Eileen D. Brewer

Early initiation of peritoneal dialysis after surgical repair of congenital heart disease

Abstract The mortality rate of infants who require renal replacement therapy after surgical repair of congenital heart disease has been reported to be 30%–79%. We report our experience with early initiation of continuous manual peritoneal dialysis (CPD) to treat fluid overload in 20 consecutive critically ill children who underwent CPD post cardiotomy. CPD catheters were inserted at the discretion of the cardiothoracic surgeon. CPD was started for evidence of total body fluid overload with inadequate urine output, and stopped when negative fluid balance was achieved and urine output improved. Median age was 10 days (range 3–186 days), mean time to start CPD post-operatively was 22 h (range 5–40 h), and mean duration of CPD was 50 h (range 13–92 h). CPD resulted in mean ultrafiltration of 93 ml/kg per day (range 43–233 ml/kg per day). Net negative fluid balance was 106 ml/kg per day (range 49–273 ml/kg per day). During CPD, the mean number of inotropes decreased from 2.2 to 1.6 (P<0.05) and urine output increased from 2.2 to 3.9 ml/kg per hour (P<0.01). No patient died during CPD or had CPD discontinued due to adverse hemodynamic effects. The overall mortality rate was 20%. We conclude that early initiation of CPD can safely and effectively promote fluid removal in infants after repair of congenital heart disease, with a lower mortality rate than has previously been reported.

Elevated FGF 23 and phosphorus are associated with coronary calcification in hemodialysis patients

Increased mortality of adult chronic hemodialysis (HD) patients is associated with coronary calcifications (CC), increased serum phosphorus (P), use of calcium (Ca)-containing P-binders, and vitamin D deficiency. Serum concentration of fibroblast growth factor 23 (FGF 23) is markedly elevated in adults receiving dialysis and is independently associated with increased mortality. Although coronary calcifications have been described in pediatric and adult HD patients, no significant association between serum FGF 23 and CC has been reported. In our study, 5/16 patients had CC. Patients with CC were older, had longer dialysis vintage and higher serum P. Serum Ca, total PTH, elemental Ca intake, and calcitriol doses were not different for CC patients. Serum FGF 23 levels were markedly elevated in all patients (mean 4,024, range 874–8,253), but significantly higher in patients with CC (4,247 ± 10,35 vs 2,427 ± 11,92, p = 0.01) and positively correlated with Agatston calcification score (r = 0.69, p = 0.003) and serum P (r = 0.49, p = 0.05). Using multivariate analysis, serum FGF 23 and serum P remained the most significant factors associated with Agatston score. This study confirms the occurrence of CC in pediatric HD patients and is the first to show a significant association between CC and elevated serum FGF 23 in children.

Characterization of insulin-like growth factor binding protein-3 in chronic renal failure serum.

ABSTRACT: IGF-binding protein-3 (IGFBP-3), usually found as glycosylated 41- and 38-kD forms, is the major serum IGFBP during extrauterine life. In normal serum IGFBP-3 binds one IGF peptide and one acid-labile (α) subunit in a high-molecular-weight (MW) complex of 150 kD. By RIA, an excess of IGFBP-3 is present in chronic renal failure (CRF) serum, where it reportedly accumulates at low MW (25–55 kD) rather than as part of the 150-kD complex. To further evaluate IGFBP-3 forms in CRF, sera were obtained from seven healthy adolescents and seven adolescents with CRF. By RIA, IGFBP-3 levels were higher in CRF than normal sera (15.4 ± 2.2 versus 10.1 ± 2.1 μ g/mL). High-MW (150-kD) fractions of CRF and normal sera, obtained by neutral size-exclusion chromatography, had equal amounts of IGFBP-3 by RIA. However, a second RIA peak of IGFBP-3, present in low-MW (35-kD) fractions of CRF but not normal sera, could account for the higher IGFBP-3 levels of CRF serum. [l25I]IGF ligand blots of whole serum and serum fractions, either with or without prior precipitation by IGFBP-3 antiserum, found levels of 41- and 38-kD IGFBP-3 forms to be similar between CRF and normal whole sera and located these forms in the high-MW (150-kD) fractions of CRF and normal sera. [125I]IGF ligand blots also identified excess IGFBP in low-MW CRF serum fractions; cross-linking these IGFBP with [125I]IGF-I, followed by precipitation with IGFBP-1, -2, and -3 antibodies, identified high levels of unsaturated IGFBP-1, IGFBP-2, and 19- and 14-kD forms of IGFBP-3 in CRF serum. These studies indicate that 1) normal levels of functional 41- and 38-kD IGFBP-3 forms are present in CRF serum, and these forms can be incorporated into the 150-kD serum complex; and 2) high RIA levels of IGFBP-3 in low-MW fractions of CRF serum are at least in part due to 19- and 14-kD IGFBP-3 forms. These studies suggest that the excess unsaturated IGFBP of CRF serum are small enough to enter interstitial tissue spaces where they may modulate IGF-I-mediated mitogenic, metabolic, and differentiative effects.

Age and ethnicity affect the risk and outcome of focal segmental glomerulosclerosis

Abstract. In patients with proteinuria, African-American (AA) ethnicity is reported to be a risk factor for focal segmental glomerulosclereosis (FSGS) and its progression to end-stage renal disease (ESRD). We reviewed our single-center experience to determine the probability of FSGS and its progression to ESRD based on ethnicity and age at presentation in children with proteinuria with or without nephrotic syndrome. Proteinuria without systemic disease or acute glomerulonephritis was the presenting feature in 17% (236/1,403) of children in the renal patient database of Texas Children’s Hospital, Baylor College of Medicine. Histopathological diagnoses were established in 107 of 236 patients (45%). FSGS was identified in 65 patients, accounting for 28% of all patients with proteinuria and 61% of patients who underwent renal biopsy. FSGS was more prevalent in AA (45%) than in non-AA patients (22%) (P=0.001), and AA patients with FSGS were older at presentation (12.7±4.4 years) than non-AA patients (5.6±4.6 years) (P<0.001). Among patients who underwent renal biopsy, increasing age at presentation increased the probability of having FSGS in AA but not non-AA patients (P=0.04). Five-year actuarial renal survival of FSGS was worse in AA (8%) than in non-AA patients (31%) (P=0.01). These data suggest an increased risk and worse outcome of FSGS in AA compared with non-AA children.

Natural logarithmic estimates of Kt/V in the pediatric hemodialysis population

The natural logarithm formula for Kt/V proposed by Daugirdas is recognized as a valid and simple alternative to formal urea kinetic modeling (UKM) in adults receiving hemodialysis. No data have been published to validate the use of this formula in infants, children, and adolescents. We compared Kt/V derived by formal UKM with the natural logarithmic formula for 103 treatments in 21 pediatric end-stage renal disease patients receiving chronic hemodialysis. Values for Kt/V derived by formal UKM ranged from 0.65 to 2.06. Patients ranged in age from 1.8 to 22.5 years and in dry weight from 10.2 to 82.5 kg. The largest percent error between the two methods for any data point was less than 6%. The total error (absolute value percent error + 2 SD) was less than 6% across the entire range of dry weights. Our data show excellent agreement between formal UKM and the natural logarithm formula for Kt/V in pediatric hemodialysis patients, even those weighing less than 30 kg. These results support the use of the natural logarithm formula as a valid alternative to formal UKM in children. The simplicity of this formula should allow for the use of Kt/V as the best measure to study the relationship between delivered dialysis dose and outcomes in children.

Ambulatory blood pressure monitoring and interdialytic weight gain in children receiving chronic hemodialysis

Volume overload appears to induce hypertension in hemodialysis patients, yet studies of the effect of hydration status on interdialytic blood pressure (BP) have yielded contradictory results. We measured interdialytic BP by ambulatory BP monitoring (ABPM) during inpatient fluid restriction in 12 children receiving chronic hemodialysis to describe the overall BP pattern and to determine the effect of weight gain on BP change. Weight was measured on admission and four times each day. For each weight, casual BP was measured and compared with the mean of 3 hours of ABPM surrounding the weight measurement. Sleep BP decreased from daytime BP by 6% for systolic BP (SBP) and 11% for diastolic BP (DBP). Sleep loads were greater than daytime loads (P < 0.01) for SBP (53% v 28%) and DBP (57% v 27%). Overall, 58% (7 of 12) of the patients had sleep SBP load greater than 50%, and 67% (8 of 12) of the patients had sleep DBP load greater than 50%. Casual and ABPM measurements of BP showed moderate correlations for SBP (r = 0.51) and DBP (r = 0.46) and mean differences between methods of 6.3 +/- 13.2 mm Hg and -1.4 +/- 12.6 mm Hg, respectively. Increases in interdialytic weight were positively associated with increases in SBP (r = 0.41; P < 0.001), and interdialytic BP changes varied closely with corresponding weight changes. We conclude that in children receiving chronic hemodialysis: (1) sleep BP decreases are attenuated and sleep BP loads are elevated, (2) casual BP correlates poorly with ABPM, and (3) interdialytic weight and BP are related.

Non-invasive intravascular monitoring in the pediatric hemodialysis population

Abstract Assessment of dry weight in pediatric hemodialysis (HD) patients is difficult, since small fluid shifts may result in dialysis-associated morbidity (DAM) and children may not verbalize complaints. Achieving dry weight is critical since chronic fluid overload can result in hypertension and left ventricular hypertrophy. To determine if non-invasive monitoring of hematocrit (NIVM) is useful in preventing DAM in pediatric HD patients, we reviewed 200 HD treatments performed with or without NIVM (no NIVM). DAM was defined as an ”event” (e.g., hypotension, headache, cramping) that required nursing intervention. Patient age, weight, and gender were similar in both groups. Desired ultrafiltration was obtained in both groups. The event rate was lower in NIVM than no NIVM for all treatments (0.22 vs. 0.3, P=0.07) and significantly lower in patients <35 kg (0.25 vs. 0.47, P=0.01). The second event rate (fraction of treatments with one event that had a subsequent event occurring at least 15 min later) was lower with NIVM (P<0.01). For the NIVM group, events in the first 90 min occurred when blood volume changed >8% per hour; 71% of events (43/60) at 90–240 min occurred when blood volume changed >4% per hour. NIVM decreases DAM in pediatric HD patients, especially those <35 kg. Ultrafiltration with blood volume change <8% per hour is safe in the 1st h and <4% after 1 h reduces DAM in children.

Acyclovir prophylaxis of varicella in children with renal disease receiving steroids

Abstract Varicella, or chickenpox, is very communicable and has been shown to be transmitted to nearly 90% of household contacts. Severe varicella infections with fatal complications have been noted in children receiving corticosteroids despite the administration of varicella-zoster immune globulin (VZIG). The use of post-exposure acyclovir prophylaxis in immunocompetent children exposed to a household contact with varicella has been shown to decrease the transmission rate of varicella significantly. We studied the safety and efficacy of acyclovir prophylaxis as an adjunctive preventive measure in 8 children (10 separate exposures) receiving corticosteroids for renal disease. Four children (6 separate exposures) served as controls. No adverse reactions were reported with the acyclovir prophylaxis. The maximum change between pre- and study serum creatinine levels was 0.1 mg/dl. None of the 8 patients who received acyclovir prophylaxis developed chickenpox. One of these 8 patients developed humoral immunity to varicella despite the absence of clinical infection. One of 4 patients who received VZIG prophylaxis alone developed chickenpox. These data support the use of acyclovir prophylaxis as an adjunctive measure to VZIG for the prevention of potentially serious varicella infection in children receiving steroids.

Insulin-like growth factor-binding protein-6 levels are elevated in serum of children with chronic renal failure: a report of the Southwest Pediatric Nephrology Study Group.

Previous studies suggest that growth retardation in children with chronic renal failure (CRF) results in part from inhibition of insulin-like growth factor (IGF) action by excess serum IGF-binding proteins (IGFBPs). Excess IGFBPs in CRF serum include IGFBP-1, -2, and -3 and a diffuse approximately 24- to 28-kDa IGFBP band identified by [125I]IGF ligand blot. The present studies characterized this diffuse approximately 24- to 28-kDa band. Initial studies identified this band as IGFBP-6, because it was immunoprecipitated by antiserum raised against a synthetic peptide of human IGFBP-6 (hIGFBP-6). Additional [125I]IGF ligand blots found that the immunoprecipitated band was 1) recognized by [125I]IGF-II but not [125I]IGF-1, 2) more abundant in CRF than in normal serum, and 3) more abundant in serum from dialyzed than nondialyzed prepubertal CRF children. Using the hIGFBP-6 antiserum in a specific and sensitive RIA, we found that serum IGFBP-6 levels were 4.7 +/- 1.7 nmol/L in 10 normal prepubertal children, 21.4 +/- 6.1 nmol/L in 44 nondialyzed prepubertal CRF children, 73.5 +/- 14.4 nmol/L in 7 dialyzed prepubertal CRF children, and 94.6 +/- 26.2 nmol/L in 14 dialyzed pubertal CRF children. IGFBP-6 levels were also elevated in 71 nondialyzed European children with CRF. In nondialyzed CRF children, serum IGFBP-6 levels 1) correlated inversely with the glomerular filtration rate, 2) did not correlate with height SD score, and 3) were not altered by 12 months of daily recombinant hGH treatment. In summary, a specific antiserum and RIA were used to demonstrate elevated levels of intact IGF-II-binding IGFBP-6 in serum of CRF children. We postulate that the excess IGFBP-6 may modulate the action of IGF-II on target tissues.

Dietary protein and growth in infants with chronic renal insufficiency: a report from the Southwest Pediatric Nephrology Study Group and the University of California, San Francisco

This report describes growth and nutrition data from the feasibility phase of a clinical trial that was designed to evaluate the effect of diet protein modification in infants with chronic renal insufficiency (CRI). The purpose of the proposed trial was to compare the safety (effect on growth in length) and efficacy [effect on glomerular filtration rate (GFR)] of a diet with a low protein:energy (P∶E) ratio versus a control diet in such patients. Twenty-four infants with GFRs less than 55 ml/min per 1.73 m2 were randomly assigned at 8 months of age to receive either a low-protein (P∶E ratio 5.6%) or control protein (P∶E ratio 10.4%) formula, which resulted in average protein intakes of 1.4 and 2.4 g/kg per day in the low and control groups, respectively. Overall energy intakes over a 10-month period of study averaged 92%±12% recommended dietary allowance (RDA) for length in the low-protein group and 92±15% RDA in the control group. Weight for age standard deviation scores (SDS) were comparably low in both groups at the time of randomization (low-protein —2.0±1.3, control −1.9±1.1) and at the end of the study (low −1.9±1.2, control −1.7±0.9). Length for age SDS at entry tended to be lower in the low-protein group but were not significantly different in the two groups (low −2.2±1.4 vs. control −1.7±1.4). However, at 18 months the low-protein group had a significantly lower SDS for length (−2.6±1.2 vs. −1.7±1.4). The length velocity SDS from 12 to 18 months were also different, with the low-protein group remaining strongly negative (−1.0±0.9) while the control group improved (−0.1±1.1). We conclude from this feasibility study that there is a need for caution in advising the use of low-protein intake in infants with CRI. However, our findings should be regarded as preliminary because of the small number of patients and the observation that the weight gains were the same in the two groups.