Eddie S. Moore's research while affiliated with University of Chicago and other places

During intrauterine life, fetal mineral accretion depends on active transfer from mother to fetus by the placenta. To evaluate the role of fetal production of 1,25-dihydroxyvitamin D in regulation of fetal phosphorus, calcium, and parathyroid homeostasis, studies were performed in ewes and their fetal lambs. Fetal nephrectomy caused a rise in fetal serum phosphorus and a fall in total calcium 5 days after nephrectomy. Fetal blood ionized calcium also fell and serum parathyroid hormone rose. In sham-nephrectomized fetuses, all four measurements were unchanged compared to control values. Simultaneous maternal values of ionized calcium were normal in control and nephrectomized fetuses. Fetal ureteral severance and drainage of urine into the fetal peritoneal cavity produced none of the effects of fetal nephrectomy. Daily intravenous injection of 1,25-dihydroxyvitamin D into fetuses after nephrectomy prevented the rise in serum phosphate, and serum calcium did not fall. The results suggest that fetal 1,25-dihydroxyvitamin D regulates fetal phosphate homeostasis, perhaps by the placenta, which in turn regulates blood-ionized calcium concentration.

Calcium requirements for growth and for skeletal mineralization during fetal life and in early postnatal development are substantial. During fetal life, significant active transfer of calcium occurs from mother to fetus via the placenta.1 At birth, the connection between mother, placenta, and infant is severed and the intestinal tract becomes the major organ of calcium acquisition for the infant. Early studies in newborn animals demonstrated increased rates of intestinal calcium absorption compared to adult animals.2 However, recent studies of vitamin D deficient and vitamin D-replete rat pups showed that intestinal calcium transport during the first two weeks of life is not meditated by 1,25-dihydroxyvitamin D as is true for adult animals.3 In these studies, a vitamin D-sensitive intestinal calcium transport system developed late in the suckling and in the early weanling period. In light of developmental changes taking place in the intestinal tract and the apparent lack of absolute dependence on vitamin D mediated intestinal calcium transport in the immediate postnatal period, we began studies on the ontogeny of intestinal calcium transport in utero. This paper reports the results of preliminary experiments carried out in fetal lambs.

Recent improvements in medical and nursing care of the newborn infant have resulted in a significant decrease in infant morbidity as well as mortality. In the main, these improvements have been technological with development of sophisticated monitoring devices and expansion of nursing care to that of clinician/practitioner with independent but supervised diagnostic and treatment skills. The latter has greatly enhanced successful implementation of improved monitoring technology. Despite technological advances, high-level care of the newborn infant requires continued use of traditional data gathering skills by history taking and physical assessment. Evaluation of the neonate with apparent oliguria is a classic example of the need to merge traditional techniques with current technology.

Factors related to changes in BP during 4 hr of conventional HD were studied in 13 children and adolescents ages 10 to 20 yr, mean 15.7. No antihypertensive medications were given before HD. Patients were dialyzed with a single-pass delivery system with either plate or hollow-fiber dialyzers while using a constant weight monitoring chair. Body weight (BW), BP, and plasma renin (PRA) and catecholamines (C) were measured immediately pre-HD and after 2 and 4 hr of HD. Mean pre-HD systolic and diastolic BP were 133±4.4 and 78±5.5 mmHg, respectively. After 2 and 4 hr of HD, mean BP was 127±5.7/76±3.0 and 127±2.4/71±5.0 mmHg. Mean pre-HD BW was 52.9±6.4 kg (29.3-80.3). Mean BW after 2 hr of HD was 52.1±6.2 kg and 51.1±6.0 kg after 4 hr of HD. Initial PRA was 6.66±2.28 ng/ml/hr (0.14 to 16.9). After 2 and 4 hr, mean PRA was 9.45±3.15 and 9.76±3.73 ng/ml/hr, respectively. There was no significant correlation between changes in BP and changes in PRA. However, there was a significant correlation between decrease in BW and decrease in BP after 4 hr of HD (r=0.914; p<0.002). These data suggest that changes in BP during HD in children do not correlate with plasma renin activity but are related to changes in total body water as previously demonstrated in adult patients.

Prior to 1958, study of renal function in the fetus was limited to analysis of bladder urine obtained from the fetus. In 1958, Alexander and Dixon1 developed exteriorization techniques that allowed investigation of renal clearances in fetal laboratory animals without onset of fetal respiration (“intact fetal preparation”). The techniques for acute study of renal function in the fetus were subsequently expanded and improved by Alexander and Dixon2 and by Smith et al.3 In 1972, Gresham et al4 reported their results of chronic studies of fetal lambs in utero for as long as 18 days. Since that time, there have been many investigations related to renal function in the developing fetus. In this chapter, we will present a review of the major work related to renal function in utero.

Compensatory renal hypertrophy was studied in fetal lambs during midgestation. Functional adaptation was correlated with anatomica and biochemical changes by measuring glomerular filtration and clearance of para-amino hippurate (PAH). Normal intrauterine body growth and kidney growth by changes in RNA and DNA over a 72-hr period were studied in twin fetuses. Seventy-two hr after left uninephrectomy in single fetuses, there was a significant increase in weight of the renoprival right kidney as well as a significant increase in renal cortical content of RNA and DNA. The rate of increase in RNA was greater than the increase in DNA. Preliminary studies suggest that an increase in renal function parallels renal hypertrophy in fetal lambs.

The frequency of hypercalciuria was determined in the families of nine hypercalciuric patients with idiopathic hypercaliuria who formed recurrent calcium oxalate renal stones. Idiopathic hypercalciuria occurred in 26 of 73 relatives, in three consecutive generations of two families and in two successive generations of four other families. Multiple siblings or children of the probands were affected in three families. Nineteen of 44 first-degree relatives (43 per cent) had idiopathic hypercalciuria, as compared to seven of 29 (29 per cent) other relatives; there was no relation to age or sex. Renal stones were formed by 19 of the 44 first-degree relatives but by none of the others; nine of the 19 were women. We conclude that there is a familial form of hypercalciuria, which appears to be transmitted as an autosomal dominant trait. Stone disease is frequent in first-degree relatives, and affects both sexes equally.

The purpose of this study was to investigate the possible role of diminished phosphate clearance by the fetal kidney in production of relative fetal hyperphosphatemia. Stimuli known to affect renal phosphate clearance in adults were investigated in young fetal lambs. Our studies confirm that the fetal lamb kidney responds to exogenous and endogenous parathyroid hormone (PTH) with inhibition of tubular phosphate reabsorption. Renal tubular phosphate reabsorption in the fetus is in part related to sodium reabsorption. These studies indicate that so-called "immaturity" of renal phosphate clearance in utero is not a significant factor in production of fetal hyperphosphatemia.