Herbert Chasis

Glomerular filtration rate, effective renal bloodflow, and maximal tubular excretory capacity in infancy

Summary 1. Glomerular filtration, effective renal plasma flow, and maximal tubular excretory capacity have been measured in twenty-one normal infants ranging in age from one-half to 110 weeks. 2. When corrected for surface area, the adult mean value for the filtrationrate is reached in some infants in ten to twenty weeks, for effective renal plasma flow and maximal tubular excretory capacity in thirty weeks. 3. If the body surface area is used as an index to general metabolism, the filtration rate, renal blood flow, and tubular excretory mass are adjusted before the end of the first year to the metabolic requirements of the body. However, in the first two or three months of life the three functions develop at different rates. The fact that the normal adult value of the CPAH/TmPAH ratio is observed served in nearly every infant suggests that the renal blood flow increases in served in nearly every infant suggests that the renal blood flow increases in proportion to the development of the renal tubules. The CM/TMPAH and CM/CPAH ratios in early infancy are, however, higher than the adult values, indicating functional imbalance between glomeruli and tubules in favor of the former. This imbalance might be related to increased glomerular pressure, disproportionally large glomerular surface, or decreased PAH extraction ratio; it is suggested that large glomerular surface and increased pressure are, perhaps, responsible for glomerular hyperfunction.

Exaggerated natriuresis in essential hypertension

P ATIENTS with essential hypertension excrete more sodium than do normotensive patients in response to the infusion of hypertonic saline solution [7-d]. The work reported in this paper attempts to assay the role of the renal tubule in the genesis of this exaggerated natriuresis. Our observations confirm the finding that exaggerated natriuresis occurs in hypertensive patients challenged with infusion of hypertonic saline solution, and we find that increased sodium excretion is also induced by infusion of hypotonic inulin and p-aminohippurate solution administered at low rates. However, the basal sodium excretion in hypertensive patients is comparable to that observed in normotensive patients, indicating that both groups are in sodium balance on the same diet; and the exaggerated natriuresis induced in hypertensive patients by infusion of hypertonic saline solution can be abolished by salt deprivation. This and other evidence indicates that the tendency to exaggerated natriuresis in hypertensive patients has an extrarenal basis.

HEMODYNAMIC ALTERATIONS IN NORMOTENSIVE AND HYPERTENSIVE SUBJECTS DURING THE PYROGENIC REACTION

It is well known that toxic substances, probably derivatives of bacterial protein (1), frequently appear in improperly distilled water. A dramatic and often potentially dangerous syndrome of chill and fever (pyrogenic reaction), occasionally complicated by peripheral circulatory collapse, follows the intravenous administration of solutions contaminated with these substances. A marked increase in renal blood flow (2), a reduction in arterial pressure (3) and an increase in cardiac output (4) have been observed during the pyro-genic reaction in normal man, indicating a marked reduction in overall peripheral resistance. Three stages of arterial pressure change have been described (3): namely, (a) a short period of elevated pressure during the chill and initial rise in temperature, (b) a phase characterized by a moderate fall in blood pressure, coinciding approximately with the appearance of renal hyperemia, and (c) a marked reduction in blood pressure with a narrowing of the pulse pressure some 4 or 5 hours after the administration of the pyrogen. Although antipyretics, such as amidopyrine, when given in adequate doses prior to injection of the pyrogen, will prevent chill and fever, they do not affect renal hyperemia or phases (b) and (c). The reduction of arterial pressure (c) is usually greater among hypertensive than among normal subjects and may be so profound as to result in a shocklike state, even in the absence of fever. It is not known whether the late reduction in blood pressure is a result of widespread vasodilation, reduced cardiac output or a combination of the two. Nor is it known whether there is any fundamental difference in response on the part of hy-pertensive as compared with normotensive individuals. The present study was undertaken to evaluate the hemodynamic factors involved in this reduction. METHODS Eight subjects, 6 of whom had essential hypertension, selected from the wards of the Third (New York University) Medical Division of Bellevue Hospital, and Evans Memorial Hospital (Boston University School of Medicine), were examined under basal conditions after several days of bed rest. All subjects were free of gross cardiac pathology. Amidopyrine in doses of 0.6 gram was given to each subject every 4 hours for 5 or 6 doses during the 24 hours immediately prior to the administration of pyrogen. Typhoid vaccine and contaminated inulin (Pfanstiehl inulin lot No. 268) were used as sources of pyrogen. Pyrogenic inulin, in doses of 100 to 200 mgm. dissolved in sterile saline and passed through a …

GLOMERULAR DYNAMICS IN THE NORMAL HUMAN KIDNEY

One of the most interesting facts about the renal circulation is that during marked changes in renal blood flow (adrenalin ischemia and pyrogenic hyperemia) the rate of glomerular filtration typically remains unchanged. This fact has been attributed to the circumstance that the changes in renal blood flow are mediated primarily by changes in the tonus of the efferent arterioles; consequently, any increase or decrease in blood flow is accompanied by a reciprocal change in glomerular filtration pressure, with the result that the filtration rate remains unchanged (3). Beyond the fact that this emphasis upon the efferent arteriole is to some extent contrary to the importance which has hitherto, chiefly for anatomical reasons, been attached to the afferent vessel, this description of the glomerular circulation presents several interesting implications. It assumes that the rate of glomerular filtration is determined solely by glomerular pressure factors, exclusive of any limitation imposed by the permeability of the glomerular membranes. There logically issues from this assumption the question whether or not filtration pressure equilibrium is normally reached in the glomerulus. The answer to this question is of practical importance in two respects. If filtration equilibrium is reached in the glomerular circulation, then this fact must set the upper limit to the hydrostatic pressure available to propel blood through the efferent arterioles and the postglomerular circulation. And in the face of a demonstration of filtration equilibrium in the normal kidney, a decrease in filtration rate in renal disease cannot logically be attributed to reduced permeability of the glomerular capillaries, in contradistinction to a decrease in filtration pressure or in total filtering

Effect of Febrile Plasma, Typhoid Vaccine and Nitrogen Mustard on Renal Manifestations of Human Glomerulonephritis

Summary Administration of plasma from patients acutely ill with pneumococcal and streptococcal infections failed to decrease proteinuria or induce diuresis in 2 patients with chronic diffuse glomerulonephritis. Induction of the pyrogenic reaction was accompanied by decrease in proteinuria on 2 occasions in one patient. We are inclined to attribute this result to the concomitant decrease in the rate of glomerular filtration. Therapeutic doses of HN2 reduced proteinuria but diuresis failed to occur in 2 patients with advanced chronic diffuse glomerulonephritis with marked renal functional impairment. However, in one patient with minimal renal functional impairment, administration of HN2 was followed on 2 separate occasions by diuresis, marked reduction in proteinuria and concomitant increase in filtration rate, a combination of effects consistent with a return of glomerular function towards normal.† Our observations indicate that reversal of renal manifestations of human glomerulonephritis can be induced by HN2. This study is being extended to include patients in earlier phases of glomerulonephritis.

RENAL FUNCTION IN THE SEPARATE KIDNEYS OF MAN. I. HEMODYNAMICS AND EXCRETION OF SOLUTE AND WATER IN NORMAL SUBJECTS

Observations have been made in 17 normotensive subjects selected from the wards of the Third (New York University) Medical Division of Bellevue Hospital. Included in this report are observations made on 4 additional subjects reported in a previous communication (2). The total group comprises 19 female and 2 male subjects between the ages of 20 and 68 years. All subjects were maintained on the regular hospital diet. Fluids were withheld for 15 hours and the test was performed in the morning on the fasting patients. After local anesthesia with 2 per cent metycaine, cystoscopy and ureteral catheterization were performed, employing Pederson multi-eyed ureteral catheters inserted to a distance of 12 to 16 cm. Large diameter catheters (no. 8 through no. 6 Fr.) were utilized to minimize leakage.1 A soft rubber catheter was placed in the bladder to detect leakage around the ureteral catheters. In none of the observations reported here did measurable leakage occur. If leakage does occur, analysis of bladder urine permits partition between the right and left kidneys if the concentrations of the test substances are

Reassurance in the Management of Benign Hypertensive Disease

The therapeutic improvement achieved by administration of drugs in arterial hypertension and other disease states is widely recognized to be due to the potency of reassurance and suggestion as well as the possible pharmacologic action of the drugs employed. In this article Dr. Goldring and his associates evaluate the effectiveness of a calculated and deliberately dramatized regimen of reassurance on the blood pressure and on the symptoms in patients with benign hypertensive disease. These results help to explain why nonscientific treatment sometimes seems to be crowned with therapeutic success.

The Distribution of Intrarenal Blood Flow in Normal and Hypertensive Man

Observations were made on eight normotensive subjects and on 12 patients with essential hypertension to determine whether the intrarenal distribution of blood flow is altered in essential hypertension. Dye-dilution curves were recorded across the renal vascular bed and a set of integral transformations, developed by Gomez, was used to determine distribution of blood flow per unit renal blood volume across the renal vascular bed from dye-dilution curves. Observations also were made on two hypertensives and two normotensives during administration of norepinephrine. The distribution of specific blood flow and the functional renal blood volume in the right kidney of patients with essential hypertension were comparable to those in normal subjects, but the mean specific blood flow was reduced in essential hypertension. Failure to demonstrate altered distribution of specific blood flow in essential hypertension indicated an absence of focal reductions in renal blood flow and that blood flow is reduced uniformly throughout the renal vascular bed in essential hypertension. This reduction in specific renal blood flow is attributed to arteriolar vasoconstriction.

Appraisal of Antihypertensive Drug Therapy

Four completed prospective studies of drug-treated and control hypertensives utilizing double blind randomized protocols are reviewed for the purpose of evaluating the evidence on which the present therapeutic crusade is based. Patients studied were predominantly male, observed for short period, had complications or died at young age, had high incidence of previous target organ vascular disease, and did not include those whose blood pressure fell to normal with hospitalization alone. Incidence of complications associated with coronary artery disease was the same in control and treated patients. The rapidly progressive disease observed in these patients differs from that described in other natural history studies. Population screening for hypertension for the purpose of instituting drug therapy is premature because the value of antihypertensive drug treatment for the general hypertensive population has not been established.

Renal Hemodynamic Response to Osmotic Diuresis in Man.

Summary The hemodynamic response to rapid infusion of hypertonic mannitol was examined in 12 normotensive subjects. At osmolar clearances of 10 to 15 ml/min glomerular filtration rate was decreased in all, the maximal reduction ranging from 19.2 to 39.4%. The maximal reduction in effective renal blood flow was less than 10% in the majority of subjects. Extraction ratio for p-aminohippurate was unchanged in the 4 subjects in whom this measurement was made. The decrease in filtration rate which occurs during osmotic diuresis as induced by mannitol probably results, at least in part, from a reduction in net filtration pressure caused by increased tubular volume and hydrostatic pressure. It is recognized that changes in the interstitial pressure and renal vasomotor activity may also participate in the renal response to hypertonic mannitol infusion.