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The assessment of renal function in infants and children is made difficult by problems in obtaining complete urine collections. The traditional and the constant-infusion methods of determining inulin and paraaminohippurate clearance were compared in 61 patients, 32 of whom had a variety of renal diseases. Glomerular filtration rates ranged from 1.6 to 133 ml per minute. Values for inulin clearance by the two methods correlated closely (r equal to 0.993) at all levels of renal function and in the presence or absence of edema. Inulin clearance by the constant-infusion technic averaged 103.2 per cent of true clearance. Correlation between the two methods of measuring para-aminohippurate clearance was r equal to 0.971, but values by the infusion method averaged 21.8 per cent above "true" clearance, presumably owing to extrarenal excretion of para-aminohippurate. The estimation of glomerular filtration rate by the technic of constant inulin infusion constitutes a simple, accurate and reproducible meth...

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.

In health, the human kidney is capable of maintaining body water, electrolyte, and acid-base equilibrium in spite of wide dietary variation. Renal disease, primary to the kidney or as part of a systemic process, is commonly accompanied by blood pressure elevation or edema, or both. Oral diuretic drugs have won general acceptance as primary therapeutic agents in mild or moderate hypertension and as part of a broader drug program for severe hypertension. Intermittent oral or parenteral diuretic therapy has greatly augmented primary therapy of edema of cardiac, hepatic, and renal origin. Attention has been called to the potential hazard of their use when impairment of renal function is severe; however, restriction is not necessary in the absence of azotemia. Frequent or excessive use of oral or parenteral diuretics is commonly associated with hypokalemic, hypochloremic alkalosis, or other electrolyte disturbances. Potassium depletion may be avoided with concurrent use of aldosterone antagonists. The use of diuretic agents in patients with impaired renal function carries distinct risks of plasma volume depletion or hypotension and further diminution of glomerular filtration. Existing electrolyte and acid-base disorders are easily aggravated. Careful sodium restriction will commonly prevent edema; however, intermittent diuretic therapy can be helpful. Hypertension can be more effectively and safely managed with sodium restriction and sympathetic nervous system inhibitors or vasodilators; however, care must be taken not to lower pressure to the point of diminishing glomerular filtration. Digitalis has proved to be not only ineffectual but also hazardous and thus contraindicated in patients with acute cardiac decompensation and renal failure; such a clinical problem constitutes an ideal indication for the use of furosemide or ethacrynic acid, which will commonly offer prompt symptomatic relief.

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.

The effects of oral treatment with methyldopa 1 to 2.75 Gm. per day for 7 to 13 days on arterial pressure, urine volume, glomerular filtration rate, renal plasma flow, and renal vascular resistance were studied in both the supine and tilted positions in 8 hospitalized patients with sustained essential hypertension and impaired renal function. Despite a decrease in arterial pressure during treatment with methyldopa, GFR did not decrease while renal plasma flow increased in the supine and tilted positions from 302 to 350 ml. per minute and from 233 to 306 ml. minute, respectively. A significant increase in urine volume was also observed in both positions. These effects of drug administration were accompanied by a decrease in renal vascular resistance. The results of this study provide a rational basis for the use of methyldopa in the treatment of ambulatory hypertensive patients with impaired renal function.

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.

Renal function tests with special reference to the renal haemodynamics have been carried out on 11 cases of renal carcinoma. Selective clearance of inulin and PAH and the extraction ratio for PAH and oxygen were determined.The kidneys with tumours showed lower urine flow, CIN, EPAH and oxygen A-V difference than the control organs. TRBF, on the other hand, was higher for the tumour group.The reduction in EPAH suggests that there was shunting of blood past active tubular epithelium; the reduction in the oxygen A-V difference shows an A-V shunting that is a blood flow via parenchyma with a lowered oxygen extraction. It would seem that the shunting increased with the malignancy of the tumour.

Summary The clinical value of various renal function tests in recurrent urinary tract infections in children has been examined. The study also includes an evaluation of glomerular capacity versus tubular capacity in recurrent urinary tract infections. There was no good correlation between blood urea nitrogen concentration and serum creatinine concentration within the normal limits for these two parameters. When blood urea nitrogen concentration and/or serum creatinine concentration were elevated, a highly significant correlation between the two parameters was found. When relating blood urea nitrogen concentration to the clearance of inulin an elevation of blood urea nitrogen concentration was not found until the filtration rate was below 50 ml/min/1.73 m2 b.s. The tubular functions were examined by studies of (a) the concentrating capacity, (b) the diluting capacity, (c) sodium reabsorption and id) renal acid-base regulation. The concentrating capacity was determined by two screening tests, maximal urine osmolality after 19 hours of fluid and food deprivation with or without injection of pitressin tannate, and by free water reabsorption. The administration of exogenous pitressin had no significant effect on maximal urine osmolality. There was a highly significant correlation between free water reabsorption and maximal urine osmolality. A highly significant correlation was also found between free water reabsorption and glomerular filtration rate. Diluting capacity was evaluated by determining minimum urine osmolality and free water clearance. A highly significant correlation between minimum urine osmolality and free water clearance was obtained. There was a good correlation between free water clearance and glomerular filtration rate. When sodium reabsorption is depressed below normal, urine sodium concentration during hydropenia is abnormally low. A normal standard bicarbonate level does not exclude a defect in renal acidifying mechanisms. A defect renal acidifying capacity could be found even in patients with normal filtration rates indicating that renal acidifying capacity might be the first sign of renal damage in children with recurrent urinary tract infections.

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 group of tests for intestinal and renal function were carried out in female patients with carcinoma of the uterine cervix before and after treatment with a combination of intracavitary radium and orthovoltage or supervoltage radiotherapy. The results were statistically evaluated and correlated with the effects of radiation known from previous clinical reports and experimental studies in animal models. No change in the concentration of urea and creatinine in serum took place, and the urea clearance (which was uncorrected for body surface area and therefore low in a number of patients prior to therapy) was likewise unaltered by therapy. A small (15 per cent) but statistically significant reduction in creatinine clearance was observed after therapy. Serum xylose levels 2 hours after a loading dose were significantly reduced, but since the 5-hour urinary excretion of xylose was not significantly altered by therapy, it is likely that delay in stomach emptying contributed to the change in serum xylose concentration. Mean daily faecal excretion of nitrogen and fat were unaltered, but the percentage of fat relative to dry weight of the stool increased, possibly as a consequence of an increase in the rate of intestinal cell desquamation. A highly significant fall in the value for the Schilling test took place after radiotherapy. While reduced glomerular filtration rate and increased utilisation of Vitamin B 12 may have contributed, the main reason for the reduction was thought to be impaired Vitamin B 12 absorption from the ileum. It is suggested that reduction in ileal function should be kept in mind in planning the nutritional requirements of anaemic subjects during pelvic irradiation, while the fall in glomerular filtration rate may lead to the prolonged action of drugs normally cleared by this mechanism.

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.

There may be an important relationship between secretion of prostaglandin(s) and renin in renal physiology since both are found in the kidney. This study was performed to determine whether the prostaglandin, PGA1, could modify the renal effects of angiotensin. Female mongrel dogs after water deprivation, supramaximal amounts of vasopressin, and desoxycorticosterone (DOCA), were studied during saline diuresis under pentobarbital anesthesia. After a control period, angiotensin II (Hypertensin) and then angiotensin II plus a prostaglandin, PGA1 (15α-hydroxy-9-oxo-10, 13-trans-prostadienoic acid) were infused via the left renal artery. Angiotensin II in subhypertensive amounts unilaterally and significantly (p

Glomerular filtration rate, urinary sodium excretion, maximum and minimumurine osmolalities, osmolal clearance, free water clearance, and negative free water clearance were measured in 8 patients with cystic fibrosis during dietary intakes of 8 Gm. and of 1 Gm. of sodium chloride to determine whether cystic fibrosis is associated with abnormal renal handling of sodium. Free water clearance was markedly reduced in the patients, and those most severely affected by the disease process had the lowest values. The administration of mannitol reversed the defect. Under hydropenic conditions negative free water clearance was lower on the low dietary salt intake and the patients most severely affected by cystic fibrosis had the lowest values. With the administration of mannitol and Pitressin, negative free water clearance was normal in all patients. The data can be interpreted as indicating that in patients with cystic fibrosis there may be increased sodium reabsorption in the renal proximal tubules with decreased delivery of sodium to more distal segments of the nephron.

SummaryThese experiments were designed to test the hypothesis that veratridine given intravenously causes a diuresis which is mediated by a decrease in plasma ADH. The results demonstrate that plasma ADH is not reduced, but rather is temporarily increased following veratridine administration. It is difficult to say which of the diverse pharmacological effects of veratridine produces the increase in ADH.Urine flow decreases immediately after veratridine is given and then tends to increase, but the increase was not significant statistically in the present experiments.We are indebted to Mrs. Pamela Geer, Mrs. Mary Ann Hill, and Dr. George Saba for technical assistance.

Chemically different Lissamine greens were investigated for their immediate and late effects on renal functional parameters. The data indicate (1) that there was no consistent change in transit times (TT) in series of up to four repeated single injections with different LG completed within 8 min. (2) proximal and distal intratubular pressure responded to a single i.v. injection of LG with two distinct pressure increments, similar for all dyes tested. The first increase (prox.: 1–3 mm Hg; dist.: 1–2 mm Hg) coincided with a blood pressure response; the second increase (prox.: 1–2 mm Hg; dist.: 0.5–1.5 mm Hg) started when LG appeared in distal convolutions. The changes in flow velocity resulting from such pressure changes would not cause any significant error in the measured TT. (3) the late effects of LG were an increase in overall reabsorption capacity (predominatly in the loop of Henle) a parallel increase in glomerular filtration rate, and an increase in urine flow and osmotic excretion rate. Proximal reabsorption rate was unaffected. No difference in response was observed between different LG. Neither GFR nor urine flow changed significantly in control experiments in which a similar osmotic activity of mannitol was injected. It is concluded that TT measurements with LG may provide valid information on tubular function; but the late effects of LG would limit its use to a single measurement at the end of an experiment.

Nephrectomy was performed in 2 elderly patients despite a significant reduction in over-all renal function. Both exhibited a surprising degree of increase in function in the remaining kidney, as measured by serial clearance studies. These findings may be important in considering ablative renal surgery in patients with preexisting diminution of renal function.

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.

Twelve patients operated on for gall bladder disease under methoxyflurane (Penthrane®) anaesthesia underwent renal function studies pre- and postoperatively. In seven of the patients the concentration of the anaesthetic agent was low, and in five a higher concentration was used. No effect on the glomerular filtration rate (endogenous creatinine clearance) and free water clearance was established. Fractional excretion of sodium decreased highly significantly in the low concentration group, but to a lesser extent in the higher concentration group. This might indicate that there was some effect on the sodium reabsorption in the tubules at methoxyflurane concentrations that were high but still within the normal range. Patients anaesthetized with halothane had a decrease of fractional excretion of sodium of the same order as those patients who received methoxyflurane in high dosage. ZUSAMMENFASSUNG 12 Patienten, die wegen Gallenblasenerkrankung unter Methoxyfluran (Penthran®) operiert wurden, wurden pra- und postoperativ Nierenfunktionsprufungen unterzogen. Bei 7 der Patienten war die Konzentration des Narkoseanges niedrig, bei 5 wurde eine hohere Konzentration verabreicht. Es zeigte sich keine Wirkung auf die glomulare Filtrationsrate (endogene Kreatinin-Clearance) und freie Wasser-Clearance. Die anteilige Natrium-Ausscheidung verminderte sich hochsignifikant in der Gruppe mit der niedrigen Konzentration, jedoch in geringerem Ausmas in der Gruppe der hoheren Konzentration. Das konnte dafur sprechen, das die Natrium-Reabsorption in den Tubulibei hohen, aber noch im Bereich des Gebrauchlichen liegenden Methoxyfluran-Konzentrationen beeinflost wurde. Patienten, welche mit Halothan narkotisiert wurden, wiesen eine Abnahme der anteiligen Natrium-Ausscheidung desselben Ausmases auf, wie diese Patienten, die Methoxyfluran in hoher Dosierung erhielten.

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

In 50 patients with prostatic hyperplasia renal function was examined in regard to 1. Incidence and type of impairment; 2. Correlations between the measures of prostatic hyperplasia and the degree of

Full-thickness bifid bladders were created in dogs. A midline episiotomy facilitated repeated hemibladder catheterization. The model has been used repeatedly over a 1-year period and consistent reproducible individual renal function data has been obtained.

SUMMARY The glomerular filtration rate (GFR), urinary concentrating and diluting capacity and sodium excretion have been determined in 17 children with previous histories of urinary tract infection confirmed by urine cultures. There were no signs or symptoms of infection at the time of the study. Renal function was found to be normal in patients with normal intravenous pyelographies (IVPs). In the patients with renal parenchymal changes a wide variety of functional changes could be found. Reduction of the glomerular filtration rate was the predominant lesion. The GFR could however not be predicted by the IVP-appearance. Most of the patients were able to increase the GFR during water diuresis. The glomerular-tubular balance for sodium was reset in 3 of the patients as manifested by an increased CNa/CIn. The concentrating capacity was also reduced in those 3 patients, indicating an impairment of the sodium reabsorption in the loop of Henle. All the patients were able to dilute the urine normally during water diuresis, but 5 of the patients were unable to increase their diluting capacity during the transition from hydropenia to water diuresis. It is noteworthy that only those patients were unable to increase the GFR significantly during the transition from hydropenia to water diuresis.

In the present series, cardiac output, renal blood flow corrected for PAH extraction rate, and glomerular filtration rate were measured in 8 patients with decompensated congestive heart failure with hyponatremia and normal or increased exchangeable sodium (dilution syndrome). The renal sodium reabsorption and oxygen consumption have also been measured. The cardiac output was reduced to less than half the normal. The renal blood flow was reduced to a greater degree than cardiac output, indicating a specific diversion of blood away from the kidneys. The glomerular filtration rate was also reduced, but to a lesser extent than the renal plasma flow, giving filtration fractions higher than usually reported. The reduction in renal blood flow and in glomerular filtration rate or the increase in filtration fraction had no relation to the magnitude of exchangeable sodium. In our patients, variations in the glomerular filtration rate revealed constancy in the sodium reabsorptive mechanism. The renal oxygen consumption was found to vary independently of the sodium reabsorption. The findings were compatible with an increased passive back diffusion of sodium in the tubular lumen in patients with advanced congestive heart failure. Data from the present study support the assumption that such passive re-entry for sodium is related to an increased filtration fraction, although other mechanisms must also be considered.