Krystyna Szprynger

Skeletal Status in Children, Adolescents and Young Adults with End-Stage Renal Failure Treated with Hemo- or Peritoneal Dialysis

Abstract: The skeletal status in 30 children, adolescents and young adults (18 females, 12 males) with end-stage renal failure (ESRF) aged 9-23 years (mean 15.8 ± 3.6 years) was evaluated using measurements of bone mineral density (BMD, g/cm2) at the spine and total body (TB) (Lunar DPX-L, USA), quantitative ultrasound (QUS) of the hand phalanges (DBM Sonic 1200, IGEA, Italy) and laboratory investigations (parathyroid hormone, serum total and ionized calcium, serum phosphate). Eleven subjects were treated with hemodialysis and 19 with peritoneal dialysis. The mean value of the amplitude-dependent speed of sound (Ad-SoS, m/s) measured by QUS was significantly decreased in comparison with the value obtained in a group of 686 age-matched controls (1942 ± 74 m/s vs 2050 ± 77 m/s, p<0.0001). BMD measurements were also decreased in comparison with mean values for the healthy population (Z-scores for spine −1.47, and for TB −1.53). Duration of dialysis correlated significantly with spine-BMD, TB-BMD and Ad-SoS (r=−0.37, r = −0.45, r=−0.55, respectively, p<0.05), while duration of ESRF did not have such an influence. Laboratory investigations did not correlate with skeletal parameters. Ad-SoS correlated significantly with spine-BMD (r= 0.45, p<0.05) and TB-BMD (r= 0.56, p<0.01). Both QUS and BMD values correlated significantly with Tanner stages (r ranged from 0.59 to 0.69, p<0.001) and did not increase with age except for correlation between age and TB-BMD. In conclusion, skeletal status in the population studied is strongly affected by ESRF. Both QUS and BMD measurements show an ability to express skeletal changes in a similar manner, though the QUS parameter seems to be more sensitive at revealing changes due to renal failure.

Serum VCAM-1, ICAM-1, and L-selectin levels in children and young adults with chronic renal failure.

Children and young adults with chronic renal failure (CRF) present with an impaired immune response. Our aim was to analyze whether leukocyte migration, determined by adhesion molecules, is disturbed in the course of CRF, hemodialysis (HD), and peritoneal dialysis (PD). Soluble (s) VCAM-1, ICAM-1, and L-selectin serum levels were evaluated by ELISA in 15 patients with CRF, 22 patients on cuprophane membrane HD, 24 patients on PD, and in 15 controls. The sVCAM-1 levels in all groups were significantly elevated compared with controls. The levels in HD patients were higher than in CRF patients (P <0.05), while levels in PD patients were higher than in CRF and HD (P <0.001 and P <0.01, respectively). The sICAM-1 concentrations in CRF and PD patients were significantly elevated compared with controls (P <0.001 and P <0.0001, respectively); in PD patients sICAM-1 levels were higher than in HD patients (P <0.001), but there were no differences between other groups. sL-selectin levels were decreased in all groups compared with controls. The levels in HD patients were the lowest and the differences, compared with CRF and PD patients, were significant (P <0.05 and P <0.01, respectively). Children and young adults with CRF and on maintenance dialysis have altered concentrations of soluble adhesion molecules, resulting from either inadequate clearance or disturbed synthesis and release. The differences in sVCAM-1 levels between CRF and both groups of patients on dialysis, as well as the differences in sL-selectin concentrations between HD and CRF patients, indicate that these disturbances are aggravated by maintenance dialysis, particularly HD.

Skeletal status in adolescents with end-stage renal failure: a longitudinal study

In a longitudinal study, bone status was assessed in adolescents and young adults aged 15.3±3.4 years at the onset of the study with end-stage renal failure (ESRF). The group consisted of 18 subjects (11 females and seven males), of whom nine patients were on hemodialysis and nine patients on peritoneal dialysis. Six patients were previous or current glucocorticoid (GCS) users. Renal failure was recognized before 6.1±4.1 years, and dialysis was performed for 3.0±2.0 years. Follow-up took placed 8.6±0.8 and 21.7±2.5 months later, and the following data were collected: bone mineral density (BMD) at the spine (s-BMD) and total body (TB-BMD) using DPX-L (Lunar, USA); quantitative ultrasound by DBM 1200 (IGEA, Italy) at the hand phalanges (Amplitude-dependent Speed of Sound, Ad-SoS), serum concentration of i-PTH, total calcium, ionized calcium and phosphate. Tanner stages were also evaluated. The mean values of BMD measurements and Ad-SoS were stable during a period of observation, and a mean Z-score for TB-BMD was significantly lower at the third versus baseline value (−1.87±1.75 versus −1.49±1.53, P<0.05). Z-scores for s-BMD and Ad-SoS decreased non-significantly. Changes in s-BMD and TB-BMD Z-scores were influenced by changes in body size and changes in biochemical parameters, and a change in Ad-SoS Z-score was not dependent on these factors. The values of second (P<0.05) and third (P<0.01) s-BMD Z-score were significantly lower in GCS treated subjects, and longitudinal change in spine Z-score was greater in GCS treated patients versus others (P<0.05). Duration of ESRF, duration and type of dialysis and gender did not influence skeletal variables. Skeletal measurements correlated significantly with Tanner stages (besides the correlation with Ad-SoS in the first measurement, r ranged from 0.5 to 0.72, P<0.05), and changes in Tanner stages observed over a period of observation did not correlate with changes in skeletal variables. Among laboratory variables, the following non-significant tendencies to change were observed: serum concentration of i-PTH and phosphate increased, and total and ionized calcium decreased. In conclusion, adolescent subjects with ESRF treated with dialysis showed stable mean values of skeletal measurements, and these were expressed as Z-scores, a tendency to drop was observed. The lack of an increase observed in normal healthy subjects of the same age, and low values in Z-scores, indicates that skeletal status is seriously affected in subjects with ESRF.

Serum Concentration of IL-2, IL-6, TNF-Alpha and Their Soluble Receptors in Children on Maintenance Hemodialysis

In chronic renal failure patients a state of immunodeficiency paradoxically coexists with the activation of immune effector cells, including monocytes and lymphocytes. The activation of these cells leads to the release of cytokines. The aim of this study was to estimate the serum concentrations of IL-2, IL-6, TNF-α and their soluble receptors: IL-2 sRα, IL-6 sR, sTNF RI in children with chronic renal failure and young adults on maintenance hemodialysis (HD). The study included 16 HD patients (11 females, 5 males) aged 11–22 (mean 16.1 ± 3.1) years and a control group of 15 age-matched healthy children. Only the mean concentration of IL-6 was similar in HD patients and the control group. The levels of the other cytokines were significantly higher in patients undergoing HD compared to the healthy subjects. No significant differences were observed between the pre- and post-dialysis values or between the values obtained using various dialyzer membranes. These data suggest that immune cells in HD children are in an activated state and that neither a single dialysis session nor the type of dialyzer membrane has an influence on the cytokines examined.

THE HEAT SHOCK PROTEIN PROFILE IN CHILDREN WITH CHRONIC KIDNEY DISEASE

♦ Objectives: Chronic kidney disease (CKD) due to inflammation, lipid disorders, and endothelial dysfunction predisposes to accelerated atherosclerosis. Elevated levels of heat shock proteins (HSPs) and antibodies against them have been described in adults with atherosclerotic lesions and cardiovascular events. However, there are no investigations of these variables in children with CKD treated conservatively or on peritoneal dialysis. Therefore, we decided to evaluate the profile of HSPs and their potential role as markers of atherosclerosis in these groups of patients. ♦ Methods: The study group consisted of 37 children with CKD treated conservatively and 19 children and young adults on automated peritoneal dialysis (APD). The control group comprised 15 age-matched subjects with normal kidney function. HSP-60, HSP-70, HSP-90alpha, anti-HSP-60, anti-HSP-70, sE-selectin, and interleukin (IL)-4 serum concentrations were assessed by ELISA; high-sensitivity C-reactive protein (hs-CRP) serum levels were assessed by nephelometry. Serum lipid profiles (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides) were also estimated. ♦ Results: HSP-90α, anti-HSP-60, and sE-selectin concentrations in the CKD and APD patients were higher than in the controls and were lower in the predialysis subjects than in the children on dialysis. Median values of anti-HSP-70 were higher in the CKD patients than in the control group. Levels of IL-4 were increased in all patients versus controls. Median values of HSP-60 were decreased in the CKD and APD children versus controls. HSP-70 and hs-CRP concentrations were comparable in all groups. ♦ Conclusions: The altered HSP and anti-HSP concentrations may imply that the response to stress conditions in the course of CKD is disturbed in children; APD does not aggravate that dysfunction in a significant way. Relationships between HSPs, lipid profile, and markers of inflammation suggest a possible role of the selected HSPs as markers of atherosclerosis in children with CKD.

Soluble adhesion molecules in children and young adults on chronic hemodialysis

Children on chronic hemodialysis (HD) present with impaired immunity that may result from disturbances in leukocyte migration, caused by changes in expression of adhesion molecules on endothelium and immunocompetent cells. However, it is still not clear whether the type of dialyzer or a single dialysis session influences the concentrations of soluble adhesion molecules in these patients. We evaluated by ELISA serum levels of soluble (s) VCAM-1, ICAM-1, L-selectin, and P-selectin in 22 patients on cuprophane HD (CU), 8 on polysulfone HD (PS), 10 on vitamin E-modified cellulose HD (VE), and 15 controls. In all HD patients, sVCAM-1 levels were elevated compared with controls and were higher in CU than in VE. The sICAM-1 concentrations were increased in VE compared with controls, but remained unchanged in CU and PS. The sL-selectin levels were reduced in all HD patients. The mean values of sP-selectin were comparable in CU, PS, and controls. The lowest levels were observed in VE. In CU patients, sVCAM-1, sICAM-1, and sP-selectin concentrations rose after HD. A single PS session had no impact on adhesion molecules, whereas a VE session increased the level of sVCAM-1. The type of dialysis membrane may change the profile of adhesion molecule concentrations, thus influencing the immune system of a child on HD. The increase in levels of adhesion molecules in the course of a single HD session, which was pronounced in CU and VE patients, suggests poor biocompatibility of these dialyzers.

Vitamins A, E and C as Non-Enzymatic Antioxidants and Their Relation to Lipid Peroxidation in Children with Chronic Renal Failure

Background: Increased lipid peroxidation (LP) and reduced enzymatic antioxidant defense have been observed in predialysis patients with advanced chronic renal failure (CRF) and in patients on maintenance hemodialysis (HD). To extend these observations, we evaluated the plasma, erythrocyte and dialysate levels of vitamins A and E and the plasma and dialysate levels of vitamin C as exogenous non-enzymatic antioxidants in children with CRF treated conservatively and on HD. The data obtained were related to LP monitored by erythrocyte malonyldialdehyde (E-MDA) and plasma organic hydroperoxide (OHP) concentrations. Patients: Forty-six predialysis children were enrolled in the study and divided into 2 groups: group I = moderate CRF (plasma creatinine <265.3 µmol/l), and group II = plasma creatinine ≧265.3 µmol/l. Group III consisted of 21 HD children. 27 age-matched healthy subjects served as a control group. Results: The plasma levels of vitamin A and vitamin C were significantly reduced in all CRF patients when compared to the controls, with the lowest values observed in children on maintenance HD (group III). Significant differences were also noted between the moderate CRF (group I) and HD (group III). Plasma levels of vitamin E were significantly decreased in moderate CRF (group I) and HD (group III) as compared to controls. In contrast, the erythrocyte vitamin A and vitamin E levels of predialysis children and HD patients were not different from the controls. The E-MDA and OHP concentrations in the 3 groups of CRF children were significantly higher than in healthy subjects. The concentration of plasma vitamin C was significantly inversely correlated with E-MDA, plasma OHP and creatinine in group I. In group II we found a significant correlation of plasma vitamin E levels with creatinine and E-MDA and a correlation of the plasma vitamin C concentration with E-MDA. Conclusion: CRF in children is associated with decreased concentrations of plasma antioxidant vitamins. This reduction is most expressed in children on maintenance HD and particularly concerns plasma vitamin C and erythrocyte vitamin E concentrations. The low levels of plasma vitamin A, E and C might result in reduced activity of the non-enzymatic antioxidant defense system and might be responsible for increased oxidative stress occurring in children with CRF.

Heat shock proteins in children and young adults on chronic hemodialysis

Chronic inflammation, lipid and autoimmune disorders are hallmarks of atherogenesis, and hemodialysis per se may be an additional factor predisposing to accelerated atherosclerosis. Elevated levels of heat shock proteins (HSP) and antibodies against these HSP have been described in adults with atherosclerotic lesions and cardiovascular events, but to date there has been a scarcity of investigations on these parameters in adult and pediatric patients on hemodialysis (HD). We have investigated the HSP profile in hemodialyzed children and the impact of a single HD session on those proteins and their correlations with known risk factors for atherosclerosis. The study group consisted of 17 children and young adults undergoing HD with polysulfone membranes. The control group comprised 15 age-matched subjects with normal kidney function. The serum concentrations of Hsp60, Hsp90alpha, anti-Hsp60, anti-Hsp70, and sE-selectin were assessed by an enzyme-linked immunosorbent assay, and serum concentration of high-sensitivity-C-reactive protein was assayed by nephelometry. The serum lipid profile [total cholesterol (CHOL), high-density lipoprotein-CHOL, low-density lipoprotein-CHOL, triglycerides] was also estimated. Compared to the control values, the median values of Hsp60 before the HD session were lower, whereas those of Hsp90alpha and anti-Hsp60 were higher. A single HD session raised the median values of Hsp60 and Hsp90alpha and decreased the concentrations of anti-Hsp60 and anti-Hsp70. In addition, the concentrations of HSPs and the antibodies against them correlated with the lipid markers both before and after HD. The altered HSP and anti-HSP concentrations in HD children, which correlated with the lipid profile and the endothelial markers, suggest a dysfunctional HSP system in this population and the possibility of HSPs being classified as new markers of atherosclerosis.

The Impact of Dialysis Modality on Serum Heat Shock Proteins in Children and Young Adults with Chronic Kidney Disease

Background/Aims: The acceleration of atherosclerosis by dialysis is not completely understood. The elevated levels of heat shock proteins (HSP) and antibodies against them were described in adults with atherosclerotic lesions, but there are no investigations on them in dialyzed patients. The aim of the studywas to evaluate the serum HSP, their connections with dialysis modality and their possible role as markers of atherosclerosis. Methods: Hsp60, Hsp90-α, anti-Hsp60 and anti-Hsp70 concentrations were assessed by ELISA in 19 children on automated peritoneal dialysis (APD) and 17 patients on hemodialysis (HD). hsCRP, sE-selectin, IL-4, IL-12 and the lipid profile were also estimated. Results: Hsp60 values were lower, whereas Hsp90-α was higher in the dialyzed children than in the controls, without any difference between the dialysis modalities. The anti-Hsp60 concentrations were increased in all patients and higher in HD patients than in APD patients. The anti-Hsp70 levels in the APD children were decreased versus controls. Anti-Hsp60 correlated with HDL-cholesterol in APD children, and with total cholesterol and LDL-cholesterol in HD patients. Anti-Hsp70 correlated with sE-selectin in HD subjects. Conclusions: The levels of antibodies against HSP seem to distinguish between the dialysis modalities and the correlations with the lipid profile and sE-selectin, suggesting their potential role as markers of atherosclerosis.

Percutaneous Endoscopic Gastrostomy as a Method of Nutrition Support in Children With Chronic Kidney Disease

Chronic kidney disease (CKD) exerts a significant impact on childrens growth and development. In infants and children with CKD, feeding-related problems are not infrequent, leading to protein-energy malnutrition and resulting in retarded physical development. Because spontaneous energy intake is usually inadequate in children with CKD, special dietary counseling with supportive procedures are often required. Placement of a percutaneous endoscopic gastrostomy (PEG) tube is one practical way to allow home tube feeding. Such nutrition support is valuable in children with CKD, and although it is not free from complications and technical problems, it seems to be helpful in providing required nutrition intake. In this report, the authors describe their own experience with PEG implantation and use in 3 children with CKD.