Fetal Glomerular Filtration Rate Research Articles

Quantification of Fetal Renal Function Using Fetal Urine Production Rate and Its Reflection on the Amniotic and Fetal Creatinine Levels During Pregnancy.

Adequate prediction of fetal exposure of drugs excreted by the kidney requires the incorporation of time-varying renal function parameters into a pharmacokinetic model. Published data on measurements of fetal urinary production rate (FUPR) and creatinine at various gestational ages were collected and integrated for prediction of the fetal glomerular filtration rate (GFR). The predicted GFR values were then compared to neonatal values recorded at birth. Collected data for FUPR across different gestational ages using both 3D (N = 517) and 2D (N = 845) ultrasound methods showed that 2D techniques yield significantly lower estimates of FUPR than 3D (p < 0.0001). A power law function was shown to best capture the change in FUPR with fetal age (FA) for both 2D (); and 3D () data. The predicted FUPR based on the observed 3D data was shown to be strongly linearly related (R2 = 0.95) to measured values of amniotic creatinine concentration (N = 664). The FUPR3D data together with creatinine levels in the fetal urine and serum resulted in median predicted fetal GFR values of 0.47, 1.2, 2.5, and 4.9 ml/min at 23, 28, 33, and 38 weeks of fetal age (50% CV), respectively. These values are in good agreement with neonatal values observed immediately at birth. The derived FUPR and creatinine functions can be utilized to assess fetal renal maturation and predict fetal renal clearance.

Longitudinal study of Cystatin C in healthy term newborns

OBJECTIVE:The purpose of this study was to determine the levels of Cystatin C in healthy term newborns in the first month of life.INTRODUCTION:Cystatin C may be a suitable marker for determining the glomerular filtration rate because it is not affected by maternal renal function.METHODS:Cohort study. Inclusion: term newborns with appropriate weight; mother without renal failure or drugs that could affect fetal glomerular filtration rate. Exclusion: malformations; hypertension or any condition that could affect glomerular filtration rate. Cystatin C (mg/L) and creatinine (mg/dl) were determined in the mother (Mo) and in the newborn at birth (Day‐0), 3rd (Day‐3), 7th(Day‐7) and 28th(Day‐28) days. Statistics: one way ANOVA and Pearson's correlation tests. Sample size of 20 subjects for α = 5% and a power test = 80% (p<0.05).RESULTS:Data from 21 newborns were obtained (mean ± standard deviation): MoCystatin C = 1.00±0.20; Day‐0 Cystatin C 1.70±0.26; Day‐3 Cystatin C = 1.51±0.20; Day‐7 Cystatin C = 1.54±0.10; Day‐28 Cystatin C = 1.51±0.10.MoCystatin C was smaller than Day‐0 Cystatin C (p<0.001), while MoCreatinine was not different from Day‐0 Creatinine. Cystatin C only decreased from Day‐0 to Day‐3 (p = 0.004) but newborns Creatinine decreased along the time. Correlations were obtained between MoCystatin C and MoCreatinine (p = 0.012), as well as Day‐3 (p = 0.047) and Day‐28 (p = 0.022) Cystatin C and Creatinine values.CONCLUSION:Neonatal Cystatin C values were not affected by MoCystatin C and became stable from the 3rd day of life.

Mechanisms of neonatal increase in glomerular filtration rate

To investigate the mechanisms responsible for the neonatal increase in glomerular filtration rate (GFR), renal function studies (whole kidney and micropuncture) were carried out in anesthesized fetal sheep (133-140 days gestation; term = 150 days) and lambs (12-18 days). Fetuses were delivered and placed in a water bath (39.5 degrees C), keeping the umbilical cord moist and intact. Lambs were studied on a thermostatically controlled heating pad. Animals were prepared for either blood flow studies or micropuncture measurements. Expected differences in blood composition and cardiovascular and renal function were observed between fetuses and lambs, and values obtained for most variables were similar to those measured in chronically catheterized unanesthetized animals. Fetal GFR was much lower than that of lambs (0.20 vs. 0.62 ml.min(-1).g kidney(-1), P < 0.001). Free-flow, stop-flow, and net filtration pressures (NFP) were lower in the fetuses than the lambs (NFP 20.8 vs. 23.8 mmHg, P < 0.001), as was the calculated ultrafiltration coefficient (0.014 vs. 0.022 ml.min(-1).g(-1).mmHg(-1), P < 0.001). Thus, we conclude that rises in both net filtration pressure and the ultrafiltration coefficient contribute to the large increase in GFR between fetal life and approximately 2 wk after birth.

Chronic effect of insulin-like growth factor I on renin synthesis, secretion, and renal function in fetal sheep.

In the adult, insulin-like growth factor I (IGF-I) increases glomerular filtration rate (GFR) and renal blood flow (RBF) during both acute and chronic treatment. To study its effects on the developing kidney, chronically catheterized fetal sheep (120 +/- 1 days gestation) were infused intravenously for up to 10 days with 80 microgram/h IGF-I (n = 5) or vehicle (0.1% BSA in saline, n = 6). In contrast to previous acute studies in adult rats and humans, after 4 h of IGF-I fetal GFR and RBF were unchanged. Fractional sodium reabsorption increased (P < 0.05). However, by 4 days, GFR per kilogram had risen by 35 +/- 13% (P < 0.05), whereas RBF remained unchanged. Tubular growth and maturation may have occurred, as proximal tubular sodium reabsorption increased by ~35% (P < 0.005). Therefore, despite a marked increase in filtered sodium (~30%, P < 0.05), fractional sodium reabsorption did not change. Although the effects of IGF-I on renal function were delayed, plasma renin activity and concentration were both elevated after 4 h and remained high at 4 days (P < 0.05). Despite this, arterial pressure and heart rate did not change. Kidneys of IGF-I-infused fetuses weighed ~30% more (P = 0.05) and contained ~75% more renin than control fetuses (P < 0.005). Thus, in the fetus, the renal effects of long-term IGF-I infusion are very different from the adult, possibly because IGF-I stimulated kidney growth.

Experimental bilateral urinary obstruction in fetal sheep: transforming growth factor-beta 1 expression.

To gain insight into the role of transforming growth factor-beta 1 (TGF-beta 1) in the development of kidney pathology following fetal obstruction, we measured TGF-beta 1 gene expression, the active peptide, and the urinary concentration in a model of fetal bilateral urinary obstruction (BUO) in sheep. Fetal lambs underwent BUO at 60 (FO-60) or 80 days (FO-80) of gestation and were studied at 120 days. Independently of the onset or duration of obstruction, all fetuses developed type IV dysplasia (IV) associated with an arrest in the nephrogenesis or hydronephrosis. Fetal glomerular filtration rate was not significantly modified, whereas sodium tubular reabsorption was significantly decreased, and urinary TGF-beta 1 concentration was elevated in hydronephrosis but not in IV. Levels of TGF-beta 1 mRNA were increased in hydronephrosis compared with normal kidneys, and active TGF-beta 1 immunoreactivity was increased in both hydronephrotic and IV kidneys. In summary, TGF-beta 1 may play a role in the development of hydronephrosis and dysplasia in kidneys following fetal BUO. Its role in the arrest of nephrogenesis observed in the IV kidneys remains to be proved.

Responses of fetal sheep to reduced maternal renal blood flow and maternal hypertension.

In 16 chronically catheterized fetal sheep the effects of reducing and restoring maternal renal blood flow (RBF) and thus inducing and reversing hypertension were studied in uninephrectomized pregnant ewes; controls were 3 fetuses that were carried by uninephrectomized ewes in which RBF was not reduced and that did not become hypertensive. Within 24-72 h of maternal RBF reduction, fetal arterial PO2 had fallen (P < 0.001) and PCO2 had increased (P < 0.025); fetal arterial pressure also increased (P < 0.005). These effects persisted, despite restoration of maternal RBF and reversal of maternal hypertension. Within 24-72 h of reduction of maternal RBF, fetal urine flow had increased (P < 0.005), and it remained elevated over the first 3 h after RBF was restored; 24-72 h later it was lower (P < 0.025) and returned to control levels. The excretion of sodium, potassium, and chloride showed a similar increase when maternal RBF was reduced (P < 0.001), with return to control values 24-72 h after RBF had been restored. Fetal glomerular filtration rate did not change; thus the natriuresis and diuresis that occurred were due to reduced tubular solute and water reabsorption (P < 0.025). These changes in fetal renal function may be related, in part, to changes in fetal PO2 and PCO2, but they are most likely due to reduced maternal renal function due to the restriction in maternal RBF, inasmuch as they were reversed when RBF was restored.

The effects of continuous drainage of fetal fluids on salt and water balance in fetal sheep.

1. In nine chronically catheterized fetuses in which all lung liquid was drained continuously from the time of surgery, the effects of continuous drainage of fetal urine for 1 week on fetal renal function, lung liquid production and salt and water balance were studied. Fetal wellbeing, as judged by fetal growth, urinary osmolality, blood gas status, arterial pressure and heart rate, was not adversely affected by urine drainage. The ewes, however, drank more water when fetal urine was drained. Thus. fetal plasma and urinary osmolalities declined (P < 0.25 and P < 0.05). 2. Fetal glomerular filtration rate fell from 75 +/- 4 ml kg-1 h-1 (+/- S.E.M., n = 9) before drainage to 54 +/- 7 ml kg-1 h-1 after drainage (n = 7; P < 0.005), and fetal renal sodium excretion also declined (P < 0.05). However, the excretion of sodium in lung liquid did not decrease and the fetal renin-angiotensin system was not activated. Fetal extracellular volume (561 +/- 44 ml kg-1, n = 7) and the calculated net sodium transfer (0.76 mmol kg-1 h-1, n = 6) and fluid transfer (15 +/- 2 ml kg-1 h-1, n = 8) to the fetus did not change. 3. It is concluded that overall fetal salt and water balance were maintained when all fetal urine and lung liquid were drained from fetal sheep in late gestation. Since drainage of urine and lung liquid considerably reduced the amniotic and allantoic fluids, transfer across the placenta and extraplacental membranes was able to compensate for the absence of these fluids. In response to the loss of sodium during drainage, fetal renal sodium conservation was about 11% of the total sodium conservation by the materno-fetal unit.

Functions of the renin-angiotensin system during development.

1. From studies in chronically catheterized fetal sheep and other species, it can be shown that the renin-angiotensin system (RAS) is active during intra-uterine life. Levels of angiotensin II (AII) in fetal sheep are similar to maternal. 2. The fetal RAS plays a role in maintenance of arterial pressure. The extent to which it does so depends on the level of activity of the system. 3. The distribution of renin within the fetal rat kidney is much more widespread than in the adult. The fetal kidney, like other vascular beds has high levels of the AT2 angiotensin receptor subtype. With maturation the proportion of the AT1 receptor subtype increases. 4. Blockade of the fetal RAS with angiotensin converting enzyme (ACE) inhibitors or with the non-peptide AII antagonist (losartan) caused a fall in fetal glomerular filtration rate (GFR) and a rise in renal blood flow (RBF). AII reverses the fall in GFR even though RBF decreases. 5. The fraction of the filtered sodium load reabsorbed by the proximal tubule was not affected when the fetal RAS was blocked by captopril or losartan. High doses of infused AII had no effect on renal reabsorption of sodium, in the short term, but in the long term depressed fractional proximal reabsorption. 6. Only in high doses does AII stimulate the secretion of aldosterone from the fetal adrenal.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of a converting enzyme inhibitor (captopril) and angiotensin II on fetal renal function.

1. Renal function was studied in chronically catheterized fetal sheep (119-128 days gestation), before and during treatment of the ewe with the angiotensin converting enzyme (ACE) inhibitor, captopril, which crosses the placenta and blocks the fetal renin angiotensin system. 2. An i.v. dose of 15 mg (about 319 micrograms kg-1) of captopril to salt-replete ewes followed by an infusion to the ewe of 6 mg h-1 (about 128 micrograms kg-1 h-1) caused a fall in fetal arterial pressure (P < 0.01), and a rise in fetal renal blood flow (RBF) from 67.9 +/- 5.6 to 84.9 +/- 8.3 ml min-1 (mean +/- s.e. mean) (P < 0.05). Renal vascular resistance and glomerular filtration rate (GFR) fell (P < 0.01); fetal urine flow (P < 0.01); fetal urine flow (P < 0.01) and sodium excretion declined (P < 0.05). 3. Ewes were treated for the next 2 days with 15 mg captopril twice daily. On the 4th day, 15 mg was given to the ewe and fetal renal function studied for 2 h during the infusion of captopril (6 mg h-1) to the ewe. Of the 9 surviving fetuses, 3 were anuric and 3 had low urine flow rates. When 6 micrograms kg-1 h-1 of angiotensin II was infused directly into the fetus RBF fell from 69 +/- 10.1 ml min-1 to 31 +/- 13.9 ml min-1, GFR rose (P < 0.05) and urine flow (P < 0.01) and sodium excretion increased in all fetuses. 4. It is concluded that the small fall in fetal arterial pressure partly contributed to the fall in fetal GFR but in addition, efferent arteriolar tone fell so that the filtration pressure fell further. Thus maintenance of fetal renal function depends on the integrity of the fetal renin angiotensin system. These findings explain why use of ACE inhibitors in human pregnancy is associated with neonatal anuria.

Fetal urine biochemistry: an index of renal maturation and dysfunction.

To construct a reference range for fetal urinary sodium, potassium, urea, creatinine, calcium and phosphate with gestation and to assess to what extent these biochemical indices are modified in fetuses with lower urinary tract obstruction. Prospective descriptive study. Royal Postgraduate Medical School London. 24 women between 17 and 35 weeks gestation with an ultrasound diagnosis of fetal lower urinary tract obstruction, with or without renal dysplasia and a control group of 26 women between 16 and 33 weeks gestation with normal amniotic fluid volume and fetal anatomy. Fetal urine samples (1-100 ml) were aspirated from the control fetuses either before termination of pregnancy (n = 9) or at the time of intrauterine transfusion for Rh alloimmunization (n = 17). The fetuses with obstructive uropathy had urine samples aspirated on one occasion (n = 14) or serially (n = 10). Relation between urine biochemistry and renal damage ascertained clinically or at postmortem. In the control group, urinary sodium and phosphate decreased and creatinine increased significantly with gestational age, consistent with increasing fetal glomerular filtration rate and progressive maturation of tubular function. Urinary sodium and calcium were significantly higher in fetuses with renal dysplasia compared with those with lower urinary tract obstruction but normal renal histology or normal clinical outcome. Serial urinary samples from fetuses with obstructive uropathy showed more pronounced deviation from the normal with increasing gestation in all fetuses with renal dysplasia. The highest sensitivity in the detection of renal dysplasia was shown by urinary calcium (100%) whereas urinary sodium showed the best specificity (80%). Renal damage is the direct effect of urinary obstruction, rather than an association so that treatment should start as soon as possible. Urinary biochemistry may be helpful in the management of these patients.

Intraruminal rehydration of ovine fetuses

During oral rehydration of adult mammals, oropharyngeal stimulation, the act of swallowing, and/or gastric factors contribute to a rapid decrease in plasma arginine vasopressin (AVP) that precedes plasma osmolality changes. To determine whether similar mechanisms are present in the developing fetus, six chronically prepared ovine fetuses were rehydrated with intraruminal (IR) distilled water infusions (1 ml.kg-1.min-1 for 60 min) after 43 +/- 3 h of maternal water deprivation. In response to maternal dehydration, significant increases were noted in maternal and fetal mean plasma osmolalities, sodium and AVP concentrations, and fetal urine osmolality. As estimated by hematocrit, fetal intravascular volume decreased by 11%. Fetal rehydration via IR distilled water infusion evoked a significant decrease in fetal plasma osmolality but no change in urine osmolality. Unexpectedly, fetal arterial blood pressure increased and arterial PO2 decreased while fetal hematocrit indicated a further 7% decrease in intravascular volume after the IR infusion. There was a nonsignificant trend toward increased fetal glomerular filtration rate, urine volume, and plasma AVP concentrations. Identical IR water infusions to five euhydrated fetuses resulted in significant decreases in fetal plasma osmolality and increases in glomerular filtration rate, urine flow, and osmolar excretion. The euhydrated fetuses also exhibited significant increases in mean arterial blood pressure and hematocrit and decreased fetal arterial PO2. These results indicate that IR water does not suppress AVP secretion in the dehydrated ovine fetus. Rather, both euhydrated and dehydrated fetuses exhibit an idiosyncratic vasoconstrictive response to IR water.

Maternal dehydration-rehydration: fetal plasma and urinary responses.

Pregnant women may be exposed to exercise, thermal, or gastrointestinal (hyperemesis) water loss, all of which commonly induce a greater than 10 mosmol increase in plasma osmolality. Although fetal osmolality is dependent on maternal osmolality, the impact of maternal dehydration and subsequent maternal rehydration on the fetus has not been explored. Five pregnant ewes with singleton fetuses (136 +/- 1 day) were water deprived for 36 h resulting in a significant increase in plasma osmolality (298 +/- 3.4 to 313 +/- 5.0 mosmol). In response to maternal dehydration, fetal plasma osmolality (297.0 +/- 4.1 to 309.3 +/- 4.1 mosmol), arginine vasopressin (AVP) levels (1.5 +/- 0.2 to 7.9 +/- 1.0 pg/ml), hematocrit (35.1 to 38.6%), and urine osmolality (161.3 +/- 10.7 to 348.9 +/- 21.9 mosmol) significantly increased. Subsequently, ewes were rehydrated over 4 h with intravenously infused 0.45% saline (20 ml.kg-1.h-1). In response to maternal rehydration, maternal and fetal plasma osmolality decreased to basal values (298.9 +/- 3.2 and 300.1 +/- 3.8 mosmol, respectively) and fetal glomerular filtration rate (1.72 +/- 0.30 to 3.08 +/- 0.66 ml/min) and urine volume significantly increased (0.33 +/- 0.02 to 0.71 +/- 0.13 ml/min). However, fetal hematocrit (37.4%), plasma AVP (3.1 +/- 0.9 pg/ml), and urine osmolality (255.4 +/- 28.8 mosmol) did not return to basal levels during the observation period. These results demonstrate fetal hyperosmolality, blood volume contraction, AVP secretion, and altered urine production in response to maternal dehydration. Despite maternal rehydration and normalization of maternal and fetal plasma osmolality, fetal endocrine and fluid responses are prolonged.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of maternal hyperglycemia on fetal renal function in sheep.

The effects of maternal hyperglycemia on fetal renal function were investigated in 10 chronically catheterized fetal sheep after the infusion of 100 g of glucose into the ewe over 30 min. Fetal blood glucose levels rose (P less than 0.001) within 15 min of completing the glucose infusion from 15.75 +/- 2.8 to 195.4 +/- 18 (SE) mg/dl (n = 10). There was a significant increase in fetal glomerular filtration rate (P less than 0.05) from 2.73 +/- 0.41 to 3.65 +/- 0.40 (SE) ml/min (n = 10) within 1.5 h of the infusion of glucose into the ewe. Urine flow rate increased from 0.38 +/- 0.06 to 0.63 +/- 0.12 (SE) ml/min (n = 10, P less than 0.001), and sodium excretion increased from 18.42 +/- 7.21 to 38.4 +/- 13.7 (SE) mumol/min (n = 10, P less than 0.002) within 2.5 h of the infusion of glucose into the ewe. The fraction of the filtered load that was excreted (urine flow rate divided by glomerular filtration rate) also increased (P less than 0.01) as did the fraction of the osmolar load (P less than 0.002). Glycosuria occurred in all fetuses within 30 min of the infusion of glucose into the ewe, and glucose excretion reached 26.16 +/- 12.36 (SE) micrograms/min (n = 8) after 1.5 h. These findings of diuresis, natriuresis, and glycosuria in response to hyperglycemia are evidence that an increased delivery of fluid into the amniotic cavity might occur after a rise in fetal plasma glucose levels.

The effects of metabolic acidosis on renal function of fetal sheep.

1. The effects of I.V. infusions of 6.7-19.3 mmol hydrochloric acid/kg on fetal renal function were studied in fourteen chronically catheterized fetal sheep aged 121-143 days. Infusion of acid caused arterial pH and plasma bicarbonate levels to fall (P less than 0.0005, P less than 0.001). These remained low for the next 3 h. Plasma chloride levels increased (P less than 0.0005). There were no other changes in plasma electrolytes nor in plasma osmolality. 2. Fetal glomerular filtration rate did not change; the fractional reabsorptions of sodium, chloride and phosphate all decreased (P less than 0.005). Initially urine volume did not change but urinary osmolality increased (P less than 0.0005). Fetal urinary pH fell abruptly, titratable acid excretion increased, urinary ammonium excretion increased (P less than 0.0005) but urinary bicarbonate excretion remained unchanged. Thus, net acid excretion increased significantly (P less than 0.0005). 3. Twenty-six hours after infusion of acid, fetal arterial pH, bicarbonate levels, urinary pH, titratable acid and ammonium excretion were no different from control. Net acid excretion was still increased (P less than 0.05), urine flow rate was less (P less than 0.01) and urinary osmolality still increased (P less than 0.05). 4. There were no differences in arterial blood gases nor in pH of four fetuses which died during or shortly after infusion of acid. However, prior to acid infusion they were already excreting significantly greater amounts of phosphate (P less than 0.01), ammonium and titratable acid (P less than 0.02). Thus the fetal kidney responds to a metabolic acidosis by excreting more acid and by generating more bicarbonate, but this response is limited.

Ultrasonic assessment of fetal kidney function in normal and complicated pregnancies

Fetal renal function was evaluated in 255 normal singleton pregnancies between 22 and 41 weeks of gestation and in 133 complicated pregnancies. Hourly fetal urinary production rate (HFUPR), fetal glomerular filtration rate (GFR), fetal tubular water reabsorption (TWR), and the effect of furosemide on fetal micturition was evaluated by ultrasound and a combination of ultrasound and biochemical tests. In normal pregnancies, the HFUPR increased from 2.2 ml/hr at 22 weeks of gestation to 26.3 ml/hr at 40 weeks of gestation. The fetal GFR was 2.66 ml/min at term, and the percentage of TWR was 78%. In complicated pregnancies, the HFUPR was above normal in 5.7% of the growth-retarded fetuses and below the tenth percentile in 58.6%. The GFR was below normal in 68.2% of the group of complicated pregnancies, but TWR did not significantly differ from that in the normal pregnancies. The effect of furosemide was the same in both growth-retarded and normal fetuses. In diabetic pregnancies, HFUPR values varied considerably and correlated with the fetal size. The HFUPR was normal in anencephalic fetuses and in 90.0% of the pregnancies with hydramnios.

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.

Role of Aldosterone on Renal Sodium and Potassium Excretion during Fetal Life and Newborn Period

The renal response to endogenous aldosterone production at different times during gestation and immediately after birth, as well as factors controlling aldosterone secretion during fetal life have been studied in 34 lamb fetuses (106-142 days of gestation, term 145 days) and in 6 newborn lambs (3-8 days postnatal age). It was demonstrated that the increase in fetal plasma aldosterone concentrations correlated with the increase in fetal plasma renin activity (PRA) (r = 0.67, p < 0.001). Moreover, it was fond that the slope of the regression line between plasma aldosterone and PRA during fetal life was significantly steeper (p < 0.05) than after birth. Significant correlation coefficients were found between the fetal urinary to plasma ratios (U/P) of sodium over potassium [(U/P)Na+/(U/P)K+] and either fetal plasma aldosterone (r = -0.53, p < 0.005) or fetal age (r = -0.52, p < 0.005). Moreover, in 7 out of 9 fetuses over 125 days, frank secretion of potassium by the fetal tubular cells was demonstrated; such a secretion was present in only 1 of the 15 fetuses between 101 and 125 days of gestation. Finally, it was demonstrated that the increase in mean arterial blood pressure during fetal life and after birth is not a major factor in the increase in fetal glomerular filtration rate during gestation or in the adaptation of glomerular filtration rate to extrauterine life.

Renal responses of the fetal lamb to fetal or maternal volume expansion.

Fetal and maternal glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume, sodium excretion, and fractional sodium reabsorption were measured in a chronically instrumented sheep preparation. Fetal GFR was essentially stable between 110 and 135 days of gestation (term = 147 days). There was a significant increase in GFR after 135 days. After the infusion of 50 ml of normal saline over a 30-minute period, fetal GFR and sodium excretion increased significantly. Fractional sodium reabsorption was significantly decreased. Thus, the fetus is capable of responding to volume expansion with saline with an increase in GFR and a decrease in fractional sodium reabsorption. After the infusion of 1000 ml of normal saline into the ewe in 1 hour, maternal GFR and RPF rose significantly. Sodium excretion rose 6-fold and fractional sodium reabsorption fell significantly. After the infusion of saline into the ewe, there was no change in fetal GFR, RPF, sodium excretion, urine volume, or fractional sodium reabsorption. Since there were no changes in fetal renal function after maternal volume expansion with saline there was no evidence for the transplacental passage of a natriuretic factor from ewe to fetus.

A combined ultrasonic and biochemical study of fetal renal function in the term fetus

The fetal glomerular filtration rate of plasma (GFR) and the percentage of fetal tubular reabsorption of water were measured by means of combined ultrasonic and biochemical methods in 20 normal and 10 complicated pregnancies. The duration of pregnancy varied from 35 to 42 wk. In normal pregnancy GFR of plasma varied from 2.0 to 7.1 ml/min (mean = 4.1) and tubular reabsorption of water ranged from 84.1 to 93.0% (mean = 89.8). There was no relationship with gestational age. In the group of complicated pregnancies —apart from one anencephalic case — no apparent difference in GFR and percentage tubular reabsorption between the group of normal (⩾- 10th percentile) and reduced fetal birth weight (< 10th percentile) was observed.