Final report of the FOPE II Pediatric Subspecialists of the Future Workgroup.

The report of the Pediatric Subspecialists of the Future Workgroup of the Second Task Force on Pediatric Education reviews the critical changes of the past 2 decades that have affected the provision of pediatric subspecialty services, education of pediatric health care providers, and the acquisition and application of new knowledge. The report considers the future needs that will determine the ability of pediatric subspecialists to meet identified goals. Recommendations for change in the education, role, and financing of the pediatric subspecialist are reported together with those of other workgroups. Pediatrics 2000;106(suppl):1224-1244; pediatric subspecialist, pediatric subspecialist workforce, education pediatric subspecialist, research pediatric subspecialist.

Evaluation of renal function during childhood.

There are several methods to evaluate renal function during childhood. The use of serum creatinine, either alone or in combination with the Schwartz formula, is reliable and quick, but requires knowledge of conceptual age. A plasma creatinine concentration of 88.4 mumol/L (1.0 mg/dL), for example, represents normal renal function in an adolescent but more than 50% loss of renal function in a 5-year-old child. A timed urine collection for creatinine clearance is another evaluative method, but the adequacy of the urine collection always should be determined first. Urea clearance rarely is used to measure GFR because of the complex factors that influence urea excretion. Measurement of the disappearance of radioactive-labeled substances in plasma can be used to determine GFR. Radionuclide renal scans also can be used and offer the advantage of estimating the GFR of each kidney. Although infants and newborns have an intact urine diluting ability, their concentrating ability is impaired. The maximal urinary concentration in the neonatal period is less than 700 mOsm/kg, but reaches adult values of 1200 mOsm/kg by 6 to 12 months of life. Similarly, the infant kidney has a limited capacity for salt regulation, predisposing the infant to salt disturbances.

Analysis of hypertension in children post renal transplantation--a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS).

Hypertension is common in children after renal transplantation and is associated with multiple factors. Data regarding the prevalence of post-transplant hypertension and the relationship between immunosuppressive drugs and the persistence of hypertension in a large population of North American children have not been available. This study was designed by the North American Pediatric Renal Transplant Cooperative Study to evaluate in a large diverse multicenter population of children the prevalence of hypertension post transplantation, the type of antihypertensive medications used to treat this hypertension and to determine the relationship between the blood pressure control and the immunosuppressive therapy. Analysis of 277 patients showed the following: (1) 70% of recipients required antihypertensive medications 1 month post transplant compared with 48% pre transplant; the incidence decreased to 59% at 24 months; (2) the majority of children received multiple drug therapy to control blood pressure; (3) hypertension can be controlled effectively despite inherent etiological factors, such as allograft source, prior hypertension and immunosuppressive therapy.

Application since 1980 of antihypertensive agents to treat pediatric disease.

Strategies for using antihypertensive agents have changed significantly since 1980. This paper reviews clinical studies devoted to the use of antihypertensive agents in children beyond the newborn period. The availability of converting enzyme inhibitors and calcium channel blockers has significantly improved BP control in children with secondary forms of hypertension. The role of antihypertensive agents to chronically treat primary hypertension in children remains unclear. Additionally, some treatment protocols used in adults that apply to the treatment of hypertensive children and that have been used in the treatment of nonhypertensive disease are discussed. Preliminary studies suggest that the rate of decline of renal function in some forms of progressive renal disease may be retarded by the use of converting enzyme inhibitors.

Hyperechoic kidneys in the newborn and young infant.

Increased echogenicity of the kidney in the newborn has many causes, some of which reflect serious renal disease. The major abnormal imaging pattern is the large, diffusely hyperechoic kidney with abnormal architecture. Its differential diagnosis includes recessive and dominant polycystic kidney disease (PKD), glomerulocystic kidney disease, and diffuse cystic dysplasia. The family history and ultrasonic screening of the parents and siblings are essential in the evaluation. The identification of associated nonrenal abnormalities is important to the recognition of syndromal cystic disease. Glomerulocystic kidney disease, which comprises sporadic and syndromal forms, appears similar to dominant PKD. While renal biopsy almost always differentiates recessive from dominant PKD, renal biopsy cannot differentiate among the forms of glomerulocystic kidney disease, except in the case of tuberous sclerosis, which has unique histopathological characteristics. Other causes of the enlarged hyperechoic kidneys with abnormal architecture include renal vein thrombosis and congenital nephrotic syndrome. A second pattern is the hyperechoic small kidney with abnormal architecture. Many of these kidneys are dysplastic and associated with urinary tract obstruction. The combination of hyperechoic parenchyma and pyelocaliceal dilatation suggests obstructive cystic dysplasia. Cortical and medullary necrosis in the newborn also causes hyperechogenicity in small kidneys. A third pattern contains those kidneys with medullary hyperechogenicity, the most common cause of which in the newborn is nephrocalcinosis associated with furosemide therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal cortical and renal medullary necrosis in the first 3 months of life.

Renal cortical necrosis, renal medullary necrosis, and combined renal cortical-medullary necrosis result from renal ischemia without vascular occlusion. Renal hypoperfusion and ischemic injury in infants have been ascribed to massive blood loss, hemolytic disease, septicemia, and severe hypoxemia. In a postmortem study we identified 82 cases among 1,638 autopsies during the 20 years between 1970 and 1989 in infants 3 months old or less at the time of death. The frequency of renal necrosis in autopsy cases increased significantly during the last 6 years of the study. The distribution of the renal lesion was cortical in 28, medullary in 23, and combined in 31. Forty infants carried diagnoses of congenital heart disease, 17 of asphyxial shock, 9 of sepsis, 3 of infectious myocarditis, 9 of major malformations, 4 of anemic shock, 1 of vascular malformation, and 1 of gastroenteritis and dehydration. A significantly higher proportion of babies with congenital heart disease had cortical involvement. Comparison of clinical characteristics revealed a significantly higher frequency of prematurity, respiratory distress syndrome, bleeding diathesis, and possibly sepsis in the children with congenital heart disease, suggesting that these factors are important in the pathogenesis of the renal lesion. Fourteen infants underwent cardiac catheterization; there was no demonstrable association between the renal lesions and the use of radiographic contrast medium. We conclude that severe congenital heart disease itself is a risk factor for life-threatening renal cortical and medullary necrosis.

Hyponatremia: pathophysiology and treatment, a pediatric perspective.

Hyponatremia is the most commonly observed electrolyte abnormality in hospitalized children. The most serious consequences of hyponatremia and its treatment involve the central nervous system (CNS). Important factors determining the development of clinical symptomatology include: the rate of fall in serum sodium, and the severity and duration of hyponatremia. Acute hyponatremia is associated with increased brain water resulting in varying grades of encephalopathy whereas the osmoregulatory mechanism allows normalization of CNS water content in chronic hyponatremia. It is recommended that the therapy for hyponatremia be initiated on the basis of the presence or absence of symptoms. An increase of 4-6 mmol/l in serum sodium over 10-15 min is recommended in symptomatic patients. Rapid correction of chronic hyponatremia may result in osmotic dehydration syndrome and therefore should be avoided.

The 1989 report of the North American Pediatric Renal Transplant Cooperative Study.

This report of the North American Pediatric Transplant Cooperative Study summarizes data contributed by 57 participating centers on 754 children with 761 transplants from 1 January 1989 to 16 February 1989. Data collection was initiated in October 1987 and follow-up of all patients is ongoing. Transplant frequency increased with age; 24% of the patients were less than 5 years, with 7% being under 2 years. Common frequent diagnoses were: aplastic/dysplastic kidneys (18%), obstructive uropathy (16%), and focal segmental glomerulosclerosis (12%). Preemptive transplant, i.e., transplantation without prior maintenance dialysis, was performed in 21% of the patients. Dialytic modalities pretransplant were peritoneal dialysis in 42% and hemodialysis in 25%. Bilateral nephrectomy was reported in 29%. Live-donor sources accounted for 42% of the transplants. Among cadaveric donors, 41% of the donors were under 11 years old. During the first post-transplant month, maintenance therapy was used similarly for live-donor and cadaver source transplants, with prednisone, cyclosporine, and azathioprine used in 93%, 83%, and 81%, respectively. Triple therapy with prednisone, cyclosporine, and azathioprine was used in 78%, 75%, and 75% of functioning cadaver source transplants at 6 months, 12 months, and 18 months as opposed to 60%, 63%, and 54% for live-donor procedures, with single-drug therapy being uncommon. Rehospitalization during months 1-5 occurred in 62% of the patients, with treatment of rejection and infection being the main causes. Additionally, 9% were hospitalized for hypertension. During months 6-12 and 12-17, 30% and 28% of the patients with functioning grafts were rehospitalized. Times to first rejection differed significantly for cadaver and live-donor transplants. The median time to the first rejection was 36 days for cadaver transplants and 156 days for live-donor transplants. Overall, 57% of treated rejections were completely reversible although the complete reversal rate decreased to 37% for four or more rejections. One hundred and fifty-two graft failures had occurred at the time of writing, with a 1-year graft survival estimate of 0.88 for live-donor and 0.71 for cadaver source transplants. In addition to donor source, recipient age is a significant prognostic factor for graft survival. Among cadaver donors, decreasing donor age is associated with a decreasing probability of graft survival. Thirty-five deaths have occurred; 16 attributed to infection and 19 to other causes. The current 1-year survival estimate is 0.94. There have been 9 malignancies.

The utility of renin profiling in childhood hypertension.

Criteria to categorize children as having hypertension associated with high, low or normal PRA as determined by the technique of renin sodium indexing; or with PRA responsiveness which was normal, suppressed or excessive after acute volume depletion induced by a loop diuretic were established in 30 normotensive adolescents. Four hour upright PRA corrected for daily sodium excretion was elevated in 16% of 43 and 84% of 25 children with essential and renal related hypertension. Low PRA was found in 5 of 43 and 0 of 25 children. In 36 children with essential hypertension evaluated after acute volume depletion, 4 and 5 had hyper- and hypo- responsive PRA compared to the 30 normotensive children. The application of these two approaches enables the renin angiotensin system to be systematically categorized in hypertensive children.

The adolescent with essential hypertension.

Clinical features in a comparably studied group of hypertensive and normotensive adolescents are described. Hypertensive hyperreninemia occurred in four of 28 hypertensive adolescents; suppressed plasma renin activity was found in five of 27 hypertensive adolescents. Only one of five adolescents identified as having suppressed plasma renin activity after ingesting a low-salt diet for three days had a hyporesponsive response to acute extracellular volume contraction. Pressure natriuresis was documented in six of 32 adolescents. Compared to normotensive, the hypertensive group was found to have elevated levels of serum uric acid. Plasma renin activity was higher in hypertensive children with hyperuricemia than in those with normouricemia. The hypertensive adolescents also had higher levels of serum calcium and phosphorus. Two-thirds of the hypertensive adolescents had echocardiographic changes of myocardial hypertrophy. No ophthalmologic nor renal abnormalities were documented in the hypertensive group. A review of factors influencing blood pressure changes during childhood and current considerations for therapy are included.

Carbonic anhydrase II deficiency in 12 families with the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification.

Osteopetrosis with renal tubular acidosis and cerebral calcification was identified as a recessively inherited syndrome in 1972. In 1983, we reported a deficiency of carbonic anhydrase II, one of the isozymes of carbonic anhydrase, in three sisters with this disorder. We now describe our study of 18 similarly affected patients with this syndrome in 11 unrelated families of different geographic and ethnic origins. Virtual absence of the carbonic anhydrase II peak on high-performance liquid chromatography, of the esterase and carbon dioxide hydratase activities of carbonic anhydrase II, and of immunoprecipitable isozyme II was demonstrated on extracts of erythrocyte hemolysates from all patients studied. Reduced levels of isozyme II were found in obligate heterozygotes. These observations demonstrate the generality of the findings that we reported earlier in one family and provide further evidence that a deficiency of carbonic anhydrase II is the enzymatic basis for the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. We also summarize the clinical findings in these families, propose mechanisms by which a deficiency of carbonic anhydrase II could produce this metabolic disorder of bone, kidney, and brain, and discuss the clinical evidence for genetic heterogeneity in patients from different kindreds with this inborn error of metabolism.