RESUMEN
Background: Among ESRD patients, obesity may improve dialysis-survival but decreases likelihood of transplantation, and as such, obesity prevalence may directly affect growth of the dialysis population. Objective: The objective of this study was to assess BMI trends in the ESRD population as compared to the general population. Materials and Methods: Incident adult ESRD patients were identified from the United States Renal Data System from 01/01/1995-12/31/2010 (n=1,458,350). Data from the Behavioral Risk Factor Surveillance System (n=4,303,471) represented the US population. Trends in BMI, obesity classes I (BMI of 30-34.9), II (BMI of 35-39.9), and III (BMI ≥ 40), were examined by year of dialysis initiation. Trends in BMI slope were compared between the ESRD and US populations using linear regression. Results: Mean BMI of ESRD patients in 1995 was 25.2 as compared to 29.4 in 2010, a 16.7% increase, while the US population's mean BMI increased from 25.3 to 27.2, a 7.5% increase. BMI increase among the ESRD population was significantly more rapid than among the US population (ß: 0.16, 95% CI: 0.14-0.18, p<0.001). Conclusions and Recommendations: Mean BMI among the ESRD population is increasing more rapidly than the US population. Given decreased access to kidney transplantation among ESRD patients with obesity, future research should be directed at controlling healthcare expenditures by identifying strategies to address the obesity epidemic among the US ESRD population.
RESUMEN
Excellent outcomes have been demonstrated among select HIV-positive kidney transplant (KT) recipients with well-controlled infection, but to date, no national study has explored outcomes among HIV+ KT recipients by antiretroviral therapy (ART) regimen. Intercontinental Marketing Services (IMS) pharmacy fills (1/1/01-10/1/12) were linked with Scientific Registry of Transplant Recipients (SRTR) data. A total of 332 recipients with pre- and posttransplantation fills were characterized by ART at the time of transplantation as protease inhibitor (PI) or non-PI-based ART (88 PI vs. 244 non-PI). Cox proportional hazards models were adjusted for recipient and donor characteristics. Comparing recipients by ART regimen, there were no significant differences in age, race, or HCV status. Recipients on PI-based regimens were significantly more likely to have an Estimated Post Transplant Survival (EPTS) score of >20% (70.9% vs. 56.3%, p = 0.02) than those on non-PI regimens. On adjusted analyses, PI-based regimens were associated with a 1.8-fold increased risk of allograft loss (adjusted hazard ratio [aHR] 1.84, 95% confidence interval [CI] 1.22-2.77, p = 0.003), with the greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI 1.75-11.48, p = 0.002), and a 1.9-fold increased risk of death as compared to non-PI regimens (aHR 1.91, 95% CI 1.02-3.59, p = 0.05). These results suggest that whenever possible, recipients should be converted to a non-PI regimen prior to kidney transplantation.
Asunto(s)
Antirretrovirales/farmacología , Rechazo de Injerto/mortalidad , Infecciones por VIH/complicaciones , Trasplante de Riñón/métodos , Complicaciones Posoperatorias/mortalidad , Inhibidores de Proteasas/farmacología , Receptores de Trasplantes , Adulto , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/tratamiento farmacológico , Rechazo de Injerto/etiología , Supervivencia de Injerto , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , Humanos , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/cirugía , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
Excellent outcomes have been demonstrated in primary human immunodeficiency virus (HIV)-positive (HIV+) kidney transplant recipients, but a subset will lose their graft and seek retransplantation (re-KT). To date, no study has examined outcomes among HIV+ re-KT recipients. We studied risk for death and graft loss among 4149 (22 HIV+ vs. 4127 HIV-negative [HIV-]) adult re-KT recipients reported to the Scientific Registry of Transplant Recipients (SRTR) (2004-2013). Compared to HIV- re-KT recipients, HIV+ re-KT recipients were more commonly African American (63.6% vs. 26.7%, p < 0.001), infected with hepatitis C (31.8% vs. 5.0%, p < 0.001) and had longer median time on dialysis (4.8 years vs. 2.1 years, p = 0.02). There were no significant differences in length of time between the primary and re-KT events by HIV status (1.5 years vs. 1.4 years, p = 0.52). HIV+ re-KT recipients experienced a 3.11-fold increased risk of death (adjusted hazard ratio [aHR]: 3.11, 95% confidence interval [CI]: 1.82-5.34, p < 0.001) and a 1.96-fold increased risk of graft loss (aHR: 1.96, 95% CI: 1.14-3.36, p = 0.01) compared to HIV- re-KT recipients. Re-KT among HIV+ recipients was associated with increased risk for mortality and graft loss. Future research is needed to determine if a survival benefit is achieved with re-KT in this vulnerable population.
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Rechazo de Injerto/mortalidad , Infecciones por VIH/mortalidad , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/mortalidad , Complicaciones Posoperatorias/mortalidad , Reoperación , Adulto , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/etiología , Supervivencia de Injerto , Infecciones por VIH/cirugía , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Humanos , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/virología , Pruebas de Función Renal , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Receptores de TrasplantesRESUMEN
For some patient subgroups, human immunodeficiency virus (HIV) infection has been associated with worse outcomes after kidney transplantation (KT); potentially modifiable factors may be responsible. The study goal was to identify factors that predict a higher risk of graft loss among HIV-positive KT recipients compared with a similar transplant among HIV-negative recipients. In this study, 82 762 deceased donor KT recipients (HIV positive: 526; HIV negative: 82 236) reported to the Scientific Registry of Transplant Recipients (SRTR) (2001-2013) were studied by interaction term analysis. Compared to HIV-negative recipients, the hepatitis C virus (HCV) amplified risk 2.72-fold among HIV-positive KT recipients (adjusted hazard ratio [aHR]: 2.72, 95% confidence interval [CI]: 1.75-4.22, p < 0.001). Forty-three percent of the excess risk was attributable to the interaction between HIV and HCV (attributable proportion of risk due to the interaction [AP]: 0.43, 95% CI: 0.23-0.63, p = 0.02). Among HIV-positive recipients with more than three HLA mismatches (MMs), risk was amplified 1.80-fold compared to HIV-negative (aHR: 1.80, 95% CI: 1.31-2.47, p < 0.001); 42% of the excess risk was attributable to the interaction between HIV and more than three HLA MMs (AP: 0.42, 95% CI: 0.24-0.60, p = 0.01). High-HIV-risk (HIV-positive/HCV-positive HLAwith more than three MMs) recipients had a 3.86-fold increased risk compared to low-HIV-risk (HIV-positive/HCV-negative HLA with three or fewer MMs)) recipients (aHR: 3.86, 95% CI: 2.37-6.30, p < 0.001). Avoidance of more than three HLA MMs in HIV-positive KT recipients, particularly among coinfected patients, may mitigate the increased risk of graft loss associated with HIV infection.
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Rechazo de Injerto/prevención & control , Infecciones por VIH/cirugía , Hepatitis C/cirugía , Fallo Renal Crónico/cirugía , Trasplante de Riñón/normas , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Supervivencia de Injerto , Infecciones por VIH/complicaciones , VIH-1/aislamiento & purificación , Hepacivirus/aislamiento & purificación , Hepatitis C/complicaciones , Prueba de Histocompatibilidad , Humanos , Fallo Renal Crónico/complicaciones , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Factores de RiesgoRESUMEN
We have investigated the potential use of peroxisome proliferator-activated receptor gamma (PPARgamma) agonists as anti-inflammatory agents in cell-based assays and in a mouse model of endotoxemia. Human peripheral blood monocytes were treated with LPS or PMA and a variety of PPARgamma agonists. Although 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) at micromolar concentrations significantly inhibited the production of TNF-alpha and IL-6, four other high affinity PPARgamma ligands failed to affect cytokine production. Similar results were obtained when the monocytes were allowed to differentiate in culture into macrophages that expressed significantly higher levels of PPARgamma or when the murine macrophage cell line RAW 264.7 was used. Furthermore, saturating concentrations of a potent PPARgamma ligand not only failed to block cytokine production, but also were unable to block the inhibitory activity of 15d-PGJ2. Thus, activation of PPARgamma does not appear to inhibit the production of cytokines by either monocytes or macrophages, and the inhibitory effect observed with 15d-PGJ2 is most likely mediated by a PPARgamma-independent mechanism. To examine the anti-inflammatory activity of PPARgamma agonists in vivo, db/db mice were treated with a potent thiazolidinedione that lowered their elevated blood glucose and triglyceride levels as expected. When thiazolidinedione-treated mice were challenged with LPS, they displayed no suppression of cytokine production. Rather, their blood levels of TNF-alpha and IL-6 were elevated beyond the levels observed in control db/db mice challenged with LPS. Comparable results were obtained with the corresponding lean mice. Our data suggest that compounds capable of activating PPARgamma in leukocytes will not be useful for the treatment of acute inflammation.
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Interleucina-6/antagonistas & inhibidores , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/farmacología , Macrófagos/inmunología , Microcuerpos/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Factores de Transcripción/metabolismo , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Administración Oral , Animales , Línea Celular , Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Experimental/metabolismo , Esquema de Medicación , Humanos , Interleucina-6/biosíntesis , Lipopolisacáridos/antagonistas & inhibidores , Activación de Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Monocitos/inmunología , Monocitos/metabolismo , Obesidad/inmunología , Obesidad/metabolismo , Receptores Citoplasmáticos y Nucleares/agonistas , Acetato de Tetradecanoilforbol/farmacología , Factores de Transcripción/agonistas , Factor de Necrosis Tumoral alfa/biosíntesisRESUMEN
Nitric oxide is believed to be a prominent mediator of inflammation based in part on the correlative expression of the inducible nitric oxide synthase (iNOS) gene in various pathologies. The resulting high output of the highly reactive molecule nitric oxide is then believed to play an important role in the evolving inflammatory response. Studies have shown that iNOS and nitric oxide are present in the tissues of patients with multiple sclerosis (MS). In rodent models of MS, experimental autoimmune encephalomyelitis (EAE), it has been shown that nonspecific NOS inhibitors partially ameliorate the disease. To determine the importance of iNOS in this model of MS, we induced EAE in mice containing a disrupted iNOS (NOS2) gene. Surprisingly, by day 24, the NOS2 knockout mice had a greater incidence of EAE than wild-type control mice (75 vs 12%), and had a higher average severity score (2.42 vs 0.44). These differences appear to result largely from the failure of the disease to remit in NOS2 KO mice. Wild-type mice have a profound ability to reverse EAE (82%) compared with the knockout mice (19%). This result implies that iNOS may in some instances play a protective role in autoimmune-mediated tissue destruction.