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     

Recombinant human growth hormone in infants and young children with chronic renal insufficiency

Children with chronic renal insufficiency (CRI) secondary to congenital structural abnormalities frequently have significant growth retardation by 2 years of age. In a multicenter placebo-controlled study of the use of recombinant human growth hormone (rhGH), 30 of 125 (24%) participants were<2.5 years of age at enrollment. Since the treatment arms of the study were balanced for age at randomization, data for these patients were examined for efficacy and safety. During the first 2 years of the study, approximately two-thirds of the patients (n=19) received rhGH 0.05 mg/kg per day subcutaneously and one-third (n=11) received placebo injections. At entry into the study, the mean (± SD) calculated creatinine clearance was 29.2±14.3 (range 12.0–63.7) ml/min per 1.73 m² in the rhGH-treated group and 23.3±15.1 (range 8.0–59.4) ml/min per 1.73 m² in the placebo-treated group. The 1st year growth rate was 14.1±2.6 cm/year for the rhGH-treated group and 9.3±1.5 cm/year in the placebo-treated group (P<0.00005). During the 2nd year of the study, the growth rate was 8.6±1.2 cm/year in the rhGH-treated group compared with 6.9±1.0 in the placebo groupP=0.025). The height standard deviation score was +2.0±0.7 for the rhGH-treated group compared with –0.2±1.1 in the placebo-treated group (P<0.00005) during the 2 years of the study. Minor adverse events occurred with similar frequency in both groups. These data suggest that rhGH is efficacious and safe in children with CRI under age 2.5 years. rhGH therapy may correct significant loss of growth at this age when used in conjunction with optimal medical management.     

Long-term prognosis of hemolytic uremic syndrome and effective renal plasma flow

The long-term prognosis of diarrhea-associated hemolytic uremic syndrome (D+ HUS) was evaluated in a cohort of 127 of 149 children who had survived the acute phase. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated by serial ⁵¹Cr-EDTA and ¹²³iodine-hippurate clearances. All children had acute renal failure during the initial phase and 74% of patients were dialyzed. During the 1st year, mean GFR and ERPF increased continuously until a plateau was reached. In the 2nd year after the diagnosis of HUS, GFR was below 80 and ERPF below 515 ml/min per 1.73 m² in 16% and 47% of patients, respectively. At the end of a median follow-up of 5.0 (range 2.0–13.2) years, the proportion of children with renal sequelae such as proteinuria ≥300 mg/l, hypertension, or a GFR <80 ml/min per 1.73 m² was 23%. Anuria of more than 7 days’ duration and hypertension during the acute phase were statistically significant risk factors for an unfavorable outcome. A reduced ERPF in the 2nd year was found in 93% of patients with sequelae. Mean filtration fraction (SD) in these patients was 0.26 (±0.07) versus 0.19 (±0.05) in patients without sequelae (P<0.0001). These data suggest that loss of nephrons during the acute phase may implicate hyperfiltration in the residual functioning kidney mass leading to progressive renal disease. ERPF in the 2nd year after D+ HUS may serve as an excellent parameter to detect patients with a high risk of an unfavorable long-term outcome. Received: 17 September 1998 / Revised: 31 March 1999 / Accepted: 1 April 1999     

Factors related to renal haemodynamics in young type-1 diabetes mellitus patients

The influence of metabolic control (HbA_1c), noradrenaline (NA) and insulin-like growth factors (IGF-I and IGF-II) on renal function and size was investigated in 11 insulin-dependent diabetes mellitus patients aged 11–17 years. Renal function was evaluated in terms of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). Renal size was determined as renal parenchymal volume (RPV) by ultrasonography. The patients' HbA_1c values ranged from 8.2% to 12.9% (normal range 5.5–8.5%) and their GFR and ERPF were higher than normal. Their IGF-II values were higher, and NA and IGF-I levels were lower than those of healthy controls. Inverse correlations between NA and GFR (r=–0.66) and NA and ERPF (r=–0.63) were found. No correlation was found between serum IGF-I and renal functional parameters. The IGF-II values correlated with GFR and HbA_1c (r=0.63,r=0.70 respectively). There were linear correlations between RPV and GFR, RPV and ERPF, HbA_1c and GFR, and ERPF and RPV. Decreased NA concentrations and increased IGF-II values appear to be factors contributing to renal hyperfunction in these patients.     

Renal function during and after childhood acute poststreptococcal glomerulonephritis

It is still debatable whether acute poststreptococcal glomerulonephritis (APSGN) can lead to permanent renal impairment. The clinical, immunological, and histological findings during the acute disease have been described thoroughly, however, the hemodynamic events are still poorly understood. In this retrospective study, the inulin and p-aminohippurate clearances were measured to evaluate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) within a month of onset of the disease (acute stage) in 26 children, and 2–12 months after onset (follow-up) in 22 children with APSGN. During the acute stage, the mean GFR was 77±23 (SD) ml/min per 1.73 m², the mean ERPF 537±138 ml/min per 1.73 m², and the filtration fraction (FF) 14%±3%, compared with values for controls of 115±11 ml/min per 1.73 m², 607±72 ml/min per 1.73 m², and 19%±2%, respectively (n=42). At follow-up, GFR was 114±15 ml/min per 1.73 m², ERPF 600±68 ml/min per 1.73 m², and FF 19%±3%. Thus, during the disease both GFR and ERPF fell below values for controls, but later were restored. The GFR, however, was more reduced than the ERPF, as indicated by the reduced FF. This might reflect a relative hyperperfusion of individual nephrons, which might start processes later deleterious to the nephrons. This finding, however, needs to be further investigated and we have therefore started a long-term follow-up of these patients. Received: 24 June 1998 / Revised: 4 December 1998 / Accepted: 7 December 1998     

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.     

Renal function and kidney size in glycogen storage disease type I

Renal failure has been reported recently as a late complication of glycogen storage disease type I (GSD I). We studied the renal function of 23 patients, mean age 10.9 years (range 2.2–21.6 years). The mean glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were 188±50 and 927±292 ml/min per 1.73 m², respectively (normal values for adult controls 90–145 and 327–697, respectively). Hyperfiltration (GFR >145 ml/min per 1.73 m²) was found in 19 of 23 patients. There was no difference in GFR and ERPF between age groups 2–10 and 11–22 years. After a mean follow-up of 2.5 years (range 1–7.5 years) GFR and ERPF did not significantly change. At follow-up 3 patients (all older than 15 years) developed persistent glomerular proteinuria (0.1, 0.5 and 0.9 g/day). Besides a slight increase in fractional excretion of ₂-microglobulin (FE-₂m) in 6 patients, proximal tubular function tests (FE-₂m, tubular reabsorption of phosphate and glucosuria) were normal. In patients with increased kidney length related to body height, GFR and ERPF were significantly higher than in patients with normal kidney length. We conclude that GSD I is characterised by hyperfiltration and hyperperfusion. The relative increment in kidney length is related to the degree of hyperfiltration.     

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.     

Urinary protein excretion and renal function in children with IgA nephropathy

Renal haemodynamics and the pattern of urinary protein excretion were studied in 38 children (21 boys, 17 girls) with biopsy-proven IgA nephropathy (IgAN), 0.4–16.8 (median 5.3) years after onset of the disease. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were evaluated by clearances of inulin and para-aminohippuric acid. Serum and urinary albumin, IgG and beta₂-microglobulin (2) were determined and the excretion rates, clearances, and fractional clearances were calculated. The patients were grouped according to the type and the amount of proteinuria. Mean GFR and ERPF were significantly decreased (107±3 and 580±17 ml/min per 1.73 m², respectively) versus controls (119±2 and 627±14 ml/min per 1.73 m², respectively). Grouped according to albumin excretion rates, non-albuminuric patients had normal GFR, while mean GFR was reduced in patients with micro-albuminuria (106±3 ml/min per 1.73 m²) and albuminuric patients (92±7 ml/min per 1.73 m²). IgG excretion increased with increasing albuminuria, but the selectivity index was lower in albuminuric patients than in patients with micro-albuminuria. Albuminuric patients had also higher blood pressure than those with micro-albuminuria. 2 excretion did not discriminate between patients with impaired renal function. The results suggest that childhood IgAN is not a benign kidney disease. After a median duration of 5 years of the disease a number of children had impaired renal function. Mean GFR was reduced most in the albuminuric patients but was also decreased in micro-albuminuric patients, indicating that micro-albuminuria may be a predictor of more severe disease.     

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.     

Early prognostic factors of infants with chronic renal failure caused by renal dysplasia

Renal dysplasia (RD) is a common cause of chronic renal failure (CRF) in children. The evolution towards end-stage renal failure is unpredictable due to the paucity of early prognostic factors. In order to identify early prognostic clinical criteria, we have retrospectively analyzed renal function and growth in 11 infants with RD and CRF from birth up to 4 years of age. Children with obstructive RD were not included. Glomerular filtration rate (GFR) was estimated from Schwartz formula. In infants with a GFR below 15 ml/min per 1.73 m² at 6 months of age (group A, n=5), kidney function did not further improve; 4 reached end-stage renal failure between 8 months and 6 years of age. In contrast, infants with a GFR above 15 ml/min per 1.73 m² at 6 months of age (group B, n=6) experienced a significant improvement in renal function during follow-up, and none required renal replacement therapy. During the first 3 months of life all infants with RD and CRF developed severe growth retardation. Between 6 months and 4 years of age, children from group B grew significantly better than those from group A. In conclusion, our experience suggests that GFR, estimated from Schwartz formula at 6 months of age, is a useful prognostic factor in infants with RD and CRF. Infants with a GFR below 15 ml/min per 1.73 m² are at risk of severe growth delay and the need for early renal replacement therapy, whereas those with a GFR above 15 ml/min per 1.73 m² have a relatively favorable long-term prognosis. Received: 4 October 1999 / Revised: 26 October 2000 / Accepted: 26 October 2000     

Prophylactic oral ganciclovir after renal transplantation-dosing and pharmacokinetics

Ganciclovir alone or in combination with hyperimmunoglobulin is replacing other treatment modalities for the prophylactic treatment of cytomegalovirus (CMV) infections. No dose recommendations are available for oral ganciclovir therapy in children with impaired renal function after renal transplantation of a kidney from a CMV IgG-positive donor. We undertook a pharmacokinetic study in 14 pediatric renal transplant recipients who were CMV IgG negative and had received a graft from a CMV IgG-positive donor. We estimated the daily dosage of oral ganciclovir in relation to the glomerular filtration rate (GFR). Oral ganciclovir was administered at a starting dose of 3 × 1 g for children with a weight above 50 kg, 3 × 750 mg for children between 50 and 37.5 kg, and 3 × 500 mg for children between 37.5 and 24 kg. The starting dose was reduced by 50% for GFR values ≤50 ml/min per 1.73 m² and by 75% for GFR values ≤25 ml/min per 1.73 m². The daily dose was divided into three daily doses unless GFR was <40 ml/min per 1.73 m², when only two daily doses were given. Doses were adjusted according to the measured plasma trough concentrations (c) using the simple formula: c _ganciclovir(measured)/c _ganciclovir(desired) = dosage rate(used)/dosage rate(adjusted). Mean stable plasma trough concentration was 0.91±0.68 μg/ml. The dosage rate, adjusted to a trough concentration of 1.0 μg/ml, correlated with the GFR. The dose per day could be calculated according to a simple equation for a GFR <100 ml/min per 1.73 m²: dosage per day (mg/kg per day) = GFR. No CMV disease developed in any of the patients during oral ganciclovir, but 1 patient developed an acute rejection episode and a positive pp65 antigen 5 weeks after discontinuation of ganciclovir. The drug was well tolerated and without side effects. Received March 3, 1997; received in revised form July 25, 1997; accepted July 30, 1997     

Donor age and graft function

We evaluated survival and renal function of cadaveric donor grafts according to donor age. The median age of the pediatric donors was 7.0 (0.7 – 16) years in 46 patients [median age 11.8 years (range) 3 – 16.8 years]. The median age of the adult donors was 34.4 (19 – 54) years in 59 patients [median age 12.1 years (range) 7 – 17.3 years]. Thirty patients were treated with azathioprine and prednisolone and 75 with cyclosporine A and prednisolone. The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) were determined by the clearances of ⁵¹chromium-EDTA and ¹²⁵iodine-hippurate 1 – 48 months after kidney transplantation. There was no difference in graft survival between pediatric and adult grafts. There were also no differences in GFR in patients receiving grafts from pediatric or adult donors; 2 – 3 months after transplantation the GFR in recipients of pediatric grafts was 62±20 ml/min per 1.73 m² compared with 61±21 in those receiving adult grafts. The ERPF in recipients of adult grafts was significantly higher in the 1st month after transplantation: 486±239 versus 362±158 ml/min per 1.73 m². From the 4th to the 6th month after transplantation this difference disappeared: the ERPF of grafts from pediatric donors was 279±131 ml/min per 1.73 m² compared with 273±123 ml/min per 1.73 m² in grafts from adult donors. Using the single-kidney GFR and ERPF on an age-matched group of probands with minor diseases as references, 2 – 3 months after transplant the mean GFR of grafts from pediatric donors increased to 118%±51%, whereas the GFR of adult donor grafts fell to 60%±22% over the same period. After 4 – 6 months the ERPF in pediatric grafts was 96%±55% compared with 50%±22% in adult grafts. We conclude that graft survival and function in children with either a pediatric or an adult graft may not differ because graft function adapts to the requirement of the recipient. Received December 6 1995; received in revised form March 19 1996; accepted March 22 1996     

The correlation between preoperative renal scintigraphy and postoperative renal function in upper urinary tract urothelial carcinoma patients following radical nephroureterectomy

ObjectiveTo predict the renal function after nephroureterectomy (NUR) for upper urinary tract urothelial cancer (UTUC) based on preoperative technetium-99m mercaptoacetyltriglycine (99mTc-MAG3) renal scintigraphy.Subjects and methodsWe retrospectively reviewed 238 patients who originally underwent nephroureterectomy for UTUC between 2007 and 2010. Of these patients, 129 underwent MAG3 renal scintigraphy before unilateral NUR. Serum creatinine was measured in all of the patients before surgery, and renal function was monitored for one year after surgery. Preoperative and postoperative eGFRs were compared and analyzed based on the preoperative MAG3 renal scintigraphy.ResultsA total of 129 patients, including 62 men (48%) and 67 women (52%) with an average age at surgery of 69.0 years (range from 48 to 87) were included in this study. The mean preoperative creatinine level was 1.42 mg/dL, and the baseline eGFR was 54.76 ml/min/1.73 m². One year after NUR, the mean creatinine level was 1.89 mg/dL, and the eGFR was 44.44 ml/min/1.73 m², a mean decrease of 18.73%. The preoperative effective renal plasma flow (ERPF) of the operated kidney was 91.65 ml/min/1.73 m², and that of the remaining kidney 158.30 ml/ min/1.73 m². The average preoperative ERPF of the resected kidney accounted for 34% of total preoperative ERPF, which was statistically significant in its relation to the decrease in eGFR. The decrease in eGFR ratio was also significantly correlated with the calculated decrease in ERPF ratio (R² = 0.279, p < 0.001). The predictive equation of renal function one year after NUR was established as following: eGFR decreased ratio = –0.80 × predictive ERPF decreased ratio +0.72.ConclusionWe developed an equation to predict postnephroureterectomy 1 year eGFR before surgery based on preoperative MAG3 renal scintigraphy results and preoperative eGFR. The equation could be more accurate in the situation if the diseased kidney is not hydronephrotic.     

A randomized cross‐over comparison of short‐term exposure of once‐daily extended release tacrolimus and twice‐daily tacrolimus on renal function in healthy volunteers

Calcineurin inhibitor nephrotoxicity remains an issue for transplant recipients. The pharmacokinetic profile (PK) of the once‐daily tacrolimus extended release (Tac‐ER) includes equivalent exposure [AUC_(0–24 h)] but lower C_max versus twice‐daily tacrolimus immediate release (Tac‐IR). We hypothesized that the unique PK profiles would result in pharmacodynamic differences in renal function. Nineteen healthy male subjects were allocated to once‐daily Tac‐ER and twice‐daily Tac‐IR in a prospective, randomized, two period, cross‐over study. Tacrolimus was titrated to achieve trough levels of 8–12 ng/ml. Twenty four hours ERPF and GFR estimated by para‐aminohippurate and sinistrin clearance were performed at baseline and at the end of each 10‐day dosing period. Mean Tac C₀ was 11.0 ± 2.2 and 11.3 ± 1.8 ng/ml for Tac‐ER and Tac‐IR, respectively. The mean Effective 24 h renal plasma flow (ERPF) was significantly higher with Tac‐ER compared with Tac‐IR (658 ± 127 vs. 610 ± 93 ml/min/1.73 m², P = 0.046). There was a trend to a greater mean GFR over 24 h for Tac‐ER at 114.5 ± 13.6 ml/min/1.73 m² compared with 108.9 ± 9.7 ml/min/1.73 m² for Tac‐IR, P = 0.116. Under controlled physiological conditions, ERPF was significantly improved with Tac‐ER compared with Tac‐IR, likely owing to the differing PKs of these tacrolimus preparations (ClinicalTrials.gov Identifier: NCT01681134).     

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.     

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.     

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.     

Dietary supplementation with fish oil modifies renal reserve filtration capacity in postoperative,cyclosporin A-treated renal transplant recipients

The effect of a daily supplementation of 6 g fish oil (30% C20:5 omega-3=EPA and 20% C22:6 omega-3=DHA) for 1 month on renal function variables was investigated in a placebo-controlled (6 g coconut oil), prospective, randomized, double-blind study in acute postoperative cyclosporin A (CyA)-treated renal transplant recipients. Seventeen patients ingested placebo capsules (EPA-) and 14 patients fish oil (EPA+). Renal function tests were performed using the simultaneous determination of 125 I-iothalamate and 131 I-hippuran clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively. Renal reserve filtration capacity was assessed by dopamine infusion, amino acid infusion, and a combination of both stimuli. After 1 month there were no significant differences in rejection episodes, CyA dose, or CyA levels. In contrast to our earlier observations, serum creatinine, creatinine clearance, GFR, and ERPF did not differ between the EPA- and EPA+ groups. Filtration fraction (FF) differed significantly, being 0.21 in the EPA- group versus 0.26 in the EPA+ group. To exclude the possible influence of a rejection episode, the nonrejecting patients were analyzed separately, creating the subgroups EPA+ re- and EPA-re-. These two groups were comparable in age, donor age, and GFR. The EPA+ re-group had a significantly lower ERPF (164 ml/min per 1.73 m²) than the EPA-re- group (262 ml/min per 1.73 m²). FF was significantly higher in the EPA+re-group (0.26) than in the EPA-re- group (0.21). Following dopamine, no significant differences in the percentage increase of GFR and ERPF between both groups were observed, while FF fell to the same extent in both groups. Following amino acids, the fish oil-treated patients had a significantly better response on GFR (EPA+re- 15.3 versus EPA-re- 10.6%; P<0.05). The near-normal FF and the better response on amino acid infusion strongly suggest that at 1 month postoperatively, the CyA- and fish oil-treated patients have more balanced renal hemodynamics than the CyA- and coconut oil-treated patients.     

Long‐term evolution,secular trends,and risk factors of renal dysfunction following cardiac transplantation

Recent reports suggest that individuals who underwent heart transplantation in the last decade have improved post‐transplant kidney function. The objectives of this retrospective study were to describe the incidence and to identify fixed and time‐dependent predictors of renal dysfunction in cardiac recipients transplanted over a 25‐year period (1983–2008). To illustrate temporal trends, patients (n = 306) were divided into five groups based on year of transplantation. The primary endpoint was the estimated glomerular filtration rate (eGFR) at year 1. Secondary endpoints were time to moderate (eGFR <60 ml/min/1.73 m²) and severe renal dysfunction (eGFR <30 ml/min/1.73 m²). Risk factor analyses relied on multivariable regression models. Kidney function was mildly impaired before transplant (median eGFR=61.0 ml/min/1.73 m²), improved at discharge (eGFR=72.3 ml/min/1.73 m²; P < 0.001), decreased considerably in the first year (eGFR = 54.7 ml/min/1.73 m²; P < 0.001), and deteriorated less rapidly thereafter. At year 1, 2004–2008 recipients exhibited a higher eGFR compared with all other patients (P < 0.001). Factors independently associated with eGFR at year 1 and with moderate and severe renal dysfunction included age, gender, pretransplant eGFR, blood pressure, glycemia, and use of prednisone (P < 0.05). In summary, kidney function worsens constantly up to two decades after cardiac transplantation, with the greatest decline occurring in the first year. Corticosteroid minimization and treatment of modifiable risk factors (hypertension, diabetes) may minimize renal deterioration.