L M Pallardó

Hospital Universitario Doctor Peset, Valenza, Valencia, Spain

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Publications (104)175.35 Total impact

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    ABSTRACT: Current therapy directed at delaying the progression of diabetic nephropathy includes intensive glycemic and optimal blood pressure control, renin angiotensin-aldosterone system blockade and multifactorial intervention. However, the renal protection provided by these therapeutic modalities is incomplete. There is a scarcity of studies analysing the nephroprotective effect of antihyperglycaemic drugs beyond their glucose lowering effect and improved glycaemic control on the prevention and progression of diabetic nephropathy. This article analyzes the exisiting data about older and newer drugs as well as the mechanisms associated with hypoglycemic drugs, apart from their well known blood glucose lowering effect, in the prevention and progression of diabetic nephropathy. Most of them have been tested in humans, but with varying degrees of success. Although experimental data about most of antihyperglycemic drugs has shown a beneficial effect in kidney parameters, there is a lack of clinical trials that clearly prove these beneficial effects. The key question, however, is whether antihyperglycemic drugs are able to improve renal end-points beyond their antihyperglycemic effect. Existing experimental data are post hoc studies from clinical trials, and supportive of the potential renal-protective role of some of them, especially in the cases of dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. Dedicated and adequately powered renal trials with renal outcomes are neccessary to assess the nephrotection of antihyperglycaemic drugs beyond the control of hyperglycaemia.
    Full-text · Article · Oct 2015 · Journal of Clinical Medicine

  • No preview · Conference Paper · May 2015
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    ABSTRACT: This study evaluated health-related quality of life (HRQOL) in a Spanish sample of chronic kidney disease patients (n = 90) undergoing different renal replacement therapies, considering the influence of treatment stressors, mood, anxiety and quality of sleep. While all patients had worse physical functioning than controls (p < .01), only those undergoing haemodialysis (HD) showed worse physical well-being, occupational functioning, spiritual fulfillment and more health interference with work (p < .05). They also obtained higher depression scores than renal transplant patients (TX) (p = .005). Those TX receiving the immunosuppressor sirolimus exhibited more cardiac/renal, cognitive and physical limitations than the rest (p < .05). Dialysis vintage correlated positively with sleep disturbances and depression scores and negatively with total Quality of Life (QLI) (p < .05). HD patients experienced more psychological distress than peritoneal dialysis patients (PD) (p = .036). Regression models including sleep, anxiety and depression were estimated for subscales of HRQOL. In TX patients, low depressive scores related to an optimal QLI in almost all subscales, while in HD patients they explained part of the variability in psychological well-being, interpersonal functioning and personal fulfillment. HD condition results in a QLI more distant to the standards of controls.
    No preview · Article · Apr 2015
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    ABSTRACT: Atypical haemolytic uraemic syndrome (aHUS) is a rare disease characterized by haemolytic microangiopathic anaemia, thrombocytopaenia and acute onset of renal failure, in the absence of Escherichia coli infection. Renal damage usually progresses to end-stage renal disease (ESRD), sometimes being accompanied by signs of extrarenal thrombotic microangiopathy (TMA). We report a case of full neurological and haematological recovery after eculizumab treatment in a patient with ESRD secondary to chronic aHUS refractory to plasmatherapy while she was under dialysis. It highlights the use of eculizumab for controlling extrarenal manifestations of aHUS in this population.
    Preview · Article · Apr 2015 · CKJ: Clinical Kidney Journal
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    ABSTRACT: Vascular calcification (VC) is common in CKD, but little is known about its prognostic effect on patients with nondialysis CKD. The prevalence of VC and its ability to predict death, time to hospitalization, and renal progression were assessed. The Study of Mineral and Bone Disorders in CKD in Spain is a prospective, observational, 3-year follow-up study of 742 patients with nondialysis CKD stages 3-5 from 39 centers in Spain from April to May 2009. VC was assessed using Adragao (AS; x-ray pelvis and hands) and Kauppila (KS; x-ray lateral lumbar spine) scores from 572 and 568 patients, respectively. The primary end point was death. Secondary outcomes were hospital admissions and appearance of a combined renal end point (beginning of dialysis or drop >30% in eGFR). Factors related to VC were assessed by logistic regression analysis. Survival analysis was assessed by Cox proportional models. VC was present in 79% of patients and prominent in 47% (AS≥3 or KS>6). Age (odds ratio [OR], 1.05; 95% confidence interval [95% CI], 1.02 to 1.07; P<0.001), phosphorous (OR, 1.68; 95% CI, 1.28 to 2.20; P<0.001), and diabetes (OR, 2.11; 95% CI, 1.32 to 3.35; P=0.002) were independently related to AS≥3. After a median follow-up of 35 months (interquartile range=17-36), there were 70 deaths (10%). After multivariate adjustment for age, smoking, diabetes, comorbidity, renal function, and level of phosphorous, AS≥3 but not KS>6 was independently associated with all-cause (hazard ratio [HR], 2.07; 95% CI, 1.07 to 4.01; P=0.03) and cardiovascular (HR, 3.46; 95% CI, 1.27 to 9.45; P=0.02) mortality as well as a shorter hospitalization event-free period (HR, 1.14; 95% CI, 1.06 to 1.22; P<0.001). VC did not predict renal progression. VC is highly prevalent in patients with CKD. VC assessment using AS independently predicts death and time to hospitalization. Therefore, it could be a useful index to identify patients with CKD at high risk of death and morbidity as previously reported in patients on dialysis. Copyright © 2015 by the American Society of Nephrology.
    Full-text · Article · Mar 2015 · Clinical Journal of the American Society of Nephrology
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    ABSTRACT: Introduction Nonmelanoma skin cancer (NMSC) is the most common malignancy in patients who have received a solid organ transplant. Multiple factors are involved in the onset of posttransplant NMSC. Objectives To analyze the relationship between new immunosuppressive drugs and the onset of NMSC in renal transplant recipients. Method This was a combined retrospective and prospective observational study in which we studied 289 patients who received a kidney transplant between January 1996 and December 2010 at Hospital Universitario Doctor Peset in Valencia, Spain. Results Seventy-three patients (25.2%) developed 162 NMSCs over a median follow-up of 72 months. There were no statistically significant differences in the onset of NMSC on comparing different induction therapy strategies involving monoclonal and polyclonal antibodies. NMSCs occurred less frequently in patients treated with mammalian target of rapamycin (mTOR) inhibitors than in those treated with other immunosuppressive regimens, although the differences were not statistically significant. Three of 5 patients with recurrent NMSC who were switched from calcineurin inhibitors to mTOR inhibitors developed additional NMSCs despite the change. Conclusions Induction therapy with monoclonal and polyclonal antibodies in renal transplant recipients is not associated with an increased risk of NMSC. While mTOR inhibitors are associated with a lower risk of posttransplant NMSC, it remains to be determined whether a switch to these drugs is useful in the management of patients who develop multiple NMSCs.
    No preview · Article · Dec 2014 · Actas Dermo-Sifiliográficas
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    ABSTRACT: Introduction: Nonmelanoma skin cancer (NMSC) is the most common malignancy in patients who have received a solid organ transplant. Multiple factors are involved in the onset of posttransplant NMSC. Objectives: To analyze the relationship between new immunosuppressive drugs and the onset of NMSC in renal transplant recipients. Method: This was a combined retrospective and prospective observational study in which we studied 289 patients who received a kidney transplant between January 1996 and December 2010 at Hospital Universitario Doctor Peset in Valencia, Spain. Results: Seventy-three patients (25.2%) developed 162 NMSCs over a median follow-up of 72 months. There were no statistically significant differences in the onset of NMSC on comparing different induction therapy strategies involving monoclonal and polyclonal antibodies. NMSCs occurred less frequently in patients treated with mammalian target of rapamycin (mTOR) inhibitors than in those treated with other immunosuppressive regimens, although the differences were not statistically significant. Three of 5 patients with recurrent NMSC who were switched from calcineurin inhibitors to mTOR inhibitors developed additional NMSCs despite the change. Conclusions: Induction therapy with monoclonal and polyclonal antibodies in renal transplant recipients is not associated with an increased risk of NMSC. While mTOR inhibitors are associated with a lower risk of posttransplant NMSC, it remains to be determined whether a switch to these drugs is useful in the management of patients who develop multiple NMSCs.
    No preview · Article · Jul 2014 · Actas Dermo-Sifiliográficas
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    ABSTRACT: Growing evidence indicates that vitamin D receptor activation may have antiproteinuric effects. We aimed to evaluate whether vitamin D supplementation with daily cholecalciferol could reduce albuminuria in proteinuric chronic kidney disease (CKD) patients. This 6-month prospective, controlled, intervention study enrolled 101 non-dialysis CKD patients with albuminuria. Patients with low 25(OH) vitamin D [25(OH)D] and high parathyroid hormone (PTH) levels (n = 50; 49%) received oral cholecalciferol (666 IU/day), whereas those without hyperparathyroidism (n = 51; 51%), independent of their vitamin D status, did not receive any cholecalciferol, and were considered as the control group. Cholecalciferol administration led to a rise in mean 25(OH)D levels by 53.0 ± 41.6% (P < 0.001). Urinary albumin-to-creatinine ratio (uACR) decreased from (geometric mean with 95% confidence interval) 284 (189-425) to 167 mg/g (105-266) at 6 months (P < 0.001) in the cholecalciferol group, and there was no change in the control group. Reduction in a uACR was observed in the absence of significant changes in other factors, which could affect proteinuria, like weight, blood pressure (BP) levels or antihypertensive treatment. Six-month changes in 25(OH)D levels were significantly and inversely associated with that in the uACR (Pearson's R = -0.519; P = 0.036), after adjustment by age, sex, body mass index, BP, glomerular filtration rate and antiproteinuric treatment. The mean PTH decreased by -13.8 ± 20.3% (P = 0.039) only in treated patients, with a mild rise in phosphate and calcium-phosphate product [7.0 ± 14.7% (P = 0.002) and 7.2 ± 15.2% (P = 0.003), respectively]. In addition to improving hyperparathyroidism, vitamin D supplementation with daily cholecalciferol had a beneficial effect in decreasing albuminuria with potential effects on delaying the progression of CKD.
    Full-text · Article · Aug 2013 · Nephrology Dialysis Transplantation
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    ABSTRACT: Delayed graft function (DGF) is a common complication after transplantation. Its incidence is increased among patients receiving a graft from an expanded-criteria donor. Urinary neutrophil gelatinase-associated lipocalin (uNGAL), an acute kidney injury marker, could in the first days after transplantation be an early marker of DGF. We collected urine samples from 38 renal transplant recipients on days 1, 3, 6, and 10 post-transplantation, and months 1 and 6 creatinine to determine uNGAL, serum creatinine, Cystatin C, and albumin/creatinine ratio. We divided the patients into 2 groups, based on whether they developed DGF. We observed that mean uNGAL concentrations, Cystatin C, serum creatinine, and albumin/creatinine ratio were significantly lower in the non-DGF cohort on all measured days. uNGAL at day 3 showed a positive correlation with serum creatinine at day 10 (R = 0.58; P < .00) and day 30 (R = 0.57; P = .016) as well as with the length of hospital stay (r = 0.47; P < .00). Receiver operating characteristic analyses performed to assess the potential of uNGAL to predict DGF showed an area under the curve for day 3 of uNGAL of 0.917 (confidence interval [CI], 0.79-1.00; P = .00), with an optimal cutoff level of 124 ng/mL, sensitivity of 80% (CI, 62%-97%), and specificity of 83% (62%-104%; P = .001). In the first days after transplantation, uNGAL could be an early marker of DGF, providing additional information to standard biomarkers and potentially helping clinicians to take early measures to mitigate DGF.
    No preview · Article · May 2013 · Transplantation Proceedings

  • No preview · Article · Jan 2013 · Transplantation
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    ABSTRACT: Non-melanoma skin cancer (NMSC) is the most frequent malignancy in organ transplant recipients. The aetiology of NMSC after transplant is multifactorial. The aim of this study was to determine the clinical and environmen-tal factors involved in the development of NMSC in a Spanish kidney transplant population from the Mediterranean region. A total of 289 patients who had received a kidney transplant during the period January 1996 to December 2010 were included in the study. Both prospective and retrospective data were used. All patients underwent a structured interview and a complete examination of the skin. After a median follow-up of 72 months (range 12-180 months), 73 of the 289 patients (25.2%) developed 162 tumours. The ratio of basal cell carcinoma to squamous cell carcinoma was 2.21:1. The cumulative incidence of NMSC increased with the duration of immunosuppression, from 20.78% at 5 years, to 37.35% at 10 years to 53.08% at 15 years after transplantation. Age at the time of transplant, phototype and occupational sun exposure were associated with a higher risk of NMSC. NMSC is a significant clinical problem in kidney transplant recipients. This has implications for the development of prevention and surveillance strategies. Clinical and environmental factors may be used to identify those patients who are at risk for NMSC.
    Preview · Article · Jan 2013 · Acta Dermato-Venereologica
  • Article: Response.
    J Kanter · A Sancho · E Gavela · L M Pallardo · C Fernandez

    No preview · Article · Jan 2013 · Transplantation Proceedings
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    ABSTRACT: Background To describe the causes of graft loss, patient death and survival figures in kidney transplant patients in Spain based on the recipient's age. Methods The results at 5 years of post-transplant cardiovascular disease (CVD) patients, taken from a database on CVD, were prospectively analysed, i.e. a total of 2600 transplanted patients during 2000–2002 in 14 Spanish renal transplant units, most of them receiving their organ from cadaver donors. Patients were grouped according to the recipient's age: Group A: <40 years, Group B: 40–60 years and Group C: >60 years. The most frequent immunosuppressive regimen included tacrolimus, mycophenolate mofetil and steroids. Results Patients were distributed as follows: 25.85% in Group A (>40 years), 50.9% in Group B (40–60 years) and 23.19% in Group C (>60). The 5-year survival for the different age groups was 97.4, 90.8 and 77.7%, respectively. Death-censored graft survival was 88, 84.2 and 79.1%, respectively, and non death-censored graft survival was 82.1, 80.3 and 64.7%, respectively. Across all age groups, CVD and infections were the most frequent cause of death. The main causes of graft loss were chronic allograft dysfunction in patients <40 years old and death with functioning graft in the two remaining groups. In the multivariate analysis for graft survival, only elevated creatinine levels and proteinuria >1 g at 6 months post-transplantation were statistically significant in the three age groups. The patient survival multivariate analysis did not achieve a statistically significant common factor in the three age groups. Conclusions Five-year results show an excellent recipient survival and graft survival, especially in the youngest age group. Death with functioning graft is the leading cause of graft loss in patients >40 years. Early improvement of renal function and proteinuria together with strict control of cardiovascular risk factors are mandatory.
    No preview · Article · Dec 2012 · Nephrology Dialysis Transplantation

  • No preview · Article · Nov 2012 · Transplantation

  • No preview · Article · Nov 2012 · Transplantation
  • C P Fernandez · T Ripolles · M J Martinez · J Blay · L Pallardó · E Gavela
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    ABSTRACT: Purpose: To evaluate the use of contrast-enhanced ultrasound (CEUS) for diagnosis of cortical necrosis in renal allografts. Materials and methods: We reviewed the medical records and imaging studies of five patients who underwent emergency transplantectomy and a histological diagnosis of cortical necrosis in the period between May 2009 and May 2011. US examinations included initially B-mode and color Doppler and then contrast-enhanced ultrasound with low mechanical index after injection of 2.4 ml of a second generation echo-signal enhancer. Renal transplant vascularization was evaluated during a period of 4 minutes including arterial, corticomedullary and nephrographic phases. Radiologic-pathologic correlation was obtained after transplantectomy in all cases. Results: Five patients with an age range between 30 and 48 years. Post-transplant color Doppler ultrasound showed decreased renal parenchymal vascularization and difficulty to find the spectral waveforms with resistive indexes greater than 0.7 in 4 of 5 patients. CEUS showed enhancement of the main arteries, followed by the enhancement of medullary pyramids, but with an unenhanced peripheral cortical continuous band viewed in all phases, a similar finding to the peripheral rim sign, pathognomonic of cortical necrosis on CT or MRI. The pathologic assessment showed violet kidneys macroscopically with hemorrhagic foci in the outer cortical that drew a well-defined band, findings agreed with CEUS findings. Conclusion: CEUS can show the typical peripheral rim sign in cases of cortical necrosis allowing a reliable and fast diagnosis of this condition and it could obviate further imaging studies or biopsy, allowing an earlier decision of nephrectomy.
    No preview · Article · Aug 2012 · Ultraschall in der Medizin
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    ABSTRACT: The development of new immunosuppressants for renal transplantation is aimed not only at improving short-term outcomes, but also at achieving better safety, cardiovascular, and metabolic profiles and at decreasing nephrotoxicity. Belatacept is a fusion protein that inhibits T cell activation by binding to CD80 and CD86 antigens. Clinical trials, particularly the BENEFIT and BENEFIT-EXT studies, have shown that belatacept preserves function and structure in renal grafts. The effects of belatacept provide long-term, sustained results, and the safety and efficacy of this drug have been demonstrated in cases of renal transplantation from expanded criteria donors. Compared to calcineurin inhibitors, belatacept is associated with a lower incidence of chronic allograft nephropathy and a more favourable cardiovascular and metabolic profile.
    No preview · Article · Apr 2012 · Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia
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    ABSTRACT: The development of new immunosuppressants for renal transplantation is aimed not only at improving short-term outcomes, but also at achieving better safety, cardiovascular, and metabolic profiles and at decreasing nephrotoxicity. Belatacept is a fusion protein that inhibits T cell activation by binding to CD80 and CD86 antigens. Clinical trials, particularly the BENEFIT and BENEFIT-EXT studies, have shown that belatacept preserves function and structure in renal grafts. The effects of belatacept provide long-term, sustained results, and the safety and efficacy of this drug have been demonstrated in cases of renal transplantation from expanded criteria donors. Compared to calcineurin inhibitors, belatacept is associated with a lower incidence of chronic allograft nephropathy and a more favourable cardiovascular and metabolic profile.
    No preview · Article · Dec 2011 · Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia
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    Full-text · Chapter · Nov 2011
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    ABSTRACT: Some renal transplant patients show cognitive, emotional, and behavioral changes as part of possible neurotoxic effects associated with immunosuppressive medication, especially tacrolimus. This study evaluated effects of immunosuppressive drugs on some cognitive tasks. Patients treated with sirolimus and cyclosporine reported some of the noncognitive side effects related to immunosuppressive treatment. We observed attention and working memory impairment in patients treated with sirolimus or tacrolimus. Performance of cyclosporine-treated subjects was similar to that of healthy volunteer controls. Since the mood, anxiety, and sleep patterns measured were unaffected, it could be concluded that the cognitive deficit found was partly related to treatment.
    No preview · Article · Nov 2011 · Journal of Clinical and Experimental Neuropsychology

Publication Stats

847 Citations
175.35 Total Impact Points

Institutions

  • 1998-2015
    • Hospital Universitario Doctor Peset
      • • Nephrology Department
      • • Servicio de Nefrología
      Valenza, Valencia, Spain
  • 2009
    • Hospital 12 de Octubre
      Madrid, Madrid, Spain
  • 2008
    • Hospital Universitario Dr. Ángel Larralde
      Valencia, Carabobo, Venezuela
  • 2007
    • Novartis
      Bâle, Basel-City, Switzerland
  • 2002
    • Hospital General Universitario Gregorio Marañón
      Madrid, Madrid, Spain
  • 1988-1995
    • Hospital Universitari i Politècnic la Fe
      • Servicio de Nefrología
      Valenza, Valencia, Spain