Biomedical subjects
Publications and source records attributed to Larry A Greenbaum.
Vesicoureteral reflux, the abnormal flow of urine from the bladder into the ureter, is one of the most common congenital anomalies found in children. The association of vesicoureteral reflux with urinary tract infections and renal scarring has important clinical implications. New insights into pathogenesis and new surgical techniques are changing the approach to the management of this disorder.
This double-blind, placebo-controlled study evaluated the safety and efficacy of intravenous (i.v.) calcitriol (Calcijex) for treatment of secondary hyperparathyroidism (secondary HPT) in pediatric end-stage renal disease (ESRD) patients on hemodialysis (HD). After a 2 to 6-week washout period of all vitamin D compounds, patients with two consecutive PTH values > 400 pg mL(-1), calcium levels < or = 10.5 mg dL(-1) and calcium x phosphorus product values < or = 70 mg2 dL(-2) were eligible for the treatment phase. Patients received a bolus injection of calcitriol or placebo three times a week, immediately after dialysis for up to 12 weeks. Initial doses (0.5-1.5 microg) were based on the severity of secondary HPT. The dose was increased every two weeks by 0.25 microg until there was at least a 30% decrease in PTH from baseline, or Ca > 11.0 mg dL(-1), or Ca x P > 75 mg2 dL(-2). Overall, 11/21 (52%) patients in the calcitriol group had two consecutive > or = 30% decreases from baseline in serum PTH compared with 5/26 (19%) patients in the placebo group (P=0.03). The mean total alkaline phosphatase decreased from 274 to 232 IU L(-1) in the calcitriol group and increased from 547 to 669 IU L(-1) in the placebo group (P=0.002). The mean bone-specific alkaline phosphatase decreased from 72.5 to 68 microg L(-1) in the calcitriol group and increased from 105.3 to 148.5 microg L(-1) in the placebo group (P=0.03). The incidence of two consecutive occurrences of elevated calcium x phosphorus (Ca x P > 75 mg2 dL(-2)) product was higher in the calcitriol group than in the placebo group (P=0.01). Two consecutive occurrences of phosphorus > 6.5 mg dL(-1) occurred in 71% of the calcitriol group and 46% of the placebo group (P=0.14). Calcium levels > 10.5 mg dL(-1) were more common in the calcitriol group than in the placebo group (P=0.01). There was a direct relationship between serum phosphorus concentration and the percentage change in PTH from baseline in both the calcitriol group (r=0.46; P<0.0001) and the placebo group (r=0.21; P=0.0005). This study demonstrates that i.v. calcitriol, at initial doses of 0.5-1.5 microg, effectively reduces PTH levels in pediatric HD patients and that patients should be closely monitored for hyperphosphatemia and elevated Ca x P product.
BACKGROUND: Children admitted to the hospital with urinary tract infections (UTIs) receive empirical antibiotic therapy. There is limited information on bacterial resistance to commonly prescribed intravenous antibiotics or on the risk factors for increased resistance in these patients. OBJECTIVES: To determine the antibiotic resistance pattern in children admitted to the hospital with UTIs, and to determine if history of UTI, antibiotic prophylaxis, or vesicoureteral reflux increases the risk of resistant organisms. DESIGN/METHODS: We reviewed all of the cases of UTI in children up to 18 years of age who were admitted during a 5-year period to Children's Hospital of Wisconsin, Milwaukee. We recorded age, sex, culture and sensitivity results, imaging that was performed, and past medical history. RESULTS: We identified 361 patients with UTIs. Escherichia coli caused 87% of the infections, although E coli was significantly less common in children receiving prophylactic antibiotics (58%; P<.001) or in children with a history of UTI (74%; P<.001). Resistance to cefotaxime sodium was 3% in the patients not receiving antibiotic prophylaxis, but was 27% in the children receiving prophylactic antibiotics (relative risk, 9.9; 95% confidence interval, 4.0-24.5; P<.001). Resistance to aminoglycoside antibiotics was 1% in the children not receiving prophylaxis and 5% in the children receiving prophylactic antibiotics. CONCLUSIONS: Children who are receiving prophylactic antibiotics and are admitted to the hospital for a UTI are often infected with an organism that is resistant to third-generation cephalosporins. These children are more appropriately treated with an aminoglycoside antibiotic.
Anemia in children with chronic kidney disease (CKD) is common secondary to inadequate erythropoietin production, iron deficiency, blood loss, inflammation, secondary hyperparathyroidism, uremic toxins, and nutritional deficiencies. Anemia has a variety of deleterious consequences, including associations with increased mortality and left ventricular hypertrophy. Recombinant human erythropoietin is effective in treating anemia in children with CKD, and recent studies show that darbepoetin alpha is an attractive alternative because it requires less frequent injections. Iron deficiency is a major cause of anemia that is resistant to erythropoietin or darbepoetin alpha. Although oral iron is effective in some patients, many children, especially those receiving hemodialysis, require intravenous iron to replenish their iron stores. Both acute dosing and chronic dosing of intravenous iron are effective in pediatric patients.
PURPOSE OF REVIEW: Obstruction can either be defined as a condition that hampers optimal renal development, or, more conservatively, as a restriction to urinary outflow that, when left untreated, will cause progressive renal deterioration. Currently, management is mostly based on the latter definition, but still remains controversial. Relevant work published before 2002 is considered because of a lack of recent literature. RECENT FINDINGS: Almost all reports comparing the primary conservative treatment of suspected obstruction versus early surgical intervention show comparable results, but there are different interpretations. The approach of 'watch and wait' for a unilateral hydronephrotic kidney with normal function is usually quite safe, with a very low risk of the permanent loss of renal function when accompanied by close monitoring, but it is certainly not without risk. At this time, the main underlying problems are that all currently applied diagnostic methods only detect effects secondary to obstruction, and the currently used definition of obstruction is based on a longitudinal observation period. The most relevant publication in the observation period was an in-depth report on a workshop in which the need for valid prospective markers for renal maldevelopment and 'significant' obstruction was expressed. SUMMARY: The optimal management of infants with congenital hydronephrosis and suspected obstruction will remain controversial until new diagnostic methods are able to discriminate between 'harmful' and 'harmless' obstruction. Most experts currently advocate primary conservative management, with close follow-up and surgical intervention only if there are signs of reduced function of the obstructed kidney.
OBJECTIVES: To compare the clearances of low molecular weight molecules using three modalities of continuous renal replacement therapy (CRRT) at the low blood flow rates typically used in pediatric patients. DESIGN: A controlled, in vitro laboratory study. SETTING: Research laboratory of a health sciences university. SUBJECTS: AN69 dialysis hemofilter. INTERVENTIONS: CRRT was performed using a 0.6 m(2) AN69 hemofilter. Human whole blood and plasma were combined to achieve a hematocrit of approximately 30%. Urea and creatinine were added to obtain concentrations of approximately 54 mmol/L of blood urea nitrogen and 1770 micromol/L of creatinine. Clearance data for urea and creatinine at a blood flow rate of 60 mL/min were generated using predilution continuous venovenous hemofiltration (CVVH), postdilution CVVH, and continuous venovenous hemodialysis (CVVHD). MEASUREMENTS AND MAIN RESULTS: Clearance of all three modalities was compared at a replacement solution (CVVH) or dialysate (CVVHD) flow rate of 16.7% of the blood flow rate. Both postdilution CVVH and CVVHD had a urea clearance of 11.3 mL/min, which was 15% greater than the 9.8 mL/min urea clearance of predilution CVVH (p <.005). Creatinine clearance with postdilution CVVH (10.7 mL/min) was 15% greater than the 9.0 mL/min clearance produced by predilution CVVH (p < 0.01). Predilution CVVH and CVVHD were compared at a flow rate of either replacement solution (CVVH) or dialysate (CVVHD) of 33% and 50% of the blood flow rate. Postdilution CVVH was not performed at high ultrafiltration rates due to the potential problem of hemoconcentration. CVVHD clearances of urea and creatinine were statistically superior to predilution CVVH at both flow rates. CONCLUSIONS: CVVHD was superior to predilution CVVH for clearance of urea and creatinine. Postdilution CVVH and CVVHD gave nearly equivalent clearances. At the low blood flow rates used in pediatric patients, which raise concerns about high ultrafiltration during postdilution CVVH causing excessive hemoconcentration and filter clotting, CVVHD appears to be the optimal modality for maximizing clearance of small solutes during CRRT.
Growth retardation is a common complication in children with chronic kidney disease. Treatable causes of growth retardation in these patients include renal osteodystrophy, metabolic acidosis, and inadequate nutritional intake. In addition, disturbances in the growth hormone-insulinlike growth factor I axis are a major cause of decreased growth. Administration of recombinant human growth hormone can overcome this problem, allowing catch-up growth and achievement of normal or improved adult height.
BACKGROUND: Nutritional vitamin D deficiency rickets occurs when children do not receive adequate vitamin D, which can be obtained from diet or manufactured in the skin when there is adequate sun exposure. A number of reports have described cases of vitamin D deficiency rickets in breastfed infants, but the public health significance of this problem in Wisconsin is unknown. OBJECTIVES: Our objectives were to identify cases of vitamin D deficiency rickets in Wisconsin infants and to determine the percentage of these infants participating in the Wisconsin Women, Infant and Children (WIC) program. METHODS: All cases of rickets due to nutritional vitamin D deficiency seen at Children's Hospital of Wisconsin or its associated outpatient clinics were identified by retrospective chart review. Data collected included date of birth, age at presentation, race, clinical presentation, diet history, history of vitamin supplementation, x-ray findings, and biochemical studies. The children with nutritional vitamin D deficiency rickets were cross-referenced with the Wisconsin WIC database. RESULTS: Fifty-one definite cases of nutritional vitamin D deficiency rickets were identified. Skeletal deformities, failure to thrive, fractures, seizures, incidental lab finding, tetany, and refusal to walk were the most common reasons for identifying rickets. All of the children were breastfed and did not receive vitamin supplementation. The infants had a mean age of 13.6 months and 46 (90%) were African American. Thirty-seven out of 51 children (73%) were enrolled in the Wisconsin WIC program. CONCLUSION: Vitamin D deficiency nutritional rickets is an important public health problem in Wisconsin. The Wisconsin WIC program may be an important site for intervention strategies.
We describe three cases of poststreptococcal glomerulonephritis (PSGN) associated with autoimmune hemolytic anemia. Along with the classic findings of PSGN, the patients had a positive direct antiglobulin test. Two patients had a cold-reacting anti-I autoantibody. This is the first description of this association. Autoimmune hemolytic anemia should be considered in children with PSGN and significant anemia or signs of hemolysis.
BACKGROUND: The American Academy of Pediatrics practice parameter for urinary tract infection suggests a repeat urine culture if the expected clinical response is not achieved within the first 48 hours of therapy. The utility of repeat urine cultures and clinical significance of fever at 48 hours is unclear. OBJECTIVES: To determine the frequency of positive repeat urine cultures in children admitted to the hospital with urinary tract infection, and to describe the fever curves of children admitted to the hospital with urinary tract infection. DESIGN AND METHODS: We reviewed all cases of urinary tract infection in children 18 years and younger who were admitted during a 5-year period to Children's Hospital of Wisconsin (Milwaukee). We recorded temperatures from hospital admission to discharge, age, sex, initial and follow-up culture results, antibiotics received, imaging performed, and medical history. RESULTS: Urinary tract infection was identified in 364 patients, and 291 (79.9%) had follow-up urine cultures. None were positive. Follow-up cultures produced 21,388.50 US dollars in patient charges. Fever lasted beyond 48 hours in 32% of patients. Older children were more likely to have fever beyond 48 hours. CONCLUSIONS: Follow-up urine cultures were of no utility in children hospitalized for urinary tract infection, including those with fever lasting beyond 48 hours or those with an underlying urologic disease. Fever beyond 48 hours is common and should not be used as a criterion for obtaining a repeat urine culture. These conclusions are valid for children with vesicoureteral reflux. Such an approach would result in significant cost savings.
A 1-year-old boy had severe anoxic brain injury owing to a cardiorespiratory arrest. He had an initial metabolic acidosis, but this largely resolved by hospital day 2. He then had a persistent, profound metabolic acidosis. Evaluation on hospital day 6 found that the patient had ketonemia, ketonuria, and a normal serum glucose level; he had received no intravenous dextrose during his hospitalization. The dextrose-free fluids were given initially to protect his brain from the deleterious effects of hyperglycemia after brain injury. Continuation beyond 24 hours was inadvertent. The initiation of dextrose-containing intravenous fluids produced a rapid resolution of his metabolic acidosis. Starvation usually produces a mild metabolic acidosis, but when combined with physiologic stress, starvation may cause a severe metabolic acidosis. Among the few reports of severe starvation ketoacidosis, our case is unique because the patient was monitored closely in an intensive care unit, allowing us to describe the time course of the acidosis in detail.
FSGS is a common indication for kidney transplantation in children. However, transplantation is often complicated by recurrence of FSGS in the transplanted kidney, resulting in nephrotic syndrome and an increased risk of graft loss. Acute treatment strategies for recurrent FSGS include plasmapheresis and increased immunosuppressive therapy. There is little information on the long-term management of immunosuppression in these patients. We describe two children who were successfully treated with plasmapheresis for recurrent FSGS that occurred immediately post-transplant. Nephrotic syndrome reappeared years later when the patients were converted from daily to alternate day prednisone. In children with a history of FSGS, caution is necessary when altering the dosing schedule of prednisone.