Glomerular filtration rate in children with solid tumors: normative values and a new method for estimation.

Many chemotherapy regimens used in children are nephrotoxic. Accurate dosing of these medications requires that some estimation of glomerular filtration rate (GFR) be performed prior to initiating chemotherapy. However, few studies evaluating normal GFR in children exist. The authors report normal values for GFR for children with nonhematogenous malignancies using a highly accurate method of directly measuring GFR and an equation for estimating absolute GFR in these children. Children with nonhematogenous malignancies with no evidence of renal involvement or prior use of nephrotoxic agents had their GFR measured using an iothalamate infusion methodology. A total of 111 children (males and females) with a mean age = 7.95 years (range 2.8 months-19.5 years) were included in the study. GFR adjusted for body surface area (mL/min/1.73 m(2)) increases in the first 2 years of life and then plateaus at a level comparable to adult values. GFR adjusted for body surface area for males >2 years = 131.3 +/- 22.5, females = 126.8 +/- 24.4 mL/min/1.73 m(2) (p value not significant). Absolute GFR in mL/min can be easily estimated by a simple formula (r(2) =.97) based on the child's weight and serum creatinine: GFR (mL/min) = k sqrt[ ( (agemos+ 6)* wt) / Cr serum ] where agemos is age in months, wt is weight in kg, and k = 1.05 for males and 0.95 for females. The accurate measurement of GFR remains vitally important in the safe and effective treatment of pediatric solid tumors. This study provides a set of normal GFR values for these children and an equation for easy estimate of absolute GFR.

Thrombogenic alleles, Escherichia coli O157:H7 infections, and hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) of childhood most commonly follows gastrointestinal infection with Escherichia coli O157:H7. This pathogen elaborates Shiga toxins that are believed to cause microvascular injury and to trigger a thrombogenic response. The exact mechanisms leading to variable disease manifestations are unknown. Allelic variation in genes encoding selected coagulation factors and inhibitors of fibrinolysis were examined to determine whether or not a causal relationship exists between hypercoagulability and the development of HUS. No correlation between the thrombogenic factor V (G1691A), factor II (G20210A), methylenetetrahydrofolate reductase (C677T), or the plasminogen activator inhibitor (PAI)-1 promotor (4G/5G) genotypes and the risk of infection with E. coli O157:H7, or the risk of development of HUS among infected patients, was found. Serum PAI-1 levels did not correlate with the PAI-1 genotype. We conclude that the alleles studied are not major risk factors for the acquisition of E. coli O157:H7 infection, or of E. coli O157:H7-related HUS.

von Willebrand factor and von Willebrand factor-cleaving metalloprotease activity in Escherichia coli O157:H7-associated hemolytic uremic syndrome.

Hemolytic uremic syndrome (HUS) usually occurs after infection with Shiga toxin-producing bacteria. Thrombotic thrombocytopenic purpura, a disorder with similar clinical manifestations, is associated with deficient activity of a circulating metalloprotease that cleaves von Willebrand factor at the Tyr842-Met843 peptide bond in a shear stress-dependent manner. We analyzed von Willebrand factor-cleaving metalloprotease activity and the status of von Willebrand factor in 16 children who developed HUS after Escherichia coli O157:H7 infection and in 29 infected children who did not develop this complication. Von Willebrand factor-cleaving metalloprotease activity was normal in all subjects, but von Willebrand factor size was decreased in the plasma of each of 16 patients with HUS. The decrease in circulating von Willebrand factor size correlated with the severity of thrombocytopenia and was proportional to an increase in von Willebrand factor proteolytic fragments in plasma. Immunohistochemical studies of the kidneys in four additional patients who died of HUS demonstrated glomerular thrombi in three patients, and arterial and arteriolar thrombi in one patient. The glomerular thrombi contained fibrin but little or no von Willebrand factor. A decrease in large von Willebrand factor multimers, presumably caused by enhanced proteolysis from abnormal shear stress in the microcirculation, is common in HUS.

Validation of PD Adequest 2.0 for pediatric dialysis patients.

Kinetic modeling has proven to be a valuable tool for peritoneal dialysis (PD) prescription in adult PD patients. The clinical application of this procedure has rarely been studied in children. We therefore evaluated the PD Adequest 2.0 for Windows program (Baxter Healthcare Co., Deerfield, IL) as a prescription aid for the management of pediatric PD patients by comparing the measured and predicted PD clearances, total drain volumes, and net ultrafiltration in 34 children (15 males) (mean age 10.9 +/- 6.0 years) receiving long-term PD. In each case, a 4-h peritoneal equilibration test was conducted with a standardized test exchange volume of 1,100 ml/m2 BSA. A total of 43 24-h dialysate (plus urine in 12) collections were analyzed. The levels of agreement between measured and predicted values for weekly peritoneal and total urea Kt/V, weekly peritoneal and total creatinine clearance, daily drain volume, net ultrafiltration and daily peritoneal urea and creatinine mass removal were assessed with correlation coefficients (re) and Bland-Altman limits of agreement. The study revealed that there is a basic level of agreement between measured and modeled values for solute removal and total drain volume, with correlation coefficients ranging from 0.75 to 0.98. In contrast, the rc for net ultrafiltration was only 0.34. The majority (75%) of patients had modeled urea and creatinine clearances that were within 20% of their measured values. These data suggest that the PD Adequest 2.0 for Windows program can predict urea and creatinine clearances with reasonable accuracy in pediatric PD patients, making it a valuable resource in prescription management.

Abnormal thiol reactivity of tropomyosin in essential hypertension and its association with abnormal sodium-lithium countertransport kinetics.

OBJECTIVES: To identify a thiol protein that is abnormal in a subgroup of essential hypertensive (EHT) patients who have a strong family history of hypertension and cardiovascular disease and have a low Km of erythrocyte Na/Li countertransport (CT). METHODS: To detect biotin maleimide labelling of a key thiol protein to investigate its reaction with N-ethylmaleimide (NEM) in normal and EHT erythrocytes. RESULTS: The thiol protein of 33 kDa apparent molecular weight (p33) identified by the loss of labelling with biotin maleimide was identified as tropomyosin due to its retarded running in 6 mol/l urea gels and immunoblotting. The NEM reaction with p33 detected by loss of subsequent biotin maleimide labelling is biphasic in normal control erythrocytes with the rate in the first 30 s double that after 30 s. In EHT erythrocytes NEM reaction (1) after 30 s is faster than normal and (2) in the first 30 s causes a paradoxical increase in apparent biotin maleimide labelling. In normal control erythrocytes, the loss of biotin maleimide labelling with NEM reaction or the faster phenylmaleimide reaction follows the same time course as the decrease in Km of Na/Li CT. CONCLUSIONS: NEM reaction with p33 requires two thiols. Only the cytoskeletal form of tropomyosin from the TM3 gene has more than one thiol group and agrees with SDS-PAGE mobility. Tropomyosin is a strong candidate to explain the familial abnormality in EHT with abnormal Na/ Li CT and it could explain many of the characteristics of this disease.

Avascular necrosis of the femoral head in children with chronic renal disease.

PURPOSE: To determine the incidence of avascular necrosis (AVN) of the femoral head in children with chronic renal failure. MATERIALS AND METHODS: Pelvic radiographs in 205 children (age range, 6 months to 16 years; mean age, 6 years +/- 3.5 [SD]) with chronic renal failure were reviewed. Serial radiographs were obtained every 6 months for 1-7 years (mean, 3 years +/- 2) to assess the presence of AVN of the femoral head; six children had metabolic renal disease, 21 had acquired renal disease, and 178 had structural renal lesions. RESULTS: Radiographic findings of AVN were seen in 14 of 205 patients (approximately one in every 15). The frequency of AVN was similar in boys and girls; AVN was observed in 11 (6.9%) of 159 boys and in three (6.5%) of 46 girls and was not related to the duration of renal disease, type of renal disease, or growth hormone therapy. Affected children were frequently asymptomatic, and, when present, the clinical complaints were mild. In two instances, AVN developed while the patients were receiving corticosteroids before entering this study. CONCLUSION: The results of this study indicate that AVN of the femoral head is a frequent complication in children with chronic renal failure, occurring in approximately 7% of this population. Unlike Legg-Calvé-Perthes disease, AVN in children with chronic renal failure is frequently asymptomatic and has no sex predilection.

Intraperitoneal administration of recombinant human growth hormone in children with end-stage renal disease.

Recombinant human growth hormone (GH) therapy has been shown to be effective in the treatment of growth failure related to growth hormone resistance among children with chronic renal failure. The traditional route of administration is subcutaneous injection. This study was designed to evaluate the effectiveness and tolerability of intraperitoneal (i.p.) administration of GH in prepubertal peritoneal dialysis patients. Nine subjects were enrolled. Eight completed 24 months of therapy with GH. Baseline height standard deviation scores (SDS) and growth velocity for the prior year were used for comparison. Peak serum GH was achieved 4 h after administration and serum half-life was 4.6 h. Mean height SDS was -3.1 at baseline, -2.5 at 1 year, and -2.3 at 2 years (NS) of GH therapy. Mean height velocity increased from a baseline of 4.6 cm/yr to 8.5 cm/yr in year 1 (P < 0.05) and 6.1 cm/yr in year 2 (NS) of i.p. GH therapy. Peritonitis infection rates were not increased from overall center rates. This research suggests that the intraperitoneal route of administration of GH can be utilized in the treatment of short stature among children requiring maintenance peritoneal dialysis therapy.

Anthropometric measures and risk of death in children with end-stage renal disease.

We evaluated the association between anthropometric measurements and death among pediatric patients with end-stage renal disease (ESRD) using data from the Pediatric Growth and Development Special Study (PGDSS) from the US Renal Data System. Height, growth velocity, and body mass index (BMI) were used for the analysis of 1,949 patients in the PGDSS. To standardize these measurements, SD scores (SDSs) were calculated using population data from the Third National Health and Nutrition Examination Survey. Using Cox proportional hazards models, we assessed the association between anthropometric measures and death, controlling for demographic factors and stratifying by age. Multivariate analysis showed that each decrease by 1 SDS in height was associated with a 14% increase in risk for death (adjusted relative risk [aRR], 1.14; 95% confidence interval [CI], 1.02 to 1.27; P = 0.017). For each 1 SDS decrease in growth velocity among patients in our sample, the risk for death increased by 12% (aRR, 1.12; 95% CI, 1.00 to 1.25; P = 0.043). There was a statistically significant U-shaped association between BMI and death (P = 0.001), with relatively low and high BMIs associated with an increased risk for death. In children with ESRD, growth delay and extremes in BMI are associated with an increased risk for mortality.

The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections.

BACKGROUND: Children with gastrointestinal infections caused by Escherichia coli O157:H7 are at risk for the hemolytic-uremic syndrome. Whether antibiotics alter this risk is unknown. METHODS: We conducted a prospective cohort study of 71 children younger than 10 years of age who had diarrhea caused by E. coli O157:H7 to assess whether antibiotic treatment in these children affects the risk of the hemolytic-uremic syndrome and to assess the influence of confounding factors on this outcome. Estimates of relative risks were adjusted for possible confounding effects with the use of logistic-regression analysis. RESULTS: Among the 71 children, 9 (13 percent) received antibiotics and the hemolytic-uremic syndrome developed in 10 (14 percent). Five of these 10 children had received antibiotics. Factors significantly associated with the hemolytic-uremic syndrome were a higher initial white-cell count (relative risk, 1.3; 95 percent confidence interval, 1.1 to 1.5), evaluation with stool culture soon after the onset of illness (relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.8), and treatment with antibiotics (relative risk, 14.3; 95 percent confidence interval, 2.9 to 70.7). The clinical and laboratory characteristics of the 9 children who received antibiotics and the 62 who did not receive antibiotics were similar. In a multivariate analysis that was adjusted for the initial white-cell count and the day of illness on which stool was obtained for culture, antibiotic administration remained a risk factor for the development of the hemolytic uremic syndrome (relative risk, 17.3; 95 percent confidence interval, 2.2 to 137). CONCLUSIONS: Antibiotic treatment of children with E. coli O157:H7 infection increases the risk of the hemolytic-uremic syndrome.

Dialysis for end-stage renal disease.

Peritoneal dialysis is the major renal replacement therapy for children with end-stage renal disease, with hemodialysis used for a substantial number of pediatric patients. Reduction of morbidity and mortality is a major goal with the use of these modalities. Adequacy of dialysis and maintenance of peritoneal membrane function are important considerations for children on long term dialysis. Both adequacy and function are important to ensure optimal growth and nutrition and improve morbidity in this population. Use of supplemental gastrostomy tube feeds has improved calorie-protein malnutrition. Therapy advancements, such as growth hormone and erythropoietin, have improved the quality of life for dialysis patients. As the survival of the pediatric patient with end-stage renal disease improves, issues regarding cardiovascular disease and other factors that increase mortality in the adult population will need to be addressed.

Peritoneal dialysis catheter infections and peritonitis in children: a report of the North American Pediatric Renal Transplant Cooperative Study.

Peritonitis and catheter-related infections remain the two most-common causes of peritoneal dialysis (PD) treatment failure. To define the frequency and risks associated with exit site/tunnel infections (ESI/TI), as well as peritonitis, in pediatric patients on PD, we undertook a retrospective cohort study of patients initiated on PD in the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). We examined demographic data and PD catheter characteristics of 1,258 patients, aged < or = 21 years, initiated on PD from 1992 to 1997. We examined the frequency and complications of ESI/TI occurring within 30 days, 6 months, and 1 year of follow-up. For peritonitis episodes, we examined patient risk factors for peritonitis. Almost 11% of patients had an ESI/TI at 30 days, 26% between 30 days and 6 months, and 30% between 6 months and 1 year of follow-up. There was no increased risk of ESI/TI associated with patient age, race, or catheter characteristics. Peritonitis occurred in dialysis patients at a rate of 1 episode per 13.2 patient months. Proportional hazards regression analysis demonstrated that black race, single-cuffed catheters, and upward pointing exit sites were independent risk factors for peritonitis in the pediatric PD population. Patients with ESI/TI had twice the risk of those without these infections of developing peritonitis or needing access revision, and an almost threefold increased risk of hospitalization for access complications/malfunction. ESI/TI occurs commonly in pediatric PD patients. These infections cause significant morbidity, through risk of peritonitis, access revision, and hospitalization for catheter complications. Further study of potentially modifiable risk factors for ESI/TI in pediatric end-stage renal disease patients is warranted.

Intraperitoneal erythropoietin in children on peritoneal dialysis: A study of pharmacokinetics and efficacy.

The pharmacokinetics and efficacy of intraperitoneal (IP) recombinant human erythropoietin (rHuEPO) were investigated in children undergoing chronic peritoneal dialysis. Eight children were administered a single dose of 100 U/kg of rHuEPO IP with 50 mL of dialysate into a dry peritoneal cavity after nighttime peritoneal dialysis. Serum erythropoietin (EPO) levels were measured at 0, 8, 12, and 24 hours. A mean peak EPO level of 187 mU/mL was obtained at 12 hours. The area under the curve was 5,818 mU/h/mL, and relative bioavailability was similar to that found using subcutaneous (SC) dosing. Nine children completed 11 to 12 weeks of IP rHuEPO therapy. The patients maintained a normal hematocrit (34% +/- 2.3%) with a mean final IP rHuEPO dosage that was not significantly greater than the mean previous SC dosage (IP, 290 +/- 194 U/kg/wk; SC, 279 +/- 126 U/kg/wk; P = not significant). There appeared to be a trend for a slightly increased risk for peritonitis compared with historical controls at our center (relative risk = 3.1; 95% confidence interval, 0.92 to 6.3). IP rHuEPO is effective in children undergoing continuous cycling peritoneal dialysis without requiring increased rHuEPO dosages, but the possibility of an increased risk for peritonitis will need to be further explored.

Safety and efficacy of erythropoietin in children with chronic renal failure.

A prospective randomized study of the use of recombinant human erythropoietin (rHuEPO) in children with chronic renal disease was conducted to assess dosing requirements and side effects. Forty-four children with chronic renal failure, aged 4 months to 21 years, were studied. Twenty-five patients were pre dialysis, 10 on peritoneal dialysis, and 9 on hemodialysis. Patients received either 150 U/kg per week or 450 U/kg per week divided thrice weekly of rHuEPO for 12 weeks or until target hemoglobin (Hb) was attained. Dose was then adjusted to maintain a normal Hb. Eighty-two percent of patients reached target Hb by 7.9+/-5.6 weeks (mean+/-SD); 95% of patients in the high-dose group and 66% in the low-dose group reached target Hb within 12 weeks. The overall median rHuEPO dose at target Hb was 150 U/kg per week. Hemodialysis patients tended to require more rHuEPO to maintain a normal Hb (median 250 U/kg per week). Transfusion requirements and panel-reactive antibody levels decreased during the 12 weeks. Iron deficiency and/or hypertension occurred in 30% of children. In conclusion, rHuEPO at 150 U/kg per week is safe and effective in treating anemia in children with chronic renal disease.

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.

Caffeine releases a glucose-primed endoplasmic reticulum Ca2+ pool in the insulin secreting cell line INS-1.

Caffeine mobilized an intracellular Ca2+ pool in intact fura-2-loaded INS-1 cells in suspension exposed to high (16 mM) [glucose], while a minor effect was observed with low (2 mM) [glucose]. Cells were kept in a medium containing diaxozide or no Ca2+ to prevent the influx of extracellular Ca2+. The caffeine-sensitive intracellular Ca2+ pool was within the endoplasmic reticulum since it was depleted by the inhibitor of the reticular Ca2+ pumps thapsigargin and the InsP3-dependent agonist carbachol. No effect of caffeine was observed in the parent glucose-insensitive RINmF5 cells. In microsomes from INS-1 but not RINmF5 cells, the type 2 ryanodine receptor was present as revealed by Western blotting. It was concluded that the endoplasmic reticulum of INS-1 cells possesses caffeine-sensitive type 2 ryanodine receptors Ca2+ channels.

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.

Glucose induces glucose 6-phosphatase hydrolytic subunit gene transcription in an insulinoma cell line (INS-1).

Primer extension analysis and RNase protection assays revealed the identity of glucose 6-phosphatase gene transcripts in both the insulinoma cell line INS-1 and hepatic cells. In transient transfection assays of INS-1 cells, using constructs between the human glucose 6-phosphatase gene promoter and a luciferase reporter gene, the reporter gene activity was induced by dexamethasone and dibutyryl cAMP. Furthermore, the promoter was regulated by the glucose concentration in the medium. This effect was dependent on glucose metabolism. The data indicated that glucose 6-phosphatase gene transcription is regulated in a similar way in the insulinoma cell line and in liver.

Conformational change of the catalytic subunit of glucose-6-phosphatase in rat liver during the fetal-to-neonatal transition.

The glucose-6-phosphatase system was investigated in fetal rat liver microsomal vesicles. Several observations indicate that the orientation of the catalytic subunit is different in the fetal liver in comparison with the adult form: (i) the phosphohydrolase activity was not latent using glucose-6-phosphate as substrate, and in the case of other phosphoesters it was less latent; (ii) the intravesicular accumulation of glucose upon glucose-6-phosphate hydrolysis was lower; (iii) the size of the intravesicular glucose-6-phosphate pool was independent of the glucose-6-phosphatase activities; (iv) antibody against the loop containing the proposed catalytic site of the enzyme inhibited the phosphohydrolase activity in fetal but not in adult rat liver microsomes. Glucose-6-phosphate, phosphate, and glucose uptake could be detected by both light scattering and/or rapid filtration method in fetal liver microsomes; however, the intravesicular glucose-6-phosphate and glucose accessible spaces were proportionally smaller than in adult rat liver microsomes. These data demonstrate that the components of the glucose-6-phosphatase system are already present, although to a lower extent, in fetal liver, but they are functionally uncoupled by the extravesicular orientation of the catalytic subunit.

Cholelithiasis following Escherichia coli O157:H7-associated hemolytic uremic syndrome.

Sequelae of Escherichia coli O157:H7-associated hemolytic uremic syndrome (HUS) 2-3 years following an outbreak in Washington State have been prospectively studied to identify predictors of adverse sequelae. Logistic regression analysis was used to examine associations between findings in the acute course and long-term renal and gastrointestinal outcomes. Twenty-one percent of patients had gastrointestinal sequelae, which included cholelithiasis resulting in cholecystectomy (3/29), persistent pancreatitis (2/29), late colon stricture (1/29), and/or glucose intolerance (1/29). Logistic regression analysis found long-term gastrointestinal sequelae were higher in patients who, during HUS, had hypertension [odds ratio (OR) = 21.2, 95% confidence interval (CI) = 1.9-164.4, P = 0.01] or gastrointestinal complications (OR = 21.2, 95% CI = 1.9-164.4, P = 0.01). Renal sequelae were seen in 35% of patients. One patient (4%) had persistent hypertension and 9 (31%) had minor urinary findings (hematuria or proteinuria). Thrombocytopenia lasting longer than 10 days during the acute illness was associated with a risk for subsequent renal sequelae (OR = 15.0, 95% CI = 1.98-1,703.0, P = 0.009). We conclude a high incidence of gastrointestinal sequelae, especially cholelithiasis presenting long after the acute illness, may be seen with HUS. The short follow-up period may underestimate the extent and severity of eventual renal sequelae.

Current advances in the therapy of chronic renal failure and end stage renal disease.

The improved outcomes recently experienced by children with chronic renal failure and end stage renal disease (ESRD) does not obviate the need to strive to better the quality of their physical, mental and emotional well-being. This article reviews some of the recent advances in the care of these children that are intended to achieve that goal. Dialysis topics include prescription, novel solutions, adequacy measures, management of anemia, and access. Transplantation areas covered include graft and patient survival, growth, organ availability, opportunistic infections and immunity, immunosuppressive agents, and transplant-related malignancies. The care of the pre-ESRD patient is discussed with a review of new data that are being compiled in this patient population.