Pauline Nelson

Accelerated growth after recombinant human growth hormone treatment of children with chronic renal failure

We studied the effect of recombinant human growth hormone treatment on five boys, aged 4.6 +/- 1.8 years, who had chronic renal failure secondary to congenital renal diseases (mean creatinine clearance (+/- SD): 18.3 +/- 6.3 ml/min/1.73 m2 (0.32 +/- 0.11 ml/sec/1.73 m2]. Patients received 0.125 mg/kg of growth hormone three times per week for 1 year. Before beginning treatment, the children had a mean annual growth velocity of 4.9 +/- 1.4 cm/yr (range 3.0 to 6.3 cm/yr), with a mean standard deviation score for a height of -2.98 +/- 0.73 (range -2.16 to -3.59). At the end of therapy, the mean growth velocity had increased to 8.9 +/- 1.2 cm/yr (range 7.5 to 10.7 cm/yr), and the mean height standard deviation score improved to -2.36 +/- 0.83 (range -1.15 to -3.18). Bone age advancement was consistent with the period of growth. Routine laboratory determinations, including results of glucose tolerance testing, did not vary significantly from pretreatment levels. These preliminary data indicate that growth-retarded children with chronic renal failure can respond to exogenous growth hormone therapy with a marked acceleration in growth velocity.

Effects of oral calcium carbonate on control of serum phosphorus and changes in plasma aluminum levels after discontinuation of aluminum-containing gels in children receiving dialysis

Orally administered calcium carbonate was evaluated as a phosphate binding agent in 15 children, ages 0.6 to 17.2 years, receiving maintenance dialysis. Changes in plasma aluminum concentration were assessed after discontinuation of treatment with aluminum-containing gels. The mean daily dose of calcium carbonate was 5.1 +/- 2.5 gm (384 +/- 315 mg/kg/day), and correlated inversely with body weight (r = 0.72, P less than 0.01) and age (r = 0.71, P less than 0.01). Mean serum calcium, phosphorus, and bicarbonate values were unchanged throughout the study. Plasma aluminum concentration fell from 90 +/- 51 to 34 +/- 22 micrograms/L (P less than 0.005). Dietary phosphorus intakes were 44 +/- 21 and 42 +/- 19 mg/kg/day during the control period and at the end of the study, respectively. Transitory hypercalcemia was the only side effect in 92% of the patients. In none of the patients did uncontrolled hyperphosphatemia, metabolic alkalosis, diarrhea, or symptoms or signs of hypercalcemia develop. Our data indicate that calcium carbonate is an effective phosphate binding agent in children receiving dialysis, and should be used in lieu of aluminum-containing gels in young children with renal failure.

Recombinant human growth hormone treatment of children following renal transplantation

Nine growth-retarded renal allograft recipients received either thrice weekly or daily subcutaneous recombinant human growth hormone (rhGH) for 6–30 months. The annualized growth velocity for the initial year of rhGH treatment was significantly greater than that of the preceding year (2.5±2.1 vs 5.7±2.7;P<0.0001). There was no advancement in bone age greater than the increase in chronological age, no significant increase in the mean fasting serum glucose or insulin levels, nor significant decrease in the calculated creatinine clearance following rhGH treatment. However, two patients experienced rejection episodes following rhGH treatment indicating the potiental adverse consequences of the treatment on allograft function. This will require further delineation in prospective controlled studies. The serum insulin-like growth factor-1 levels significantly increased at 6 months (P<0.009) and 12 months (P<0.002) following rhGH treatment compared with baseline values. These preliminary data indicate that rhGH treatment may be effective in improving the growth velocity of growth-retarded renal allograft recipients.

Recombinant human growth hormone treatment of children with chronic renal failure: long-term (1- to 3-year) outcome.

Treatment of nine boys, aged 2.8–16.3 years, with growth retardation consequent to chronic renal failure (CRF), with recombinant human growth hormone (rhGH) for 12–36 months demonstrated a significant improvement in growth velocity at each 12-month interval compared with that achieved the year prior to treatment. Despite the acceleration in growth velocity the bone age did not increase more than the increase in chronological age during the period of treatment. The mean calculated creatinine clearance did not decrease significantly during the 36 months of treatment; however, two patients required institution of dialysis at 18 and 30 months following the initiation of rhGH treatment. There was no exacerbation of the glucose intolerance of uremia following rhGH treatment. Currently, six of seven patients who have been treated for more than 24 months have achieved sufficient acceleration of growth velocity to attain a standard deviation score that was more positive than −2.00, and are above the 5th per centile for chronological age on the growth curve. These data indicate that rhGH treatment of growthretarded children with CRF results in accelerated growth velocity during the 2nd and 3rd years of treatment, and demonstrate the potential for such children to achieve normal stature for chronological age despite the continued presence of renal failure.

Continuous Ambulatory Peritoneal Dialysis in Children

This article reviews in detail the evolution of peritoneal dialysis to its current status and presents the authors’ results with this new dialysis technique.

Hyperlipidemia in pediatric patients undergoing peritoneal dialysis

We evaluated serial measurements of serum lipid levels in 68 patients aged 12.6±4.7 years undergoing treatment with continuous ambulatory peritoneal dialysis/continuous cycling peritoneal dialysis (CAPD/CCPD). Fasting mean levels of triglycerides (TG) and cholesterol (C) were elevated above the 95th percentile of published normal values by 102% and 19%, respectively, at the start of dialysis. Except for a shortterm decrease in TG levels at 6 and 9 months, no significant change in mean lipid levels was observed during a follow-up period of 2 years. At initiation of dialysis, elevated TG and C levels were present in 90% and 69% of the patients, respectively. The prevalence of hyperlipidemia (HL) varied between 63% and 88% (TG) and 61% and 93% (C), respectively, during the follow-up period. TG and C levels were not correlated with caloric intake (evaluated in 17 patients), serum albumin levels, treatment modality (CAPD or CCPD), a history of the nephrotic syndrome, or previous treatment with hemodialysis or transplantation. However, a significant inverse correlation was observed between age and serum lipids at the initiation of dialysis treatment and after 1 year (TG:r=−0.40; C:r=−0.44). Our data indicate a high prevalence of HL but no significant change of serum lipid levels during 2 years of treatment with CAPD/CCPD.

Comparison of continuous cycling peritoneal dialysis with continuous ambulatory peritoneal dialysis in children

The clinical courses in 10 pediatric patients undergoing CAPD for 15.0 +/- 2.8 months and subsequently CCPD for 9.3 +/- 3.2 months were evaluated. During CAPD patients received four or five daily exchanges, and during CCPD five 2-hour nocturnal cycles over 10 hours plus a diurnal dwell. The only significant biochemical difference during CAPD compared with CCPD was the serum creatinine concentration (9.7 +/- 1.0 mg/dl vs 10.8 +/- 0.9 mg/dl, P less than 0.01). The peritonitis rate was one episode every 10.7 patient months during CAPD, compared with one episode every 8.5 patient months during CCPD. There were 21 episodes of exit site infection during CAPD versus 17 during CCPD. Mechanical complications included five ventral hernias in three patients and six peritoneal leaks in three patients during CAPD; two patients had two hernias and two patients had two peritoneal leaks during CCPD. Our results indicate adequate control of the biochemical abnormalities of uremia with CCPD, with the exception of the serum creatinine concentration.

Experience with continuous cycling peritoneal dialysis during the first year of life

The clinical experience in eight infants aged 5.8±2.3 (SD) months at the initiation of continuous cycling peritoneal dialysis (CCPD) is described. BUN, creatinine, albumin, calcium, phosphorus and alkaline phosphatase measurements were performed serially and no changes were seen throughout the follow-up period. Mean total energy and protein intake were 94±8% and 79±9% of the recommended. The initial and final standard deviation scores (SDS) for height were −1.42±1.32 and −2.47±1.36 (P<0.001), respectively. The SDS for body weight and head circumference were −1.67±0.71 and −1.67±1.04, respectively, at the beginning of the study and −1.83±0.98 and −1.88±1.52, respectively, at the end of the period of observation. The incidence of peritonitis was one episode every 11.6 patient months; six patients developed nine hernias. The present study demonstrates that CCPD is an acceptable dialytic modality, with minimal morbidity, for the management of infants awaiting renal transplantation.

Lipoproteins in children treated with continuous peritoneal dialysis

ABSTRACT: Total lipids, lipoprotein-lipids, and apolipo-proteins were studied in plasma of 20 patients, aged 13.9 ± 3.4 y (mean ± SD, range 7.4 to 19 y), who were treated with continuous peritoneal dialysis for a period of 2.1 ± 1.2 (range 0.5 to 4.9) y. Measurements included total plasma cholesterol and triglycerides, triglycerides in the very low density fraction, and cholesterol in the very low density, low density, and high density fractions, as well as apo A-I and apo B. The results were compared with values in 17 healthy control subjects, aged 13.0 ± 5.1 (range 5.1 to 19) y. The patients had significantly elevated levels of total plasma triglycerides, triglycerides in the very low density fraction, total plasma cholesterol, cholesterol in the very low density fraction, and cholesterol in the low density fraction, whereas levels of cholesterol in the high density fraction were normal. Plasma apo B levels were elevated, but apo A-I levels were not different from controls. In addition, the nutritional status of the patients was assessed and apo A-I and apo B concentrations were measured in the dialysate of 10 patients. The losses of apo A-I and apo B in dialysate averaged 13.4 ± 7.4 and 2.1 ± 3.1 mg/kg/d, respectively. Lipoprotein profiles were not correlated with nutritional status. We conclude that pediatric patients treated with continuous peritoneal dialysis have atherogenic lipoprotein profiles, cholesterol ratios, and apolipoprotein ratios, but normal cholesterol in the high density fraction and apo A-I levels despite considerable apo A-I losses in the dialysate.

Prospective evaluation of aluminum loading from formula in infants with uremia

Assessment of potential aluminum loading from regular ingestion of a commercial infant formula (Similac PM 60/40), as the only milk substitute, was made in 14 infants aged 9.6 +/- 4.4 months who were also undergoing continuous cycling peritoneal dialysis. Tissue aluminum accumulation was assessed by serial measurements of plasma aluminum levels, from the increment in plasma aluminum after a standardized deferoxamine infusion, and from quantitative histomorphometry of bone and measurements of total bone aluminum content. Initial mean plasma aluminum levels were 0.61 +/- 0.32 mumol/L, (normal 0.30 +/- 0.04 mumol/L), and values were less than 0.92 mumol/L during the follow-up of 20 +/- 8 months. Plasma aluminum levels increased from 0.59 +/- 0.18 to 0.88 +/- 0.22 mumol/L after a single dose of deferoxamine. The histochemical stain for bone aluminum was negative for all patients, and the bone aluminum content was 0.27 +/- 0.22 mmol/kg dry weight (normal 0.08 +/- 0.04 mmol/kg dry weight). Thus the infant formula Similac PM 60/40 can be safely used in infants with chronic renal failure.