Exogenous α-synuclein hinders synaptic communication in cultured cortical primary rat neurons.

Amyloid aggregates of the protein α-synuclein (αS) called Lewy Bodies (LB) and Lewy Neurites (LN) are the pathological hallmark of Parkinson's disease (PD) and other synucleinopathies. We have previously shown that high extracellular αS concentrations can be toxic to cells and that neurons take up αS. Here we aimed to get more insight into the toxicity mechanism associated with high extracellular αS concentrations (50-100 µM). High extracellular αS concentrations resulted in a reduction of the firing rate of the neuronal network by disrupting synaptic transmission, while the neuronal ability to fire action potentials was still intact. Furthermore, many cells developed αS deposits larger than 500 nm within five days, but otherwise appeared healthy. Synaptic dysfunction clearly occurred before the establishment of large intracellular deposits and neuronal death, suggesting that an excessive extracellular αS concentration caused synaptic failure and which later possibly contributed to neuronal death.

Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome.

UNLABELLED: Incident vertebral fractures and lumbar spine bone mineral density (BMD) were assessed in the 12 months following glucocorticoid initiation in 65 children with nephrotic syndrome. The incidence of vertebral fractures was low at 12 months (6 %) and most patients demonstrated recovery in BMD Z-scores by this time point. INTRODUCTION: Vertebral fracture (VF) incidence following glucocorticoid (GC) initiation has not been previously reported in pediatric nephrotic syndrome. METHODS: VF was assessed on radiographs (Genant method); lumbar spine bone mineral density (LS BMD) was evaluated by dual-energy X-ray absorptiometry. RESULTS: Sixty-five children were followed to 12 months post-GC initiation (median age, 5.4 years; range, 2.3-17.9). Three of 54 children with radiographs (6 %; 95 % confidence interval (CI), 2-15 %) had incident VF at 1 year. The mean LS BMD Z-score was below the healthy average at baseline (mean ± standard deviation (SD), -0.5 ± 1.1; p = 0.001) and at 3 months (-0.6 ± 1.1; p < 0.001), but not at 6 months (-0.3 ± 1.3; p = 0.066) or 12 months (-0.3 ± 1.2; p = 0.066). Mixed effect modeling showed a significant increase in LS BMD Z-scores between 3 and 12 months (0.22 SD; 95 % CI, 0.08 to 0.36; p = 0.003). A subgroup (N = 16; 25 %) had LS BMD Z-scores that were ≤-1.0 at 12 months. In these children, each additional 1,000 mg/m(2) of GC received in the first 3 months was associated with a decrease in LS BMD Z-score by 0.39 at 12 months (95 % CI, -0.71 to -0.07; p = 0.017). CONCLUSIONS: The incidence of VF at 1 year was low and LS BMD Z-scores improved by 12 months in the majority. Twenty-five percent of children had LS BMD Z-scores ≤-1.0 at 12 months. In these children, LS BMD Z-scores were inversely associated with early GC exposure, despite similar GC exposure compared to the rest of the cohort.

The development of bone mineral lateralization in the arms.

UNLABELLED: Bone mineral content (BMC) is known to be greater in the dominant arm after the age of 8 years. We studied a group of children and found that BMC sidedness gradually increased up to the age of 6 years and then remained stable into late adolescence. INTRODUCTION: Bone mineral content (BMC) exhibits sidedness in the arms after the age of 8 years, but it is not known whether BMC is greater in the dominant arm from birth or whether lateralization develops in early childhood. To address this, we examined bone mineral status in relation to handedness and age. METHODS: Subjects (N = 158) were children recently initiating glucocorticoids for underlying disease (leukemia 43 %, rheumatic conditions 39 %, nephrotic syndrome 18 %). Handedness was determined by questionnaire and BMC by dual-energy X-ray absorptiometry. RESULTS: Median age was 7.2 years (range, 1.5 to 17.0 years), 49 % was male, and the spine BMD Z-score was -0.9 (SD, 1.3). By linear regression, BMC sidedness in the arms was significantly related to age (r = 0.294, p = 0.0005). Breakpoint analysis revealed two lines with a knot at 6.0 years (95 % CI, 4.5-7.5 years). The formula for the first line was: dominant:nondominant arm BMC ratio = 0.029 × age [in years] + 0.850 (r = 0.323, p = 0.017). The slope of the second line was not different from 0 (p = 0.332), while the slopes for the two lines were significantly different (p = 0.027). CONCLUSIONS: These results show that arm BMC sidedness in this patient group develops up to age 6 years and then remains stable into late adolescence. This temporal profile is consistent with mechanical stimulation of the skeleton in response to asymmetrical muscle use as handedness becomes manifest.

Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome.

SUMMARY: Eighty children with nephrotic syndrome underwent lumbar spine densitometry and vertebral morphometry soon after glucocorticoid initiation. We found an inverse relationship between glucocorticoid exposure and spine areal bone mineral density (BMD) Z-score and a low rate of vertebral deformities (8%). INTRODUCTION: Vertebral fractures are an under-recognized complication of childhood glucocorticoid-treated illnesses. Our goal was to study the relationships among glucocorticoid exposure, lumbar spine areal BMD (LS BMD), and vertebral shape in glucocorticoid-treated children with new-onset nephrotic syndrome. METHODS: Lateral thoracolumbar spine radiography and LS BMD were performed in 80 children with nephrotic syndrome (median age 4.4 years; 46 boys) within the first 37 days of glucocorticoid therapy. Genant semiquantitative grading was used as the primary method for vertebral morphometry; the algorithm-based qualitative (ABQ) method was used for secondary vertebral deformity analysis. RESULTS: Six of the 78 children with usable radiographs (8%; 95% confidence interval 4 to 16%) manifested a single Genant grade 1 deformity each. All deformities were mild anterior wedging (two at each of T6, T7, and T8). Four of the 78 children (5%; 95% confidence interval 2 to 13%) showed one ABQ sign of fracture each (loss of endplate parallelism; two children at T6 and two at T8). Two of the children with ABQ signs also had a Genant grade 1 deformity in the same vertebral body. None of the children with a Genant or ABQ deformity reported back pain. An inverse relationship was identified between LS BMD Z-score and glucocorticoid exposure. CONCLUSIONS: Although we identified an inverse relationship between steroid exposure and LS BMD soon after glucocorticoid initiation for childhood nephrotic syndrome, there was only a low rate of vertebral deformities. The clinical significance of these findings requires further study.

Assessment of arterial stiffness from ambulatory blood pressure monitoring in children with diabetes mellitus type-1 (DMT1).

Pulse pressure (PP) and ambulatory arterial stiffness index (AASI) can be calculated from ambulatory blood pressure (BP) monitoring (ABPM) and have been suggested as markers of arterial stiffness and predictors of cardiovascular mortality. We retrospectively evaluated PP and AASI from ABPM records in 84 children (43 boys) with diabetes mellitus type-1 (DMT1) compared with 27 non-diabetic normotensive children. Based on office BP and ABPM, patients with DMT1 were divided into three groups: 24/84 (29%) had hypertension (DM HTN), 33/84 (39%) were normotensive (DM NT) and 27/84 (32%) had white-coat hypertension (DM WCH). DM WCH and DM HTN patients had significantly higher PP when compared with DM NT and NT patients alone (47.62 ± 7.31 and 47.43 ± 8.68 versus 41.45 ± 4.44 and 42.18 ± 5.97, respectively, P=0.0002). Similarly, AASI was significantly elevated in both DM WCH and DM HTN patients when compared with NT patients (0.35 ± 0.14 and 0.36 ± 0.15 versus 0.23 ± 0.15, respectively, P=0.007). In conclusion, children with DMT1 and hypertension, including WCH, had significantly higher PP and AASI levels when compared with normotensive patients. This suggests that these children may be at an increased risk for developing cardiovascular complications later on in life.

Experimental analysis and computational modeling of interburst intervals in spontaneous activity of cortical neuronal culture.

Rhythmic bursting is the most striking behavior of cultured cortical networks and may start in the second week after plating. In this study, we focus on the intervals between spontaneously occurring bursts, and compare experimentally recorded values with model simulations. In the models, we use standard neurons and synapses, with physiologically plausible parameters taken from literature. All networks had a random recurrent architecture with sparsely connected neurons. The number of neurons varied between 500 and 5,000. We find that network models with homogeneous synaptic strengths produce asynchronous spiking or stable regular bursts. The latter, however, are in a range not seen in recordings. By increasing the synaptic strength in a (randomly chosen) subset of neurons, our simulations show interburst intervals (IBIs) that agree better with in vitro experiments. In this regime, called weakly synchronized, the models produce irregular network bursts, which are initiated by neurons with relatively stronger synapses. In some noise-driven networks, a subthreshold, deterministic, input is applied to neurons with strong synapses, to mimic pacemaker network drive. We show that models with such "intrinsically active neurons" (pacemaker-driven models) tend to generate IBIs that are determined by the frequency of the fastest pacemaker and do not resemble experimental data. Alternatively, noise-driven models yield realistic IBIs. Generally, we found that large-scale noise-driven neuronal network models required synaptic strengths with a bimodal distribution to reproduce the experimentally observed IBI range. Our results imply that the results obtained from small network models cannot simply be extrapolated to models of more realistic size. Synaptic strengths in large-scale neuronal network simulations need readjustment to a bimodal distribution, whereas small networks do not require such changes.

Network bursts in cortical cultures are best simulated using pacemaker neurons and adaptive synapses.

One of the most specific and exhibited features in the electrical activity of dissociated cultured neural networks (NNs) is the phenomenon of synchronized bursts, whose profiles vary widely in shape, width and firing rate. On the way to understanding the organization and behavior of biological NNs, we reproduced those features with random connectivity network models with 5,000 neurons. While the common approach to induce bursting behavior in neuronal network models is noise injection, there is experimental evidence suggesting the existence of pacemaker-like neurons. In our simulations noise did evoke bursts, but with an unrealistically gentle rising slope. We show that a small subset of 'pacemaker' neurons can trigger bursts with a more realistic profile. We found that adding pacemaker-like neurons as well as adaptive synapses yield burst features (shape, width, and height of the main phase) in the same ranges as obtained experimentally. Finally, we demonstrate how changes in network connectivity, transmission delays, and excitatory fraction influence network burst features quantitatively.

Latency-related development of functional connections in cultured cortical networks.

To study plasticity, we cultured cortical networks on multielectrode arrays, enabling simultaneous recording from multiple neurons. We used conditional firing probabilities to describe functional network connections by their strength and latency. These are abstract representations of neuronal pathways and may arise from direct pathways between two neurons or from a common input. Functional connections based on direct pathways should reflect synaptic properties. Therefore, we searched for long-term potentiation (this mechanism occurs in vivo when presynaptic action potentials precede postsynaptic ones with interspike intervals up to approximately 20 ms) in vitro. To investigate if the strength of functional connections showed a similar latency-related development, we selected periods of monotonously increasing or decreasing strength. We observed increased incidence of short latencies (5-30 ms) during strengthening, whereas these rarely occurred during weakening. Furthermore, we saw an increased incidence of 40-65 ms latencies during weakening. Conversely, functional connections tended to strengthen in periods with short latency, whereas strengthening was significantly less than average during long latency. Our data suggest that functional connections contain information about synaptic connections, that conditional firing probability analysis is sensitive enough to detect it and that a substantial fraction of all functional connections is based on direct pathways.

Conditional firing probabilities in cultured neuronal networks: a stable underlying structure in widely varying spontaneous activity patterns.

To properly observe induced connectivity changes after training sessions, one needs a network model that describes individual relationships in sufficient detail to enable observation of induced changes and yet reveals some kind of stability in these relationships. We analyzed spontaneous firing activity in dissociated rat cortical networks cultured on multi-electrode arrays by means of the conditional firing probability. For all pairs (i, j) of the 60 electrodes, we calculated conditional firing probability (CFP(i,j)[tau]) as the probability of an action potential at electrode j at t = tau, given that one was detected at electrode i at t = 0. If a CFP(i,j)[tau] distribution clearly deviated from a flat one, electrodes i and j were considered to be related. For all related electrode pairs, a function was fitted to the CFP-curve to obtain parameters for 'strength' and 'delay' (i.e. maximum and latency of the maximum of the curve) of each relationship. In young cultures the set of identified relationships changed rather quickly. At 16 days in vitro (DIV) 50% of the set changed within 2 days. Beyond 25 DIV this set stabilized: during a week more than 50% of the set remained intact. Most individual relationships developed rather gradually. Moreover, beyond 25 DIV relational strength appeared quite stable, with coefficients of variation (100 x SD/mean) around 25% in periods of approximately 10 h. CFP analysis provides a robust method to describe the underlying probabilistic structure of highly varying spontaneous activity in cultured cortical networks. It may offer a suitable basis for plasticity studies, in the case of changes in the probabilistic structure. CFP analysis monitors all pairs of electrodes instead of just a selected one. Still, it is likely to describe the network in sufficient detail to detect subtle changes in individual relationships.

Prevalence of complications in children with chronic kidney disease according to KDOQI.

The Kidney Disease Outcome and Quality Initiative (KDOQI) Group recommended guidelines for the monitoring and treatment of chronic kidney disease (CKD) in 2002. These recommendations were based on the prevalence of known complications as seen in adults. In children, the exact prevalence of these complications is unknown. We therefore conducted a cross-sectional study of 366 patients with CKD in a single center to analyze the prevalence of these complications across all stages of kidney disease. Patients were categorized to their KDOQI stage of CKD according to their estimated renal function as determined from serum cystatin C. Fifty seven percent of patients had CKD stage 1, 29.0% stage 2, 10.4% stage 3 and 4.1% stages 4+5. Uropathies (31%) were the most prevalent causes of CKD. Glomerular disease accounted for 27%. The overall prevalence of complications was as follows: hypertension 70.2%, anemia 36.6%, proteinuria 11.5%, and metabolic bone disease 16.9%. Metabolic bone disease and anemia occurred frequently, even with a glomerular filtration rate >60 ml/min/1.73 m2. Growth failure (11.5%) was also common and is not a component of the KDOQI guidelines for CKD in children. The prevalence of all complications increased with worsening stage of kidney disease (all P-values significant). In summary, this study supports the KDOQI guidelines in defining and staging CKD in children. This study also highlights the differences in the causes and complications that occur in CKD between adults and pediatrics. We recommend modification of the KDOQI guidelines for children to reflect the differences described in this paper.

[What is new in pediatric nephrology?]. / Quoi de neuf en néphrologie pédiatrique?

Recent advances in the knowledge of physiology, genetics, imaging, and therapeutics have lead to novel practical approaches in paediatric nephrology. Many inherited syndromes have been revisited in order to identify precise renal diseases at the molecular level. In addition, a large number of epidemiological studies and clinical trials have allowed guidelines and recommendations to be provided for chronic and end-stage renal failure, urinary tract infection, glomerular diseases, etc.

Ambulatory blood pressure monitoring in children after renal transplantation.

Arterial hypertension is a common complication in children after renal transplantation and the control of hypertension is often difficult. This retrospective investigates the prevalence and rate of control of hypertension using ambulatory blood pressure monitoring (ABPM) in 45 children (mean age 14.1 +/- 4.3 years, mean time after renal transplantation 2.2 +/- 2.7 years), all on cyclosporine or tacrolimus, azathioprine or mycophenolate mofetil plus daily steroids. The overall prevalence of hypertension was 82%. None of the transplanted children had normal blood pressure without antihypertensive therapy (ie, spontaneous normotension). Twenty percent of children had untreated hypertension, 18% had controlled hypertension, and 62% had uncontrolled hypertension. Prevalence of the nondipping phenomenon was 53%. The mean number of antihypertensive drugs (without diuretic monotherapy) in treated patients was 1.9 drugs per patient. The prevalence of arterial hypertension in children after renal transplantation is high and the control of hypertension is often unsatisfactorily low.

Tissue HHV6 and 7 determination in pediatric solid organ recipients--a pilot study.

Herpes virus infections remain a major challenge in solid organ transplantation. HHV6 and 7 blood viral load was associated with pathology after renal transplantation. Little is known about the significance of tissue HHV6 and 7 infections. A total of 18 tissue biopsies (13 kidney, three GI and two BAL) from nine pediatric transplant patients (five kidney, two liver, one combined liver and kidney and one bone marrow transplant) were subjected to blood HHV6 IgG and IgM testing. In addition, tissue HHV6 and 7 semi-quantitative PCR analysis with subsequent detection by ELISA and quantitative methods were applied to the same samples. We also studied four native kidney biopsies of children with other kidney disease. The results of the biopsies were correlated with clinical data. Of the transplant patients, 78% were HHV6 IgG positive. Six of nine had a positive IgM on at least one occasion, however, only two of nine transplant patients were symptomatic with a mixed CMV/EBV septic picture of multi-organ failure. Only these two patients had a significant tissue viral load for HHV6. Additionally, a very significant tissue viral load for HHV6 was detected in an immunocompromised patient 3 wk after a roseola-like febrile illness. The HHV6 copies were 31, 88 and 206 per 10 microL of DNA, respectively. In the patient who also had the fourth positive ELISA for HHV6 PCR product, the Multiplex PCR and restriction enzyme assay on its PCR product revealed a significant contribution by HHV7, while the HHV6-B signal was rather weak. Significant tissue HHV6 loads can be found in tissue biopsies from organ recipients with significant illness and also in native kidneys after primary infection. This may explain the high prevalence of HHV6 in transplanted kidneys. Further studies on HHV6 and 7 using molecular techniques should be supported.

Universal approach to pharmacokinetic monitoring of immunosuppressive agents in children.

Current data indicate that pharmacokinetic (PK) monitoring of cyclosporin microemulsion (CsA) should be performed using the 2-h concentration (C2), that tacrolimus (Tac) is commonly monitored using the trough level, and mycophenolate mofetil (MMF) should be monitored using the 1-h (C1), 2-h (C2) and 6-h (C6) concentrations. The three differing time-point requirements are cumbersome, and we aimed to develop universal guidelines for all three drugs using a large number of full PK profiles in children. One-hundred and twenty two stable pediatric patients, receiving either CsA (165 PK profiles, 69 patients, 24 with concomitant MMF) or Tac (122 PK profiles, 53 patients, 18 with MMF) were analyzed retrospectively. Pearson r for the CsA C2 was 0.90 [95% confidence interval(CI): 0.86-0.92], for Tac C2 r was 0.86 (95% CI: 0.80-0.90), and for MPA C2 r was 0.77 (95% CI: 0.68-0.83), respectively. For MPA, at least three time-points are required to accurately estimate the area under the concentration-time curve (AUC), and C1, C2 and C6 serve as best markers. Excellent AUC estimations could be obtained from a limited sampling strategy from C1, C2 and C6 or C0, C1, C2 and C4 with clinically acceptable errors for all three drugs. The AUC can be estimated with great precision by using an identical approach for all three drugs. Target AUCs for a given time-point after transplantation remain to be established.

[Turner syndrome: overview of problems, present status, proposals for care and a protocol for monitoring in childhood, adolescence and adulthood]. / Turneruv syndrom: prehled problematiky, soucasný stav, návrh koncepce péce a protokol sledování v detství, adolescenci a v dospelosti.

BACKGROUND: Girls and adolescents with Turner syndrome (TS) usually receive intensive medical care in a multidisciplinary team, coordinated by paediatric endocrinologist. Majority of them are discharged from specialist clinics following the induction of puberty and attainment of final height. Patients with Turner syndrome have a reduced life expectancy, they are known to have multi-system impairments in addition to the short stature and to the absence of sexual development. Aim of this study is to propos a continuous follow-up by multidisciplinary team of physicians starting in childhood and following the discharge from the paediatric care. METHODS AND RESULTS: This paper highlights the medical and psychosocial problems associated with Turner syndrome in childhood, adolescence and in adulthood. Analysis of these problems served as a background to management strategy. CONCLUSIONS: Women with Turner syndrome are at risk of number of medical problems. Quality of their life and the life expectancy can be improved with increasing awareness to comorbities associated with Turner syndrome. Assisted reproduction technologies has recently offered a chance for pregnancy and delivery of a healthy child also to women with Turner syndrome. Therefore, long-term follow-up by multidisciplinary team of physicians knowledgeable about these medical problems is necessary. Introduction of a centralised system of systematic multidisciplinary approach to patients with Turner syndrome from childhood and adolescence to adulthood seems to be very important.

Repeated ambulatory blood pressure monitoring in adolescents with mild hypertension.

The reproducibility of serial measurements of ambulatory blood pressure monitoring (ABPM) has not been well explored in children. We performed 24-h ABPM in 59 subjects (38 boys) aged 8-19 years with repeatedly elevated casual blood pressure (BP). According to the results of ABPM, the individuals were divided into a hypertensive group (mean 24-h systolic or diastolic BP >95th percentile for height, n=28) and a normotensive group (n=31). No antihypertensive agents were given. Both groups were reexamined after 1 year. In the hypertensive group, systolic and diastolic BP dropped significantly by an average of 2.1-4.5 mmHg when measured either during the daytime or over 24 h, but not at nighttime. In the normotensive group, only small BP changes were observed except for a significant increase in systolic BP at night. At the repeat examination after 1 year, 54% of the originally hypertensive subjects were defined as normotensive and 23% of the originally normotensive subjects as hypertensive. The study indicates that a single ABPM measurement is not sufficient for definitive classification of young individuals into hypertensives or normotensives.

Body composition in children after renal transplantation.

This study examines changes in body composition after renal transplantation (Tx) in 16 children who underwent dual-energy X-ray absorptiometry examination within 6 months preceding Tx; the examination was then repeated every 6 to 12 months after Tx. Body composition was analyzed with regard to whole-body bone mineral content (BMC), lean body mass (LBM), and fat body mass (FBM). Median BMC decreased from the initial value of +0.98 standard deviation scores (SDS) to -0.55 SDS during the first 3 months after Tx, and a further decrease was noted at the end of month 6 (M6; -1.34 SDS) and M12 after Tx (-1.32 SDS). Improvement was observed during the second year after Tx (P for global changes < 0.0001). LBM and FBM also changed significantly during the 2 years after Tx (P = 0.006 and P = 0.0001, respectively). LBM decreased during the first 3 months after Tx (median change, 0.71 SDS) and remained less than 0 SDS in all but 4 patients. Median LBM did not decrease to less than -1 SDS during the entire study period. Conversely, median FBM increased by a median of 3.73 SDS during the first 3 months and remained elevated during the first 12 months after Tx, with a subsequent decrease at 2 years after Tx. No significant correlation was found between cumulative doses of prednisone and BMC, FBM, or LBM at any interval if absolute values were considered. However, relative changes in FBM correlated significantly with relative changes in prednisone cumulative doses.

[Dual X-ray absorptiometry (DEXA) in children with chronic diseases]. / Zastosowanie metody absorcjometrii promieniowania rentgenowskiego o podwójnej energii (DEXA) u dzieci z chorobami przewleklymi.

Dual energy X-ray absorptiometry (DEXA) can be used for the measurement of bone density at the level of lumbar spine, whole body scan, and also for the measurement of bone mass content (BMC), lean body mass (LBM), and fat body mass (FBM). Although this method has been originally developed for the diagnosis and monitoring of osteoporosis in adults, it is used in children with chronic diseases like chronic renal failure, chronic gastrointestinal and rheumatological diseases. However, children with chronic disease often demonstrate statural growth disturbances and decreased growth velocity. Therefore, their actual height does not correspond to the actual chronological age. Normal values of DEXA for a given age are based on data from children with normal height. Interpretation of DEXA regardless of the actual height, which is usually stunted, may lead to false conclusions and wrong therapeutic attitudes. Thus, when interpreting results obtained in such patients a few transformations and calculations should be done.

[Renal transplantation in children in the Czech Republic]. / Wyniki przeszczepiania nerek u dzieci w Republice Czeskiej.

The aim of the study is to review results of pediatric renal transplantation in center in Prague, Czech Republic. Results are compared with the registry data from Europe and United States. Patients, who underwent RTx at the University Hospital Motol, Prague (Czech Republic) between 1977 and the end of 1999, were analyzed. Since 1977 128 Rtx from cadaveric donors were performed in children in mean age 12.8 +/- 4.1 years. In 1977-1987, patients were treated with prednisone and azathioprine, and since 1988, cyclosporine A, added to prednisone and azathioprine. Sequential quadruple immunosuppression was used only in few highly sensitized patients. Acute graft rejections were treated with methylprednisolone pulses, antithymocyte globulin and monoclonal antibodies OKT3, in selected cases. In 1988 and 1999 cyclosporine A was replaced by tacrolimus as initial immunosuppression in some patients. The number of Tx ranged between 5 and 13 per year. Patients and graft survival were significantly lower in the first time period 1977-1987 with a median patients 5-year survival rate of only 50% and graft survival 30%. In the last period (1988-1999) 5-year patients survival is 90% and 5-year graft survival is 68% (p = 0.01). Two cases of posttransplant lymphoproliferative disease were diagnosed so far. One of them died several months after RTx, the other received cytostatic therapy for Hodgkin tumor and graft function was maintained. Main causes of graft failure were chronic rejection followed by acute steroid resistant rejections, severe cytomegalovirus infections, noncompliance, vascular thrombosis, and recurrence of original disease.