The Measurement of Glomerular Filtration. Creatinine, Sucrose and Urea Clearances in Subjects Without Renal Disease 1

Winkler, Alexander W.; Parra, J B

doi:10.1172/jci100912

Cited by 21 publications

(14 citation statements)

References 28 publications

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“…The method of conducting the observations in fasting human subjects has been described elsewhere (3). Sam or not glomerular filtration was reduced.…”

Section: Methods (A) Generalmentioning

confidence: 99%

The Toxicity of Orally Administered Potassium Salts in Renal Insufficiency 1

Winkler¹,

Hoff²,

Smith³

1941

J. Clin. Invest.

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Smillie (1) in 1915 reported the sudden collapse of a patient with nephritis seven hours after the oral administration of 10 grams of potassium chloride. He attributed this collapse to an excessive accumulation of potassium in the body owing to impaired excretion. The patient ultimately recovered. Smillie also found that sudden death commonly followed the oral administration of potassium salts to rabbits with uranium nephritis. Similar amounts were without effect in control animals. He reported no chemical determinations of potassium in the serum or urine. Smillie's observations have frequently been cited as indications of the possibility of potassium poisoning in renal insufficiency. However, the complex extrarenal changes which occur in uranium nephritis and the peculiarly specialized character of the rabbit kidney make it improper to generalize from these experiments concerning oral potassium poisoning. There is, on the other hand, reason for minimizing the danger of toxicity from potassium in human nephritis. High concentrations of potassium in the serum are rare even in the most advanced nephritis (2), although these patients may ingest considerable amounts of meat and other foods containing potassium, and although they must continually be liberating potassium from the breakdown of tissue.In the present study an attempt is made to ascertain whether humans or animals can be poisoned by oral administration of potassium. Potassium salts were administered to human subjects with and without renal impairment, and the concentrations of potassium in serum and urine followed at intervals thereafter. In another type of experiment, dogs whose ureters had been tied received potassium salts by stomach tube. Frequent electrocardiographic observations and chem-'Aided by grants from the Ella Sachs Plotz fund, ical determinations of potassium in serum were used for the detection and estimation of toxic effects of potassium in these animals (10). METHODS (A) GeneralThe method of conducting the observations in fasting human subjects has been described elsewhere (3). Samples of urine and of serum were obtained at intervals before and after the ingestion of potassium salts. Urine specimens were collected without catheterization. Usually considerable water was given during the course of the experiment. Potassium salts were administered either in capsules, followed by water, or dissolved in tomato juice. Urea clearances were determined in all experiments, and in some, sucrose clearances were measured after preliminary intravenous injections of sucrose. Both sucrose and urea clearances vary with the glomerular filtration rate and in renal disease are reduced in about the same proportion as the filtration rate (3, 4). Accordingly, they may both be used as relative measures of glomerular filtration. Potassium was determined as the chloroplatinate by the method of Hald (5). Clearances were calculated by the general method previously described (3).

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“…The method of conducting the observations in fasting human subjects has been described elsewhere (3). Sam or not glomerular filtration was reduced.…”

Section: Methods (A) Generalmentioning

confidence: 99%

The Toxicity of Orally Administered Potassium Salts in Renal Insufficiency 1

Winkler¹,

Hoff²,

Smith³

1941

J. Clin. Invest.

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“…Winkler and Parra (5) observed that, following the ingestion of a single dose of creatinine, its clearance and the creatinine/sucrose clearance ratio behave rather erratically, but are generally depressed as the experiment progresses. These authors believe that the curvilinear relationship, as previously described, is not a dependent one.…”

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confidence: 99%

On the Renal Tubular Excretion of Creatinine in Normal Man1

Shannon¹,

Ranges²

1941

J. Clin. Invest.

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The demonstration that in man the renal excretion of exogenous creatinine 1 takes place in part by an active tubular process depends upon two experimental findings (1). The plasma clearance of creatinine in the normal individual is invariably in excess of the simultaneously determined inulin clearance, which is accepted as a valid measure of glomerular filtration rate (2). Furthermore, raising the plasma creatinine from low to high concentrations depresses its clearance toward that of inulin, which appears to be its limiting value. However, contrary to similar findings in the dogfish (3) and chicken (4), this depression is not completely reversible.More recently, both the presence and the significance of the curvilinear relationship between plasma concentration and renal excretion of creatinine have been questioned. Winkler and Parra (5) observed that, following the ingestion of a single dose of creatinine, its clearance and the creatinine/sucrose clearance ratio behave rather erratically, but are generally depressed as the experiment progresses. These authors believe that the curvilinear relationship, as previously described, is not a dependent one. They suggest that its presence in the original experiments was incidental to an experimental routine which usually resulted in the high plasma concentrations being observed later than the low ones. Findley (6) later re-examined the relationship between plasma concentration and renal excretion over a range of plasma values of 1.0 to 14.0 mgm. per cent. His findings are precisely the same as those previously reported by Cope (7). That is, a linear relationship between these two variables obtains if one arbitrarily corrects the observed plasma concentration by -0.5 mgm. per cent of assumed non-creatinine chromogenic material. He did not consider the depression of the creatinine 1 In this report, unless specifically stated to the contrary, the term creatinine may be taken to mean exogenous creatinine.clearance at higher plasma levels valid evidence of tubular excretion, since the concentrations necessary to demonstrate the phenomenon were " far beyond the physiological range." The linear relationship limited to the lower plasma values was then advanced as evidence opposing the renal tubular excretion of creatinine. This conclusion would favor Rehberg's (8) original contention that creatinine is excreted solely by glomerular filtration.More recently, Rehberg (9) has called attention to the demonstration by Abdon (10) that the administration of creatinine leads to the appearance in the plasma of a substance resembling creatinphosphoric acid. It is Rehberg's belief that the tubules do not participate in the excretion of preformed creatinine but rather that they may transfer creatinine which has its origin in the plasma in some more complex compound, such as that described by Abdon. This is an important consideration, since this type of compound would yield true creatinine in ordinary plasma filtrates and behave as suclh toward both specific and nonspecific analytical metho...

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“…Numerous investigators have examined the simultaneous creatinine and urea clearances in normal man and in subjects with acute or chronic diffuse glomerulonephritis, among whom may be mentioned Rehberg (24,25), Holten and Rehberg (13,14), Cope (6), Hayman, Halsted, and Seyler (12), Ellis and Weiss (8,9,), Cambier (5), Covian and Rehberg (7), Winkler and Parra (38,39), Bjering (3) and Bing and Bjering (2). The most important facts established by these investigations are that the urea clearance (with few questionable exceptions) is less than the creatinine clearance, and that in renal disease the two clearances are reduced in a roughly parallel manner.…”

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confidence: 99%