Dexamethasone protects from renal ischemia/reperfusion injury: a possible association with SGK-1.

Previous experimental data suggest that steroids might have protective effects during hypoxic/ischemic injury of various organs. In this study, the association between dexamethason (Dexa) treatment and the anti-apoptotic SGK-1 was tested in ischemic renal injury. In vitro, HK-2 cells were exposed to 24 h hypoxia, and the effect of Dexa incubation on SGK-1 expression / activation and on cell death was studied. In an in vivo rat model of unilateral renal IR, animals were treated with Dexa, and serum renal function parameters, tissue injury and SGK-1 expression and localization were examined after different reperfusion times (2 h, 4 h and 24 h). Dexa at a dose of 2 mg/L exerted a protective effect on cell survival assessed by LDH release and vital staining paralleled by marked up-regulation of SGK-1. In rats, 2 mg/kg Dexa treatment 24 h prior to ischemia resulted in less severe tissue injury and ameliorated urea nitrogen levels 24 h after reperfusion. Furthermore, SGK-1 expression and phosphorylation were higher in Dexa animals demonstrated by Western blot and immunofluorescence technique. Our results provide novel data on the signalling mechanism of Dexa under hypoxia / ischemia and further support that Dexa emerges as an attractive pharmacological agent for the prevention of ischemic injury.

The importance of different immunosuppressive regimens in the development of posttransplant diabetes mellitus.

Solid-organ transplantation is the optimal long-term treatment for most patients with end-stage organ failure. After solid-organ transplantation, short-term graft survival significantly improved (1). However, due to chronic allograft nephropathy and death with functioning graft, long-term survival has not prolonged remarkably (2). Posttransplant immunosuppressive medications consist of one of the calcineurin inhibitors in combination with mycophenolate mofetil (MMF) or azathioprine (Aza) and steroids. All of them have different adverse effects, among which posttransplant diabetes mellitus (PTDM) is an independent risk factor for cardiovascular (CV) events and infections causing the death of many transplant patients and it may directly contribute to graft failure (3). According to the criteria of the American Diabetes Association (4), diabetes mellitus (DM) is defined by symptoms of diabetes (polyuria and polydipsia and weight loss) plus casual plasma glucose concentration ≥ 11.1 mmol/L or fasting plasma glucose (FPG) ≥ 7.0 mmol/L or 2-h plasma glucose level ≥ 11.1 mmol/L following oral glucose tolerance test (OGTT). This metabolic disorder occurring as a complication of organ transplantation has been recognized for many years. PTDM, which is a combination of decreased insulin secretion and increased insulin resistance, develops in 4.9/15.9% of liver transplant patients, in 4.7/11.5% of kidney recipients, and in 15/17.5% of heart and lung transplants [cyclosporine A (CyA)/tacrolimus (Tac)-based regimen, respectively] (5). Risk factors of PTDM can be divided into non-modifiable and modifiable ones (6), among which the most prominent is the immunosuppressive therapy being responsible for 74% of PTDM development (7). Emphasizing the importance of the PTDM, numerous studies have determined the long-term outcome. On the basis of these studies, graft and patient survival is tendentiously (8) or significantly (9, 10) decreased for those developing PTDM.

Heat shock protein polymorphism predisposes to urinary tract malformations and renal transplantation in children.

BACKGROUND: Anatomical malformations of the kidney and urinary tract account for 17% of pediatric renal transplantation procedures. Heat shock proteins (HSPs) are molecular chaperones with a protective function that promotes cell survival. HSP72 is an endogenous ligand for toll-like receptor TLR4, thereby stimulating innate immunity. Both in adults and children, decreased expression of HSP70s is associated with a number of kidney diseases. OBJECTIVE: To assess the prevalence of HSPA1A G(190)C, HSPA1B A(1267)G, and TLR4 A(896)G polymorphisms in children who had undergone kidney transplantation. PATIENTS AND METHODS: Genotypes were analyzed using allele-specific polymerase chain reaction in 41 pediatric recipients. Allelic prevalence was related to reference values in 65 age- and sex-matched healthy children. RESULTS: Clinical data did not reveal a difference between any of the groups. HSPA1B (1267)GG genotype and HSPA1B (1267)G allele were observed more frequently in the transplant recipients compared with the control group: AA vs AG: odds ratio [OR], 12.6; 95% confidence interval [CI], 1.58-100.0; P = .004; AA vs GG: OR, 20.80; 95% CI, 2.32-187.00; P = .01; and A vs G: OR, 2.10; 95% CI, 1.19-3.07; P = .01. Furthermore, the prevalence of the HSPA1B (1267)GG genotype was greater in transplant recipients with vs without urinary tract malformations: AG vs GG: OR, 0.10; 95% CI, 0.09-0.48; P = .007. No differences were observed in the other studied polymorphisms. CONCLUSION: Our findings suggest an association between the carrier status of HSPA1B (1267)G with urinary tract malformations, leading to end-stage renal disease requiring kidney transplantation. This observation raises further questions about the clinical and therapeutic relevance of this polymorphism to pediatric nephrology.

Lifestyle, body composition, and physical fitness changes in Hungarian school boys (1975-2005).

General socioeconomic conditions as well as the physical environment have undergone remarkable changes in Hungary during the past 30 years. Unfortunately, these positive processes have resulted in a reduction of habitual physical activity along with unfavorable changes in dietary habits. Therefore, the purpose of the present study was to compare some selected morphological and functional parameters of 7-14-year-old Hungarian schoolboys living in the middle of the 1970s and at the beginning of the new millennium. It was hypothesized that there would be significant differences in morphological and functional characteristics of the Hungarian schoolboy populations, because they were assessed 30 years apart. Means of height, body mass, body mass index (BMI), the sum of five skinfold tests, percentage of body fat, and two running performance times (400 m and 1,200 m) of the boys (N = 3,672) studied in 1975 were compared to those of the boys (N = 3,758) in 2005. Data were analyzed using two-tailed independent samples t tests (p < .05). We observed significant secular changes in body mass and height. In addition, boys in 2005 had significantly more subcutaneous fat compared to 1975. The running times for the two distances were significantly poorer at the time of the second investigation. The remarkable and unfavorable changes in body composition and cardiorespiratory performance were attributed to the continuously decreasing intensity of habitual physical exercise and a lifestyle that had become more sedentary (watching TV playing computer games, etc.). Radical interventions are necessary to reduce these risks associated with the high prevalence of cardiovascular disease in Hungary, and the challenge to resolve the problem requires combined efforts at the educational, societal, corporate, and governmental levels.

Post-transplant diabetes mellitus in children following renal transplantation.

PTDM plays a role in chronic allograft nephropathy and decreases graft and patient survival. Considering the serious outcome of chronic hyperglycemia, the importance of early recognition and the few data in children, in this retrospective analysis we studied the characteristics and risk factors of PTDM in 45 pediatric renal transplant recipients receiving Tac or CyA-based immunosuppression. Fasting blood sampling and OGTT were performed. PTDM has been developed in six patients (13%), while seven children (16%) had IGT, with the overall incidence of a glucose metabolic disorder of 29% in pediatric renal transplants. Patients in the PTDM + IGT group were younger and had higher systolic blood pressure and serum triglyceride level than children with normal glucose tolerance. Multivariate analysis identified Tac treatment, Tac trough level, steroid pulse therapy and family history of diabetes to be associated with the onset of PTDM. In pediatric renal transplants, OGTT and frequent assessment of blood glucose levels might be essential not only in the post-transplant management, but also prior to transplantation, particularly with family history of diabetes. Careful monitoring and modified protocols help to minimize the side effects of Tac and corticosteroids.

Effects of 3 hours a week of physical activity on body fat and cardio-respiratory parameters in obese boys.

The prevalence of overweight or fat children and adolescents has markedly increased in Hungary during the past three decades. Among the possible factors insufficient physical activity and a relative or absolute excess of calorie intake associated to it can be regarded as the most important ones. The aim of the study was to analyse the effects of a 20-week aerobic exercise on body composition and on the exercise tested cardio-respiratory functions in 10-year-old obese boys. Obesity was defined by a BMI greater than the cut-off value reported by Cole and co-workers (5) and a relative body fat content above 30% (13). Of the study group 21 volunteer children completed the program; the contrast group contained 28 obese boys. Mean calendar age was 10.03 +/- 0.26 in the study group (S) and 9.88 +/- 0.29 in the control group (C). The members of group S had two curricular physical education (PE) classes a week and three extracurricular aerobic physical activity sessions of 60 min net time in the afternoon, on Mondays (swimming and water games), Wednesdays (folk dance) and Fridays (soccer). Group C had only 2 PE classes a week. Anthropometric and spiroergometric data were collected in the middle of January and June of 2004. Relative body fat content and BMI did not increase during the observation period in contrast to the significant increase of both in the control group. Peak minute ventilation, aerobic power, oxygen pulse, and running distance (performed on a treadmill) increased in group S, and did not change in group C. The program was considered successful despite that the changes in the observed physiological and physical indicators appeared to be slight. However, the 5-month elevated level of physical activity brought about such development in the physical status of the obese subjects that might be an appropriate basis for regular training. Fortunately, the cardio-respiratory functions of the investigated boys were not affected yet by obesity, consequently the really dramatic change in their further lifestyle exclusively depends on their decision.

Overweight and obesity in 7 to 10-year-old Hungarian boys. Short communication.

Increasing prevalence of overweight and obesity is a serious social and health problem both in the economically developed and developing countries. Despite this fact the nation-wide growth studies completed in Hungary during the past 30 years had not categorised the children either by body fat content or nutritional status. The aim of the study was to estimate the prevalence of overweight and obese boys in the country at the beginning of the new millennium. Height, body mass and four skinfold thicknesses were measured in 7173 volunteer boys aged between 7 and 10 and living in various urban and rural settlements of Hungary between 2003 and 2005. Nutritional status was qualified by the BMI and relative body fat content. The significantly increasing prevalence with age of overweight and obesity ranged between 10.3 and 23.4%. The results showed the joint effects of a secular trend of growth and of a remarkably changed lifestyle. Of these the consequences of the lifestyle are the more important ones. The high and possibly further increasing prevalence of child-age overweight and obesity reminds one of the observations of Kopp and associates (5), namely that of the increased prevalence of chronic childhood diseases during the past 15 years. More intense habitual physical activity and dramatic changes in dietary habits still promise some solution. No one should reckon, however, with the efficiency of physical education at the schools with its very few classes.