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PubMed1984

Renal sodium handling in minimal change nephrotic syndrome.

Renal sodium handling was studied in 23 children at three different stages of the minimal change nephrotic syndrome--the oedema forming state, proteinuric steady state, and remission. Clearances of inulin and para-aminohippuric acid and urinary sodium excretion were determined basally, after intravenous infusion of isotonic saline and hyperoncotic albumin, and after furosemide injection. Absolute and fractional basal sodium excretion were significantly lower in oedema forming patients than in proteinuric patients in steady state, and non-proteinuric patients. In contrast to proteinuric patients in steady state and non-proteinuric patients, the oedema forming patients failed to respond to isotonic saline infusion with increased sodium excretion. After diuretic blockade with furosemide, the fractional sodium excretion of the oedema forming patients increased to values no different from those of the non-proteinuric patients, whereas the fractional sodium excretion of the steady state patients increased to significantly higher values. The plasma aldosterone concentration was within normal limits in 11 of 14 proteinuric patients, and did not correlate with the basal sodium excretion. Thus, sodium retention in the minimal change nephrotic syndrome was found only in oedema forming patients, and since this is not related to the plasma aldosterone concentration it may be caused by an intrarenal mechanism, probably sited in distal parts of the nephron.

Adolescent↗
PubMed1991

Long-term follow up of renal function in IgA nephropathy.

Fifty one children with IgA nephropathy verified at biopsy have been followed up clinically and functionally for 0.4-16.8 years from the onset of symptoms. Renal function was evaluated by determining the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) from the clearances of inulin and para-aminohippuric acid. Fifteen (29%) of the children had raised serum creatinine concentrations at the onset. Mean GFR was significantly lower than that of controls at the first investigation. During the follow up GFR and ERPF decreased and were significantly lower than in the controls after eight years of disease. The significant fall in renal function was found in children with proteinuria and especially in boys, in whom GFR and ERPF decreased from a mean (SEM) of 117 (5) and 616 (31) at 2.8 years to 97 (6) and 509 (36) ml/min/1.73 m2 at 7.5 years. Patients with raised serum creatinine concentrations at the onset had significantly lower GFRs, and patients with macroscopic haematuria at this time did not show decreased renal function at follow up. In conclusion, children with IgA nephropathy do not seem to have a benign clinical course. Boys with proteinuria show a significant decrease in renal function during follow up.

Adolescent↗
PubMed1991

Renal histological changes in relation to renal function and urinary protein excretion in IgA nephropathy.

Renal function and urinary protein excretion (UPE) were investigated at the time of kidney biopsy in 24 children with IgA nephropathy. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by clearances of inulin and para-aminohippuric acid. For UPE albumin, IgG, beta 2 microglobulin, and creatinine were analysed. Glomerular global/segmental sclerosis and crescents in the biopsy specimens were assessed, and glomerular and tubulointerstitial changes classified on a five degree scale. The patients with tubulointerstitial or mesangial biopsy changes or glomerular sclerosis had significantly lower GFR than those without corresponding lesions. Patients with segmental sclerosis also had higher excretion rates of IgG, which increased with increasing segmental sclerosis. Six patients had GFRs below 2SD of the controls. Within the group of patients with reduced GFR overt albuminuria, a raised excretion rate of IgG, interstitial fibrosis, and advanced mesangial lesions were more frequent. A rising excretion rate of IgG seems to indicate both reduced GFR and increasing segmental glomerulosclerosis and may be a marker of progressive disease.

Adolescent↗
PubMed1977

Compensatory renal hypertrophy in dogs: single nephron glomerular filtration rate.

Sodium ferrocyanide was used to measure the intrarenal distribution of single nephron glomerular filtration rate (SNGFR) in remaining kidneys of dogs, 10 d after contralateral nephrectomy. It was first demonstrated that the renal function of both kidneys in situ was comparable. Following right nephrectomy, the urine volume, p-aminohippuric acid clearance, creatine clearance, osmolar clearance, fractional excretion of potassium, and sodium excretion of the left kidney increased. Fractional excretion of sodium, free water clearance, and filtration fraction remained unchanged. Following that 10-d period, left kidney weight exceeded that of the previously removed contralateral kidney by 50%, indicating that most of the compensatory hypertrophy had already occurred. No significant difference in the length of the proximal tubule nor in the diameter of the glomeruli of superficial (SUP) and juxtamedullary (JM) nephrons of either kidney could be demonstrated. Most importantly, the ratio of radioactivity in the SUP/JM nephrons of the residual kidney was comparable with that previously observed in normal dog kidneys. Thus, the increase in total kidney GFR is explained through a proportional increase in the SNGFR of the SUP and JM nephrons.

Animals↗
PubMed1984

Renal function in rats with innervated and denervated kidneys before and during sodium pentobarbital anesthesia.

We have used a model for measuring renal clearances in the undisturbed rat to assess the role of the renal nerves in the depression of renal function during sodium pentobarbital anesthesia. One group of rats was studied with renal nerves intact and a second group was studied 7-9 days after bilateral renal denervation. Rats were prepared by placement of cannulae an average of 5 days prior to the clearance experiments. Renal function was measured before and after the injection of saline as the control vehicle and 2-3 days later, before, and after the injection of sodium pentobarbital (50 mg/kg) in the same rat. Sodium pentobarbital produced comparable decreases in glomerular filtration rate, para-aminohippuric acid clearance, urine flow rate, and sodium excretion in rats with denervated or innervated kidneys. Injection of saline resulted in no differences in measured variables between the rats with intact or sectioned renal nerves. Sodium pentobarbital caused a drop in arterial pressure in the denervated group but not in the innervated group. In a second series of experiments rats with denervated kidneys were implanted with an inflatable occluder around the aorta. This occluder was inflated to limit the drop in arterial pressure during anesthesia. When the blood pressure to the kidneys was maintained, renal function did not decrease during sodium pentobarbital anesthesia. These experiments suggest that the renal nerves are involved in the decrease in renal function during sodium pentobarbital anesthesia.

Anesthesia↗
PubMed1978

Pulmonary absorption of drugs in the neonatal rat.

To compare the pulmonary absorption of drugs in newborn rats (3-27 days old) with that in adults, 0.01-0.1 ml of Krebs-Ringer phosphate solution (pH 7.4) containing a drug was administered to anesthetized animals by way of a catheter introduced through a tight-fitting tracheal cannula. After various times, lungs and trachea were removed and assayed for drug that remained. Semilogarithmic plots of percent drug remaining against time yielded a straight line for each compound. The lipid-soluble drugs procaine amide and sulfisoxazole were absorbed at similar rates in newborn and adult rats. In contrast, the lipid-insoluble drugs tetraethylammonium, p-aminohippuric acid, and mannitol were absorbed approximately 2 times more rapidly in younger rats (3-12 days) than in older animals (18 day, 27 day, or adult). The results suggested that the respiratory tract membranes of 3- to 12-day-old rats have a greater porosity than those of older animals.

Absorption↗
PubMed2003

Characterization of an organic anion transport system in a placental cell line.

Transporters within the placenta play a crucial role in the distribution of nutrients and xenobiotics across the maternal-fetal interface. An organic anion transport system was identified on the apical membrane of the rat placenta cell line HRP-1, a model for the placenta barrier. The apical uptake of 3H-labeled organic anion estrone sulfate in HRP-1 cells was saturable (Km = 4.67 microM), temperature and Na+ dependent, Li+ tolerant, and pH sensitive. The substrate specificity of the transport system includes various steroid sulfates, such as beta-estradiol 3,17-disulfate, 17 beta-estradiol 3-sulfate, and dehydroepiandrosterone 3-sulfate (DHEAS) but does not include taurocholate, p-aminohippuric acid (PAH), and tetraethylammonium. Preincubation of HRP-1 cells with 8-bromo-cAMP (a cAMP analog) and forskolin (an adenylyl cyclase activator) acutely stimulated the apical transport activity. This stimulation was further enhanced in the presence of IBMX (a phosphodiesterase inhibitor). Together these data show that the apical membrane of HRP-1 cells expresses an organic anion transport system that is regulated by cellular cAMP levels. This transport system appears to be different from the known taurocholate-transporting organic anion-transporting polypeptides and PAH-transporting organic anion transporters, both of which also mediate the transport of estrone sulfate and DHEAS.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Effect of vasopressin on atrial natriuretic peptide release and renal function in dogs.

To assess the effect of arginine vasopressin (AVP) and 1-deamino-8-D-AVP (DDAVP) on atrial natriuretic peptide (ANP) release, renal water and electrolyte excretion, and cardiovascular function, AVP and DDAVP were administered at a dose of 10 ng.kg-1.min-1 iv for 30 min into anesthetized dogs receiving saline infusion at a rate of 1 ml.kg-1.min-1 (n = 12). In the control study, saline was infused alone (n = 6). AVP potentiated the plasma ANP response to an increase in plasma volume produced by saline infusion, increased mean arterial blood pressure (MAP), and exaggerated the natriuresis and kaliuresis. DDAVP did not potentiate the increase in plasma ANP but enhanced the natriuresis without any rise in MAP. Saline alone increased plasma ANP as well as sodium and potassium excretion with no changes in MAP. Inulin and p-aminohippuric acid clearances did not change during these studies. The results suggest that in hydrated dogs, AVP may increase ANP release and arterial blood pressure via the vasopressor activity of AVP and potentiate the natriuresis and kaliuresis, but the increased ANP may play little role in the natriuresis.

Animals↗
PubMed1986

Renin-angiotensin system, converting-enzyme inhibition and kidney function in aging female rats.

The age-related changes in the renin-angiotensin system were investigated in normotensive 3-, 10-, 20-, and 30-mo-old female Wistar rats. Plasma renin concentration and immunofluorescent renal renin index remained constant from 3 to 10 mo, then decreased as the animals become older, whereas plasma concentration of renin substrate diminished slightly between 10 and 20 mo and plasma converting-enzyme activity was not modified with age. Acute inhibition of converting-enzyme activity by intravenous administration of 0.1 mg/100 g body wt S 9780 (the diacid form of S 9490) was followed by a 7- to 8-mmHg decrease in arterial pressure and a concomitant 10-12% increase in inulin and p-aminohippuric acid (PAH) clearance in the 10- and 20-mo-old rats. On the other hand, neither glomerular filtration rate, PAH clearance nor arterial blood pressure were affected by converting-enzyme inhibition in the 30 mo-old rats. These results indicate that the activity of the renin-angiotensin system is progressively reduced with age and suggest that angiotensin II does not play an important role in the maintenance of blood pressure and kidney hemodynamics in normotensive female senescent rats.

Aging↗
PubMed1988

Model for evaluating avian renal hemodynamics and glomerular filtration rate autoregulation.

Multiple vascular connections in normal avian kidneys make it difficult to experimentally manipulate renal blood flow patterns and perfusion pressures. In this study, hemostatic clips were used to obstruct the ureter of one kidney at the level of the ischiadic artery (IA) in anesthetized 3-wk-old chicks (Gallus domesticus). Kidney tissue upstream from the ureteral obstruction degenerated, leaving an intact caudal renal division with one route of arterial inflow branching from the IA. Renal function studies were conducted, using general anesthesia, when the birds reached 12-15 wk of age. A snare placed around the IA was used to unilaterally decrease renal arterial perfusion pressure (RAPP) for the experimental kidney. Under control conditions (snare loose), urine flow rates (UFR), glomerular filtration rates (GFR), clearance of p-aminohippuric acid, and fractional excretion of Na, K, Ca, and PO4 did not differ significantly, per gram of kidney weight, when experimental and intact contralateral kidneys were compared. Gradual tightening of the IA snare reduced RAPP stepwise. UFR decreased significantly from the initial control value when RAPP reached 40 mmHg, and urine flow ceased completely when RAPP reached 30-35 mmHg. In four of five birds, GFR did not decrease significantly between 110 and 60 mmHg but did decrease significantly below 60 mmHg. Urine osmolality was inversely correlated with UFR. Clearance of PAH did not decrease significantly from control values as RAPP ranged from 100 to 37 mmHg, possibly caused by increased renal portal blood flow. Overall, these results provide the first direct demonstration that in domestic fowl GFR is autoregulated at reduced RAPP.

Animals↗
PubMed1989

Clearance and urinary excretion of vasopressin in conscious dogs.

The purpose of this study was to determine the relationship between plasma arginine vasopressin (PAVP) levels and the urinary clearance rate, the nonurinary plasma clearance rate, and the urinary excretion rate of AVP. Female conscious dogs were given an intravenous infusion of p-aminohippuric acid and inulin, and, after a 90-min control period, the infusion was either continued or AVP was added to the infusate to produce doses of 0, 40, 100, and 200 microU.kg-1.min-1 for the last 90 min of the experiment. The resulting PAVP levels were 1.2, 8.2, 11.4, and 21.6 microU/ml, respectively. The urinary clearance rate of AVP nearly doubled between the infusion rates of 0 and 100 microU.kg-1.min-1. Likewise, the nonurinary plasma clearance rate of AVP also nearly doubled between the infusion rates of 40 and 100 microU.kg-1.min-1. However, at the rate of infusion of 200 microU.kg-1.min-1, both the urinary and nonurinary clearance rates were unchanged compared with the 100-microU.kg-1.min-1 rate. The largest incremental rise in PAVP was observed between the doses of 100 and 200 microU.kg-1.min-1, when the clearance rates were apparently plateaued. The urinary excretion rate of AVP was linearly correlated with PAVP (R = 0.91) under the conditions of this study. The results suggest that the measurement of the urinary excretion rate of AVP is a reliable method of assessing PAVP and that the clearance of AVP increases when PAVP is elevated.

Animals↗
PubMed1990

Renal and systemic hemodynamic responses to sustained submaximal exertion in horses.

We investigated the effects of 1 h of sustained submaximal exertion on the renal and systemic hemodynamics of six horses. The horses ran on a treadmill at a speed that produced heart rates of 55-60% of each horse's maximum heart rate. Exertion produced heart rates of 121 +/- 6.6 and 126 +/- 6.1 (SE) beats/min after 15 and 60 min, respectively. Cardiac output increased significantly (P less than 0.05) from 70.1 +/- 3.1 to 246.2 +/- 4.7 ml.min-1.kg body wt-1 after 15 min of exertion and thereafter did not change. There was no significant change from rest in p-aminohippuric acid and creatinine clearances, filtration fraction, or renal blood flow during exertion. Plasma total solid concentration and hematocrit increased by 3.8 and 8.6%, respectively, between 20 and 60 min of exertion. Pulmonary artery temperature increased significantly from 37.6 degrees C at rest to 38.6 degrees C at 60 min of exertion. This study demonstrates the ability of the horse to maintain renal hemodynamics similar to resting values and systemic hemodynamics at steady-state values despite hemoconcentration and increased body temperature during sustained submaximal exertion.

Animals↗
PubMed1991

Renal and humoral responses to sustained cardiopulmonary baroreceptor deactivation in humans.

The renal and neurohumoral effects of prolonged cardiopulmonary baroreflex unloading and the relationship of these changes to urinary sodium excretion have not been well documented in humans. In this study, 12 normal males underwent lower body negative pressure at -15 mmHg for 90 min, a maneuver that deactivates cardiopulmonary baroreceptors. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction (FF) were measured in eight of these subjects using inulin and p-aminohippuric acid clearance techniques. During reduction of central venous pressure, arterial blood pressure and heart rate did not change. Plasma concentrations of atrial natriuretic factor (ANF) decreased markedly (22 +/- 2 to 12 +/- 1 pg/ml, P = 0.0001) as did the second messenger of ANF's biological action, guanosine 3',5'-cyclic monophosphate, whereas renin and vasopressin were not significantly altered. There was a significant rise in plasma norepinephrine (1.6 +/- 0.2 to 2.4 +/- 0.4 nmol/l, P = 0.03). GFR (104 +/- 9 to 68 +/- 6 ml/min, P = 0.007) and FF (0.18 +/- 0.01 to 0.14 +/- 0.01, P = 0.007) decreased significantly, with maintenance of ERPF. There was a significant antinatriuresis without an antikaliuresis and a significant reduction in free water clearance. These changes in renal hemodynamics are unlike the known effects of renal vasoconstrictors, and the alterations in solute and free water clearance are consistent with the removal of the known actions of ANF from tubular target sites. Taken together, our findings suggest that a mechanism other than activation of vasoconstrictors, possibly the diminution of the influence of ANF on the kidney, may be operative in the renal adjustments to cardiopulmonary baroreflex deactivation in humans.

Adult↗
PubMed1991

Spontaneously hypertensive rats demonstrate increased renal vascular alpha 1-adrenergic receptor responsiveness.

To determine alpha 1-adrenergic receptor responsiveness of the renal vasculature in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), phenylephrine (2.5 or 5.0 micrograms.kg-1.min-1 iv) or saline was infused. Effective renal blood flow (ERBF) and glomerular filtration rate were determined by p-aminohippuric acid and inulin clearances, respectively. Peritubular capillary, proximal tubular, and stop-flow pressures (SFP) were measured by micropuncture. Phenylephrine decreased ERBF (6.27 +/- 0.48 to 4.55 +/- 0.65 ml.min-1.g-1; P less than 0.05) and increased arterial pressure and SFP (31.5 +/- 0.9 to 34.2 +/- 1.0 mmHg) in SHR. It only increased arterial pressure and ERBF in WKY without changing SFP. Afferent arteriolar resistance (RA) and glomerular capillary pressure (PG) remained unchanged, whereas efferent resistance (RE) decreased in WKY; in contrast, RA, RE, and PG increased in SHR (RA 21.2 +/- 2.0 to 38.1 +/- 7.1 mmHg.ml-1.min.g, RE 6.9 +/- 0.6 to 13.9 +/- 3.8 mmHg.ml-1.min.g; and PG 49.6 +/- 0.9 to 53.7 +/- 1.1 mmHg; all P less than 0.05). These data demonstrated increased SHR afferent and efferent arteriolar responsiveness; WKY efferent arteriolar hyperresponsiveness was not observed. The findings support the concept of augmented intrarenal vascular alpha 1-adrenergic responsiveness in hypertension that may predispose to subsequent glomerular hypertension.

Animals↗
PubMed1992

Use of a thermal pulse decay system to assess avian renal blood flow during reduced renal arterial perfusion pressure.

Using a simplified avian kidney model, renal arterial perfusion pressure (RAPP) was reduced from 120 (control) to 70 mmHg (near the glomerular filtration rate autoregulatory limit) and then to 46 mmHg (below the glomerular filtration rate autoregulatory range) in kidneys with ambient or partially restricted renal portal flow. Renal blood flow (RBF) was measured with a thermal pulse decay (TPD) system, using TPD thermistor probes inserted at three locations to evaluate regional differences in RBF. The clearance (CPAH) and extraction of p-aminohippuric acid were used to calculate renal plasma flow (RPF). CPAH, RPF, and RBF values were consistently lower for kidneys with restricted portal flow than for kidneys with ambient portal flow. Reducing RAPP to 46 mmHg did not significantly reduce CPAH, RPF, or RBF in the ambient group but did significantly reduce CPAH and RPF (regressed on RAPP) in the restricted group. RBF was not significantly affected when RAPP was reduced in the restricted group, although significant regional differences in blood flow were recorded. Renal vascular resistance decreased significantly as RAPP was reduced to 46 mmHg in the ambient group, confirming the renal autoregulatory response. In separate validation studies, significant reductions in RBF were detected by the TPD system during acute obstructions of portal and/or arterial flow. Overall, the results support previous evidence that avian RBF remains constant over a wide range of RAPPs. Observations of nonuniform intrarenal distributions of portal blood flow suggest that the portal system maintains the constancy of RBF in regions with proportionately high portal-to-arterial flow ratios.

Analysis of Variance↗