Filtration Rate In Response Research Articles

AST-120 to Target Protein-Bound Uremic Toxins Improves Cardiac Output and Kidney Oxygenation in Experimental Chronic Kidney Disease

Introduction: Chronic kidney disease (CKD) is a global health problem with increasing incidence which is closely associated with cardiac dysfunction. In CKD, uremic toxins accumulate as kidney function declines. Additionally, high salt intake is a growing health issue worldwide which can exacerbate kidney disease. In this study, we investigated the effect of reducing plasma levels of protein-bound uremic toxins in a rat model of CKD, challenged with high salt intake and compared the effects to those of conventional treatment using an angiotensin-converting enzyme inhibitor (ACEI). Methods: In rats, the right kidney and 2/3 of the left kidney were surgically removed (5/6 nephrectomy). Animals were fed a normal-salt diet and randomized to either no treatment (control) or chronic treatment with either the oral absorbent AST-120 to reduce plasma levels of protein-bound uremic toxins or the ACEI enalapril to inhibit angiotensin II signaling for 5 weeks. Following treatment, kidney function was measured before and after a week of high salt intake. Cardiac output and markers of oxidative stress were measured at the end of the study period. Results: Treatment with AST-120 resulted in decreased levels of the uremic toxin indoxyl sulfate, improved cardiac output (mL/min: AST-120 44.9 ± 5.4 compared to control 26.6 ± 2.0; p < 0.05), and decreased urinary oxidative stress. ACEI reduced oxidative stress in kidney tissue and improved the glomerular filtration rate in response to high salt intake (mL/min: ACEI 1.5 ± 0.1; compared to control 1.1 ± 0.1; p < 0.05). Both interventions improved intrarenal oxygen availability (mm Hg: AST-120 42.8 ± 0.8; ACEI 43.2 ± 1.9; compared to control 33.4 ± 1.3; p < 0.05). Conclusion: AST-120 administered to reduce plasma levels of uremic toxins, such as indoxyl sulfate, has potential beneficial effects on both cardiac and kidney function. Targeting uremic toxins and angiotensin II signaling simultaneously could be an efficient strategy to target both cardiac and kidney dysfunction in CKD, to further slow progression of disease in patients with CKD.

MO366: Renal Functional Reserve as a Marker to Stratify the Risk of Kidney Injury in Hematopoietic Stem Cell Transplantation

Abstract BACKGROUND AND AIMS Haematopoietic stem cell transplantation (HSCT) is an effective treatment for myelo-lymphoproliferative disorders. Acute kidney injury (AKI) is a major complication of HSCT (incidence ≈15%–60%), usually occurs in the first 100 days post-transplant, and is associated with a significant increase in mortality and morbidity. In addition, it can lead to chronic renal failure (CKD). There are no scores to predict which patients will develop AKI or CKD post-HSCT. Routine pre-HSCT evaluation only considers the estimated glomerular filtrate value (eGFR) without examining the renal functional reserve (RFR). RFR is defined as the ability of the kidney to increase its glomerular filtration rate in response to higher functional demand (as in the case of HSCT). METHOD This prospective study aimed to evaluate the ability of RFR in HSCT candidate patients to stratify the risk of AKI incidence within 100 days of transplantation and predict eventual functional recovery. The secondary purpose was to identify the risk factors for the onset of AKI. A total of 41 HSCT candidate patients with normal baseline GFR (bGFR) were included in the study. A total of 15 days before the HSCT, a multiparametric nephrological evaluation and RFR test (RFR-T) were performed using an oral protein load (1–1.2 g/kg) with freeze-dried products (Prother®) and 10 mL/kg of oral hydration. GFR after protein loading (glomerular stress filtration rate, sGFR) and bGFR were measured with body surface corrected endogenous creatinine clearance (CrCl). Blood samples were taken at predefined time intervals concerning oral protein load (120–180–240 min). RFR was defined as the difference between the maximum value of sGFR and bGFR expressed as a percentage (normal RFR &amp;gt; 25%). RESULTS No correlation was found between bGFR and RFR values. Consistent with the literature, 25 of 41 patients (61%) developed AKI. Comparing the group that developed AKI with those that did not, no statistically significant differences emerged related to demographic, clinical, or multiparameter screening characteristics. RFR was lower in AKI + patients than in AKI- patients, with a value at the borderline of statistical significance (P = 0.06). Among the 25 patients who developed AKI, 7 patients (30%) recovered normal renal function in the follow-up, while 18 patients (70%) developed CKD. 71% of patients who recovered renal function demonstrated an RFR value&amp;gt;25%; no demographic and multiparameter screening variables correlated with the development of post-HSCT CKD. CONCLUSION RFR is a dynamic parameter with respect to the bGFR. It allows the identification of conditions of subclinical functional deterioration, capable of affecting both the onset of AKI and CKD post-HSCT. No other multiparameter screening variable has shown potential utility in this type of predictive assessment. The stratification of the risk of kidney injury through RFR represents the most promising marker in this sense. A reliable prediction of the risk of renal complication in these patients could lead to accurate multidisciplinary management able to improve the prognosis quoad vitam (severe in the case of AKI post-HSCT) and quoad valetudinem (severe in case of CKD post-HSCT).

Expert Perspective: An Approach to Refractory Lupus Nephritis.

Systemic lupus erythematosus affects the kidneys in ~50% of all patients, and lupus nephritis (LN) is the most common manifestation of kidney involvement. Despite prompt diagnosis and treatment with aggressive immunosuppression, a significant proportion of LN patients do not respond to treatment and are considered to have refractory LN. Several factors other than drug resistance, such as nonadherence to treatment, undertreatment with conventional drugs, the effects of accumulated chronic damage, and genetic factors, may contribute to a poor response to treatment and should be considered. We define refractory LN as no change in (or worsening of) proteinuria and/or estimated glomerular filtration rate in response to 2 different standard-of-care induction regimens after 4-6 months in patients who are adherent to treatment. For patients who have LN that is truly refractory to standard of care, B cell-targeted therapy, specifically rituximab (RTX), is the most common next step. There is limited evidence available on alternative rescue therapies that may be used when there is no response to RTX. These include anti-CD38, leflunomide, intravenous immunoglobulin, plasma exchange, autologous stem cell transplantation, chimeric antigen receptor T cell therapy, anticomplement therapy, and interleukin-2 therapy.

Correlates and Consequences of an Acute Decline in Estimated Glomerular Filtration Rate in Response to the SGLT-2 Inhibitor Dapagliflozin

Correlates and Consequences of an Acute Decline in Estimated Glomerular Filtration Rate in Response to the SGLT-2 Inhibitor Dapagliflozin

Effects of temperature, salinity and body size on the physiological responses of the Iwagaki oyster Crassostrea nippona

The physiological responses of the juvenile Crassostrea nippona in terms of filtration, oxygen consumption and ammonia excretion to changes in temperature (16–32°C), salinity (15–35 psu) and body size (small, medium and large) were investigated. In this study, the values of filtration rate (FR), oxygen consumption rate (OCR) and ammonia excretion rate (AER) increased with temperature rising from 16°C to 24°C, reaching the highest values at 24°C and 28°C; with any further increase in temperature above this limit, these values decrease drastically (p < .05). The highest Q10 coefficients were 2.75 for large, 3.54 for medium at 16–20 and 3.47 for small size at 20–24°C respectively. Moreover, the responses of FR and OCR were found to be influenced significantly by salinity, tending to increase concomitantly with salinity up to 25–30 psu, though the values of these parameters were diminished dramatically (p < .05) above this level, showing a reverse pattern from that observed in AER, which firstly decreased to the lowest level at 25 and 30 psu, and then severely (p < .05) increased to the highest level at 35 psu. In addition, the low O:N ratios of all sizes of C. nippona at 16°C and 30–35 psu were indicative of a protein-dominated catabolism, whereas the O:N ratios of large size at 20–32°C and all sizes at 20–30 psu, indicating that the metabolic energy from protein diminished and lipid and carbohydrate were used as the energy substrates. Physiological rates of C. nippona were well correlated with its size. The average values of mass exponents (b-values) estimated in the present study were 0.657 for OCR and 0.776 for AER at different temperatures, and 0.647 for OCR and 0.767 for AER at varying salinities, signifying that physiological process of C. nippona becomes relatively slower with increasing body size regardless of temperature or salinity. Finally, our results confirm that the optimal temperature and salinity for juvenile C. nippona lie within 24–28°C and 25–30 psu respectively. The results of physiological traits in response to environmental factors of this species are informative in site selection for the cultivation.

Impaired Renal Autoregulation in Susceptible Models of Renal Disease

One of the major functions of the kidney is to maintain constant renal blood flow and glomerular filtration rate in response to increases in renal perfusion pressure. This phenomenon is referred to autoregulation and involves two independent mechanisms: tubular glomerular feedback and myogenic response. The latter, the renal myogenic response, involves constriction of the preglomerular vasculature to increases in transmural pressure. Over the last three decades, there has been substantial evidence that demonstrates that the myogenic response plays an important role in protecting the kidney from hypertension-induced renal injury. Furthermore, impairment of the renal myogenic response allows the transmission of systemic pressures to the glomerular capillaries leading to the development of glomerular injury and progressive proteinuria during hypertension. This review article discusses the role of the myogenic response in the pathogenesis of renal disease in various genetic and experimental rodent models that develop hypertension-induced renal injury.

Renal hemodynamic effect of cyclooxygenase 2 inhibition in young men and women with uncomplicated type 1 diabetes mellitus

In experimental studies, cyclooxygenase 2 (COX2)-derived vasodilatory prostaglandins play a more prominent role in arterial vasoregulation in females. The gender-dependent effect of COX2 modulation in humans with type 1 diabetes mellitus (DM) is unknown. Accordingly, we examined the renal hemodynamic role of prostaglandins by assessing the response to COX2 inhibition in young men and women with type 1 DM. We also used a graded ANG II infusion to determine whether gender-based differences were mediated by effects of COX2 inhibition on the renin angiotensin system (RAS). We hypothesized that COX2 inhibition would be associated with preferential vasoconstriction in women and would augment their response to ANG II. Baseline renal function and the response to an ANG II infusion were assessed during clamped euglycemia, and again after COX2 inhibition (200 mg celecoxib daily for 14 days) in 12 men and 9 women after 1 wk on a controlled protein and sodium diet. COX2 inhibition was associated with increases in filtration fraction (P = 0.045) and renal vascular resistance and a decline in renal blood flow (P = 0.04) in women compared with men. Before COX2 inhibition, women exhibited a decline in glomerular filtration rate in response to ANG II. COX2 inhibition abolished this effect, whereas the response was not altered in men. In summary, COX2 inhibition was associated with hemodynamic effects that differed based on gender. The ANG II response suggests that with uncomplicated type 1 DM, prostaglandins may contribute to RAS-mediated gender differences. Our results are consistent with experimental data suggesting augmented female prostanoid dependence.

Subchronic organismal toxicity, cytotoxicity, genotoxicity, and feeding response of pacific oyster (Crassostrea gigas) to lindane (γ‐HCH) exposure under experimental conditions

This study evaluated organismal toxicity, cytotoxicity, and genotoxicity and the filtration rate in response to different concentrations of subchronic lindane (gamma-hexachlorocyclohexane [gamma-HCH]), exposure (12 d) in adult Pacific oysters Crassostrea gigas. Oysters were exposed in vivo in laboratory aquaria to 10 different concentrations (0.0-10.0 mg/L) of gamma-HCH. The median lethal concentration (LC50) after 12 d was calculated as 2.22 mg/L. Cytotoxic effects were observed in hemocytes, where the mean cell viability was significantly decreased at 1.0 mg/L of gamma-HCH after 12 d. Genotoxicity of gamma-HCH measured by single cell gel electrophoresis assay, in hemocytes was evident at 0.7 mg/L of gamma-HCH after 12 d. After 4 h of exposure to gamma-HCH, filtration rates were reduced compared with controls to 65.8 and 38.2% at concentrations of 0.3 and 0.7 mg/L, respectively, and after 11 d of exposure, filtration rates were reduced to 60.4 and 30.9% at concentrations of 0.1 mg/L and higher. These results show the subchronic effects of gamma-HCH at different concentrations and effect sensitivities are categorized as filtration rate < genotoxicity < cytotoxicity < mortality. The relevance of integral toxicity evaluation, considering different endpoints from molecular, cellular, and individual levels is discussed.

Is it the low-protein diet or simply the salt restriction?

Dietary factors, such as salt and protein intake, may play an important role in the progression of kidney disease. Consequently, dietary manipulations of these constituents are of interest both in experimental models of kidney disease and in clinical trials with patients with chronic kidney disease to assess whether modification of these exposures will result in a stabilization of disease progression.

Renal functional reserve in obesity hypertension

The capacity to increase glomerular filtration rate in response to an acute oral protein load is known as the renal functional reserve; the loss of such capacity is used as a marker of hyperfiltration. This physiological response in obese hypertensives is not yet fully understood. We aimed to study the interdependent effects of obesity and hypertension on renal reserve, taking into account renal kallikrein and nitric oxide in the modulation of that parameter. Fourteen obese hypertensives (mean age, 50.5 +/- 0.9 years) and nine lean hypertensives (mean age, 50.6 +/- 2.7 years) were evaluated. Renal haemodynamics and the levels of serum nitric oxide and urinary kallikrein were assessed at baseline and after a protein load (1 g/kg of body weight). An increase in the following parameters was observed when comparing obese and lean hypertensives: basal glomerular filtration rate; renal plasma flow; and urinary kallikrein and nitric oxide levels (129.2 +/- 2.9 vs. 101.4 +/- 3.4 ml/min/1.73 m2; 587.5 +/- 18.2 vs. 502.8 +/- 16.7 ml/min/1.73 m2; 0.120 +/- 0.02 vs. 0.113 +/- 0.02 mU/ml; 23.2 +/- 0.8 vs. 19.5 +/- 1.2 mmol/ml, respectively). The renal reserve was lower in obese hypertensives when compared with that of lean hypertensives (4.1 +/- 0.5 vs. 11.8 +/- 0.8 ml/min, p < 0.005). After a protein load, contrasting with the lean group, inability to elevate the nitric oxide serum levels and a lower increase in urinary kallikrein were observed in the obese group. These data suggest that obese hypertensives lose renal reserve earlier in the evolution to renal dysfunction. This may be due to the defective modulation of renal vasodilatation mechanisms by renal kallikrein and nitric oxide production.

Impairment of tubuloglomerular feedback regulation of GFR in ecto-5′-nucleotidase/CD73–deficient mice

Adenosine coordinates organ metabolism and blood supply, and it modulates immune responses. In the kidney it mediates the vascular response elicited by changes in NaCl concentration in the macula densa region of the nephron, thereby serving as an important regulator of GFR. To determine whether adenosine formation depends on extracellular nucleotide hydrolysis, we studied NaCl-dependent GFR regulation (tubuloglomerular feedback) in mice with targeted deletion of ecto-5′-nucleotidase/CD73 (e-5′NT/CD73), the enzyme responsible for adenosine formation from AMP. e-5′NT/CD73–/– mice were viable and showed no gross anatomical abnormalities. Blood pressure, blood and urine chemistry, and renal blood flow were not different between e-5′NT/CD73+/+ and e-5′NT/CD73–/– mice. e-5′NT/CD73–/– mice had a significantly reduced fall in stop flow pressure and superficial nephron glomerular filtration rate in response to a saturating increase of tubular perfusion flow. Furthermore, whereas tubuloglomerular feedback responses did not change significantly during prolonged loop of Henle perfusion in e-5′NT/CD73+/+ mice, a complete disappearance of the residual feedback response was noted in e-5′NT/CD73–/– mice over 10 minutes of perfusion. The contractile response of isolated afferent arterioles to adenosine was normal in e-5′NT/CD73–/– mice. We conclude that the generation of adenosine at the glomerular pole depends to a major extent on e-5′NT/CD73–mediated dephosphorylation of 5′-AMP, presumably generated from released ATP.

Impairment of tubuloglomerular feedback regulation of GFR in ecto-5'-nucleotidase/CD73-deficient mice.

Adenosine coordinates organ metabolism and blood supply, and it modulates immune responses. In the kidney it mediates the vascular response elicited by changes in NaCl concentration in the macula densa region of the nephron, thereby serving as an important regulator of GFR. To determine whether adenosine formation depends on extracellular nucleotide hydrolysis, we studied NaCl-dependent GFR regulation (tubuloglomerular feedback) in mice with targeted deletion of ecto-5'-nucleotidase/CD73 (e-5'NT/CD73), the enzyme responsible for adenosine formation from AMP. e-5'NT/CD73(-/-) mice were viable and showed no gross anatomical abnormalities. Blood pressure, blood and urine chemistry, and renal blood flow were not different between e-5'NT/CD73(+/+) and e-5'NT/CD73(-/-) mice. e-5'NT/CD73(-/-) mice had a significantly reduced fall in stop flow pressure and superficial nephron glomerular filtration rate in response to a saturating increase of tubular perfusion flow. Furthermore, whereas tubuloglomerular feedback responses did not change significantly during prolonged loop of Henle perfusion in e-5'NT/CD73(+/+) mice, a complete disappearance of the residual feedback response was noted in e-5'NT/CD73(-/-) mice over 10 minutes of perfusion. The contractile response of isolated afferent arterioles to adenosine was normal in e-5'NT/CD73(-/-) mice. We conclude that the generation of adenosine at the glomerular pole depends to a major extent on e-5'NT/CD73-mediated dephosphorylation of 5'-AMP, presumably generated from released ATP.

Cyclic GMP Mediates Influence of Macula densa Nitric Oxide over Tubuloglomerular Feedback

Background: Tubuloglomerular feedback (TGF) stabilizes nephron function by eliciting reciprocal changes in single-nephron glomerular filtration rate in response to changes in salt reaching the macula densa. Nitric oxide (NO) modulates TGF, making it less reactive. NO could come from NO synthase (NOS) in mesangium or microvessels (NOS III) or from neuronal NOS (NOS I) in the macula densa. Cyclic GMP is second messenger for many NO functions. Methods: Rat micropuncture was performed to confirm that macula densa NOS I makes the NO which modulates TGF and that cyclic GMP is a second messenger for this. The range of TGF was determined by measuring the single-nephron glomerular filtration rate while perfusing Henle’s loop. The TGF slope was calculated from the response to flow perturbations in free-flowing nephrons using a noninvasive optical technique to measure flow. The NO-cyclic GMP axis was manipulated by tubular microperfusion of the antagonists S-methyl-thiocitrulline (SMTC) and 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) and NO donor (spermine NONOate). Results: SMTC and ODQ each increased slope and range of TGF and tended to shift it leftward. NONOate reversed the effects of SMTC, but not of ODQ. Conclusion: Cyclic GMP mediates desensitization of TGF by macula densa NOS I.

Ammonia functions as a regulatory molecule to mediate adjustments in glomerular filtration rate in response to changes in metabolic rate

In mammals, varying in size from mouse to elephant there is a close linkage between metabolic rate (MR) and glomerular filtration rate (GFR). This linkage has evolved because of the necessity to excrete nitrogenous wastes generated predominately by amino acid catabolism. A similar linkage is observed in birds, reptiles and fish, although in the latter vertebrate group gill excretion rate and GFR need to be considered as an interdependent co-ordinated system. A change in the rate of amino acid catabolism will result in a change in the rate of production of nitrogenous wastes requiring excretion and hence GFR (or GFR plus gill excretory rate in fish) must be appropriately re-set. It is hypothesized that ammonia functions as a regulatory molecule to mediate adjustments in excretory rate (GFR or GFR plus gill excretory rate) in response to such changes in amino acid catabolism.

The selective adenosine A 1 receptor antagonist KW-3902 prevents radiocontrast media-induced nephropathy in rats with chronic nitric oxide deficiency

Several studies have recently suggested a principal role of adenosine in the pathogenesis of radiocontrast media-induced nephropathy. In the present experiments, we therefore investigated the renal protective effects of 8-(noradamantan-3-yl)-1,3-dipropylxanthine (KW-3902), a potent and selective adenosine A 1 receptor antagonist, on radiocontrast media-induced nephropathy in the model of the N-ϖ-nitro- l-arginine methyl ester ( l-NAME) hypertensive, chronic nitric oxide (NO)-depleted rat. Chronic NO depletion was induced by pretreatment with l-NAME, 50 mg/ml, added to drinking water for 8 weeks. Clearance experiments were performed in anesthetized rats and glomerular filtration rate was assessed prior to and following the application of high osmolar radiocontrast media (sodium diatrizoate, 3 ml/kg, i.v.) or an equivalent volume of isoosmolar mannitol to examine the role of hyperosmolarity in radiocontrast media-induced nephropathy. Subgroups received KW-3902 (0.1 mg/kg, i.v.), 20 min prior to radiocontrast media administration. Age-matched, untreated rats served as controls. Radiocontrast media application induced a significant decline in glomerular filtration rate in l-NAME hypertensive animals, whereas no effects were observed in control rats. KW-3902 fully prevented the drop in glomerular filtration rate in response to radiocontrast media in l-NAME hypertensive rats. No renal hemodynamic alterations were observed in mannitol-infused animals. The present experiments demonstrate that the decrease in glomerular filtration rate following radiocontrast media occurred independently of the osmotic load, and that KW-3902 effectively prevented the radiocontrast media-induced deterioration in renal function. KW-3902 may be especially beneficial in patients at high risk for developing acute renal failure following radiocontrast media application or in patients in which extracellular fluid volume expansion is limited by clinical conditions such as congestive heart failure.

Potential role of luminal potassium in tubuloglomerular feedback.

Transport through the Na+-2Cl(-)-K+ cotransporter in the luminal membrane of macula densa cells is considered critical for tubuloglomerular feedback (TGF). Although various studies could support the importance of luminal Na+ and Cl-, the role of luminal K+ in TGF has not been thoroughly addressed. The study presented here examines this issue in nephrons with superficial glomeruli of anesthetized male Munich-Wistar-Frömter rats. Ambient Na+ concentration in early distal tubular fluid was approximately 22 mM, suggesting collection sites relatively close to the macula densa segment. First, it was found that ambient early distal tubular K+ concentration is approximately 1.3 mM, i.e., close to the K+ affinity of the Na+-2Cl(-)-K+ cotransporter in the thick ascending limb. Second, it was observed that a change in late proximal tubular flow rate, i.e., a maneuver that is known to induce a TGF response, significantly alters early distal tubular K+ concentration. Third, previous experiments failed to show an inhibition in TGF response during retrograde perfusion of the macula densa with K+-free solutions. Because of a potential K+ influx into the lumen between the perfusion site and the macula densa, however, the K+ channel blocker U37883A was added to the K+-free perfusate. TGF response was assessed as the fall in nephron filtration rate in response to retrograde perfusion of the macula densa segment from early distal tubular site. It was observed that luminal U37883A (100 microM) significantly attenuated TGF. Because adding 5 mM KCl to the perfusate restored TGF in the presence of U37883A and because the inhibitory action of U37883A on tubular K+ secretion was confirmed, the effect of U37883A on TGF was most likely caused by inhibition of K+ influx into the perfused segment, which decreased luminal K+ concentration at the macula densa. The present findings support a potential role for luminal K+ in TGF, which is in accordance with a transmission of the TGF signal across the macula densa via Na+-2Cl(-)-K+ cotransporter.

Renal hemodynamics in essential hypertension. Racial differences in response to changes in dietary sodium.

Previous studies have suggested striking racial differences in hypertension-related renal disease. To explore potential mechanisms responsible for these differences, we investigated changes in renal hemodynamics in white and black essential hypertensive patients in response to alterations in dietary sodium. Patients were untreated, age-matched, and blood pressure-matched white (n = 59) and black (n = 22) males with essential hypertension. Studies were conducted on an inpatient metabolic ward and included assessment of blood pressure, urinary sodium excretion, glomerular filtration rate, renal plasma flow, and renal blood flow after 5 days each of high and low salt diets. In response to high dietary salt intake, both white and black patients demonstrated significantly higher mean arterial pressure, renal plasma flow, and renal blood flow, and there were no racial differences in the changes in these parameters. However, whites and blacks differed significantly in glomerular filtration rate, with black hypertensive patients showing an increase in glomerular filtration rate (+17.3 +/- 5.3 mL/min per 1.73 m2, F = 7.586, P = .007) and white hypertensive patients showing no change (-0.2 +/- 3.3 mL/min per 1.73 m2) in response to high dietary sodium. These data demonstrate racial differences in the autoregulation of glomerular filtration rate in response to changes in dietary sodium. These differences suggest that glomerular hyperfiltration in response to a high salt diet may be a mechanism contributing to the racial disparity in hypertension-related renal disease.

A Role for Tubuloglomerular Feedback in Chronic Partial Ureteral Obstruction

Animals with partial ureteral obstruction have an inability to increase urinary output and glomerular filtration rate in response to an extracellular volume expansion. The mechanism may be a paradoxical resetting of tubuloglomerular feedback in the obstructed kidney, which impacts the roles of arachidonic acid metabolites and kinins in renal function.

Renal functional reserve in the early stage of experimental diabetes.

The role of renal functional reserve (RFR; increase in plasma flow and glomerular filtration rate in response to protein loading) as an indicator of increased glomerular hydrostatic pressure and flow was evaluated in recent-onset poorly controlled diabetic rats. Streptozocin-induced diabetic (STZ-D) rats were studied with micropuncture (MP) technique after 10-15 days of diabetes (daily blood glucose level 15.3-18 mmol). We also studied STZ-D rats treated with the converting-enzyme inhibitor (CEI) enalapril or the angiotensin II (ANG II) receptor antagonist DuP 753 (DuP) for 3 days before MP. Nondiabetic rats (NOR) served as controls. Glomerular hemodynamics and proximal tubular reabsorption were measured in the control period and during intravenous glycine infusion. In NOR rats, glycine increased single-nephron plasma flow (SNPF) and single-nephron glomerular filtration rate (SNGFR). Although STZ-D rats did not exhibit hyperfiltration, SNGFR and SNPF were not modified by glycine, defining loss of RFR. CEI rats responded to glycine with an increase in SNGFR due to a rise in SNPF and a rise in the ultrafiltration coefficient. Interestingly, loss of RFR in STZ-D rats was associated with a decrease in absolute proximal reabsorption. The decrease in absolute proximal reabsorption was corrected by both CEI and DuP, although glomerular vasodilation was restored only in the CEI group. In conclusion, at the early stage of diabetes mellitus, loss of RFR does not detect hyperfiltration, but rather the presence of a tubular alteration probably dependent on ANG II.(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of small-scale spatio-temporal heterogeneity in phytoplankton abundance for energy flow in Mytilus edulis

The effect of small-scale heterogeneity of phytoplankton abundance on mussel (Mytilus edulis L.) energy flow was studied by comparing filtration rate, consumption and assimilation efficiency in two groups of mussels fed under constant (control) and fluctuating (24 min) seston regimes of the same average. The experiment was carried out twice. Mussels appeared to regulate their filtration rate in response to varying seston concentration in one experiment, but not in the other. This behavioral difference may have been caused by differences in mean food level. Mean consumption was not different in the two feeding regimes, but assimilation efficiency was probably lower under fluctuating seston concentration. This suggests that small-scale heterogeneity in phytoplankton abundance would not affect the total transfer of energy between plankton and benthos. However, since a higher proportion of consumed energy was probably lost as faeces and/or pseudofaeces under the fluctuating seston regime, it may be expected that growth rate of mussels is depressed by small-scale heterogeneity in phytoplankton availability.