Successful treatment of Aspergillus peritonitis in a child undergoing continuous cycling peritoneal dialysis.

There are increasing numbers of reports of peritonitis caused by fungi in children undergoing continuous cycling peritoneal dialysis. Most of these cases are due to the Candida species, although other fungi have been reported. We report the first case (to our knowledge) of successfully treated Aspergillus peritonitis in a child on continuous cycling peritoneal dialysis.

Reduced alternative complement pathway control protein levels in anorexia nervosa: response to parenteral alimentation.

Serum levels of 16 proteins, including 11 component and control proteins of the complement system were determined before and after nutritional repletion in five female patients with severe malnutrition secondary to anorexia nervosa. Before parenteral alimentation significantly decreased serum levels were found for IgG, IgM, transferrin, Clq, C2, C3, factor B, beta lH, C3b inactivator, properdin, and C4 binding protein. A significant increase in posttreatment serum levels compared with pretreatment levels were found for transferrin, C3, factor B, beta lH, and C3b inactivator. Of the proteins measured, the C3b amplification loop control and component proteins, beta lH, C3b inactivator, C3, and factor B rose to the normal range in response to therapy most rapidly. In the absence of an acute phase reaction, these proteins appear to be particularly good indices of malnutrition and its response to therapy.

Influence of diurnal blood pressure variations on target organ abnormalities in adolescents with mild essential hypertension.

As hypertensive target-organ damage has been associated with diminished diurnal blood pressure (BP) variation in adults, we compared diurnal BP patterns of hypertensive adolescents with left ventricular hypertrophy with normotensive and hypertensive adolescents with normal left ventricular mass. In addition, the frequency of microalbuminuria (Malb), hyperfiltration, and reduced renal functional reserve (RFR) was evaluated in adolescents with normal BP and untreated borderline and mild essential hypertension. Thirty-three normotensive (NT) adolescents, 14.5+/-2.1 years (mean +/- SD), and 29 untreated borderline and mildly hypertensive (HT) adolescents, 14.6+/-2.4 years, wore the SpaceLabs 90207 ambulatory BP monitor for 24 h. Left ventricular mass was measured by M-mode echocardiography and then indexed (LVMI) to the cube of height. Creatinine clearance (Clcr) and urine Malb was measured on 24 h collection and RFR by change in creatinine clearance after an oral protein load. Diurnal BP change was expressed as the absolute and percent day-night BP fall and cusum derived plot height (CPH) and circadian alteration magnitude (CDCAM). Groups were compared using analysis of covariance with adjustments for race, gender, and body mass index. All NT and 19 HT subjects (HT-1) had normal LVMI at 22.2+/-5.3 and 25.8+/-3.8 g/m3, respectively. Ten HT (HT-2) had increased LVMI of 36.9+/-5.2 g/m3. No significant difference was found for absolute or percent day-night BP fall or CDCAM between groups. Nocturnal systolic BP was correlated most closely with LVMI (r = 0.41, p = .001). Clcr, Malb, and RFR did not differ between the groups. In conclusion, adolescents with borderline and mild essential hypertension and left ventricular hypertrophy have similar levels of diurnal BP fall, urine Malb excretion, and RFR compared to normotensive and hypertensive adolescents with normal left ventricular mass.

The use of an anaerobic incubator for the isolation of anaerobes from clinical samples.

An anaerobic incubator was compared with a standard jar system for the isolation of anaerobes from clinical material. Seventy specimens were selected as likely to yield anaerobes: 342 different anaerobes were isolated in the incubator and 347 in anaebrobic jars. These included Bacteroides spp (43%), Peptococcus spp (26%), Peptostreptococcus spp (13%), Veillonella spp (7%), Fusobacterium spp (7%), Clostridium spp (2%) and miscellaneous Gram-positive nonsporing bacilli (2%). Differences in isolation rates for each system were inconsistent and minor. Sixteen anaerobes were chosen for quantitative tests at the beginning and end of the study period. Miles and Misra counts showed a slight advantage of the incubator for F nucleatum, but no difference for B fragilis, B thetaiomicron, B uniformis, B bivius, B corrodens, F mortiferum, Ps anaerobius, P prevotii or Propionibacterium acnes. In almost all cases, colonies in anaerobic jars were slightly larger than those in the incubator. Disc antibiotic sensitivity tests gave the same results in each system, at the beginning and end of the study period. The anaerobic incubator provides an effective means of isolation of anaerobes in a clinical laboratory. However, several design features of the prototype would require change if the system were introduced.

Diurnal blood pressure patterns in normotensive and hypertensive children and adolescents.

As abnormalities in diurnal ambulatory blood pressure (BP) have been associated with hypertensive target organ damage in adults, we investigated the diurnal systolic BP (SBP) and diastolic BP (DBP) patterns of 54 normotensive children, age 13.4 +/- 3.0 years, and 45 untreated borderline and mildly hypertensive children, age 14.4 +/- 2.6 years. Subjects wore the SpaceLabs 90207 ambulatory BP monitor for 24 h. BP was measured q 15 min from 08.00-21.00 h then q 30 min from 21.00-08.00 h. Nocturnal BP fall, the night-day ratio and cusum derived measures were calculated from time-weighted daytime and night-time SBP and DBP. The groups were compared using analysis of covariance with adjustment for age, race, gender and body mass index. The influence of age, gender and race on the diurnal BP profile was also examined. Nocturnal SBP fall was greater in hypertensive compared to normotensive subjects (17.1 +/- 6.7 vs 14.6 +/- 7.1 mm Hg; unadjusted mean +/- s.d., P = 0.022). Normotensive and hypertensive groups did not differ in nocturnal DBP fall or SBP or DBP night-day ratio. Race appeared to influence the diurnal BP pattern as black subjects had less nocturnal SBP fall (12.9 +/- 6.9 vs 17.1 +/- 6.5 mm Hg; P < 0.005) and a higher night-day SBP ratio (90.1 +/- 5.3 vs 86.7 +/- 4.6%; P < 0.005) than white subjects. In conclusion, hypertensive children and adolescents have a similar diurnal BP pattern as their normotensive counterparts, except that the entire BP profile is shifted upward with a greater absolute fall in SBP at night. Race also appears to influence the diurnal BP profile of normotensive and hypertensive children and adolescents.

Diagnostic and prognostic significance of glomerular epithelial cell vacuolization and podocyte effacement in children with minimal lesion nephrotic syndrome and focal segmental glomerulosclerosis: an ultrastructural study.

Children with minimal lesion nephrotic syndrome (MLNS) may later develop focal segmental glomerulosclerosis (FSGS). It has been suggested that a low percentage of epithelial podocyte effacement (EPE) and a high degree of epithelial cell vacuolization (ECV) in nonsclerotic glomeruli presage FSGS, and that extensive epithelial cell vacuolization in biopsies clearly showing FSGS predicts a poor clinical outcome. To investigate these contentions, we examined by electron microscopy three glomeruli from each of the first biopsies of 30 patients. Ten patients (group 1) had MLNS, 10 (group 2) had FSGS, and 10 (group 3) had MLNS which progressed to FSGS. Clinical data was obtained by retrospective review of medical records. The percent of epithelial podocyte effacement was calculated by computerized linear tracing and epithelial cell vacuolization was scored semiquantitatively from 0-3. (formula; see text) The percent podocyte effacement in each group was the same and does not distinguish MLNS from FSGS. Group 2 had more extensive epithelial cell vacuolization than group 1 (p less than 0.04) and the same as group 3 (p = 0.16). The combined ECV score for groups 2 and 3, however, was significantly greater than for group 1 (p less than 0.025) suggesting that epithelial cell vacuolization may indeed be a marker of FSGS. The extent of epithelial cell vacuolization did not correlate with creatinine clearance at latest follow-up, and thus does not predict clinical outcome.

Mesangial IgG in childhood minimal change disease: clinical relevance.

The clinical courses of five children with the nephrotic syndrome and renal biopsies diagnosed as minimal change disease (MCD) by light microscopy but with mesangial immune deposits of IgG (> or = 2+) and no dominant or codominant IgA were reviewed retrospectively to determine if the presence of significant mesangial deposits of IgG has prognostic implications and to evaluate the treatment these patients received. All five of the children were steroid dependent or resistant initially, and four received cyclosporine or cytotoxic agents later. After a mean follow-up period of 2.9 years for four and 20 years for one, all are in remission. All have normal renal function with no hypertension. These results suggest that the deposition of IgG in the mesangium of biopsies from patients with MCD by light microscopy may predict a more difficult course initially and may require more aggressive treatment to achieve permanent remission.

Membranoproliferative glomerulonephritis in two sibships.

In one sibship, a brother had membranoproliferative glomerulonephritis (MPGN) Type III and a sister, Type I. In both children, clinical and laboratory manifestations were typical. In another sibship, both boys had Type I MPGN by glomerular morphology but over a 4 year period of follow-up, neither had hematuria or hypocomplementemia, both common manifestations of this type. Several other reports give suggestive evidence of MPGN in siblings but details are scanty. The familial nature of the disease adds to the earlier observation of its predilection for the white race to strengthen the concept that genetic factors are involved in its origin.

Hyponatremia.

This article provides a useful clinical classification of hyponatremic states based upon plasma tonicity and extracellular fluid volume. The pathophysiology of hyponatremia induced by hypovolemic, euvolemic, and hypervolemic conditions is discussed. An approach to the treatment of each category of hyponatremia is presented.

Issues in adolescent gynecologic care.

Adolescence is a period of transition from childhood to adulthood. During this period, the potential for high-risk behaviors that may negatively impact on gynecologic health care are great. To enhance the potential for optimal care of this group of individuals, the physician must understand that (1) adolescents must be active participants in the decision making concerning their gynecologic health, (2) adolescents need to be able to communicate their concerns about gynecologic health in a confidential forum, and (3) there are areas of early gynecologic development and maturation for which anticipatory guidance is required.

Effect of hyperparathyroidism on response to erythropoietin in children on dialysis.

The response to recombinant human erythropoietin (rHuEPO), 50 units/kg thrice weekly, was studied prospectively in 17 children and adolescents with end-stage renal disease who were either transfusion dependent or had hematocrits < 25%. For convenience, rHuEPO was given intravenously to 12 hemodialysis (HD) patients and subcutaneously to 5 peritoneal dialysis (PD) patients. Blood pressure, hematocrit, iron indices, and serum potassium, calcium, phosphorus, alkaline phosphatase, urea nitrogen, and intact parathyroid hormone (PTH) were monitored serially. When serum ferritin was < 100 ng/ ml during therapy, 6 patients received iron supplementation. rHuEPO therapy eliminated frequent transfusions in all patients; 11 of 17 patients reached the target hematocrit of 30%-33% by week 16 of rHuEPO, 50 units/kg thrice weekly. The 5 PD patients treated subcutaneously reached target at week 6 +/- 1; 6 HD patients treated intravenously reached target at week 11 +/- 3; 6 additional HD patients never reached target at this dose; 5 of 6 had pre-rHuEPO serum PTH levels >400 pg/ml, significantly higher than those of the other patients (P < 0.005); 3 of 6 later reached a hematocrit of 30%-33% after the rHuEPO dose was increased to 120-130 units/kg thrice weekly. We conclude that most pediatric dialysis patients can be treated successfully with rHuEPO, 50 units/kg thrice weekly, unless the serum PTH concentration is markedly elevated, in which case a higher dose is likely to be needed.

Acute tubulointerstitial nephritis in children: clinical, morphologic, and lectin studies. A report of the Southwest Pediatric Nephrology Study Group.

Clinical histories and renal biopsies were reviewed in 12 children with acute tubulointerstitial nephritis, which was drug related in eight, idiopathic in one, and multifactorial in three. Presentation with rashes and hypertension was most common in patients with drug-associated nephritis. Eosinophils, which were present in the majority of the renal biopsies, did not distinguish between drug-related and non-drug-related disease. The majority of the children had a good outcome irrespective of the insulting agent. Frequent tubular basement membrane breaks were identified in seven of the biopsies but were not associated with a poor outcome. Proximal tubule brush border thinning, demonstrated by periodic acid-Schiff and Tetragonolobus lotus staining, paralleled the severity of acute renal failure. Lectin and immunohistochemical techniques to identify proximal tubules (Tetragonolobus lotus), thick ascending limb of Henle (anti-Tamm-Horsfall protein antibodies), and collecting ducts (Arachis hypogaea) allowed better delineation of sites of inflammation and injury, showed collecting tubules to be involved in all cases, and demonstrated that small atrophic tubules were able to maintain the ability to stain with the appropriate lectin/antibody. It is proposed that studies using these techniques may better identify the nephron sites involved in a variety of renal diseases involving tubular segments.

Use of pump-assisted hemofiltration in children with acute renal failure.

In critically ill children, acute renal failure (ARF) is associated with a high mortality. To assess the outcome and complications of pump-assisted hemofiltration (PAHF) using a standard volumetric pump to regulate blood flow, we retrospectively reviewed our experience in 52 patients with ARF treated with PAHF from 1989 to 1995. These patients ranged in age from < 1 month to 19 years and in weight from 2 to 125 kg. The most common underlying diagnoses were congenital heart disease and infection. The duration of PAHF averaged 9 +/- 8 days (range 24 h to 43 days). Hemodiafiltration for solute control was required in 40 patients. Total fluid intake while on PAHF was 136 +/- 95 ml/kg per day, while urine output and ultrafiltration averaged 15 +/- 24 ml/kg per day and 89 +/- 58 ml/kg per day, respectively. Management of laboratory abnormalities was efficient with only 4 patients requiring 1 or 2 additional treatments of hemodialysis for control of uremia. Complications included hyponatremia in 13 patients, hypokalemia in 14 patients, hypovolemia in 8 patients, hyperglycemia in 6 patients, and bleeding in 9 patients. No complications specifically related to use of the volumetric infusion pump for PAHF were noted. PAHF using a volumetric infusion pump for blood flow regulation in critically ill children with ARF is a practical and efficient therapy.

Gentamicin disposition and effect on development of renal function in the very low birth weight infant.

The steady-state pharmacokinetics, renal function and quantitative beta 2-microglobulin (beta 2-M) excretion were prospectively evaluated in 22 very low birth weight (VLBW) infants (700-1,470 g birth weight and 25-33 weeks gestational age) receiving 2.4 mg/kg gentamicin at randomly assigned 12- or 18-hour dosing intervals. Gentamicin trough concentrations were significantly lower in only those infants greater than 1,000 g birth weight on the 18-hour schedule (p less than 0.05). ESTRIP analysis of gentamicin disposition at steady state revealed a biexponential function with half-life (mean +/- SEM), 9.78 +/- 0.86 h, plasma clearance 0.64 +/- 0.06 ml/kg/min and volume of distribution 0.50 +/- 0.03 liter/kg. Serum creatinine at steady state correlated with half-life (p less than 0.01), plasma clearance (p less than 0.01), and trough levels (p less than 0.001). Despite the frequent occurrence of gentamicin trough levels persistently greater than 2.0 micrograms/ml, renal function matured normally as serum creatinine progressively decreased (p less than 0.001) and creatinine clearance progressively increased (p less than 0.001) with advancing conceptional age. Urinary excretion of beta 2-M, thought to be a marker of proximal tubular damage from gentamicin, did not correlate with elevated trough levels, and was in fact lower in those infants with the highest measured trough levels (p less than 0.001). Nephrotoxicity was suspected in only 2 infants both of whom had additional renal insult during the first few days of life. Despite the frequent occurrence of elevated gentamicin trough levels and prolonged elimination half-life in these VLBW infants, their renal function matured normally throughout therapy and nephrotoxicity from gentamicin, as evidenced by beta 2-microglobulinuria, did not occur.

Pharmacokinetics of moxalactam in anuric children and during hemodialysis.

Pharmacokinetics of moxalactam were determined in children with chronic renal failure during a 4-hour hemodialysis or an interdialytic period following a 50 mg/kg dose. Mean elimination half-life during dialysis was 3.9 hours compared to 12.9 hours during the interdialytic period. Mean clearance of moxalactam was 86 ml/minute during hemodialysis and 25 ml/minute between dialysis. Mean dialyzer clearance of moxalactam was 45 ml/minute. The mean fraction of moxalactam removed during a 4-hour hemodialysis was 18% in nine children. In anuric children, a 50 mg/kg dose of moxalactam should be given every 48 hours in an interdialytic period and a 25 mg/kg dose given after each dialysis.

Glomerular lesions in adolescents with gross hematuria or the nephrotic syndrome. Report of the Southwest Pediatric Nephrology Study Group.

We report clinical and pathological data in 56 adolescents presenting with gross hematuria (GH) and 65 presenting with idiopathic nephrotic syndrome (INS). IgA nephropathy (present in 52%) and other mesangial lesions were found in the majority of the 56 patients with GH. Many of these patients had complex urological procedures prior to consideration of a nephrological problem. This often led to significant delays in making the appropriate diagnosis. Pathological lesions in the 65 patients with INS included minimal change NS (MCNS) in 31%, membranous glomerulonephritis (MGN) and focal segmental glomerulosclerosis (FSGS) in 18.5% each, and membranoproliferative GN (MPGN) in 12%. In 47 of the patients with INS, in whom no specific treatment had been given prior to renal biopsy, MCNS and MGN were observed with a similar frequency (26% and 23%, respectively), with FSGS and MPGN being found in 21% and 11%. These results indicate that the pathological lesions in adolescents with INS who undergo a renal biopsy more closely resemble those in adults, and are usually more severe than those in young children. However, it should be noted that our study was retrospective. Hence, there were probably some adolescents with INS who had a successful response to therapy and therefore did not have a renal biopsy performed.

Pump-assisted hemofiltration in infants with acute renal failure.

Hemofiltration is accepted management for acute renal failure in critically ill patients. However, in infants, obtaining arterial access or adequate flow through the access is often difficult. We report our technique and experience with pump-assisted hemofiltration (PAHF) in ten infants with acute renal failure. In five patients, double-lumen venous catheters provided access, while two catheters at separate sites were used in the remaining patients. In all patients, hemofilters were used with standard intravenous tubing added to pre-filter tubing and placed through a standard volumetric infusion pump for regulation of blood flow. The infants, aged 5-575 days, weighed from 2.8 to 11.4 kg and had primary diagnoses of post-operative congenital heart disease in five, sepsis in four, and renal dysplasia in one. The duration of PAHF averaged 158 +/- 115 h (range 20-332 h). Complications included bleeding at a catheter or surgical site in one patient each and asymptomatic hyponatremia in five patients. Thus, with adequate nurse training, PAHF using a volumetric infusion pump for blood regulation can be acceptable therapy in acute renal failure in infants.

Renal handling of beta 2-microglobulin in patients with cystic fibrosis.

We evaluated the renal handling of beta 2-microglobulin (beta 2-M) and creatinine in healthy outpatients (n = 6), normal children hospitalized for infections treated with antibiotics (not including an aminoglycoside) (n = 4); outpatients with cystic fibrosis (CF; n = 12), and hospitalized patients with CF (n = 6) who received a 10- to 14-day course of antibiotic treatment that included an aminoglycoside. The serum beta 2-M concentrations in the normal outpatients (2020.1 +/- 276.6 micrograms/L) were significantly lower (p less than 0.05) than those observed for outpatients (2833.3 +/- 202.6 micrograms/L) or patients with CF (2861.8 +/- 340.5 micrograms/L. There were no significant differences found for creatinine clearance or fractional excretion of beta 2-M when subjects without CF were compared with those with the disease. Furthermore, no significant differences were observed in hospitalized patients with CF when creatinine clearance and fractional excretion of beta 2-M were compared between the initiation and conclusion of aminoglycoside treatment. Glomerular filtration and proximal tubular reabsorption of beta 2-M were not altered in patients with CF. These findings do not support a global defect in proximal renal tubular reabsorption as the underlying cause for altered aminoglycoside clearance in patients with CF.

Risk factors for bone mineral density loss in pediatric renal transplant patients.

Bone mineral density (BMD) is decreased in both adult and pediatric renal transplant recipients. To investigate the risk factors associated with this decrease in BMD post-renal transplant, we studied 33 children, aged 7-22 yr, who had received a renal transplant from 0.3 to 10 yr prior to this study. BMD analysis of the total body, spine, and femur was carried out by using dual-energy X-ray absorptiometry (DEXA). Age, weight, Tanner stage, time on dialysis prior to transplantation, cumulative corticosteroid dosage, and cyclosporin A (CsA) dosage since transplantation, and use of corticosteroid therapy prior to transplantation, were recorded. Spine, femur, and total body BMD Z-scores were greater than two standard deviations (2 SD) below the mean in 45%, 42%, and 17% of patients, respectively. Age correlated inversely with total body and spine BMD Z-scores (p = 0.001 and p = 0.008); no child under 14 yr of age had a total body or spine BMD Z-score greater than 2 SD below the mean for age. Patients at a Tanner stage of 4 or 5 had lower total body and spine BMD Z-scores than did patients at Tanner stages 1-3 (p = 0.043). Time post-transplant correlated inversely with both spine and total body BMD Z-score (p = 0.013 and p = 0.023). Only total body BMD Z-score correlated inversely with cumulative corticosteroid dose (in g, p = 0.045). BMD did not correlate with cumulative CsA dose. Black patients tended to have decreased total body BMD compared with Caucasian patients. In pediatric renal transplant patients, decreases in BMD start in adolescence. Risk factors for BMD loss in these patients include increasing age, time post-transplant, increasing Tanner stage, and ethnicity. Longitudinal studies in these patients and strategies to improve BMD are needed.