Peter Herin

Renal function in very low birth weight infants: Normal maturity reached during early childhood

Development of glomerular and tubular renal function is delayed in preterm infants. To study the pattern of maturation during infancy and childhood, we re-evaluated renal function in 22 very low birth weight infants--in 14 of the infants at 18 months postconceptional age (9 months corrected age) and in the remaining 8 infants at 8 years of age. The glomerular filtration rate remained lower at 9 months corrected age than in term infants of the same postconceptional age: 82 +/- 23 versus 125 +/- 18 ml/min per 1.73 m2 (p < 0.001). At 8 years of age the glomerular filtration rate did not differ from that of healthy control subjects. Effective renal plasma flow, filtration fraction, albumin excretion, maximal concentrating ability, and kidney size determined by ultrasonography were all normal at 8 years of age. We conclude that renal function, which is markedly reduced during the neonatal period in very low birth weight infants, reaches normal maturity by 8 years of age but not by 9 months corrected age.

Ontogeny of Single Glomerular Perfusion Rate in Fetal and Newborn Lambs

Summary: The developmental pattern of regional glomerular density and glomerular perfusion rate (GPR) was studied in 20 chronically catheterized fetal lambs between 106 and 140 days of gestation (term, 145 days) and in six newborn lambs between 3 and 19 days of age. The present study demonstrates for the first time in lambs that the nephrogenic zone disappears around 130 days of gestation and that the total glomerular counts per kidney in fetuses over 130 days (468296 ± 41173 glomeruli per kidney) is not significantly different than in newborn lambs (433704 ± 21553). Glomerular density, determined in four cortical zones (zone I being the outermost portion of the cortex) did not show any significant changes during fetal life; however, significant decreases in glomerular density were observed in each cortical zone after birth. The relative distribution of glomeruli during fetal life decreased in the outer portion (zones I and II) and increased in the inner portion (zones III and IV) of the cortex as fetuses matured and approached term. After birth, this difference became even more prominent; the outer cortical fraction (zone I) decreased from 49.6 ± 2.9% in fetuses of less than 120 days to 37.8 ± 1.5% (P < 0.05) in newborn lambs, whereas the fraction found in zone III increased from 14.9 ± 1.3% to 20.8 ± 0.7% (P < 0.05). Small but significant increases in glomerular filtration rate (GFR) (P < 0.01) and total renal blood flow (P < 0.05) were observed during fetal life: GFR and total renal blood flow increased, respectively, from 1.84 ± 0.11 and 37 ± 2 ml/min in fetuses <120 days to 3.05 ± 0.2 and 46 ± 4 ml/min in fetuses >130 days gestation. During the same period, filtration fraction (FF) did not increase significantly whereas a significant (P < 0.01) 58% increase in FF was observed after birth: FF increased from 10.16 ± 0.74% in fetuses >130 days gestation to 16.12 ± 1.66% in newborn lambs. Renal vascular resistance decreased from 1.03 ± 0.08 mm Hgml-1 min-1 in fetuses >130 days to 0.51 ± 0.05 mm Hgml-1min-1 (P < 0.01) in newborn lambs. Glomerular perfusion rate (GPR), computed for each cortical zone did not change significantly during the last trimester of gestation. After birth, GPR increased almost three times in zones I and II (from 69.2 ± 8.9 and 53.6 ± 4.2 nl/min in fetuses >130 days to 206.9 ± 16.8 and 161.3 ± 20.7 nl/min in newborn lambs, respectively), doubled in zone III (from 55.6 ± 10 nl/min in fetuses >130 days to 119.5 ± 8.9 nl/min in newborn lambs) and remained unchanged in zone IV when compared to fetal GPR values. After birth, the increase in GFR correlated closely with the GPR increase in zone I (r = 0.87) and zone II (r = 0.87), suggesting that the developmental pattern of GFR after birth may depend on the increase in GPR in the outer zones of the renal cortex.Speculation: The addition of new nephron units may be an important determinant of glomerular filtration rate (GFR) in fetuses of less than 130 days of gestation. In fetuses over 130 days of gestation, the addition of new nephron units is no longer a factor to explain the increase in fetal GFR but other factors such as increases in surface area for filtration, effective filtration pressure and capillar filtration coefficient may then play an important role. After birth, one can speculate that a decrease in glomerular vascular resistance is a major determinant in the postnatal increase in glomerular perfusion rate and GFR.

Renal function in dogs with chronic moderate unilateral ureteral obstruction

Partial obstruction of the left ureter was created in seven dogs. Renal function was studied 3 weeks later. Total renal blood flow (RBF) and intrarenal blood flow distribution were studied using the microsphere technique. Glomerular filtration rate (GFR), effective renal plasma flow (CPAH) and the excretion of sodium and osmolar substances were determined using the clearance technique. RBF, GFR and CPAH in the hydronephrotic kidney were reduced to approximately 30% of the same parameters in the contralateral kidney. Urinary sodium excretion was consistently lower in the hydronephrotic than in the contralateral kidney. Volume expansion with isotonic saline solution revealed that this reduction of sodium excretion from the hydronephrotic kidney was out of proportion to the extent of GFR reduction. The contralateral unobstructed kidney did not compensate for this salt retention by increasing its sodium excretion.

Endogenous nitric oxide in the upper airways of healthy newborn infants.

The endogenous production of nitric oxide (NO) in the upper airways was studied in healthy newborn infants within the first minutes after delivery(N = 2) and at postnatal ages of 1 and 24 h (N = 13). Measurements were made in infants born vaginally or by cesarean section and at various times after the rupture of membranes. Gas was sampled from the nose and pharynx, and NO concentrations were determined by a fast response chemiluminescence analyzer. Sampling from the nose at a constant flow of 20 mL/min gave 0.27 ± 0.01 parts per million (mean ± SEM, ppm) of NO, independent of age and mode of delivery (vaginal delivery and cesarean section). Allowing NO to accumulate in the nose for 15-120 s yielded peak concentrations up to 4.6 ppm. A 30% increase was noted between 1 and 24 h of age. We conclude that nasal peak NO concentrations in the ppm range can be demonstrated in the healthy newborn infant within the first hour after birth. Consequently autoinhalation of endogenously produced upper airway NO may play a role in the adaptation of the respiratory system to postnatal life in the human.

Maturational changes in glomerular perfusion rate and glomerular filtration rate in lambs.

Extract: The developmental pattern of the glomerular filtration rate (GFR), the regional glomerular density, and glomerular blood flow, as well as that of the cardiac output, blood pressure, and hematocrit has been followed in 2—79-day-old lambs. The glomerular perfusion rate (GPR), i.e., the glomerular blood flow, has been derived by determining the regional renal blood flow with microspheres and dividing it by the number of glomeruli per unit of renal tissue at that cortical depth assuming that practically all of the spheres are trapped in the glomeruli. The GFR per gram of renal tissue increased more rapidly during the first days of life, whereas the total GFR appeared to increase more linearly with age. The glomerular density fell in all cortical layers. The fall was slightly more pronounced in the inner cortex. The glomerular blood flow was recorded in three zones: the outer 10% of the cortex, which contained an aglomerular as well as a high density glomerular zone; the mid 65% of the cortex, which on gross inspection appeared fairly homogeneous; and the inner 25% of the cortex, which corresponded to the juxtamedullary zone. In all zones the GPR increased with age. The increase was most pronounced in the inner cortex in the oldest animals. The largest scatter of data was found in the outer cortex as a result of the heterogeneity of that zone. The cortical profile for the GPR did not change much with age, which indicated that in the lamb no intrarenal redistribution of blood flow of greater importance occurs during the postnatal development. In the inner and midcortex the GPR increased in proportion to the cardiac output. In the outer cortex the data indicate that GPR increased somewhat more rapidly than cardiac output. The development of the total GFR has been related to the development of the GPR in the inner and midcortex since those two zones contain more than 90% of all glomeruli. During the first period of life the GFR increased more rapidly than the GPR. This coincided with the time when the most rapid fall in hematocrit was recorded. Thus the development of the glomerular plasma flow and the GFR appeared to follow closely.Speculation: In the growing animal as well as in the adult the glomerular plasma flow appears to be the main determinator of the glomerular filtration rate (GFR). Inasmuch as the arterial blood pressure in infants is close to the level at which the renal blood flow is autoregulated in the mature kidney, the GFR might be more susceptible to fluctuations in infants.

Capillary Blood Cell Velocity in Full-Term Infants as Determined in Skin by Videophotometric Microscopy

ABSTRACT: In order to study the neonatal microcirculation, the capillary hemodynamics in skin was investigated in 43 full-term infants 2–7 days after birth. The nailfold capillaries of the thumb were visualized by means of television microscopy and the capillary blood cell velocity (CBV) was videophotometrically quantified in 107 microvessels. The skin temperature, mean arterial blood pressure, and heel puncture hematocrit were measured simultaneously to evaluate any relation with the CBV. The mean CBV in all infants was 0.38 ± 0.21 mm/s, with a range of 0.04 to 1.2 mm/s in individual capillaries. There was no correlation between CBV and skin temperature (27–33° C), mean arterial blood pressure (44–68 mm Hg), or postnatal age. However, a significant correlation was found between the log CBV and the skin prick hematocrit (r = −0.64, p < 0.001). It is concluded that the mean CBV during the 1st wk of life is not significantly different from the capillary velocity reported in adults. Normal variations in skin temperature and mean arterial blood pressure, as well as age differences 2–7 days after birth, do not significantly influence the neonatal skin capillary blood flow. However, the hematocrit is of major importance for skin capillary perfusion in the newborn infant.

Intracranial Arterial Blood Flow Velocity and Brain Blood Flow during Hypocarbia and Hypercarbia in Newborn Lambs: A Validation of Range-Gated Doppler Ultrasound Flow Velocimetry

ABSTRACT: A transfontanellar range-gated ultrasound Doppler technique for recording blood flow velocity in an artery on the base of the skull was validated in eight anesthetized newborn lambs during hypo-, normo-, and hypercarbia. Blood flow velocity was linearly related to PaCO2 from 20 to 80 mm Hg; mean blood flow velocity (Vmean) (r = 0.86, p < 0.001), peak systolic blood flow velocity (r 0.83, p < 0.001), and end-diastolic blood flow velocity (r 0.87, p < 0.001). Vmean changed 2.0% per mm Hg of PaCO2. A linear relationship was demonstrated between brain blood flow (BBF), as determined by the microsphere method, and PaCO2 (r = 0.91, p < 0.001), with BBF changing 3.6%/mm Hg of PaCO2. Blood flow velocity was linearly related to BBF in the PaCO2 range studied; Vmean (r = 0.89, p < 0.001), peak systolic blood flow velocity (r = 0.87, p < 0.001), and end-diastolic blood flow velocity (r = 0.87, p < 0.001). However, Vmean predicted only approximately 55% of the change in BBF, which suggests a concomitant change in the cross-sectional area of the artery being studied. Despite this limitation, these data suggest that blood flow velocity, recorded by a transfontanellar range-gated Doppler technique from one of the two main arteries perfusing the brain, provides qualitative information on changes in BBF.

Regulation of Renal Water Excretion in Newborn Full-term Infants

ABSTRACT. The renal response to low (45 ml/kg) and high (73 ml/kg) fluid intake was studied during an 8‐hour period in healthy 3–4‐day‐old full‐term infants. 20 infants received low fluid (LF) intake and 15 infants received high fluid (HF) intake. HF significantly increased urine flow and significantly decreased urine osmolality but did not influence glomerular filtration rate measured as the clearance of creatinine. Serum arginine vasopressin (s‐AVP) was not different in the LF and HF groups and did not correlate to urine osmolality. Urinary sodium excretion was significantly correlated to the diuresis. Conclusion: Following high fluid intake full‐term infants are capable to adaptively excrete larger urine volumes and more dilute urine by mechanisms independent of AVP. S‐AVP appears to relate differently to the state of hydration and to urine osmolality in infants than in adults.

Congenital Arrhythmias with Supraventricular Tachycardia in the Perinatal Period

Abstract. Fourteen cases with perinatal tachyarrhythmia are described. Intra‐uterine cardiac arrhythmia was observed in 8 cases: 6 with paroxysmal supraventricular tachycardia (PST) and 2 with atrial flutter, all but one with variable AV‐block, and heart rate ranging between 120–230 beats/min. Caesarean section was performed because of suspected asphyxia in 4 cases and delivery by vacuum extraction in 2 of the 8 cases. All 6 cases first appearing in the first 4 days of life had PST with a heart rate varying from 210–310. Congestive heart failure, occurring in 10 cases in the total series, developed significantly earlier in the patients with intra‐uterine diagnosed tachycardia. No cause was found in 10 cases, and only 2 cases displayed the Wolff‐Parkinson‐White (WPW) syndrome. The importance of early ECG recording in all neonates with arrhythmia is stressed. An increased use of the fetal ECG is recommended in cases with rapid or irregular fetal heart sounds. The delivery should be accelerated when the fetal heart rate is constantly more than 200 beats/min.

Skin microcirculation in neonatal polycythaemia and effects of haemodilution. Interaction between haematocrit, vasomotor activity and perfusion

The cutaneous microcirculation was investigated before and 2–4 h after haemodilution in 13 newborn infants with polycythaemia. Skin microvascular perfusion was related to the haematocrit and to the presence of rhythmical changes in blood flow, reflecting vasomotor activity. The microcirculation was studied with a laser Doppler fluxmeter in a superficial microvascular bed represented by the dorsal hand skin. In five subjects, it was possible to combine laser Doppler flux measurements with microscopic quantitations of blood cell velocity in single, nailfold capillaries. In neonates less than 12 h postnatal age (n= 6), microvascular perfusion was only one‐third that of the equally polycythaemic, but older infants (n= 7, p < 0.01). The higher perfusion in the older neonates with polycythaemia was associated with rhythmical variations in blood flow (3–5 cycles/min). There was no difference in skin temperature, blood pressure or heart rate between the two age groups. After haemodilution, the younger infants had developed rhythmical blood flow variations with the same characteristics as in the older group, in which the flow pattern was unchanged. In association, the laser Doppler flux had increased 304% in the younger and 73% in the older group (median values, p<0.05 versus pretreatment values). The post‐treatment change in laser Doppler flux corresponded to an increase in nailfold capillary blood cell velocity from 0.08 (0.02–0.23) mmjs prior to haemodilution to 0.21 (0.07–0.32) mmjs after treatment (n = 5, p < 0.05). Skin microcirculatory effects of neonatal polycythaemia and haemodilution vary in relation to vasomotor activity.