Paul D. Doolan

A clinical appraisal of the plasma concentration and endogenous clearance of creatinine

Abstract The normal values for the plasma concentration, excretion and twenty-four hour endogenous clearance of creatinine are given. Thirty men and thirty women were studied and in fifteen of each sex, measurements of both creatinine and true creatinine in the plasma were made. The non-creatinine chromogen did not influence the variability of the plasma values within a single individual or among a group of individuals. Correlation analyses revealed that the sex difference in plasma concentration and clearance could be removed by correcting for lean body weight. In ten additional subjects, there was no difference in one hour clearance values measured in the morning and afternoon, but these values did exceed the twenty-four hour values by some 7 to 11 per cent. In eighty patients with evidence of renal disease, it was found that if the plasma creatinine was less than 1.25 mg.100ml. in men and less than 1.1 mg.100ml. in women, the clearance value is normal unless the patient has extensive muscular wasting. If the plasma concentration is 1.25 to 1.75 mg.100ml. in men or 1.1 to 1.4 mg.100ml. in women, the clearance may vary from definitely low to normal values. With values greater than 1.1.75 mg.100ml. in men and 1.4 mg.100ml. in women, the clearance is always low. Comparable relationships exist with true creatinine measurements. It is concluded that clearance measurements should be made and reliance not placed on the value predicted from the concentration of true creatinine in the plasma. The variability of the values in patients with evidence of renal disease was no greater for creatinine than for true creatinine measurements, and the information provided with each method was in close agreement. Either method is suitable for clinical purposes but a preference is expressed for true creatinine measurements if the plasma values are low normal or less. It is concluded that restrictive measures designed to minimize the variability resulting from changes in diet and the amount of physical activity are not justified. Similarly, corrections for surface area and lean body weight improve the normal values but are of limited usefulness in patients with evidence of renal disease. Creatinine formation in the body is briefly reviewed and instances of diminished production are commented on. Although clearance measurements offer the best means of detecting definite impairment of renal excretory function, the wide range of normal values limits the usefulness of such measurements in detecting lesser amounts of renal damage. Particular emphasis is therefore placed on the value of serial determinations in uncovering early renal impairment and in evaluating borderline values as well as the patients prognosis and the influence of therapy. The opinion is expressed that one hour clearance measurements provide information as useful as that obtained when twenty-four hour urine collections are used.

Renal clearance of eighteen individual amino acids in human subjects.

Studies of renal clearance of individual amino acids have been comparatively few in number. With the exception of those of Sheffner, Kirsner, and Palmer (1) such investigations have been performed solely on experimental animals and in certain respects the results which they have yielded have been conflicting. In part, the conflict has arisen because of the limited specificity of the analytical methods which the earlier investigators were forced to employ (2-7). Beyer and his associates (8-12), and Kamin and Handler (13), using the more specific methods of microbiological assay, were able to define these areas of conflict as well as to confirm and extend certain of the earlier findings. The most important findings of these previous investigations and the present state

THE APPLICATION OF HEMODIALYSIS TO THE TREATMENT OF BARBITURATE POISONING

Current methods of treatment of barbiturate poisoning, which consist of supportive measures aimed towards maintenance of life until the drug can be excreted or metabolized, have occasioned considerable dissatisfaction because of their lack of specificity. Ideal therapy must be directed toward either more rapid removal or accelerated detoxification of the barbiturate preparation. The closest approach to this goal has been the use of massive intravenous infusions to initiate diuresis with consequently more rapid urinary excretion of the drug. Morbidity and mortality in a significant number of patients with barbiturate toxicity are not directly related to the primary depressant effect of the drug. Many patients, especially in the older age group, die because of respiratory difficulties. Morbidity at all ages is often increased by such complications. The number and severity of these could be reduced if the drug were removed from the body more rapidly, thus shortening the period of coma. The application of massive hydration (1) or cross-circulation of a poisoned dog with a large untreated animal (2) has been shown to permit survival of narcotized dogs given doses of barbiturate that ordinarily prove fatal. These studies indicated that permanent fixation of barbiturate to tissues is not the major factor in mortality and strongly suggested that beneficial effect might result from lowering of the blood barbiturate level, irrespective of the total amount of barbiturate contained within the body. Hemodialysis will not remove substances that are firmly attached to protein. Brodie and his associates (3) have presented evidence that only a certain portion of the circulating barbiturate is so

Renal clearance of lysine in cystinuria: Pathogenesis and management of this abnormality

Abstract Cystinuria is an inherited abnormality in which unusually large amounts of cystine, lysine, arginine and ornithine are excreted in the urine. Simultaneous measurements of the inulin and lysine clearances indicate that in the fasting state a very small amount of lysine is reabsorbed from the glomerular filtrate. The renal tubules are unable to reabsorb any additional amount and, on loading with lysine, their clearance value approaches that of inulin. A suggested explanation for this tubular defect is that in the homozygous form of cystinuria the transport system is present in only trace amounts. The transport system may be of the membrane carrier type and its limited capacity is exceeded even in the fasting state. Any reabsorption which does occur is accomplished by an active mechanism and passive diffusion plays no role of significance. Patients with cystinuria respond normally to the administration of glycine and arginine in that the excretion of glycocyamine is increased. Therapeutic efforts directed at the specific tubular defect appear to hold little promise. The decrease in cystine excretion which can be accomplished by dietary restriction should not be neglected. The addition of a methyl donor to a restricted dietary intake offers no additional advantage. Measures directed at rendering the physicochemical environment less conducive to precipitation deserve further study.

Effect of spirolactone SC 8109 on renal function in normal human subjects.

Summary Five normal, male, human subjects have been studied by the classical clearance technics during salt deprivation before and after therapy with the steroid-17-spirolactone, SC 8109. No change in the glomerular filtration rate or effective renal plasma flow could be demonstrated but a definite sodium diuresis and potassium retention occurred in response to the spirolactone. A small increase in free water clearance was seen in 4 of 5 subjects studied. These observations localize the effect of spirolactone to the renal tubule.

Effect of administration of ACTH and cortisone upon blood glutathione levels.

Summary Blood glutathione (GSH) and total glutathione (GSH plus GSSG) were determined in eleven patients during ACTH therapy and in eleven patients during the administration of cortisone. GSH values were significantly decreased from a pretreatment average of 36.6 mg per 100 cc to 26.9 mg by ACTH while cortisone produced a decrease from an average pretreatment value of 35.0 mg per 100 cc to 29.1 mg. The latter decrease, statistically, is of a low order of significance. The total glutathione values showed no changes following the administration of either ACTH or cortisone. During treatment with ACTH the greatest decrease in blood GSH occurred in the patients showing the greatest increase in blood sugar. There is suggestive evidence that although patients with normal glucose tolerance may show diabetic patterns during treatment, those who demonstrate mildly diabetic patterns prior to therapy show no further decrease in glucose tolerance and minimal reduction in GSH values after ACTH or cortisone therapy.

Excretion of amino acids in nephrosis.

Summary (1) By microbiological assay, concentrations of 18 amino acids have been examined in the blood and urine of patients with nephrosis and in normal individuals under various circumstances. There were observed in an adult male patient, with nephrotic syndrome associated with glomerulonephritis, large increases over the normal rates of urinary excretion of many amino acids, both essential and nonessential, but more notably of the essential. A female adult patient, with clinical findings only of nephrosis, showed considerably less deviation from normal with a trend toward increased excretion of amino acids in the fasting state. There was a general tendency to moderately low concentrations of several amino acids in the blood of both nephrotic subjects. 2) After elevation of the blood concentrations by intravenous loading of a mixture of amino acids, the percentage of filtered amino acids (determined by simultaneous measurement of inulin clearance) which were excreted generally increased in the case of normal individuals as well as in the nephrotic subjects. No. consistent differences could beobserved between normal and nephrotic subjects as a result of “loading” of the blood with amino acids. 3) Intravenous administration of ACTH for 9 to 10 days to 2 normal subjects and 1 nephrotic subject produced no distinct changes in rates of excretion of amino acids in the normal individuals. but appeared to be associated with a moderate decrease in excretion of virtually all amino acids in the patient with nephrosis. Further study is required to confirm this observation.

POST-TRAUMATIC ACUTE RENAL INSUFFICIENCY COMPLICATED BY HYPERNATREMIA

Excerpt Prolonged oliguria after severe injury is a problem of major importance in military medicine. According to Lucke it was the form of fatal kidney disorder most frequently encountered during ...

Gastrocolostomy: Clinical Observations and Experimental Studies

Summary A patient survived 66 days after removal of the entire small intestine, half of the colon and the pyloric end of the stomach, being maintained by near total parenteral alimentation. More than an adequate volume of fluid had to be prescribed daily as a vehicle of caloric intake and as a means of maintaining the patency of the veins. Phlebitis and the usual discomfort associated with prolonged infusions occurred, and, when an additional liter of saline was added to the regimen, pulmonary edema resulted. Two separate instances of hypokalemic, hypochloremic alkalosis were treated, and inferential evidence obtained that the concurrent restriction of sodium along with potassium administration expedites the correction of this type of alkalosis. There was no correlation between serum and gastric concentrations of potassium. The nitrogen balance studies revealed only a small amount of nitrogen excretion despite an inadequate caloric intake and the presence of stress. Several facts and theories are offered as an explanation for this finding. Potassium was given intermittently to test its effect on nitrogen balance but no definitive conclusions were reached. Some gastric absorption of glucose, Aminosol solution, methionine, and glycine was demonstrated but there was no evidence of absorption of glucose or Aminosol from the rectum. The difficulties in supplying an adequate caloric intake by present-day methods were demonstrated and reemphasized.