Publications by authors named "Margarita Rufino"

19 Publications

  • Page 1 of 1

Artery Wall Assessment Helps Predict Kidney Transplant Outcome.

PLoS One 2015 12;10(6):e0129083. Epub 2015 Jun 12.

Nephrology Department, Hospital Universitario de Canarias, CIBICAN, University of La Laguna, Instituto Reina Sofía de Investigación Renal (IRSIN), Tenerife, Spain.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129083PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466324PMC
April 2016

Early association of low-grade albuminuria and allograft dysfunction predicts renal transplant outcomes.

Transplantation 2012 Feb;93(3):297-303

Nephrology Department, Hospital Regional Universitario Carlos Haya, Málaga, Spain.

Background: 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.

Methods: 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).

Results: 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).

Conclusions: 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.
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http://dx.doi.org/10.1097/TP.0b013e31823ec0a7DOI Listing
February 2012

Type 1 diabetes increases the expression of proinflammatory cytokines and adhesion molecules in the artery wall of candidate patients for kidney transplantation.

Diabetes Care 2012 Feb 30;35(2):427-33. Epub 2011 Dec 30.

Research Unit, University Hospital of the Canary Islands, Tenerife, Spain.

Objective: 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).

Research Design And Methods: 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.

Results: 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.

Conclusions: 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.
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http://dx.doi.org/10.2337/dc11-1665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263898PMC
February 2012

Renin-angiotensin system blockade and kidney transplantation: a longitudinal cohort study.

Nephrol Dial Transplant 2012 Jan 28;27(1):417-22. Epub 2011 May 28.

Nephrology Department, Hospital Regional Universitario Carlos Haya, Málaga, Spain.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.
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http://dx.doi.org/10.1093/ndt/gfr276DOI Listing
January 2012

Disproportionately high incidence of diabetes-related end-stage renal disease in the Canary Islands. An analysis based on estimated population at risk.

Nephrol Dial Transplant 2010 Jul 11;25(7):2283-8. Epub 2010 Jan 11.

Nephrology Section, Hospital Universitario de Canarias, Santa Cruz de Tenerife, La Laguna, Spain.

Background: An exceptionally high incidence of diabetes-related end-stage renal disease (DM-ESRD) has been reported in the Canary Islands. This phenomenon was attributed to an increased prevalence of diabetes in this community. We compared the incidence of DM-ESRD in the Canary Islands with the rest of Spain among the estimated number of individuals at risk (people with diabetes in the population).

Methods: The population-at-risk was calculated using census population figures and estimates of self-reported diabetes prevalence from the Spanish National Health Survey in the years 2003 and 2006. The incidence of DM-ESRD for the same years was obtained through Spanish regional registries. The independent effect of age, community of residence and calendar year was estimated with a Poisson regression model. Age-standardized acceptance rate ratios were calculated for each community.

Results: Overall DM-ESRD incidence in the Canary Islands population-at-risk was 1209.9 per million population (pmp) in 2003 and 1477.3 pmp in 2006. Rates for the remaining Spanish regions ranged from 177.3-984.9 pmp. The incidence was higher in the Canary Islands across all age groups, but was most striking for patients > or =75 years. Diabetes prevalence in the general population was greater in the two youngest age strata and diminished from 75 years on in the Canary Islands, in comparison with other areas of Spain. Using a cluster of three communities with the lowest incidence as a reference, the relative risk of DM-ESRD in the Canary Islands population-at-risk was 3.88 [95% confidence interval (CI): 3.07-4.89]. Age-standardized acceptance ratios (95% CI) in the Canary Islands were 2.21 (1.85-2.61) in 2003 and 2.73 (2.34-3.17) in 2006.

Conclusions: Individuals with diabetes in the Canary Islands present a disproportionately high incidence of ESRD. Diabetic Canary inhabitants are exposed to the disease for a longer time and therefore, may be more vulnerable to the development of chronic diabetes complications, including ESRD.
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http://dx.doi.org/10.1093/ndt/gfp761DOI Listing
July 2010

A novel risk score for mortality in renal transplant recipients beyond the first posttransplant year.

Transplantation 2009 Sep;88(6):803-9

Nephrology Department, Hospital Universitario de Canarias, Tenerife, Spain.

Background: 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.

Methods: 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.

Results: 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.

Conclusion: This new index is an accurate tool to identify high-risk patients for mortality after KT.
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http://dx.doi.org/10.1097/TP.0b013e3181b4ac2fDOI Listing
September 2009

Similar renal decline in diabetic and non-diabetic patients with comparable levels of albuminuria.

Nephrol Dial Transplant 2010 Mar 17;25(3):835-41. Epub 2009 Sep 17.

Nephrology Section, Hospital Universitario de Canarias, Santa Cruz de Tenerife, La Laguna, Spain.

Background: Diabetes is the main cause of ESRD, and albuminuria is a major determinant of adverse renal outcome. Likewise, albuminuria is an intermediate risk factor of chronic kidney disease (CKD) progression in diabetic patients. Our aim was to compare the rate of renal decline in diabetic and non-diabetic CKD patients (GFR < 50 ml/min) with comparable levels of albuminuria.

Methods: In this observational study, 333 patients (age 67 +/- 15 years, 46% diabetics) were included during a 7.5-year period. The mean follow-up was 30 +/- 18 months (range 4-79). The influence of study variables was evaluated applying a time-dependent Cox model and slope-based outcome using a linear regression model.

Results: The diabetes condition was associated with adverse outcome in univariate analysis, and after adjusting for age, sex and systolic blood pressure. However, when controlling for albuminuria (a time-dependent covariate), diabetes did not show any association with outcome. In addition, the mean slope of renal decline was similar in diabetic and non-diabetic patients when controlling for albuminuria. The urinary albumin-creatinine ratio was a robust predictor of poor outcome in uni- and multivariate models. In the diabetic group, time-varying glycosilated haemoglobin did not influence renal outcome in the Cox model, and time-varying albuminuria remained a strong predictor of outcome.

Conclusions: Diabetic patients have a poorer renal outcome, but at comparable levels of albuminuria renal decline is similar in diabetic and non-diabetic patients. Albuminuria is a risk factor for renal decline, and the main target to delay progression in patients, diabetics or non-diabetics, with moderate to advanced CKD.
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http://dx.doi.org/10.1093/ndt/gfp475DOI Listing
March 2010

Predicting delayed graft function and mortality in kidney transplantation.

Transplant Rev (Orlando) 2008 Jan;22(1):21-6

Department of Nephrology, Hospital Universitario de Canarias, Ofra s/n, 38320 La Laguna, Tenerife, Spain.

Kidney transplantation (KT) is the treatment of choice for end-stage renal failure, but such patients are increasingly older and have additional comorbid conditions leading to high mortality rates after transplantation. Delayed graft function is a common complication after KT, especially in recipients who receive expanded criteria donor, and these complications are associated with a poorer graft survival in the long term. Taken together, an appropriate assessment of comorbidity grouped in prognostic indexes could be a useful tool to make crucial therapeutic decisions at the time of transplant. Allocation systems based upon a recipient risk score, as well as identification of risk factors for delayed graft function, may improve outcomes after KT. The aim of this review is to assess the contribution and utility of comorbid conditions, grouped in prognostic indexes to predict and improve kidney transplant outcomes.
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http://dx.doi.org/10.1016/j.trre.2007.09.007DOI Listing
January 2008

Impact of cold ischemia time on renal allograft outcome using kidneys from young donors.

Transpl Int 2008 Oct 24;21(10):955-62. Epub 2008 Jun 24.

Department of Nephrology and Research Unit, Hospital Universitario de Canarias, La Laguna, Tenerife, The Canary Islands, Spain.

Prolonged cold ischemia time (CIT) is associated with delayed graft function and worse kidney transplant (KT) outcome, but the effect of CIT on long-term allograft survival in KT from younger donors has not been well established. We investigated the predictive value of CIT exposure on long-term death-censored graft loss in 829 KT recipients from younger donors (<50 years) that were performed in our center between 1991 and 2005. Overall death-censored graft failure rate was significantly higher in CIT>or=19 h group versus CIT<19 h group (26 vs. 16.5%; P = 0.002). Significant differences were also observed when patients with primary nonfunctioning graft were excluded (21 vs. 14%; P = 0.020) and in patients who received tacrolimus plus mycophenolate mofetil (12 vs. 4%; P = 0.05). By multivariate Cox analysis, CIT was found to be independently associated with death-censored graft loss with a 20% increase for every 5 h of CIT [relative risk (RR) 1.04; 95% Confidence Interval (CI): 1.01-1.1; P = 0.021]. Likewise, graft loss risk significantly increased in CIT>or=19 h group versus CIT<19 h group (RR 1.5; 95%CI: 1.1-2.1; P = 0.023). Prolonged CIT is an independent predictor of graft survival in KT from younger donors. Efforts at minimizing CIT (<19 h) should improve transplant outcome significantly in this population.
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http://dx.doi.org/10.1111/j.1432-2277.2008.00708.xDOI Listing
October 2008

The GLUT-1 XbaI gene polymorphism is associated with vascular calcifications in nondiabetic uremic patients.

Nephron Clin Pract 2008 3;108(3):c182-7. Epub 2008 Mar 3.

Nephrology Service, Hospital Universitario de Canarias, La Laguna, Spain.

Background: Glucose transporters mediate the facilitative uptake of glucose into cells, with GLUT-1 being the predominant isoform in vascular smooth muscle cell (VSMC). Clones of human cells overexpressing the GLUT-1 transporter showed a high increase in intracellular glucose concentrations, mimicking the diabetic milieu. It is possible that high intracellular glucose together with uremic factors may play an important role in vascular calcification by transforming VSMC into osteoblast-like cells. The XbaI polymorphism in the GLUT-1 gene has been linked to variations in GLUT-1 expression, with consequent changes in intracellular glucose concentration.

Methods: To assess the association between the GLUT-1 XbaI gene polymorphism and the presence of VC in nondiabetic uremic patients, a total of 105 nondiabetic patients on hemodialysis were studied. VC were evaluated by conventional simple X-ray. Mean values of serum calcium, phosphorous, cholesterol, triglycerides, HbA1c, PTH and insulin were measured. Height, weight, BMI and waist circumference were also determined. The GLUT-1 XbaI polymorphism in the second intron of the gene was ascertained by means of the polymerase chain reaction and restriction fragment length polymorphism analysis on DNA isolated from peripheral blood DNA. In the absence of an XbaI site, a fragment of 305 bp was seen (so-called x allele), whereas fragments of 232 and 73 bp were generated if the XbaI site was present (X allele).

Results: Genotype distribution in all patients was similar to the Caucasian population. However, when the patients were grouped according to the presence or absence of VC, there were marked differences in the frequency of the GLUT1 genotypes: the xx GLUT-1 genotype was more prevalent in the group with VC (30.7 vs. 4.5%, p = 0.001). Stepwise logistic regression demonstrated that the xx GLUT-1 genotype was independently associated with the presence of VC after adjusting for other variables such as age, calcium x phosphrus product, BMI and time on dialysis (OR 7.68; 95% CI 1.28-45.7).

Conclusions: GLUT-1 XbaI gene polymorphism is associated with vascular calcifications in nondiabetic uremic patients.
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http://dx.doi.org/10.1159/000118940DOI Listing
May 2008

Randomized controlled study comparing reduced calcineurin inhibitors exposure versus standard cyclosporine-based immunosuppression.

Transplantation 2007 Sep;84(6):706-14

Nephrology Section and Research Unit, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain.

Background: Immunosuppressive regimens based on low doses of cyclosporine A (CsA) or tacrolimus (TAC) may improve short-term outcome after kidney transplantation (KT), but the optimal immunosuppressive protocol is currently unknown.

Methods: This study compared the 24-month efficacy and safety of two immunosuppressive regimens using reduced calcineurin inhibitors (CNIs) exposure with standard dosage of CsA in 240 patients who were randomized into three groups: group A (n=80): Thymoglobulin, CsA (4 mg/kg twice daily) plus azathioprine (1.5 mg/kg once daily); group B (n=80): basiliximab, CsA (2 mg/kg/ twice daily) plus mycophenolate mofetil (MMF; 1 g twice daily); and group C (n=80): basiliximab, TAC (0.05 mg/kg/ twice daily) plus MMF (1 g twice daily). Steroid administration was identical for all groups.

Results: A significantly better creatinine clearance at 12 months, estimated by Cockcroft-Gault (57+/-12, 65.2+/-20, 73.5+/-27 ml/min, P=0.044), the Jelliffe-2 (51.5+/-16, 56+/-19, 59.4+/-19 ml/min/1.73 m2, P=0.041) and the Modification of Diet in Renal Disease equations (53+/-17, 58.5+/-20, 61.6+/-22 ml/min/1.73 m2, P=0.035), was observed in group C compared with group A. No significant differences were observed between groups B and C. The incidence of biopsy-proven acute rejection was similar between groups (15%, 13.8%, and 16.3%). In addition, patient and graft survival at 24 months were not different between groups. Adverse effects were similar among groups, but cytomegalovirus infections was significantly higher in group A (41% vs. 20% vs. 25%; P=0.008).

Conclusions: Immunosuppressive regimens with reduced CNI exposure provide similar preservation of renal function compared with standard dose of CsA after KT and do not lead to underimmunosuppression.
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http://dx.doi.org/10.1097/01.tp.0000282872.17024.b7DOI Listing
September 2007

Time-dependent changes in cardiac growth after kidney transplantation: the impact of pre-dialysis ventricular mass.

Nephrol Dial Transplant 2007 Sep 17;22(9):2678-85. Epub 2007 May 17.

Department of Nephrology, Hospital Universitario de Canarias, E-38320, La Laguna, Tenerife, Spain.

Background: Left ventricular hypertrophy (LVH) is common in chronic kidney disease (CKD), including kidney transplant recipients. However, time-related left ventricular mass changes (DeltaLVM) from pre-dialysis stage to beyond the first post-transplant year have not been clearly identified.

Methods: We studied a cohort of 60 stages 4-5 CKD patients without overt cardiac disease, who underwent three echocardiograms during follow-up: at pre-dialysis stage, on dialysis and after kidney transplantation (KT). Multiple linear regression was used to model DeltaLVM from baseline study. Cox proportional analysis was used to determine risk factors associated with either de novo LVH or>20% DeltaLVMI over time.

Results: Patients with baseline LVH (n=37; 61%) had a higher body mass index (BMI) than those without LVH (n=23; 39%) (P=0.013). BMI, haemoglobin levels (P=0.047) and non-use of angiotensin-converting enzyme inhibitors (ACEI) (P=0.057) were associated with baseline left ventricular mass index (LVMI). Twelve out of 23 patients (52%) with normal LVM at baseline, developed either de novo LVH or>20% DeltaLVMI at follow-up. On the other hand, 29 (78%) of those with initial LVH maintained this abnormality, and 8 (22%) normalized LVM post-transplantation. Factors associated with DeltaLVMI were age (P=0.01), pre-dialysis LVMI (P<0.0001), serum creatinine (P=0.012) and the use of ACEI post-transplantation (P=0.009). In Cox analysis, pre-dialysis LVMI was associated with de novo LVH or>20% DeltaLVMI over time (hazard ratio 1.009; 95% confidence interval 1.004 to 1.015; P=0.001).

Conclusions: Successful KT may not completely normalize LVM post-transplantation. Pre-dialysis LVMI, traditional risk factors and no use of ACEI may perpetuate cardiac growth following KT.
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http://dx.doi.org/10.1093/ndt/gfm247DOI Listing
September 2007

Retrospective analysis of surgical complications following cadaveric kidney transplantation in the modern transplant era.

Nephrol Dial Transplant 2006 Oct 4;21(10):2908-15. Epub 2006 Jul 4.

Service of Nephrology, Hospital Universitario de Canarias, E-38208 La Laguna, Tenerife, Spain.

Background: Risk factors for surgical complications (SCs) following kidney transplantation in the modern transplant era need to be identified to perform appropriate prophylactic interventions.

Methods: Records from 870 consecutive adult cadaveric kidney transplants done at a single centre were reviewed. SCs were classified into four groups: (i) vascular (12%, thrombosis or stenosis); (ii) haemorrhagic (12%); (iii) ureteral (7.5%, leaks and stenosis) and (iv) wound (16%, lymphocoeles or dehiscences).

Results: One or more SCs occurred in 299 (34%) patients, with multiple SCs in 65 (7.4%). By logistic regression analysis, recipient vessel atherosclerosis and delayed graft function (DGF) were significantly associated with both thrombotic complications [odds ratio (OR) 4, 95% confidence interval (CI), 1.4-11, P = 0.010 and OR 3.8, 1.3-12, P < 0.00001, respectively] and graft artery stenosis (OR 2.9, 1.2-6.8, P = 0.015 and OR 5.6, 2.3-13.4, P < 0.0001, respectively). Acute rejection increased the risk of graft artery or ureteral stenosis by 2.5 (CI 1.02-6.4, P = 0.045) and 3.3 (CI 1.1-10, P = 0.034), respectively. Older recipients were related to urinary leak (OR 1.04, CI 1.01-1.07, P = 0.011). Difficult bench surgery, DGF and the use of antiplatelet drugs increased the risk of bleeding by 3.6 (CI 1.9-6.4, P < 0.0001), 2.7 (CI 1.5-4.7, P < 0.0001) and 1.8 (CI 1.03-3.29, P = 0.038), respectively. Each month on dialysis increased the risk by 1.02 (CI 1.01-1.03, P = 0.002). Sirolimus increased the risk for wound SCs by 4.1 (CI 2.1-8.3, P < 0.0001) and obesity, retransplant and acute rejection were additional risk factors.

Conclusions: Adult renal transplant recipients at risk for SCs can be identified by age, DGF, graft vessel and recipient atheromatosis, difficult bench surgery, obesity, rejection and the use of antiplatelet drugs and rapamycin.
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http://dx.doi.org/10.1093/ndt/gfl338DOI Listing
October 2006

Clinical impact of preexisting vascular calcifications on mortality after renal transplantation.

Kidney Int 2005 May;67(5):2015-20

Nephrology Section, Research Unit, Hospital Universitario de Canarias, Instituto Reina Sofia de Investigación, La Laguna, Tenerife, Spain.

Background: Vascular calcifications (VC) are a well-known cardiovascular risk factor (CVRF) in uremic patients. However, their role on mortality after renal transplantation (RT) is unclear.

Methods: In 1117 RT recipients, we investigated the association between long-term survival and the presence of VC, evaluated by preoperative posteroanterior plain radiography from aorto-iliac region, at the time of RT. The primary study outcome was all-cause mortality. Other perioperative CVRF were also collected.

Results: VC were observed in 273 patients (24.4%) before RT; additionally, 132 (12%) patients died during follow-up, due, mainly, to cardiovascular (39%) or infectious (24%) complications. As expected, patients with VC showed a higher age and a greater number of CVRF than those without VC. Overall mortality rate was also higher in VC group (19 vs. 9.5%; P= 0.0001), as well as cardiovascular mortality (9.5 vs. 3.1; P= 0.048). Multivariate Cox model showed that VC were predictor of overall mortality [relative risk (RR) 1.8; 95% CI 1.1-2.8; P= 0.015] and cardiovascular mortality (RR 2.6; 95%CI 1.1-6); P= 0.033), independently of other CVRF. An interaction between the presence of VC and diabetes was found. The effect of VC on mortality was evident in nondiabetic patients, that is, those with VC had a significantly higher mortality rate than patients without VC (21 vs. 9%; P= 0.0001). By contrast, these differences were not observed in diabetic patients (16.5 vs. 14.3%; P= 0.656).

Conclusion: VC evaluated by a simple and inexpensive plain radiography are an independent predictor of cardiovascular and all-cause mortality following RT. This finding may encourage the implementation of appropriate therapeutic strategies after RT.
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http://dx.doi.org/10.1111/j.1523-1755.2005.00303.xDOI Listing
May 2005

A novel prognostic index for mortality in renal transplant recipients after hospitalization.

Transplantation 2005 Feb;79(3):337-43

Nephrology Section, Research Unit, Hospital Universitario de Canarias, Instituto Reina Sofía de Investigación, La Laguna, Tenerife, Spain.

Background: Prognostic indices that estimate long-term mortality are essential not only to compare different clinical studies and populations but also to perform the most appropriate therapeutic interventions. All-cause mortality is high after renal transplantation (RTx), but no prognostic index has focused on predicting mortality in RTx. We developed and tested a prognostic index for mortality in RTx after hospitalization.

Methods: We retrospectively analyzed survival in 1,293 RTx recipients who were randomly assigned to two groups: a modeling population (n=646), used to create the new index, and a testing population (n=647), used to test this index. Patients were stratified into three risk groups (low, medium, and high) by combining peritransplant risk factors for mortality (beta-coefficient), using a simple eight-point check list: age, pretransplant cardiovascular disease, renal dysfunction at discharge, cardiac hypertrophy, vascular calcification, diabetes, time on dialysis, and acute tubular necrosis.

Results: Overall lower survival rates were observed with increasing risk classes in the testing population (log-rank test=18; P=0.0001). The 8-year survival rates ranged from 94% in the lowest-risk group to 59% in the highest-risk group. The area under the receiver operating characteristic curve was 0.63. Mortality risk (Cox analysis) significantly increased with increasing risk classes (medium risk: relative risk=3.8, 95% confidence interval=1.5-9.5, P=0.004; high risk: relative risk=6.3, 95% confidence interval=2.4-16.2, P=0.0001).

Conclusions: This simple prognostic index applicable at the bedside may accurately predict survival in RTx recipients after discharge. Consequently, targeted treatment interventions may be indicated for minimizing mortality, especially in high-risk groups.
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http://dx.doi.org/10.1097/01.tp.0000151003.30089.31DOI Listing
February 2005

Predialysis nephrologic care and a functioning arteriovenous fistula at entry are associated with better survival in incident hemodialysis patients: an observational cohort study.

Am J Kidney Dis 2004 Jun;43(6):999-1007

Nephrology Section, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.

Background: Late nephrologist referral may adversely affect outcome in patients initiating maintenance hemodialysis therapy, mostly with temporary catheters that may further increase morbidity and mortality. Our aim was to evaluate the influence of 2 variables on mortality: presentation mode (planned versus unplanned) and type of access (arteriovenous fistula [AVF] versus temporary catheter) at entry.

Methods: This was a 3-center, 5-year, prospective, observational, cohort study of 538 incident patients. Measurements included presentation mode, type of access, renal function and biochemical test results at entry, and stratification of risk groups. Main outcome measures were mortality and hospitalization.

Results: Of 281 planned patients (52%), 73% initiated therapy with an AVF. Of 257 unplanned patients (48%), 70% initiated therapy with a catheter (P < 0.001). Multivariate Cox analysis showed that unplanned presentation (hazard ratio [HR], 1.73; 95% confidence interval [CI], 1.23 to 2.44) and initiation of therapy with catheter (HR, 1.75; 95% CI, 1.25 to 2.46) were independently associated with greater mortality and similar HRs after adjusting for confounders. At 12 months, the number of deaths was 3 times higher in both the unplanned versus planned groups and catheter versus AVF groups. The joint effect of unplanned dialysis initiation and catheter use had an additive impact on mortality (HR, 2.89; 95% CI, 1.97 to 4.22). Greater hematocrit (HR, 1.04; 95% CI, 1.01 to 1.09) and albumin level (HR, 1.79; 95% CI, 1.37 to 2.33) showed an independent association with survival, underscoring the benefits of predialysis care. Using Poisson regression, all-cause hospitalization (incidence rate ratio, 1.56; 95% CI, 1.36 to 1.79; P < 0.001) and infection-related (incidence rate ratio, 2.62; 95% CI, 1.91 to 3.59; P < 0.001) and vascular access-related (incidence rate ratio, 1.49; 95% CI, 1.15 to 1.94; P < 0.003) admissions were higher in unplanned patients initiating therapy with a catheter than in planned patients initiating therapy with an AVF, after adjusting for confounders.

Conclusion: Unplanned dialysis initiation and temporary catheter were independently associated with greater mortality rates in incident patients. The combined influence of both variables was associated with greater morbidity and mortality than either variable alone.
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http://dx.doi.org/10.1053/j.ajkd.2004.02.012DOI Listing
June 2004

Heart valve calcification and calcium x phosphorus product in hemodialysis patients: analysis of optimum values for its prevention.

Kidney Int Suppl 2003 Jun(85):S115-8

Nephrology Section, University Hospital of Canary Islands, Santa Cruz de Tenerife, Spain.

Background: Prevalence of valve calcification (VC) in end-stage renal disease (ESRD) patients is high and information regarding modifiable predictors is scarce. Our aim was to determine the prevalence of VC in our maintenance hemodialysis (HD) population, and the optimal Ca x P value that most accurately predicted the presence of VC after controlling for comorbidities.

Methods: This was a cross-sectional observational study of a cohort of 52 stable patients on maintenance HD for more than 12 months. Mean 12 months serum biochemical data (calcium, phosphorus, PTH, lipids) and M-mode 2D echocardiogram were used to evaluate the presence or absence of mitral and aortic VC and ventricular geometry.

Results: Twenty patients (38.4%) presented with VC. Patients with VC were more commonly diabetic and showed higher levels of serum phosphorus, Ca x P product, total and LDL cholesterol, and poor ventricular geometry, as compared to patients without VC. Moreover, they required higher doses of both CaCO3 and Al(OH)3. Logistic regression analysis showed that VC was independently influenced by age, Ca x P, and diabetes. ROC curves illustrated that a Ca x P>43 mg2/dL2 was the optimal value in terms of sensitivity and specificity for predicting the presence of VC in our patient population.

Conclusion: These findings highlight the importance of applying more vigorous measures for Ca x P control.
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http://dx.doi.org/10.1046/j.1523-1755.63.s85.27.xDOI Listing
June 2003

High prevalence of overweight in a stable Spanish hemodialysis population: a cross sectional study.

J Ren Nutr 2003 Jan;13(1):52-9

Nephrology Section, University Hospital of Canary Islands, Santa Cruz de Tenerife, Canary Islands, Spain.

Objective: In the general population, the prevalence of overweight is high and is considered a mortality risk factor. In maintenance hemodialysis (MHD) patients reports regarding overweight and its predictors are scarce. Our aim was to evaluate the prevalence and predictors of overweight in MHD patients, supplemented with additional follow-up data on mortality.

Methods: Retrospective, observational, cross-sectional study of 190 white, noncomplicated patients on MHD recruited from 5 Spanish dialysis centers. Three anthropometric indexes were scored (relative body weight, skinfold thickness, and midarm muscle circumference), and body mass index (BMI) and dietary intake during a 5-day period were recorded. Patient survival was evaluated during a mean follow-up period of 25 +/- 20 months.

Results: Undernutrition (score < 7) was detected in only 15% of patients, and no patient had severe malnutrition (score < 4). The percentage of patients scored below 7, was similar in nondiabetics and type 2 diabetic patients, whereas it was significantly higher in type 1 diabetics (P =.002). Notably, 38% of patients (38% of nondiabetics, 50% of type 2 diabetics, and none of the type 1 diabetics) were overweight (BMI > or = 25 kg/m(2)). To evaluate the predictors of overweight, a stepwise logistic regression analysis was performed entering age, sex, time on dialysis, caloric intake normalized for ideal energy requirements, and protein intake. Overweight was independently influenced only by ageing (odds ratio [OR], 1.04; confidence interval [CI], 1.02-1.07; P =.0007) and female gender (OR, 2.05; CI, 1.09-3.86; P <.0001). By Cox proportional multivariate analysis, survival was positively influenced by BMI (RR, 0.88, CI, 0.79-0.97; P <.01). As expected, albumin also had a positive influence whereas age and diabetes had a negative influence on survival. This preliminary result suggests that a higher BMI may exert a protective role on survival.

Conclusion: Overweight represents the predominant nutritional abnormality in our MHD population, especially in the elderly, women, and type 2 diabetics.
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http://dx.doi.org/10.1053/jren.2003.50004DOI Listing
January 2003

Dietary fish oil does not influence acute rejection rate and graft survival after renal transplantation: a randomized placebo-controlled study.

Nephrol Dial Transplant 2002 May;17(5):897-904

Nephrology Section, Research Unit, University Hospital of the Canary Islands, La Laguna, Tenerife, Spain.

Background: Dietary fish oil, rich in omega-3 polyunsaturated fatty acids, decreases TNF-alpha, IL-1beta and IL-2 levels, which may benefit renal transplant recipients. To explore this possibility, we studied the effect of fish oil on the incidence of acute rejection, in situ expression of interleukins (TNF-alpha, IL-1beta and IL-2) and renal function after renal transplantation.

Methods: In a double-blind clinical trial, 86 subjects with no immunological risk randomly received either 6 g/day of fish oil (fish oil group; n=46) or soy oil (control group; n=40) during the first 3 months after transplantation. The mRNA expression of interleukins (TNF-alpha, IL-1beta and IL-2) was determined by RT-PCR using fine-needle aspiration during follow-up (at baseline and the 1st, 2nd and 3rd month after renal transplantation), as well as during acute rejection episodes and after anti-rejection therapy. The glomerular filtration rate was determined at baseline, and at 1 and 3 months post-graft by [(51)Cr]EDTA clearances.

Results: The incidence of acute rejection during the first post-transplant year was similar in both groups (44 vs. 47%), as was 1-year graft survival (86 vs. 89%). There were no differences between groups in overall renal expression of interleukins in patients who did not suffer rejections during the study. At rejection episodes, the fish oil group showed a trend toward a lower renal expression of TNF-alpha (3.7+/-6.8 vs. 15+/-18.6 TNF-alpha/actin, ratio of arbitrary optical units; P=0.05). In addition, a trend toward a lower IL-1beta expression after therapy was observed in the fish oil group (49.3+/-54 vs. 84.4+/-59 IL-1beta/actin, ratio of arbitrary optical units; P=0.05). However, the severity of acute rejections (Banff criteria) as well as renal function after anti-rejection treatment were similar in both groups. Finally, a greater reduction in triglyceride levels was observed in the fish oil group compared with the control group (-6.6+/-52.7 vs. 12.7+/-40.2%; P<0.05).

Conclusions: Treatment with fish oil during the first 3 months post-transplantation does not influence acute rejection rate and has no beneficial effect on renal function or graft survival.
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http://dx.doi.org/10.1093/ndt/17.5.897DOI Listing
May 2002
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