Augmentation Of Glomerular Filtration Rate Research Articles

Protein intake and renal function in older patients.

Chronic kidney disease (CKD) is highly prevalent in elderly patients. There is growing recognition of the importance of attention to dietary protein intake (DPI) in this population given their predisposition to age-related changes in kidney function and coexisting comorbidities (i.e., hypertension). We reviewed the impact of DPI on kidney health and survival and the role of dietary protein management in older CKD patients. While kidney function parameters including glomerular filtration rate (GFR) and renal plasma flow are slightly lower in elderly patients irrespective of CKD status, the kidneys' ability to compensate for increased DPI by augmentation of GFR is preserved until 80 years of age or less. However, long-term consumption of high DPI in individuals of older age and/or with CKD may contribute to kidney function deterioration over time. Prescription of a plant-dominant low-protein diet of 0.6-0.8 g/kg/day with more than 50% from plant sources or very low protein diets less than 0.45 g/kg/day supplemented with essential amino acids or their keto-analogues may be effective in preserving kidney function in older patients and their younger counterparts, while also monitoring for development of protein-energy wasting (PEW). Using tailored precision nutrition approaches in prescribing plant-dominant low DPI that also maintains adequate energy and nitrogen balance may ameliorate kidney function decline while also preventing development of PEW in elderly patients with CKD.

Calcium antagonists and the kidney. Implications for renal protection.

During the past decade, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they alter dramatically the response of this preparation to vasoconstrictor agents. Our recent studies using the isolated perfused hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, demonstrated that the preferential augmentation of glomerular filtration rate observed in the isolated perfused kidney is attributable to preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations have not been fully delineated, the results of recent studies indicate that calcium antagonists exert salutary effects on renal function in clinical settings characterized by impaired renal hemodynamics. Such disorders include radiocontrast-induced nephrotoxicity and transplant-associated acute renal insufficiency. It is apparent, however, that the renal hemodynamic effects of calcium antagonists commend their use in the management of essential hypertension.

Calcium antagonists and the kidney.

Recently, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonist exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists markedly augment glomerular filtration rate but produce only a modest improvement in renal perfusion. Utilizing the isolated perfused hydronephrotic rat kidney model that permits direct visualization of afferent and efferent arterioles, we have demonstrated that this preferential augmentation of glomerular filtration rate is primarily attributable to a selective vasodilation of pre-glomerular vessels. Although the clinical implications of such observations are not yet clear, preliminary studies in experimental animal models indicate that calcium antagonists may exert salutary effects on renal function in clinical settings that are characterized by impaired renal hemodynamics. The possible benefits of calcium antagonists in ameliorating the development of renal dysfunction in patients in whom there is increased risk for the development of acute renal insufficiency remain to be evaluated.

Calcium antagonists and renal hemodynamics

During the past decade, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of this preparation to vasoconstrictor agents. Our recent studies with the isolated perfused hydronephrotic rat kidney model, which permits visualization of afferent and efferent arterioles, have demonstrated that the augmentation of glomerular filtration rate observed in the isolated perfused kidney is attributable to preferential vasodilation of preglomerular vessels. Although the clinical implications of such observations have not been fully delineated, the results of recent studies indicate that calcium antagonists exert salutary effects on renal function in patients with impaired renal hemodynamics. Such disorders include radiocontrast-induced nephrotoxicity and transplant-associated acute renal insufficiency. It is apparent, however, that the effects of calcium antagonists on renal blood flow commend their use in the management of essential hypertension.

Cytochrome P-450 arachidonate metabolites in rat kidney: characterization and hemodynamic responses

Rat kidney cortical and medullary microsomal fractions catalyzed cytochrome P-450-linked metabolism of arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs) (56 +/- 6% of total products in cortex and 10% in medulla) and 19- and 20-hydroxyeicosatetraenoic acids (19- and 20-OHAA) (36 +/- 4% in cortex and 90% in medulla). In addition, endogenous renal generation of EETs was established by negative ion-chemical ionization mass spectrometry. The total amount of EETs present in the rat kidney was approximately 1 microgram/g wet tissue. The responses to renal arterial administration of 20-OHAA and 5,6-EET were evaluated in anesthetized euvolemic rats. 20-OHAA resulted in ipsilateral dose-dependent natriuresis without affecting systemic or renal hemodynamics or glomerular filtration rate (GFR). Equimolar doses of 5,6-EET resulted in dose-dependent renal vasoconstriction and reduced GFR but were without effect on arterial pressure or sodium excretion. During cyclooxygenase inhibition, 5,6-EET caused renal vasodilatation and augmentation of GFR. These data establish the capacity of rat kidney to metabolize AA through cytochrome P-450-dependent oxygenases and demonstrate the endogenous formation of the resulting eicosanoids. Monooxygenase and epoxygenase products exert effects on renal blood flow, GFR, and urinary sodium excretion rate, suggesting their potential relevance in the regulation of renal function.

Effects of amlodipine on renal hemodynamics

Recently, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of the kidney to vasoconstrictor agents. This study examined the effects of the novel dihydropyridine amlodipine on the hemodynamic response of the isolated perfused kidney to angiotensin II. Amlodipine completely reversed the angiotensin II-induced decrement in glomerular filtration rate of this model (0.72 ± 0.15, 0.26 ± 0.10 and 0.73 ± 0.12 ml/min/g for control, angiotensin II and angiotensin II plus 0.1 μM amlodipine, respectively). In contrast, amlodipine only partially restored renal perfusate flow (35.8 ± 2.7, 14.7 ± 1.9 and 23.7 ± 2.5 ml/min/g for control, angiotensin II and angiotensin II plus amlodipine), thereby increasing filtration fraction. These findings are consistent with previous observations from this laboratory indicating that dihydropyridines predominantly vasodilate preglomerular renal resistance vessels and through this mechanism exert a preferential augmentation of glomerular filtration rate.

Calcium antagonists and the kidney.

Recently, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions, permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists markedly augment the glomerular filtration rate, but produce only a modest improvement in renal perfusion. By use of the postischemic, hydronephrotic rat kidney model, which permits direct visualization of afferent and efferent arterioles, it can be demonstrated that the above-mentioned preferential augmentation of glomerular filtration rate may be attributable to a selective vasodilation of preglomerular vessels. Although the clinical implications of such observations are not yet clear, preliminary studies in experimental animal models indicate that calcium antagonists might exert salutary effects on renal function in clinical settings characterized by impaired renal hemodynamics. There is a need to carry out prospective studies to determine the benefits of calcium antagonists in ameliorating the development of renal dysfunction in patients at risk of acute renal insufficiency.

Renal Hemodynamic Effects of Calcium Antagonists

Recently, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists markedly augment glomerular filtration rate but produce only a modest improvement in renal perfusion. This preferential augmentation of glomerular filtration rate may be attributable to a selective vasodilation of preglomerular vessels. Although the clinical implications of such observations are not yet clear, preliminary studies in experimental animal models indicate that calcium antagonists may exert salutary effects on renal function in clinical settings that are characterized by impaired renal hemodynamics. The possible benefits of calcium antagonists in ameliorating the development of renal dysfunction in patients in whom there is increased risk for the development of acute renal insufficiency remain to be evaluated.

Renal Hemodynamic Effects of Calcium Antagonists

Recently, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists markedly augment glomerular filtration rate but produce only a modest improvement in renal perfusion. This preferential augmentation of glomerular filtration rate may be attributable to a selective vasodilation of preglomerular vessels. Although the clinical implications of such observations are not yet clear, preliminary studies in experimental animal models indicate that calcium antagonists may exert salutary effects on renal function in clinical settings that are characterized by impaired renal hemodynamics. The possible benefits of calcium antagonists in ameliorating the development of renal dysfunction in patients in whom there is increased risk for the development of acute renal insufficiency remain to be evaluated.

Renal hemodynamic effects of calcium antagonists

Although the cardiovascular actions of calcium antagonists have been studied extensively, it is only recently that attention has focused on the effects of calcium antagonists on renal function. Variable actions of calcium antagonists on renal hemodynamics have been observed when these agents are used in experimental animal models. In contrast, when administered in vitro to the isolated perfused kidney, calcium antagonists demonstrate more predictable actions. Calcium antagonists do not affect the vasodilated isolated kidney, but they do dramatically alter the response of the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists produce a modest improvement in renal perfusion and significantly augment glomerular filtration rate. This preferential augmentation of glomerular filtration rate may be attributable to a selective vasodilation of pre-glomerular vessels. Although the clinical implications of such observations are not yet clear, preliminary studies indicate that calcium antagonists may exert salutary effects on renal function in clinical settings that are characterized by impaired renal hemodynamics. The possible benefits of calcium antagonists in ameliorating the development of renal dysfunction in patients in whom there is increased risk for the development of acute renal insufficiency remain to be evaluated.

Modification of the renal hemodynamic response to vasoconstrictors by calcium antagonists.

Theoretical considerations suggest that the renal response to calcium antagonists may vary depending on the factors influencing basal vascular tone. Studies were conducted using the isolated perfused rat kidney to determine the response to calcium antagonists under conditions in which the determinants of renal vascular tone were accurately defined. With this model, calcium antagonists elicit vasodilation only in the presence of a vasoconstrictor. In this setting, however, the degree of vasodilation elicited depends on the nature of the vasoconstrictor employed. Thus, the reduction in renal perfusate flow (RPF) elicited by KCl-induced depolarization was completely reversed by the calcium antagonist, nitrendipine. In contrast, identical levels of vasoconstriction elicited by norepinephrine or angiotensin II were only partially reversed, suggesting that these agonists activate the renal vasculature by mechanisms that are more complex than membrane depolarization. Examination of the response of glomerular filtration rate (GFR) revealed that in the presence of norepinephrine and angiotensin II, nitrendipine exerted a preferential augmentation of GFR. Thus, concentrations that produced only modest effects on RPF increased GFR to levels equal to or exceeding control values. This selective augmentation of GFR did not occur during the renal vasoconstriction elicited by KCl. It is proposed that renal microvessels exhibit regional heterogeneity in regard to activation mechanisms and sensitivity to calcium antagonists. Calcium antagonists may selectively attenuate agonist-induced vasoconstriction of preglomerular vessels.