Eddie S. Moore

Effects of positive pressure ventilation on intrarenal blood flow in infant primates.

Extract: Measurement of intrarenal distribution of renal blood flow by injection of radionuclides in 3—5-day-old infant monkeys showed a preponderance of outer cortical over inner cortical flow with flow rates of 4.23 and 2.54 ml/min/g, respectively. Intermittent positive pressure ventilation (IPPV) causes a reversal of this flow pattern. The theoretical difference in nephron function in these two areas suggests that this reversal in intrarenal flow induced by IPPV may have important clinical implications.Speculation: Extrarenal stimuli such as IPPV causes a redistribution of intrarenal blood flow in infant primates. Any stimuli that results in increased production of epinephrine or similar compounds may be responsible for this redistribution by a local effect on outer cortical blood vessels. Our data further suggest that antidiuretic hormone may influence intrarenal blood flow in addition to altering tubular membrane permeability.

Internal arteriovenous fistulae for dialysis in children

Abstract The dangers of hemorrhage, infection, and thrombosis that attend the use of external silastic-teflon arteriovenous cannulas can be largely avoided by creation of internal arteriovenous fistulae. The advantages of a fistula are particularly evident when children are maintained on hemodialysis. It is recommended that fistulae be made several months before dialysis is needed since optimal vein wall hypertrophy and dilatation will be achieved in the interim.

Parathyroidectomy in children with chronic renal failure.

Abstract Severe bone disease complicates chronic renal failure in children more frequently than in adults. The bony changes of renal origin are regularly reversed by successful renal transplantation. When a renal transplant cannot be accomplished at an early date, this osteodystrophy may become disabling. Under these circumstances bony changes are not arrested by medical therapy and subtotal parathyroidectomy is indicated. Parathyroidectomy consistently reverses the progression of renal osteodystrophy, relieves symptoms, and effects healing. This surgery can be done safely and is well tolerated.

Compensatory renal hypertrophy in fetal lambs.

Summary: 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. Seventytwo 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.Speculation: In midgestation, compensatory renal hypertrophy occurs by both an increase in cell size and by hyperplasia. The rate of increase is greater than that previously demonstrated in the postnatal period. Functional adaptation parallels renal compensatory hypertrophyin utero

Renal phosphate clearance in fetal lambs.

Summary: 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.Speculation: The fetal kidney responds early in gestation to stimuli that influence renal clearance of phosphate in adults.

1621 APICAL MEMBRANE LIPID FLUIDITY (LF) INFLUENCES PHOSPHATE (Pi) TRANSPORT IN FETAL KIDNEY

Plasma Pi in early life is high and renal Pi excretion low relative to that in adults. Renal tubular Pi transport kinetics and membrane LF was investigated in apical membrane vesicles (BBMV) in 6 fetal (F) lambs and pregnant ewes (E).Results:KmPi was similar in BBMV in the F and E but Vmax Pi was greater in F. Alkaline phosphatase enrichment, lipid saturation index and [cholesterol/phospholipid], [sphingomyelin/phosphatidylcholine] ratios were not different, however, protein/lipid ratios was higher in E. The results demonstrate greater renal tubular Pi transport capacity in F compared to E and increased VmaxPi in F is due, in part, to greater membrane LF. Relative increased VmaxPi in F may be due to difference in carrier function rather than to an increase in carrier concentration. This may involve more rapid cycling of Pi carrier from lumen to cytoplasmic surfaces in F.

1622 K+ STIMULATED PHOSPHATE (Pi) CO-TRANSPORT IN FETAL LAMB (FL) KIDNEY

In the adult kidney, carrier mediated Pi co-transport is highly Na+ specific. Studies in our laboratory showed that Pi uptake (PiU) in renal brush border membrane vesicles (BBMV) from FL kidneys is also stimulated by Na+. In contrast to the adult, we report here that carrier mediated PiU in FL renal BBMV is also energized by a K+ gradient ([K+]o>[K]i). BBMV from 5 FL kidneys were prepared by CaCl2 precipitation and verified by marker enzyme assays, electron microscopy, and PiU into osmoticaly active vesicles. Peak 60s PiU with a 100mM Na+ and K+ gradient was 1968±65 and 1010±133 pMol/mg BBMV protein, respectively (p<.01). PiU for each was greater than diffusion PiU (p<.001 each). The effect of trans-stimulation was studied by preloading BBMV with 5mM Pi. Initial 12s PiU in preloaded BBMV was 1007±181 pMol/mg BBMV protein and was 4-fold higher than PiU in non-loaded BBMV (p<.001). The effect of extravesicular (O) pH was studied by measuring initial 15s PiU in BBMV with constant intravesicular pH 7.4 and varying O pH from 6.0, 7.4 and 8.0. PiU was 700±64, 1983±230 and 411±10 pMol/mg BBMV protein for OpH 6.0, 7.4 and 8.0 respectively. PiU at pHO=pHi was higher than that for OpH 6.0 and OpH 8.0 (p<.01; p<.001). The results demonstrate K+-Pi symport in FL kidney. The co-transport system may represent shared affinity by K+ with Na+ for the cation site on the carrier or a different carrier system.

PHOSPHATE |[lpar]|Pi|[rpar]| TRANSPORT IN RENAL BRUSH BORDER MEMBRANES |[lpar]|BBMV|[rpar]| IN NEWBORN PUPPIES |[lpar]|P|[rpar]|

Renal Pi excretion (UPiV) is low in newborn infants and is not correlated with a low GFR. To further investigate UPiV in neonates, we measured Pi uptake (PiU) by Millipore filtration in BBMV in 7 P at 10 days of age and in 3 adult dogs (D). BBMV were prepared by differential centrifugation and transport after 1h incubation in extravesicular media (EM) with [sucrose] from 0.3 to 1.0 osm varied inversely with [1/osm] (r=.95, p<.05) indicating PiU into osmotically active BBMV. Results, x, ±SEM, nMol/mg protein: (a-p<.01; b-p<.005; c-p<.001)Na+-G PiU at 15s in P remained linear with EM [substrate] 0.1-3.0 mMol (r=0.99, p<.001); however, 0-Na+ PiU was saturated at 1.0-2.0 mMol with an apparent Km of 0.84 mMol and Vmax of 382.2 nMol/15·mg protein. The results suggest that non-Na+-Dep active PiU may explain in part low UPiV in young infants.

Highlights: Renal Concentrating Capacity in the Newborn. Development, clinical Disorders, Evaluation, and Management.

Polyuria, the excretion of an excessive volume of dilute urine, is a potentially lethal disorder in the neonate. Since body water accounts for roughly 60-70 percent of lean body mass in the newborn, loss of body water without adequate replacement may lead to circulatory collapse and death of the infant. The capacity of the kidneys to elaborate urine hypertonic to plasma or the concentrating capacity, involves many physiologic processes. These include countercurrent multiplication, recycling of filtered urea, antidiuretic hormone (ADH), solute delivery to the distal nephron, and the adenylate cylase (cyclic AMP) system. Although urine elaborated by the kidney in utero is normally hypotonic to plasma, development of the capacity to excrete a concentrated urine begins early in fetal life.

1526 HUMORAL (H) CONTROL OF COMPENSATORY RENAL GROWTH (CRG)

In vivo study of H control of CRG was done in ewes and their twin fetal lambs (FL) at 100-140 d gestation. In 9 controls, fetus A (FA) was removed by cesarean section and fetus B (FB) was then removed either 30, 60, 90, or 180 min later. Both kidneys in each fetus were removed and total DNA/RNA content or the rate of 14C-choline incorporation (14C-chol) into renal phospholipids was measured. Mean 14C-chol in FB was greater than that for FA (p<.01) at each time interval and increased with time in both FA and FB; however, the difference between FB and FA did not change with time. In experimental group I (G-I), left uninephrectomy (LUN) was performed in the ewe immediately after removal of FA (n=4). In group II (G-II), FB was removed 90 min after LUN in the ewe (n=5). In G-I, mean total DNA/RNA in both kidneys in FB was significantly higher than that for both kidneys in FA (p<.05). In G-II, mean rate of 14C-chol in both kidneys in FB was significantly greater than that for the controls (p<.001). In vitro study of H factors was done in 6 adult Sprague-Dawley rats. Renal cortical slices incubated with serum from rats 60-90 min after LUN had a 26% greater 14C-chol compared to controls. These data demonstrate in vivo and in vitro evidence for a transplacental humoral factor modulating renal growth in utero.Supported by NIH Research Grant HD 11821 and Chicago Heart Association Research Grant A79-37.