Inferior Outcomes on the Waiting List in Low-Volume Pediatric Heart Transplant Centers.

Low case volume has been associated with poor outcomes in a wide spectrum of procedures. Our objective was to study the association of low case volume and worse outcomes in pediatric heart transplant centers, taking the novel approach of including waitlist outcomes in the analysis. We studied a cohort of 6482 candidates listed in the Organ Procurement and Transplantation Network for pediatric heart transplantation between 2002 and 2014; 4665 (72%) of the candidates underwent transplantation. Candidates were divided into groups according to the average annual transplantation volume of the listing center during the study period: more than 10, six to 10, three to five, or fewer than three transplantations. We used multivariate Cox regression analysis to identify independent risk factors for waitlist and posttransplantation mortality. Of the 6482 candidates, 24% were listed in low-volume centers (fewer than three annual transplantations). Of these listed candidates in low-volume centers, only 36% received a transplant versus 89% in high-volume centers (more than 10 annual transplantations) (p < 0.001). Listing at a low-volume center was the most significant risk factor for waitlist death (hazard ratio [HR] 4.5, 95% confidence interval [CI] 3.5-5.7 in multivariate Cox regression and HR 5.6, CI 4.4-7.3 in multivariate competing risk regression) and was significant for posttransplantation death (HR 1.27, 95% CI 1.0-1.6 in multivariate Cox regression). During the study period, one-fourth of pediatric transplant candidates were listed in low-volume transplant centers. These children had a limited transplantation rate and a much greater risk of dying while on the waitlist.

Kidney and pancreas transplantation in the United States, 1999-2008: the changing face of living donation.

The waiting list for kidney transplantation continued to grow between 1999 and 2008, from 41 177 to 76 089 candidates. However, active candidates represented the minority of this increase (36 951-50 624, a 37% change), while inactive candidates increased over 500% (4226-25 465). There were 5966 living donor (LD) and 10 551 deceased donor (DD) kidney transplants performed in 2008. The total number of pancreas transplants peaked at 1484 in 2004 and has declined to 1273. Although the number of LD transplants increased by 26% from 1999 to 2008, the total number peaked in 2004 at 6647 before declining 10% by 2008. The rate of LD transplantation continues to vary significantly as a function of demographic and geographic factors, including waiting time for DD transplant. Posttransplant survival remains excellent, and there appears to be greater use of induction agents and reduced use of corticosteroids in LD recipients. Significant changes occurred in the pediatric population, with a dramatic reduction in the use of LD organs after passage of the Share 35 rule. Many strategies have been adopted to reverse the decline in LD transplant rates for all age groups, including expansion of kidney paired donation, adoption of laparoscopic donor nephrectomy and use of incompatible LD.

Successful use of Tesio catheters in pediatric patients receiving chronic hemodialysis.

Semipermanent venous catheters remain the most commonly used access for chronic hemodialysis (HD) in pediatric patients. The recent availability of Tesio catheters in 7 and 10 F has expanded available HD catheter options for children and adolescents. We report our experience with Tesio catheter survival, complications, and effect on dialysis adequacy in comparison to standard dual-lumen (DL) catheters in our pediatric HD patients. Demographic data were similar between the two groups. Overall actuarial survival was significantly longer for Tesio versus DL catheters (46% versus 0% at 1 year; P = 0.003). A comparison of smaller catheters (7 F Tesio catheter, 8 or 10 F DL catheter) showed that smaller Tesio catheters had a significantly longer survival (median survival, 244 versus 13 catheter-days; P < 0.01). Tesio 10 F catheters also survived significantly longer than the larger 11.5 and 12 F DL catheters (P < 0.02). Catheter sepsis occurred less frequently with Tesio catheters (one episode/20 catheter-months) than DL catheters (one episode/5 catheter-months) despite the longer duration of Tesio catheters. Adequate dialysis (single-pool Kt/V > 1.2) was delivered with the same frequency, but for a longer duration with Tesio catheters (76% +/- 32% over 100 monthly measurements versus DL catheter, 57% +/- 45% over 54 monthly measurements). Our clinical practice was to replace cuffed catheters when adequate dialysis could not be delivered. We conclude that Tesio catheters provide superior performance compared with DL catheters in terms of catheter survival, infection rates, and duration of adequate performance.

Long-term treatment of focal segmental glomerulosclerosis in children with cyclosporine given as a single daily dose.

Cyclosporine (CsA) has been successfully used for treatment of children with focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome (NS) for the last decade. Response rates of 50% to 100% have been reported using twice-daily dosing of 5 to 32 mg/kg/d, achieving trough blood levels of 70 to 500 ng/mL. Treatment has been associated with a high incidence of side effects, including nephrotoxicity, hypertension, gingival hyperplasia, and hirsutism. To determine whether once-daily low-dose CsA could minimize side effects and still induce remission, 21 children with biopsy-proven FSGS and NS, each treated with CsA, 4.6 +/- 0.8 mg/kg/d, with no predetermined target trough blood levels, were studied. Eleven of 21 children (52%) attained complete remission and 5 of 21 children (24%) attained partial remission, for a total response rate of 76%. Mean time to response was 2.8 +/- 0.8 months, and mean duration of therapy was 20.6 +/- 13.7 months. CsA dosage was tapered or stopped in 9 responders; 3 of these patients maintained remission at last follow-up 6 to 13 months later, and 6 patients relapsed at 1.5 to 18.7 months (mean, 8.7 months). Five of these 6 patients responded again when CsA therapy was restarted or the dosage was increased. Twelve of 16 responders were still being administered CsA at last follow-up 11 to 60 months (mean, 24.6 months) later. Five of 21 patients (24%) had no response to CsA during 2 to 27 months of therapy; 4 of these 5 patients developed end-stage renal disease after CsA therapy was stopped. Side effects of CsA therapy were minimal: 1 patient each developed new-onset hypertension or gingival hyperplasia, and no patient had hirsutism or nephrotoxicity. Single daily low-dose CsA appears to be effective for long-term treatment of children with FSGS and NS, with fewer side effects than twice-daily dosing.

Outcome in children receiving continuous venovenous hemofiltration.

OBJECTIVE: Continuous venovenous hemofiltration (CVVH) alone or with dialysis (D) has become an important supportive therapy for critically ill children with acute renal failure. Previous reports of pediatric patient outcome either mix CVVH/D with other renal replacement modalities or do not examine severity of illness. The current study examines only outcomes of children receiving CVVH/D using Pediatric Risk of Mortality (PRISM) scores to control for severity of illness. PATIENTS: Twenty-one patients (mean age: 8.8 +/- 6.3 years; mean weight: 28.3 +/- 20.8 kg) received 22 courses of CVVH/D. OUTCOMES: Nine (42.8%) of 21 patients survived. Nine (75%) of 12 deaths occurred within 25 days of pediatric intensive care unit (PICU) admission. Mean PRISM score at PICU admission and CVVH initiation were 13.1 +/- 5.8 and 15.4 +/- 8.9, respectively. Mean patient weight, age, PRISM score at PICU admission and at CVVH/D initiation, maximum pressor number, estimated glomerular filtration rate at CVVH/D initiation and change in mean airway pressure did not differ between survivors and nonsurvivors. The degree of fluid overload at CVVH/D initiation was significantly lower in survivors (16.4% +/- 13.8%) compared with nonsurvivors (34.0% +/- 21.0%), even when controlled for severity of illness by PRISM score. Mean cost of providing CVVH/D accounted for only 1% of total PICU cost per patient. CONCLUSIONS: The pattern of early multiorgan system failure and death, minimal relative cost of CVVH/D provision, and potential for improved outcome with initiation of CVVH/D at lesser degrees of fluid overload are factors that may support early initiation of CVVH/D in critically ill children with acute renal failure.

Non-invasive intravascular monitoring in the pediatric hemodialysis population.

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.

A survey of pediatric nephrologists on adolescent sexual health.

Chronic renal disease often has an adverse effect on adolescent physiologic and psychosocial development. The severity of the disease may necessitate that the pediatric nephrologist be the adolescent's main medical provider and the most available physician to screen for adolescent health risk behaviors. The purpose of this study was to determine pediatric nephrologists' practices of sexual history taking and diagnosis and treatment of sexually transmitted infections in their adolescent patients. A survey was performed on a convenience sample of 66 pediatric nephrologists attending an educational seminar on adolescent care at the 1997 national meeting of the American Society of Pediatric Nephrology. The outcome measures included physicians' reports of interviewing adolescents alone and screening for sexually transmitted infections. Fifty-six percent reported interviewing adolescents alone, 55% routinely ask female adolescents about sexual intercourse (53% ask males) and 10% routinely perform pelvic exams. Current practice in this selected sample of pediatric nephrologists, who by their attendance at the seminar may represent those most motivated to do screening, still leaves adolescents with chronic renal disease potentially at risk for sexually transmitted infections and pregnancy. Educational efforts should be directed at increasing routine confidential sexual history taking for adolescents with chronic renal disease.

Vascular C3 deposits on renal biopsy in pediatric patients with hematuria.

Isolated deposition of the third component of complement (C3) in the renal arterioles has been noted on biopsy specimens in patients with hematuria. This entity is of little known significance and reports of this finding in pediatric patients with hematuria are rare. We reviewed the clinical histories and biopsies of 17 children with hematuria and vascular C3 deposition on biopsy at Texas Children's Hospital over an 14-year period. The mean age of presentation was 10.8 (range 4.5-16.6) years with a male preponderance (71%). Family history for hematuria was positive in 6 of 17 patients (35%). Light microscopy was normal or showed only minor abnormalities. Immunofluorescence was negative for IgA and IgG in all patients. Seven patients (41.1%) were noted to have diffuse or focally thin basement membranes on electron microscopy in addition to positive C3 immunofluorescence. The mean follow-up time was 23.8 months, during which 2 of 17 patients (12%) developed worsening proteinuria. The etiopathogenesis of this condition remains unclear, but an underlying immunological process cannot be ruled out. It is possible that this condition represents a stage of an acute glomerulonephritis. Clinical follow-up of these patients is warranted, as the long-term prognosis remains unclear.

Logarithmic extrapolation of a 15-minute postdialysis BUN to predict equilibrated BUN and calculate double-pool Kt/V in the pediatric hemodialysis population.

Blood urea nitrogen (BUN) concentration rebounds logarithmically for 1 hour after a hemodialysis treatment. We have previously devised and evaluated an equilibrated Kt/V (eqKt/V) estimation method using logarithmic extrapolation of the BUN increase from 30 seconds to 15 minutes postdialysis in six pediatric hemodialysis patients. The current study evaluates logarithmic extrapolation in 15 additional pediatric patients. Mean measured equilibrated BUN (eqBUN) and estimated BUN at equilibrium (estBUN) using logarithmic extrapolation were 23.1 +/- 9.2 and 23.0 +/- 9.4 mg/dL, respectively. The mean absolute difference between estBUN and eqBUN was 0.7 +/- 0. 4 mg/dL (range, 0.1 to 1.55 mg/dL). All treatments had an absolute difference less than the SD of the laboratory measurement itself. The mean absolute percentage of difference between eqKt/V using eqBUN and estimated double-pool equilibrated Kt/V (estKt/V) using estBUN from logarithmic extrapolation was 3.4% +/- 2.3% and did not vary as a function of patient size, urea generation rate, dialyzer urea clearance, Kd/V, or ultrafiltration fraction. Mean absolute percentages of difference between eqKt/V and Kt/V estimated by the Tattersall, Daugirdas, or Maduell formulas were 4.5% +/- 3.9%, 4.4% +/- 3.7%, and 6.7% +/- 8.3%, respectively. Total percentages of error (absolute mean percentage of error + 2 SD) between eqKt/V and estKt/V by logarithmic extrapolation or the Tattersall, Daugirdas, or Maduell formulas were 8.0%, 12.3%, 11.8%, and 22.3%, respectively. The greater accuracy of logarithmic extrapolation compared with other methods of double-pool Kt/V estimation held true for patients weighing less than 35 kg. We have validated the use of an easy and accurate method requiring only an additional 15-minute posttreatment BUN level to estimate double-pool Kt/V in children.

Acyclovir prophylaxis of varicella in children with renal disease receiving steroids.

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.

Use of anti-hypertensive medications and post-transplant renal allograft function in children.

Post-transplant hypertension is a common occurrence in children. The relative effect of this hypertension on renal allograft function is uncertain. Examining the accumulated data for pediatric renal transplant recipients at our institution from monthly visits for up to three years, we determined whether the use of anti-hypertensive medications (anti-HTN medications) was associated with allograft dysfunction. Monthly clinical data included height, weight, serum creatinine, cyclosporin A (CsA) trough levels, number of acute rejection episodes, and number of anti-HTN medications. Estimated glomerular filtration rate (eGFR) was calculated monthly for each patient using the Schwartz formula. Time post-transplant was grouped into 6-month intervals. One thousand three hundred and sixty-three monthly data sets from 6 months (n = 76 patients) to 3 yr post-transplant (n = 47 patients) were analyzed. Overall mean eGFR was 75 mL/min/1.73 m2 at 6 months and 54 mL/min/1.73 m2 at 3 yr. A lower eGFR was found at all post-transplant time intervals for patients receiving anti-HTN medications compared with those who were not (p < 0.01). This lower eGFR was found at some but not all times post-transplant when patients were grouped by donor type or history of acute rejection episodes and analyzed separately. Mean CsA trough levels were higher at all post-transplant time intervals in patients receiving anti-HTN medications (p < 0.05). While a causal relationship between post-transplant hypertension and graft dysfunction cannot be established from this study, we conclude that the need for anti-HTN medications is associated with worse allograft function.

Serial estimation of glomerular filtration rate in children after renal transplant.

Evaluation of serial monthly estimated glomerular filtration rate (eGFR) may be useful for studying pediatric renal allograft outcome. To determine the validity of this approach, we reviewed our single-center experience in pediatric renal transplant recipients to determine the effect of risk factors for renal allograft failure on eGFR. Clinical parameters recorded monthly through 5 years post transplant allowed serial assessment of eGFR. Monthly clinical data included height, weight, serum creatinine, cumulative number of acute rejection episodes, cyclosporine dose, and cyclosporine trough levels. From these data, eGFR was calculated monthly for each patient using the Schwartz formula. Time post transplant was grouped in 6-month intervals and plotted against mean eGFR to compare eGFR in patients grouped by demographic and clinical factors; 1,786 monthly data sets from 6 months post transplant (n=76 patients) to 5 years post transplant (n=25 patients) were analyzed. Overall mean eGFR from 6 months to 1 year was 75 ml/min per 1.73 m(2) and from 4. 5 to 5 years 46 ml/min per 1.73 m(2). eGFR was lower at all time intervals for recipients of cadaver versus living-related donor grafts, and patients with >/=1 versus 0 acute rejections (P<0.01). After 1 year, eGFR was lower in black patients compared with white or Hispanic patients (P<0.01). Cyclosporine dose greater than 5 mg/kg per day was associated with better early and worse late graft function. These results are similar to those reported in multi-center studies using the outcome variable of graft failure and suggest that serial eGFR may be valid as an outcome variable to study chronic renal allograft dysfunction in children.

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

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.

Evaluation and prediction of urea rebound and equilibrated Kt/V in the pediatric hemodialysis population.

The posthemodialysis blood urea nitrogen (BUN) concentration rebounds for 30 to 60 minutes after hemodialysis in adults. Timing of the posttreatment BUN sample has a significant impact on the calculation of Kt/V. Urea rebound and its effect on Kt/V have not been extensively studied in children and adolescents. We evaluated posthemodialysis urea rebound after 46 treatments in 18 pediatric patients with end-stage renal disease. BUN levels were drawn at 30 seconds and 5 and 15 minutes posttreatment. From these values, a logarithmic regression curve was derived that defined percentage of urea rebound (%UR) = -0.254 + 10.9*log(t), (r = 0.79). Using this equation, we estimated BUN, %UR, and Kt/V at equilibration (50 minutes) for each treatment. Estimated mean %UR was 18.7%. Single-pool Kt/V (spKt/V) and estimated double-pool Kt/V (estKt/V) values were significantly different (P < 0.0001). %UR and percentage of difference between spKt/V and estKt/V did not vary as a function of dry weight, body surface area, or K/V. To test the validity of logarithmic extrapolation, additional BUN levels were drawn at 30 seconds and every 10 minutes for 1 hour postdialysis in six patients. Percentage of difference between estKt/V and measured equilibrated Kt/V was 3.6% +/- 1.7%. Our results show %UR has a significant impact on the calculation of Kt/V in children, does not vary with patient size, and is similar to that seen in adults. We have devised an easy and accurate method to predict equilibrated BUN and calculate double-pool Kt/V in children, which requires only an additional 15-minute posttreatment BUN sample.

Adverse effect of peritonitis on peritoneal membrane function in children on dialysis.

The effect of peritonitis on peritoneal membrane solute transport characteristics was determined as part of a multicenter study in children on continuous ambulatory/cycling peritoneal dialysis. Ninety-three children each underwent a 4-h peritoneal equilibration test (PET) with 1,100 ml/m2 2.5% Dianeal for determination of mass transfer area coefficients (MTAC), dialysate to plasma ratios (D/P) for creatinine and urea at 0, 30, 60, 120, 180, and 240 min and dialysate glucose levels at 0, 30, 60, 120, 180, and 240 min for calculation of D/Do. The mean age of the study cohort was 10.1 +/- 5.6 years (range 0.1-19 years). There were 162 historical episodes of peritonitis; at the time of the PET tests, 36 children had never had an episode of peritonitis (group I) while 57 children had a history of one or more episodes of peritonitis (group II). In group II children, the 4-h glucose D/Do was significantly lower and the 4-h D/P creatinine ratio, the creatinine MTAC, and the glucose MTAC were significantly higher (each P < 0.05) than in group I. In children with a history of peritonitis caused by Gram-negative organisms, the 4-h glucose D/Do (P < 0.05) and the creatinine MTAC (P < 0.05) were significantly lower and the glucose MTAC (P = 0.07) nearly significantly lower than in children without a history of peritonitis. Linear regression analysis did not demonstrate a correlation between any of the variables and duration of peritoneal dialysis, while the rate of peritonitis was weakly correlated with glucose MTAC (r = 0.34, P < 0.05) and with 4-h glucose D/Do (r = -0.222, P < 0.01). We conclude that children with a history of peritonitis have peritoneal membranes that are more permeable to glucose and creatinine than children without a history of peritonitis, and that the peritoneal membranes of children who have had peritonitis caused by Gram-negative organisms are also more permeable to creatinine and glucose. Such changes are likely to have an adverse effect on membrane function and could eventually contribute to ultrafiltration failure.

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.

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.

Effects of chronic renal failure and growth hormone on serum levels of insulin-like growth factor-binding protein-4 (IGFBP-4) and IGFBP-5 in children: a report of the Southwest Pediatric Nephrology Study Group.

Children with chronic renal failure (CRF) have high serum levels of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1), -2, and -6. The excess IGFBP-2 and -1 may play a role in the growth failure of CRF children by sequestering IGF peptides. In contrast, IGFBP-3 levels rise with GH treatment of CRF children, suggesting a role for IGFBP-3 in their accelerated growth. The present studies used sensitive and specific antisera to characterize levels and forms of IGFBP-4 and -5 in serum from CRF children. By RIA, the mean baseline serum level of IGFBP-4 was high in CRF children compared to that in normal children, but the IGFBP-4 level in CRF serum did not correlate with height SD score; by immunoblot, high CRF levels were associated with increases in both intact and fragmented IGFBP-4. Mean RIA levels of IGFBP-5 were comparable in sera from CRF and normal children. Treating CRF children with GH for 12 months increased serum IGFBP-4 levels by 26% and IGFBP-5 levels by 49%, as determined by RIA; levels of IGFBP-5, but not IGFBP-4, correlated significantly with serum levels of IGF-I, IGF-II, IGFBP-3, and acid-labile subunit and with growth rate in these GH-treated children. In summary, IGFBP-4 levels are high in serum of CRF children, and GH increases serum levels of IGFBP-4 and IGFBP-5 in these children. The data suggest a role for IGFBP-5 in the accelerated growth of GH-treated CRF children, perhaps as part of a ternary complex with acid-labile subunit and IGFs. Additional studies on the relationship between intact IGFBP-4 levels and growth are needed to determine what role IGFBP-4 plays in the linear growth process in vivo.

Pediatric experience with intradialytic parenteral nutrition and supplemental tube feeding.

Good nutrition is necessary to maximize the potential for growth and development in the pediatric age-group, but children, like adults with chronic renal failure and end-stage renal disease, may be anorectic and eat poorly. Infants and adolescents are at special risk because of the intense demands of growth during the first 2 years of life and again during puberty. Neurodevelopment is also adversely affected by poor nutrition, especially in infants. Approximately two-thirds of pediatric dialysis patients are treated with chronic peritoneal dialysis, which results in significant protein losses in the dialysis effluent that can contribute to protein-calorie malnutrition. Meeting the nutritional needs of pediatric patients usually requires supplemental sources, such as intradialytic parenteral nutrition (IDPN) or tube feeding. Little is known about the effectiveness or desirability of IDPN in pediatric patients. More studies, especially of amino acid-based dialysis fluids for chronic peritoneal dialysis, need to be done before making IDPN a standard for pediatrics. Supplemental nasogastric or gastrostomy tube feedings have been very successful in maintaining and improving growth in infants, but no studies are available to evaluate their success in older children and adolescents. Recombinant growth hormone therapy, in addition to good nutrition and control of other growth factors such as acidosis, renal osteodystrophy, and chronic volume depletion, may be necessary for most growth-retarded children with chronic renal failure to achieve normal adult height.

Increasing incidence of childhood class V lupus nephritis.

OBJECTIVE: Class V lupus nephritis (LN) is reported to occur in 0-23% of patients with LN. To better characterize pediatric LN, we determined at a single center (1) the relative frequency of Class V LN on first and serial biopsies, (2) the frequency of transformation between LN classes on serial biopsies, (3) types of treatment received and outcome to date of different classes of LN. METHODS: All pediatric renal biopsies from 1985 to the present performed for diagnosis and classification of suspected LN were reviewed. Biopsy results were grouped into 2-3 year time intervals to assess trends in the distribution of WHO class diagnoses over time. RESULTS: Sixty patients underwent 97 renal biopsies. Class V LN was present in 28% (17/60) of patients on first biopsy, and in 37% (22/60) on most recent biopsy. Class V LN on first biopsy increased from 17% (8/46) before 1995 to 64% (9/14) after 1995 (p < 0.001). Age at presentation, age at biopsy, time to biopsy, and types of treatment did not differ before and after 1995. Transformation to Class V LN occurred in 19% (5/27) of patients having repeat biopsies. No transformation from Class V LN occurred on repeat biopsy. Renal outcome was available in 48 patients with followup of 4.7 +/- 3.2 years for Class V LN, and 5.2 +/- 2.4 years for non-Class V LN. Five percent (1/20) of Class V LN patients had renal dysfunction or had died compared to 21% (6/28) of non-Class V LN patients (p = NS). CONCLUSION: We found (1) a greater frequency of Class V LN than has been reported, (2) a recent increase in the incidence of Class V LN at our institution, (3) frequent transformation between classes on serial biopsies, and (4) no regression of Class V lesions in patients who had repeat biopsies.