Technical problems in the micropuncture determination of nephron filtration rate and their functional implications

Summary The theory of a functional coupling between distal tubular fluid composition and glomerular filtration rate implies that the blockade of flow at a proximal site should lead to a marked increase of GFR. This potential alteration of steady state GFR was studied by comparing the influence of sampling from distal or proximal sites on the filtration rate of identical nephrons. During antidiuresis an average GFR of 25.2 nl/min±7.5 S.D. was found in distal collections, while proximally collected samples gave an average GFR of 34.5 nl/min±8.4 S.D. This difference of 9.3 nl/min is highly significant (p<0.001). During saline diuresis a mean nephron GFR of 41.6 nl/min±5.0 was found by distal sampling and of 45.3 nl/min±5.4 by proximal sampling (p>0.05). The proximal-distal difference in nephron GFR is interpreted to indicate the operation of a tubulo-glomerular feedback control system. Thus, a true steady-state GFR probably cannot be obtained by proximal fluid collection.Even in the presence of high intratubular pressures and unusually short oil blocks no evidence of sample contamination by retrograde fluid flow past an injected oil block was obtained.The application of a counter-pressure to the sampling pipette which has been recommended by Gertzet al. [5] as a means to standardize fluid collections, was found to lead to abnormally high intratubular pressures. The reason for this finding appears to be an unexpectedly high and inconstant tip resistance to flow during fluid flow into the pipette.     

The effect of saline infusion and hemorrhage on glomerular filtration pressure and single nephron filtration rate

Summary Single nephron filtration rate (GFRs) and effective glomerular filtration pressure (EFP) measured as the difference between intratubular stop-flow (SFP) and free-flow pressures (FFP), were determined in control rats and following saline infusion or hemorrhage. Infusion of isotonic or 4% NaCl increased EFP and GFRs without significantly affecting TF/P inulin. These findings could not be related to changes in arterial blood pressure. Controlled bleeding produced a marked decrease in EFP and in GFRs, again without significant change in TF/P-inulin. In both infusion and hemorrhage the change in GFRs was disproportionately greater than the change in EFP. Analysis of the components of the filtration process suggests that elevation of EFP is attended by an increase in permeability of the filtering membrane. This sensitive dependence of GFRs upon EFP, combined with a demonstrated constancy of total kidney GFR (GFR_T) over a wide range of urine concentrations and flow rates, connotes a close regulation of EFP in this experimental animal.Supported by Deutsche Forschungsgemeinschaft.     

The effect of experimental alterations in urine concentration on nephron filtration rate

Summary Experiments were performed to clarify the cause of the dependency of juxtamedullary nephron filtration rate (JN-GFR) on the diuretic state of the animal. Using the ferrocyanide technique of de Rouffignacet. al. [5] the distribution of nephron filtration rates was determined during selective modification of final urine osmolarity by papillary superfusion with concentrated or isotonic solutions. Papillary superfusion with a 2000 mosmolar solution led to a mean urine osmolarity of 1848±78 mOsm/l. JN-GFR displayed a mean increase of 66.6% over the superficial nephron filtration rate (SN-GFR). When the superfusion fluid was isotonic urine osmolarity averaged 754±53 mOsm/l and JN-GFR increased by a mean of only 26.3% over the SN-GFR. Using the micropuncture technique it was shown that SN-GFR in a given animal was not altered when the superfusion fluid was interchanged. We conclude therefore that the change in the percentage increase in GFR from superficial to juxtamedullary nephrons is caused by a change of juxtamedullary nephron filtration rate. Since plasma ADH concentration was not altered this effect appears to be elicited by the changed medullary solute concentration rather than by a vasomotor action of the antidiuretic hormone.This work was supported by the Deutsche Forschungsgemeinschaft.     

Regulation of superficial nephron filtration rate by tubulo-glomerular feedback

Summary Possible regulation of glomerular filtration rate by tubulo-glomerular feedback from a late tubular site was studied in microperfusion experiments on rats. During perfusion of loops of Henle with varying flow rates and different perfusion solutions, filtration rate of the perfused nephrons was measured by total proximal fluid collection and inulin determination. During perfusion with isotonic Ringer's solution nephron filtration rate decreased significantly with increasing perfusion rates. Since proximal intratubular pressure was experimentally kept constant, this response must reflect decreased glomerular capillary pressure. Increasing the flow rate during perfusion with isotonic sodium sulfate or mannitol solutions was not associated with significant changes of filtration rate. Thus some correlate of the flow rate of normal loop of Henle fluid can affect filtrate formation. Such an effect may be mediated by the juxtaglomerular apparatus. Our results are consistent with the concept that the triggering signal is a function of the amount of distal sodium that is able to permeate the cell membrane at the receptor site rather than of distal intratubular sodium concentration.On leave from the Department of Physiology, University of Melbourne as recipient of a scholarship from the Deutscher Akademischer Austauschdienst.     

Micropuncture studies on the filtration rate of single superficial and juxtamedullary glomeruli in the rat kidney

Summary Single nephron filtration rates of superficial and juxtamedullary nephrons were determined in high and low sodium rats. Single nephron GFR was calculated from TF/P inulin and tubular flow rate in superficial nephrons and single juxtamedullary GFR from corresponding data in long loops of Henle. In low sodium rats superficial nephron GFR was 23.5±6.4 (SD)×10^–6 ml/min×g KW, juxtamedullary nephron GFR was 58.2±13.6 and total kidney GFR (C _In) was 0.94±0.16 ml/min×g KW. Using these single nephron values, total kidney GFR and a total number of 30,000 glomeruli per kidney, the number of superficial and juxtamedullary glomeruli was calculated to be 23,267 and 6,733, respectively. During high sodium diet superficial nephron GFR increased to 38.1±11.3 and single juxtamedullary GFR decreased to 16.5±6.6, total kidney GFR increasing to 1.01±0.24. Calculation again revealed the same distribution of the two nephron types. End-proximal TF/P inulin in superficial nephrons was 2.36±0.36 in low sodium and 2.31±0.28 in high sodium rats. Loops of Henle TF/P inulin and intratubular flow rate were inversely related: the highest TF/P inulin values and lowest intratubular flow rates were found in the descending limb. These data quantify the distribution of superficial and juxtamedullary nephrons on a functional basis and suggest a mechanism by which the kidney adjusts sodium excretion by altering the contribution of each nephron type to total kidney GFR.Supported by the Deutsche Forschungsgemeinschaft and the U.S. Department of the Army, through its European Research Office.     

Single nephron glomerular filtration rate ratios of superficial,intercortical and juxtamedullary nephrons in rats during development

Summary In 20, 40 and 60-day-old rats the filtration rate was studied, using Baines modification of Hanssen's Na₄Fe(¹⁴CN)₆ method enabeling the determination of single nephron glomerular filtration rate (SNGFR) ratio between superficial (S), intercortical (I) and juxtamedullary (J) nephrons. The proximal tubule lengths were determined as well. A close correlation was obtained between age and S/I, I/J and S/J of proximal tubule lengths and between age and I/J, S/J¹⁴C-activities of ferrocyanide. Presented findings confirm the data on the increasing role of superficial nephrons in the course of postnatal development of rat.     

Resetting of tubulo-glomerular feedback sensitivity by dietary salt intake

Summary Tubulo-glomerular feedback participates in the regulation of superficial nephron filtration rate, SN-GFR [13,29,30,32]. In the present experiments we investigated the possibility that the feedback response is modulated by salt intake. Five groups of rats were pretreated with diets containing different intake. Five groups of rats were pretreated with diets containing different amounts of sodium chloride in either food or drinking water. Estimated NaCl intake ranged from about 0.5 to 12 mEq per day and rat. Feedback response was tested in individual nephrons by comparing SN-GFR's derived from either distal tubular segments (i.e. with the macula densa region being perfused at normal rates) or end-proximal segments (i.e. with the flow in the macula densa region being acutely reduced). In accordance with earlier observations [8, 28], proximal SN-GFR exceeded the distal value in salt-deprived and control animals by 8.7 nl/min±8.6 (P<0.05) and 7.6 nl/min±5.4 (P<0.001) respectively. In contrast, rats supplied with 6, 11, or 12 mEq Na/day showed a proximal-distal SN-GFR difference of 1.4 nl/min ±8.5 (P<0.05), 1.2 nl/min±6.7 (P>0.05), and 4.6 nl/min±8.8 (P<0.001). Thus, elevation of NaCl intake either abolishes or diminishes feedback sensitivity in the subnormal flow range. We conclude that tubulo-glomerular feedback sensitivity is reset when sodium chloride intake is altered.Work performed during tenure of an Alexander von Humboldt-Dozentenstipendium.     

The effect of antidiuretic hormone on the distribution of nephron filtration rates in rats with hereditary diabetes insipidus

Summary The effect of antidiuretic hormone on the distribution of nephron filtration rates was studied in rats with hereditary diabetes insipidus using the Hanssen method for determination of nephron filtration rates as modified by de Rouffignacet al. [18]. Conversion of water diuresis to antidiuresis by infusion of ADH resulted in a moderate, but highly significant increase in the filtration rate of the juxtamedullary nephrons, while the nephrons of all other cortex regions filtered at an unaltered rate. A mechanism based on the action of ADH on distal nephron water permeability is proposed as an explanation: water inflow into the medulla very likely decreases when water diuresis is converted to antidiuresis. This occasions a rise in medullary osmolality which then causes an increase in the apparent viscosity of the blood flowing through the vasa recta. This is responsible for a rise in juxtamedullary postglomerular resistance which results in an increase in the effective filtration pressure and thus in the juxtamedullary nephron filtration rate. The results suggest that an increased juxtamedullary filtration rate participates in the establishment and maintenance of the inner medullary solute gradients, possibly as a consequence of an increased solute delivery to the ascending limbs of the long loops of Henle.This work was supported by the Deutsche Forschungsgemeinschaft.On leave from the University of Melbourne as a recipient of a scholarship from the Deutscher Akademischer Austauschdienst.     

Détermination du taux individuel de filtration glomérulaire des néphrons accessibles et inaccessibles à la microponction

Résumé Nous présentons dans ce travail une modification de la technique de Hanssen qui permet de la rendre quantitative.Un indicateur glomérulaire marqué (ferrocyanure de sodium¹⁴C) est perfusé à des rats anesthésiés jusqu'à l'obtention d'une concentration plasmatique stable. Puis 20 l d'une solution à 10% de ferrocyanure non marqué sont injectés rapidement au dessus de l'artère rénale gauche. Quelques secondes plus tard, le pédicule rénal gauche est lié. Le ferrocyanure contenu dans le rein est alors précipité sous forme de bleu de Prusse insoluble, puis les tubules proximaux sont disséqués après macération. De la radioactivité contenue dans le néphron entre le glomérule et le précipité de ferrocyanure non marqué (radioactivité qui correspond donc au¹⁴C ferrocyanure filtré pendant un temps déterminé) et de la concentration plasmatique de cet indicateur, on déduit le débit de filtration (fg) du néphron considéré.Les résultats obtenus chez trois rats non diurétiques sont donnés à titre d'exemple. La fg de néphrons superficiels et profonds ayant une longueur moyenne de tubule proximal de 7,6 mm et 8,9 mm respectivement a été calculée à partir de l'équation de la droite de régression décrivant la variation de la fg en fonction de la longueur du tubule proximal: elle a été trouvée égale à 29,1 nl/min pour les néphrons superficiels et 40,1 nl/min pour les néphrons profonds.La validité de la technique est attestée 1. par le fait que la filtration glomérulaire totale du rein, calculée à partir des fg, est sensiblement identique à celle mesurée quelques minutes plus tôt (C _in 2. par le fait que les valeurs des fg ainsi que les corrélations anatomo-fonctionnelles rapportées sont identiques à celles obtenues par la technique de Hanssen, 3. enfin par le fait que les fg des néphrons superficiels sont semblables à celles habituellement mesurées par microponction.Notre technique conserve tous les avantages de la méthode de Hanssen, mais elle en supprime les inconvénients liés à l'hétérogénéité de distribution dans le rein de l'indicateur marqué puisqu'ici, au lieu d'être administré en une seule injection, le ferrocyanure marqué est perfusé à l'animal; de plus, elle permet une mesure quantitative des valeurs individuelles de fg même sur des reins anuriques.

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Determination of glomerular filtration rate of individual nephrons accessible and inaccessible to micropuncture

Summary We describe a modification of Hanssen's technique. Anesthetized rats were infused with a¹⁴C–Na-ferrocyanide solution. At equilibrium, 20 l of a 10% non labelled ferrocyanide solution were injected as a short pulse above the left renal artery. A few seconds later, the left renal pedicle was tied. Ferrocyanide contained within the kidney was precipitated as insoluble Prussian blue and the proximal tubules were microdissected after maceration. From the radioactivity contained within the nephron from the glomerulus to the precipitate of non labelled ferrocyanide (radioactivity which is due to the¹⁴C filtered during a given time) and from the¹⁴C plasmatic concentration, we deduced the single glomerular filtration rate (SGFR) of the nephron.Three non diuretic rats are given as example. The SGFR of superficial and juxtamedullary nephrons was respectively equal to 29,1 nl/min and 40,1 nl/min when calculated for the mean value of the length of their proximal tubules (respectively 7.6 mm and 8.9 mm) from the equation of the regression line which described the correlation between SGFR and the length of the proximal tubule.The reliability of the technique is supported 1. by the fact that the value of the GFR of the whole kidney calculated from SGFR's was the same asC _in measured just prior, 2. by the fact that SGFR values and the anatomo-physiological correlations were identical to those obtained with the Hanssen's technique, 3. and by the fact that the SGFR of superficial nephrons agree with most of those obtained with the micropuncture techniques.Most of the criticisms of Hanssen's technique, which arise from the observation that the bolus of labelled precipitate is sometimes inhomogenously distributed from one region of the kidney to another, are not valid here because instead of being injected as a pulse, the¹⁴C-ferrocyanide is infused continuously into the animal. Moreover, our technique allows measurements of SGFR's even in non urine forming kidneys.

Docteur en médecine, Attaché de recherche à l'Institut National de la Santé et de la Recherche Médicale.     

Single glomerular filtration rate of superficial and Juxta-medullary nephrons in the rat during different types of arterial hypertension

Summary The single nephron glomerular filtration rate (SNGFR) of superficial (S) and juxtamedullary (JM) nephrons were measured using¹⁴C-ferrocyanide infusion technique in rats under 3 different states of hypertension: acute hypertensions obtained either by bilateral carotid clamping (CC) or by contralateral renal ischemia (CI), and chronic Goldblatt hypertension. The juxtaglomerular index (JGI) was determined on the experimental kidneys.During acute hypertensions the JGI was normal, the granularity being more marked for the superficial than for the deep cortex. SNGFRs were higher in the JM (CC=39.2±3.4 SE nl/min; CI=41.0±4.5) than in the S (CC=30.3±2.5 CI=30.3±3.0) nephrons. These values are not different from those of normal rats. In the untouched kidney of Goldblatt rats the JGI was equal to zero. There was a general increase in SNGFRs. This increase was more marked for the S than for the JM nephrons, and the SNGFRs equalized in these two categories of nephrons (S=73.0±8.4; JM=74,7±8.2).From these observations, it is suggested that the renin content of the juxtaglomerular apparatus may play some role in the absolute value and intrarenal distribution of SNGFRs.This work was supported in part by a grant D.G.R.S.T. No. 7172 2726.Chargé de recherches à l'INSERM.     

The influence of sampling technique on the micropuncture determination of GFR and reabsorptive characteristics of single rat proximal tubules

Summary Studies have been carried out in order to assess the validity of the determination of the single nephron filtration rate by micropuncture techniques. By means of a double microscope and two investigators operating simultaneoulsy, intratubular pressure and single nephron transit time were recorded during sampling. The data indicate that collection of tubular fluid by means of aspiration significantly accelerates transit time, decreases intratubular pressure, and results in an increase of single nephron filtration rate. In contrast, spontaneously flowing collections were associated with insignificant alterations of transit time and intratubular pressure. Technical details underlying these observations have to some extent been delineated. The importance of these data with respect to artifactual alterations of single nephron parameters is discussed.Supported by a Medical Research Fellowship of the Medical Research Council fo Canada.     

Function of juxtamedullary nephrons in normotensive and chronically hypertensive rats

Summary The function of juxtamedullary nephrons was investigated by micropuncture of long loops of Henle at the exposed papilla in normal rats and in the untouched kidney of rats with experimental hypertension (unilateral Goldblattclip). With increasing blood pressure (range from 90–190 mm Hg) a continuous rise in juxtamedullary single nephron glomerular filtration rate was observed. Juxtamedullary single nephron GFR averaged 60×10^–6 ml/min/g K.W. in the control group (mean arterial blood pressure 116 mm Hg) and 114×10^–6 ml/min/g K.W. in the hypertensive group (mean arterial blood pressure (164 mm Hg). There was no change in superficial single nephron GFR (30×10^–6 ml/min/g K.W.) but a slight increase in total kidney GFR from 1.07 to 1.28 ml/min g K.W. In both the normotensive and the hypertensive animals, tubular fluid-to-plasma (TF/P) inulin ratio and intratubular flow rate in the descending limb of the long loops of Henle were not statistically different from those found in the ascending limb. Intratubular flow rate in the hypertensive rats was twice as high as in the controls; the mean TF/P inulin ratios in the two groups did not differ from each other. Appearance time of lissamine green in the long loops of Henle and in the collecting ducts was shortened in the hypertensive animals. It is concluded that there is no autoregulation of glomerular filtration rate in juxtamedullary nephrons. The increased juxtamedullary GFR may contribute to the elevated urinary excretion of the unclipped kidney in hypertensive rats.This paper was presented before the German Physiological Society, Mainz, March 1969 [11].     

Reduction of the glomerular filtration rate by the efferent blood from a kidney taken from a previously dehydrated dog

Summary The two kidneys of one dog were perfused separately with the same blood pool and at a constant arterial pressure. After the control periods, one of the kidneys was replaced by another one taken from a dehydrated dog. The presence of the dehydrated kidney resulted in significant and almost immediate decreases of creatinin clearance, urine flow and sodium excretion by the contralateral kidney, without any change in the overall renal blood flow. These changes disappeared, after the removal of the dehydrated kidney. They were not observed if the dehydrated kidney was replaced either by a kidney taken from a salt-depleted, non water-deprived dog, or by a simple arterio-venous shunt. These results suggest that in the status of dehydration, the kidney releases some humoral material which might be responsible for the decrease of the measured GFR (C creat) perhaps by the way of permeability changes.     

Serum cystatin C is a sensitive early marker for changes in the glomerular filtration rate in patients undergoing laparoscopic surgery

OBJECTIVE:

Pneumoperitoneum during laparoscopy results in transient oliguria and decreased glomerular filtration and renal blood flow. The presence of oliguria and elevated serum creatinine is suggestive of acute renal injury. Serum cystatin C has been described as a new marker for the detection of this type of injury. In this study, our aim was to compare the glomerular filtration rate estimated using cystatin C levels with the rate estimated using serum creatinine in patients with normal renal function who were undergoing laparoscopic surgery.

METHODS:

In total, 41 patients undergoing laparoscopic cholecystectomy or hiatoplasty were recruited for the study. Blood samples were collected at three time intervals: first, before intubation (T1); second, 30 minutes after the establishment of pneumoperitoneum (T2); and third, 30 minutes after deflation of the pneumoperitoneum (T3). These blood samples were then analyzed for serum cystatin C, creatinine, and vasopressin. The Larsson formula was used to calculate the glomerular filtration rate based on the serum cystatin C levels, and the Cockcroft-Gault formula was used to calculate the glomerular filtration rate according to the serum creatinine levels.

RESULTS:

Serum cystatin C levels increased during the study (T1 = T2<T3; p<0.05), whereas serum creatinine levels decreased (T1 = T2>T3; p<0.05). The calculated eGlomerular filtration rate-Larsson decreased, whereas the eGlomerular filtration rate-Cockcroft-Gault increased. There was no correlation between cystatin C and serum creatinine. Additionally, Pearson''s analysis showed a better correlation between serum cystatin C and the eGlomerular filtration rate than between serum creatinine and the eGlomerular filtration rate.

CONCLUSION:

This study demonstrates that serum cystatin C is a more sensitive indicator of changes in the glomerular filtration rate than serum creatinine is in patients with normal renal function who are undergoing laparoscopic procedures.     

Micropuncture study of handling of phosphate by proximal and distal nephron in normal and parathyroidectomized rat. Evidence for distal reabsorption

Summary The handling of phosphate by the nephron of the rat was investigated by proximal and distal tubular micropunctures in three experimental conditions: 1. in normal animals, 2. several days after parathyroidectomy (chronic) and 3. immediately after parathyroidectomy (acute).In proximal tubules of normal animals phosphate reabsorption appears to be gradient limited. The concentration gradient is already reached in the early proximal. Consequently, proximal phosphate reabsorption is almost completed in this segment. Moreover, reabsorption is higher in early proximal in normal than in acute although the reverse is observed at the late accessible proximal. This indicates that the initial part of the proximal nephron in normal has an increased capacity to reabsorb phosphate.Comparison of phosphate delivery at early distal and late proximal tubule suggests that, in normal and chronic, phosphate reabsorption either stops in the pars recta or is compensated by a net addition.Phosphate delivery is higher in superficial distal tubules than in ureteral urine, which is interpreted as a phosphate reabsorption by the terminal nephron since the heterogeneity of the nephrons population cannot explain the results. There are several arguments suggesting that this reabsorption is an active process. Moreover it appears to be inhibited by PTH.Supported by grants from I.N.S.E.R.M., C.N.R.S., C.E.A. and Fondation pour la Recherche médicale.     

Effect of barbiturates on GFR and fluid reabsorption along proximal convoluted tubules and loops of henle in rats

Summary In the present study we investigated the possibility that GFR and fluid reabsorption are systematically altered by dose and/or structure of different barbiturate compounds. The results show that filtration and absorption rates are identical in rats anaesthetized with 100 or 150 mg/kg BW. Elevating the administered amount by intravenous injections of inactin did not alter renal functions compared to values measured immediately before the additional administration. No differences of GFR and absorption rates were noted when the effect of inactin, amytal, and nembutal in doses necessary to induce and maintain anaesthesia was compared. Absolute and fractional absorption was observed to decrease by 20 to 25% in the first 3 h after induction of anaesthesia independent of the anaesthetic used. Our results suggest that filtration and absorption rates are not systematically modified by specific anaesthetic effects, at least not when doses are kept close to the necessary minimum.Work performed during tenure of an Alexander von Humboldt-Dozentenstipendium.     

Micropuncture study of fluid handling in the cat kidney

Summary Superficial proximal and distal tubules of both kidneys of pentobarbital-anesthetized cats, infused with 2.5% (w/v) polyfructosan in Ringer solution at 0.45 ml/min, were micropunctured. Whole one-kidney GFR averaged 4.1 ml/min. SNGFR averaged 15 nl/min in 51 determinations and was proportional to whole-kidney GFR in individual cats. Absolute fluid reabsorption along the length of the accessible portion of the proximal tubule was 1.6 nl/min·mm. The length of the whole proximal tubule was 6 mm as measured from the glomerulum to the descending thin limb of Henle's loop. The length of the distal tubule was 3.5 mm from the macula densa to the first branching of the collecting duct. Proximal fluid was isoosmolar with plasma whereas fluid entering the distal tubule was markedly hyposmolar. Late distal tubular fluid samples were also isosmolar. The cat appears. to be well suited for micropuncture experiments in terms of freedom from respiratory movements and the presence of surface distal tubules.Supported by the Swiss National Science Foundation, Grant 3.3730.74Preliminary communication: Experientia32, 779 (1976)Performed during tenure as an International Exchange Fellow of the Swiss National Science Foundation, Grant 880.292.74     

Architecture of the mesonephric nephron in pig and rabbit

Summary As a precondition for determining nephron profiles in sections, mature mesonephric nephrons from pig and rabbit embryos were isolated by a maceration technique in order to demonstrate nephron architecture, length, and diameter. In the pig the proximal tubule is largely constant. In the distal tubule the pre-attachment zone shows the greatest variation. The zone of attachment to the corpuscle and the ventrolaterally directed post-attachment coil has a predictable course as does the collecting tubule. In contrast to earlier reports, the nephron shows no drastic differences in tubule diameter and is up to 33 mm long. The proportional length of the three major nephron segments is surprisingly constant. The rabbit nephron, although much shorter (4 mm) and simpler, with an almost S-shaped pattern, is less easily understood in sections. Marked irregularities in its course are caused by the different behaviour of the terminal proximal segment. The distal tubule shows an ampullary dilatation in the attachment zone but can be very narrow in the pre-attachment part.     

An analysis of the determinants of nephron filtration rate.

Studies on glomerular filtration in the Munich-Wistar rat, a strain with surface glomeruli, have permitted for the first time the evaluation of the four factors that determine filtration rate: 1) the rate of nephron plasma flow (RPF), 2) the glomerular hydrostatic pressure gradient (deltaP) from capillary to Bowman's space, 3) systemic oncotic pressure (piA), and 4) the glomerular permeability coefficient (LpA), and their respective roles in producing change in filtration rate. The process of filtration in the Munich-Wistar rat is characterized by filtration pressure equilibrium and, therefore, filtration should be highly plasma flow-dependent. Analysis of data from this strain suggests that multiple factors can change LpA, and, at least in animals which do not achieve filtration pressure equilibrium, these alterations in LpA can influence the final filtration rate. Multivariate statistical analysis in a variety of experimental conditions in the Munich-Wistar rat suggest that changes in RPF remain the major mediator of change in nephron filtration rate, both in rats at filtration pressure equilibrium and in disequilibrated animals. Although the glomerulus is an ultrafilter driven by hydrostatic forces, changes in deltaP assume a lesser role in producing alterations in filtration rate.     

Development of glomerular filtration rate and electrolyte and osmolal clearance in the late-embryonic and newly hatched chicken

Summary Techniques have been developed for collection of urine in embryonic and newly hatched chickens for the purpose of studying the development of renal function.The reliability of EDTA-⁵¹Cr as a substitute for inulin-¹⁴C in the determination of GFR was studied. Since inulin and EDTA-⁵¹Cr clearances in the hatched chicken averaged 1.61±0.23 (S.E.) ml/min per kg body weight and 1.58±0.27 ml/min per kg body weight, respectively, EDTA-⁵¹Cr clearance was considered a suitable measure of GFR.GFR increased significantly in the first few days after hatching. Filtration rate was 0.068±0.008 (S.E.) ml/min per g kidney weight in the embryo and increased to 0.148±0.008 ml/min per g shortly after hatching. By nine days after hatching GFR had risen to 0.290±0.015 ml/min per g, a value comparable to that reported for the adult.Clearances of sodium, potassium, chloride and total osmolyte also increased with age. When these clearances were corrected for changing glomerular filtration rates the embryonic chicks were found to excrete a greater percentage of the filtered load. These results show that adult levels of glomerulo-tubular balance are not attained until after hatching.A preliminary report of this work has already been published [3].