R García-Maset

Fundació Puigvert, Barcino, Catalonia, Spain

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Publications (11)27.75 Total impact

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    ABSTRACT: The increasing number of podocyte-expressed genes implicated in steroid-resistant nephrotic syndrome (SRNS), the phenotypic variability, and the uncharacterized relative frequency of mutations in these genes in pediatric and adult patients with SRNS complicate their routine genetic analysis. Our aim was to compile the clinical and genetic data of eight podocyte genes analyzed in 110 cases (125 patients) with SRNS (ranging from congenital to adult onset) to provide a genetic testing approach. Mutation analysis was performed by sequencing the NPHS1, NPHS2, TRPC6, CD2AP, PLCE1, INF2, WT1 (exons 8 and 9), and ACTN4 (exons 1 to 10) genes. We identified causing mutations in 34% (37/110) of SRNS patients, representing 67% (16/24) familial and 25% (21/86) sporadic cases. Mutations were detected in 100% of congenital-onset, 57% of infantile-onset, 24 and 36% of early and late childhood-onset, 25% of adolescent-onset, and 14% of adult-onset patients. The most frequently mutated gene was NPHS1 in congenital onset and NPHS2 in the other groups. A partial remission was observed in 7 of 26 mutation carriers treated with immunosuppressive agents and/or angiotensin-converting enzyme inhibitors. Patients with NPHS1 mutations showed a faster progression to ESRD than patients with NPHS2 mutations. None of these mutation carriers relapsed after kidney transplantation. We propose a genetic testing algorithm for SRNS based on the age at onset and the familial/sporadic status. Mutation analysis of specific podocyte-genes has a clinical value in all age groups, especially in children.
    Clinical Journal of the American Society of Nephrology 03/2011; 6(5):1139-48. · 5.07 Impact Factor
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    ABSTRACT: To date, very few cases with adult-onset focal segmental glomerulosclerosis (FSGS) carrying NPHS2 variants have been described, all of them being compound heterozygous for the p.R229Q variant and one pathogenic mutation. Mutation analysis was performed in 148 unrelated Spanish patients, of whom 50 presented with FSGS after 18 years of age. Pathogenicity of amino acid substitutions was evaluated through an in silico scoring system. Haplotype analysis was carried out using NPHS2 single nucleotide polymorphism and microsatellite markers. Compound heterozygous or homozygous NPHS2 pathogenic mutations were identified in seven childhood-onset steroid-resistant nephrotic syndrome (SRNS) cases. Six additional cases with late childhood- and adult-onset SRNS were compound heterozygotes for p.R229Q and one pathogenic mutation, mostly p.A284V. p.R229Q was more frequent among SRNS cases relative to controls (odds ratio=2.65; P=0.02). Significantly higher age at onset of the disease and slower progression to ESRD were found in patients with one pathogenic mutation plus the p.R229Q variant in respect to patients with two NPHS2 pathogenic mutations. NPHS2 analysis has a clinical value in both childhood- and adult-onset SRNS patients. For adult-onset patients, the first step should be screening for p.R229Q and, if positive, for p.A284V. These alleles are present in conserved haplotypes, suggesting a common origin for these substitutions. Patients carrying this specific NPHS2 allele combination did not respond to corticoids or immunosuppressors and showed FSGS, average 8-year progression to ESRD, and low risk for recurrence of FSGS after kidney transplant.
    Clinical Journal of the American Society of Nephrology 02/2011; 6(2):344-54. · 5.07 Impact Factor
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    ABSTRACT: Mutations in the NPHS1 gene cause congenital nephrotic syndrome of the Finnish type presenting before the first 3 months of life. Recently, NPHS1 mutations have also been identified in childhood-onset steroid-resistant nephrotic syndrome and milder courses of disease, but their role in adults with focal segmental glomerulosclerosis remains unknown. Here we developed an in silico scoring matrix to evaluate the pathogenicity of amino-acid substitutions using the biophysical and biochemical difference between wild-type and mutant amino acid, the evolutionary conservation of the amino-acid residue in orthologs, and defined domains, with the addition of contextual information. Mutation analysis was performed in 97 patients from 89 unrelated families, of which 52 presented with steroid-resistant nephrotic syndrome after 18 years of age. Compound heterozygous or homozygous NPHS1 mutations were identified in five familial and seven sporadic cases, including one patient 27 years old at onset of the disease. Substitutions were classified as 'severe' or 'mild' using this in silico approach. Our results suggest an earlier onset of the disease in patients with two 'severe' mutations compared to patients with at least one 'mild' mutation. The finding of mutations in a patient with adult-onset focal segmental glomerulosclerosis indicates that NPHS1 analysis could be considered in patients with later onset of the disease.
    Kidney International 10/2009; 76(12):1268-76. · 8.52 Impact Factor
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    ABSTRACT: Mutations in the TRPC6 gene have been reported in six families with adult-onset (17-57 years) autosomal dominant focal segmental glomerulosclerosis (FSGS). Electrophysiology studies confirmed augmented calcium influx only in three of these six TRPC6 mutations. To date, the role of TRPC6 in childhood and adulthood non-familial forms is unknown. TRPC6 mutation analysis was performed by direct sequencing in 130 Spanish patients from 115 unrelated families with FSGS. An in silico scoring matrix was developed to evaluate the pathogenicity of amino acid substitutions, by using the bio-physical and bio-chemical differences between wild-type and mutant amino acid, the evolutionary conservation of the amino acid residue in orthologues, homologues and defined domains, with the addition of contextual information. Three new missense substitutions were identified in two clinically non-familial cases and in one familial case. The analysis by means of this scoring system allowed us to classify these variants as likely pathogenic mutations. One of them was detected in a female patient with unusual clinical features: mesangial proliferative FSGS in childhood (7 years) and partial response to immunosupressive therapy (CsA + MMF). Asymptomatic carriers of this likely mutation were found within her family. We describe for the first time TRPC6 mutations in children and adults with non-familial FSGS. It seems that TRPC6 is a gene with a very variable penetrance that may contribute to glomerular diseases in a multi-hit setting.
    Nephrology Dialysis Transplantation 06/2009; 24(10):3089-96. · 3.37 Impact Factor
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    ABSTRACT: According to literature, patient and graft survival is better in living donor renal transplants (LRT) than in cadaver renal transplants (CRT). Objective: To study factors that determine the best results in LRT related to those of CRT, found in univariate studies. Renal transplants (RT) done in Catalonia during the 1990-2004 period, performed in patients over 17 years (135 LRT and 3.831 CRT), have been analyzed (retransplants were not included). The data come from the Renal Patients Transplant Registry (RMRC). Student's t-test and chi2 test have been used for mean and for proportions comparisons, respectively. To analyze univariate and multivariate survival, actuarial method and Cox regression have been used, respectively. Estimated creatinine clearance has been studied and its data have been showed through Selwood modified Analysis. As it happens with other great RT patients series, the RMRC analysis, globally and without any adjustment, shows that patient and graft survival in LRT is better than that obtained with CRT. When we studied which variables explain these results, we found that main factors were smaller recipient age and the short time on dialysis. The great influence of both factors has been published in a large number of papers, explaining the differences obtained on the transplanted renal patient survival. Once adjusted the analysis by the different factors that influence the survival of the patient and the graft, there are no differences in the obtained results, since the best outcomes of the TRV are due to factors like the smaller recipient age and the advanced TR.
    Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 02/2008; 28(2):159-67. · 1.27 Impact Factor
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    ABSTRACT: Prophylactic and pre-emptive therapy with oral valganciclovir for cytomegalovirus infection in renal transplant recipients. Background: Cytomegalovirus infection is a very important health problem in solid organ transplant recipients (SOT). Once-daily valganciclovir has been shown to be as clinically effective and well tolerated as oral ganciclovir tid in the prevention of CMV infection in high risk SOT recipients. The aim of the present study was to evaluate the incidence and severity of CMV disease in 150 renal transplant recipients that received either prophylactic [high risk group (HR), N = 66] or pre-emptive [low risk group (LR), N = 84] therapy with oral valganciclovir (900 mg/day vo) for three months according to their basal risk. Patients were monitored for signs and symptoms of CMV disease and CMV plasma viral load was assessed weekly. A total of 31 patients (47%) of the HR and 26 patients (31%) of the LR presented a positive CMV PCR result. Twelve patients (14.3%) in the LR that had a high viral load (CMV PCR > 1,000 copies/mL) but remained asymptomatic received pre-emptive therapy. Four patients (4.7%) in the LR, after an average time of 35 days after transplant and two patients (4.5%) in the HR, after prophylactic treatment was completed, developed CMV disease. The disease was mild-moderate in most of the cases. Those patients that developed CMV disease responded to treatment with iv ganciclovir for 14 days followed by treatment with oral valganciclovir for up to three months. Prophylactic treatment with oral valganciclovir for CMV prevention is only required in high risk solid organ transplant recipients.
    Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 01/2008; 28(3):293-300. · 1.27 Impact Factor
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    ABSTRACT: Background: According to literature, patient and graft survival is better in living donor renal transplants (LRT) than in cadaver renal transplants (CRT). Objective: To study factors that determine the best results in LRT related to those of CRT, found in univariate studies. Patients and Methods: Renal transplants (RT) done in Catalonia during the 1990-2004 period, performed in patients over 17 years (135 LRT and 3.831 CRT), have been analyzed (retrans-plants were not included). The data come from the Renal Pa-tients Transplant Registry (RMRC). Student's t-test and χ 2 test were used to compare means and proportions, respectively. To analyze univariate and multivariate survival, actuarial method and Cox regression have been used, respectively. Estimated crea-tinine clearance has been studied and its data have been sho-wed through Selwood modified Analysis. Results: As it happens with other great RT patients series, the RMRC analysis, globally and without any adjustment, shows that patient and graft survival in LRT is better than that obtained with CRT. When we studied which variables explain these results, we found that main factors were smaller recipient age and the short time on dialysis. The great influence of both factors has been published in a large number of papers, explaining the differen-ces obtained on the transplanted renal patient survival. Conclusions: Once adjusted the analysis by the different factors that influence the survival of the patient and the graft, there are no differences in the obtained results, since the best outcomes of the TRV are due to factors like the smaller recipient age and the advanced TR. RESUMEN Introducción: Según la literatura hay una mejor supervi-vencia del paciente e injerto en los trasplantes renales (TR) realizados con órganos procedentes de donante vivo. Objetivos: Estudiar los factores que determinan los mejo-res resultados en el trasplante de donante vivo (TRV) res-pecto al de donante cadáver (TRC), hallados en estudios univariados. Pacientes y métodos: Se analizan los primeros TR realiza-dos en Cataluña en el período 1990-2004 en mayores de 17 años (135 TRV y 3.831 TRC). Los datos proceden del Regis-tro de enfermos renales de Cataluña (RMRC). Se ha utiliza-do la t-Student para la comparación de medias y el test de la χ 2 para la de proporciones. Para el análisis univariado de la supervivencia se ha utilizado el método actuarial y la re-gresión de Cox para el multivariado. Se ha estudiado la depuración estimada de la creatinina y sus datos se han representado con el análisis de Selwood modificado. Resultados: Al igual que ocurre con las grandes series de trasplantados renales, el RMRC objetiva que, globalmente y sin ningún tipo de ajuste, el TRV presenta mejores resul-tados de supervivencia de paciente e injerto que el TRC. Cuando estudiamos los factores más relevantes para expli-car estos resultados, obtenemos que los más determinan-tes son la menor edad del receptor y el menor tiempo en diálisis. Numerosas publicaciones han demostrado que ambos factores tienen una gran influencia sobre la super-vivencia del paciente trasplantado renal, condicionando la diferencia en las supervivencias obtenidas. Conclusiones: Una vez ajustado el análisis por los diferen-tes factores que intervienen en la supervivencia del pa-ciente y del injerto, no existen diferencias en los resulta-dos obtenidos por los dos tratamientos, ya que los mejores resultados del TRV son debidos a factores como la menor edad del receptor y el TR anticipado. Palabras clave: Trasplante renal de donante vivo. Supervivencia. Comparación de resultados. Registros.
    01/2008;
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    ABSTRACT: To describe the general characteristics of living-donor renal transplantation (LRT) in Catalonia, and to compare results with those of the cadaveric donor renal transplant (CRT). Four hundred seventy-three LRTs have been performed in Catalonia since 1965. Transplantations carried out between 1980 and 2003, according to the RMRC data, were reviewed. The most frequent degrees of kinship are parents-children (48%), spouses (22%), and siblings (18%). Around 68% of the donors were women. Around 56% of recipients were men. The transplant was advanced in approximately 30% of the cases. The mean cold ischemia was 2 hours. Seven percent showed delayed graft function (DGF). Forty-nine percent of the patients had glomerular filtration >60 mL/min after 1 year. Patient survival at 1, 5, 10, and 20 years were 99%, 97%, 93%, and 82% in LRT; and 96%, 90%, 80%, and 62% in CRT (P < .00001). Graft survivals over the same periods were 91%, 76%, 58%, and 32% in LRT, and 85%, 69%, 49%, and 23% in CRT (P = .00008). The graft mean life was 12 years (LRT) and 10 years (CRT). Graft survivals, censoring deaths over the same periods, were 93%, 79%, 62%, and 39% in LRT, and 89%, 77%, 62%, and 37% in CRT (P = .3). Mean life was 14 years in both cases. The recipients mean age was 31 (LRT), and 44 years (CRT), whereas the donor mean age was 51 (LRT), and 42 years (CRT). LRT results were excellent both regarding DGF and patient and graft survivals. They were not comparable to CRT due to the different characteristics of the recipients. LRT is a good solution to reduce waiting lists.
    Transplantation Proceedings 11/2005; 37(9):3682-3. · 0.95 Impact Factor
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    ABSTRACT: A tendency to increased body mass index (BMI) occurs after renal transplantation. The objective of this study was to analyze the causes and consequences of this weight gain. Two hundred twelve renal transplant recipients were divided into 3 groups according to the evolution of their BMI: BMI loss (group 1); BMI increase <10% (group 2); and BMI increase >10% (group 3). The mean BMI gain was 6.2%, weight gain was 3.9 kg, and BMI gain was 1.4 kg/m(2). The patients in group 3 were younger, but there were no other significant differences in gender, preoperative diabetes, acute rejection, or prior BMI. Blood pressure was similar in all 3 groups, but more group 3 patients needed antihypertensive treatment. A progressive increase in total and low-density lipoprotein (LDL)-cholesterol was also observed as patients showed increased BMI. No differences were observed regarding carbohydrate metabolism. Groups 1 and 3 showed a more unfavorable micro-inflammatory profile. The creatinine clearance level was better in group 3 compared with group 1. We found no differences regarding the number of nonfatal postoperative cardiovascular events.
    Transplantation Proceedings 11/2005; 37(9):3839-41. · 0.95 Impact Factor
  • J M Díaz, Ll Guirado, C Facundo, R García-Maset, R Solà
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    ABSTRACT: The goal of the donor evaluation is to ensure the suitability, safety and well being of the donor. In order to avoid important omissions, the evaluation of potential living kidney donors should be carried according to a protocol that includes a logical sequence of complementary explorations. Old age alone is not an absolute contraindication to donation but the evaluation should be more rigorous, because increased age may be associated with more post-operative complications after nephrectomy and renal function and long term graft survival could be shorter than the ones obtained from younger living donors. A body mass index of more than 35 kg/m2 should be an absolute contraindication to renal donation. Between 30 and 35 kg/m2 the donor evaluation should be more rigorous and it should be recommended to lose weight before nephrectomy. Hypertension is one of the most common reasons to declare a potential kidney donor unsuitable. Evidence of organ damage is an absolute contraindication to kidney donation. The donation is only reasonable when hypertension is well controlled with less than two drugs. To excluded diabetes mellitus all donors should have a fasting plasma glucose measurement. Diabetes mellitus is an absolute contraindication to living donation such as an impaired glucose tolerance or impaired fasting glucose with a family history of type 2 diabetes mellitus. Another contraindication to living donation is malignant disease, and the same standards should be adopted for cadaveric donors. The exceptions are low-grade non-melanoma skin cancer and carcinoma in situ of the uterine cervix. The presence of active infection usually precludes donation. It is very important to perform a routine test for viral infections. HIV, hepatitis B and C infection of the donor are usually a contraindication to living donor. CMV donor and recipient status should be taken into account before transplantation, and the recipients at risk for CMV disease should recieve prophylactic treatment according to the transplant unit policy.
    Nefrologia: publicacion oficial de la Sociedad Espanola Nefrologia 02/2005; 25 Suppl 2:51-6. · 1.27 Impact Factor
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    ABSTRACT: RESUMEN Introducción: Según la literatura hay una mejor supervi-vencia del paciente e injerto en los trasplantes renales (TR) realizados con órganos procedentes de donante vivo. Objetivos: Estudiar los factores que determinan los mejo-res resultados en el trasplante de donante vivo (TRV) res-pecto al de donante cadáver (TRC), hallados en estudios univariados. Pacientes y métodos: Se analizan los primeros TR realiza-dos en Cataluña en el período 1990-2004 en mayores de 17 años (135 TRV y 3.831 TRC). Los datos proceden del Regis-tro de enfermos renales de Cataluña (RMRC). Se ha utiliza-do la t-Student para la comparación de medias y el test de la χ 2 para la de proporciones. Para el análisis univariado de la supervivencia se ha utilizado el método actuarial y la re-gresión de Cox para el multivariado. Se ha estudiado la depuración estimada de la creatinina y sus datos se han representado con el análisis de Selwood modificado. Resultados: Al igual que ocurre con las grandes series de trasplantados renales, el RMRC objetiva que, globalmente y sin ningún tipo de ajuste, el TRV presenta mejores resul-tados de supervivencia de paciente e injerto que el TRC. Cuando estudiamos los factores más relevantes para expli-car estos resultados, obtenemos que los más determinan-tes son la menor edad del receptor y el menor tiempo en diálisis. Numerosas publicaciones han demostrado que ambos factores tienen una gran influencia sobre la super-vivencia del paciente trasplantado renal, condicionando la diferencia en las supervivencias obtenidas. Conclusiones: Una vez ajustado el análisis por los diferen-tes factores que intervienen en la supervivencia del pa-ciente y del injerto, no existen diferencias en los resulta-dos obtenidos por los dos tratamientos, ya que los mejores resultados del TRV son debidos a factores como la menor edad del receptor y el TR anticipado. Palabras clave: Trasplante renal de donante vivo. Supervivencia. Comparación de resultados. Registros. SUMMARY Background: According to literature, patient and graft survival is better in living donor renal transplants (LRT) than in cadaver renal transplants (CRT). Objective: To study factors that determine the best results in LRT related to those of CRT, found in univariate studies. Patients and Methods: Renal transplants (RT) done in Catalonia during the 1990-2004 period, performed in patients over 17 years (135 LRT and 3.831 CRT), have been analyzed (retrans-plants were not included). The data come from the Renal Pa-tients Transplant Registry (RMRC). Student's t-test and χ 2 test were used to compare means and proportions, respectively. To analyze univariate and multivariate survival, actuarial method and Cox regression have been used, respectively. Estimated crea-tinine clearance has been studied and its data have been sho-wed through Selwood modified Analysis. Results: As it happens with other great RT patients series, the RMRC analysis, globally and without any adjustment, shows that patient and graft survival in LRT is better than that obtained with CRT. When we studied which variables explain these results, we found that main factors were smaller recipient age and the short time on dialysis. The great influence of both factors has been published in a large number of papers, explaining the differen-ces obtained on the transplanted renal patient survival. Conclusions: Once adjusted the analysis by the different factors that influence the survival of the patient and the graft, there are no differences in the obtained results, since the best outcomes of the TRV are due to factors like the smaller recipient age and the advanced TR.