Genetic and metabolic determinants of increased plasma plasminogen activator inhibitor-1 activity in children with renal transplants

Aldámiz‐Echevarría, Luis; Sanjurjo, Pablo; Vallo, Alfredo; Aguirre, Mireia; Pérez-Nanclares, Gustavo; Gimeno, Pilar; Rueda, Miguel R.; Ruíz, José Ignacio; Rodríguez‐Soriano, Juan

doi:10.1007/s00467-003-1157-6

Cited by 8 publications

(16 citation statements)

References 45 publications

(42 reference statements)

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“…Increased plasma PAI-1 activity, inflammatory status, as judged by values of plasma CRP, and insulin resistance are independent but closely related markers of atherogenesis [29,30,31,32]. In this same group of transplanted patients we found that plasma PAI-1 activity was significantly elevated and correlated positively with CRP, fasting insulinemia, and the HOMA index [4]. The finding in the present study of an association between plasma PAI-1 activity and total fat intake was expected [33].…”

Section: Discussionsupporting

confidence: 55%

“…The data depicted in Table 2 have been reported previously [3,4]. A number of transplanted children had a cluster of risk factors predisposing to cardiovascular disease: high plasma levels of triglycerides, total cholesterol, and low-density lipoprotein (LDL)-cholesterol, insulin resistance, hyperhomocysteinemia, high plasma PAI-1 activity, and elevated CRP.…”

Section: Plasma Biochemical Profilementioning

confidence: 92%

“…Although the risk for cardiovascular disease in transplanted children is in part genetically determined [3,4,8], it may also be influenced by diet. It is well accepted that the dramatic surge of cardiovascular disease and type 2 diabetes observed in the western world over the last decades is mainly due to an increased intake of fat, and especially of saturated fat.…”

Section: Introductionmentioning

confidence: 98%

“…It has variously been attributed to factors such as hypertension, dyslipidemia, hyperhomocysteinemia, obesity, insulin resistance, post-transplant diabetes, immunosuppressive therapy, etc. [2,3,4,5,6]. The atherogenic risk is associated with a chronic inflammatory process that leads to progressive endothelial cell dysfunction with infiltration of macrophages, liberation of cytokines, activation of platelets, and hypercoagulability, all resulting in the development of atheromatous lesions [7].…”

Section: Introductionmentioning

confidence: 99%

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Influence of diet on atherogenic risk in children with renal transplants

et al. 2004

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Cardiovascular disease is one of the main causes of morbidity and mortality in recipients of renal transplants. Although the risk for cardiovascular disease is in part genetically determined, it may also be influenced by diet. The aim of the present study was to analyze the cross-sectional association of dietary intake of nutrients with biochemical markers of atherogenic risk. The influence of diet on the plasma profile of fatty acids was specifically investigated. Twenty-nine children and adolescents (mean age 14 years, range 6-18 years) with stable renal transplants and on a normal diet recorded their food intake for a period of 3 days. The mean calorie intake was 40.6 kcal/kg per day (protein provided 16% of total calories, carbohydrates 45%, and fat 39%). Plasma levels of total cholesterol and low-density lipoprotein-cholesterol were significantly and positively related to intake of monounsaturated fatty acids ( r=0.66, P =0.007 and r =0.62, P =0.02, respectively) and to plasma levels of elaidic acid, a trans fatty acid ( r=0.43, P =0.02 and r =0.54, P =0.01, respectively). Insulin resistance, estimated from values of plasma glucose ( r=0.70, P =0.03), plasma insulin ( r=0.59, P =0.02), and HOMA index ( r=0.62, P =0.01), was also directly related to the intake of monounsaturated fatty acids. Plasma plasminogen activator inhibitor-1 activity correlated positively with total fat intake ( r=0.59, P =0.04). Plasma levels of homocysteine were negatively related to the intake of carbohydrates ( r=-0.62, P =0.02). We conclude that reasonable dietary recommendations to minimize the atherogenic risk in children with stable renal transplants should include a protein intake adjusted to the requirements for age, a large intake of carbohydrates leading to a low glycemic load, and a fat intake of less than 30% of the total calorie intake. The amount of monounsaturated and trans fatty acids in the diet should be especially limited. A sufficient intake of polyunsaturated fatty acids, with an adequate ratio between omega 6 and omega 3 components, should also be provided.

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Section: Discussionsupporting

confidence: 55%

Section: Plasma Biochemical Profilementioning

confidence: 92%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Influence of diet on atherogenic risk in children with renal transplants

et al. 2004

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“…This risk persists after renal transplantation because of many factors such as hypertension, dyslipidemia, hyperhomocysteinemia, hyperparathyroidism, obesity, insulin resistance, posttransplant diabetes, and immunosuppressive therapy, among others (2)(3)(4)(5)(6).…”

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confidence: 99%

The Arginine-Creatine Pathway is Disturbed in Children and Adolescents With Renal Transplants

Andrade¹,

Rodríguez‐Soriano²,

Prieto³

et al. 2008

Pediatr Res

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Cardiovascular disease is an important cause of morbidity in recipients of renal transplants. The aim of the present study was to analyze the status of the arginine-creatine pathway in such patients, given the relationship between the arginine metabolism and both renal function and the methionine-homocysteine cycle. Twentynine children and adolescents (median age 13, range 6 -18 years), who had received a renal allograft 14.5-82.0 months before, were recruited for the study. On immunosuppressive therapy, all patients evidenced an adequate level of renal function. Plasma concentrations of homocysteine and glycine were significantly higher, whereas urinary excretions of guanidinoacetate and creatine were significantly lower than controls. Urinary excretions of guanidinoacetate and creatine correlated positively with creatinine clearance. Urinary excretion of creatine was negatively correlated with plasma concentration of homocysteine. The demonstration of disturbances in the arginine-creatine pathway in patients with well-functioning renal transplants and in absence of chronic renal failure represents a novel finding. We speculate that the low urinary excretion of guanidinoacetate and creatine is probably related to the nephrotoxic effect of immunosuppressive therapy and to defective methylation associated with the presence of hyperhomocysteinemia. (Pediatr Res 64: [218][219][220][221][222] 2008)

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A study on glucose metabolism in a small cohort of children and adolescents with kidney transplant

Giordano

Colella

Dammacco

et al. 2006

J Endocrinol Invest

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Post-transplant diabetes mellitus (PTDM) and impaired glucose tolerance are now considered among the major adverse events following organ transplantation. The present study was aimed at investigating the regulation of glucose metabolism in pediatric recipients of a kidney transplant (KT), receiving tacrolimus or cyclosporine A-based immunosuppression. Twelve subjects, eight males and four females, aged 12.1+/-3.8 yr, and with a mean time from KT of 45.6 months were enrolled in the study. All patients had a basal evaluation of fasting glucose (GF), fasting insulin (IF), C-peptide and glycated hemoglobin (HbA1c) levels. They then underwent oral glucose tolerance test (OGTT), with measurement of blood glucose and insulin concentration. Two children had impaired GF, associated with supernormal HbA1c levels, one patient showed impaired glucose tolerance, none had PTDM. Peripheral insulin resistance, as measured by quantitative insulin sensitivity check index (QUICKI) and homeostasis model assessment estimate of insulin sensitivity (HOMA-IR) index, was enhanced in 3 patients. Subsequently, GF significantly increased with time from transplant (p=0.01), while fasting C-peptide and the area under the curve of insulin correlated with creatinine clearance. In conclusion, our results, although generated in a small sample size, would suggest that long-term follow-up of children receiving a KT should extend to explore the response to oral glucose load and at least the basal measure of insulin response.

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Genetic and metabolic determinants of increased plasma plasminogen activator inhibitor-1 activity in children with renal transplants

Cited by 8 publications

References 45 publications

Influence of diet on atherogenic risk in children with renal transplants

Influence of diet on atherogenic risk in children with renal transplants

The Arginine-Creatine Pathway is Disturbed in Children and Adolescents With Renal Transplants

A study on glucose metabolism in a small cohort of children and adolescents with kidney transplant

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