RESUMEN
Insufficient hemodynamics during agonal phase-ie, the period between withdrawal of life-sustaining treatment and circulatory arrest-in Maastricht category III circulatory-death donors (DCD) potentially exacerbate ischemia/reperfusion injury. We included 409 Dutch adult recipients of DCD donor kidneys transplanted between 2006 and 2014. Peripheral oxygen saturation (SpO2-with pulse oximetry at the fingertip) and systolic blood pressure (SBP-with arterial catheter) were measured during agonal phase, and were dichotomized into minutes of SpO2 > 60% or SpO2 < 60%, and minutes of SBP > 80 mmHg or SBP < 80 mmHg. Outcome measures were and primary non-function (PNF), delayed graft function (DGF), and three-year graft survival. Primary non-function (PNF) rate was 6.6%, delayed graft function (DGF) rate was 67%, and graft survival at three years was 76%. Longer periods of agonal phase (median 16 min [IQR 11-23]) contributed significantly to an increased risk of DGF (P = .012), but not to PNF (P = .071) and graft failure (P = .528). Multiple logistic regression analysis showed that an increase from 7 to 20 minutes in period of SBP < 80 mmHg was associated with 2.19 times the odds (95% CI 1.08-4.46, P = .030) for DGF. In conclusion, duration of agonal phase is associated with early transplant outcome. SBP < 80 mmHg during agonal phase shows a better discrimination for transplant outcome than SpO2 < 60% does.
Asunto(s)
Funcionamiento Retardado del Injerto/mortalidad , Rechazo de Injerto/mortalidad , Hemodinámica , Fallo Renal Crónico/cirugía , Trasplante de Riñón/mortalidad , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/métodos , Adulto , Presión Sanguínea , Muerte , Funcionamiento Retardado del Injerto/etiología , Selección de Donante , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Oxígeno/metabolismo , Perfusión , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , SístoleRESUMEN
In renal transplantation, use of calcineurin inhibitors (CNIs) is associated with nephrotoxicity and immunosuppression with malignancies and infections. This trial aimed to minimize CNI exposure and total immunosuppression while maintaining efficacy. We performed a randomized controlled, open-label multicenter trial with early cyclosporine A (CsA) elimination. Patients started with basiliximab, prednisolone (P), mycophenolate sodium (MPS), and CsA. At 6 months, immunosuppression was tapered to P/CsA, P/MPS, or P/everolimus (EVL). Primary outcomes were renal fibrosis and inflammation. Secondary outcomes were estimated glomerular filtration rate (eGFR) and incidence of rejection at 24 months. The P/MPS arm was prematurely halted. The trial continued with P/CsA (N = 89) and P/EVL (N = 96). Interstitial fibrosis and inflammation were significantly decreased and the eGFR was significantly higher in the P/EVL arm. Cumulative rejection rates were 13% (P/EVL) and 19% (P/CsA), (p = 0.08). A post hoc analysis of HLA and donor-specific antibodies at 1 year after transplantation revealed no differences. An individualized immunosuppressive strategy of early CNI elimination to dual therapy with everolimus was associated with decreased allograft fibrosis, preserved allograft function, and good efficacy, but also with more serious adverse events and discontinuation. This can be a valuable alternative regimen in patients suffering from CNI toxicity.
Asunto(s)
Everolimus/uso terapéutico , Fibrosis/tratamiento farmacológico , Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto/efectos de los fármacos , Trasplante de Riñón/efectos adversos , Prednisolona/uso terapéutico , Antiinflamatorios/uso terapéutico , Femenino , Fibrosis/etiología , Rechazo de Injerto/etiología , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , DesteteRESUMEN
Cyclosporine, everolimus, and tacrolimus are the cornerstone of immunosuppressive therapy in renal transplantation. These drugs are characterized by narrow therapeutic windows, highly variable pharmacokinetics (PK), and metabolism by CYP3A enzymes. Recently, the decreased activity allele, CYP3A4*22, was described as a potential predictive marker for CYP3A4 activity. This study investigated the effect of CYP3A4*22, CYP3A5*3, and CYP3A combined genotypes on cyclosporine, everolimus, and tacrolimus PK in renal transplant patients. CYP3A4*22 carriers showed a significant lower clearance for cyclosporine (-15%), and a trend was observed for everolimus (-7%) and tacrolimus (-16%). Patients carrying at least one CYP3A5*1 allele had 1.5-fold higher tacrolimus clearance compared with noncarriers; however, CYP3A5*3 appeared to be nonpredictive for everolimus and cyclosporine. CYP3A combined genotype did not significantly improve prediction of clearance compared with CYP3A5*3 or CYP3A4*22 alone. These data suggest that dose individualization of cyclosporine, everolimus, or tacrolimus therapy based on CYP3A4*22 is not indicated.CPT: Pharmacometrics Systems Pharmacology (2014); 3, e100; doi:10.1038/psp.2013.78; published online 12 February 2014.
RESUMEN
Although increased longevity of grafts has led to a growing number of long-term kidney transplant recipients, knowledge about the perceived health of these patients remains limited. A cross-sectional sample of 609 patients (60% response) was stratified into a short-term (≤1 year), midterm (>1 and ≤8 years), and long-term cohort (>8 and ≤15 years posttransplantation). Cohorts were compared for perceived health (Visual Analogue Scale of the EQ-5D), number of symptoms, and number of comorbidities by analysis of variance/covariance and multivariate regression analyses. Long-term patients reported more symptoms, (F[2, 606] = 3.09, P = .046) and more comorbidities, (F[2, 588] = 4.75, P = .009) but similar levels of perceived health, (F[2, 550] = 2.37, P > .05). Furthermore, symptoms were less influential for perceived health among long- versus short-term (z = -2.08, P = .038) or midterm cohorts (z = -2.60, P = .009). Previously identified predictors of perceived health accounted for less variance in the long-term as opposed to short-term (z = 4.30, P < .001) and midterm cohort (z = 2.07, P = .039). Despite more symptoms and comorbidities, the perceived health of long-term kidney transplant recipients was comparable to the short- and midterm, possibly due to selective survival or patient adjustment. Because kidney function and symptoms were predominantly associated with short-term perceived health, there is an urgent need to identify variables associated with long-term perceived health.
Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Estado de Salud , Trasplante de Riñón , Percepción , Adolescente , Adulto , Anciano , Distribución de Chi-Cuadrado , Comorbilidad , Estudios Transversales , Femenino , Encuestas de Atención de la Salud , Indicadores de Salud , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenAsunto(s)
Sistema del Grupo Sanguíneo ABO , Incompatibilidad de Grupos Sanguíneos/inmunología , Trasplante de Riñón/métodos , Leucoencefalopatía Multifocal Progresiva/diagnóstico , Leucoencefalopatía Multifocal Progresiva/etiología , Glomerulonefritis por IGA/complicaciones , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Isoxazoles/uso terapéutico , Trasplante de Riñón/efectos adversos , Leflunamida , Paresia/etiología , Paresia/terapia , Insuficiencia Renal/complicaciones , Insuficiencia Renal/terapia , Riesgo , Resultado del Tratamiento , Virosis/complicacionesRESUMEN
Cardiovascular disease (CVD) is the main cause of mortality in renal transplant recipients (RTR). Classical factors only partly explain the excess risk. We hypothesized that high EPO--a marker for inflammation, angiogenesis and hypoxia--is associated with CVD in RTR. A total of 568 RTR (51±12 years; 45% female; creatinine clearance (CrCl) 57±20 mL/min/1.73 m(2)) were included at median 6 [IQR 3-11] years after transplantation. Subjects on exogenous EPO and ferritin-depleted subjects were excluded. Median EPO level was 17.3 [IQR 11.9-24.2] IU/L. Gender-stratified tertiles of age-corrected EPO were positively associated with waist circumference (but not BMI), CVD history, time since transplantation, diuretics, azathioprine, CRP, mean corpuscular volume and triglyceride levels, and inversely with CrCl, RAAS-inhibition, cyclosporine, hemoglobin, total- and HDL-cholesterol. During follow-up for 7 [6-7] years, 121 RTR (21%) died, 64 of cardiovascular (CV) causes. Higher EPO (per 10 IU/L) was associated with total (HR1.16 [1.04-1.29], p = 0.01) and CV mortality (HR1.22 [1.06-1.40], p = 0.005), independent of age, gender, hemoglobin, inflammation, renal function and Framingham risk factors. Thus, EPO and mortality are linked in RTR, independent of potential confounders. This suggests that yet other mechanisms are involved. Dissecting determinants of EPO in RTR may improve understanding of mechanisms behind excess CV risk in this population.
Asunto(s)
Biomarcadores/sangre , Enfermedades Cardiovasculares/mortalidad , Eritropoyetina/sangre , Trasplante de Riñón/efectos adversos , Factores de Edad , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Causas de Muerte/tendencias , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Complicaciones Posoperatorias , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Factores Sexuales , Tasa de Supervivencia/tendenciasRESUMEN
Female kidneys and kidneys from small donors have been suggested to perform worse after kidney transplantation. Here, we evaluate the impact of gender and body dimensions on posttransplantation GFR in living donor transplantation. Two hundred and ninety-three donor-recipient pairs, who were transplanted at our center were evaluated. All pairs had detailed renal function measurement ((125) I-iothalamate and (131) I-hippuran) 4 months predonation in the donor and 2.5 months posttransplantation in donor and recipient. For 88 pairs, 5 years of recipient follow-up was available. Delta GFR was calculated as (recipient GFR-donor single kidney GFR). Recipients of both male and female kidneys had similar renal function at early and long term after transplantation. Male recipients had higher ERPF, ΔGFR and ΔERPF at both time points. Kidneys of donors smaller than their recipient had higher ΔGFR and ΔERPF than kidneys of larger donors at both time points (p < 0.05). In multivariate analysis, ΔGFR was predicted by donor/recipient BSA-ratio together with transplantation related factors (R(2) 0.19), irrespective of donor and recipient gender. In conclusion, in living donor transplantation, female kidneys perform as well as male donor kidneys. Kidneys adapt to the recipient's body size and demands, independent of gender, without detrimental effects in renal function and outcome up to mid-long term.
Asunto(s)
Tamaño Corporal , Trasplante de Riñón , Riñón/fisiopatología , Donadores Vivos , Adulto , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Cardiovascular disease (CVD) is a leading cause of mortality in renal transplant recipients (RTRs). Metabolic syndrome (MS) is highly prevalent in RTRs. Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic component of MS. We investigated associations of NAFLD markers with MS and mortality. RTRs were investigated between 2001 and 2003. NAFLD markers, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (AP) were measured. Bone and nonbone fractions of AP were also determined. Death was recorded until August 2007. Six hundred and two RTRs were studied (age 52+/-12 years, 55% men). At baseline 388 RTRs had MS. Prevalence of MS was positively associated with liver enzymes. During follow-up for 5.3[4.5-5.7] years, 95 recipients died (49 cardiovascular). In univariate Cox regression analyses, GGT (HR=1.43[1.21-1.69], p<0.001) and AP (HR=1.34[1.11-1.63], p=0.003) were associated with mortality, whereas ALT was not. Similar associations were found for cardiovascular mortality. Adjustment for potential confounders, including MS, diabetes and traditional risk factors did not materially change these associations. Results for nonbone AP mirrored that for total AP. ALT, GGT and AP are associated with MS. Of these three enzymes, GGT and AP are associated with mortality, independent of MS. These findings suggest that GGT and AP are independently related to mortality in RTRs.
Asunto(s)
Hígado Graso/complicaciones , Trasplante de Riñón/mortalidad , Síndrome Metabólico/complicaciones , Adulto , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Biomarcadores/sangre , Estudios de Cohortes , Hígado Graso/sangre , Hígado Graso/enzimología , Femenino , Humanos , Estimación de Kaplan-Meier , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/fisiología , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/enzimología , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , gamma-Glutamiltransferasa/sangreRESUMEN
With more marginal deceased donors affecting graft viability, there is a need for specific parameters to assess kidney graft quality at the time of organ procurement in the deceased donor. Recently, kidney injury molecule-1 (Kim-1) was described as an early biomarker of renal proximal tubular damage. We assessed Kim-1 in a small animal brain death model as an early and noninvasive marker for donor-derived injury related to brain death and its sequelae, with subsequent confirmation in human donors. In rat kidney, real-time PCR revealed a 46-fold Kim-1 gene upregulation after 4 h of brain death. In situ hybridization showed proximal tubular Kim-1 localization, which was confirmed by immunohistochemistry. Also, Luminex assay showed a 6.6-fold Kim-1 rise in urine after 4 h of brain death. In human donors, 2.5-fold kidney injury molecule-1 (KIM-1) gene upregulation and 2-fold higher urine levels were found in donation after brain death (DBD) donors compared to living kidney donors. Multiple regression analysis showed that urinary KIM-1 at brain death diagnosis was a positive predictor of recipient serum creatinine, 14 days (p < 0.001) and 1 year (p < 0.05) after kidney transplantation. In conclusion, we think that Kim-1 is a promising novel marker for the early, organ specific and noninvasive detection of brain death-induced donor kidney damage.
Asunto(s)
Muerte Encefálica/metabolismo , Moléculas de Adhesión Celular/metabolismo , Trasplante de Riñón/fisiología , Riñón/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores Virales/metabolismo , Obtención de Tejidos y Órganos , Animales , Biomarcadores/metabolismo , Biopsia , Modelos Animales de Enfermedad , Femenino , Supervivencia de Injerto/fisiología , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Riñón/patología , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Ratas , Ratas Endogámicas F344 , Análisis de RegresiónRESUMEN
Renal functional reserve could be relevant for the maintenance of renal function after kidney donation. Low-dose dopamine induces renal vasodilation with a rise in glomerular filtration rate (GFR) in healthy subjects and is thought to be a reflection of reserve capacity (RC). Older age and higher body mass index (BMI) may be associated with reduced RC. We therefore investigated RC in 178 consecutive living kidney donors (39% males, age 48 +/- 11 years, BMI 25.5 +/- 4.1). RC was determined as the rise in GFR ((125)I-iothalamate), 4 months before and 2 months after donor nephrectomy. Before donor nephrectomy, GFR was 114 +/- 20 mL/min, with a reduction to 72 +/- 12 mL/min after donor nephrectomy. The dopamine-induced rise in GFR of 11 +/- 10% was reduced to 5 +/- 7% after donor nephrectomy (p < 0.001). Before donor nephrectomy, older age and higher BMI did not affect reserve capacity. After donor nephrectomy, the response of GFR to dopamine independently and negatively correlated with older age and higher BMI. Moreover, postdonation reserve capacity was absent in obese donors. The presence of overweight had more impact on loss of RC in younger donors. In conclusion, donor nephrectomy unmasked an age- and overweight-induced loss of reserve capacity. Younger donors with obesity should be carefully monitored.
Asunto(s)
Enfermedades Renales/patología , Enfermedades Renales/cirugía , Trasplante de Riñón/métodos , Riñón/patología , Riñón/fisiología , Donadores Vivos , Nefrectomía/métodos , Adulto , Factores de Edad , Anciano , Envejecimiento , Índice de Masa Corporal , Femenino , Hemodinámica , Humanos , Masculino , Persona de Mediana Edad , Obesidad , SobrepesoRESUMEN
A 52-year-old man presented 8 months after transplantation with an intrarenal mass, which proved to be caused by an infection with Nocardia farcinica. Because of the potential fatal course of nocardiosis, transplantectomy was performed and long-term antibiotic treatment was instituted. Three-and-a-half years later, this patient underwent successful re-transplantation under co-trimoxazole prophylaxis. At present, more than 1 year after his second transplant has been performed, there are no signs of recurrence of Nocardia infection. To our knowledge, this is the first report of a patient with nocardiosis with an intrarenal abscess as presenting symptom.
Asunto(s)
Absceso/etiología , Enfermedades Renales/etiología , Trasplante de Riñón/efectos adversos , Nocardiosis/etiología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Obesity is a risk factor for renal graft loss. Higher body mass index (BMI) in native kidneys is associated with glomerular hyperfiltration. Whether higher BMI in renal transplants is associated with hyperfiltration is unknown. We investigated the impact of BMI on renal hemodynamics 1 year post-transplant. We analyzed glomerular filtration rate (GFR, (125)I-iothalamate) and effective renal plasma flow (ERPF, (131)I-hippurate) in 838 kidney transplants. Data were analyzed for all patients and for the subpopulation without diabetes. Long-term impact of BMI and renal hemodynamics were explored by Cox-regression. With higher BMI GFR and filtration fraction (FF) increased significantly. Multivariate analysis supported impact of BMI on GFR (adjusted r(2) of the model 0.275) and FF (adjusted r(2) of the model 0.158). This association was not explained by diabetes mellitus. On Cox-regression analysis, lower GFR and higher FF were independent determinants of overall graft loss and graft loss by patient mortality. Lower GFR and higher BMI were determinants of death-censored graft loss, with borderline contribution of higher FF. In renal transplants higher BMI is independently associated with higher GFR and FF one year posttransplant, suggesting glomerular hyperfiltration with altered afferent-efferent balance. Mechanisms underlying the long-term prognostic impact of hyperfiltration deserve further exploration.
Asunto(s)
Índice de Masa Corporal , Tasa de Filtración Glomerular , Rechazo de Injerto/diagnóstico , Trasplante de Riñón , Riñón/irrigación sanguínea , Circulación Renal , Adulto , Estudios Transversales , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
UNLABELLED: OBJECTIVE. To describe the experience with combined liver and kidney transplantation at the University Medical Centre Groningen, The Netherlands. DESIGN. Retrospective. METHOD: Data were analysed from all patients who underwent combined liver and kidney transplantation in the University Medical Centre Groningen, in the period November 1994-December 2005. RESULTS: During the study period 582 orthotopic liver transplantations and 1026 isolated kidney transplantations were performed. 16 patients underwent combined liver and kidney transplantation: 4 were children (aged 17 months-16 years) and 12 were adults (aged 19-59 years). For all patients, both organs were obtained from the same post-mortem donor. Indications for combined liver and kidney transplantation were primary hyperoxaluria type I (n=6), polycystic liver and kidney disease (n=3) and unrelated liver and kidney failure (n=7). The 1- and 5-year survival rate was 88% (14/16), which was not significantly different from the results after isolated liver transplantation. Two patients died 11 days and 74 months after combined transplantation, due to complications from unsuccessful retransplantation of the liver for hepatic artery thrombosis and secondary biliary cirrhosis, respectively. A third patient died 51 days after combined transplantation due to sepsis. CONCLUSION: Combined liver and kidney transplantation was a life-saving intervention in this selected group of patients with combined liver and kidney failure. Patient survival was comparable to that of patients undergoing isolated liver transplantation.
Asunto(s)
Fallo Renal Crónico/cirugía , Trasplante de Riñón , Fallo Hepático/cirugía , Trasplante de Hígado , Adolescente , Adulto , Niño , Preescolar , Femenino , Supervivencia de Injerto , Humanos , Hiperoxaluria Primaria/complicaciones , Lactante , Trasplante de Riñón/métodos , Trasplante de Riñón/mortalidad , Trasplante de Hígado/métodos , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Complicaciones Posoperatorias/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Obesity is a risk factor for renal damage in native kidney disease and in renal transplant recipients. Obesity is associated with several renal risk factors such as hypertension and diabetes that may convey renal risk, but obesity is also associated with an unfavorable renal hemodynamic profile independent of these factors, and that may exert effects on renal damage as well. In animal models of obesity-associated renal damage, micro-puncture studies showed glomerular hypertension and hyperfiltration. In humans an elevated glomerular filtration rate has been demonstrated in several studies, sometimes associated with hyperperfusion as well, independent of blood pressure or the presence of diabetes. An elevated filtration fraction was found in several studies, consistent with glomerular hypertension. This renal hemodynamic profile resembles the hyperfiltration pattern in diabetes and is therefore assumed to be a pathogenetic factor in renal damage. Of note, the association between body mass index and renal hemodynamics is not limited to overt obesity or overweight, but is also present across the normal range, without a particular threshold. Multiple factors are assumed to contribute to these renal hemodynamic alterations, such as insulin resistance, the renin-angiotensin system and the tubulo-glomerular responses to increased proximal sodium reabsorption, and possibly also inappropriate activity of the sympathetic nervous system and increased leptin levels. Obesity has a high world-wide prevalence. On a population-basis, therefore, its contribution to long-term renal risk may be considerable, especially as it is usually clustered with risk factors like hypertension and insulin resistance. In short-term studies the renal hemodynamic alterations in obesity and the associated proteinuria were reversible by weight loss, and renin-angiotensin system-blockade, respectively. These interventions are therefore likely to have the potential to limit the renal risks of obesity.
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Enfermedades Renales/fisiopatología , Obesidad/fisiopatología , Circulación Renal/fisiología , Animales , Humanos , Enfermedades Renales/epidemiología , Obesidad/epidemiología , Factores de RiesgoRESUMEN
Kidney transplantation from living donors is important to reduce organ shortage. Reliable pre-operative estimation of post-donation renal function is essential. We evaluated the predictive potential of pre-donation glomerular filtration rate (GFR) (iothalamate) and renal reserve capacity for post-donation GFR in kidney donors. GFR was measured in 125 consecutive donors (age 49 +/- 11 years; 36% male) 119 +/- 99 days before baseline GFR (GFRb) and 57 +/- 16 days after donation (GFRpost). Reserve capacity was assessed as GFR during stimulation by low-dose dopamine (GFRdopa), amino acids (GFRAA) and both (GFRmax). GFRb was 112 +/- 18, GFRdopa 124 +/- 22, GFRAA 127 +/- 19 and GFRmax 138 +/- 22 mL/min. After donation, GFR remained 64 +/- 7%. GFRpost was predicted by GFRb(R2 = 0.54), GFRdopa(R2 = 0.35), GFRAA(R2 = 0.56), GFRmax(R2 = 0.55)and age (R2 = -0.22; p < 0.001 for all). Linear regression provided the equation GFRpost = 20.01 + (0.46*GFRb). Multivariate analysis predicted GFRpost by GFRb, age and GFRmax(R2 = 0.61, p < 0.001). Post-donation renal function impairment (GFR < or = 60 mL/min/1.73 m2) occurred in 31 donors. On logistic regression, GFRb, body mass index (BMI) and age were independent predictors for renal function impairment, without added value of reserve capacity. GFR allows a relatively reliable prediction of post-donation GFR, improving by taking age and stimulated GFR into account. Long-term studies are needed to further assess the prognostic value of pre-donation characteristics and to prospectively identify subjects with higher risk for renal function loss.
Asunto(s)
Selección de Donante , Tasa de Filtración Glomerular/fisiología , Trasplante de Riñón , Riñón/fisiología , Donadores Vivos , Femenino , Estudios de Seguimiento , Humanos , Donadores Vivos/clasificación , Masculino , Persona de Mediana Edad , NefrectomíaRESUMEN
The renal artery resistance index (RI), assessed by Doppler ultrasonography, was recently identified as a new risk marker for late renal allograft loss. This finding requires confirmation since RI in that study was not measured at predetermined time points and ultrasonography is operator-dependent. We investigated the predictive value of renal vascular resistance (RVR), a less operator-dependent method as assessed by mean arterial pressure divided by renal blood flow, for the prediction of recipient mortality and death-censored graft loss. RVR was compared to commonly used risk markers such as creatinine clearance (CrCl), serum creatinine (SCreat) and proteinuria (UProt) in 793 first-time cadaveric renal transplant recipients at predetermined time points after transplantation using receiver operating characteristics (ROC) and Cox survival analyses. The present study showed that RVR is a prominent risk marker for recipient mortality and death-censored graft loss. However, the predictive value of RVR for recipient mortality owed mainly to the impact of mean arterial blood pressure. In contrast, RVR constituted more than the sum of its components for death-censored graft loss, but showed less predictive value than SCreat in univariate analysis. As the assessment of RVR is expensive and time-consuming, we believe that RVR holds no clinical merit for the follow-up of renal transplant recipients.
Asunto(s)
Trasplante de Riñón/fisiología , Circulación Renal/fisiología , Resistencia Vascular/fisiología , Adulto , Antihipertensivos/uso terapéutico , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Diuréticos/uso terapéutico , Femenino , Humanos , Trasplante de Riñón/mortalidad , Trasplante de Riñón/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Proteinuria , Flujo Sanguíneo Regional , Análisis de Supervivencia , Trasplante Homólogo , Insuficiencia del TratamientoRESUMEN
A 37-year-old woman presented with malaise, upper abdominal pain and fever seven months after renal transplantation. She was seronegative for cytomegalovirus (CMV) and had received a kidney from a seropositive donor. She had received CMV prophylaxis (oral ganciclovir) for three months after transplantation. During this period all tests for CMV remained negative. On admission, she presented with symptoms compatible with an acute abdomen and with deterioration of renal function. On emergency laparotomy a perforation of the ileum was found. The resected specimen showed an ulcer with vasculitis at the site of perforation, with both microscopic (owl's eye inclusion bodies), as well as immunohistochemical evidence for a CMV infection. CMV can reactivate (usually in the first three months) after transplantation, sometimes resulting in serious morbidity. The use of antiviral prophylaxis during and after transplantation has certainly decreased the number and severity of CMV infections. This case illustrates that life-threatening infections such as CMV can still emerge a long time after transplantation. Unrelenting awareness of this condition is mandatory, even after apparently adequate anti-CMV prophylaxis.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/etiología , Ganciclovir/uso terapéutico , Trasplante de Riñón/efectos adversos , Adulto , Citomegalovirus/fisiología , Infecciones por Citomegalovirus/prevención & control , Femenino , Humanos , Factores de Tiempo , Activación ViralRESUMEN
BACKGROUND: After kidney transplantation, a decreased graft survival is seen in grafts from brain dead donors compared to living donors, possibly related to a progressive inflammatory reaction in the graft. In this study, we focused on the effects of brain death on the inflammatory response (adhesion molecules, leukocyte infiltration, and gene expression) and stress-related heat shock proteins in the human kidney. Research outcomes and clinical donor parameters were linked to outcome data after transplantation. METHODS: Human kidney biopsy specimens were obtained during organ retrieval from brain dead and living organ donor controls. On these specimens, immunohistochemistry and semiquantitative RT-PCR were performed. Regression analyses were performed connecting results to outcome data of kidney recipients. RESULTS: In brain death, immunohistochemistry showed an increase of E-selectin and interstitial leukocyte invasion versus controls; RT-PCR showed an increase of gene expression of HO-1 and Hsp70. One and 3 years after transplantation, high ICAM and VCAM expression proved to have a negative effect on kidney function in brain dead and living kidneys, while HO-1 proved to have a strongly positive effect, but only in kidneys from living donors. CONCLUSIONS: E-selectin expression and interstitial leukocyte accumulation in brain dead donor kidneys indicate an early phase inflammatory state prior to organ retrieval. Also, brain death causes a stress-related response resulting in upregulation of potentially protective heat shock proteins. The upregulation of HO-1 is beneficial in living donor kidneys, but might be inadequate in brain death.
Asunto(s)
Muerte Encefálica , Inflamación/fisiopatología , Trasplante de Riñón/fisiología , Donadores Vivos , Donantes de Tejidos , Biopsia , Quimiocina CCL2/genética , Selectina E/genética , Estudios de Seguimiento , Regulación de la Expresión Génica , Proteínas HSP70 de Choque Térmico/genética , Hemo Oxigenasa (Desciclizante)/genética , Hemo-Oxigenasa 1 , Humanos , Inmunohistoquímica , Trasplante de Riñón/patología , Proteínas de la Membrana , Nefrectomía , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Recolección de Tejidos y Órganos/métodos , Factor de Crecimiento Transformador beta/genética , Resultado del TratamientoRESUMEN
BACKGROUND: Azathioprine is widely used in Crohn's disease. A major drawback is the occurrence of side-effects, especially acute pancreatitis. Acute pancreatitis is rarely seen when azathioprine is used for other diseases than Crohn's disease. AIM: To survey side-effects of azathioprine after liver or renal transplantation, for systemic lupus erythematosis, Wegener's granulomatosis, autoimmune hepatitis, rheumatoid arthritis, ulcerative colitis or Crohn's disease. METHODS: A computerized search using the term 'azathioprine' or 'imuran' was performed on the Hospital Information System of the university hospital Groningen, resulting in 1564 patients matching our criteria. RESULTS: Eleven of 224 patients with Crohn's disease experienced acute pancreatitis (4.9%) compared with two of 129 (1.5%) with autoimmune hepatitis, two of 388 (0.5%) after renal transplantation, one of 254 (0.4%) after liver transplantation. Acute pancreatitis was more prevalent in Crohn's disease compared with any other disease. Azathioprine-toxicity necessitating withdrawal occurred significantly (P < 0,05) more in rheumatoid arthritis (78 of 317), ulcerative colitis (20 of 94) and Crohn's disease (52 of 224) compared with systemic lupus erythematosis (five of 73), Wegener's granulomatosis (six of 85), autoimmune hepatitis (eight of 129), after liver transplantation (17 of 254) and after renal transplantation (22 of 388). CONCLUSIONS: Acute pancreatitis is strongly associated with Crohn's disease and rarely occurs with other underlying conditions. Overall azathioprine-induced toxicity and the necessity of withdrawal is more common in inflammatory bowel disease and rheumatoid arthritis compared with other diseases.
Asunto(s)
Antimetabolitos/efectos adversos , Azatioprina/efectos adversos , Enfermedad de Crohn/tratamiento farmacológico , Pancreatitis/inducido químicamente , Enfermedad Aguda , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The influence of CsA withdrawal on the glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) was prospectively studied in nine stable liver transplant recipients. Before CsA withdrawal (test 1), and 6 months thereafter (test 2) the renal function was determined by measuring GFR and the ERPF with 125I-iothalamate and 131I-hippuran respectively. The renal function was also stimulated with dopamine, with an amino-acid infusion and a combination of both. After CsA withdrawal the GFR increased, median from 74 ml min-1 to 90 ml min-1, (P < 0.04). The ERPF also increased, median from 310 ml min-1 to 380 ml min-1, (P < 0.03). In test 1 as well as in test 2 the renal function could be stimulated, especially with dopamine. GFR and ERPF improved, even after more than 2 years of CsA treatment. These results suggest that long-term CsA treatment impairs the renal function, though in these liver transplant patients CsA treatment did not prevent afferent and efferent arteriolar vasodilatation after renal stimulation. This reversible intrarenal vasoconstriction during CsA treatment may predict renal improvement after CsA withdrawal.