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The reciprocals of the blood urea nitrogen and plasma creatinine levels, the maximum specific gravity of the urine after vasopressin, and three modified forms of the phenolsulphonphthalein (P.S.P.) excretion test were found to be directly related to the glomerular filtration rate (G.F.R.) in hospital patients. From 34 to 75 patients were studied for each test, and in 21 patients all tests were performed concurrently. The plasma creatinine level and the 15-minute urinary excretion of P.S.P. were found to be the most useful simple tests of renal function and gave sufficiently accurate estimates of total function (G.F.R.) to justify their more extensive use. The G.F.R. (ml./min./1.73 sq. m. of body surface area) could be calculated from each test, using the following equations:- [Formula: see text] G.F.R. = 3.15 x P.S.P.% + 19, where P.S.P.% is the 15-minute urinary excretion of P.S.P., expressed as a percentage of the administered dose. Satisfactory estimates of G.F.R. were also given by the simplified relationships [Formula: see text]. In the presence of impaired renal function more accurate estimates of G.F.R. were obtained from the plasma creatinine and P.S.P. excretion tests (S.D. of estimate 8 and 13 ml./min. respectively). It was thought that these tests could well replace the commonly used blood urea nitrogen estimation as simple tests of renal function.

The effects of the massive administration of dexamethasone on renal function during and after extracorporeal circulation have been studied clinically on sixty patients undergoing open heart surgery and experimentally on ten mongrel dogs undergoing total body perfusion, and the following results have been obtained: 1. Dexamethasone, given in massive doses, in-creases the urinary output during and after total body perfusion. The increased urinary volume is not due to water diuresis, but is due to solute diuresis. 2. One mg/kg of dexamethasone, given before perfusion, may be an adequate dose, but its effects on renal function might differ between children and adults. 3. Glomerular filtration rate and renal blood flow may be satisfactorily maintained during and after perfusion due to the decreased renal vascular resistance brought on by a massive administration of dexamethasone, although no significant difference could be clinically demonstrated. 4. Dexamethasone may act on the distal renal tubules, but, judging from the alterations of excreted electrolytes and osmolality in cases of massive administration, it may also effect the proximal renal tubules. 5. Dexamethasone may have no effect on the plasma antidiuretic hormone.

Comprehensive one-day renal function tests in 20 patients with a history of analgesic abuse showed varying degrees of chronic renal failure in all. There was no evidence of a selective defect in proximal tubular function, while a defective concentrating mechanism, usually considered necessary for the diagnosis of analgesic-induced renal damage, could be demonstrated in only 16 patients. A urinary acidification defect associated with a concentrating defect was found in nine cases and was thought to reflect specific collecting duct dysfunction. Urinary ammonium excretion was reduced in 13 subjects, owing to a reduced number of functioning nephrons or inadequate acidification, or both. Low citrate excretion was frequently encountered, and this, as well as defective urinary acidification, may play some part in predisposing patients with analgesic nephropathy to intrarenal calcification and progressive renal failure.

Six patients with complete heart block provided an opportunity to study renal hemodynamic responses to increases in heart rate produced by an artificial pacemaker. Observations were made at rest and following exercise during idioventricular rhythm and slow rates and were repeated after increasing the rate to 70/min by means of an artificial pacemaker. Ability to excrete a water load was impaired at the slow idioventricular rate; this was associated with a reduced glomerular filtration rate. No acute improvement in renal function occurred with pacemaker-induced increase in heart rate except in the presence of congestive heart failure. With long-term pacing (7 to 8 months), the glomerular filtration rate and the ability to excrete solute-free water increased in all patients studied. The acute increase in free water clearance which occurred with increased heart rate in the presence of congestive heart failure suggests that decreased renal perfusion may be responsible for the inability to excrete excess water. The dilutional hyponatremia in congestive heart failure may be explained on this basis. Changes in indices of cardiac function in these patients were similar to those reported by others. No change in resting cardiac output occurred at heart rates between 40 and 70/min in the absence of congestive heart failure. The response to exercise, however, was greater at the higher rates.

A one-week introductory course in clinical biochemical and research techniques was devised to provide a brief but concentrated experience for interested persons. Urinary creatinine concentrations were measured to demonstrate acceptable degrees of precision of a method (co-efficients of variation, 0·5-2·4%), and to give confidence by favourable comparison with routine laboratory results (day 2, mean 0·95 vs 0·94 mg/ml). Subjects then submitted themselves to one-day renal function testing, and subsequently measured their own urinary acid-base parameters by autotitrimetry and glomerular filtration rates by spectrophotometry. The values obtained for the latter fell within the normal range (85-124% of normal, corrected for age and surface area). Finally, statistical methods and a small desk-top computer were employed to compute linear regression equations, correlation coefficients, and t tests from the week's data. The course contained a number of features which stimulated learning, including active participation by the learner, and the use of meaningful materials to induce both desire for success and tolerance of mistakes.

A comprehensive one-day renal function test consisting of a single outpatient visit lasting nine hours, with a minimum of time off work or away from home, is described in detail. Although a large number of laboratory tests are performed in one day, patients usually appreciate thoroughness, and the cost is more than offset by the saving in occupancy of hospital beds and by the early and precise diagnosis of reversible aspects of renal disease. Some aspects of improved methodology, such as the sequential determination of minimum urinary pH, bicarbonate, titratable acid, ammonium, and total acid on a single sample using an automatic titrator, are given in detail. Clinical application of the comprehensive nine-hour renal function testing system is illustrated by the result sheet of a patient with analgesic nephropathy, who was shown in one day to have secondary severe renal failure (glomerular filtration rate 20% of normal for age and surface area), renal tubular acidosis of the distal gradient type (minimum urinary pH 6·20), increased urinary white cell excretion rate, hyaline casts, and absence of red cell casts, consistent with a diagnosis of analgesic nephropathy and urinary tract inflammation. Normal values with 95% range for this laboratory are also given. This testing system has been found to be very useful in investigating patients with analgesic nephropathy, renal tubular acidosis, and after renal transplantation.

Bradykinin (0.05, 0.1 and 0.2μg/kg/min) and eledoisin (0.5, 1.0, 5.0 and 10.0ng/kg/min) were infused directly into the left renal artery of anesthetized dogs to demonstrate the effects of these peptides on renal function. Urinary volume, endogenous creatinine clearance (GFR), PAH clearance (RPF) and excretion of electrolytes were increased by infusion of these two peptides, but no constant change was observed in UK/UNa ratio. These data demonstrate that the increase in urinary output and electrolyte excretion is caused by the augmentation of tubular load of solutes which resulted from the increase of RPF and GFR. Tachyphylaxis was observed in dogs which received repeated infusions of bradykinin but this phenomenon was less distinct in the case of eledoisin.

Follow-up studies of renal function in patients with spinal cord injuries of traumatic origin

Drip infusion pyelography consistently results in dense nephrograms and excellent opacity of the upper and lower urinary tracts. This is secondary to flooding the urinary system with highly concentrated contrast medium.The effect of drip infusion pyelography on glomerular filtration rate, renal plasma flow, urine volume, osmolar clearance, blood pressure, pulse rate, and blood urea nitrogen was studied. The only significant effect was a marked increase in urine volume and osmolar clearance. Drip infusion pyelography has no deleterious effect upon kidney function and presents no greater incidence of toxic reactions than the low dosage standard intravenous pyelography. This method greatly increases the capabilities of intravenous urography, frequently eliminating the need for retrograde contrast studies.

The course of hypertension within the first 2 months after kidney transplantation was correlated with renal function, plasma renin activity (PRA), and the daily maintenance dose of prednisone in 18 homograft recipients. During acute rejection blood pressure (BP) closely correlated with PRA. Patients with normal homograft function showed an increase in BP early after transplantation which in most returned to normal 3-8 weeks later. In the latter group no correlation could be found between the level of BP and PRA, however the BP correlated closely with the dose of prednisone. These observations suggest that during acute rejection the increase in BP may at least partly be mediated by a renal pressor mechanism, whereas with normal renal function the high dose of glucocorticoids may play an important role in the development of hypertension.

Diagnostic procedures and long-term prognosis in bilateral renal cortical necrosis. Thirty-eight patients with bilateral renal cortical necrosis (BRCN) were studied with special reference to etiology, diagnostic procedures and ultimate prognosis. BRCN was of obstetrical origin in 26 patients and more frequent during the third trimester of pregnancy (21%) than earlier (1.5%). Renal biopsy, renal arteriography and hemodynamic data were useful procedures in the early differentiation of total from patchy BRCN. In patients with patchy BRCN, the percentage of destroyed glomeruli on the kidney biopsy specimen was lower than in those with total BRCN, renal arteriography showed that the cortical nephrogram was present but non-homogeneous and mean renal blood flow (MRBF) (85Kr method) fell within the range observed in patients with acute tubular nephropathy undergoing full recovery. In patients with total BRCN, cortical tissue was uniformly necrotic, the cortical nephrogram was completely absent, MRBF was always below 50 ml/100 g·min and a first component was never recognizable. Biological evidence of intravascular coagulation was inconstant. Intrarenal vascular thrombi were only found in the renal biopsy specimens of those patients with short survival. Partial recovery occurred in 16 patients and GFR increased over a one year period. Subsequent deterioration of renal function occurred in nine patients requiring chronic hemodialysis and/or renal transplantation. Diagnostic et pronostic lointain des necroses corticales bilaterales des reins. Trente-huit malades atteints de necrose corticale bilaterale des reins (NCR) ont ete specialement etudies du point de vue de l'etiologie, des methodes de diagnostic et du pronostic lointain. La NCR a ete d'origine obstetricale chez 26 malades et a ete plus souvent observee pendant le troisieme trimestre de la grossesse (21%) que plus precocement (1, 5%). La biopsie renale, l'arteriographie renale et les donnees hemodynamiques ont ete utiles pour distinguer les NCR totales et partielles. Chez les malades atteints de NCR partielle, la biopsie renale a montre que le pourcentage de glomerules detruits etait plus bas que dans les NCR totales, l'arteriographie renale a montre que la nephrographie corticale etait presente mais non-homogene et le flux sanguin renal moyen (FSRM) (methode au 85Kr) restait compris dans les limites observees chez les malades atteints de nephropathie tubulaire aigue avec guerison complete. Chez les malades atteints de NCR totale, le tissu renal cortical etait uniformement necrotique, la nephrographie corticale totalement absente, le FSRM etait toujours inferieur a 50 ml/100 g·mn et aucun premier composant n'etait individualisable. Les preuves biologiques d'une coagulation intravasculaire ont ete inconstantes. Des thrombi vasculaires intrarenaux n'ont ete rencontres en biopsie que chez les malades ayant une courte survie. Une recuperation partielle a ete observee chez 16 malades et la FG a continue a s'elever au-dela de la premiere annee. Une aggravation secondaire de la fonction renale est survenue chez neuf malades, necessit ant des hemodialyses periodiques et/ou une transplantation renale.

Uranyl nitrate-induced acute renal failure in the rat: Micropuncture and renal hemodynamic studies. Rats were studied after uranyl nitrate administration to define the mechanism(s) responsible for acute renal failure (ARF). Early (six hours) in the course of ARF, proportional decreases occurred in renal blood flow rate (RBF) and whole kidney and single nephron glomerular filtration rates (GFR), to 64%, 67% and 69% of control values, respectively. The stability of single nephron GFR at puncture sites more distal to the glomerulus, appearance of i.v. administered lissamine green in distal tubules and relatively normal proximal intratubular hydrostatic pressure are not consistent with a dominant role for transtubular "leak" of glomerular filtrate or tubular obstruction in the diminution of GFR at six hours. At 48 hr, further proportioned decrements in RBF and GFR, to 29% and 26% of control values, respectively, were observed. Proximal single nephron GFR values could only be obtained at earlier puncture sites suggesting that micropuncture studies late in this model of ARF were limited by uranyl nitrate-induced anatomic alterations. Analyses of 133 Xe washout, 85 Kr autoradiographs and silicone rubber renal vascular casts demonstrated progressive, patchy renal cortical ischemia. The data suggest that altered renal hemodynamics were responsible for diminished renal function after uranyl nitrate administration in the rat although "leak", especially at 48 hr, was not conclusively excluded. Insuffisance renale aigue par le nitrate d'urane: Etude hemodynamique et par microponctions. Des rats ont ete etudies apres administration de nitrate d'urane afin de preciser le ou les mecanismes de l'insuffisance renale aigue (ARF). Au cours de cette ARF il apparait precocement (six heures) une diminution proportionnelle du debit sanguin renal total (RBF), de la filtration glomerulaire globale et des filtrations glomerulaires individuelles respectivement a 64%, 67% et 69% des valeurs controles. La stabilite de la filtration glomerulaire individuelle a distance du glomerule, l'apparition du vert de lissamine dans les tubes distaux et la pression hydrostatique intratubulaire proximale proche de la normale ne sont pas en faveur d'un role important d'une "fuite" transtubulaire du filtrat glomerulaire ou d'une destruction tubulaire dans la diminution de GFR a la 6e heure. Apres 48 heures, une diminution proportionnelle encore accrue de RBF et GFR est observee, respectivement, a 29% et 26% des valeurs controles. Les debits de filtration individuels des nephrons ne peuvent etre mesures qu'en des sites proximaux proches des glomerules, ce qui suggere que les etudes tardives par microponctions de ce modele d'ARF sont limitees par les alterations anatomiques liees au nitrate d'urane. L'analyse du lavage au 133 Xe, des autoradiographies avec 85 Kr et des moulages vasculaires par le silicone montrent une ischemie corticale progressive et irreguliere. Ces resultats suggerent que des modifications hemodynamiques sont responsables de la diminution de la fonction renale apres nitrate d'urane chez le rat, quoique la "fuite", particulierement a la 48e heure, ne soit pas definitivement exclue.

Pargyline exerts its antihypertensive effect via a predominant reduction in peripheral vascular resistance, whereas cardiac output is not altered significantly. The effect on renal blood flow is inconsistent, but a significant reduction in glomerular filtration rate does occur. Therefore the drug should be used with appropriate caution in patients with significant impairment of renal function. The hemodynamic response observed with pargyline is similar to that obtained with other MAO inhibitors.

Effects of renal artery occlusion on kidney function in the rat. The left renal artery of anesthetized rats was completely occluded for one hour. Kidney function after restoration of blood flow was studied using clearance and micropuncture techniques. Whole kidney inulin clearance was decreased to 10% of normal after artery occlusion, and fluid reabsorption was markedly depressed. Single nephron glomerular filtration rate (SNGFR), measured by free-flow collection from superficial proximal tubules, was 22 ±8.2 (SD) nl/min (N=32) after ischemia versus 30±5.8 (N=38) in normal kidneys. Fluid reabsorption, measured with the split-droplet technique, was decreased to 63% of normal after one hour of artery occlusion. Intraluminal serum albumin (5 g/100 ml) had no effect on fluid reabsorption in ischemia-damaged kidneys. Tubular leakiness to inulin was demonstrated by microinjection of 14 C-inulin solutions into single proximal tubules. The dilated appearance of superficial proximal tubules, increased proximal tubule hydrostatic pressure, and slow movement of dye down some nephrons suggest obstruction. In this model of acute renal failure, renal insufficiency appears to be primarily due to tubular leakiness and obstruction. Effets de l'occlusion de l'artere renale sur la fonction du rein chez le rat. L'artere renale gauche de rats anesthesies a ete completement occluse pendant 1 heure. Apres la restauration du debit sanguin la fonction du rein a ete etudiee par les techniques de clearance et de microponctions. La clearance globale de l'inuline est diminuee a 10% des valeurs normales apres l'occlusion et la reabsorption d'eau est considerablement diminuee. Le debit de filtration individuel des nephrons, mesure par la collection en flux libre dans des tubes proximaux superficiels est de 22 ± 8,2 ( sd ) nl/min (N = 32) apres l'ischemie et de 30 ± 5,8 (N = 38) dans les reins normaux. La reabsorption d'eau, mesuree par la technique de la split-droplet, est diminuee a 63% des valeurs normales apres une occlusion d'une heure. La serum albumine intraluminale (5 g/100 ml) n'a pas d'effets sur la reabsorption d'eau dans les reins leses par l'ischemie. La permeabilite tubulaire a l'inuline a ete demontree par des micro injections de solutions d'inuline- 14 C dans des tubes proximaux. L'aspect dilate des tubes proximaux superficiels, l'augmentation de la pression hydrostatique tubulaire proximale et la lenteur du transit d'un colorant le long de certains nephrons suggerent une obstruction. Dans ce modele d'insuffisance renale aigue le deficit de la fonction renale parait etre lie principalement a la permeabilite et a l'obstruction tubulaires.

High peridural blocks with 2 per cent lidocaine were studied in 20 normal volunteers 21 to 43 years of age. Epinephrine 1:200,000 was incorporated into the local anesthetic solution used to produce blocks in ten of the subjects. The following control measurements were made: mean arterial pressure, central venous pressure, cardiac rate, output and stroke volume, total peripheral resistance, pH Paco2 Paco2 glomerular filtration rate {GFR) and effective renal plasma flow (ERPF). These measurements were repeated at 15-minute intervals until cutaneous analgesia disappeared. With lidocaine alone, there were BO significant systemic cardiovascular changes, although maximum decreases of 9 per cent in GFR and 15 per cent in ERPF were seen. Epinephrine caused highly significant cardiovascular changes attributable to beta-receptor stimulation. The maximum changes were: mean arterial pressure –21 per cent, cardiac rate +26 per cent, cardiac output +68 per cent, stroke volume +34 per cent, total peripheral resistance –49 per cent, CFR –11 per cent, and ERPF –26 per cent. The differences between GFR values in the two groups were not significant, but the greater decrease in ERPF when epinephrine was added was significant and was due primarily to decrease in mean arterial pressure.

The unanesthetized rabbit has been found to be a satisfactory animal for studying the renal circulation. Techniques for measuring renal clearances and cardiac output, for carrying out renal vein catheterization, and for measuring renal clearances separately for each kidney are described. Normal values are presented from data obtained from 86 rabbits. Renal blood flow and glomerular filtration rate were found to be stable, judged by the reproducibility of these measurements over a period of three hours. Renal PAH extraction ratios averaged 95.5% in 16 unanesthetized animals. In 12 animals renal blood flow was 6% higher in one chronically denervated kidney than in the contralateral innervated kidney, indicating a low degree of sympathetic vasoconstriction in the normal resting circulation of the rabbit. All the results were obtained in the rabbit in the course of moderate water and mannitol diuresis.

1. The stop flow procedure was used to compare the urinary creatinine: inulin ratios in male and female rats; to confirm previous evidence for secretion of creatinine by the renal tubule in the male rat, and to assess the effect of androgenic hormones on this property of the renal tubule in the female rat. 2. The creatinine:inulin ratios in free flow and all stop flow samples in the female rat were close to unity, confirming the absence of secretion of creatinine. 3. In the male rat the ratios in the free flow samples exceeded 1·2. In samples proximal to the sodium minimum the ratio rose to a peak of 1·56, and then declined to the free flow level. 4. Female rats pre-treated with androgenic hormones exhibited a male type pattern. A single intramuscular dose of testosterone, or daily injections of progesterone for 1 month, had a similar effect. The free flow ratios rose to 1·2 and on stop flow a proximal secretory peak was seen. 5. Two conclusions may be drawn—the creatinine clearance is a valid measure of glomerular filtration rate in the female rat, but not in the male; and the secretion of creatinine is a function of the proximal tubular cells which can be influenced by androgenic hormones in the rat.

To determine the validity of endogenous creatinine clearance as a measure of glomerular filtration rate in patients with renal disease 308 simultaneous determinations of inulin clearance and endogenous creatinine clearance were reviewed and analysed. The ratio of creatinine clearance/inulin clearance increased progressively with the decline in inulin clearance, while the finding of a normal endogenous creatinine clearance masked a definite but mild decrease of glomerular filtration rate in 42% of the patients and a moderate decrease of glomerular filtration rate in 23%. This indicates that with declining glomerular filtration rates the endogenous creatinine clearance progressively overestimates actual glomerular filtration rates. Hence a single determination of creatinine clearance can be misleading as a screening measurement of glomerular filtration rate.

The renal function, including sodium excretion rates, were studied in 27 patients with early essential hypertension, before and during angiotensin infusions. The patients had a preparatory period of salt loading for four days taking a supplement of 7 g of NaCl. Determinations were made during two 30-minute periods before the angiotensin and for two 30-minute periods afterward. Arterial blood pressure was increased in all 27 patients and renal plasma flow decreased in 25. The glomerular filtration rate changes were not statistically significant, showing some increase in 15 and a decrease in 11 patients. When the group was divided into those in which there was a decrease in sodium excretion (11 patients), and those in which there was an increase in sodium excretion (16 patients), with angiotensin infusion, a correlation with the control blood pressure was evident. The patients in whom an increase occurred had a control mean blood pressure greater than 136 mm Hg, and those exhibiting a decrease of sodium excretion, a blood pressure less than 136 mm Hg. Salt excretion did not correlate with the increment in blood pressure or renal resistance changes. The minor changes in glomerular filtration of sodium of the two groups could not explain the different excretory patterns which are attributed to an alteration of the tubular transport of sodium.

Extract: A child with growth retardation, hypokalemic alkalosis, and urinary salt losing is described. Pressor response to angiotensin II was reduced and renal biopsy showed striking hyperplasia of the juxtaglomerular apparatus. Renal tubular function was studied in the patient and in healthy control subjects during hypotonic saline diuresis. Glomerular filtration rate (GFR) was 128 ml/min/ 1.73 m2 in the patient and 129 ± 30 ml/min/1.73 m2 in the control subjects. Fractional sodium delivery to the distal nephron, as estimated by ( + CNa)/100 ml GFR, was 13.3 ml and 11.1 ± 3.5 ml in the patient and normal subjects, respectively. Sodium transport at the diluting segment [( / + CNa) × 100] was markedly impaired in the patient, 32% versus 80% ± 9.2% in the control subjects. The natriuretic effect of chlorothiazide was normal in the patient, which suggests that the reabsorptive capacity of the thiazide-sensitive segment of the distal nephron is preserved. The evidence presented suggests that the defective reabsorption of sodium in the patient is due to an impaired sodium transport in the ascending limb of Henle's loop. The present study raises the possibility that a similar tubular defect may be responsible for the impaired renal handling of sodium that is often observed in patients with Bartter's syndrome. Speculation: Impaired transport of sodium localized in the distal nephron, that results in failure of the kidney to conserve salt adequately, is probably the primary disorder in some patients with Bartter's syndrome.

1. The renal excretion of water and electrolytes was examined in starved ducks maintained on fresh water and on hypertonic saline containing 284 mM/1. NaCl and 6.0 mM/l. KCl. 2. No significant differences were observed in the urine flow, glomerular filtration rate, renal plasma flow and the excretory rates of K+, NH4+ and inorganic phosphate between these two groups of birds. 3. The excretory rates of Na+, Cl- and Ca2+ were significantly higher in saline-maintained birds than in the freshwater-maintained birds. 4. NH4+ appeared to be a major cationic component which occupied over half of the available osmotic space in the urine of both the freshwater-maintained and saline-maintained birds. 5. In saline-maintained birds the excretion of K+ and inorganic phosphate appeared to be independent of the available osmotic space in the urine whereas the excretion of Na+ and Cl- appeared to be very dependent upon this factor. 6. These observations suggest that the kidneys of the saline-maintained bird constitute the primary pathway for the excretion of K+, NH4+ and inorganic phosphate, and that with respect to the excretion of Na+ they constitute a relatively minor pathway. This work was supported by research grants to W.N.H. from the National Science Foundation (grant no. GB 3896) and the Committee on Research, University of California. N.D.E.A. (Title IV) pre-doctoral fellow.

Extract: The compensatory growth of the single and transplanted kidney is demonstrated by the improvement of glomerular filtration rate (GFR) of the single kidney to achieve 50–90% of the normal value. The compensatory renal tubular acid excretion is also studied. It is clearly demonstrated that in response to a standard ammonium chloride load (75 mEq/m2) systemic acidosis (tCO2 0.95), i.e., each remaining nephron is excreting acid normally (or supernormally) and is supportive of the “intact nephron” hypothesis. The data show a marked difference in urinary pH during acidosis between the two transplant groups: 50% of the cadaveric allografts have an inability to lower urine pH below 5.4 compared with 10% only of the live-related allografts which show such a defect. This would imply that cadaver allografts are more susceptible to an acute acid load. Speculation: The ischemia sustained at the time of transplantation results in acute tubular damage and proportionate lowering of the glomerular filtration rate which account for the impaired acidification capacity in the kidney allografts. It is also possible that circulatory damage to the glomeruli may occur in the transplantation process. It is even possible that intrarenal circulation may be altered by either transplantation or nephrectomy; although, admittedly, this last possibility seems quite unlikely. It is open to speculation what effect the age difference between the donors and the recipients may have on their different responses to acute metabolic acidosis.

A reduction in effective (nonportal) plasma volume is considered the basis for renal sodium retention, a spontaneous reduction in glomerular filtration rate (GFR), and a fall in GFR occurring during drug-induced diuresis in patients with cirrhosis and ascites. In the present study the concept of a reduced effective plasma volume in cirrhosis is challenged by two lines of evidence, even though effective plasma volume itself could not be measured. (a) Total plasma volume failed to rise in 10 patients with the spontaneous loss of ascites, the appearance of sodium in the urine, and a rise in GFR. Portal pressure remained constant in these patients as ascites left, suggesting that effective plasma volume had not increased while portal plasma volume decreased. (b) Reduction of GFR could not be prevented in five patients with cirrhosis and ascites while total plasma volume was prevented from falling with albumin infusions during drug-induced diuresis. Reduction of GFR during drug-induced diuresis in 15 patients with cirrhosis and ascites was completely reversed with saline infusion despite continued diuresis with the identical drugs, excluding drug nephrotoxicity as the cause for the reduced GFR. The ascites of cirrhosis might no longer be regarded as a cause of effective plasma volume contraction, stimulating renal sodium retention and a reduction in GFR. More likely, this form of ascites is a result of plasma volume expansion and sodium retention. The causes for renal sodium retention and a spontaneous reduction in GFR remain unknown. The cause for a fall in GFR during drug-induced diuresis also remains unknown, but effective plasma volume contraction and drug nephrotoxicity seem excluded.

Fine polyethylene tubes were inserted in the ureters of female rats under nembutal anesthesia. Several hrs. later, the rats were injected intravenously with creatinine. Every 5 mins. urine was collected for 30mins. following the injection then the animals were sacrificed. A linear line was obtained when the rate of creatinine excretion was plotted on a logarithmic scale against time, and the rate of creatinine excretion at the time of sacrifice was obtained by extrapolation. Creatinine clearance was 1.94ml/min. or 0.87ml/min./100g body weight. No difference was found in creatinine clearance of rats between low phosphorus diet and control normal diet groups. Parathyroidectomy caused only a slight and statistically insignificant decrease in creatinine clearance. Renal net reabsorption of phosphorus increased by 26% after low phosphorus intake and 48% after parathyroidectomy. The result supports the view that the parathyroids have an influence on renal tubules.

Serial measurements of glomerular filtration rate (GFR), independent and simultaneous clearances and extractions of para-aminohippurate (PAH), radiohippuran, and iodopyracet (Diodrast) were made in 11 adults and one child who received renal transplants from living donors. Measurements were made within 3 hours and repeated two to four times during the following 14 days. Immediately after transplantation, PAH clearance averaged 385 ml/min (range, 218 to 510), GFR averaged 54 ml/min (range, 22 to 87), renal plasma flow (RPF) averaged 672 ml/min (range, 309 to 1424), and marked vasodilatation was present with an average renal blood flow (RBF) of 979 ml/min (range, 435 to 2,114). As observed in other studies, immediate diuresis and natriuresis but no glycosuria occurred. Extraction ratios for PAH ( E PAH) were below normal, ranging from 0.59 to 0.94, and those for 125 (or 131) I-hippuran, and 131 I-Diodrast were even lower. Extraction ratio for PAH to radiohippuran averaged 1.43 in 17 simultaneous studies. However, RPF measured simultaneously with these agents was the same, indicating a true difference in transport of these substances. The low extraction ratio for PAH, 131 (or 125) I-hippuran and 131 I-Diodrast was not related to depression of the maximal tubular transport of PAH and may have been a consequence of vasodilatation and increased RBF. Another observation made on these kidneys was a low filtration fraction which averaged 0.089. These hemodynamic changes did not appear to relate to circulating factors in the anephric recipient since they persisted throughout the 13-day study period in eight patients. In four patients showing transient rejection, GFR and the clearance of PAH and 131 I-hippuran decreased proportionately more than RBF. It is concluded that marked vasodilatation and a low filtration fraction are characteristic of uncomplicated renal allotransplantation in man, and that early rejection is expressed by measurable decreases in the clearances of PAH and inulin despite maintenance of RBF. These changes were present prior to clinical evidence of rejection.

Clearance studies were performed on 49 split-bladder dogs with a unilateral pyelonephritic or remnant kidney and three patients with unilateral kidney disease to examine the effects of an acute saline load on the diseased kidney (DK) as opposed to a simultaneously studied, contralateral control kidney (CK), which also served to maintain a nonuremic environment. Before saline loading, base line studies in many of the dogs and the three humans were in agreement with previously published data. However, in dogs with a severe pyelonephritic lesion, a greater difference in DK vs. CK fractional excretion of sodium (FE(Na)) and water was noted, whose magnitude was inversely correlated with the level of glomerular filtration rate (GFR) and maximum urine osmolality of DK compared to CK. An acute saline load (75 ml/kg) resulted in an inhibition of fractional sodium and water reabsorption in the diseased dog kidney which was disproportionately greater than in the simultaneously studied CK, regardless of the type or severity of the lesion. While mean DK GFR for all dogs increased 15% more than CK GFR, failure of FE(Na) to increase after induction of a disproportionate increase in DK GFR with parathyroid hormone suggested that the saline-induced disproportionate increase in GFR was not solely responsible for the exaggerated inhibition of fractional sodium and water reabsorption in the diseased dog kidney. Studies in the three patients after saline loading (25 ml/kg) revealed a similar disproportionate resetting of glomerulotubular balance.Thus, regardless of base line function before expansion, the unilaterally diseased kidney of dog and man possesses unique characteristics in the absence of uremia which render it more reactive to the stimuli produced by acute saline loading. This suggests that the intrarenal environment of the kidney with a reduced nephron population may under some circumstances serve as a determinant of its function.

Micropuncture study in rats with experimental glomerulonephritis. Experiments were carried out to study the function of individual nephrons in rats with membranous glomerulonephritis produced by the intravenous administration of rabbit anti-rat-kidney serum. The nephritic animals developed massive proteinuria, hypoalbuminemia, hypercholesterolemia, edema and ascites. Considerable heterogeneity of nephron function was observed in nephritic rats. Some proximal nephrons showed normal glomerulotubular balance while others had low glomerular filtration rates (GFR) associated with high tubular fluid/plasma inulin ratios. Mean single nephron GFR and total GFR were decreased in nephritic rats while proximal half-time of reabsorption and transit time were increased. Free flow pressure in proximal tubules was within normal limits while glomerular filtration pressure was significantly reduced. In average terms, the fractional reabsorption of sodium along the diseased nephron was not different from controls; however, due to the reduced filtered load, less sodium was excreted per kg rat. The nephritic rat was also not able to concentrate the urine to the extent of the normal.