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D E Oken

Publications and source records attributed to D E Oken.

At least 19 recordsLinked to original sources
PubMed1994

Renal and extrarenal considerations in high-dose mannitol therapy.

It is well recognized that the large doses of mannitol used in treating cerebral edema alter extracellular fluid (ECF) volume, osmolality, and composition to a degree which, under some circumstances, can lead to acute renal failure, cardiac decompensation, and other difficulties. It is less well appreciated that the patient's body habitus, age, total body water content relative to body weight, pretreatment plasma sodium concentration and plasma osmolality, and the presence of edema or ascites also can influence the degree of ECF change and the rate of mannitol excretion to a significant degree. Here, we show how these changes occur and the way in which their magnitude can be predicted prior to therapy so as to minimize the risk of an adverse result.

Acute Kidney Injury↗
PubMed1990

Renal epithelial amino acid concentrations in mercury-induced and postischemic acute renal failure.

The concentration of 18 alpha-amino acids (AAs) in plasma and renal cortical cell water were measured 3 or 24 hr after 1 hr of unilateral renal artery clamping or 24 or 48 hr after 15 mg/kg body weight HgCl2 injection sc as a test of epithelial integrity. Cellular glycine (Gly), hydroxyproline (Hpr), ornithine (Orn), phenylalanine (Phe), serine (Ser), and tryptophan (Trp) concentrations were depressed 24 hr after HgCl2 (p less than 0.05), but the remaining 12 AAs were not distinguishable from control despite the presence of severe renal failure. ARginine (Arg), glutamic acid (Glu), and valine (Val) also were decreased (P less than 0.05) 24 hr later, but concentrations of half of all measured AAs were still normal. Cellular alanine (Ala), Arg, Glu, Gly, Phe, and Ser concentrations were decreased 3 hr after ischemia, p less than 0.05, but 12 AAs were unchanged and only Arg, Phe, Ser, and threonine (Thr) were reduced 24 hr after ischemia was reversed. Concentrations of even the most affected AAs remained notably higher than in plasma in both forms of acute renal failure (ARF). Total loss of AAs from a small proportion of tubular cells would be hidden by essentially normal concentrations in the rest, and such losses may well have occurred. Unless cellular AAs in ARF are almost completely bound, however, the well-maintained cell:plasma AA concentration ratios indicate that cellular energetics were adequate for AA uptake and that epithelial permeability to AAs in the vast majority of cells was not greatly disturbed. Such findings suggest that most of the epithelium, although seriously damaged, had remained viable.

Acute Kidney Injury↗
PubMed1989

Does the ultrafiltration coefficient play a key role in regulating glomerular filtration in the rat.

Various experimental maneuvers, hormones, and pharmacological agents are reported to exert their effects on glomerular filtration largely or exclusively by changing the ultrafiltration coefficient (Kf) of the filtration barrier. In light of a number of uncertainties discussed in this review, however, it is by no means certain that the Kf actually does play this central role in the physiological regulation of glomerular function.

Animals↗
PubMed1989

Glomerular hemodynamics in established glycerol-induced acute renal failure in the rat.

The glomerular dynamic correlates of failed filtration were studied in volume replete rats with established glycerol-induced acute renal failure (ARF). Over one-half of all nephrons formed virtually no filtrate, while the single nephron glomerular filtration rate (SNGFR) of fluid-filled nephrons, measured at the glomerulotubular junction to preclude the possibility of covert tubular leakage, averaged one-sixth of control (P less than 0.001). Even that low mean value was elevated by a few nephrons with a near normal SNGFR. Renal failure thus reflected both total filtration failure in the majority of nephrons and massively reduced filtration in most of the remainder. Glomerular capillary pressure (Pg) averaged some 14 mmHg below control (P less than 0.001), whereas the arterial colloid osmotic and Bowman's space pressures were not significantly altered. Renocortical and whole kidney blood flow were also unchanged. Marked internephron functional heterogeneity precluded estimates of the ultrafiltration coefficient. However, the fall in SNGFR correlated well with the markedly depressed Pg and afferent net filtration pressure (delta PnetA, P less than 0.001), which in turn were caused by increased preglomerular resistance and a reciprocal fall in efferent arteriolar resistance. This complex change in intrarenal resistances was largely, if not entirely, responsible for failed filtration in this ARF model.

Acute Kidney Injury↗
PubMed1987

Glomerular hemodynamics in mercury-induced acute renal failure.

As manifest by tubular collapse and the virtual absence of flow into the glomerulotubular junction (GTJ), filtration in most nephrons (SNGFR) of rats poisoned with 9 mg/kg body wt HgCl2 16 to 28 hours earlier was virtually absent. Arterial colloid osmotic pressure (COPA) and Bowman's space pressure (PBS) were modestly depressed (P less than 0.05 or below), and mean blood pressure was reduced from 115 +/- 2 mm Hg (SEM) to 97 +/- 1 mm Hg (P less than 0.001). Glomerular capillary hydraulic pressure (Pg), 25.6 +/- 1.3 mm Hg was some 24 mm Hg lower than control (P less than 0.001) and yielded a net afferent effective filtration pressure (Pnet) of 4.1 +/- 1.2 mm Hg. Excluding three rats with values greater than 10 mm Hg, Pnet averaged 2.0 +/- 0.9 mm Hg (N = 17 rats) versus 20.0 +/- 1.8 mm Hg in controls (N = 10, P less than 0.001), the former being statistically almost indistinguishable from 0 mm Hg and barely able to support any filtration. This decrease in Pg was caused by a major increase in preglomerular resistance (RA) and a reciprocal fall in efferent arteriolar resistance (RE), the RA/RE ratio of 7.2 +/- 0.8 being fourfold higher than control (P less than 0.001). Renocortical blood flow was not different from control (P greater than 0.2). A wide spread of Pg values in individual glomeruli and the absence of tubular flow despite the appearance of i.v. injected lissamine green in a quadrant of surface glomeruli suggested the possibility of a greatly increased, glomerular capillary resistance. It is concluded that reciprocal changes in RA and RE are the immediate cause of filtration failure in this form of ARF and that, in the virtual absence of filtration, tubular leakage can play no important role. Since PBS was depressed in both the developmental and established phases of ARF, tubular obstruction appears to play no direct role in the pathogenesis of this particular model of murine acute renal failure.

Acute Kidney Injury↗
PubMed1985

Effects of intra-animal nephron heterogeneity on studies of glomerular dynamics.

Quintuplicate determinations of the parameters measured in studies of glomerular dynamics revealed that the intra-animal coefficients of variation for Bowman's space and star vessel pressures, nephron filtration rate, and filtration fractions were 54 to 72% larger than the corresponding interanimal coefficients of variation; those for glomerular capillary pressure were more nearly equal. With a net efferent filtration pressure (delta PE) of 10.6 +/- SEM 1.9 mm Hg, the rats were far from filtration pressure equilibrium and the calculated ultrafiltration coefficient (Kf) of 2.1 +/- SEM 0.2 nl/min X mm Hg was lower than in many other studies. Statistical analysis revealed that the precision of estimates of both the measured and the derived parameters in glomerular dynamic studies is affected appreciably by ignoring the intra-animal effect. The importance of the intra-animal variance in glomerular dynamic studies is greatest when only one or two samples of each measured parameter are obtained in every rat (k = 1 or 2) and least when k is large. Triplicate sampling provides combined SEMs that are not greatly larger than those obtained with k = 5, however, and offers the greatest economy in studies of glomerular dynamics. The number of animals required to provide values with delta PE and Kf that are within +/- 20% of the "true" values is rather large.

Animals↗
PubMed1985

An alternate method for estimating efferent arteriolar plasma colloid osmotic pressure.

The colloid osmotic pressure (COP) of efferent arteriolar plasma in glomerular dynamic studies generally is estimated from the measured protein concentration (CE) while the nephron filtration fraction (SNFF) is derived from CE and the systemic plasma protein concentration (CA) according to the equation SNFF = (1 - CA/CE). Estimates of both SNFF and COPE are quite sensitive to small errors in protein measurement, however, with a putative coefficient of variation of +/- 5% in protein measurement at a typical SNFF of 0.33, for example, providing an uncertainty (i.e., +/- SD) of +/- 14% in the SNFF estimate and +/- 2.4 mmHg in the estimated COPE value. In this study, we evaluated in vitro the precision with which the COP of plasma samples can be estimated after ultrafiltration by coupling direct oncometry of native plasma with isotopically measured filtration fractions derived employing nanoliter and microliter volumes and applying a modification of the equation of Ladegaard-Pedersen (Scand. J. Clin. Lab. Invest. 23: 153-158, 1969). The measured and estimated oncotic pressures were then compared. The mean differences between theoretic and measured COP values at filtration fractions of less than 0.1, 0.1-0.2, 0.2-0.3 and greater were: -0.4 +/- 0.8 (SE) (n = 22); 1.8 +/- 1.1; 3.9 +/- 1.0; and 6.0 +/- 1.7%, respectively. It is concluded that the coupling of direct oncometric measurement of arterial plasma colloid osmotic pressure with isotopically determined filtration fractions provides a satisfactory estimate of COPE that is suitable for studies of glomerular dynamics.

Animals↗
PubMed1984

Hemodynamic basis for human acute renal failure (vasomotor nephropathy).

Oliguric acute renal failure in man is characterized by intense outer cortical vasoconstriction and a marked increase in preglomerular resistance. The degree of preglomerlar resistance change needed to cause the expected 50 to 80 percent fall in blood flow far exceeds the level that would totally abolish filtration. By contrast, equal 3.0-fold increases in both pre- and postglomerular resistance provide this same degree of ischemia but leave filtration very well maintained. Such a scenario seems unlikely, however, since it would entail a mere 15 to 25 percent decrease in preglomerular resistance vessel caliber rather than the extreme attenuation observed. By contrast, there are reasons to believe that preglomerular constriction may be accompanied by postglomerular vascular relaxation. In sum, unless cortical ischemia reflects precisely matched increases in pre- and postglomerular resistances, filtration failure is inevitable in human vasomotor nephropathy.

Acute Kidney Injury↗
PubMed1983

Theoretical analysis of pathogenetic mechanisms in experimental acute renal failure.

A network thermodynamic model of glomerular dynamics has been employed to determine the degree of change in individual glomerular vascular resistances, hydraulic conductivity and proximal tubule pressure that, singly or in concert, could lower GFR to the degree expected in experimental acute renal failure (ARF). In both the rat and dog, the analysis shows that filtration failure is not achieved until preglomerular resistance (RA) is increased at least twofold or postglomerular resistance (RE) is decreased by 74% or more with all other determinants held at control values. Tubular obstruction alone will not provide failed filtration until tubule pressure is increased to 30 to 40 mm Hg in the rat and 44 mm Hg in the dog. A much smaller change in tubular pressure can contribute greatly to the development of filtration failure, however, when occurring in association with major change in individual vascular resistances. Glomerular capillary resistance must be increased to a value more than twice the normal sum of RA and RE (greater than fivefold in the dog), and glomerular capillary hydraulic conductivity lowered to below 5% of control, as isolated changes, before full filtration failure is approached. There is no reason to believe that most forms of ARF relate to only a single abnormality, however, and the effect of concomitant changes in individual resistances, hydraulic conductivity and proximal tubule pressure on glomerular filtration and blood flow is presented in the text and figures. A possible mechanism by which altered blood viscosity at the efferent arteriole may contribute to ARF is discussed and quantified. The degree of change in any determinant required to exert a given effect on filtration is independent of etiology, thus rendering the results of this analysis equally valid for any other pathological event which causes a significantly reduced GFR in the rat or dog.

Acute Kidney Injury↗
PubMed1982

An analysis of glomerular dynamics in rat, dog, and man.

A network thermodynamic model was utilized to assess similarities and dissimilarities in the predicted response of human, rat, and dog glomeruli to change in the independent variables regulating glomerular filtration. The analysis in rat and dog employed basal values reported in the micropuncture literature. The analysis in man was based on a calculated total nephron vascular resistance (Rt) of 1.2 X 10(10) dyne sec cm-5 with a range of pre- (Ra) and postglomerular (Re) resistances and capillary hydraulic conductivities (Kf) that would provide a nephron blood flow (GBF) of approximately 550 nl/min and single nephron filtration rate (SNGFR) of approximately 65 nl/min. The maximal putative value for Ra/Re in man was approximately 1.1, a ratio demanding a Kf greater than 20 nl/min mm Hg to obtain the required SNGFR. Solitary changes in Ra and Re, glomerular capillary resistance, proximal tubule pressure, serum protein concentration, total vascular resistance, and Kf were induced and the resultant effect on SNGFR was examined in the three species. The relationship between changes in individual resistances, glomerular blood flow, glomerular filtration, and glomerular capillary pressure also was assessed. The patterns of response in man and dog, determined by the model, were remarkably similar and distinct from those of the rat in many regards. Except when the maximal possible Ra/Re ratio is assumed for man, filtration pressure equilibrium was not found; plasma flow dependence of SNGFR was not evident in rat, dog, or man. The differences in SNGFR control predicted for the rat, on the one hand, and dog and man on the other may have distinct physiologic significance.

Animals↗
PubMed1982

Internephron heterogeneity of filtration fraction and disparity between protein- and hematocrit-derived values.

The variability of single nephron filtration fraction (SNFF) and the relationship between filtration fractions determined simultaneously from 125I albumin (SNFFALB) and hematocrit (SNFFHCT) values were assessed by multiple samplings, 5 to 8 per kidney, in normal, hydropenic, Munich-Wistar rats. Single nephron filtration rate (SNGFR) measurements served as an independent marker of internephron heterogeneity. Whether derived as SNFFALB or SNFFHCT, a wide degree of internephron variability in SNFF, comparable to that found for SNGFR (P greater than 0.2) was observed in all kidneys. Hematocrit-derived SNFF values, however, were some 80% higher than those obtained with 125I albumin (SNFFHCT 0.447 +/- SEM 0.016 versus SNFFALB 0.258 +/- 0.009, P less than 0.001). The disparity in results obtained by the two methods disappears if the efferent arteriolar hematocrit (Hctg) is assigned a value 17 +/- SEM 1.4% higher than the corresponding femoral arterial hematocrit and might well be a reflection of the perfusion of superficial glomeruli with erythrocyte rich blood produced by the "plasma-skimming" phenomenon. The data suggest that multiple estimates of SNGFR and SNFF in a given rat kidney are needed to provide representative mean values for glomerular dynamic studies.

Animals↗
PubMed1981

A network thermodynamic model of glomerular dynamics: application in the rat.

A model of glomerular dynamics has been developed by using network thermodynamics and the SPICE 2 computer program to further explore the determinants of glomerular filtration. The model is designed to be holistic and self-adjusting, taking cognizance of and permitting quantitation of the secondary alterations in individual effective glomerular resistances, glomerular blood and plasma flow, capillary oncotic pressure and glomerular capillary pressure, which inevitably result when any parameter affecting glomerular dynamics changes. Such automatic adjustment adds to the precision of computation and is unique to the present model. Few assumptions are introduced, independent variables (arterial pressure, individual resistances, hydraulic conductivity, hematocrit, and serum protein concentration) being entered whereas values for the dependent variables are determined by the computer. In rats, filtration pressure equilibrium is seen not to obtain either under physiologic conditions or with reasonably large changes in any of the independent variables. Capillary pressure is shown to be affected by any maneuver that modulates single nephron GFR (SNGFR) and flow across the efferent arteriole (for example, tubule pressure, serum protein concentration) even when arteriolar caliber is held constant. The axial rise in colloid oncotic pressure and serum protein concentration along the capillary is found to be neither linear nor semilogarithmic, a characteristic that reflects on equations used to determine capillary hydraulic conductivity. Isolated change in afferent arteriolar resistance is shown by the model to produce a linear relationship between glomerular plasma flow and capillary pressure, and thus between the former parameter and filtration. Large solitary increases in efferent arteriolar resistance raise SNGFR and a 60% fall in resistance virtually abolishes filtration while exerting little change in blood flow. Concomitant and equal alterations of afferent and efferent arteriolar resistances cause filtration to rise linearly with blood flow but to produce minor change in glomerular capillary pressure, an example of true plasma flow dependence. Plasma flow dependence is, however, found to be unique to this particular circumstance under physiologic conditions. Adding an optional element that automatically adjusts effective efferent arteriolar resistance as a function of Hct2 has but modest effects on glomerular dynamics except when systemic hematocrit is substantially altered. The data and conclusions derived in this study are based on typical values for resistances, hydraulic conductivity, systemic protein concentration, hematocrit, and arterial and tubular pressures reported for normal hydropenic rats. They will not necessarily hold in other species in which these values may be distinctly different.

Animals↗
PubMed1981

Filtration pressure equilibrium: a statistical analysis.

Statistical analysis of data in published micropuncture studies was applied to determine: a) the number of rats and samples of glomerular capillary pressure (Pg), end-capillary oncotic pressure (COPE), and proximal tubule pressure (Pt), needed in a single study to state with 95% confidence that a measured mean net efferent effective filtration pressure (delta P*E) is within +/- mmHg of any true value, delta PE; b) the effect of intra-animal variation in Pg, COPE, and Pt values on the number of experiments needed; and c) the probability of obtaining a value for delta P*E that meets this criterion in multiple trials. Assuming no intra-animal variation in Pg, Pt, and COPE values and employing published interanimal variances, at least 42 rats should be studied in any series to show that -1 mmHg less than or equal to (delta P*E -- delta PE) less than or equal to 1 mmHg within 95% confidence limits. If intra-animal variances are 60% of the interanimal variances, 67 rats are needed to obtain that degree of confidence when a single measurement of Pt, Pg, and COPE is made in each rat, and 47 animals are required with five measurements per rat. A value for delta P*E within 2-3 mmHg of its true value is, however, attainable with confidence using a far smaller number of animals per series.

Animals↗