Impairment of renal sodium excretion in tropical residents – phenomenological analysis

There is evidence of impaired renal sodium excretion in salt-sensitive African Blacks. A decreased rate of renal sodium chloride (NaCl) excretion, low plasma renin activity and a tendency to elevated blood pressure are the hallmarks of salt sensitivity. Recent evidence indicates that increased proximal and distal tubular fluid reabsorption in some tropical residents may explain the impaired sodium excretion in these people. In this study of a cohort population, we speculated that subjects selected from that population might be salt-sensitive. We therefore measured the sodium balance in 10 normotensive male subjects over 10 consecutive days, after they had ingested a normal or a high amount of sodium, as NaCl (salt) in their diet. We quantified their renal sodium excretion rate by phenomenological analysis of their sodium balance data. We also measured plasma renin activity for 7 consecutive days in a separate group of 6 male and 4 female subjects in order to assess the state of their renin/angiotensin system. We selected all our subjects from a cohort population of 269 subjects randomly selected from a community known to have a high prevalence of primary hypertension. Our data on two separate groups of subjects from the same cohort population revealed delayed renal sodium excretion with t _1/2 of about 5 days, compared to published data for normal individuals with t _1/2 of less than 24 h. Also, plasma renin activity levels were low. Hence, our subjects are salt-sensitive. Quantification of their renal impairment is important for various reasons: it heightens one’s appreciation of the problem of salt retention in African Blacks who are salt-sensitive and it also underlines the importance of the need for further research into the benefits of dietary salt restriction for reducing cardiovascular mortality in African populations, as has been done in some Western countries. Received: 4 March 1999 / Accepted: 12 May 1999     

Effect of saline infusion on kidney and collecting duct function in atrial natriuretic peptide (ANP) gene "knockout" mice.

Atrial natriuretic peptide (ANP) is thought to play a role in renal regulation of salt balance by reducing tubular reabsorption of sodium and chloride. Therefore, in the chronic absence of this hormone, a defect of salt excretion should be evident. We used an ANP gene deletion model to test this premise. F2 homozygous mutant mice (-/-) and their wild-type littermates (+/+) were fed an 8% NaCl diet prior to an acute infusion of isotonic saline. Arterial blood pressures, renal excretions of salt and water, as well as collecting duct transport of fluid and electrolytes were measured. Pressures were significantly higher in -/- compared with +/+ mice (139 +/- 4 vs. 101 +/- 2 mmHg; 1 mmHg = 133.3 Pa). There was no difference in glomerular filtration rate (-/- = 0.84 +/- 0.06; +/+ = 0.81 +/- 0.04 mL x min(-1) x g(-1) kidney weight). In the collecting duct, sodium and chloride reabsorptions were significantly higher in the -/- group than in the +/+ group. As a result, natriuresis and chloruresis were relatively reduced (U(Na)V: -/- = 8.6 +/- 1.1; +/+ = 14.0 +/- 1.1; U(Cl)V: -/- = 10.1 +/- 1.4; +/+ = 16.0 +/- 1.1 micromol x min(-1) x g(-1) kidney weight). We conclude that the absence of endogenous ANP activity in mice on a high-salt diet subjected to acute saline infusion causes inappropriately high reabsorption of sodium and chloride in the medullary collecting duct, resulting in a relative defect in renal excretory capacity for salt.     

Renal mechanisms involved in stress-induced antinatriuresis and antidiuresis in rats

The present study was conducted to investigate if changes in sodium and water excretion in stressed animals were due to modifications in the glomerular filtration rate (GFR) and to determine the participation of angiotensin II (Ang II) and alpha and beta-adrenoceptors on sodium and water renal excretion in rats subjected to immobilization stress (IMO). Male Wistar rats (250-300 g) were randomly separated into five different groups and vehicle (0.9% NaCl) via intraperitoneal (i.p.) or propanolol (3 mg/kg i.p.) or captopril (6 mg/kg i.p.) or yohimbine (3 mg/kg i.p.) or prazosin (1 mg/kg i.p.) were injected respectively. During experimental measurements, the animals were kept in metabolic cages for 6 h and sodium, potassium and water renal excretion and saline (1.5% NaCl) and water intake were determined at day 1 (drug effect) and day 7 (drug + IMO effects). GFR was measured by creatinine clearance in control and IMO rats. A stress-induced antinatriuresis and antidiuresis was reversed by alpha 1 and alpha 2-adrenoceptor antagonists, while captopril inhibited only the antidiuresis and propranolol had no effect on either parameter. No differences were observed in creatinine clearance in the studied groups. Since yohimbine blocks alpha 2-adrenoceptors and prazosin blocks alpha 1-adrenoceptors and alpha 2B-adrenoceptors, the stress-induced renal sodium reabsorption mainly could be attributed to alpha 2B-adrenoceptors. The present results indicate that beta-adrenoceptors do not participate in this response and, Ang II only reverses the antidiuresis and shows a slight participation in antinatriuresis. The increment in sodium and water reabsorption caused by IMO occurred without changes in the glomerular filtration rate.     

The effects of reducing dietary nitrogen and of increasing sodium chloride intake on urea excretion and reabsorption and on urine osmolality in sheep.

Renal responses to reducing dietary nitrogen were studied in four ewes during intravenous infusion of arginine vasopressin. The fall in urea excretion and in plasma urea concentration was accompanied by significant reduction in GFR and in urine osmolality. The fraction of filtered urea reabsorbed increased despite reduction in the urea U/P concentration ratio and this increase was sustained when the urea U/P ratio was further reduced at higher urine flows observed when the drinking water was replaced with saline. This procedure also sustained the RPF which in the absence of additional salt was significantly reduced on the low protein diet. It is suggested that the fall in GFR and the increase in the fraction of filtered urea reabsorbsed may contribute to nitrogen economy and that the increase in fractional reabsorption and the reduction in urine osmolality on the low protein diet provided evidence of active reabsorption of urea by renal tubules.     

Renal function in the freshwater rainbow trout after dietary cadmium acclimation and waterborne cadmium challenge

Renal function was examined in adult rainbow trout (Oncorhynchus mykiss) after chronic exposure to a sublethal level of dietary Cd (500 mg/kg diet) for 52 d and during a subsequent challenge to waterborne Cd (10 microg/L) for 72 h. Dietary Cd had no major effects on UFR (urine flow rate) and GFR (glomerular filtration rate) but caused increased renal excretion of glucose, protein, and major ions (Mg(2+), Zn(2+), K(+), Na(+), Cl(-) but Ca(2+)). However, dietary Cd did not affect any plasma ions except Na(+) which was significantly elevated in the Cd-acclimated trout. Plasma glucose and ammonia levels fell by 25% and 36% respectively, but neither plasma nor urine urea was affected in Cd-acclimated fish. Dietary Cd exposure resulted in a remarkable increase of Cd load in the plasma (48-fold, approximately 22 ng/mL) and urine (60-fold, 8.9 ng/mL), but Cd excretion via the kidney was negligible on a mass-balance basis. Clearance ratio analysis indicates that all ions, Cd, and metabolites were reabsorbed strongly (58-100%) in both na?ve and dietary Cd exposed fish, except ammonia which was secreted in both groups. Mg(2+), Na(+), Cl(-) and K(+) reabsorption decreased significantly (3-15%) in the Cd-exposed fish relative to the control. Following waterborne Cd challenge, GFR and UFR were affected transiently, and only Mg(2+) and protein excretion remained elevated with no recovery with time in Cd-acclimated trout. Urinary Ca(2+) and Zn(2+) excretion rates dropped with an indication of renal compensation towards plasma declines of both ions. Cadmium challenge did not cause any notable effects on urinary excretion rates of metabolites. However, a significant decrease in Mg(2+) reabsorption but an increase in total ammonia secretion was observed in the Cd-acclimated fish. The study suggests that dietary Cd acclimation involves physiological costs in terms of renal dysfunction and elevated urinary losses.     

Study of Na+ and Water Transport in the Pigeon and Chicken Kidney by Lithium Clearance Method under Conditions of Water and Salt Load: Regimes of Renal Net Reabsorption and Net Secretion of Li+

The water (intestinally) and salt (intravenously) loads of a sufficient intensity (about 120 ml water or 9 mmol NaCl per kg body mass) caused a reversible conversion (of duration of 30–40 min) in the renal Li transport, i.e., transition from net reabsorption of this ion (FE_Li = C_Li/GFR < 1) to its net secretion (FE_Li > 1), where C_Li—lithium clearance, GFR—glomerular filtration rate, ⁶⁵ZnDTPA clearance. Maximal values of the fractional lithium excretion (FE_Li) amounted to about 1.5 and 2.0 after the water and salt loads, respectively. A repeated salt load (4–5 NaCl injections by 9 mmol/kg at 20–40 min intervals) induced a long (2–3 h) net secretion of lithium in the chicken kidney. This regime of renal functioning was characterized by abundant urination (20–30 ml/kg/h) and a substantial increase of the Na⁺ concentration in blood plasma (from 138 ± 9 to 172 ± 10 mM, the mean ( standard deviation) and in urine (to 157 ± 19 mM). The data obtained were considered in terms of a hypothesis suggesting that the renal lithium secretion indicates the appearance of net water and Na⁺ secretion in the proximal tubule of the avian kidney in response to water and salt load. The fractional reabsorption of Na⁺ and water in the chicken kidney were calculated by means of lithium clearance during both the net reabsorption and the secretion of lithium in the kidney. In the former regime of renal functioning (FE_Li < 1), regardless of changes in lithium reabsorption (up to its complete cessation at FE_Li = 1), the kidney as a whole reabsorbs about 99% of filtered Na⁺, while distal reabsorption of this ion accounts for about 98%. The corresponding values for water reabsorption are about 96 and 92%, respectively. At FE_Li > 1, the fractional reabsorption of Na⁺ and water decrease significantly: the minimal values amount to about 60%, while the mean values, about 80%.     

Regulation of salt gland, gut and kidney interactions

Marine birds can drink seawater because their cephalic 'salt' glands secrete a sodium chloride (NaCl) solution more concentrated than seawater. Salt gland secretion generates osmotically free water that sustains their other physiological processes. Acclimation to saline induces interstitial water and Na move into cells. When the bird drinks seawater, Na enters the plasma from the gut and plasma osmolality (Osm(pl)) increases. This induces water to move out cells expanding the extracellular fluid volume (ECFV). Both increases in Osm(pl) and ECFV stimulate salt gland secretion. The augmented intracellular fluid content should allow more rapid expansion of ECFV in response to elevated Osm(pl) and facilitate activation of salt gland secretion. To fully utilize the potential of the salt glands, intestinally absorbed NaCl must be reabsorbed by the kidneys. Thus, Na uptake at gut and renal levels may constrain extrarenal NaCl secretion. High NaCl intake elevates plasma aldosterone concentration of Pekin ducks and aldosterone stimulates intestinal and renal water and sodium uptake. High NaCl intake induces lengthening of the small intestine of adult Mallards, especially males. High NaCl intake has little effect on glomerular filtration rate or tubular sodium Na uptake of birds with competent salt glands. Relative to body mass, kidney mass and glomerular filtration rate (GFR) are greater in birds with salt glands than in birds that do not have them. Birds with salt glands do not change GFR, when they drink saline. Thus, their renal filtrate contains excess Na that is, in some species, almost completely renally reabsorbed and excreted in a more concentrated salt gland secretion. Na reabsorption by kidneys of other species, like mallards is less complete and their salt glands make less concentrated secretion. Such species may reflux urine into the hindgut, where additional Na may also be reabsorbed for extrarenal secretion. During exposure to saline, marine birds maintain elevated aldosterone levels despite high Na intake. Marine birds are excellent examples of physiological plasticity.     

Infiltrating T lymphocytes in the kidney increase oxidative stress and participate in the development of hypertension and renal disease

The present studies examined the role and mechanism of action of infiltrating T lymphocytes in the kidney during salt-sensitive hypertension. Infiltrating T lymphocytes in the Dahl salt-sensitive (SS) kidney significantly increased from 7.2 ± 1.8 × 10(5) cells/2 kidneys to 18.2 ± 3.9 × 10(5) cells/2 kidneys (n = 6/group) when dietary NaCl was increased from 0.4 to 4.0%. Furthermore, the expression of immunoreactive p67(phox), gp91(phox), and p47(phox) subunits of NADPH oxidase was increased in T cells isolated from the kidneys of rats fed 4.0% NaCl. The urinary excretion of thiobarbituric acid-reactive substances (TBARS; an index of oxidative stress) also increased from 367 ± 49 to 688 ± 92 nmol/day (n = 8/group) when NaCl intake was increased in Dahl SS rats. Studies were then performed on rats treated with a daily injection of vehicle (5% dextrose) or tacrolimus (0.25 mg·kg(-1)·day(-1) ip), a calcineurin inhibitor that suppresses immune function, during the period of high-NaCl intake (n = 5/group). In contrast to the immune cell infiltration, increased NADPH oxidase expression, and elevated urine TBARS excretion in vehicle-treated Dahl SS fed high salt, these parameters were unaltered as NaCl intake was increased in Dahl SS rats administered tacrolimus. Moreover, tacrolimus treatment blunted high-salt mean arterial blood pressure and albumin excretion rate (152 ± 3 mmHg and 20 ± 9 mg/day, respectively) compared with values in dextrose-treated Dahl SS rats (171 ± 8 mmHg and 74 ± 28 mg/day). These experiments indicate that blockade of infiltrating immune cells is associated with decreased oxidative stress, an attenuation of hypertension, and a reduction of renal damage in Dahl SS rats fed high salt.     

Effects of exenatide on glycemia and renal water and ion excretion differ in frogs and rats

The aim of this study was to compare the effects of exenatide, a glucagon-like peptide-1 (GLP-1) mimetic, on glucose and water–salt homeostasis in animals with different levels of renal proximal tubular reabsorption, rats (Rattus norvegicus) and frogs (Rana temporaria). Following the glucose tolerance test, in rats exenatide promoted fast recovery of normoglycemia, whereas in frogs it delayed this process. In water-loaded rats, exenatide augmented solute-free water clearance and enhanced natriuresis in furosemide-treated animals. In frogs, exenatide did not alter the urinary flow rate, urinary sodium excretion and solute-free water clearance under water diuresis and furosemide treatment. It is suggested that the involvement of GLP-1 in regulation of water–salt homeostasis in mammals was preceded by a key evolutionary transformation, the increase in the glomerular filtration rate and proximal tubular reabsorption.     

Sodium excretion rates and renal responses to acute salt loading in the European starling

Summary Renal clearance studies were performed in European starlings (Sturnus vulgaris) in order to determine the extent of ureteral sodium excretion under control conditions and during an acute, hyperosmotic salt stress. These experiments also estimated the contribution of the lower intestine (colon and cloaca) to postrenal solute reabsorption by making both cloacal and ureteral urine collections in the same birds. A comparison of ureteral vs cloacal excretion rates found significantly higher sodium (9.09±1.30 vs 1.03±0.38 Eq·kg^–1·min^–1) and chloride (4.15±0.56 vs 1.00±0.38 Eq·kg^–1·min^–1) excretion rates during the ureteral collections. Fractional excretion of sodium was also significantly higher during ureteral collections, but this value did not exceed 1% of the filtered sodium load during either collection series. Urine flow rate was significantly higher during cloacal collections, suggesting osmotic back-flux of water across the cloacal wall. Infusion of a 1M NaCl solution resulted in rapid increases in glomerular filtration rate (GFR), urine flow rate, and urine osmolality. Fractional sodium and water reabsorption decreased by 11% and 4%, respectively. Glomerular counts and size distribution profiles, measured by in vivo alcian blue labelling, provided no evidence for a reduction in the number of filtering glomeruli during hyperosmotic saline loading. We conclude that renal sodium excretion rates for the starling are similar to those seen in other avian species and in mammals. These studies also provide direct evidence for postrenal modification of urine in this species, even under conditions of continuous flow. Acute hyperosmotic salt stress can, under some conditions, cause increased rather than decreased GFR, indicating multiple regulatory pathways. Finally, there was no evidence in these studies for glomerular shutdown in response to salt loading.     

Renal blood flow, early distal sodium, and plasma renin concentrations during osmotic diuresis

Inconsistencies in previous reports regarding changes in early distal NaCl concentration (ED(NaCl)) and renin secretion during osmotic diuresis motivated our reinvestigation. After intravenous infusion of 10% mannitol, ED(NaCl) fell from 42.6 to 34.2 mM. Proximal tubular pressure increased by 12.6 mmHg. Urine flow increased 10-fold, and sodium excretion increased by 177%. Plasma renin concentration (PRC) increased by 58%. Renal blood flow and glomerular filtration rate decreased, however end-proximal flow remained unchanged. After a similar volume of hypotonic glucose (152 mM), ED(NaCl) increased by 3.6 mM, (P < 0.01) without changes in renal hemodynamics, urine flow, sodium excretion rate, or PRC. Infusion of 300 micromol NaCl in a smaller volume caused ED(NaCl) to increase by 6.4 mM without significant changes in PRC. Urine flow and sodium excretion increased significantly. There was a significant inverse relationship between superficial nephron ED(NaCl) and PRC. We conclude that ED(Na) decreases during osmotic diuresis, suggesting that the increase in PRC was mediated by the macula densa. The results suggest that the natriuresis during osmotic diuresis is a result of impaired sodium reabsorption in distal tubules and collecting ducts.     

Glomerulotubular balance, dietary protein, and the renal response to glycine in diabetic rats

The glomerular filtration rate (GFR) normally increases during glycine infusion, which is a test of "renal reserve." Renal reserve is absent in diabetes mellitus. GFR increases after protein feeding because of increased tubular reabsorption, which reduces the signal for tubuloglomerular feedback (TGF). Dietary protein restriction normalizes some aspects of glomerular function in diabetes. Renal micropuncture was performed in rats 4-5 wk after diabetes was induced by streptozotocin to determine whether renal reserve is lost as a result of altered tubular function and activation of TGF, whether 10 days of dietary protein restriction could restore renal reserve, and whether this results from effects of glycine on the tubule. TGF activation was determined by locating single-nephron GFR (SNGFR) in the early distal tubule along the TGF curve. The TGF signal was determined from the ionic content of the early distal tubule. In nondiabetic rats, SNGFR in the early distal tubule increased during glycine infusion because of primary vasodilation augmented by increased tubular reabsorption, which stabilized the TGF signal. In diabetic rats, glycine reduced reabsorption, thereby activating TGF, which was largely responsible for the lack of renal reserve. In protein-restricted diabetic rats, the tubular response to glycine remained abnormal, but renal reserve was restored by a vascular mechanism. Glycine affects GFR directly and via the tubule. In diabetes, reduced tubular reabsorption dominates. In low-protein diabetes, the vascular effect is enhanced and overrides the effect of reduced tubular reabsorption.     

Renal function in the choline deficient rat.

Abnormalties in renal concentrating ability and free water reabsorption, and a diminished sodium excretion, glomerular filtration rate, and effective renal plasma flow were observed in adolescent rats which ingested a lipotrope deficient diet for 10 months.     

Endogenous sodium pump inhibitors and age-associated increases in salt sensitivity of blood pressure in normotensives

Factors that mediate increases in salt sensitivity of blood pressure with age remain to be clarified. The present study investigated 1) the effects of high-NaCl intake on two Na pump inhibitors, endogenous ouabain (EO) and marinobufagenin (MBG), in middle-aged and older normotensive Caucasian women; and 2) whether individual differences in EO and MBG are linked to variations in sodium excretion or salt sensitivity. A change from 6 days of a lower (0.7 mmol.kg(-1).day(-1))- to 6 days of a higher (4 mmol.kg(-1).day(-1))-NaCl diet elicited a sustained increase in MBG excretion that directly correlated with an increase in the fractional Na excretion and was inversely related to age and to an age-dependent increase in salt sensitivity. In contrast, EO excretion increased only transiently in response to NaCl loading and did not vary with age or correlate with fractional Na excretion or salt sensitivity. A positive correlation of both plasma and urine levels of EO and MBG during salt loading may indicate a casual link between two Na pump inhibitors in response to NaCl loading, as observed in animal models. A linear mixed-effects model demonstrated that age, dietary NaCl, renal MBG excretion, and body mass index were each independently associated with systolic blood pressure. Thus, a sustained increase in MBG in response to acutely elevated dietary NaCl is inversely linked to salt sensitivity in normotensive middle-aged and older women, and a relative failure of MBG elaboration by these older persons may be involved in the increased salt sensitivity with advancing age.     

肾髓质诱导型一氧化氮合酶在动脉血压调控中的作用

本文通过慢性血液动力学实验,观察了肾髓质局部输入诱导型一氧化酶（ｉＮＯＳ）抑制剂ＡＧ（ａｍｉｎｏｇｕａｎｉｄｉｎｅ）对Ｄａｈｌ盐敏感大鼠（ＤＳ）、Ｄａｈｌ盐抵抗大鼠（ＤＲ）及ＳＤ（Ｓｐｒａｇｕｅ Ｄａｗｌｅｙ）大鼠动脉血压的影响,并测定了一氧化氮（ＮＯ）代谢终产物ＮＯ２及ＮＯ３含量（ＵＮＯＸ）、ｉＮＯＳ活性、肾功能以及血浆肾素活性（ＰＲＡ）。结果表明：ＡＧ能明显放大高盐（８％）引起的ＤＳ及ＳＤ大鼠     

Effect of dietary energy intake on tubular reabsorption of urea in sheep

The aim of the experiment was to determine the effect of dietary energy intake on renal urea excretion in sheep with different nitrogen intakes. The control sheep, with a high nitrogen and energy intake, were given a daily feed dose of 21.18 g N and 15.2 MJ digestible energy (DE). The two experimental groups, with an equal, low nitrogen intake, were given diets with a different energy content. The high energy diet contained 3.63 g N and 14.18 MJ DE, the low energy diet 3.4 g N and 6.44 MJ DE. After nine weeks' adaptation to the diets, renal functions were measured by a standard clearance technique. It was found that, under stable urine flow conditions, both groups given the low nitrogen diet had a significantly lower glomerular filtration rate, fractional urea excretion and total urea excretion. A reciprocal comparison of these two groups showed that fractional urea excretion by the sheep with a high energy intake was significantly lower than in the group with a low energy intake. There were no differences in the glomerular filtration rate. A raised dietary energy intake in the presence of a low nitrogen intake caused marked natriuresis and kaliuresis. The results indicate that a raised dietary energy intake can be a significant factor in potentiating the renal effect of urea retention in sheep with a low nitrogen intake.     

Renal effects of an acute NaCl load in chronic nitric oxide blockade-induced hypertensive rats

Nitric oxide (NO) controls blood pressure and plays a role in the water and sodium handling by the kidneys. Inhibition of NO synthesis with competitive L-arginine analogues leads to increased renal vascular resistance and raised systemic and glomerular blood pressure. The effects of chronic NO-synthesis inhibition by N(G)-nitro L-arginine methyl-esther (L-NAME) in the disposal of an acute NaCl load are studied on fourteen male Munich-Wistar rats. Eight of which were given L-NAME (100 mg/L) in the drinking water for 21 days. Six control rats differed only in not receiving L-NAME. As expected, significant hypertension and a marked renal vasoconstriction were accompanied by a decline in renal plasma flow, without changes in glomerular filtration rate, with filtration fraction thus being increased in the NO-blocked rats. In the basal state there was no significant reduction of sodium urinary excretion in the L-NAME treated rats. Both groups of rats elicited an increase in urinary sodium excretion after the NaCl load which was initially more evident and longer in the L-NAME treated group. The ratio of Na+ excreted to Na+ infused was similar between the groups. This observation suggests that in this model of chronic inhibited NO rats, the disposal of an acute sodium load is reached. The existence of a delayed mechanism in renal excretion of Na+ by the chronic NO-blocked rats could be suggested.     

Acute Kidney Injury Urinary Biomarker Time-Courses

Factors which modify the excretion profiles of acute kidney injury biomarkers are difficult to measure. To facilitate biomarker choice and interpretation we modelled key modifying factors: extent of hyperfiltration or reduced glomerular filtration rate, structural damage, and reduced nephron number. The time-courses of pre-formed, induced (upregulated), and filtered biomarker concentrations were modelled in single nephrons, then combined to construct three multiple-nephron models: a healthy kidney with normal nephron number, a non-diabetic hyperfiltering kidney with reduced nephron number but maintained total glomerular filtration rate, and a chronic kidney disease kidney with reduced nephron number and reduced glomerular filtration rate. Time-courses for each model were derived for acute kidney injury scenarios of structural damage and/or reduced nephron number. The model predicted that pre-formed biomarkers would respond quickest to injury with a brief period of elevation, which would be easily missed in clinical scenarios. Induced biomarker time-courses would be influenced by biomarker-specific physiology and the balance between insult severity (which increased single nephron excretion), the number of remaining nephrons (reduced total excretion), and the extent of glomerular filtration rate reduction (increased concentration). Filtered biomarkers have the longest time-course because plasma levels increased following glomerular filtration rate decrease. Peak concentration and profile depended on the extent of damage to the reabsorption mechanism and recovery rate. Rapid recovery may be detected through a rapid reduction in urinary concentration. For all biomarkers, impaired hyperfiltration substantially increased concentration, especially with chronic kidney disease. For clinical validation of these model-derived predictions the clinical biomarker of choice will depend on timing in relation to renal insult and interpretation will require the pre-insult nephron number (renal mass) and detection of hyperfiltration.     

Molecular advantage of diferric transferrin in delivering iron to reticulocytes: a comparative study

Administration of aprotinin, a kallikrein inhibitor, to anesthetized rats infused with 0.9% saline solution to expand the extracellular fluid volume resulted in blunted natriuresis and diuresis. Urine flow declined from 27.1 +/- 2.6 to 8.0 +/- 0.9 microliter/min/100 g body wt while sodium and potassium excretion were reduced 63 and 45%, respectively (P less than 0.01). Mean blood pressure and glomerular filtration rate were not significantly altered by aprotinin. Acute or chronic pretreatment with DOCA, to enhance kinin synthesis, failed to modify the renal excretory response to aprotinin suggesting that saline loading alone was able to induce kinin generation fully in these rats. The results indicate that aprotinin enhanced the reabsorption of filtrate in rats expanded with isotonic saline and imply an influence of renal kinins on the tubular transport of salt and water.     

The function of innervated kidneys during stimulation of the carotid chemoreceptors under constant renal perfusion pressure]

The carotid chemoreceptors of narcotized, vagotomized and spontaneously breathing hydropenic cats in hypertonic mannite diuresis were stimulated by perfusion with venous blood penic cats in hypertonic mannite diuresis were stimulated by perfusion with venous blood for 70 min. Elevation of blood pressure at the innervated kidneys was prevented by an automatically controlled balloon located within the aorta. Stimulation of the chemoreceptors intensified respiration and raised the arterial systemic pressure. With the renal arteries at constant pressure, the effective renal plasma flow and the glomerular filtration rate significantly declined. The filtration fraction remained unchanged. The absolute urinary and sodium excretion did not change significantly, whereas the fractional time-volume, fractional sodium excretion, and the fractional osmotic excretion significantly increased. The fractional tubular reabsorption of osmotically free water was significantly enhanced. These reactions subsided during subsequent perfusion of the glomerula carotici with arterial blood. The results suggest that tubular sodium reabsorption is inhibited by stimulation of the carotid chemoreceptors, although re-adjustment of renal perfusion and filtrate volume cannot be excluded.