Connective tissue metabolism in children with chronic renal failure

To assess the characteristics of connective tissue metabolism in chronic renal failure (CRF), urinary excretion of glycosaminoglycan (GAG) fractions and hydroxyproline (HYP) was determined in ten patients with CRF and in ten age-matched healthy children. CRF was found to be associated with elevated free HYP (19.9±6.1 vs 9.8±3.6 mol/day,P<0.05) and depressed peptide HYP excretion (33.1±13.5 vs 225.2±17.7 mol/day,P<0.01), a low rate of total GAG excretion (7.0±2.4 vs 16.1±1.9 mol uronic acid/day,P<0.05) with low chondroitin 4 — sulphate + chondroitin 6 — sulphate (Ch-Ss) (14.0±9.9 vs 65.0±22.1%) and a high proportion of non-sulphated or under-sulphated fractions, i.e. hyaluronic acid + chondroitin + heparan sulphate (HA+Ch+HS) (75.3±11.4 vs 31.5±5.7%). Urinary 3-methyl-histidine (3-met-HIS) excretion and plasma essential free amino acids did not differ in the two groups. In response to haemodialysis no consistent change occurred in urinary excretion of 3-met-HIS, peptide-bound HYP, total GAG or percentage distribution of individual GAG fractions. After haemodialysis all plasma amino acids decreased significantly, and there was a significant increase in urinary excretion of free HYP (P<0.05). We conclude that the alterations in urinary excretion of total and individual GAGs observed in CRF may reflect disturbed connective tissue metabolism which does not appear to be accounted for by protein malnutrition or enhanced protein breakdown and remains uninfluenced by haemodialysis therapy.     

Etiology of chronic renal failure in Turkish children

The etiology of chronic renal failure (CRF) was studied in 459 Turkish children (205 girls, 254 boys) for the period January 1979-December 1993. Their mean age at onset of CRF was 9.5±4.2 years (range 1–16 years); CRF was defined as a glomerular filtration rate (GFR) below 50 ml/min per 1.73 m² for at least 6 months. When a GFR determination was not available, the serum creatinine concentration was used: greater than 1 mg/dl for children aged 1–3 years, greater than 1.5 mg/dl for those 3–10 years and greater than 2 mg/dl for those 10–16 years. Primary renal disorders were as follows: reflux nephropathy 32.4% glomerular diseases 22.2%, hereditary renal disorders 11.4%, amyloidosis 10.6%, urinary stones 8% and other renal disorders 15.4%. Twenty-three cases of reflux nephropathy (15.4%) were associated with neural tube defects (NTD) and 20 (13.4%) were caused by infravesical obstruction. CRF caused vesicoureteral reflux associated with NTD and amyloidosis are more frequent in our series compared with west European and Nordic countries.     

Psychiatric disorders in children with chronic renal failure

Psychiatric assessment was done according to the DSM-IV TR criteria in 19 children with predialysis chronic renal failure (CRF) and 19 children with end-stage renal disease on regular hemodialysis. The prevalence rate of psychiatric disorders in all the studied patients was 52.6%. Adjustment disorders were the most common disorders (18.4%), followed by depression (10.3%) and neurocognitive disorders (7.7%). Anxiety and elimination disorders were reported in 5.1 and 2.6%, respectively. The disorders were more prevalent (P=0.05) in dialysis (68.4%) than in predialysis patients (36.8%). The presence of psychiatric disorders was not significantly correlated with sex, severity of anemia, duration of CRF or the efficiency or the duration of hemodialysis. In conclusion, psychiatric disorders were prevalent in our patients, especially in those on hemodialysis. Both adjustments with depression and depressive disorders were the most common psychiatric disorders. This array of disorders was more likely explained by the difficulties encountered in living with CRF rather than by demographic or physical factors.     

Growth in young children with chronic renal failure

Statural growth and its relation to growth potential, renal function, blood urea nitrogen (BUN), mineral metabolism hormones and dietary intake were studied in 17 prepubertal children (aged 1.6–9.3 years) on conservative treatment for chronic renal failure due to tubulo-interstitial nephropathy. Statural growth (height SDS) was related to the degree of renal failure, was more retarded than ossification, and was independent of the chronological age of the patients. We observed that the lower the glomerular filtration rate (GRF), the lower was the growth potential (increased bone age/statural age ratio). Growth velocity may be normal regardless of statural and bone maturation delay and the degree of renal insufficiency. Impaired growth rate correlated with parathyroid hormone levels, caloric intake and increased blood urea nitrogen during the year of observation. These data show that comprehensive monitoring and suitable treatment must be performed in order to prevent growth retardation at any GFR level.     

Evaluation of aortic stiffness in children with chronic renal failure

The measurement of aortic stiffness (As) [aortic strain (S), pressure strain elastic modulus (Ep) and pressure strain normalized by diastolic pressure (Ep*)] is suggested as an excellent marker of subclinical arterial sclerosis. We aimed to investigate the presence of As and to determine the relationship between As and some risk factors in children with chronic renal failure (CRF). Twenty-six pre-dialysis (PreD) [female/male (F/M) 7/19] patients and 23 chronic peritoneal dialysis (CPD) (F/M 13/10) patients were assessed. Twenty-nine healthy children were selected as a control group (F/M 14/15). We determined anemia, abnormal calcium/phosphate metabolism, hypertension, diastolic dysfunction, increased left ventricular mass (LVM), hypertriglyceridemia, increased stiffness (Ep, Ep*), and decreased strain (S) in the CRF (PreD and CPD) group compared with the controls (P < 0.05). Presence of renal disease, LVM and usage of angiotensin-converting enzyme inhibitor (ACE-I) in all groups; female gender, duration of disease and the usage of anti-hypertensive drug therapy in CRF patients; and LVM and LVM index in healthy children were found to be independent predictors for aortic stiffness and/or strain. In conclusion, CRF is associated with significant arterial functional abnormalities in uremic children and not controlled by dialysis treatment. These results suggest that, even in young children, uremia has a profound impact on arterial function.     

Low-dose subcutaneous recombinant erythropoietin in children with chronic renal failure

In a multicentre trial, low-dose subcutaneous recombinant human erythropoietin (r-Hu EPO) was evaluated in 22 children aged 4 months to 16 years with anaemia of chronic renal failure over a 12-month period. A starting dosage of 50 U/kg twice weekly was given until a target haemoglobin of 9–11 g/dl was achieved. The dosage was increased by 50 U/kg per week, each 4 weeks, if the haemoglobin did not increase by 1 g/dl per month. When the target haemoglobin was achieved, the same weeekly dosage was given as a single injection. After 10 weeks, the mean haemoglobin increased from 6.7±0.7 to 9.6±1.9 g/dl (P<0.001) and the haematocrit from 19.8%±2.4% to 29.3%±6.3% (P<0.001). By 4 months the target haemoglobin was achieved in 19 patients on 50 U/kg twice weekly and 1 patient on 75 U/kg twice weekly. Two children with severe renal osteodystrophy failed to respond to 95 U/kg and 150 U/kg twice weekly. The maintenance weekly dose of r-Hu EPO in 9 children over 4–12 months ranged between 45 and 125 U/kg. The Wechsler intelligence score increased in 11 children from 92±16 to 97±17 over the 12-month period (P=0.007). No adverse effects were recorded. A starting dose of r-Hu EPO of 50 U/kg subcutaneously twice weekly is recommended as effective and safe for the majority of children with anaemia of chronic renal failure.     

Effect of enteral feeding on lipid subfractions in children with chronic renal failure

The anorexia of chronic renal failure (CRF) is frequently managed with enteral feeds using combinations of commercial preparations, glucose polymers and fat emulsions. Such feeds might predispose to atherogenic blood lipid profiles. Our aim, therefore, was to compare the blood lipid profiles of enterally fed and non-enterally fed children. Plasma lipid subfractions were measured in 37 children with CRF managed conservatively and 10 managed with peritoneal dialysis (PD); 10 of the children were tube fed, 5 of whom were on PD. Results were compared between these groups. Overall, triglycerides (TGs, mean ± SD) were high (2.3±1.4 mmol/l) and total cholesterol (TC) was at the upper limit of normal (5.2±1.5 mmol/l). Low-density lipoprotein (LDL), high-density lipoprotein (HDL), apoprotein A1 (apo A1), A2 (apo A2) and B (apo B), and lipoprotein (a) [Lp(a)] were within the normal range. There was an inverse correlation between TGs and glomerular filtration rate (P = 0.0001). There were no differences in the levels of TC, TG, LDL, HDL, apo A1, apo A2 or Lp(a) between tube-fed and non-tube-fed children. We conclude that enteral feeding does not enhance hyperlipidaemia. Received August 19, 1997; received in revised form December 19, 1997; accepted January 2, 1998     

Nutritional management of children with chronic renal failure

Current information on the adaptations to progressive loss of renal function is presented. The assessment of renal function in infants and children using serum creatinine concentration and its derivatives is considered as are various methods for assessment of growth. Children with creatinine clearances less than 50% of normal, who do not have uremic symptoms (and who are not on dialysis), should be ingesting diets providing close to 100% of the RDA for calories with 8% of the calories as protein. Recommendations for nutritional management of children on chronic peritoneal dialysis are also presented.     

Spiroergometric performance of children and adolescents with chronic renal failure

Maximal physical performance (Wmax), maximal oxygen consumption ( O₂max), maximal carbon dioxide production ( CO₂max) and blood lactate (L) levels were measured in 34 paediatric patients with chronic renal failure (CRF) and 25 controls by spiroergometric testing on a bicycle ergometer. No patient was treated with erythropoietin. The workload was increased step-wise by 0.5 W/3 min up to a Wmax determined from the attainment of O₂max. In patients on conservative treatment (CT), on haemodialysis (HD) and after transplantation (TP) median Wmax per kilogram body weight was reduced to 76%, 73% and 73% of controls (C), respectively. In CT and HD patients O₂max and CO₂max were decreased to an even higher extent. The ventilatory anaerobic threshold, calculated from the levelling off of the respiratory equivalent E/ O₂) during increasing workload, was only slightly higher in patients than in C when related to Wmax (NS). The physiological rise in L during exercise was blunted in CRF; 72% of patients on CT or HD did not exceed the expected threshold L level of 4 mmol/l; after TP the L changes normalized. The findings indicate that most children and adolescents with CRF are able to attain maximal physical performance but both the aerobic and the anaerobic capacity are often reduced. Preliminary findings indicate that treatment of renal anaemia with erythropoietin is able to considerably improve Wmax and O₂max in paediatric HD patients.     

Neurologic development of children with severe chronic renal failure from infancy

A literature review was conducted to summarize current understanding of the effects of severe chronic renal failure (CRF), when present from infancy, on neurologic development. Data were obtained from the results of 95 examinations performed in 85 patients, most of whom had been studied after 12 months of age, or following initiation of maintenance dialysis or successful transplantation. CRF was diagnosed at birth or during the neonatal period in 71.7% of these patients; serum creatinine concentrations or calculated clearances were 2.0 mg/dl (177 mol/l) or <15 ml/min per 1.73 m², respectively, in 75.8%. Head circumferences were >2 standard deviations below the mean for age in 33 of 51 (64.7%) patients. Developmental delay was identified in 63.2% of all cases, and in 29 of 48 (60.4%), 16 of 19 (84.2%), and 4 of 13 (30.7%) patients studied while receiving conservative management or maintenance dialysis, or following successful transplantation, respectively. Moderate to severe delays were commoner for gross motor and language development. No significant relationships could be identified between age or severity of CRF at diagnosis and either the prevalence or severity of developmental delay. Other factors that may have contributed to observed developmental delays are also discussed, including aluminum loading, hyperparathyroidism, undernutrition, and psychosocial problems. New data are presented and discussed, and recommendations for future studies provided.     

Homocysteine and left ventricular hypertrophy in children with chronic renal failure

Hyperhomocysteinemia is recognized as an independent risk factor for cardiovascular disease, especially atherosclerosis, in adult patients with chronic renal failure (CRF). However, there is little information about the relationship between plasma homocysteine levels and left ventricular hypertrophy. The aim of this study was to determine plasma homocysteine levels and risk factors for left ventricular hypertrophy and to investigate the relationship between plasma homocysteine concentration and left ventricular mass index (LVMI) in children with CRF. The homocysteine level was measured by high-performance liquid chromatography and LVMI was calculated using echocardiographic findings in 27 children with CRF and 16 healthy controls. The mean LVMI and mean plasma homocysteine concentration in the CRF group, especially in patients with end-stage renal disease, were statistically higher than the control group (P<0.05). There was no correlation between LVMI and plasma homocysteine concentration. There was a positive correlation between plasma homocysteine concentration and serum creatinine level. There was a positive correlation of LVMI with creatinine and blood pressures (systolic, diastolic, and mean arterial pressure). There was a negative correlation of LVMI with hemoglobin level in multiple linear regression analysis. In our view homocysteine does not have a direct effect on left ventricular structure and left ventricular hypertrophy is the end organ damage associated with hypertension, anemia, and CRF. More prospective studies are needed to better clarify the inter-relationships of plasma homocysteine level and left ventricular structure in children with CRF.     

Pubertal growth in children with chronic renal failure on conservative treatment

The pubertal growth spurt was followed for at least 3 years in 5 boys and 6 girls with chronic renal failure on conservative treatment. The peak height velocity averaged 8.6 cm/year (range 5.8–10.1 cm/year) in males and 8.2 cm/year (range 6.4–11.5 cm/year) in females. In none was the pubertal growth spurt below the 3rd percentile for chronological age. At the end of the follow-up period, all patients but 2 had stature within the normal limits of parental target. The relative variation of height averaged —0.013 standard deviation scores per year. On the whole, the pubertal growth spurt was normal in subjects with chronic renal failure on conservative treatment.     

Expression of scavenger receptor CD36 in chronic renal failure patients

BACKGROUND: Patients with chronic renal failure (CRF) are at increased risk of atherosclerosis development. One of the major steps in pathogenesis of atherosclerosis is formation of foam cells. Scavenger receptor CD36 is among the major receptors for oxidized low density lipoproteins (oxLDL) and therefore it plays a crucial role in foam cell formation. The aim of the present study was to investigate the expression of CD36 on blood monocytes of CRF patients. METHODS: Expression of CD36 on blood monocytes of CRF patients treated with hemodialysis (HD), peritoneal dialysis (PD), those not yet on dialysis (predialysis), and controls was assessed with the use of flow cytometry. Additionally, the major lipid peroxidation markers, malondialdehyde (MDA) and 4-hydroxyalkenals (HAE), were measured. Further, impact of treatment with HMG-CoA reductase inhibitors (statins) on CD36 expression in CRF patients was evaluated. RESULTS: Expression of monocyte CD36, measured as mean fluorescence intensity (MFI) was significantly higher in HD and PD patients, when compared to controls without renal insufficiency (respectively: 1011 +/- 288 and 1000 +/- 309 vs. 710 +/- 313; P < 0.01 for both groups). This was not the case in predialysis group (828 +/- 363 vs. 710 +/- 313). Higher concentrations of lipid peroxidation indicators, MDA and HAE were observed in all three subgroups of CRF patients (2.1 +/- 0.51, 2.02 +/- 0.27, and 1.81 +/- 0.53 microm in HD, PD, and predialysis group, respectively, vs. 1.13 +/- 0.59 microm in controls; P < 0.01). Patients treated with statins showed significantly lower CD36 expression than patients without statin therapy. CONCLUSIONS: The present study, for the first time, demonstrates increased expression of CD36 scavenger receptor in CRF patients. This may be a possible risk factor for accelerated atherogenesis observed in this group of patients.     

Progression of chronic renal failure in children with dysplastic kidneys

The aim of this study is to describe progression of chronic renal failure (CRF) in children with renal malformations and to study factors influencing this progression. We reviewed retrospectively 176 children with CRF secondary to renal dysplasia, reflux nephropathy or renal obstruction with at least 5 years of follow-up. Serum creatinine was recorded at least every third month, and an estimated glomerular filtration rate (eGFR) was calculated. Number of febrile urinary tract infections (UTI), blood pressure, albuminuria (UaUc), and number of functioning kidneys was also recorded. We found that the development of renal function could be separated into three time periods: (1) During the first years of life, 82% of the children showed early improvement of their kidney function, which lasted until a median age of 3.2 years (median improvement 6.3 ml/year). (2) From the age of 3.2 years until 11.4 years, 52.5% of the studied children showed a stable kidney function, whereas in 47.5%, kidney function immediately started to deteriorate. (3) Around puberty, 42.9% started deterioration in kidney function, whereas 57.1% even after puberty showed a stable function. Patients with UaUc >200 mg/mmol deteriorated faster (−6.5 ml/min per 1.73 m² per year compared with −1.5 ml/min per 1.73 m² per year) in those with UaUc <50 mg/mmol. Children with more than two febrile UTIs, hypertension or an eGFR at onset of less than 40 ml/min per 1.73 m² deteriorated faster than the others. Most children experienced early improvement of kidney function. The further prognosis, early or late deterioration of kidney function or stable function during the whole follow-up, was related to albuminuria, number of febrile UTIs, eGFR at onset of deterioration, hypertension and puberty.     

Nutritional status of children with moderate chronic renal failure

Nutritional status was evaluated in 15 children (11 males) with moderate chronic renal failure (CRF). Two 3-day prospective dietary records, anthropometric measures and biochemical determinations were performed 3 months apart. Energy, protein, carbohydrate, fat, polyunsaturated, monounsaturated and saturated fatty acid intakes, expressed as percentages of international recommendations, were 87±14, 223±42, 73±12, 110±27, 55±31, 129±51 and 111±26%, respectively. The relative distribution of calories was 15±2% from proteins, 48±5% from carbohydrates and 37±5% from lipids. Anthropometric indices, expressed as standard deviation score, were: weight –0.50±0.8, height –0.94±1.3, growth velocity –0.61±1.8, triceps skinfold thickness –0.30±0.6, subscapular skinfold thickness –0.19±0.8, mid-arm muscle circumference 0.38±0.3 and body mass index –0.22±1.0. Serum concentrations of albumin, total protein, transferrin, IgG, IgA, IgM, C3 and C4 and blood lymphocyte counts were within normal limits. The mean serum insulin-like growth factor-I concentration, expressed as standard deviation score, as 0.74±1.5. No anthropometric or biochemical signs of malnutrition were found in children with moderate CRF. However, their dietary intake of calories and carbohydrates was low and the protein and saturated fatty acid intake excessively high.     

Children with chronic renal failure in Sweden 1978–1985

A survey of chronic renal failure (CRF) in Swedish children was carried out for the period 1978–1985, using age-related cut-off levels for creatinine concentrations corresponding approximately to a glomerular filtration rate of 30 ml/min per 1.73 m². The mean annual incidence of CRF was 6.9 and of terminal renal failure (TRF) 4.4/million children. The prevalence increased during the study period, for preterminal renal failure from 14.1 (1978) to 26.1 (1985) and for TRF from 12.4 to 16/million children. The main groups of primary renal disease were malformations (42%), hereditary disorders (27%), and glomerular diseases (14%), while pyelonephritis with vesico-ureteral reflux only made up 5%.     

Renal function in predialysis children with chronic renal failure treated with erythropoietin

To assess the effect of long-term administration of human recombinant erythropoietin (EPO) on renal function, 11 anemic children aged 1.4 – 17.2 years were followed for 10 – 61 (mean 31) months on treatment. During EPO therapy the mean hemoglobin rose from 8.1 to 11.1 g/dl at the last observation. The final maintenance dose ranged between 70 and 300 U/kg per week. The rate of deterioration of renal function was calculated by comparing the slope of the regression lines of reciprocal serum creatinine values (SCr) derived from a mean of 20 values per patient obtained over 8 – 50 (mean 29) months before and a mean of 24 SCR values during EPO therapy. The individual slopes improved after initiation of EPO therapy in all but 3 patients, but the mean change of slope (from –0.0521 to –0.0299) was not significant. The study suggests that in most children with predialysis chronic renal failure long-term administration of EPO is not associated with accelerated deterioration but rather with delayed deterioration of renal function. Received August 30, 1995; received in revised form November 16, 1995; accepted April 10, 1996     

Psychosocial adaptation of children and adolescents with chronic renal failure

In a multicentre study comprising five paediatric nephrology centres in Western Germany, psychosocial and educational parameters were assessed (during 1987) in 479 children and adolescents with chronic renal failure (CRF) in order to gain insight into their psychosocial adaptation to the disease. At the time of assessment, 31% of patients were on conservative treatment, 14% on haemodialysis, 9% on continuous ambulatory peritoneal dialysis and 46% had a functioning transplant. The mean age at assessment was 13.6 years. Additional disabilities were noted in 29% of patients. School attendance of the 233 children of school age was in general satisfactory; 22% of patients attended schools for disabled or handicapped children. Vocational training was frequently inadequate, especially for dialysed patients, and only 14 of 53 adolescents over 16 years had graduated. Of 49 adult patients, only 21 were in some form of employment. A lack of age-appropriate independence was observed in a large proportion (86%) of patients over 17 years, who continued to live with their parents or other persons taking care of them, whilst only 14% were living alone or with a partner. We conclude that, despite improved survival, psychosocial adaptation continues to be impaired in paediatric patients with CRF, especially in adolescents and those on dialysis.