José Manuel González-Posada

Universidad de La Laguna, San Cristóbal de La Laguna, Canary Islands, Spain

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Publications (65)205.89 Total impact

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    ABSTRACT: Formulas do not estimate renal function with acceptable precision and accuracy. We compared 51 creatinine-based and/or cystatin c-based formulas with a gold standard (iohexol plasma clearance) in 193 renal transplant recipients using concordance correlation coefficient, total deviation index, coverage probability and the error in chronic kidney disease (CKD) stage classification. No formula showed a concordance correlation coefficient greater than 0.90 (average for creatinine-based formulas: ∼0.70 and for cystatin c-based formulas: ∼0.85). A wide total deviation index was observed: approximately 70% (creatinine-based) and approximately 50% (cystatin c-based), indicating that 90% of the estimations showed bounds of error of ±70% or ±50%, respectively, compared with the gold standard. No formula included 90% of the estimations within a coverage probability of ±10%. Half the CKD stages classified by creatinine-based formulas were incorrect, mainly due to overestimation of renal function. One of 3 CKD stages diagnosed by cystatin c-based formulas was incorrect, with both overestimation and underestimation. Overall, the formulas showed very low precision and accuracy and a high degree of error in reflecting real renal function. In conclusion, formulas do not properly reflect renal function in kidney transplantation, which makes their use in clinical practice unreliable. Moreover, their use in clinical trials should be avoided.
    No preview · Article · Aug 2015 · Transplantation
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    ABSTRACT: Kidney transplant recipients have high cardiovascular risk, and vascular inflammation may play an important role. We explored whether the inflammatory state in the vessel wall was related to carotid intima-media thickness (c-IMT) and patient survival following kidney transplantation. In this prospective observational cohort study we measured c-IMT and expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery in 115 kidney transplant candidates. Another c-IMT measurement was done 1-year post-transplantation in 107. By stepwise multiple regression analysis we explored factors associated with baseline c-IMT and their changes over time. Multivariate Cox regression analysis was constructed to identify risk factors for mortality. A worse cardiovascular profile (older age, smoker, diabetic, carotid plaque, systolic blood pressure and vascular calcification) and higher VCAM-1 levels were found in patients in the highest baseline c-IMT tertile, who also had a worse survival. Factors independently related to baseline c-IMT were age (β=0.369, P<0.0001), fasting glucose (β=0.168, P=0.045), smoking (β=0.228, P=0.003) and VCAM-1 levels (β=0.244, P=0.002). Independent factors associated with c-IMT measurement 1-year post-transplantation were baseline c-IMT (β=-0.677, P<0.0001), post-transplant diabetes (β=0.225, P=0.003) and triglycerides (β=0.302, P=0.023). Vascular VCAM-1 levels were associated with increased risk of mortality in bivariate and multivariate Cox regression. Notably, nearly 50% of patients showed an increase or maintenance of high c-IMT 1 year post-transplantation and these patients experienced a higher mortality (13 versus 3.5%; P=0.021). A worse cardiovascular profile and a higher vascular VCAM-1 protein levels at time of KT are related to subclinical atheromatosis. This could lead to a higher post-transplant mortality. Pre-transplant c IMT, post-transplant diabetes and triglycerides at 1-year post-transplantation may condition a high c-IMT measurement post-transplantation, which may decrease patient survival.
    Full-text · Article · Jun 2015 · PLoS ONE
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    ABSTRACT: Introduction and Aims: Quantification of BKV-load and BKV-specific immunity have been evaluated to monitor BKV-replication. Particular risk factors, long-term outcome, and markers characterizing kidney transplant recipients (KTRs) at increased risk of BK viremia, however, remain poorly described. Methods: We analyzed all adult KTRs at our single transplant center transplanted between 2004 and 2012. 103 (11.9%) of 862 KTRs were diagnosed with BK viremia, among which 24 KTRs (23.3%) showed progression to BKV-associated nephropathy with allograft loss in 3 cases (12.5%). An age-, gender, and maintenance immunosuppression-matched control group of 235 KTRs was used for comparison. Samples were collected before transplantation and at +1, +2, and +3 months posttransplantation. BKV-specific, CMV-specific, and alloreactive T-cells were measured using an interferon-γ Elispot assay. The extent of immunosuppression was quantified by measures of immune function including lymphocyte subpopulations and serum cytokine levels. Results: Upon multivariate analysis CMV reactivation, lymphocyte depletion induction, and acute rejection were more frequent in KTRs developing BK viremia (p<0.05). Seven-year graft survival and estimated GFR were significantly lower in KTRs with BK viremia (p=0.005). KTRs developing early BKV-replication showed significantly increased frequencies of BKV-specific T-cells directed to Large T-antigen prior to transplantation (p<0.001). Shortly after transplantation, however, BKV-specific T-cells were significantly decreased or undetectable (p<0.001). In addition CD3+, CD4+, and CD8+ T-cell counts, and interferon-γ serum levels were significantly lower in KTRs with BK viremia at +1 month after transplantation (p<0.05). KTRs with BK viremia showed significantly higher alloreactive T-cells (p=0.018). Conclusions: Our results suggest that BKV-specific cellular immunity is triggered by subclinical activation of BKV infection prior to transplantation. In KTRs developing BK viremia identified risk factors and overimmunosuppression result in a decline of BKV-specific T-cells insufficient to further regulate BKV-replication. BKV infection may have significant effects on augmentation of alloreactive T cells. Both cross-reactivity of alloreactive T-cells with viral antigens and bystander activation may contribute to allograft injury.
    Full-text · Article · May 2014 · Nephrology Dialysis Transplantation

  • No preview · Article · Jan 2014 · Clinica chimica acta; international journal of clinical chemistry
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    ABSTRACT: In Spain, an increasing number of transplant patients alternate their follow-up visits between transplant and non-transplant centers. Consequently, integral care programs between these centers should be developed for transplant patients. However, coordination between centers is sometimes suboptimal, formal referral from the transplant center to the non-transplant center according to a protocol does not always occur, and nephrologists working in non-transplant centers do not always have the resources required for adequate follow-up. In this article, we present 2 models (in Galicia and the Canary Islands) in which coordinated management between the transplant and the non-transplant center is required, given the characteristics of the territory. These models offer many advantages for patients and professionals in both types of center. The organization of these centers may serve as a model for progressive collaboration between transplant and non-transplant centers in other autonomous regions of Spain.
    Full-text · Article · Mar 2013 · Diálisis y Trasplante
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    ABSTRACT: Data on the combined associations of albuminuria and estimated glomerular filtration rate (eGFR) with renal transplant outcomes are limited. Our objective was to explore how renal transplant outcomes could be predicted by a combined variable of early low-grade albuminuria and allograft dysfunction. We studied a cohort of adult deceased-donor kidney transplant recipients who were subdivided into four groups according to median albuminuria (100 mg/day, interquartile range, 0-470 mg/day) and median eGFR (60 mL/min/1.73 m(2); interquartile range, 30-73 mL/min/1.73 m(2)) at third month posttransplantation as follows: group I (albuminuria <100 and eGFR >60, n=238); group II (albuminuria ≥100 and eGFR >60, n=151); group III (albuminuria <100 and eGFR ≤60; n=167); and group IV (albuminuria ≥100 and eGFR ≤60, n=228). Death-censored graft survival was significantly lower in group IV compared with the rest (P<0.0001). Multivariate Cox regression analysis using fixed and time-dependent covariates showed that the combination of low-grade albuminuria and lower eGFR was associated with graft failure (hazard ratio, 2.2, 95% confidence interval, 1.3-3.7; P=0.003). Likewise, but to a lesser extent, the risk of mortality was increased for group IV (hazard ratio, 1.7, 95% confidence interval, 1.01-2.8; P=0.042). Early association of low-grade albuminuria and allograft dysfunction represents an important risk factor of graft failure and mortality. This additive effect should be considered to identify individuals at risk for adverse kidney transplantation outcomes.
    No preview · Article · Feb 2012 · Transplantation
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    ABSTRACT: Diabetes may accelerate atheromatosis in uremic patients. Our aim was to assess the influence of type 1 diabetes on the atheromatosis-related inflammation in patients with chronic kidney disease (CKD). We analyzed the expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery walls of type 1 diabetic patients with CKD (n = 22) and compared it with nondiabetic uremic patients (n = 92) at the time of kidney transplantation. We evaluated the expression of interleukin (IL)-6, monocyte chemotractant protein (MCP)-1, vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule-1, and the activation of nuclear factor-κβ p65 (NFkB-p65). Common carotid intima-media thickness (c-IMT) was determined by conventional echography. IL-6, MCP-1, and VCAM-1 proteins were elevated in type 1 diabetic patients compared with nondiabetic subjects (P < 0.05). The nuclear localization of NFkB-p65 was higher in type 1 diabetic patients (P < 0.01) and correlated with the levels of MCP-1 in this group (r = 0.726, P < 0.001). Arterial fibrosis correlated with IL-6 and MCP-1 levels (r = 0.411, P < 0.001 and r = 0.378, P = 0.001). A significant correlation was observed between VCAM-1 levels and both the degree of arterial narrowing and c-IMT. Type 1 diabetes produces a proinflammatory state in the arteries of end-stage CKD patients, with increased levels of IL-6, MCP-1, and VCAM-1, as well as a greater degree of p65 activation, which are associated with more severe vascular lesions and higher c-IMT. Although causality is not demonstrated, these findings support the major role of inflammation in type 1 diabetic patients with CKD.
    Full-text · Article · Dec 2011 · Diabetes care
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    ABSTRACT: The beneficial effect of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) in kidney transplant recipients on modern immunosuppression is not yet well established. Our objective was to investigate the impact of the use of ACEI/ARB on patient and graft survival in a cohort of kidney transplant recipients. A total of 990 patients, who received a single deceased donor kidney at our institution between 1996 and 2005, were included in this longitudinal cohort study. All-cause mortality and death-censored graft loss were the primary outcomes. We used traditional time-dependent Cox model (unweighted) and inverse-probability-of-treatment weighting of marginal structural models (weighted Cox model), controlling for time-dependent confounding by indication. A total of 414 patients (42%) received ACEI/ARB through the study period (median duration 14 months, interquartile range 6-40 months). ACEI/ARB use was associated with reduction of risk for mortality in the crude [hazard ratio (HR) 0.627, 95% confidence interval (CI) 0.412-0.953] and adjusted Cox analysis (HR 0.626, 95% CI 0.407-0.963). Similar results were observed after adjusting for confounding by indication (HR 0.629, 95% CI 0.407-0.973). By contrast, ACEI/ARB use was not associated with significant improvement of graft survival after kidney transplantation. ACEI/ARB prescription may be suggested as beneficial among multiple medications for reducing mortality in kidney transplant recipients, but its use was not associated with longer graft survival.
    Full-text · Article · May 2011 · Nephrology Dialysis Transplantation

  • No preview · Article · Jul 2010 · Transplantation
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    ABSTRACT: Background. New-onset diabetes after transplantation (NODAT) is associated with poorer outcomes in kidney transplantation (KT). Thus, identification of modifiable risk factors may be crucial for ameliorating the impact of this entity on transplant outcomes. We assessed the relationships between the weight, body mass index (BMI) and weight gain with NODAT. Methods. We retrospectively analysed 2168 KT performed in Spain during 1990, 1994, 1998 and 2002, with a functioning graft after the first year. At 1 year after KT, three groups were considered: (i) NODAT group (n = 215); (ii) impaired fasting glucose (IFG) group (n = 389); (iii) control group (n = 1564). Results. The incidence of NODAT was 10.8%, 9.9% and 10.0% at 3, 12 and 24 months post-transplantation, respectively. Older recipient age (P < 0.0001) and greater use of tacrolimus (P < 0.0001) were observed in NODAT group. Obesity was more frequent in NODAT group (P < 0.0001), but patients with NODAT had a lower weight gain during the first year after KT (P = 0.038). On multivariate analysis, independent risk factors associated with the development of NODAT were: recipient age [odds ratio (OR): 1.060, P = 0.0001], tacrolimus (OR: 1.611, P = 0.005), triglycerides (OR: 1.511, P = 0.018), positive hepatitis C virus (HCV) status (OR: 1.969, P = 0.001) and pre-transplant body mass index (BMI) (OR: 1.135, P = 0.0001), but not the weight gain. Conclusions. BMI, but not the weight gain at 1 year after transplant, is an independent risk factor for NODAT. Tailoring clinical strategies may minimize the impact of this complication.
    Full-text · Article · Jun 2010 · NDT Plus
  • G Pérez-Suárez · D Marrero · R Rodríguez · P Delgado · M Cobo · J M González-Posada · D Hernández
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    ABSTRACT: Goodpasture's syndrome is a rare autoimmune disorder characterized by rapidly progressive glomerulonephritis (RPGN) and alveolar hemorrhage in the presence of antiglomerular basement membrane (anti-GBM) antibodies. Central nervous system involvement is highly unusual in the absence of anti-neutrophil cytoplasmic antibodies. We report the case of a 20-year-old man with RPGN accompanied by bloody sputum, tonic-clonic seizure and high titers of anti-GBM antibody. After treatment with immunosuppressants and plasmapheresis, the patient showed reduced anti-GBM antibody titers and improved neurologic and respiratory symptoms, but renal failure persisted, requiring hemodialysis. Twenty months later, with the disease in remission, he underwent deceased-donor renal transplantation.
    No preview · Article · Jan 2010 · Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia
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    ABSTRACT: In our Universitary Hospital of Canarias we iniciated in May 2008 a induction therapy protocol for sensitized patients receiving cadaveric renal graft using intravenous immunoglobulins, plasmapheresis and rituximab plus immunosuppression with prednisone, tacrolimus and mycophenolate mofetil. We present the results of four patients. Everyone had anti-HLA antibodies rate (PRA by CDC) more than 75%, were on a waiting list during 4 to 17 years and follow-up time was 10-14 months after transplantation. Patient and graft survival in this period was 100%. Only one patient suffered a humoral acute rejection and another one cellular rejection, in both cases reversible with treatment. During the first year, no evidence of de novo donor-specific antibodies was detected. All patients had significantly reduced the CD19+ cells percentage after infusion of rituximab. Neurological symptoms suggestive of progressive multifocal leukoencephalopathy or serious viral infections after transplantation have not been observed. Additionally, no immediate side effects were observed after administration of medication. In summary, induction therapy by combining immunoglobulin, plasmapheresis and rituximab in hypersensitive patients allows the realization of deceased kidney transplantation with good results in the short and medium-term without serious side effects. It remains to know whether this success will continue in the long term.
    No preview · Article · Jan 2010 · Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia
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    ABSTRACT: In our Universitary Hospital of Canarias we iniciated in May 2008 a induction therapy protocol for sensitized patients receiving cadaveric renal graft using intravenous immunoglobulins, plasmapheresis and rituximab plus immunosuppression with prednisone, tacrolimus and mycophenolate mofetil. We present the results of four patients. Everyone had anti-HLA antibodies rate (PRA by CDC) more than 75%, were on a waiting list during 4 to 17 years and follow-up time was 10-14 months after transplantation. Patient and graft survival in this period was 100%. Only one patient suffered a humoral acute rejection and another one cellular rejection, in both cases reversible with treatment. During the first year, no evidence of de novo donor-specific antibodies was detected. All patients had significantly reduced the CD19+ cells percentage after infusion of rituximab. Neurological symptoms suggestive of progressive multifocal leukoencephalopathy or serious viral infections after transplantation have not been observed. Additionally, no immediate side effects were observed after administration of medication. In summary, induction therapy by combining immunoglobulin, plasmapheresis and rituximab in hypersensitive patients allows the realization of deceased kidney transplantation with good results in the short and medium-term without serious side effects. It remains to know whether this success will continue in the long term.
    Full-text · Article · Dec 2009 · Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia
  • G. Pérez-Suárez · D. Marrero · R. Rodríguez · P. Delgado · M. Cobo · J.M. González-Posada · D. Hernández
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    ABSTRACT: Goodpasture's syndrome is a rare autoimmune disorder characterized by rapidly progressive glomerulonephritis (RPGN) and alveolar hemorrhage in the presence of anti-glomerular basement membrane (anti-GBM) antibodies. Central nervous system involvement is highly unusual in the absence of anti-neutrophil cytoplasmic antibodies. We report the case of a 20-year-old man with RPGN accompanied by bloody sputum, tonic-clonic seizure and high titers of anti-GBM antibody. After treatment with immunosuppressants and plasmapheresis, the patient showed reduced anti-GBM antibody titers and improved neurologic and respiratory symptoms, but renal failure persisted, requiring hemodialysis. Twenty months later, with the disease in remission, he underwent deceased-donor renal transplantation.
    No preview · Article · Dec 2009 · Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia
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    ABSTRACT: Although pancreas transplantation (PT) is the treatment of choice in selected diabetic patients, the International Pancreas Transplant Registry (IPTR) has reported important differences in activity between USA and Europe. Of all cases reported, 75% are from USA and only 23% from Europe. Therefore, an analysis of PT activity in selected European countries (SEC) and USA was performed. Materials and methods. We compared national data reports (2002-06) of deceased donors (DD) and deceased solid organ transplantation (DSOT), with special attention to PT activity from 13 SEC countries (375 million inhabitants) and USA (298 million inhabitants). The number of PT performed in USA was 2-fold higher than in SEC, with the annual rate >2.4 times higher in USA [5.08-4.64 versus 1.61-1.91 per million population (p.m.p.)]. DD and other DSOT activity rates were only slightly higher in USA. In SEC, important differences in PT activity rate were found between countries in the same year (0-6.21 p.m.p.) and in the same country between different years (6.21-2.47 p.m.p.), unrelated to DD or other DSOT activity rate. PT activity rate increased in SEC from 1.61 to 1.91 p.m.p. but decreased in six countries. The waiting list for PT at the end of 2006 was almost 2-fold higher in USA than in SEC. Differences in PT activity rate between 13 SEC countries and USA were not related to DD or other DSOT activity. Different waiting list inclusion criteria or incidence of diabetes complications may be considered in more specific studies.
    Full-text · Article · Nov 2009 · Nephrology Dialysis Transplantation
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    ABSTRACT: All-cause mortality is high after kidney transplantation (KT), but no prognostic index has focused on predicting mortality in KT using baseline and emergent comorbidity after KT. A total of 4928 KT recipients were used to derive a risk score predicting mortality. Patients were randomly assigned to two groups: a modeling population (n=2452), used to create a new index, and a testing population (n=2476), used to test this index. Multivariate Cox regression model coefficients of baseline (age, weight, time on dialysis, diabetes, hepatitis C, and delayed graft function) and emergent comorbidity within the first posttransplant year (diabetes, proteinuria, renal function, and immunosuppressants) were used to weigh each variable in the calculation of the score and allocated into risk quartiles. The probability of death at 3 years, estimated by baseline cumulative hazard function from the Cox model [P (death)=1-0.993592764 (exp(score/100)], increased from 0.9% in the lowest-risk quartile (score=40) to 4.7% in the highest risk-quartile (score=200). The observed incidence of death increased with increasing risk quartiles in testing population (log-rank analysis, P<0.0001). The overall C-index was 0.75 (95% confidence interval: 0.72-0.78) and 0.74 (95% confidence interval: 0.70-0.77) in both populations, respectively. This new index is an accurate tool to identify high-risk patients for mortality after KT.
    No preview · Article · Sep 2009 · Transplantation

  • No preview · Conference Paper · Jan 2009
  • J.M. González-Posada · D Hernández · A Martin · J.M. Raya · S Pitti · A Bonilla · I Astigarraga · A Alarcó
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    ABSTRACT: We describe a severe case of hemophagocytic lymphohistiocytosis (HLH), secondary to a candida glabrata retroperitoneal abscess in a 41-year-old simultaneous pancreas-kidney transplantation (SPKT) recipient. Despite percutaneous abscess drainage and antifungal therapy, general status deteriorated with persistent fever, severe pancytopenia and liver dysfunction. Presence of hypertriglyceridemia, very high serum levels of ferritin and hemophagocytosis in a bone-marrow aspirate gave the diagnosis of HLH. Of note, change from tacrolimus to cyclosporine together with dexamethasone produced rapid response with status improvement. We concluded that HLH, a rare but often fatal condition characterized by excessive activation of lymphocytes and macrophages, is a diagnostic and therapeutic challenge in solid-organ transplanted patients and must be suspected in the presence of fever, blood cytopenia and liver dysfunction. Specific antiinfectious therapy together with cyclosporine and dexamethasone may be a therapeutic approach.
    No preview · Article · Aug 2008 · Clinical nephrology

  • No preview · Article · Jul 2008 · Transplantation

  • No preview · Article · Jul 2008 · Transplantation