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Rationale & Objective Remission of proteinuria has been shown to be associated with lower rates of kidney disease progression among people with focal segmental glomerulosclerosis (FSGS). The goal of this study was to evaluate whether reductions in proteinuria after treatment are associated with greater kidney survival. Study Design Cohort analysis of clinical trial participants. Setting & Participants Patients with steroid-resistant FSGS enrolled in a randomized treatment trial that compared cyclosporine with mycophenolate mofetil plus dexamethasone. Predictors Reduction in proteinuria measured during 26 weeks after initiating treatment. Outcomes Repeated assessments of estimated glomerular filtration rate (eGFR) and time to a composite outcome of kidney failure or death assessed between 26 weeks and 54 months after randomization. Analytical Approach Multivariable linear mixed-effects models with participant-specific slope and intercept to estimate the association of change in proteinuria over 26 weeks while receiving treatment with the subsequent slope of change in eGFR. Multivariable time-varying Cox proportional hazards models were used to estimate the association of changes in proteinuria with time to the composite outcome. Results 138 of 192 trial participants were included. Changes in proteinuria over 26 weeks were significantly related to eGFR slope. A 1-unit reduction in log-transformed urinary protein-creatinine ratio was associated with a 3.90 mL/min/1.73 m2 per year increase in eGFR (95% CI, 2.01-5.79). This difference remained significant after adjusting for complete remission. There was an analogous relationship between time-varying proteinuria and time to the composite outcome: the HR per 1-unit reduction in log-transformed urinary protein-creatinine ratio was 0.23 (95% CI, 0.12-0.44). Limitations Limited to individuals with steroid-resistant FSGS followed up for a maximum of 5 years. Conclusions These findings provide evidence for the benefit of urinary protein reduction in FSGS. Reductions in proteinuria warrant further evaluation as a potential surrogate for preservation of kidney function that may inform the design of future clinical trials.

The review provides a historical perspective on the convergence of our understanding of the physiology and pathophysiology of bone, calcium, phosphorus, vitamin D, parathyroid hormone, and FGF-23 their impact on rickets.

Summary Background and objectives FSGS histologic variants have correlated with outcomes in retrospective studies. The FSGS Clinical Trial provided a unique opportunity to study the clinical impact of histologic variants in a well defined prospective cohort with steroid-resistant primary FSGS. Design, setting, participants, & measurements Renal biopsies of 138 FSGS Clinical Trial participants aged 2–38 years enrolled from 2004 to 2008 were analyzed using the Columbia classification by core pathologists. This study assessed the distribution of histologic variants and examined their clinical and biopsy characteristics and relationships to patient outcomes. Results The distribution of histologic variants was 68% (n=94) FSGS not otherwise specified, 12% (n=16) collapsing, 10% (n=14) tip, 7% (n=10) perihilar, and 3% (n=4) cellular. Individuals with not otherwise specified FSGS were more likely to have subnephrotic proteinuria (P=0.01); 33% of teenagers and adults had tip or collapsing variants compared with 10% of children, and subjects with these variants had greater proteinuria and hypoalbuminemia than not otherwise specified patients. Tip variant had the strongest association with white race (86%) and the lowest pathologic injury scores, baseline creatinine, and rate of progression. Collapsing variant had the strongest association with black race (63%, P=0.03) and the highest pathologic injury scores (P=0.003), baseline serum creatinine (P=0.003), and rate of progression. At 3 years, 47% of collapsing, 20% of not otherwise specified, and 7% of tip variant patients reached ESRD (P=0.005). Conclusions This is the first prospective study with protocol-defined immunomodulating therapies confirming poor renal survival in collapsing variant and showing better renal survival in tip variant among steroid-resistant patients.

Changes in proteinuria have been suggested as a surrogate outcome for kidney disease progression to facilitate the conduct of clinical trials. This report summarizes a workshop sponsored by the National Kidney Foundation and US Food and Drug Administration (FDA) with the following goals: (1) to evaluate the strengths and limitations of criteria for assessment of proteinuria as a potential surrogate end point for clinical trials in chronic kidney disease (CKD), (2) to explore the strengths and limitations of available data for proteinuria as a potential surrogate end point, and (3) to delineate what more needs to be done to evaluate proteinuria as a potential surrogate end point. We review the importance of proteinuria in CKD, including the conceptual model for CKD, measurement of proteinuria and albuminuria, and epidemiological characteristics of albuminuria in the United States. We discuss surrogate end points in clinical trials of drug therapy, including criteria for drug approval, the definition of a surrogate end point, and criteria for evaluation of surrogacy based on biological plausibility, epidemiological characteristics, and clinical trials. Next, the report summarizes data for proteinuria as a potential surrogate outcome in 3 broad clinical areas: early diabetic kidney disease, nephrotic syndrome, and diseases with mild to moderate proteinuria. We conclude with a synthesis of data and recommendations for further research. At the present time, there appears to be sufficient evidence to recommend changes in proteinuria as a surrogate for kidney disease progression in only selected circumstances. Further research is needed to define additional contexts in which changes in proteinuria can be expected to predict treatment effect. We recommend collaboration among many groups, including academia, industry, the FDA, and the National Institutes of Health, to share data from past and future studies.

Participants of the first colloquium of the Residency Review and Redesign in Pediatrics (R3P) Project considered possible scenarios affecting pediatric practice over the next 15 to 20 years and speculated about the knowledge and skills that pediatricians would need to care for children, adolescents, and young adults in the future. They concluded that the imponderables and complexity of that undertaking fell into the category of a “wicked problem” with no unique solutions. The specifics of the future cannot be predicted, but the themes important to thinking about the future are clear and must be incorporated into thinking about pediatric residency education.

The American Academy of Pediatrics is committed to working to ensure that workplaces and educational settings in which pediatricians spend time are free of sexual harassment. The purpose of this statement is to heighten awareness and sensitivity to this important issue, recognizing that institutions, clinics, and office-based practices may have existing policies.

The Centers for Medicare & Medicaid Services' (CMS) end-stage renal disease (ESRD) Clinical Performance Measures (CPM) Project has collected data on all adolescent hemodialysis patients since 2000. Thus, by 2002 data were available on all adolescents on hemodialysis in the USA for 3 consecutive years. Possible associations between clinical parameters and linear growth in this cohort were evaluated. Ninety-four adolescents were on hemodialysis for the 3 study years. The mean height standard deviation score (ht SDS) fell from -1.97 to -2.36 over the 3 study years. Compared with patients with ht SDS > or =-1.88, patients with ht SDS

A 4-year-old boy weighing 15 kg presented with a 3-day history of vomiting, decreased appetite, and 2 days of nonbloody diarrhea. He was “warm to the touch” according to the parents, but no direct measurement of temperature was taken. An older sibling had had a similar illness 5 days prior to the onset of vomiting by the patient. For the previous 2 days, the patient had ingested only water, apple juice, and non-cola soft drinks. The parents believed that his urine output had dropped but only in the previous 12 hours. The patient’s past medical history and review of systems were unremarkable. He took no medications on a chronic basis, although acetaminophen in appropriate doses was used by the family “when the child felt warm” (2–3 times/day). On physical examination, he was mildly irritable and appeared somewhat uncomfortable while sitting quietly on his parent’s lap. The oral temperature was 38.2◦C

Physicians giving children fluid therapy today seldom encounter overt dehydration or signs of shock that call for rapid and aggressive extracellular fluid (ECF) expansion. Physicians in the era when severe diarrheal dehydration was common first restored ECF' with isotonic saline, a then planned maintenance and replacement therapies, using hypotonic saline. Today, physicians plan fluid therapy mostly for children with pneumonia, meningitis, other acute disorders, or for children scheduled for surgery. These children are seldom overtly dehydrated or in shock. Common practice in this setting is to initiate fluid therapy with hypotonic saline as maintenance therapy. However, hyponatremia has been a worrisome complication with this practice. 1,2,3 In extreme cases, convulsions, brain injury, or death have resulted.4 Two recent articles 5,6 have recommended giving maintenance therapy as isotonic saline to avoid this risk. While authors of these articles have done a service in calling attention to the problem of hyponatremia, we believe their remedy has risks of its own. Our analysis of the cases we reviewed suggests a more physiologic approach, using tested principles of fluid therapy. In this report, we review maintenance therapy, cite clinical findings in the cases we surveyed that support subtle hypovolemia as the common cause of hyponatremia, describe the role of rapidly giving isotonic saline to correct hypovolemia, cite risks of using isotonic saline as maintenance therapy, and define a physiologically based fluid therapy protocol that avoids hyponatremia.

In 2000 and 2001, The Centers for MedicareMedicaid Services (CMS) End-Stage Renal Disease (ESRD) Clinical Performance Measures (CPM) project collected data on all in-center hemodialysis (HD) patients in the United States agedor=12 and18 years. There were 433 of 486 (89%) patients and 435 of 516 (84%) patients who had the minimum required data submitted and were included in the 2000 and 2001 study years, respectively. There were 188 patients (43%) who had data submitted in both study years, providing longitudinal data on this cohort. A comparison of clinical parameters on these 188 patients in the 2000 and 2001 study years reveals significant improvement in mean calculated spKt/V (1.50+/-0.36 vs. 1.58+/-0.30, P0.01), mean hemoglobin (11.0+/-1.6 g/dl vs. 11.5+/-1.3 g/dl, P0.001), mean ferritin (286+/-278 ng/ml vs. 460+/-353 ng/ml, P0.001), mean transferrin saturation (27.8+/-15.1% vs. 31.3+/-15.0%, P0.05), mean serum albumin as measured by the bromocresol green method (3.83+/-0.54 g/dl vs. 3.95+/-0.42 g/dl, P0.01), and mean height standard deviation score (-1.814+/-1.756 vs. -1.699+/-1.657, P0.05). In addition, 20 of 29 (69%) patients who had a spKt/V1.2 in the 2000 study year had a spKt/V1.2 in the 2001 study year. Of 68 (44%) patients who had a catheter as their HD access in the 2000 study year, 30 had an arteriovenous fistula or graft in the 2001 study year and 49 of 80 (61%) patients who had a mean hemoglobin11 g/dl in the 2000 study year had a hemoglobin11 g/dl in the 2001 study year. In summary, these longitudinal data demonstrate significant improvements in nearly all clinical parameters studied in these adolescent HD patients.

Oxidative stress, an antioxidant/pro-oxidant imbalance, in patients with juvenile essential hypertension was measured via several biochemical parameters. As the blood pressure is associated with the body mass index (BMI), results were compared with those on BMI-matched controls.A prospective observational study at a university teaching hospital.Children and adolescents with essential hypertension (mean standard deviation: age 14.4 +/- 3.1 years, BMI 25.0 +/- 6.9 kg/m(2), n = 52) before any treatment, and controls with a similar BMI distribution (age 14.3 +/- 4.3 years, BMI 24.4 +/- 6.6 kg/m(2), n = 48).Measurements were made of the plasma levels of (1) nitrites + nitrates, an indirect measure of available nitric oxide; (2) lipid peroxidation end-products, as malondialdehydes and free thiols; and (3) the redox status of the red blood cell glutathione, as a new oxidative stress parameter.There were decreased plasma levels of nitrates and increased levels of lipid peroxidation end-products in the hypertensive patients, resulting in a consistent increase in the plasma lipid peroxidation/nitric oxide ratio as compared with the controls with the same BMI (P0.01). This ratio additionally correlated directly with both the systolic and diastolic blood pressures for the overall patient population (P0.001). A significant glutathione depletion in the red blood cells resulted in an elevated ratio of oxidized/reduced forms with a reduced antioxidant protective capacity in the hypertensive patients versus the BMI-matched controls (P0.001).The presence of systemic oxidative stress was proven in hypertensive children and adolescents, irrespective of their BMI.

The M235T polymorphism of the angiotensinogen (ANG) gene, the I/D polymorphism of the angiotensin converting enzyme (ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor (AT1R) gene were identified in 70 patients with end-stage renal disease [20 pediatric ESRD, aged 14.9+/-3.1, years blood pressure (BP) 139+/-14/91+/-13 mmHg, 50 adult ESRD, aged 48.7+/-18.7 years, BP 149.1+/-24/96.9+/-12 mmHg], 35 with juvenile essential hypertension (JEHT, aged 14.4+/-2.7 years, 24-h mean BP 135.37+/-7.37/72.4+/-7.68 mmHg), 130 adult healthy normotensive controls (aged 34.9+/-8.1 years, BP 117.8+/-8.7/78.7+/-8.5 mmHg), and 20 pediatric controls (aged 13.2+/-1.2 years, BP 109+/-6.5/71+/-5.9 mmHg). The ACE gene polymorphism was determined by polymerase chain reaction and the ANG and AT1R gene polymorphisms by single-step LightCycler technology. The ACE gene distribution of the Hungarian controls did not differ from the results of the other Caucasian populations. In JEHT and pediatric ESRD patients, the MT genotype of ANG was more frequent than in controls (JEHT 80%, pediatric ESRD 74% versus controls 50%, P0.02). The DD genotype of ACE was over-represented in pediatric ESRD compared with controls (ESRD 45% versus controls 22%, P0.05). There was a non-significant increase in the CC genotype frequency of AT1R in adult patients with ESRD compared with controls. In conclusion, there was an increased frequency of the ACE DD genotype in pediatric ESRD, which could be a genetic risk factor for the development of ESRD. Furthermore, there was a significant increase in MT genotype frequency of ANG M235T polymorphism in pediatric ESRD and JEHT. The role of AT1R gene polymorphism needs further investigation.

Childhood hypertension necessitates a careful approach to diagnosis and a tailored approach to management. Hypertension in children should not be considered a rare condition. The diagnosis of hypertension must be assessed carefully, with attention to age, sex, and height standards. Also, careful attention should be given to the methods used to measure blood pressure. Once the diagnosis is made and the underlying etiologies have been evaluated and managed as necessary, both nonpharmacologic and pharmacologic approaches to treatment have been used. Nonpharmacologic approaches, especially weight reduction and increased physical activity, are beneficial. If pharmacologic approaches are needed, the goal of therapy should be to reduce blood pressure below the 95th percentile in the easiest, most effective manner that causes the fewest side effects. Angiotensin-converting enzyme inhibitors, calcium-channel blockers, alpha and beta blockers, and diuretics have all been used in children. Newer antihypertensives, such as angiotensin receptor blockers, are now being tested.

Genetic variants in apolipoprotein L1 (APOL1) confer risk for kidney disease. We sought to better define the phenotype of APOL1-associated nephropathy. The FSGS Clinical Trial involved 138 children and young adults who were randomized to cyclosporin or mycophenolate mofetil plus pulse oral dexamethasone with a primary outcome of proteinuria remission. DNA was available from 94 subjects who were genotyped for APOL1 renal risk variants, with two risk alleles comprising the risk genotype. Two APOL1 risk alleles were present in 27 subjects, of whom four subjects did not self-identify as African American, and 23 of 32 (72%) self-identified African Americans. Individuals with the APOL1 risk genotype tended to present at an older age and had significantly lower baseline eGFR, more segmental glomerulosclerosis and total glomerulosclerosis, and more tubular atrophy/interstitial fibrosis. There were differences in renal histology, particularly more collapsing variants in those with the risk genotype (P=0.02), although this association was confounded by age. APOL1 risk genotype did not affect response to either treatment regimen. Individuals with the risk genotype were more likely to progress to ESRD (P

Three hundred fifty-nine chronic dialysis patients (85 employed and 274 nonemployed) were surveyed to identify/verify those characteristics which differentiate between employed versus nonemployed status. Education emerged as a significant correlate of employment, as noted by previous investigators, whereas, unlike previous research, neither mode of dialysis, length of time on dialysis, number of comorbid conditions, nor cause of renal failure (eg, diabetes) were associated with employment status. Measures of functional status (MOS SF-20 and Karnofsky) were positively associated with employment. Furthermore, patients' perceptions that their health limited the type and amount of work that they could do were negatively associated with employment. In addition, using a series of de novo items, we found subjects' beliefs about dialysis patients' ability to work to be a "self-fulfilling prophecy" with regard to employment status. That is, patients who themselves believed that dialysis patients should work and had this notion reinforced by significant others were more likely to be employed. Interestingly, 21 percent of unemployed patients reported that they were both able to work and wanted to return to work. Because it is consistently reported that only a small percentage of dialysis patients are employed, targeting the patients who are both willing and able to work for vocational rehabilitation might significantly increase the numbers of employed dialysis patients.

There are a large number of causes of chronic renal disease in children. This review updates recent findings on conditions that arise in childhood that lead to chronic kidney disease in adulthood (eg, polycystic kidney disease, reflux nephropathy) or cause chronic kidney disease in childhood. Recent studies addressing the etiology and genetics of chronic kidney disease, as well as its pathophysiology, prognosis, and treatment, are discussed.

The effects of chronic lead administration on renal function and cytoarchitecture and on the immunohistochemical localization of glutathione S-transferase (GST) isoenzymes were determined. Pregnant rats were given 250 ppm lead acetate in drinking water from conception until weaning and mothers and pups received 500 ppm of lead acetate from weaning until termination at either 3 or 7 weeks of age. Light and electron microscopic studies after 3 weeks of lead administration showed tubular injury with frequent mitoses noted in proximal tubular cells and, after 7 weeks of treatment, interstitial fibrosis, characteristic intranuclear inclusions, and tubular injury characterized by both nuclear and cytoplasmic pleomorphism. Rats treated with lead for 7 weeks showed significantly lower body weights and creatinine clearances than age-matched control animals. Immunohistochemical studies of glutathione transferase subunits in control rats showed unique isoform localization in each segment of the nephron; treatment with lead caused large increases in immunoreactive protein of Yc, Yk, Yb1, and Yp GST subunits in proximal tubules. No increases in the antioxidant enzymes copper-zinc superoxide dismutase, catalase, and glutathione peroxidase were found in lead-treated rats, but there was a diffuse lead-related increase in immunoreactive protein for manganese superoxide dismutase throughout the renal cortex. Our results demonstrate large lead-induced increases of specific isoforms of glutathione S-transferase in specific kidney cell types and show that these increases preceded irreversible renal damage.

The effects of acute and chronic exposure to lead on glutathione S-transferase (GST) isoforms were determined in developing kidney in the rat. The ontogeny of glutathione S-transferase isoforms was characterized as were the effects of depletion of dietary calcium on glutathione S-transferase isoform profiles in control and lead-treated rats. In the acute exposure experiments, rats of 14 and 50 days of age received three daily injections of lead acetate (114 mg/kg) and in the chronic exposure studies, rats received lead acetate at doses ranging from 50 to 500 ppm in their drinking water. Lead acetate administration in these chronic studies began 1 day after conception. Acute and chronic lead exposure had similar effects, causing increases in all but one glutathione S-transferase isoform (Yb3); these increases were markedly exacerbated by dietary calcium depletion. In all lead paradigms, GST subunits Yb1 and Yp showed the largest increases--greater than 25-fold in rats fed a low-calcium diet. GST subunit Yb3 showed small increases in the 14-day acute lead and the 4 week low-calcium animals and did not increase in other groups. Lead-related increases in GSTs were partially reversed by transferring animals previously receiving lead to lead-free water for a 4-week period. Kidneys of rats fed the low-calcium diet did not have detectable GST Yk, but in rats on this low-calcium diet that received 500 ppm lead; this GST isoform was found at levels comparable to those in control rats fed lab chow.

Summary Background and objectives In the FSGS Clinical Trial, 22 cyclosporine-treated and 20 mycophenolate/dexamethasone-treated patients experienced a complete or partial remission after 26 weeks, completed 52 weeks of treatment, and were studied through 78 weeks. Herein, changes in the urine protein/creatinine ratio (UP/C) and estimated GFR (eGFR) throughout the entire study period are defined. Design, setting, participants, and measurements The FSGS Clinical Trial, which was conducted from November 2004 to January 2010, enrolled patients aged 2–40 years, with eGFR ≥40 ml/min per 1.73 m2 and UP/C >1 mg/mg after ≥4 weeks of corticosteroid therapy. Both groups received lisinopril or losartan throughout the study. UP/C and eGFR were measured at 0, 26, 52, and 78 weeks. Results The median UP/C in the cyclosporine- and mycophenolate/dexamethasone-responsive patients fell by 89.8% and 82.7% at 52 weeks; the fall was largely sustained at 78 weeks (74.7% and 80.3%, respectively). The mean eGFR fell by 19.4% in the cyclosporine group and rose by 7.0% in the mycophenolate mofetil/dexamethasone group at 52 weeks, but subsequently rose by 16.4% and fell by 2.6%, respectively, in the two groups from 52 to 78 weeks. Conclusions In this subset of responding FSGS patients, the improvement in UP/C after cyclosporine or mycophenolate/dexamethasone treatment was largely sustained for 6 months after therapy. Reduction in eGFR in the cyclosporine group was improved 6 months after cyclosporine was stopped although the levels were lower than baseline in seven patients who entered the study with decreased eGFR.

PubMedID: 23138488 Overexpression of soluble urokinase receptor (suPAR) causes pathology in animal models similar to primary FSGS, and one recent study demonstrated elevated levels of serum suPAR in patients with the disease. Here, we analyzed circulating suPAR levels in two cohorts of children and adults with biopsy-proven primary FSGS: 70 patients from the North America-based FSGS clinical trial (CT) and 94 patients from PodoNet, the Europe-based consortium studying steroid-resistant nephrotic syndrome. Circulating suPAR levels were elevated in 84.3% and 55.3% of patients with FSGS patients in the CT and PodoNet cohorts, respectively, compared with 6% of controls (P

Galloway-Mowat syndrome is an autosomal recessive disorder presenting as early-onset nephrotic syndrome and central nervous system abnormalities, including microcephaly and developmental delays. Neurologic findings are universal in children with this disorder, and often precede renal abnormalities. However, relatively few descriptions of associated neurologic features are available. We describe two pairs of siblings with Galloway-Mowat syndrome who illustrate the spectrum of neurologic findings, to increase awareness of this syndrome among pediatric neurologists.

Because controlled trials in adults have shown accelerated deterioration of renal function in a small number of patients receiving calcitriol for renal osteodystrophy, we initiated a prospective, randomized, double-blind study of the use of calcitriol versus dihydrotachysterol in children with chronic renal insufficiency. We studied children aged 1½ through 10 years, with a calculated glomerular filtration rate between 20 and 75 ml/min per 1.73 m 2 , and with elevated serum parathyroid hormone concentrations. Ninety-four patients completed a mean of 8.0 months of control observations and were randomly assigned to a treatment period; 82 completed the treatment period of at least 6 months while receiving a calcitriol dosage (mean±SD) of 17.1±5.9 ng/kg per day or a dihydrotachysterol dosage of 13.8±3.3 μg/kg per day. With treatment the height z scores for both calcitriol- and dihydrotachysterol-treated groups showed no differences between the two groups. In relation to cumulative dose, there was a significant decrease in glomerular filtration rate for both calcitriol and dihydrotachysterol; for calcitriol the rate of decline was significantly steeper ( p =0.0026). The treatment groups did not differ significantly with respect to the incidence of hypercalcemia (serum calcium concentration >2.7 mmol/L (>11 mg/dl)). We conclude that careful follow-up of renal function is mandatory during the use of either calcitriol or dihydrotachysterol because both agents were associated with significant declines in renal function. There was no significant difference between calcitriol and dihydrotachysterol in promoting linear growth or causing hypercalcemia in children with chronic renal insufficiency. Dihydrotachysterol, the less costly agent, can be used with equal efficacy.

(ABP). AMSPDC paid the ABP for Ms Bartholomew’s services, but also benefited greatly from the ABP’s largesse; in 2009, Degnon Associates assumed this role. In 2007, AMSPDC leadership undertook a strategic planning initiative that led to the development of AMSPDC’s current mission (‘‘to pursue optimal health outcomes of children through the development of successful academic pediatric departments across North America’’) and vision (‘‘to be the major voice for academic pediatrics in North America’’) statements, value statement, and revised bylaws. 2 Although a major focus of AMSPDC has been to serve as a forum for mutual support, interactions, and information sharing for academic pediatric chairs during the last 50 years, the organization has also established a legacy of several major accomplishments. Some of these accomplishments are highlighted below in each of the major core academic missions of research, education, advocacy, and mentorship. Research

The combination of microcephaly, gyral abnormalities, developmental delay, and a glomerulopathy constitutes a recognizable syndrome. The inheritance is autosomal recessive. Additional abnormalities may include seizures, minor facial anomalies, and hiatal hernia. Onset of proteinuria often occurs in the first 3 months of life, but always before age 3 years. A uniform pattern of renal histologic changes has not been found. There is no effective treatment for the neurologic or renal manifestations of this condition. The prognosis is extremely poor; every patient but one has died before age 5 1/2 years. Antenatal diagnosis may be possible.

1. To understand that disorders of sodium balance are related to conditions that alter extracellular fluid volume.

This policy statement articulates the positions of the American Academy of Pediatrics on graduate medical education and the associated costs and funding mechanisms. It reaffirms the policy of the American Academy of Pediatrics that graduate medical education is a public good and is an essential part of maintaining a high-quality physician workforce. The American Academy of Pediatrics advocates for lifelong learning across the continuum of medical education. This policy statement focuses on the financing of one component of this continuum, namely residency education. The statement calls on federal and state governments to continue their support of residency education and advocates for stable means of funding such as the establishment of an all-payer graduate medical education trust fund. It further proposes a portable authorization system that would allocate graduate medical education funds for direct medical education costs to accredited residency programs on the basis of the selection of the program by qualified student or residents. This system allows the funding to follow the residents to their program. Recognizing the critical workforce needs of many pediatric medical subspecialties, pediatric surgical specialties, and other pediatric specialty disciplines, this statement maintains that subspecialty fellowship training and general pediatrics research fellowship training should receive adequate support from the graduate medical education financing system, including funding from the National Institutes of Health and other federal agencies, as appropriate. Furthermore, residency education that is provided in freestanding children's hospitals should receive a level of support equivalent to that of other teaching hospitals. The financing of graduate medical education is an important and effective tool to ensure that the future pediatrician workforce can provide optimal heath care for infants, children, adolescents, and young adults.

This report describes the serum osteocalcin values in children with mild to moderate, but relatively stable, renal dysfunction followed in the Growth Failure in Children With Renal Diseases Study. This report is derived from data obtained during the control period (6 months) before the initiation of vitamin D therapy. Up to three measurements per patient were obtained. Serum osteocalcin concentration was compared with creatinine clearance (glomerular filtration rate) calculated by the Schwartz formula; with serum concentrations of alkaline phosphatase, parathyroid hormone, and bicarbonate; and with the percentages of the recommended dietary allowances of calories and protein ingested. By standard correlation techniques, there appeared to be an inverse correlation between calculated creatinine clearance and serum osteocalcin concentration, and a direct correlation between serum osteocalcin and parathyroid hormone values. However, when we employed a statistical technique that takes into account repeated measures in the same patient, no correlation was found between calculated glomerular filtration rate and serum osteocalcin concentration, and no direct correlation was found between serum osteocalcin and parathyroid hormone values. The lack of a correlation between calculated glomerular filtration rate and serum osteocalcin values may be due to large fluctuations in the serum osteocalcin concentration, even though renal function is relatively stable.

In a prospective, controlled study, plasma and urinary taurine concentrations were determined weekly, between postnatal weeks 3 and 18, in (1) seven sick infants (gestational age less than 28 weeks, birth weight less than or equal to 1000 gm) who received a taurine-free total parenteral nutrition solution for 32 to 49 days (group P) and who subsequently were formula fed and (2) eight sick infants matched by gestational age and birth weight, who received formula or human milk from day 3 to 4 of life (group E). Ten healthy full-term infants ranging in age from 1 to 18 weeks and fed with formula provided normal values (group C). Significantly lower mean plasma taurine values (range 1.59 to 3.43 mumol/dl) were found between postnatal weeks 3 and 7 in group P compared with group E (range 5.54 to 6.97 mumol/dl) and with group C (5.6 +/- 0.34 mumol/dl). After initiation of feeding, plasma taurine concentrations in group P increased to normal. Markedly elevated values of mean fractional excretion of taurine, 38% to 56%, were found between weeks 3 and 5 in group P and E compared with group C (15.5 +/- 3.2%). In contrast, during the same period, low urinary taurine values (4.9% to 6.7%) were found in two larger, older infants receiving total parenteral nutrition whose plasma taurine values were in the normal range. After week 5, urinary taurine values were in the control range in all groups. We conclude that the absence of taurine in total parenteral nutrition solutions administered to very low birth weight infants and the limited ability of the immature kidney to adapt to low taurine intake by "up-regulation" of tubular taurine reabsorption may result in depleted taurine body pools during the first weeks of life. This inability to conserve taurine by the immature nephron could potentially have a deleterious effect on the developing brain and retina in these infants, and indicates a possible need for taurine supplementation.

Fifty years after the publication of a prescription for maintenance fluid therapy, concerns have been raised about the use of hypotonic fluids in hospitalized children. We discuss what maintenance fluid therapy is or what it is not; where maintenance fluid therapy has been misused. We also discuss concerns with the immediate adoption of isotonic fluid as maintenance fluid without careful consideration and testing.

Background Recent pre-clinical studies have shown that complement activation contributes to glomerular and tubular injury in experimental FSGS. Although complement proteins are detected in the glomeruli of some patients with FSGS, it is not known whether this is due to complement activation or whether the proteins are simply trapped in sclerotic glomeruli. We measured complement activation fragments in the plasma and urine of patients with primary FSGS to determine whether complement activation is part of the disease process. Study Design Plasma and urine samples from patients with biopsy-proven FSGS who participated in the FSGS Clinical Trial were analyzed. Setting and Participants We identified 19 patients for whom samples were available from weeks 0, 26, 52 and 78. The results for these FSGS patients were compared to results in samples from 10 healthy controls, 10 patients with chronic kidney disease (CKD), 20 patients with vasculitis, and 23 patients with lupus nephritis. Outcomes Longitudinal control of proteinuria and estimated glomerular filtration rate (eGFR). Measurements Levels of the complement fragments Ba, Bb, C4a, and sC5b-9 in plasma and urine. Results Plasma and urine Ba, C4a, sC5b-9 were significantly higher in FSGS patients at the time of diagnosis than in the control groups. Plasma Ba levels inversely correlated with the eGFR at the time of diagnosis and at the end of the study. Plasma and urine Ba levels at the end of the study positively correlated with the level of proteinuria, the primary outcome of the study. Limitations Limited number of patients with samples from all time-points. Conclusions The complement system is activated in patients with primary FSGS, and elevated levels of plasma Ba correlate with more severe disease. Measurement of complement fragments may identify a subset of patients in whom the complement system is activated. Further investigations are needed to confirm our findings and to determine the prognostic significance of complement activation in patients with FSGS.

Fluid therapy restores circulation by expanding extracellular fluid. However, a dispute has arisen regarding the nature of intravenous therapy for acutely ill children following the development of acute hyponatraemia from overuse of hypotonic saline. The foundation on which correct maintenance fluid therapy is built is examined and the difference between maintenance fluid therapy and restoration or replenishment fluid therapy for reduction in extracellular fluid volume is delineated. Changing practices and the basic physiology of extracellular fluid are discussed. Some propose changing the definition of "maintenance therapy" and recommend isotonic saline be used as maintenance and restoration therapy in undefined amounts leading to excess intravenous sodium chloride intake. Intravenous fluid therapy for children with volume depletion should first restore extracellular volume with measured infusions of isotonic saline followed by defined, appropriate maintenance therapy to replace physiological losses according to principles established 50 years ago.

Everyone wants to get better health and better care at a lower cost. Research shows that interprofessional care is more …

Growth failure is an important problem in children with renal failure. Even after renal transplantation their growth rates may be lower than normal, and "catch-up" growth does not occur. Therefore there is great interest in giving growth hormone (GH) after transplantation. Clinical observations and theoretic considerations call into question whether GH after transplantation is safe. Studies have shown a more rapid than normal decline in renal function after the initiation of GH therapy. This result could be explained by the effects of GH on the immune response. Growth hormone is known to modulate (usually upregulate) the immune response and could be a reason for the increased loss of renal function caused by rejection. It could also be explained by the long-term effects of GH on the injured kidney. Experimental data (generally not in the transplantation model) suggest that exogenous GH given after renal injury or reduced renal mass leads to a more rapid development of glomerular sclerosis and reduced renal function. GH should not be administered to children after renal transplantation until all safety questions have been answered in prospective clinical trials.

This statement discusses the importance of pediatrician-workforce issues and their relevance to the provision of pediatric health care. It reviews previous work in the health policy arena on physician and pediatrician workforce. Key pediatrician-workforce trends are described, including the growth in the number of pediatricians in relation to the child population, the increase in the number of female pediatricians, the role of international medical graduates, the diversity of the pediatrician workforce, the contributions of internal medicine-pediatrics physicians, the increasing number of nonpediatrician providers of pediatric care, geographic distribution of physicians, and the future of pediatric subspecialists. Methods of influencing the pediatrician workforce are also considered. In the concluding series of recommendations, the statement identifies both overarching policy goals for the pediatrician workforce and implementation strategies designed to ensure that all of America's infants, children, adolescents, and young adults have access to appropriate pediatric health care.

The effective and efficient delivery of children's health care depends on the pediatrician workforce. The number, composition, and distribution of pediatricians necessary to deliver this care have been the subject of long-standing policy and professional debate. This technical report reviews current characteristics and recent trends in the pediatric workforce and couples the workforce to a conceptual model of improvement in children's health and well-being. Important recent changes in the workforce include (1) the growth in the number of pediatricians in relation to the child population, (2) increased numbers of female pediatricians and their attainment of majority gender status in the specialty, (3) the persistence of a large number of international medical graduates entering training programs, (4) a lack of ethnic and racial diversity in pediatricians compared with children, and (5) the persistence of marked regional variation in pediatrician supply. Supply models projecting the pediatric workforce are reviewed and generally indicate that the number of pediatricians per child will increase by 50% over the next 20 years. The differing methods of assessing workforce requirements are presented and critiqued. The report finds that the pediatric workforce is undergoing fundamental changes that will have important effects on the professional lives of pediatricians and children's health care delivery.