Growth of children following the initiation of dialysis: a comparison of three dialysis modalities

Maintenance dialysis usually serves as an interim treatment for children with end-stage renal disease (ESRD) until transplantation can take place. Some children, however, may require dialytic support for an extended period of time. Although dialysis improves some of the problems associated with growth failure in ESRD (acidosis, uremia, calcium, and phosphorus imbalance), many children continue to grow poorly. Therefore, three different dialysis modalities, continuous ambulatory peritoneal dialysis (CAPD), cycler/intermittent peritoneal dialysis (CPD), and hemodialysis (HD), were evaluated with regard to their effects on the growth of children initiating dialysis and remaining on that modality for 6–12 months. Growth was best for children undergoing CAPD when compared with the other two modalities with regard to the following growth parameters: incremental height standard deviation score for chronological age [–0.55±2.06 vs. –1.69±1.22 for CPD (P<0.05) and –1.80±1.13 for HD (P<0.05)]; incremental height standard deviation score for bone age [–1.68±1.71 vs. –2.45±1.43 for CPD (P=NS) and –2.03±1.28 for HD (P=NS)]; change in height standard deviation score during the dialysis period [0.00±0.67 vs. –0.15±.29 for CPD (P=NS) and –0.23±.23 for HD (P=NS)]. The reasons why growth appears to be best in children receiving CAPD may be related to its metabolic benefits: lower levels of uremia, as reflected by the blood urea nitrogen [50±12 vs. 69±16 mg/dl for CPD (P<0.5) and 89±17 for HD (P<0.05)], improved metabolic acidosis, as indicated by a higher serum bicarbonate concentration [24±2 mEq/l vs. 22±2 for CPD (P<0.05) and 21±2 for HD (P<0.05)]. In addition, children undergoing CAPD receive significant supplemental calories from the glucose absorbed during dialysis. CAPD, and possibly, other types of prolonged-dwell daily peritoneal dialysis appear to be most beneficial for growth, which may be of particular importance for the smaller child undergoing dialysis while awaiting transplantation.     

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.     

Beneficial in vitro effect of N-acetyl-cysteine on oxidative stress and apoptosis

Chronic renal failure (CRF) is usually accompanied by abnormalities of both humoral and cellular immune response. The aim of the study was to investigate the influence of N-acetyl-cysteine (NAC) on intracellular oxidative stress and apoptosis rate of T lymphocytes in children with CRF. Twenty-two children (aged 4–16, mean 7.4) with CRF treated with dialysis were enrolled in the study. Intracellular reactive oxygen species (ROS) production was quantified by mean rhodamine 123 (RHO) fluorescence intensity with flow cytometry. Annexin V FITC was used for identifying apoptotic cells. Mean fluorescence intensity (MFI), which reflected intracellular oxidative stress in T lymphocytes, was increased in patients with CRF compared with the controls (CD3+: 31.58±11.58 vs 22.55±4.97, p =0.043; CD3+CD4+: 32.50±8.59 vs 27.75±12.76, NS; CD3+CD8+: 32.10±11.85 vs 20.77±4.89, p =0.012). Apoptotic T lymphocytes occurred more frequently in patients with CRF treated with hemodialysis (HD) (11.36±6.96%) than in the controls (6.14%±3.36%; p =0.025). After 24 h incubation with NAC MFI and apoptosis rate decreased significantly in all subpopulations of lymphocytes. NAC, as a strong antioxidant, has a favorable effect on intracellular oxidative stress and apoptosis rate of T lymphocytes in patients with CRF. A decreased apoptosis rate may have positive effect on functional abnormalities of T cells already found in patients with CRF.     

Does long-term treatment of renal anaemia with recombinant erythropoietin influence oxidative stress in haemodialysed patients?

Background. Patients with end-stage renal failure undergoing haemodialysis (HD) are exposed to oxidative stress. Increased levels of malondialdehyde (MDA) were demonstrated in plasma of uraemic patients, indicating accelerated lipid peroxidation (LPO) as a consequence of multiple pathogenetic factors. The aim of our investigation was to examine the role of renal anaemia in oxidative stress in HD patients. Methods. MDA and 4-hydroxynonenal (HNE) were measured in three groups of patients undergoing HD: group I comprised eight patients with a blood haemoglobin (Hb) <10 g/dl (mean Hb=8.1±1.3 g/dl), and group II were eight patients with a Hb <10 g/dl (mean Hb=12.4±1.9 g/dl); none of these 16 patients had been treated with human recombinant erythropoietin (rHuEpo). Group III comprised 27 patients with a mean Hb of 10.5±1.6 g/dl after long-term rHuEpo treatment. Results. Mean plasma concentrations of both MDA and HNE were significantly higher (P<0.0001) in all 43 HD patients than in 20 healthy controls (MDA 2.85±0.25 vs 0.37± &mgr;M, HNE 0.32± vs 0.10±0.01 &mgr;M). Comprising the three groups, it was shown that HD patients with a Hb <10 g/dl had significantly higher plasma levels of LPO products (MDA 3.81±0.86 &mgr;M, HNE 0.45±0.07 &mgr;M) than HD patients with a Hb > 10 g/dl (MDA 2.77±0.58 &mgr;M, HNE 0.25±0.05 &mgr;M), and than HD patients treated with rHuEpo (MDA 2.50±0.12 &mgr;M, HNE 0.29±0.03 &mgr;M). Furthermore, an inverse correlation between plasma concentration of LPO products and haemoglobin levels was seen (r=0.62, P<0.0001). Conclusion. Radical generation in HD patients might be caused in part by renal anemia itself. Treatment with rHuEpo may decrease radical generation effectively in HD patients due to the increase in the number of red blood cells and blood haemoglobin concentration. Keywords: erythropoietin; haemodialysis; HNE; lipid peroxidation; MDA; renal anaemia      

Mortality trends in pediatric patients with chronic renal failure

Mortality trends were analyzed in 441 children and adolescents with chronic renal failure (CRF) observed over a 24-year period before and after institution of renal replacement therapy (RRT). A total of 93 patients died. Overall mortality rate (MR) per 100 patient years decreased from 6.6 in 1969–1978 to 2.5 in 1979–1988 and increased slightly to 2.9 in 1989–1992. The fall involved all four modes of treatment: conservative hemodialysis (HD), continuous peritoneal dialysis (CPD), and transplantation (TX). From 1979–1988 to 1989–1992 MR on conservative and on dialysis treatment changed only slightly and was similar on HD and CPD. An alarming rise in MR was noted after TX in 1989–1992, mainly due to malignant tumors. In 44 patients who died on conservative treatment, the reasons for non-acceptance for RRT were analyzed: in 22 multi-morbidity was the main reason, usually because of a congenital neurological disorder. Some patients died from advanced uremia or unexpected events after the decision to institute RRT. Our experience demonstrates a persistent mortality in pediatric patients with CRF, which in recent years is primarily ascribed to congenital multi-morbid conditions which make RRT unfeasible, infections on dialysis treatment, and malignancies after TX.     

Growth hormone for children with chronic renal failure and on dialysis

We studied all children with CRF who received recombinant human growth hormone (rhGH) for more than a year (mean±SD duration of therapy 3.7±2.5 years) over an 11-year period. There were 32 children. Twenty-one children were conservatively managed, with a mean glomerular filtration rate (GFR) of 24±12 mL min^–1/1.73 m² at the start of rhGH. Their height standard deviation score improved from –2.5±1.4 to –2.1±0.7 at 1 year (P=0.3), –2.0±0.7 at 2 years (P=0.01), and –1.6±0.6 at 3 years (P=0.001). After that there was no improvement. Eleven children were on dialysis, six on haemodialysis (HD) and five on peritoneal (PD). Ht SDS improved from –2.7±0.5 to –2.3±0.5 at 1 year (P=0.02). Thereafter there was no further improvement. RhGH was stopped because of transplantation in 29 patients at a mean±SD age of 12.1±4.0 years. Mean Ht SDS was –1.8±0.8 at transplant and there was no change over the following 5 years. In conclusion, treatment with rhGH resulted in improvement in Ht SDS in conservatively managed CRF for up to 3.0 years and for 1 year in children on dialysis. Discontinuation of rhGH after transplantation resulted in little change in Ht SDS.     

Low-density lipoprotein subfraction profiles in chronic renal failure

Background: Small low-density lipoprotein (LDL) particle size, a newly recognized risk factor for cardiovascular disease in the general population, is frequently associated with hypertriglyceridaemia, the predominant plasma lipid abnormality present in uraemia. Methods: Plasma lipids and LDL subfraction profiles were examined in 33 non-dialysed patients with chronic renal failure (predial), 40 patients on continuous ambulatory peritoneal dialysis (CAPD), 42 haemodialysis patients (HD), 47 renal transplant recipients (RTR), and 44 controls. LDL subfractions separated by gel electrophoresis were scored by densitometric analysis (higher scores indicate profiles comprising smaller particles). Results: All groups with renal failure had significantly elevated (mean±SD) LDL scores (predial 1.36±0.6, CAPD 1.71±0.9, HD 1.68±0.9, RTR 1.92±0.8 vs control 0.87±0.4, all P<0.001), this being the only lipid abnormality detected in the predialysis patients. In CAPD and HD patients, LDL scores were associated with serum triglyceride (r=0.81, P<0.0001 and r=0.70, P<0.01 respectively), cholesterol (r=0.55, P<0.001 and r=0.49, P<0.01) and HDL-cholesterol (r=-0.43, P<0.01 and r=-0.51, P<0.01), whilst no such relationship was seen in the predialysis and RTR groups, suggesting that other factors were important. Conclusions: The presence of small LDL particles appears to be an early and unexplained feature of the uraemic dyslipidaemia. This abnormality persists after renal transplantation and may represent an important atherogenic risk factor. Key words: LD subfractions; renal failure; transplants      

Long-term renal follow-up of extremely low birth weight infants

There is evidence that low birth weight caused by intrauterine growth retardation adversely affects normal renal development. Very little information on this issue is available on children born very prematurely. This investigation examined clinical and functional renal parameters in 40 children (23 boys, 17 girls) ranging in age between 6.1 and 12.4 years and weighing less than 1000 g at birth. Results were compared to those obtained in 43 healthy children of similar age and gender. Study subjects were significantly smaller and thinner than control subjects (mean height SDS: –0.36 vs. +0.70; and mean BMI SDS: –0.56 vs. +1.18). Systolic, diastolic, and mean blood pressures did not differ from those of controls. Renal sonography revealed no abnormality, and mean percentiles for renal length and volume appeared normal. In comparison with controls, plasma creatinine concentration (0.62±0.1 vs. 0.53±0.1 mg/dl) and estimated creatinine clearance (117±17 vs. 131±17 ml min^–1 1.73 m^–2) differed significantly. No significant differences were observed in microalbuminuria values, but five study subjects (12.5%) presented values above the upper limit of normality. A defect in tubular phosphate transport was also evident: TmP/GFR (3.6±0.4 vs. 4.2±0.8 mg/dl) and TRP (83±5% vs. 90±4%) were significantly lower, and urinary P excretion, estimated by the ratio UP/UCr, was significantly higher (1.2±0.4 vs. 0.9±0.4 mg/mg) than controls. Urinary calcium excretion, estimated by the UCa/UCr ratio, was also significantly higher (0.15±0.07 vs. 0.12±0.09 mg/mg). These data clearly demonstrate that both GFR and tubular phosphate transport are significantly diminished in school-age children born with extreme prematurity, probably as a consequence of impaired postnatal nephrogenesis.     

Continuous Ambulatory Peritoneal Dialysis (CAPD) Adequacy Influences Serum Free Carnitine Level

Objective: An evaluation of serum free carnitine level in CAPD patients in relation to dietary intake, nutritional status and CAPD adequacy and duration. Study design: Food diaries, nutritional (total body mass, lean body mass, serum level of proteins, carnitine, cholesterol) and adequacy (Kt/V, PCR, tCcr, EN) parameters were obtained in 23 CAPD patients. Results: Normal carnitine level (41.8±6.7 µmol/l) was found in 17 patients being on CAPD through 11.1±9.6 months, whereas in 6 persons treated with CAPD through 9.7±4.1 months carnitine level was 25.4±5.7 µmol/l. Significant differences between low and normal carnitine groups were in tCcr (82.7±16.7 v. 65.9±13.2 l/wk/1.73 m² BSA), effluent volume (10.9±0.8 v. 9.9±1.5 l/day), effluent glucose concentration (729=167 v. 530±220 mg/dl) and serum globulin level (22.6±6.4 v. 29.3±4.4 g/l). Significant correlation coefficients (for n=23) were found between serum carnitine level and effluent volume (r=–0.509) or plasma globulin level (r=+0.522). Conclusion: Patients with higher CAPD adequacy show lower serum free carnitine levels and this is related to higher effluent volumes.     

Cyclosporin A therapy for severe Henoch-Schönlein nephritis with nephrotic syndrome

To evaluate the efficacy of cyclosporin A (CyA) for treating severe Henoch-Schönlein nephritis (HSN), seven patients with nephrotic syndrome, aged 3.9–13.8 years (mean 6.5 years), were analyzed retrospectively. Mean follow-up times were 5.5 years (range 2–9 years). All underwent renal biopsy before treatment, and follow-up renal biopsy was performed in six of the seven patients. All patients improved, with 24-h protein declining from a mean of 9.2 g/m²/day (range 1.5–16 g/m²/day) to 0.3 g/m²/day (range 0.03–1.2 g/m²/day) (p=0.016) and serum albumin increasing from a mean of 2.1 g/dl (range 1.5–2.4 g/dl) to 4.6 g/dl (range 3.5–5.3 g/dl) (p=0.016) after CyA therapy. The activity index decreased significantly at the second renal biopsies obtained at a mean interval of 11.7 months after the first (6.4±3.3 vs 3.5±1.2, p=0.042, respectively), while the chronicity index and the tubulointerstitial scores did not change. On the immunofluorescent findings at the second biopsies, the degree of deposits of immunoglobulins such as IgA, IgM, C3, and fibrinogen decreased in five of the six patients. Although this case series is without controls, our study suggests that CyA may be beneficial to a subset of HSN patients with nephrotic syndrome.     

Endothelin-1 in children with chronic renal failure

Endothelin-1 (ET-1) was meansured after extraction from plasma of normal adults (5.9±1.9 pg/ml,n=22), normal children (7.1±1.86 pg/ml,n=29), nonhaemodialysed children with chronic renal failure (CRF) (11.1±1.8 pg/ml),n=10), renal graft recipients (9.5±3.4 pg/ml,n=37), haemodialysed children 24 h after a haemodialysis session (20.02±10.9 pg/ml,n=26) and haemodialysed children before and after a haemodialysis session (15.31±10.6 and 13.8±8.5 respectively,n=14). A sensitive and specific radioimmunoassay was used. ET-1 was significantly higher in non-haemodialysed CRF children and in renal graft recipients than in normal children (P<0.001 andP<0.01, respectively) and significantly higher in haemodialysed children when compared with normal children, non-haemodialysed CRF children and renal graft recipients (P<0.001). ET-1 concentrations were similar in normal children and normal adults. ET-1 was inversely correlated with glomerular filtration rate in non-haemodialysed CRF children (r=–0.39,P<0.01) and positively correlated with extracellular volume in haemodialysed children (r=0.435,P<0.03). After haemodialysis, ET-1 increased in 6 and decreased in 8 of the 14 children studied before and after a haemodialysis session.     

The effect of growth hormone on the growth failure of chronic renal failure

To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX,n=40), GH-treated nephrectomized rats (NX+GH,n=18), sham-operated rats fed ad libitum (SHAMAL,n=27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF,n=10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean±SEM) 49±3 and 54±4 mg/dl, respectively, compared with 16±4 and 19±0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0±3.3 g) and length (3.5±0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2±4.0 g,P<-0.0001 and 4.1±0.2 cm,P<-0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2±5.0 g) and length (3.4±0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81±2 mg/dl versus 55±3 mg/dl in SHAMAL (P0.0001), was not increased in the NX+GH group, 87±3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities.     

Aberrant activation of the TNF-alpha system and production of Fas and scavenger receptors on monocytes in patients with end-stage renal disease

Ten patients with nondialyzed chronic renal failure (CRF), 14 receiving continuous ambulatory peritoneal dialysis (CAPD), 16 receiving hemodialysis (HD), and 10 normal controls (NC), were evaluated. Levels of Fas antigen (CD95), scavenger receptors (CD36 and CD68), and tumor necrosis factor-receptor 2 (CD120b) on monocytes were measured using flow cytometry. All patients showed lymphocytopenia, and monocyte counts were decreased in those with CRF. Fas levels were higher in patients receiving HD than the others, and were higher in the CRF and CAPD groups than in controls. CD120b levels were similar to those of Fas. Monocyte CD36 levels in the dialysis groups were significantly higher than in the CRF and NC groups. CD68 was also significantly elevated in HD patients. Fas levels were positively correlated with those of CD120b and CD68. The patient groups showed higher levels of apoptotic markers and scavenger receptors, combined with activation of the TNF-alpha system, especially in patients receiving HD.     

Intestinal bacteria-derived putrefactants in chronic renal failure

Background. Phenols and indoles are fermentation products and putrefactants of intestinal bacterial origin. They present a problem in chronic renal failure and hemodialysis patients because they accumulate in the body as uremic toxins. Methods. A comparative study was performed in groups of patients with chronic renal failure (CRF) before the initiation of dialysis, hemodialysis patients (HD), and healthy adults to investigate changes in intestinal flora and to measure the blood levels of uremic toxins. Results. The level of Escherichia coli was significantly increased in the CRF and HD groups compared with the healthy controls (P= 0.02, controls vs CRF before dialysis; P= 0.0014, controls vs HD). Fecal concentrations of phenol and scatole were most highly elevated in the HD group, and the difference between the CRF and HD groups was significant (P= 0.02 for phenol; P= 0.01 for scatole). Serum concentrations of phenol, p-cresol, and indican were significantly elevated in the CRF group (P= 0.01; P= 0.008; and P < 0.0001 vs controls, respectively). For indican, a correlation was found between fecal and serum concentrations only in the HD group (correlation coefficient of 0.821; P= 0.04). In the CRF group, a correlation was obtained between the urine and serum concentrations of phenol and p-cresol (0.852, P= 0.01; 0.758, P= 0.02, respectively). A correlation was also found between the serum concentrations of indican and serum creatinine (SCr) (0.610; P= 0.004) and β2-microglobulin (β2-MG) (0.739; P= 0.005). Conclusions. An abnormal balance of intestinal bacterial flora and increased intestinal bacteria-derived putrefactants were observed in the CRF group. The increased concentration of toxins with renal sclerosing effects, such as indican, may contribute to further deterioration of renal function. Received: September 14, 2001 / Accepted: February 13, 2002     

Pediatric acute renal failure: outcome by modality and disease

Two hundred and twenty-six children who underwent renal replacement therapy (RRT) from 1992 to 1998 were retrospectively reviewed. The mean age, at the onset of RRT, was 74±11.7 months and weight was 25.3±9.7 kg. RRT therapies included hemofiltration (HF; n=106 children for an average of 8.7±2.3 days), hemodialysis (HD; n=61 children for an average of 9.5±1.7 days), and peritoneal dialysis (PD; n=59 children for an average of 9.6±2.1 days). Factors influencing patient survival included: (1) low blood pressure (BP) at onset of RRT (33% survival with low BP, vs 61% with normal BP, vs 100% with high BP; P<0.05), (2) use of pressors anytime during RRT (35% survival in those on pressors vs 89% survival in those not requiring pressors; P<0.01), (3) diagnosis (primary renal failure with a high likelihood of survival vs secondary renal failure; P<0.05), (4) RRT modality (40% survival with HF, vs 49% survival with PD, vs 81% survival with HD; P<0.01 HD vs PD or HF), and (5) pressor use was significantly higher in children on HF (74%) vs HD (33%) or PD (81%; P<0.05 HD vs HF or PD). In conclusion, pressor use has the greatest prediction of survival, rather than RRT modality. Patient survival in children with the need for RRT for ARF is similar to in adults and, as in adults, is best predicted by the underlying diagnosis and hemodynamic stability. Received: 15 February 2001 / Revised: 5 June 2001 / Accepted: 8 August 2001     

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.     

Differential effects of recombinant human growth hormone on glomerular filtration rate and renal plasma flow in chronic renal failure

In normal subjects recombinant human growth hormone (rhGH) increases glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) through the action of insulin-like growth factor-I (IGF-I). We have measured clearance of inulin and para-aminohippuric acid in 18 children with chronic renal failure (CRF) during their 1st year of rhGH treatment to look at the immediate (first 3 h), short-term (1 week) and long-term (1 year) effects of treatment. On day 1 mean (range) age was 9.1 (4.9–13.9) years, GFR 19 (9–58) and ERPF 77 (34–271) ml/min per 1.73 m². During treatment height velocity increased from 4.5 (1.7–6.5) to 9.5 (4.8–12.7) cm/year (P<0.0001). Two children required dialysis after 0.75 years and 1 child was electively transplanted after 0.5 years. There were no other serious adverse events. GFR and ERPF were unchanged in the 3 h following rhGH. GFR remained constant on day 8, 22 (6–56) and after 1 year, 20 (9–59) ml/min per 1.73 m². ERPF increased to 96 (33–276) ml/min per 1.73 m² on day 8P=0.005), and remained elevated, but not significantly so, at 99 (24–428) ml/min per 1.73 m² at 1 year. Fasting IGF-I increased from 147 (46–315) ng/ml to 291 (61–673) by day 8P<0.003), and to 341 (101–786) ng/ml at 1 year. There was no correlation between the change in IGF-I and renal function. Blood pressure, albumin excretion and dietary protein intake were unchanged by treatment. The significance of increased ERPF after 1 week of rhGH in CRF is unclear, but long-term follow-up of renal function is indicated.     

Paraoxonase, anti-oxidant response and oxidative stress in children with chronic renal failure

Increased oxidative stress is believed to contribute to an increased risk of cardiovascular disease in uraemia. In children with chronic renal failure (CRF), an anti-oxidant enzyme, paraoxonase (PON), that inhibits oxidation of LDL-cholesterol, has not been previously investigated. In this study we aimed to investigate PON activity, total anti-oxidant response (TAR), total peroxide (TPX), oxidative stress index (OSI) and some pro-oxidant cytokines in 29 children with CRF [mean age 10.2±3.5 years; 19 pre-dialysis, ten on continuous ambulatory peritoneal dialysis (CAPD)] and in 25 control subjects. Children with CRF had lower PON and TAR and higher TPX and OSI values than did controls (P<0.05). Except for lower TAR and serum albumin levels of the CAPD subgroup (P<0.05), other parameters were similar in non-dialysis and CAPD patients (P>0.05). Patients had significant positive correlation between TAR and serum albumin (P<0.05). Serum urea had significant positive correlation with TPX and OSI (P<0.05). Increased oxidative stress and decreased anti-oxidants measured by serum PON activity and TAR were found in children with CRF. We can hypothesize, on the basis of statistical correlations, that low levels of serum albumin and high levels of uraemic metabolites might be responsible for increased oxidative stress in children with CRF. Further studies with larger sample sizes are needed to verify these results.     

Glutathione peroxidase activity in patients with renal disorders

Background Glutathione peroxidase (GPx) protects cells from oxidative damage by catalyzing the reduction of both organic and hydrogen peroxides, using glutathione as a reducing agent. Both plasma GPx (P-GPx) and erythrocyte GPx (E-GPx) have been identified in human blood. Kidney proximal tubular cells are the main source of GPx activity in the plasma. Oxidative damage has been reported to participate in the progression and complications of renal diseases.Methods The activities of both E-GPx and P-GPx were determined, using Randox commercial kits, in 12 patients with nephrotic syndrome (NS), 48 patients with renal impairment (RI), and 50 patients with chronic renal failure on maintenance hemodialysis (HD; before as well as immediately after dialysis), and in 50 healthy volunteers who served as controls.Results Compared to the results in healthy controls, P-GPx activity was reduced in the HD group and the RI group, whereas the NS group showed no significant difference from the control. The HD group showed a higher drop in P-GPx (reduced to 36.6% of the mean control value) than the RI group (reduced to 61.8% of the mean control value). Further analysis of the RI group showed a highly significant negative correlation between P-GPx activity and serum creatinine level (r = −0.691; P < 0.001). Also, a highly significant negative correlation was found between P-GPx and blood urea nitrogen (r = −0.792; P < 0.001). However, E-GPx activity showed no significant correlation with either serum creatinine or blood urea nitrogen.E-GPx was reduced to 55.2% and 68.9% of the mean control 1 value in the NS group and the RI group respectively, while the HD group showed no significant change. Further analysis of the RI group found that E-GPx activity showed no significant correlation with either serum creatinine or blood urea nitrogen. In HD patients, GPx activity was measured before and immediately after hemodialysis. E-GPx activity was similar before and after dialysis, without a significant difference (pre-dialysis, 37.7 ± 13.5 U/g hemoglobin [Hb]; post-dialysis, 38.72 ± 12.31 U/g Hb). However, P-GPx activity was significantly increased (pre-dialysis, 254.4 ± 62.6 U/ml; post-dialysis, 296.98 ± 74.04 U/ml; P < 0.001), but it was still significantly lower when compared to that in the healthy controls.Conclusions P-GPx activity is an important test to assess the oxidative damage in patients with kidney diseases. The progression of renal disorders is accompanied by a decrease in P-GPx activity, but not by a decrease in E-GPx activity. Thus, we conclude that P-GPx activity largely depends on physiological renal function, whereas E-GPx activity does not.