Disparities in policies, practices and rates of pediatric kidney transplantation in Europe.

We aimed to provide an overview of kidney allocation policies related to children and pediatric kidney transplantation (KTx) practices and rates in Europe, and to study factors associated with KTx rates. A survey was distributed among renal registry representatives in 38 European countries. Additional data were obtained from the ESPN/ERA-EDTA and ERA-EDTA registries. Thirty-two countries (84%) responded. The median incidence rate of pediatric KTx was 5.7 (range 0-13.5) per million children (pmc). A median proportion of 17% (interquartile range 2-29) of KTx was performed preemptively, while the median proportion of living donor KTx was 43% (interquartile range 10-52). The median percentage of children on renal replacement therapy (RRT) with a functioning graft was 62%. The level of pediatric prioritization was associated with a decreased waiting time for deceased donor KTx, an increased pediatric KTx rate, and a lower proportion of living donor KTx. The rates of pediatric KTx, distribution of donor source and time on waiting list vary considerably between European countries. The lack of harmonization in kidney allocation to children raises medical and ethical issues. Harmonization of pediatric allocation policies should be prioritized.

Bone density in renal transplant recipients and in patients with chronic kidney disease: a follow-up study in children and adolescents.

AIMS: Disturbances in mineral and bone metabolism are common in patients with chronic kidney disease. The purpose of this follow-up study was to compare the change of bone mineral density in patients with chronic kidney disease to those who have received the renal transplant. METHODS: The study included 47 children and adolescents: 16 with mild to moderate kidney disease, 14 on dialysis and 17 patients with renal transplant. At the baseline and follow-up visits, regular biochemistry, anthropometry and bone mineral density were measured. To minimize the effect of skeletal size, bone mineral apparent density (BMAD; g/cm3) was calculated. RESULTS: The mean height was below one standard deviation from reference values in patients on dialysis and in those with renal transplant. After correction for age, baseline and follow-up BMAD did not differ significantly between patients after transplantation and those with chronic kidney disease. The increase of BMAD between two measurements (mean period 16.0 +/- 4.4 months) was not significantly higher in patients with kidney transplant compared to those with chronic kidney disease. The significant predictors of BMAD were PTH in patients with chronic kidney disease and duration of steroid therapy in patients with renal transplant. CONCLUSIONS: The results showed that bone density in children and adolescents, even several years after kidney transplantation, did not significantly change over time comparing to patients with chronic kidney disease. Hyperparathyroidism and steroid therapy were the most important risk factors for the slow increase of bone density.

Does mycophenolate mofetil increase the incidence of cytomegalovirus disease compared with azathioprine after cadaveric kidney transplantation?

Although most of the published papers had not found increase in the incidence of CMV disease in kidney transplant recipients treated with mycophenolate mofetil (MMF), we had feeling from everyday practice that after its introduction number of patients with CMV disease has increased. To test this hypothesis, we performed retrospective analysis of our database, comparing the incidence of CMV disease in patients treated with azathioprine (AZA) and patients treated with MMF. CMV disease was defined as CMV antigenemia (positive CMV pp65 determined by ELISA test) plus any of the following: decrease leucocytes or platelets, increased transaminases, increase in serum creatinine. The azathioprine treated group (AZA group) included 280 patients (132 female) treated for 17,672 months with AZA + Cyclosporine A (CyA) + steroid, or AZA + steroid, while the MMF group included 219 patients (112 female) treated for 5079 months with MMF + CyA + steroid, or MMF + steroid. There was no difference in acute rejection episodes between the AZA and the MMF group. The AZA group had 51 CMV disease episodes (1 episode per 346.5 treatment months), and the MMF group experienced 43 episodes (1 per 118.1 months) (P < .01). Mean onset of CMV disease was 32.65 +/- 47.69 (SD) months after transplantation in the AZA group, and 3.72 +/- 4.43 in the MMF group. There was no difference between two treatment groups regarding the donor-recipient CMV status mismatch. Despite having the increased incidence of CMV disease, MMF group had less severe disease compared to AZA group with decrease in leukocyte count in 11.6% vs 15.7% of episodes, decrease in platelet count in 20.9% vs 21.6%, elevation of transaminases in 18.6% vs 29.4% respectively, and finally increase in serum creatinine greater than 20% in 51.2% in MMF vs 74.5% in AZA group. Five patients from the AZA group experienced CMV pneumonitis with the mortality rate of 80%. Only one patient from the MMF group had CMV pneumonitis, and he survived. According to our results, patients treated with MMF have increased risk for development of CMV disease. However, the disease course is less severe, and less frequently accompanied with deterioration of renal function in comparison to the AZA group.

Interleukin-6, transforming growth factor-beta 1, and bone markers after kidney transplantation.

The aim of this study was to investigate the relationship between interleukin 6 (IL-6), transforming growth factor (TGF)-beta 1, IL-6 soluble receptors, and biochemical parameters of bone turnover after kidney transplantation. Of 64 patients enrolled in the study, 19 received the kidney transplant 2 to 12 months before the study, and 45 within the previous 15 to 175 months. We measured IL-6, TGF-beta 1, intact parathyroid hormone (PTH) bone alkaline phosphatase (BALP), osteocalcin (OC), and procollagen type I propeptide (P1CP) concentrations in the serum, and deoxypyridinoline crosslinks (DPD) in the urine of the patients. In 16 patients in the first posttransplantation year, the concentrations of IL-6 (P = 0.02), TGF-beta 1 (P = 0.01), BALP (P = 0.0002), OC (P = 0.001), and DPD (P = 0.01) were significantly higher than in patients with longer posttranslation period. Statistically significant negative correlation was found between post-transplantation time and IL-6 (P = 0.04), BALP (P = 0.003), OC (P = 0.0009), P1CP (P = 0.03), and DPD (P = 0.01) concentrations. Repeated measurements of the investigated parameters in the first post-transplantation year showed a significant decrease only in TGF-beta I level. In all patients, IL-6 correlated positively with PTH (P = 0.0009) and DPD (P = 0.03), and IL-6 soluble receptor (IL-6 sR) with DPD (P = 0.03). A decrease in IL-6 and TGF-beta 1 concentrations that paralleled the decrease in bone turnover markers in the posttransplantation period indicated that IL-6 and TGF-beta 1 were probably involved in the bone turnover after kidney transplantation.

Platelet serotonin concentration in dialysis patients with somatic symptoms of depression.

Platelet serotonin (5-HT) concentration was measured in 65 male and 45 female chronic renal patients on hemodialysis (HD) with different somatic symptoms of depression (crying spells, irritability, sleep disturbance, fatigability, loss of appetite, weight loss, somatic preoccupation and loss of libido), to find out the relationship between the severity of symptoms and platelet 5-HT concentration. Male and female patients had significantly lower platelet 5-HT concentration than 62 male and 38 female healthy subjects. Gender-differences in platelet 5-HT values observed in healthy subjects were not found in patients. Platelet 5-HT concentration differed in the groups of patients with the different scores of particular somatic symptoms (loss of appetite and loss of libido), but was similar in patients with other somatic symptoms. There was no relationship between platelet 5-HT concentration and the severity of somatic symptoms, or between platelet 5-HT concentration and age of the patients. Gender-related differences in the occurrence of somatic symptoms were detected in patients with the different degrees of weight loss, somatic preoccupation and loss of libido. Our results suggest that platelet 5-HT concentration could not be used as a biological marker for the severity of somatic symptoms in chronic renal patients on HD.

Assessment of difference between calculated and measured blood hydrogen carbonate concentration by anion gap.

Differences between calculated and measured hydrogen carbonate concentrations can pose a serious problem not only in monitoring severely ill patients, but also in those on hemodialysis. The purpose of this study was to investigate the possibility of estimation of differences between the calculated and measured hydrogen carbonate concentration by anion gap. The study included patients from regular hemodialysis program, and from Departments of Surgery, of Neurology and of Internal Medicine. Our results showed a 16% difference between measured and calculated hydrogen carbonate. Anion gap is a very useful parameter in assessing electrolyte disturbances. The discrepancy between the measured and calculated hydrogen carbonate concentration also increased with the rise in anion gap. Our results showed the possibility to determine the level of concentration difference by anion gap. This could be useful in situations such as metabolic acidosis, characterised by striking changes in electrolyte concentrations.

Biochemical parameters of bone turnover in kidney transplant recipients.

Impairment of bone remodelling due to chronic renal failure persists even after successful kidney transplantation. Bone turnover was assessed in 22 kidney transplant recipients by measurement of serum bone markers: total (tALP) and bone alkaline phosphatase (bALP), osteocalcin (OC), procollagen I C-terminal propeptide (PICP), collagen I C-terminal telopeptide (ICTP), and iPTH. The patients were on dialysis 56.6 +/- 43.1 months before transplantation (mean +/- SD) and 34.2 +/- 23.0 months had elapsed after transplantation. The bone markers were within the reference range in 23% of patients for iPTH, 73% for tALP and 82% for bALP, 41% for OC, 73% for PICP and 50% for ICTP. A positive correlation was found between dialysis duration and ICTP, and iPTH and bone formation markers (OC, bALP). The obtained results indicate that bone turnover was increased after kidney transplantation, with prevailing bone resorption, which seems to be influenced by dialysis duration.

Evolution of renal replacement therapy in Central and Eastern Europe 7 years after political and economical liberation. Central and Eastern Europe Advisory Board in Chronic Renal Failure.

PURPOSE OF THE STUDY: The conditions of renal replacement therapy (RRT) were very poor in the countries located in Central and Eastern Europe (CEE) when they were members of the so-called 'socialist bloc'. The aim of the present analysis was to document the impact of the socioeconomic changes on dialysis therapy in the CEE countries. DESIGN: This was a special survey with the participation of 12 CEE countries, with data obtained through national registries (with the exception of Russia). RESULTS: During the period 1990-1996 the number of haemodialysis units increased by 56% and the number of centres performing peritoneal dialysis by 296%. The number of patients increased respectively by 78% (haemodialysis) and 306% (peritoneal dialysis). The percentage of patients with diabetic nephropathy and elderly patients rose dramatically during this period. One of the main reasons of such expansion was the rapid development of peritoneal dialysis programmes in the majority of the CEE countries. The introduction of modern haemodialysis machines and a wider choice of different dialysers and concentrates permitted individualization of dialysis procedures. These points and the wider use of erythropoietin had a positive influence on quality of life and treatment outcome. There was also a notable increase in the number of transplant centres, but less so of the number of transplanted patients. CONCLUSION: Renal replacement therapy experienced a major expansion in the CEE countries. Despite the progress achieved, the level of RRT is not yet completely satisfactory in most CEE countries.

Treatment of end-stage renal disease in central and eastern Europe: overview of current status and future needs.

The situation of end-stage renal disease (ESRD) patients in central and eastern Europe was very poor for many years during the so called socialistic era. Economical and political liberation resulted in the significant growth of renal replacement facilities in this region. The number of hemodialysis units increased significantly (56%) during the period 1990-1996, and the number of patients treated with this modality has risen by 75%. More dramatic progress was achieved in peritoneal dialysis. The number of units performing this method of renal replacement therapy (RRT) increased by 277% and the number of patients by more than 300%. Not only quantitative but also qualitative changes were observed. More modern hemodialysis machines installed in the vast majority of units allow for the performance of bicarbonate dialysis, controlled ultrafiltration, and sodium profile modeling. Also, a wider choice of biocompatible dialyzers has become available during the last few years. The number of centers performing renal transplantation has increased significantly, but the number of renal transplants has not followed this progress. Despite all the progress, further development of all RRT methods is necessary to achieve acceptance rates comparable to those observed in developed countries.

Aluminium in water for preparation of dialysate and in serum of dialysed patients.

The aim of this study was to develop and verify the electrothermal atomic absorption method for aluminium determination in human serum and correlate the concentration of aluminium in serum of patients on dialysis and in water for preparation of dialysate. Two centres were included: centre A with accidentally enhanced concentration of aluminium in water for preparation of dialysate and centre B with very low water aluminium. Aluminium level in serum of healthy people was also analysed. The results showed that the analytical method was reproducible and sufficiently accurate in determining serum and water aluminium. Normal values obtained for aluminium in the sera of healthy people ranged from 0.9 to 12 micrograms/L and were significantly lower than all values obtained from the dialysis centre A. The aluminium concentration in serum of dialysed patients displayed linear correlation to aluminium concentration in water used for preparation of dialysate.

Bioequivalence of two oral cyclosporine preparations.

A comparison of bioequivalence of two cyclosporine (CAS 59865-13-3) preparations was performed. Ten cyclosporine treated patients with transplanted kidneys were included. Criteria were successful transplantation and minimum period from transplantation of at least 6 months. Two months before the experiment, cyclosporine concentrations had to be in therapeutic range without significant oscillation, and kidney function stabile. There had to be no signs of cyclosporine nephrotoxicity. During the objective biochemical analysis it was not allowed to find malfunction in any of the patient's organ important for cyclosporine pharmacokinetics. Cyclosporine concentrations in whole blood were measured with a specific fluoroimmunoassay. Cyclosporine and metabolites concentrations were measured with radioimmunoassay with non-specific antibody. Mean value and standard deviations and shape of distribution were calculated for all numeric data of patients, measured biochemical and other laboratory parameters. Variance analysis for all measured cyclosporine concentrations according to sampling times (C0 to C12, maximal concentrations C(M), time to maximal concentrations t(M), times of absorption delaying t(Lag) and area under the measured concentration curves (AUC) were statistically checked. According to these data it is concluded that the preparations are bioequivalent; a time to reach maximum concentration was slightly shorter for test preparation (2.5 and 3.2 h, respectively), but not statistically significant. There are no significant differences between the areas under the concentration curves (1667 and 1665 ng.h/ml, respectively). After the calculation of pharmacokinetic parameters of concentration data measured by a non-specific method a significant difference for areas under concentration curves was seen (3709 and 4600 ng.h/ml, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

The role of plasma exchange in the treatment of severe forms of hemolytic-uremic syndrome in childhood.

Therapeutic plasma exchange (PE) or plasma-pheresis has been used in recent years in the treatment of severe hemolytic uremic syndrome (HUS) in children. We analyzed the benefit of PE and peritoneal dialysis (PD) in 9 children, 6 boys and 3 girls, aged 1-10 years, from 1983-1993. All children came from different geographical regions, and all had the sporadic form of the illness. Three patients had the gastrointestinal form, 5 had respiratory prodromes while 1 child developed HUS during the course of varicella. Seven children were hypertensive, but only in 3 was hypertension persistent. The child with varicella had a transient complement decrease. Five children were treated with PE. In 4 children, fresh frozen plasma (FFP) was used as replacement fluid, and human albumin was used in 1 child. Four children were treated with PD and infusions of FFP. Rapid recovery of renal function was observed in 5 patients whereas in 2 oliguric children the recovery of renal function ensued within 1 and 2 months, respectively. Two children developed terminal renal failure (TRF) (in 1 child the treatment was very delayed, and in other child HUS developed following varicella). Only 1 boy had relapses of the disease followed by impairment of renal function from which he gradually recovered. During the 3-10 year follow-up period, only the child with relapses was hypertensive while the others had normal clinical and laboratory parameters. We suggest that PE plays an important role in the early treatment of severe forms of HUS in children.

[Long-term follow-up of related kidney donors after nephrectomy]. / Visegodisnje pracenje srodnih davatelja nakon donorske nefrektomije.

From 1973 to July 1990, 183 kidney transplantations were performed at the Transplantation Unit of the Department of Urology--Faculty of Medicine--University of Zagreb. Out of these, 57 were from the living related donors. The research included 50 (88%) living related donors (28 mothers, 12 fathers, 5 brothers and 5 sisters) followed up from 1 to 15 years after donor nephrectomy. The donors' health conditions were evaluated by clinical-laboratory examinations (biochemical tests, renal function tests, urinoculture, ultrasound, isotopic renal studies, arterial blood pressure). In 48 (96%) neither morphological nor functional changes of the urinary system were found. A certain number of donors requested a transfer to less physically strenuous jobs. Except for the grafts functioning well in the recipients, the results also showed that the quality of donors' lives remained unchanged.

[The nail-patella syndrome]. / Nail-patella sindrom.

The nail-patella syndrome (synonym of onychoosteodysplasia) is considered to be an autosomal dominant hereditary disease affecting numerous tissues of ectodermal and mesodermal origin. The changes are mostly found on nails, patellae, eyes and joints. The symptoms of nephropathy are present in 30% to 40% of patients, and renal insufficiency with typical signs of the syndrome in 25% of patients. This report describes a female patient with renal insufficiency on chronic hemodialysis treatment, in whom diagnosis of the nail-patella syndrome has been made at 36 years of age. The incidence of the syndrome has been noted in 11 members of the patient's family, but without clinical signs of nephropathy.

[Immunologic and clinical definition of the rejection reaction in kidney transplantation]. / Imunolosko i klinicko definiranje reakcija odbacivanja transplantiranog bubrega.

In the evaluation of the immunological state of a kidney transplant there is no reliable diagnostic test. Therefore, several various tests should always be applied. The aim of this study was to define the type of immunological reaction (cellular or humoral) that causes the rejection of transplanted kidney. A group of 45 patients with a kidney transplant were tested 175 times, in various phases of the kidney transplant, starting on the day of transplantation up to several months posttransplant. Specific antibodies (SA) and specific cytotoxic lymphocytes (SCL) directed against donor cells in lymphocyte-mediated cytolysis tests in the presence of antibodies (ADLMC) or without them (LMC) were determined. LMC was significantly correlated with acute rejection (85%). In the phase of clinical quiscence of the kidney transplant LMC was positive in 4% of the cases. During the period of chronic rejection it was positive in 75% of the cases. ADLMC test is significantly correlated with chronic rejection (88%). In the period of acute rejection it was positive in 27% while in clinical quiscence in 11% of the cases. Twenty-two patients with non-immunological disorders of the kidney transplant were tested 62 times. LMC test was always negative, while ADLMC test was positive in 6.4% of the cases. These tests prove to be good parameters for defining immunological reaction. Thus, they can be of great importance in determining adequate immunosuppressive therapy. Negative results of tests in non-immunological disorders of graft function are highly significant.

[Mycetismus in children--report of an epidemic of poisoning]. / Micetizam u djece--u povodu jedne epidemije otrovanja.

In the autumn of 1988 an outbreak of mushroom poisoning occurred in the surroundings of Zagreb. In less than 3 week period about 140 cases of poisoning were recorded, 17 of whom were children treated at the Department of Pediatrics. Nine children developed gastrointestinal and 18 phalloid syndrome. In the differential diagnosis of each gastroenterocolitis, mushroom poisoning should be taken into consideration, especially during warm and wet summer and autumn. The detection and identification of the poison is the main principle in diagnostics and medical treatment of each poisoning, thus of mushroom poisoning. Incriminated mushroom was identified in 21 of 27 patients (77.8%). Timely application of general therapeutic procedures, especially thorough gastric lavage in each patient, and application of plasmapheresis in case of Amanita phalloides poisoning have been found effective in reducing lethality and in rapid clinical recovery. Of the total number of 18 Amanita phalloides poisoned children, 4 died which is a lethality rate of 22%. In health education it should be pointed out that there are no simple methods for distinguishing edible mushrooms from poisonous ones.

[Use of recombinant erythropoietin on secondary anemia in patients in the terminal phase of renal insufficiency on hemodialysis]. / Znacenje primjene rekombiniranog eritropoetina na sekundarnu anemiju kod bolesnika u terminalnoj fazi bubrezne insuficijencije na hemodijalizi.

A group of 6 patients with a history of end-stage renal insufficiency on hemodialysis was receiving erythropoietin (EPO) in a dosage of 50 IU/kg body weight i. v. The hemogram values were followed regularly every week and the patients underwent other laboratory evaluations every month. At the beginning of the study, the number of erythrocytes amounted to 2.2 +/- 0.3 x 10(12)/l. After 4 weeks it was 2.3 +/- 0.4 (NS) (p = 0.001), after 8 weeks 2.8 +/- 0.4 (p = 0.007), and after 12 weeks 3.2 +/- 0.3. At the beginning, hemoglobin was 70 +/- 8 g/l, after 4 weeks 76.3 +/- 13.7 (NS), after 8 weeks 95.7 +/- 14.3 (p = 0.008), and after 12 weeks 102.2 +/- 12 (p = 0.001). The hematocrit value rose from 21.4 +/- 3.4 at the beginning of the study to 32.1 +/- 3.6 (p = 0.001) after 12 weeks. The trial showed no significant effect of EPO on serum potassium which amounted to 5.3 +/- 0.4 mmol/l at the beginning of the trial and 5.6 +/- 0.8 (NS) after 12 weeks; the rate of the rise of platelets from 132.8 +/- 2.4 x 10(9)/l to 155.2 +/- 42.2 was not significant either. The results demonstrate a marked improvement in the red blood cells of patients receiving EPO in the end-stage of renal insufficiency and its influence on their general condition. One female patient was excluded from the study participation because of a severe bone pain.