Renal Capacity Research Articles

Defect of urinary acidification during fasting

The capacity of the kidney to secrete hydrogen ions against a gradient was evaluated during fasting. Six healthy obese individuals were subjected to the short ammonium chloride loading test before and after 8 days of fasting. Fasting was continued for an additional 5 days, during which each subject was given 300 mEq. of potassium chloride. After the potassium replacement, a third ammonium chloride loading test was performed. The results demonstrated that after 8 days of fasting the renal capacity to depress the urine pH after ammonium chloride loading was completely lost, but that this impairment was reversed by the administration of potassium chloride.

Iatrogenic Hypophosphatemia in Infants ith Renal Insufficiency

The brief report of W. F. Dodge and L. B. Travis concerning Iatrogenic Hypophosphatemia in Infants with Renal Insufficiency (Pediatrics, 35: 792, 1965) prompts me to air my doubts in A Letter to the Editor about the value of restriction of phosphate intake as a means of treatment for hypocalcemia and hyperphosphatemia encountered in infants with renal insufficiency. The difficulties posed by decreased renal capacity for phosphate clearance in renal insufficiency are well recognized. The importance of deficient intestinal absorption of calcium in renal insufficiency is, however, often overlooked.

FACTORS INFLUENCING THE LABILITY OF HUMAN RENAL BLOOD FLOW.

0 xygen and other metabolite transport is a yprimary function of blood, but the peculiar relationship of renal functional capacity to blood volume flow and pressure is expressed in terms of glomerular filtration, tubular transport, renin production,3 and probably other metabolic activities. In the normal young adult in a state of rest, and with a hydration/urinary output ratio in excess of 2 ml. per minute, at least 25 percent of the cardiac output perfuses approximately 300 Gm. of renal tissue; this is equivalent to 600 ml. of blood flow per minute per kidney. The Olympic sprinter may temporarily reduce renal blood flow to the point of anuria. Between these compensatory values are all patients who have obstructive disease of the renal arteries, renal transplantation, anesthesia, or other conditions which alter renal blood flow. Adequate perfusion of the renal vascular system requires definition in scientific terminology relating renal mass, mainstem arterial pressure, and peripheral resistance as equated to volume flow in time. Clearance ratios and tubular maxima, measured by either chemical or radioisotope techniques, are our best indices of renal functional capacity, but for purposes of the surgeon they have limitations: They are not technically applicable within the time and

Studies on Creatinine Metabolism in Kwashiorkor and Marasmus

VIN0DINI REDDY, MB. B.S. , D.C. H. C HILDREN suffering from kwashiorkor excrete low amounts of creatinine in unine’3 as do children suffering from � The increase in urinary creatinine following nutnitional recovery has been ascribed to increase in muscle mass.5 It has also been observed that an abrupt increase in urinary creatinine occurs during the first few days of therapy which cannot be explained on the basis of new muscle formation.4’5 Based upon their observations in patients with kwashiorkor that serum creatinine levels, although not high initially, decrease markedly during therapy-a decrease which parallels the increase in urinary creatinine-�Arroyave et al.3 have suggested that in the edematous phase of kwashiorkor, the renal capacity to eliminate creatinine may be reduced. The studies of Vinodini et al.4 on marasmic subjects in whom edema was absent have shown that even in these subjects there is a small but consistent increase of about 10 per cent in urinary creatinine within 48 hours after the institution of high protein diets. This would then suggest that factors other than renal are also involved in the pattern of creatinine excretion in protein-calorie deficient children. Studies on creatinine in blood and creatinine metabolism in undernourished children have been few. In the present study, levels of creatine, creatinine and its precursors, guanidineacetic acid and arginine, have been determined in the blood of subjects suffering from

The Effect of Salt Intake on the Size and Function of the Salt Gland of Ducks

THE salt gland or nasal gland of marine birds is capable of eliminating sodium chloride as a highly concentrated solution. This enables these birds to tolerate the ingestion of sea water or food with a high salt content. Terrestrial birds, which lack an extra-renal excretory mechanism have, in general, a low tolerance to salt because their kidneys cannot produce a urine with high salt content. Apparently all marine birds have utilized the extra-renal mechanism for salt elimination; an increased renal capacity for salt excretion does not seem to have been a feasible evolutionary approach to this problem. The few passerine birds that have a high salt tolerance, however, seem to represent an exception that may provide interesting material for the student of avian evolution.

Acute renal conservation of sodium in hypertension.

It is well established that patients with essential hypertension have an exaggerated natriuretic response to the rapid intravenous administration of sodium. 1-4 While the mechanisms responsible for the enhanced natriuresis of essential hypertension remain unknown, a defect in the renal tubular capacity to conserve sodium has been proposed as a possible explanation. 5 Most of the available literature relating to salt conservation in patients with hypertension is concerned with the response to chronic salt restriction. The experiments of Black 6 and Renwick 7 seem to offer conclusive proof that the hypertensive patient conserves sodium normally under these conditions. However, these chronic experiments may not be applicable to the problem of exaggerated natriuresis, because the latter occurs only in response to an acute stimulus for sodium excretion. The enhanced natriuretic response is a transient one and is followed by a rate of sodium excretion comparable to that of the normotensive subject.

Renal Functional Capacities Following One-Stagenephrectomy and Heminephrectomy in Dogs

Renal Functional Capacities Following One-Stagenephrectomy and Heminephrectomy in Dogs

Acid-secreting function of the renal tubule

From the University of Louisville School o[ Medicine, Louiwi l le , Ky. These investigations were supported in part by Grants A-461, A-4618, [rom the National Insti tutes of Heal th and the United States Health Services; in part by Contract DA-49-OO7-MD, M R D B , SGO, United States Army; and in part by a grant #ore the American Heart Association. ~Address, Division o[ Experimental Medicine, School o] Medicine, University o[ Louisville, Louisville 2, Ky. ~Advanced Research Fellow o[ the American Heart Association. tThe exact number o[ equivalents o[ H+ ions ]ormed [rora phospholipids and nucleoproteins depends upon the amount o] sodium and the pH o] the ingested /oodstuffs. stant. I t follows that there must be a mechanism for removal of acid or else the pH and bicarbonate content of body fluid would be reduced to fatally low levels. The presence of such a mechanism in the kidney is well known and its failure in renal insufficiency results in retention of phosphoric and sulfuric 1 acids with consequent acidosis. Excretion of urine rich in titratable acid and low in p H relative to blood (during ingestion of acid-ash diets) indicates renal capacity of removing surplus acid from the blood. Conversely, excretion of urine of pH greater than that of blood indicates renal capacity of removing surplus alkali from the blood. With both acidification and alkalinization functions, the kidney can maintain the pH of body fluids at constant and optimal levels of 7.40 _+ 0.05. 2 B. Renal sources of acid. Acid fed into the transport machinery is derived from two products of renal cell metabolism, CO2 and H + ions: 1. Metabolic CO~ provides hydrogen ions by the reaction,

6-CHLORO,6-DEHYDRO,17α-ACETOXYPROGESTERONE: ITS POSSIBLE ACTION AS AN ALDOSTERONE ANTAGONIST

6-Chloro,6-dehydro,17α-acetoxyprogesterone (RS-1280) is a potent progestational agent, hence it was studied to determine whether or not it was an aldosterone antagonist. The study was carried out in 5 patients with cirrhosis of the liver and ascites, under constant metabolic conditions, with a previous examination of the renal capacity of each patient to excrete water, sodium and potassium under basal conditions and also when benzothiadiazine and mercurial diuretics were administered. In each case, RS-1280 was administered and its effect compared with that of a known aldosterone antagonist (spironolactone). By this means it was demonstrated that RS-1280 has no anti-aldosterone action, although it has a natriuretic effect in cirrhotic patients with a normal capacity to excrete sodium.

Cortisone-induced polyuria following hypophysectomy

1. 1. A study has been made of the nature of the polyuria induced by cortisone occurring in two patients who had undergone hypophysectomy. 2. 2. In these two patients the polyuria has been shown not to be due to an increase in the load of urinary solute nor to deterioration in those renal functions concerned with water conservation. 3. 3. The view that the phenomenon is due to primary polydipsia seems inescapable. A review of the literature suggests that this mechanism is probably responsible for the syndrome in similar patients described by other workers, with the exception of the patient reported by Leaf et al. [2] in whom alteration in solute load determined the increase in urinary volume. In these circumstances it is inappropriate to refer to the syndrome as diabetes insipidus. 4. 4. In our patients the administration of cortisone has been shown to improve the renal capacity to absorb solute-free water during osmotic diuresis under conditions of hydropenia. 5. 5. This effect is discussed in the light of the Wirz countercurrent hypothesis and in relation to the view that the action of ADH is one of increasing the permeability of the renal tubules to the movement of water along osmotic gradients. The increase in solute-free water reabsorption brought about by cortisone might then be explained by the effect of the steroid in augmenting reabsorption of sodium.

THE INFLUENCE OF SURGERY ON RENAL FUNCTION IN INFANCY AND CHILDHOOD

There was no statistical difference in the mean excretion rate of sodium following a test load of hypertonic sodium chloride solution between "control" infants and infants, studied 12 to 24 hours after a variety of surgical procedures. Normal infants between the ages of 1 and 9 months, when given a hypertonic sodium chloride load, excrete sodium at a rate comparable to adults. Two of thirteen infants in the post-surgical period excreted sodium at a rate lower than one standard deviation below the mean for the group. Possible reasons for the lowered excretion rate in these two infants are discussed. Four olden children, given a smaller sodium load than the infants, had a lower excretion rate of sodium pre-surgically. Three of these four children excreted sodium at a lower rate after surgery than they did before surgery. The possible reasons for this are discussed. As measured by glomerular filtration rate, concentration of sodium in the urine, U/P ratio for sodium and the relationship of sodium to water excretion, there does not appear to be an intrinsic defect of renal capacity in handling sodium in the post-surgical state, even in the patients with a lowered sodium excretion rate. From the data collected in this study, there seems to be no reason for altering the generally accepted principles of parenteral fluid therapy in regard to sodium and chloride for the uncomplicated post-surgical patient, following recovery from anesthesia, from that designed for sick children in general.

Relation between tubular transport of inorganic phosphate and bicarbonate in the dog.

It has been demonstrated that the renal capacity to reabsorb inorganic phosphate is depressed if the plasma CO2 concentration is increased to such a level that bicarbonate is excreted in the urine. That this situation was not the result of alkalosis per se was demonstrated by the infusion of ‘Diamox.’ This agent caused a mild acidosis, and yet at the same time depressed phosphate reabsorption. Moreover, since ‘Diamox’ also caused a decrease in the total reabsorption of bicarbonate these results appear to be explicable only on the assumption that bicarbonate may be reabsorbed by two different mechanisms. The first, and possibly major pathway is one involving carbonic anhydrase. The second pathway is one in which bicarbonate is reabsorbed as such. It is along this second pathway that bicarbonate competes with phosphate for reabsorption. This assumption was given more weight by the findings that Tm phosphate was depressed by respiratory alkalosis, or by raising the bicarbonate and CO2 levels of the plasma in such a way as to maintain the blood ph at the control level.

Studies on the interrelationships of the adrenal cortex and renal ammonia excretion by the rat.

It has been demonstrated recently that the renal capacity of the adrenalectomized animal to secrete ammonium and hydrogen ions is deficient under normal conditions and under conditions of moderate to severe acid stress (Sartorius et al., 1952). Failure to salvage adequately fixed base from the tubular urine in exchange for hydrogen or ammonium ions, results not only in increased loss of base but in a disturbance of body acid base balance. These facts probably account for the chronic acidosis and the poor tolerance to acid stress commonly exhibited by animals with adrenal insufficiency. The present study was undertaken (a) to determine the capacity of normal and adrenalectomized animals to excrete ammonia and titratable acid when acutely subjected to mild and severe acid stress, (b) to assess the effects of desoxycorticosterone acetate and adrenal cortical extract on ammonia and titratable acid excretion by the adrenalectomized and normal rat,

Physiopathologic study of a case of mercurial poisoning

SummaryReport on a case of acute poisoning by Hg oxycyanide.Spontaneous recovery after five days of complete anuria.The restoration of the renal function was followed by :a) daily clearances of creatinine, urea, Na + , Cl— and K+ and by two functional tests measuring the inulin clearance and the renal capacity to excrete glucose at increasing plasma levels. These tests were performed on 8 successive urinary collection periods of 15 minutes. The observations were as follows :a) Creatinine and urea clearances are equal and increase simultaneouly from 0,7 and 0,52 to 23,6 and 26,4 during the 8 days following the restoration of diuresis. Thereafter creatinine clearances increased more rapidly than urea clearances.b) K clearance is the first to reach its normal value. It is higher than that of all the other components of urine during the six first days of diuresis. This fact is interpreted as a proof of the capacity of the distal nephron to secrete K.c) The amount of glucose excreted on the third day of restored diuresis remains, despite a very decreased renal function, a linear function of the plasma level of glucose. TmG = 5,28 mgr/minute. Mean threshold = 0,66. The glomerular filtration calculated from the slope of the line relating glucose excreted to the plasma level is 7,9 cc/minute. This is equal to the clearances of inulin, creatinine and urea.d) The same test performed 14 days later shows a quite different picture. TmG has a normal value 273,8 mgr/minute. Mean threshold = 2,87 gr 0,00. The appearance threshold of glucose is still decreased (1.1 gr. 0/00) and is the last remaining abnormality.e) At that time (16th day of restored diuresis) the proximal tube has recovered the ability to secrete creatinine at increased plasma levels. The ratio, creatinine clearance inuline clearance = 1,32 as compared to the value (0,89) obtained on the previous test.

Renal tubular excretory capacity for penicillin in health and in subacute bacterial endocarditis

I T has been amply shown that penicillin is largely excreted by the kidneys without appreciable destruction in the body’ and that this process occurs rapidly’ thus playing an important part in limiting the usefulness of that drug in the treatment of infection. The belief that penicillin leaves the kidneys not only through glomerular filtration but also by tubular excretion has been substantiated by the work of Rantz and Kirby2 on penicillin clearances. These investigators showed that the amount of blood cleared of penicillin by the kidneys per minute compared with that cleared of diodrast, another substance excreted by the renal tubules.3 In addition the clearance values of penicillin are far higher than those of such drugs as inulin which is known to be excreted solely by glomerular filtration. Rammelkamp and Bradley,4 who showed that elimination of penicillin is retarded when penicillin and diodrast are given simultaneously, suggested that there existed between these two drugs a competition for the same mechanism of tubular excretion. This has also been shown to be true of paraaminohippuric acid. 5 It was of practical importance, therefore, to know the maximal tubular excretory capacity (TM,) of the kidneys for penicillin since doses of the drug surpassing TM, would be expected to produce relatively more rapid rises in the blood levels of penicillin than amounts under this level. It is already known that with renal damage penicillin excretion is hindered along with other renal functions and that high and sustained blood levels may follow relatively small doses. 6 In diseases in which renal damage occurs and which are susceptible to treatment with penicillin renal failure might then paradoxically exert a favorable influence on the direct outcome of the illness. One disease to which these events are applicable is subacute bacterial endocaiditis which in most cases has been found highly amenable to penicillin and in which a high percentage of cases has more or less renal damage.’ It is of interest then to know of how much importance the renal damage in subacute bacterial endocarditis is in producing higher than usual blood levels of penicillin. Loewe, Rosenblatt and Alture-Werber8 found that in a case of a patient with resistant endocarditis receiving large doses of penicillin by continuous intravenous drip the serum levels of penicillin began to rise above the expected levels when a dose of 625,000 units per hour was reached. It was suggested that at this. dosage the TM of penicillin had been attained. It has been shown that with lower continuous intravenous dosages the rise in serum penicillin concentration is directly proportional to the increase in dose.2 With these points in mind, serum levels, urinary excretion and serum clearances of penicillin in normal individuals and in patients with subacute bacterial endocarditis have been studied. * From the Department of Medicine, Stanford University School of Medicine, San Francisco, Calif.

Influence of Eosinophile Cells of Hypophysis on Kidney Function

White, Heinbecker and Rolf1 reported that removal of the glandular division of the hypophysis in dogs resulted in a reduction of 50% or more in inulin and diodrast clearances and in maximal tubular excretion of diodrast at high plasma levels. These changes indicate a depression of renal blood flow and of renal tubular excretory capacity and were in evidence within 7 days after the removal of the glandular hypophysis. They have persisted under observation for a period of 2 years. It can be stated, therefore, that the glandular hypophysis exercises a humoral influence on the kidney. Evidence that the eosinophile cells of the hypophysis are responsible for this influence is presented in this paper.Observations on the urea clearance of 5 patients with acromegaly revealed values of 130, 83, 135, 231, and 100%, respectively, of the normal standard. Three of these values are definitely above the upper limit of normal. An eosinophil tumor was found at autopsy in the first of these patients. The kidneys weighed 42...

FURTHER STUDIES OF RENAL FUNCTION IN RENAL, CARDIORENAL AND CARDIAC DISEASES

The objects of this investigation are (1) to ascertain the value of quantitative determinations of the diastatic activity 1 of urine in revealing renal functional capacity in cardiac, cardiorenal and renal cases ; (2) to compare in the same group of cases the findings of diastase, urea and phthalein in the urine with those of urea, total incoagulable nitrogen and cryoscopy in the blood, and (3) to compare the relative value and limitations of the tests of retention with those of excretion. Renal functional capacity is usually ascertained in one of two ways : (1) Tests of excretory capacity through the quantitative determination of the secretion of various substances in the urine — dyes, methylene blue, indigocarmin, rosanilin and phthalein ; other chemicals, potassium iodid, lactose, salicylates, sodium chlorid, urea, sugar following phloridzin and the enzyme, diastase. (2) Tests of retention through the determination of the concentration of certain substances in

THE VALUE AND LIMITATIONS OF FUNCTIONAL RENAL TESTS

In ascertaining the functional capacity of the kidney, judicious selection of tests is the key to the maximum amount of information from the minimum expenditure of time and energy. The number of tests is now so large that it is impossible to utilize all in any individual case. It is unnecessary, moreover, since all of the available information is forthcoming at times from a single test or from a proper combination of a small number of tests. In order that the proper selection may be made, however, an insight into the value, limitations, advantages or disadvantages, peculiarities and significance of the findings, together with intimacy with technic concerned, is essential. Renal functional capacity is usually ascertained in one of two ways: first, by tests of excretory capacity through the quantitative determination of various substances in the urine—dyes, methylene blue, indigocarmin, rosanilin, phenolsulphonephthalein, other chemicals—potassium iodid, lactose, sodium chlorid, urea,