Effect of cyclosporin A on glomerular filtration rate in children with minimal change nephrotic syndrome

Cyclosporin A (CyA) is now commonly used in the management of children with steroid-dependent nephrotic syndrome. In order to assess nephrotoxicity related to CyA therapy, we measured glomerular filtration rate (GFR) on 123 occasions in 24 children with minimal change nephrotic syndrome receiving CyA. GFR was estimated from the plasma clearance of⁵¹chromium-EDTA every 3 months during CyA therapy of up to 27 months duration. There was a significant reduction in GFR after 3 months of CyA therapy [118±33 (SD) to 93±24 ml/min per 1.73 m²] but no further fall thereafter, although the reduction in GFR was sustained for the duration of CyA therapy. This reduction in GFR appeared to be reversible upon cessation of CyA, but careful monitoring of renal function is necessary in such patients to prevent the development of longer term nephrotoxic sequelae.     

Frequently relapsing nephrotic syndrome: treatment with mycophenolate mofetil

Long-term treatment with cyclosporin A (CyA) of children with frequently relapsing steroid-sensitive nephrotic syndrome (SSNS) carries the risk of nephrotoxicity. We have analyzed renal function in 23 children with SSNS during CyA therapy. Repeated measurements of glomerular filtration rate (single-shot ⁵¹Cr-EDTA clearance) showed a decline from 131±21 ml/min per 1.73 m² to 116±27 ml/min per 1.73 m² at last follow-up. Similarly, effective renal plasma flow (simultaneous ¹²³I-hippurate clearance) was correlated with duration of CyA treatment, and showed a decline from 980±318 ml/min per 1.73 m² to 724±242 ml/min per 1.73 m². In a pilot study we investigated the effect of mycofenolate mofetil (MMF) in 7 children with a median age of 12.7 years [6 with minimal change nephrotic syndrome (MCNS), 1 with focal segmental glomerulosclerosis (FSGS)] with signs of nephrotoxicity because of long-term CyA therapy. Only 1 patient with SSNS showed a relapse during MMF therapy. In the patient with FSGS, MMF was started in addition to CyA, resulting in complete remission for a follow-up of 28 months. This preliminary study demonstrates that children with MCNS treated with CyA may be successfully converted to MMF without major side effects. In all cases, including FSGS, MMF had a beneficial effect on renal function. These data should be confirmed by a prospective randomized clinical trial.     

Bone histology in steroid-treated children with non-azotemic nephrotic syndrome

Patients with nephrotic syndrome (NS) and normal glomerular filtration rate (GFR) frequently exhibit abnormalities of calcium and vitamin D homeostasis, mainly hypocalcemia and reduced circulating vitamin D metabolites. These abnormalities have been linked to alterations of bone histology in adults with non-azotemic NS, particularly osteomalacia and excessive bone resorption. Whether similar abnormalities of bone histology occur in children and adolescents with NS, particularly in those requiring prolonged treatment with corticosteroids, remains largely unknown. Thus, bone histomorphometry and selected bone-modulating hormones were studied in eight children (aged 2–16 years) with normal GFR (range 85–169 ml/min per 1.73 m²) and NS. All patients received corticosteroids for at least 12 months prior to bone biopsy. At the time of bone biopsy, the urine protein/creatinine ratio was elevated (2.1±3.6), while the average concentrations of parathyroid hormone (36±13 pg/ml), 25-hydroxyvitamin D [25(OH) D] (22±14 ng/ml), and 1,25(OH)₂D (59±22 pg/ml) were normal. Bone histomorphometry displayed focal osteomalacia (OM) and mild increased bone resorption in most patients. The mineralization lag time, an indicator of the degree of osteomalacia, correlated with the time elapsed since the original diagnosis of NS (r=0.93, P<0.0005). Overt hyperparathyroidism was not evident, but increased eroded perimeter and elevated bone formation rate (BFR) were evident in two patients, suggesting high-turnover bone disease. The BFR was inversely correlated with the administered dose of prednisone at the time of biopsy (r=–0.78, P<0.05) and one patient exhibited low bone turnover changes. The growth velocity standard deviation score (SDS) at time of biopsy ranged from –1.6 to 3.2, resulting in a height SDS range of –1.9 to 0.6. The height SDS at time of bone biopsy correlated inversely with the dose of administered glucocorticoid (r=–0.71, P<0.05) and with the duration of the disease (r=–0.7, P=0.05). These data, albeit preliminary, demonstrate that children with NS treated with prolonged corticosteroid therapy exhibit bone histopathological changes without a concomitant impairment in GFR. While the OM appears to be related to the disease process, the alterations of bone formation and the adynamic changes are likely the result of the corticosteroid therapy. The potential consequences of these findings on adult bone mass and ultimate height deserve further studies.     

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.     

Chronic allograft nephropathy and mycophenolate mofetil introduction in paediatric renal recipients

Mycophenolate mofetil (MMF) introduction with concurrent reduction in calcineurin inhibitors has been shown to be beneficial in chronic allograft nephropathy (CAN) in adults. MMF was introduced to 19 children with CAN 26.3±5.8 (range 3.1–82.6) months after transplantation. Patients were followed up for a mean of 13.2±2.9 (range 1.2–51.1) months. The mean initial MMF dose was 660±56 mg/m² per day, increased to 1,042±73 mg/m² per day a year later. Cyclosporin was reduced from 138±10 mg/m² per day at MMF introduction, to 116±15 mg/m² per day at 6 months and 107±24 mg/m² per day at 1 year. Six months prior to MMF introduction GFR deteriorated by –32.7±7.3 ml/min per 1.73m² per year. Six months after the introduction of MMF, GFR improved by +26.2±7.1 ml/min per 1.73m² per year (P <0.001). The introduction of MMF significantly reduced both the graft rejection rate (P=0.01) and systolic blood pressure (P=0.01), without a significant change in antihypertensive treatment. Haematological parameters did not significantly differ before and after MMF introduction. The introduction of MMF in paediatric renal transplant recipients with CAN may cause a significant improvement in GFR in both the short-term and the long-term and may well have a beneficial effect on systolic blood pressure. MMF has the potential to enable CNI-sparing protocols to be adopted.Preliminary results of this study were presented at the 7th Annual Congress of the British Transplantation Society, 2004, Birmingham, UK, and at the 13th Congress of the Internal Pediatric Nephrology Association, 2004, Adelaide, Australia     

Effect of cyclosporin a on proteinuria in patients with Alport's syndrome

Eight patients with Alport's syndrome and massive proteinuria (129±60.57 mg/m² per hour) were treated with cyclosporin A (CyA) for 8 months. The average dose of CyA administered to all patients was 4.21±0.26 mg/kg per day and blood CyA levels of 63.4±4.1 ng/ml were attained. In five patients, proteinuria abated during the 3rd week of treatment. In the remaining three, all of whom had low creatinine clearance (82.0, 46.0 and 43.2 ml/min per 1.73 m² respectively), proteinuria persisted but at levels lower than before treatment: 32.5±15.9 mg/m² per hour versus 183.3±29.7 mg/m² per hour. No permanent decrease in creatinine clearance was observed in any of these patients throughout treatment. In those patients in whom proteinuria abated, it reappeared 2 weeks after discontinuation of CyA treatment. We observed no significant increases in angiotensin II plasma levels in our patients during CyA administration. Although we have shown that CyA will reduce massive proteinuria in patients with Alport's syndrome, we cannot yet recommend its use as a therapeutic measure.     

Optimising nutrition in chronic renal insufficiency—progression of disease

There is a lack of evidence to support the belief that dietary measures are beneficial in slowing the progression of chronic renal insufficiency (CRI). We prospectively monitored nutrient intakes and progression of CRI over a 2-year period in children aged 2–16 years with differing levels of severity of CRI, as part of their ongoing joint medical/dietetic care. Children were grouped following [⁵¹Cr]-labelled EDTA glomerular filtration rate (GFR, ml/min per 1.73 m²) estimations, into normal kidney function [GFR >75, mean 106 (SD 19.5), n =58], providing baseline data only, mild (GFR 51–75, n =25), moderate (GFR 25–50, n =21), and severe (GFR <25, n =19) CRI. Children with CRI were followed for 2 years, with 51 completing the study (19 mild, 19 moderate, 13 severe CRI) and were excluded if they subsequently required dialysis. Regular medical and dietary advice was provided and yearly 3-day semi-quantitative dietary diaries and baseline and 6-monthly measurements of blood pressure and urinary protein/creatinine ratio were obtained. Mean reductions in estimated GFR over 2 years were –9.4, –5.8, and –6.0 ml/min per 1.73 m² for mild, moderate, and severe CRI, respectively. Mean systolic blood pressure standard deviation score (SDS) fell significantly in all groups by 0.7 SDS, whereas there was little change in proteinuria. From reported dietary intakes, median sodium intakes increased (+10 mmol/day) and protein intakes decreased (–0.4 g/kg per day). Median phosphate intakes did not change significantly, whereas calcium intakes fell in all groups, with an overall median of –20% reference nutrient intake (RNI) (F =33.3, P <0.001). Of children with moderate CRI, 65% finished with calcium intakes below 80% RNI, and parathyroid hormone (PTH) concentrations significantly increased in this group (F =6.0, P =0.021). Higher phosphate and sodium intakes were associated with greater deterioration in estimated GFR in children with mild CRI (r ²=0.30, P =0.02; r ²=0.31, P =0.02, respectively). There was no such correlation for protein intake or PTH. This study emphasises the need for a joint medical and dietetic approach and indicates a number of interventions other than protein restriction, which could be commenced early in children with CRI in an attempt to delay progression.     

Effects of repeated courses of daily steroids and of persistent proteinuria on linear growth in children with nephrotic syndrome

The growth-inhibitory effects of courses of daily steroid therapy and of persistent proteinuria were assessed in 125 Indian and African children with nephrotic syndrome (NS) who were followed for an average of 3.9 years (range 0.25–14 years). Among the biopsied patients, 81% of Indians had minimal — change nephropathy and 49% of Africans had membranous nephropathy. The mean height standard deviation score (SDS) in 87 children who had received prednisone for an average of 36 weeks (range 4–250 weeks) was compared with that in 38 patients who had been managed symptomatically. Heights of untreated African children with persistent proteinuria were within the normal range for age, race and sex. The height SDS±SD for 77 Indian children in the prednisonetreated group was –1.06±1.44, which was not significantly different from –0.92±0.96 observed among 6 children in the untreated group (P=0.75). In Africans the height SDS in 10 prednisone-treated children was –1.82±0.81 which was similar to that observed (P=0.74) in 32 untreated patients –1.77±1.61. No significant correlation was found between the duration of prednisone therapy and height SDS for individual children among the 87 treated patients using regression analysis. The findings remained unchanged when children who had received less than 12 weeks of prednisone were excluded, or when comparison were drawn between those treated for less than and longer than 36 weeks. We conclude that courses of daily steroids or persistent proteinuria do not inhibit linear growth in Indian and African children with NS.     

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.     

Effects of growth hormone administration in pediatric renal allograft recipients

The efficacy of recombinant human growth hormone (rGH) was assessed in five pediatric allograft recipients with severe growth retardation despite successful renal transplants. rGH 0.05 mg/kg per dose was given six times weekly by subcutaneous injection to five prepubertal children (mean age 15.2±2.0 years) all of whom had bone ages less than or equal to 12 years (10.0±1.4 years), a height standard deviation score of less than –2.5 (–4.9±1.5), no evidence of catch-up growth, a calculated glomerular filtration rate (GFR) of more than 40ml/min per 1.73 m² (51±6.8 ml/min per 1.73 m²), and stable renal function on alternate-day prednisone (16.7±2.6 mg/m² per dose). Growth hormone profiles were abnormal in all children before treatment. rGH administration led to a significant increase in both growth rate (3.5±1.6 cm/year pre therapy, 8.5±1.4 cm/year post therapy,P<0.001) and percentage of expected growth velocity for bone age (67±31% pre therapy, 163±27% post therapy,P<0.001) with evidence of true catch-up growth. During the study period, three children had the appearance of secondary sexual characteristics, and one had premature advancement of his bone age. GFR decreased in three children, and in one rGH was discontinued due to a steady rise in serum creatinine. No significant changes were seen in serum calcium, phosphorus, cholesterol, triglycerides, glucose, or thyroid function, although a significant increase in alkaline phosphatase was found. In summary, growth-retarded pediatric renal allograft recipients may have abnormal endogenous GH production and respond favorably to rGH. The potential risk of deterioration in renal function due to rGH-induced hyperfiltration must be investigated.     

Vitamin E therapy in IgA nephropathy: a double-blind,placebo-controlled study

IgA nephropathy is the world's most common primary glomerulonephropathy. Recent evidence in a rat model implicated excessive production of oxygen-free radicals in the pathogenesis and suggested that vitamin E-treatment ameliorated progression. We studied this antioxidant therapy on the glomerular filtration rate (GFR), proteinuria and hematuria in biopsy-proven IgA nephropathy in children. The duration of treatment or placebo was 2 years, with vitamin E treatment consisting of 400 IU/day in children weighing <30 kg, and twice that dose for those >30 kg. We measured GFR at entry, midpoint and exit. At baseline and at 4-month intervals after randomization, urinary protein/creatinine ratios and urinalysis were examined. The mixed model procedure with log transformation was used in data analysis to test treatment difference as well as the potential time effect. Fifty-five patients were randomized and 38 completed at least 1 year of follow-up. At entry, the clinical characteristics were not different between the treatment and placebo groups. There was a trend toward better preservation of GFR in vitamin E-treated versus placebo patients, 127±50 vs. 112±31 ml/min/1.73 m², respectively (P=0.09). The urinary protein/creatinine ratio was significantly lower in the vitamin E-treated group vs. placebo; 0.24±0.38 vs. 0.61±1.37 (P<0.013). However, there was no difference in the prevalence of hematuria between the groups. Vitamin E treatment in our study patients was associated with significantly lower proteinuria, but no effect on hematuria. While there was a trend toward stabilization of GFR in the vitamin E-treated patients, long-term treatment and follow-up are needed to determine whether antioxidant therapy is associated with preservation of renal function in IgA nephropathy.     

Effects of growth hormone on kidney function in pediatric transplant recipients

Recent evidence suggests that treatment with recombinant human growth hormone (rhGH) after a successful kidney transplant improves the growth rate of children with short stature. We prospectively investigated eight children (6 boys, 2 girls), focusing on acute rejection episodes and changes in serum creatinine levels during rhGH treatment. The children (mean age 11.6±3.4 years) received rhGH daily (0.04–0.05 mg/kg subcutaneously). Seven patients completed at least 12 months (20±8 months) of rhGH treatment. Their mean serum creatinine level was 1.3±0.7 mg/dl 12 months before, and increased to 3.4±4.2 mg/dl after 12 months of rhGH treatment, but did not achieve statistical significance (P=0.06). Their mean calculated glomerular filtration rate was 58±20 ml/min per 1.73 m² 12 months before, and decreased to 38±21 ml/min per 1.73 m² 12 months before, and decreased to 38±21 ml/min per 1.73 m² after 12 months of rhGH treatment, but did not achieve statistical significance (P=0.08). Of the seven patients, two developed acute rejection after 5 and 6 rejection-free years; three lost their grafts and returned to dialysis. These preliminary observations describe untoward renal events in children receiving rhGH treatment after a kidney transplant.     

Renal handling of uric acid under cyclosporin A treatment

The renal handling of uric acid during cyclosporin A (CyA) treatment was investigated by clearance studies using 24-h urine collections in 28 paediatric renal transplant recipients (CyA group), and the results were compared with those of 19 renal transplanted children treated with azathioprine and prednisolone (AZA group), 35 children with chronic renal failure (CRF) and 10 children with normal renal function (N group). Serum uric acid levels were significantly higher in the CyA group (567±156 mol/l) compared with the AZA group (378±98), the CRF group (415±119) and the N group (290±68). Mean uric acid clearances in each group measured 3.9±2.8 ml/min per 1.73 m² (CyA), 5.6±3.4 (AZA), 4.0±2.2 (CRF) and 8.4±3.7 (N). Calculation of the net tubular uric acid reabsorption per millilitre glomerular filtration rate revealed a significantly increased value of 0.53±0.15 mol/ml in the CyA group (P<0.01) compared with 0.34±0.08, 0.29±0.15 and 0.27±0.07 mol/l for the AZA, CRF and N groups respectively. We therefore conclude that CyA treatment is associated with an increased net tubular reabsorption of uric acid, which may lead to hyperuricaemia.     

Mycophenolate mofetil in steroid/cyclosporine-dependent/resistant nephrotic syndrome

Attempts to minimize the effects of prolonged steroid use in steroid-dependent nephrotic syndrome (SDNS) and the need to overcome steroid resistance (SRNS) justifies immunosuppressant therapy. We report our experience in a cohort of patients with SD/SRNS during the administration of mycophenolate mofetil (MMF) in a prospective protocol initiated in January 2001. Twenty-six children with idiopathic nephrotic syndrome were included (21 steroid dependent and 5 steroid resistant), whose response did not change after sequential treatment with cyclophosphamide (CPM) and cyclosporine (CsA). Histopathologic patterns were: 11 minimal change disease (MCD), 1 diffuse mesangial proliferation (DMP), 13 focal segmental glomerulosclerosis (FSGS) and membranous 1 glomerulonephritis (MGN). The median age of onset of NS was 2.8 years (range 1.2–12.5), and treatment with MMF was performed at a median age of 11.4 years (range 5–17) with an initial dose of 600 mg/m²/12 h, adjusted to maintain levels of mycophenolic acid (MPA) at 2.5–5 mcg/ml. The planned duration of study to assess treatment efficacy was 6 months. The mean MMF dose required was 624 (SD=136) mg/m²/12 h (range 415–970), which maintained mean C₀-MPA levels of 2.9 (SD=1.17) mcg/ml (range 1.2–5.9 mcg/ml). In the five patients with SRNS, only one achieved complete remission. In the patients with SDNS, steroid sparing was achieved in 15 and 9 remained in remission on MMF monotherapy. Withdrawal of MMF resulted in immediate relapse in 47%. In our study, MMF was a useful immunosuppressant due to its fewer undesirable effects and similar efficacy to other drugs used. It appears effective for the maintenance of remission in SDNS patients, with a response similar to that of CsA.     

Differential risk of remission and ESRD in childhood FSGS

Focal segmental glomerulosclerosis (FSGS) is the leading cause of steroid-resistant nephrotic syndrome in childhood and the most common form of end stage renal disease (ESRD) from glomerular disease. In order to assess the risk of progression of children with primary FSGS and the impact of proteinuria remission status on disease progression, we undertook this study to describe a cohort of 60 children and adolescents from the Glomerular Disease Collaborative Network. Of the 60 patients included in the cohort, 58% were African American. Median age was 16 years. Proteinuria ranged from 1.0–24.0 g/day/1.73 m²; 57% were hypertensive, and the median estimated glomerular filtration rate (eGFR) was 90.2 ml/min/1.73 m². Complete remission was achieved in 20%, partial remission in 33%, and 47% have not achieved remission during follow-up with all prescribed therapy. Only ACE-I/ARB therapy was predictive of proteinuria remission in multivariate analysis (hazard ratio [HR] 3.35; 95% confidence interval [CI] 1.42–7.92). Renal survival was much improved in patients with complete or partial remission compared with no remission in univariate analysis. In multivariate analysis comparing no remission status, complete remission was associated with a 90% decreased risk of ESRD (HR 0.10, 95% CI 0.01–0.79, p =0.03). In summary, proteinuria remission status is a valid predictor of long-term renal survival in children with FSGS.     

Factors influencing the response to growth hormone in children with renal disease

The effects of age, height velocity over the preceding year, glomerular filtration rate (GFR) and prednisolone dose on growth response have been assessed by single and multiple linear regression analysis in 23 prepubertal children [age, mean (SD), 8.2 (2.5) years] with chronic renal failure (CRF) and 16 prepubertal children [12.1 (2.3) years] with renal transplants treated for 1 year with recombinant human growth hormone (rhGH), 30 U/m² per week. Height velocity [mean (SD), cm/year increased from 4.7 (1.3) to 9.7 (2.1) (P<0.0001) in the CRF group and 3.1 (1.6) to 7.3 (2.8) (P<0.0001) in the transplant group. In the CRF group, there was a correlation between age and height velocity, both in the pretreatment year (r=–0.755,P<0.0001) and during treatment (r=–0.421,P=0.045). There was no correlation between pretreatment height velocity or GFR and response to rhGH. In the transplanted children height velocity during the treatment year correlated with age (r=–0.647,P=0.007), prednisolone dose (r=–0.689,P=0.003), GFR (r=0.542,P=0.030) and pretreatment height velocity (r=0.655,P=0.006). Multiple regression analysis showed prednisolone dose and age to be the most important predictors of response.     

Renal function following kidney transplantation in children treated with cyclosporine

The study was performed to evaluate the longterm renal function of children treated with cyclosporine after kidney transplantation. Renal function was determined with clearances of inulin and aminohippurate sodium for evaluating glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Thirty-six children aged 0.4–16.2 (median 6.9) years at transplantation were examined within 5 months of transplantation and then yearly over 0.3–7.1 years. Twenty-five children and young adults, 1.5–20 (median 7.7) years of age, with solitary kidneys because of renal agenesis or nephrectomy, served as controls. The GFR and ERPF within 1 year of transplantation were significantly lower than those of controls (65±19 and 345±88 vs 96±12 and 474±91 ml/min per 1.73 m², respectively). GFR remained constant 4 years after transplantation, but ERPF decreased significantly. Significant inverse correlations were found between GFR within 5 months of transplantation and the mean cyclosporine concentration and the number of rejection episodes. The frequency of hypertension decreased from 82% within 5 months of transplantation to 0% after 4 years. The absolute GFR increased during follow-up. In conclusion, kidney transplantation results in a reduced renal function compared with that of solitary native kidneys. The reduction in renal function correlated with the number of rejection episodes and the cyclosporine load. The increase in absolute GFR during follow-up suggests a remaining capacity for growth and/or compensatory hypertrophy.     

Optimising nutrition in chronic renal insufficiency—growth

The need to optimise nutrition to promote growth in infants with chronic renal insufficiency (CRI) is well recognised, but there is less enthusiasm for such an approach in older children and those with milder degrees of CRI. Energy intakes and growth outcomes were prospectively monitored over a 2-year period in children aged 2–16 years with differing levels of severity of CRI, as part of their ongoing joint medical/ dietetic care. Children were grouped following [⁵¹Cr]-labelled EDTA glomerular filtration rate (GFR, ml/min per 1.73 m²) estimations, into normal kidney function [GFR >75, mean 106 (SD 19.5), n =58], providing baseline data only, mild (GFR 51–75, n =25), moderate (GFR 25–50, n =21), and severe (GFR <25, n=19) CRI. Children were followed for 2 years, with 51 completing the study (19 mild, 19 moderate, 13 severe CRI), and were excluded if they required dialysis. None received growth hormone. Regular dietary advice was provided and yearly 3-day semi-quantitative dietary diaries and baseline and 6-monthly anthropometric measurements were obtained. Mean height standard deviation score (SDS) was maintained in those with mild and moderate CRI and significantly increased in children with severe CRI [0.1 SDS (0.32 SD), F =9.45, 1 df, P =0.003]. There was a non-significant reduction in energy intake from dietary records overall (median –8.5% estimated average requirement), associated with poor adherence to supplements in severe CRI and under-reporting in the mild group. An increase in height or body mass index SDS, however, was observed in all children who took the supplements as prescribed. A correlation between change in energy intake and change in height SDS was observed in severe CRI ( r ²=0.58, P =0.011). Regular dietetic advice, with particular attention to adherence to optimise energy intake, may improve growth, irrespective of age and should form an integral part of the clinical care package.     

Nutrition and growth in relation to severity of renal disease in children

Practical joint medical/dietetic guidelines are required for children with chronic renal insufficiency (CRI). Nutritional status and growth were compared in 95 children (59 male) >2 years age with CRI, grouped following [⁵¹Cr]-labelled EDTA glomerular filtration rate (GFR, ml/min/1.73 m²) estimations into ’normal’ kidney function [GFR>75 (mean 104 (SD 18.9), n=35], mild (GFR 51–75, n=23), moderate (GFR 25–50, n=19) and severe CRI (GFR<25, n=18). Anthropometry [weight (wt.), height (ht.), and body mass index (BMI)], laboratory investigations and a 3-day dietary record were obtained. All anthropometric indices deteriorated with worsening renal function, from mean SD scores for wt., ht. and BMI in ’normal’ children of 0.32 (SD 1.2), 0.4 (SD 1.0) and 0.1 (SD 1.3), respectively, to values of –1.28 (SD 1.1; P<0.001), –1.52 (SD 1.1; P<0.001) and –0.42 (SD 1.1;NS) in severe CRI. Mean total energy intake decreased from 103% (SD 17) estimated average requirement (EAR) in ’normal’ children to 85% EAR (SD 27; P=0.004) in severe CRI. Mean serum PTH concentrations (normal laboratory range 12–72 ng/l) were higher in moderate [67 ng/l (SD 58), P<0.001] and severe CRI [164 ng/l (SD 164), P<0.001] and mean serum phosphate concentrations were higher in severe CRI (1.54 mmol/l (SD 0.17), P=0.009) compared to ’normal’. Disturbances in nutritional intakes, bone biochemistry and growth occur early in CRI and suggest the need for joint medical/dietetic intervention in children with mild and moderate CRI, in addition to those with more severe CRI. Received: 13 March 2000 / Revised: 11 July 2000 / Accepted: 14 July 2000     

The immune status of uraemic children/adolescents with chronic renal failure and renal replacement therapy

In adults with chronic renal failure (CRF) and/or renal replacement therapy (RRT) various immunological abnormalities have been described, but few data are available for the paediatric age group. We performed basic in vitro immunological studies in 26 patients 10 months–19 years of age with advanced renal failure, 11 with CRF (creatinine clearance 16.8±5.2 ml/min per 1.73 m²), 15 on RRT with haemodialysis (HD;n=9) and continuous ambulatory peritoneal dialysis (CAPD;n=6) as well as in 16 healthy controls. None had clinical evidence of deranged immune function. No significant differences were found in the percentages of B- and T-cells, T-cell subsets CD3, CD4, CD8 and mitogenic responses to phytohaemagglutinin and concanavalin A (Con A) between RRT patients (HD=CAPD) and control children. Most parameters in CRF patients were also normal, although they had a low percentage of B-cells (12.1±4.1; RRT: 19.7±6.5; controls: 18.5±7.1;P<0.01), relatively low levels of serum immunoglobulin G (948.4±209.4 mg/dl; HD: 1374.7±235.2 mg/dl;P<0.01; CAPD: 966.3±430.2 mg/dl, NS) and a high normal response to Con A (34.3±13.6 cpm ×10^–3; RRT: 34.5±11.3 cpm ×10^–3; controls: 23.4±9.9 cpm ×10^–3,P<0.01). All these values were, however, well within the normal accepted range. These data indicate that children/adolescents with CRF and/or RRT have no significant basic in vitro immunological defects. This study did not test the functional immune status of the young uraemic patients.