receptor agonist, is equal or superior to latanoprost and superior to timolol in lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension. In addition, travoprost 0.004% is significantly better than either latanoprost or timolol in lowering intraocular pressure in black patients. Travoprost is safe and generally well tolerated in the studied patient population.
Asunto(s)
Antihipertensivos/uso terapéutico , Cloprostenol/uso terapéutico , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Prostaglandinas F Sintéticas/uso terapéutico , Timolol/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Cloprostenol/administración & dosificación , Cloprostenol/efectos adversos , Cloprostenol/análogos & derivados , Método Doble Ciego , Color del Ojo/efectos de los fármacos , Femenino , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Presión Intraocular/efectos de los fármacos , Iris/efectos de los fármacos , Latanoprost , Masculino , Persona de Mediana Edad , Hipertensión Ocular/tratamiento farmacológico , Hipertensión Ocular/fisiopatología , Soluciones Oftálmicas , Trastornos de la Pigmentación/inducido químicamente , Profármacos/uso terapéutico , Prostaglandinas F Sintéticas/administración & dosificación , Prostaglandinas F Sintéticas/efectos adversos , Seguridad , Timolol/administración & dosificación , Timolol/efectos adversos , Travoprost , Resultado del TratamientoRESUMEN
BACKGROUND: The risk of progressing to end-stage renal disease in children with lupus glomerulonephritis is 18% to 50%. Published reports of transplantation secondary to end-stage renal failure in adult patients with systemic lupus erythematosus (SLE) demonstrate equivalent patient and graft survival. The purpose of this analysis is to compare patient and graft outcomes of pediatric SLE renal transplant recipients with an age-, race-, and gender-matched control group. METHODS: A retrospective analysis of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database identified 100 renal transplants performed in 94 young SLE patients. A control group of 470 children having received 501 renal transplants was identified. RESULTS: The SLE cohort was primarily female (82%), non-Caucasian (61%), adolescents and differed from the control group in being less likely to be preemptively transplanted, in receiving longer pretransplant dialysis, and in being likely to have received more than five pretransplant transfusions. After transplantation, there were no differences seen in patient survival at 3 years (89% vs. 95%, SLE vs. control) or in overall graft failure rates (31% vs. 29%, SLE vs. control). There was a trend toward poorer graft survival in non-white SLE patients receiving living donor grafts compared with white SLE patients. An increased graft failure rate was seen among those SLE cadaveric transplant recipients receiving peritoneal dialysis before transplant compared with controls and compared with SLE patients receiving hemodialysis. No differences were seen in rates of acute tubular necrosis or overall acute rejection incidence, although there was a significant increase in the percentage of living donor SLE patients who experienced greater than four rejection episodes. There were nonsignificant trends toward increased graft loss due to patient death with a functioning graft as well as increased mortality secondary to infection in the SLE patients. CONCLUSIONS: The results of renal transplantation in young SLE patients are comparable to those seen in an age-, race- and gender-matched control group. The similar patient and graft survival is seen despite the SLE patients having an underlying disease with multiorgan involvement and despite receiving immunosuppression for potentially prolonged periods before transplantation. No outcome differences were seen except for an unexplained increase in the incidence of recurrent rejections (> or =4) in the living donor SLE patients as well as increased graft failure rate in those patients receiving cadaveric renal transplants after a period of peritoneal dialysis. The nonsignificant trends toward increased graft failures in non-white SLE patients receiving living donor grafts, increased graft loss secondary to death with a functioning graft, as well as the increased mortality due to infection deserve recognition and further study.
Asunto(s)
Trasplante de Riñón , Lupus Eritematoso Sistémico/cirugía , Adolescente , Estudios de Casos y Controles , Niño , Bases de Datos Factuales , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Fallo Renal Crónico/etiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Lupus Eritematoso Sistémico/complicaciones , Nefritis Lúpica/etiología , Nefritis Lúpica/cirugía , Masculino , América del Norte/epidemiología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Hemolytic uremic syndrome (HUS) is the cause of renal failure in 2-4% of children on dialysis. After renal transplantation, HUS can recur, but recurrence rate and risk factors are controversial. METHODS: We reviewed the recurrence of HUS within the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) registry and used a separate questionnaire to ascertain additional clinical information. RESULTS: Of 68 renal allografts, HUS recurred in 6 allografts (8.8%) occurring in five patients (8.2%). Four patients had atypical HUS, whereas one patient had classic HUS. HUS recurred after transplantation in 33 days or less in all but one allograft. Outcome was poor with five of six allografts lost, despite treatment with fresh-frozen plasma or plasmapheresis. Cyclosporine had no effect on outcome or HUS recurrence. CONCLUSIONS: The risk of HUS recurrence in the allograft is 8-9% and is heightened in atypical HUS. Treatment was not effective and graft outcome was poor. Cyclosporine does not affect HUS recurrence.
Asunto(s)
Síndrome Hemolítico-Urémico/complicaciones , Fallo Renal Crónico/etiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Adolescente , Niño , Preescolar , Femenino , Rechazo de Injerto/etiología , Síndrome Hemolítico-Urémico/terapia , Humanos , Masculino , Recurrencia , Sistema de Registros , Insuficiencia del TratamientoRESUMEN
Chromatin remodeling complexes such as SWI/SNF use the energy of ATP hydrolysis to remodel nucleosomal DNA and increase transcription of nucleosomal templates. Human heat shock factor one (hHSF1) is a tightly regulated activator that stimulates transcriptional initiation and elongation using different portions of its activation domains. Here we demonstrate that hHSF1 associates with BRG1, the ATPase subunit of human SWI/SNF (hSWI/SNF) at endogenous protein concentrations. We also show that hHSF1 activation domains recruit hSWI/SNF to a chromatin template in a purified system. Mutation of hHSF1 residues responsible for activation of transcriptional elongation has the most severe effect on recruitment of SWI/SNF and association of hHSF1 with BRG1, suggesting that recruitment of chromatin remodeling activity might play a role in stimulation of elongation.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas Nucleares/metabolismo , Factores de Transcripción/metabolismo , Activación Transcripcional , Sitios de Unión , Cromatina , ADN Helicasas , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/aislamiento & purificación , Células HeLa , Factores de Transcripción del Choque Térmico , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/aislamiento & purificación , Humanos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/aislamiento & purificación , Proteínas Recombinantes de Fusión/metabolismo , Moldes Genéticos , Factores de Transcripción/genética , Factores de Transcripción/aislamiento & purificaciónRESUMEN
BACKGROUND: Posttransplant lymphoproliferative disorder (PTLD) is an important complication of transplantation. The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) database has documented 56 cases of PTLD, the largest such series to date. METHODS: We analyzed the available longitudinal and multicenter data in the NAPRTCS database to evaluate the demographic and therapeutic risk factors and the temporal trends for PTLD in children after renal transplantation. RESULTS: The overall incidence of PTLD was 1.2% of all patients or 298/100,000 posttransplantation years of follow-up. However, this incidence increased from 254/100,000 years between 1987 and 1991 to 395/100,000 years from 1992 onwards. In the same periods, the time to PTLD decreased from a median of 356 days (range 843048) to a median of 190 days (range 42-944). PTLD occurred with greater frequency in white children (P=0.003) and in cadaver donor transplants (P=0.019), but there was no significant predilection for gender, younger children (0-5 years), or primary diagnosis. No significant difference was found in the use of anti-T-cell antibodies or in doses of CsA, azathioprine, or prednisone at 1 month, 6 months, and 1 year. Between 1996 and 1997, 69 patients were initiated with tacrolimus. Eight cases of PTLD were identified in these recipients to date (prevalence rate 11.5%), compared with 46/4084 (1.1%) where cyclosporine was used (P<0.0001). CONCLUSIONS: There is a trend towards increasing incidence and earlier occurrence of PTLD in the pediatric renal transplant population. White race and cadaver donor sources are risk factors not reported before. Continued monitoring of tacrolimus immunosuppression is important.
Asunto(s)
Trasplante de Riñón , Trastornos Linfoproliferativos/epidemiología , Complicaciones Posoperatorias/epidemiología , Negro o Afroamericano , Cadáver , Niño , Preescolar , Bases de Datos Factuales , Estudios de Seguimiento , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Lactante , Trasplante de Riñón/inmunología , Donadores Vivos , Sistema de Registros , Factores de Riesgo , Factores de Tiempo , Donantes de Tejidos , Estados Unidos , Población BlancaRESUMEN
SWI-SNF alters DNA-histone interactions within a nucleosome in an ATP-dependent manner. These alterations cause changes in the topology of a closed circular nucleosomal array that persist after removal of ATP from the reaction. We demonstrate here that a remodeled closed circular array will revert toward its original topology when ATP is removed, indicating that the remodeled array has a higher energy than that of the starting state. However, reversion occurs with a half-life measured in hours, implying a high energy barrier between the remodeled and standard states. The addition of competitor DNA accelerates reversion of the remodeled array by more than 10-fold, and we interpret this result to mean that binding of human SWI-SNF (hSWI-SNF), even in the absence of ATP hydrolysis, stabilizes the remodeled state. In addition, we also show that SWI-SNF is able to remodel a closed circular array in the absence of topoisomerase I, demonstrating that hSWI-SNF can induce topological changes even when conditions are highly energetically unfavorable. We conclude that the remodeled state is less stable than the standard state but that the remodeled state is kinetically trapped by the high activation energy barrier separating it from the unremodeled conformation.
Asunto(s)
Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/metabolismo , Proteínas Nucleares , Nucleosomas/metabolismo , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Adenosina Trifosfato/metabolismo , ADN/química , ADN/metabolismo , ADN Helicasas , Estabilidad de Medicamentos , Células HeLa , Histonas/metabolismo , Humanos , Técnicas In Vitro , Conformación de Ácido Nucleico , Nucleosomas/química , Plásmidos/química , Plásmidos/metabolismoRESUMEN
There are limited data addressing the issue of final adult height following treatment with recombinant human growth hormone (rhGH). Utilizing the chronological age of 18 years as the arbitrary age of final adult height for children with chronic renal insufficiency, all patients enrolled in the North American Pediatric Renal Transplant Cooperative Study prior to January 1999, and who had at least one follow-up visit at age 18 years or older, were evaluated. When comparing the final adult height in those patients receiving prior rhGH with a group not receiving rhGH, the delta height standard deviation score was greater in the rhGH treatment group.
Asunto(s)
Envejecimiento/fisiología , Estatura/efectos de los fármacos , Hormona de Crecimiento Humana/uso terapéutico , Adulto , Supervivencia de Injerto , Humanos , Trasplante de Riñón , Estudios Multicéntricos como Asunto , Proteínas Recombinantes/uso terapéutico , Sistema de Registros , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To evaluate post-transplant outcomes for patients treated with human growth hormone (rhGH) during the course of chronic renal insufficiency (CRI). STUDY DESIGN: Patients (the "cohort" group) were identified who had been enrolled in 2 controlled studies to determine the efficacy and safety of rhGH in growth-retarded children with CRI and were subsequently enrolled in the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) and received a renal transplant. Patient survival, graft survival, time to first acute rejection episode, causes of graft failure, adverse events, and serial growth data from transplant to 60 months were evaluated. Data from the cohort group of 102 patients were compared with data from 4913 primary transplants from "other NAPRTCS" recipients (the "control" group). RESULTS: No significant difference was seen in patient survival or graft survival, incidence of acute rejection episode, or time to first rejection episode between the cohort and control groups. No specific adverse events were attributable to previous rhGH treatment. Only 2 patients had post-transplant lymphoproliferative disease in the cohort group, with no other malignancies reported. The mean height z scores in the cohort group at baseline and 60 months after transplant were -1.92 and -1.90, and the Deltaz score at 60 months was +0.20 compared with the control group (-1.88 and -2.10). CONCLUSIONS: Treatment of growth-retarded patients with CRI does not adversely affect graft function after renal transplantation. "Catch-down" growth does not occur after renal transplantation.
Asunto(s)
Rechazo de Injerto/inducido químicamente , Rechazo de Injerto/epidemiología , Hormona de Crecimiento Humana/efectos adversos , Fallo Renal Crónico/complicaciones , Trasplante de Riñón , Adolescente , Niño , Preescolar , Estudios de Cohortes , Enanismo/complicaciones , Enanismo/tratamiento farmacológico , Femenino , Supervivencia de Injerto , Hormona de Crecimiento Humana/uso terapéutico , Humanos , Lactante , Fallo Renal Crónico/cirugía , MasculinoRESUMEN
Peritonitis and catheter-related infections remain the two most-common causes of peritoneal dialysis (PD) treatment failure. To define the frequency and risks associated with exit site/tunnel infections (ESI/TI), as well as peritonitis, in pediatric patients on PD, we undertook a retrospective cohort study of patients initiated on PD in the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). We examined demographic data and PD catheter characteristics of 1,258 patients, aged < or = 21 years, initiated on PD from 1992 to 1997. We examined the frequency and complications of ESI/TI occurring within 30 days, 6 months, and 1 year of follow-up. For peritonitis episodes, we examined patient risk factors for peritonitis. Almost 11% of patients had an ESI/TI at 30 days, 26% between 30 days and 6 months, and 30% between 6 months and 1 year of follow-up. There was no increased risk of ESI/TI associated with patient age, race, or catheter characteristics. Peritonitis occurred in dialysis patients at a rate of 1 episode per 13.2 patient months. Proportional hazards regression analysis demonstrated that black race, single-cuffed catheters, and upward pointing exit sites were independent risk factors for peritonitis in the pediatric PD population. Patients with ESI/TI had twice the risk of those without these infections of developing peritonitis or needing access revision, and an almost threefold increased risk of hospitalization for access complications/malfunction. ESI/TI occurs commonly in pediatric PD patients. These infections cause significant morbidity, through risk of peritonitis, access revision, and hospitalization for catheter complications. Further study of potentially modifiable risk factors for ESI/TI in pediatric end-stage renal disease patients is warranted.
Asunto(s)
Infecciones/epidemiología , Diálisis Peritoneal/efectos adversos , Peritonitis/epidemiología , Cateterismo , Niño , Preescolar , Femenino , Humanos , Lactante , Infecciones/etiología , Infecciones/microbiología , Masculino , América del Norte/epidemiología , Peritonitis/etiología , Peritonitis/microbiología , Factores de RiesgoRESUMEN
The North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) group has analyzed its database from January 1987 to October 1998. During this time we enrolled 6,395 transplants: of these, 5,323 were primary and 1,072 were repeat transplants. Overall, 30.8% (483/1,566) of the grafts failed as a result of chronic rejection. For living donor (LD) grafts, the failure rate as a result of chronic rejection was 32% (175/553), and it was 30% (308/1,013) for cadaveric donor (CD) transplants. A proportional hazards model identified first acute rejection, multiple rejections, and a late acute rejection as risk factors for the development of chronic rejection. Additional risk factors for the development of chronic rejection were African-American race, a repeat transplant, and a cyclosporin A (CsA) dose of < 5 mg/kg/day. Our analysis found that one acute rejection episode increases the risk of chronic rejection graft failure three-fold. Patients with two or more acute rejections have a 12-fold increased relative risk (RR) of chronic rejection graft loss (CRGL). A late acute rejection (> 365 days post-transplant) increases the RR by six-fold. Two or more acute rejections, when the first is a late initial rejection, increases the RR 26-fold. Based on this information we have initiated a multicenter trial of intervention in patients with one or more acute rejections.
Asunto(s)
Rechazo de Injerto/epidemiología , Trasplante de Riñón , Enfermedad Aguda , Niño , Preescolar , Enfermedad Crónica , Femenino , Rechazo de Injerto/etiología , Humanos , Incidencia , Masculino , América del Norte/epidemiología , Modelos de Riesgos Proporcionales , Sistema de Registros , Factores de RiesgoRESUMEN
Since 1991, more than 50% of pediatric transplant recipients have received a living donor (LD) kidney, and approximately equals 85% of these allografts were one-haploidentical parental kidneys. Short-term (1 yr) and long-term (5 yr) graft survival of LD kidneys are 10% and 15% better, respectively, than that of cadaver donor (CD) kidneys. Because of these results, children are frequently not placed on a cadaver waiting list until the possibility of a LD is excluded--a process that may take up to 1 yr. The hypothesis for this study was that the graft outcome of a six-antigen-matched CD kidney is superior to that of a one-haploidentical LD kidney, and that children are at a disadvantage by not being placed on a CD list whilst waiting for a LD. The database of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) for 11 yrs (1987-98), was reviewed to identify children who were recipients of a six-antigen-matched CD kidney (primary and repeat transplants), and those who were recipients of a one-haploidentical LD kidney (primary and repeat transplants). Using standard statistical methods, the morbidity, rejection episodes, post-transplant hospitalizations, renal function, long- and short-term graft survival, and half-life of primary recipients were compared in the two groups. Unlike adult patients, only 2.7% (87/3313) of CD recipients in the pediatric age range received a six-antigen-matched kidney, and the annual accrual rate over 11 yrs was never higher than 4%. Comparison of 57 primary six-antigen-CD kidneys (PCD) with 2,472 primary LD (PLD) kidneys revealed that morbidity, rejection rates, and ratios were identical in the two groups. Renal function and subsequent hospitalizations were also identical in the two groups. Five-year graft survival of the PCD group was 90% compared with 80% for the PLD group, and the half-life of the PCD group was 25 +/- 12.9 yrs compared with 19.6 +/- 1.3 yrs. Our data suggest that the six-antigen-matched CD kidney may have less graft loss as a result of chronic rejection and would therefore confer a better long-term outcome. Based on these findings we recommend that all children, whilst waiting for a LD work-up, be listed with the United Network for Organ Sharing (UNOS) registry for a CD kidney.
Asunto(s)
Supervivencia de Injerto/genética , Trasplante de Riñón , Cadáver , Niño , Antígenos HLA/genética , Haploidia , Humanos , Donadores Vivos , América del Norte , Sistema de Registros , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
We define delayed graft function (DGF) as the need for dialysis during the first post-transplant week. We analyzed 5272 transplants, of which 2486 were of living donor (LD) and 2786 were of cadaver donor (CD) origin. Twelve per cent (620/5272) of all patients developed DGF. Donor specific rates were 5.6% for LD and 19.1% for CD patients. Factors predictive of DGF in CD patients were: African-American race (25%), prolonged cold ischemia (24%), absence of T-cell induction antibody therapy and absence of HLA-DR matching. The relative risk (RR) for graft failure due to DGF was 6.02 (p < 0.001) in LD patients and 2.58 (p < 0.001) for CD recipients. Two-year graft survival (GS) in LD patients without DGF was 89.6%, compared to 41.6% for those with DGF (p < 0.001); in CD patients it was 80.2% and 49.5%, respectively (p < 0.001). Censoring for primary non-function, GS for LD patients with a functioning graft at 30 d post-transplant and no DGF was 91.5%, compared to 70.1% for those with DGF (p < 0.001); GS for CD patients was 83.8% and 68.7%, respectively (p < 0.001). However, when patients whose grafts had failed during the first year were censored no differences in GS were noted between patients with and without DGF for either LD or CD recipients. To determine whether DGF acts as an independent risk factor for graft failure, patients were segregated into four groups: rejection with DGF; rejection without DGF; DGF without rejection; and no DGF, no rejection. When these groups were compared DGF emerged as an independent risk factor for graft failure. This large study reviewing pediatric renal transplantation over 10 yr clearly delineates the role of DGF as a major risk factor for graft failure.
Asunto(s)
Rechazo de Injerto/etiología , Supervivencia de Injerto/fisiología , Trasplante de Riñón/fisiología , Riñón/fisiología , Adolescente , Niño , Preescolar , Rechazo de Injerto/fisiopatología , Rechazo de Injerto/terapia , Humanos , Incidencia , Lactante , Recién Nacido , Diálisis Renal , Estudios Retrospectivos , Factores de RiesgoRESUMEN
This report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS), covering the years 1987-96 (January 15, 1997), analyzed data on 4898 patients who received 5362 transplants. Over the 10 yr of the study, 21.3% of the patients were under the age of 6 yr. Of the disorders that lead to end-stage renal disease (ESRD), structural and developmental anomalies of aplasia, dysplasia, and obstructive uropathy accounted for over 1500 patients. Despite the potential therapies for focal segmental glomerulosclerosis (FSGS), there has been little change in its incidence and this lesion continues to be the most common cause of renal failure and transplantation among acquired diseases. Eighty-nine per cent of patients with a functioning graft continue to receive cyclosporin A (CsA) 5 yr post-transplantation, and 84% of patients continue to receive azathioprine (AZA), whereas 26% of patients receive alternate-day steroid therapy at 4 yr post-transplant. Thirty-seven per cent of the living donor (LD) recipients and 47% of cadaver donor (CD) recipients were treated with the polyclonal T-cell antibody ATG/ALG for induction, and the monoclonal T-cell antibody, OKT3, was utilized for induction in 12% of LD patients and in 19% of CD patients. Twenty-five per cent of the 5362 transplants (1333) have failed over the 10-yr period. Graft survival is 90% at 1 yr and 74% at 6 yr for LD kidneys, and is 80% at 1 yr and 58% at 6 yr for CD patients. The most common cause for graft failure (30%) is chronic rejection. For recipients of LD grafts, relative risk (RR) factors for graft survival are African-American race (RR = 2.1, p < 0.001) and greater than five prior transfusions (RR = 1.6, p < 0.001). Prophylactic anti-T-cell antibody reduces the risk of graft failure (RR = 0.76, p = 0.009). For recipients of cadaver kidneys, risk factors are: recipient age < 2 yr (RR = 2, p < 0.001), donor age < 6 yr (RR = 1.3, p = 0.005), and absence of induction T-cell antibody (RR = 1.31, p < 0.001).
Asunto(s)
Enfermedades Renales/cirugía , Trasplante de Riñón/estadística & datos numéricos , Adolescente , Adulto , Informes Anuales como Asunto , Niño , Preescolar , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Terapia de Inmunosupresión , Lactante , Enfermedades Renales/inmunología , Trasplante de Riñón/inmunología , Donadores Vivos , Masculino , América del Norte , Factores de TiempoRESUMEN
The 1996 annual report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) summarizes data submitted from 130 centers on 2,208 patients in whom 2,787 independent courses of dialysis were performed between 1 January 1992 and 16 January 1996. Approximately two-thirds of the dialysis population were maintained on peritoneal dialysis (PD), with automated PD remaining the preferred modality. There were 964 episodes of peritonitis in 1,018 patient years, yielding an overall peritonitis rate of 1 episode every 13 patient months. More PD patients attended school full time than hemodialysis (HD) patients at baseline (77% vs. 45%), which continued at 6, 12, and 24 months of followup. There were fewer Hispanic patients who were full-time students, whether on HD or PD, compared with white or black patients; 18% of Hispanic patients did not attend school, even though they were medically capable. The majority of dialysis courses terminated due to transplantation (54%), with change in dialysis modality the next most-common reason (28%). Early dialysis termination for any reason was seen more often in HD than PD (40% vs. 23% at 6 months), but by 24 months similar percentages of PD and HD courses had been terminated (75% HD, 72% PD). The most-common PD access was a Tenckhoff catheter with a single cuff, a straight tunnel and lateral exit site. The majority of HD accesses were external percutaneous catheters, with the sublcavian vein the most-common site. Erythropoietin was administered in 93% of HD and PD patients at 24 months.
Asunto(s)
Diálisis Peritoneal/estadística & datos numéricos , Diálisis Renal/estadística & datos numéricos , Adolescente , Negro o Afroamericano/estadística & datos numéricos , Estatura , Peso Corporal , Niño , Preescolar , Educación , Femenino , Hispánicos o Latinos , Humanos , Lactante , Trasplante de Riñón , Masculino , América del Norte , Diálisis Peritoneal/efectos adversos , Diálisis Peritoneal/métodos , Peritonitis/etiología , Diálisis Renal/métodos , Población BlancaRESUMEN
Hypertension after renal transplantation occurs commonly and, in adults, is associated with decreased graft survival. The North American Pediatric Renal Transplant Cooperative Study database was analyzed to determine: (1) the percent use of antihypertensive (anti-HTN) medication based on donor type, race, age, and acute rejection status; and (2) whether use of anti-HTN medication is associated with higher rates of subsequent graft failure. Data regarding anti-HTN medication use was available in 5251 renal allografts (4821 patients) with >30 d graft function. Posttransplant follow-up data were collected at 30 d, 6 mo, 12 mo, and then annually for 5 yr. At each follow-up, patients were selected for further analysis if the graft was functioning at that visit and subsequent follow-up data were available. Overall, anti-HTN medication use was 79% on day 30 and 58% at 5 yr. At each follow-up, anti-HTN medication use was higher (P < 0.01) for cadaveric donor versus living related donor, blacks versus whites, age >12 versus <12 yr, and > or = 1 versus 0 acute rejection episodes. Anti-HTN medication use at each annual follow-up was associated with significantly higher rates of subsequent graft failure. Multiple regression analysis controlling for all factors associated with increased use of anti-HTN medications revealed a relative risk of graft failure for use of anti-HTN medication of greater than 1.4 (P < 0.001). In recipients of cadaveric allografts, only acute rejection status predicted subsequent graft failure more strongly than use of anti-HTN medications. These data suggest that hypertension after renal transplantation in children, as evidenced by use of anti-HTN medications, is associated with increased rates of subsequent graft failure.
Asunto(s)
Antihipertensivos/efectos adversos , Rechazo de Injerto/epidemiología , Hipertensión/tratamiento farmacológico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/estadística & datos numéricos , Distribución por Edad , Antihipertensivos/uso terapéutico , Niño , Preescolar , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Humanos , Hipertensión/etiología , Lactante , Recién Nacido , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Trasplante de Riñón/mortalidad , Masculino , Prevalencia , Modelos de Riesgos Proporcionales , Sistema de Registros , Análisis de Regresión , Factores de Riesgo , Trasplante Homólogo/efectos adversos , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: To compare the incidence of encapsulated bleb after trabeculectomy in eyes with and without previous argon laser trabeculoplasty and to assess other risk factors for encapsulated bleb development. METHODS: After medical treatment failure, eyes enrolled in the Advanced Glaucoma Intervention Study (AGIS) were randomly assigned to sequences of interventions starting with either argon laser trabeculoplasty or trabeculectomy. In the present study we compared the clinical course for 1 year after trabeculectomy in 119 eyes with failed argon laser trabeculoplasty with that of 379 eyes without previous argon laser trabeculoplasty. Data on bleb encapsulation were collected at the time that the encapsulation was diagnosed, and 3 and 6 months later. RESULTS: Of multiple factors examined in the AGIS data for the risk of developing encapsulated bleb, only male gender and high school graduation without further formal education were statistically significant. Encapsulation occurred in 18.5% of eyes with previous argon laser trabeculoplasty failure and 14.5% of eyes without previous argon laser trabeculoplasty (unadjusted relative risk, 1.27; 95% confidence limits = 0.81, 2.00; P = .23). After adjusting for age, gender, educational achievement, prescribed systemic beta-blockers, diabetes, visual field score, and years since glaucoma diagnosis, this difference remains statistically not significant. Four weeks after trabeculectomy, mean intraocular pressure was 7.5 mm Hg higher in eyes with (22.5 mm Hg) than without (15.0 mm Hg) encapsulated bleb; at 1 year after trabeculectomy and the resumption of medical therapy when needed, this excess was reduced to 1.4 mm Hg. CONCLUSIONS: This study, as did two previous studies, found male gender to be a risk factor for bleb encapsulation. Four studies, including the present study, have reported a higher rate of encapsulation in eyes with previous argon laser trabeculoplasty; in two of the studies, one of which was the present study, the rate was not statistically significantly higher; in the other two studies the rate was significantly higher. The 4-week postoperative mean intraocular pressure was higher in eyes with than without encapsulated bleb; with the resumption of medical treatment the two means converged after 1 year.
Asunto(s)
Enfermedades de la Conjuntiva/etiología , Quistes/etiología , Glaucoma de Ángulo Abierto/cirugía , Trabeculectomía/efectos adversos , Anciano , Enfermedades de la Conjuntiva/epidemiología , Enfermedades de la Conjuntiva/patología , Tejido Conectivo/patología , Quistes/epidemiología , Quistes/patología , Femenino , Humanos , Incidencia , Presión Intraocular , Terapia por Láser , Masculino , Factores de Riesgo , Factores Sexuales , Estados Unidos/epidemiologíaRESUMEN
The 1996 annual report of the Chronic Renal Insufficiency Arm of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) summarizes descriptive data and highlights important features on 1,725 patients from 130 centers. This database contains information on patients with an estimated glomerular filtration rate (GFR) < or = 75 ml/min per 1.73 m2 as calculated by the Schwartz formula, who were treated on or after 1 January 1994. Thus this report reflects 2 years of data entry. Analysis of the data revealed that nearly two-thirds of patients registered had a structural anomaly. On average, patients were 1.5 standard deviations below age- and sex-specific norms for height, and 0.6 standard deviations below weight norms. Mean serum creatinine for the entire group was 2.4 mg/dl and 68% of patients had a baseline GFR of at least 25 ml/min per 1.73 m2. The mean hematocrit for all children at registration was 33.3 +/- 6.3%, and did not vary among age groups. Overall, 30.9% of patients had a hematocrit < 30%. Only 12.8% of patients were receiving Epoetin therapy. Although still in infancy, the Chronic Renal Insufficiency Arm of the NAPRTCS database in providing important insights into this disorder.
Asunto(s)
Fallo Renal Crónico/epidemiología , Adolescente , Adulto , Factores de Edad , Anemia/complicaciones , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Niño , Preescolar , Femenino , Tasa de Filtración Glomerular , Trastornos del Crecimiento/etiología , Humanos , Lactante , Recién Nacido , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/etiología , Pruebas de Función Renal , Masculino , América del Norte/epidemiologíaRESUMEN
Sickle cell disease is a rare cause of end-stage renal disease (ES-RD) in pediatrics accounting for only 0.5% and 0.2% of the patients registered in the dialysis and transplant arms of the NAPRTCS database, respectively. Accordingly, the single-center experience with this disorder is extremely rare, and little information on patient and graft outcome is available. Between 1989-1995, 9 patients with sickle cell nephropathy (5 male and 4 female) received 10 transplants [7 cadaver (CAD) and 3 living-related donor (LRD)]. The mean age at the time of the first transplant was 16.0 +/- 1.6 years. Prior to transplantation, all patients received maintenance dialysis (4 HD, 4 PD, 1 HD/PD) for 21.4 +/- 16.1 months (range 3-47 months), and all had received > 5 lifetime random blood transfusions. There was a mean 15.9 consecutive days of hospitalization from transplantation to discharge. Initial immunosuppression consisted of methyl predinsolone/prednisone (9 patients) cyclosporine (7 patients) and azathioprine (8 patients). ATG/ALG or OKT3 were used in 3 CAD transplants. There have been 21 acute rejection episodes in 7 of the 9 patients. Two patients had no rejections and 2 patients had 6 rejections each. Six of the 21 rejection episodes occurred within the first 100 days post-transplant. Nine (43%) of the rejections were completely reversed, the reversal rate varying from 71% for first rejections to 29% for second and subsequent rejections. Four (40%) of the 10 grafts have failed. Graft survival at 12 and 24 months post-transplant is 0.89 +/- 0.11 and 0.71 +/- 0.18, respectively. Patient survival is 89%. The present experience suggests that renal transplantation is a viable option for the adolescent patient with sickle cell nephropathy and ESRD.