The Path to Wearable Ultrafiltration and Dialysis Devices

Wearable blood processing devices offer an attractive solution to problems inherent in clinic-based, intermittent end-stage renal disease therapies. What is involved in transitioning even a part of the current clinic-based population to ambulatory therapy has not been clearly enumerated. This paper addresses what a first-generation wearable device might accomplish, how issues of safety will need to be addressed, and what will make the device attractive to, and manageable by, the patient. Medical, technological, and economic issues are identified

Dependence of Saline-Induced Natriuresis upon Exposure of the Kidney to the Physical Effects of Extracellular Fluid Volume Expansion

In many previous studies, the natriuresis induced by saline loading has been demonstrated to persist even though glomerular filtration rate (GFR) has been decreased to below pre-expansion levels by a reduction in renal artery pressure. In such studies, however, the kidney has been exposed to the effects of volume expansion for varying periods of time before renal artery pressure was controlled. The present experiments were designed to evaluate whether this period of exposure induces critical changes in intrarenal factors that are responsible for the natriuresis. Experiments were carried out in rats, in which renal artery pressure was decreased to 70 mm Hg either at the onset of saline loading (immediate clamping experiments) or after 45 min of saline loading had elapsed (delayed clamping experiments). In the delayed clamping experiments, consonant with previous studies, mean sodium excretion, 3.2 μeq/min, remained markedly increased above control, despite a reduction in GFR to 91% of the hydropenic control value. In contrast, when renal artery pressure was comparably reduced at the onset of saline loading mean sodium excretion was only trivially increased, 0.4 μeq/min, although GFR increased to 140% of the hydropenic control value. These results exclude an important role for either a circulating hormone or a reduction in plasma oncotic pressure in the natriuretic response to saline loading, and indicate that intrarenal factors are the critical determinants of the natriuresis. We have used the difference in response to saline loading in the immediate and delayed clamping experiments to evaluate the role of two intrarenal factors, interstitial hydrostatic pressure and renal plasma flow. Interstitial pressure changes were estimated from changes in tubular pressure and diameter by using the in situ compliance characteristics of the tubules. In a group of rats saline loaded without aortic clamping, interstitial pressure increased by 4-5 mm Hg and renal plasma flow increased by 2.5 ml/min. During the period of reduced renal artery pressure, however, neither interstitial pressure nor renal plasma flow was detectably increased above control in either the immediate or the delayed clamping experiments. The only noteworthy difference between the experiments in which a natriuresis occurred (unclamped and delayed clamping studies) and the experiments in which no natriuresis occurred is that in the former group the kidney was at least transiently exposed both to an increase in renal plasma flow and interstitial pressure. These findings indicate, first, that extracellular fluid volume expansion can induce a natriuresis only if the kidney has been exposed to at least a transient increase in either interstitial hydrostatic pressure or renal plasma flow (or both); and, second, that a sustained increase in interstitial pressure and renal plasma flow is not required for the natriuresis to persist

Effect of variations in dietary sodium intake on sodium excretion in mature rats

Effect of variations in dietary sodium intake on sodium excretion in mature rats. Sprague-Dawley rats weighing 400g or more were studied to determine whether their continued weight gain affects renal sodium handling. Rats maintained on a wide range of sodium intakes gained 3.9 ± 0.4 g/day. The intercept of a linear regression of intake against urinary excretion provided an estimate of the minimum daily requirement for sodium intake of 247 ±33 µEq/day. When more than this required amount was ingested, the animals excreted the excess quantitatively in the urine. When less was ingested they continued to gain weight at a slower rate, 1.6 ± 0.6 g/day, and remained in positive sodium balance. Nonetheless, they developed a sodium deficit manifested as retention of a sodium challenge. Thus, on an adequate dietary intake the normal physiological state of Sprague-Dawley rats of this size is one of chronic sodium retention rather than neutral sodium balance. In contrast, when inadequate sodium is ingested a deficit develops in the absence of external losses. These observations have important implications for the interpretation of studies of renal sodium handling in these animals.Effet de variations de l'apport sodé alimentaire sur l'excrétion sodique de rats matures. Des rats Sprague-Dawley pesant 400g ou plus ont été étudiés pour déterminer si leur prise de poids continue affecte l'élimination sodée rénale. Des rats maintenus à des apports sodés très variés gagnaient 3,9 ± 0,4 g/jour. L'interception de la régression linéaire de l'apport en fonction de l'excrétion sodée fournissait une estimation de l'apport quotidien minimum nécessaire en sodium, 247 ± 33 µEq/jour. Lorsque plus que cette quantité nécessaire était ingéré, les animaux excrétaient quantitativement cet excès dans les urines. Lorsqu'ils ingéraient moins, ils continuaient à prendre du poids plus lentement, 1,6 ± 0,6 g/jour, et restaient en balance sodée positive. Néanmoins, ils développaient un déficit sodé se manifestant par la rétention d'une surcharge sodée. Ainsi, lors d'un apport alimentaire adéquat, l'état physiologique normal des rats Sprague-Dawley de cette taille est une rétention chronique du sodium, plus qu'une balance sodée neutre. A l'opposé, lorsqu'insuffisamment de sodium est ingéré, un déficit se développe en l'absence de pertes externes. Ces observations ont des implications importantes pour l'interprétation des études de l'élimination rénale du sodium chez ces animaux