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At least 91 records · Page 5

Renal responses to central vascular expansion are suppressed at night in conscious primates

The renal and hemodynamic responses of squirrel monkeys to central vascular volume expansion induced by lower body positive pressure (LBPP) during the day and night are investigated. Twelve unanesthetized animals trained to sit in a metabolism chair in which they were restrained only at the waist by a partition separating upper and lower body chambers were subjected to 4 h of continuous LBPP during the day and night, and hemodynamic, urinary and drinking data were monitored. LBPP during day and night is found to induce similar increases in central venous pressure, rises in heart rate and elevations in mean arterial blood pressure. However, although daytime LBPP induced a significant increase in urine flow and sodium excretion, a marked nocturnal inhibition of the renal response to LBPP is observed. Analysis of the time course and circadian regulation patterns of the urinary responses suggests that several separate efferent control pathways are involved.

Kass, D. A.↗

Computer simulation analysis of the behavior of renal-regulating hormones during hypogravic stress

A computer simulation of a mathematical circulation model is used to study the alterations of body fluids and their electrolyte composition that occur in weightlessness. The behavior of the renal-regulating hormones which control these alterations is compared in simulations of several one-g analogs of weightlessness and space flight. It is shown that the renal-regulating hormones represent a tightly coupled system that responds acutely to volume disturbances and chronically to electrolyte disturbances. During hypogravic conditions these responses lead to an initial suppression of hormone levels and a long-term effect which varies depending on metabolic factors that can alter the plasma electrolytes. In addition, it is found that if pressure effects normalize rapidly, a transition phase may exist which leads to a dynamic multiphasic endocrine response.

Leonard, J. I.↗

The behavior of renal-regulating hormones during hypogravic stress

The regulation of fluid and electrolyte behavior during space flight is believed to be under control, in large part, of a group of hormones which have their major effects on renal excretion. The hormones studied include renin-angitensin, aldosterone, and antidiuretic hormone (ADH). The regulatory systems of these renal-regulating hormones as they act individually and in concert with each other are analyzed. The analysis is based on simulations of the mathematical model of Guyton. A generalized theory is described which accounts for both short-term and long-term behavior of this set of hormones.

Leonard, J. I.↗

Effects of 30 day simulated microgravity and recovery on fluid homeostasis and renal function in the rat

Transition from a normal gravitational environment to that of microgravity eventually results in decreased plasma and blood volumes, increasing with duration of exposure to microgravity. This loss of vascular fluid is presumably due to negative fluid and electrolyte balance and most likely contributes to the orthostatic intolerance associated with the return to gravity. The decrease in plasma volume is presumed to be a reflection of a concurrent decrease in extracellular fluid volume with maintenance of normal plasma-interstitial fluid balance. In addition, the specific alterations in renal function contributing to these changes in fluid and electrolyte homeostasis are potentially responding to neuro-humoral signals that are not consistent with systemic fluid volume status. We have previously demonstrated an early increase in both glomerular filtration rate and extracellular fluid volume and that this decreases towards control values by 7 days of simulated microgravity. However, longer duration studies relating these changes to plasma volume alterations and the response to return to orthostasis have not been fully addressed. Male Wistar rats were chronically cannulated, submitted to 30 days heat-down tilt (HDT) and followed for 7 days after return to orthostasis from HDT. Measurements of renal function and extracellular and blood volumes were performed in the awake rat.

Tucker, Bryan J.↗

[Volume Homeostasis and Renal Function in Rats Exposed to Simulated and Actual Microgravity]

This project has investigated mechanisms that influence alterations in compartmental fluid and electrolyte balance in microgravity and evaluates countermeasures to control renal fluid and electrolyte losses. Determining the alterations due to space flight in fluid compartments and renal function is an important component in understanding long term adaptation to spaceflight and the contribution to post-flight orthostatic intolerance. Four definition phase studies and two studies examining neuro-humoral and vascular mechanisms have been completed.

Tucker, Bryan J.↗

Neocytolysis Contributes to the Anemia of Renal Disease

Neocytolysis is a recently described physiologic process effecting selective hemolysis of young red blood cells in circumstances of plethora. Erythropoietin depression appears to initiate the process, providing rationale to investigate its contributions to the anemia of renal disease. When erythropoietin therapy was withheld, four of five stable hemodialysis patients demonstrated Cr-51 red cell survival patterns indicative of neocytolysis; red cell survival was short in the first 9 days, then normalized. Two of these patients received oral (13)C-glycine and (15)N-glycine and showed pathologic enrichment of stool porphyrins by the most recently ingested isotope when EPO therapy was held. This confirms selective hemolysis of newly-released red cells. (One patient had chronic hemolysis by isotope studies of blood and stool.) Thus, neocytolysis can contribute to the anemia of renal disease and explains some unresolved issues about such anemia. One implication is the prediction that intravenous bolus erythropoietin therapy is metabolically and economically inefficient compared to lower doses given more frequently subcutaneously.

Rice, Lawrence↗

Effects of Increased CO2 Level on the Well-Being, Growth and Renal Function of Rats

On the Space Shuttle the mean CO2 levels have been 0.3% which is ten times normal air, while there have been extended periods with mean levels of 0.7% and peak concentrations of 2%. On the Space Station the projected mean concentration of CO2 is 0.7% and not to exceed 1.0%. To ensure that high level of CO2 does not compromise the integrity of the science on the Space Station, the effects of chronic exposure to high levels of CO2 were investigated. Following 7 days of cage adaptation animals exposed to 2% CO2 for 30 days were compared to control (ambient air) animals and the effects on the well-being, growth and renal function analyzed. Ten male rats per group were placed in individual metabolic cages which allowed monitoring of daily food and water consumption, as well as feces and urine to be collected. Cages were placed in a plexiglass chamber with internal environment controlled by a computer in conjunction with gas sensors. The elevated CO2 was held constant at 2.0 +/- 0.03% and the O2 at 20.9 +/- 0.15%. Body weight and food and water intake were measured daily for the first ten days of exposure and then every three to four days for the remaining three weeks. Urine was measured for pH, CO2 (as an indicator for bicarbonate) and ammonia (as an indicator for ammonium). During 2% CO2 exposure, animal growth, weight, food and water consumption were within normal ranges suggesting that their well-being was not affected. Urine pH decreased from 7.12 to 6.77 over the first 6 days of exposure and increased the following 24 days returning to pre-exposure levels. Urine NH4+ increased 68% the first 6 days then dropped to and remained at 29% higher than pre-exposure level. Urine bicarbonate concentration did not change the first 6 days, but significantly increased by day 30. These results of chronic exposure to 2% C02 are consistent with renal compensation for respiratory acidosis which may impact science conducted on the Space Shuttle or the Space Station if CO2 levels reach 2%.

Lang, C.↗

Renal Response to Chronic Centrifugation in Rats

Previously reported effects of chronic centrifugation on renal function in mammals are contradictory. The present study was conducted as an effort to provide a comprehensive analysis of renal response to chronic centrifugation (12 days at +2 Gz). Sixteen male Sprague-Dawley rats (210-230 g) were used: eight centrifuged (EC) and eight off centrifuge controls (OCC). During centrifugation EC had lower body weight and food consumption. EC showed a decrease (72%) in water intake for the first two days (T1 and T2) followed by significant increases from T4-T6. EC urine output increased two-fold over the first four days, returning to baseline by T9. EC urea excretion was elevated on T3 through T5. Creatinine, Na(+), K(+), and osmolar excretion were lower than OCC over the last four days of the study. Assuming constant plasma osmolarity and creatinine levels, EC free water clearance (C(sub H2O)) was elevated significantly on T4 when the peak urine output was exhibited. EC also had a greater C(sub H2O) over the last four days, associated with a significantly lower osmolar clearance and GFR. The initial diuresis exhibited during centrifugation can be attributed to a reduced water resorption and increased urea excretion. This diuresis was mediated independent of changes in GFR over the first eight days. However, differences in excretion seen after eight days of centrifugation are probably GFR mediated which would imply animals established a new homeostatic setpoint by that time. Centrifugation elicites an acute alteration in fluid homeostasis followed by adaptation within a week.

Ortiz, Rudy M.↗

Neocytolysis contributes to the anemia of renal disease

Neocytolysis is a recently described physiological process affecting the selective hemolysis of young red blood cells in circumstances of plethora. Erythropoietin (EPO) depression appears to initiate the process, providing the rationale to investigate its contributions to the anemia of renal disease. When EPO therapy was withheld, four of five stable hemodialysis patients showed chromium 51 (51Cr)-red cell survival patterns indicative of neocytolysis; red cell survival was short in the first 9 days, then normalized. Two of these four patients received oral 13C-glycine and 15N-glycine, and there was a suggestion of pathological isotope enrichment of stool porphyrins when EPO therapy was held, again supporting selective hemolysis of newly released red cells that take up the isotope (one patient had chronic hemolysis indicated by isotope studies of blood and stool). Thus, neocytolysis can contribute to the anemia of renal disease and explain some unresolved issues about such anemia. One implication is the prediction that intravenous bolus EPO therapy is metabolically and economically inefficient compared with lower doses administered more frequently subcutaneously.

Non-NASA Center↗

Alteration of renal function of rats following spaceflight

Following spaceflight, changes in renal function of humans have been suggested. To assess the effects of readaptation on renal function, urine was collected from male rats ( approximately 245 g) over a 2-wk period following a 14-day spaceflight. Rats were assigned to three groups: flight animals (n = 6), flight controls (n = 6) housed in the flight cages on the ground, and vivarium controls (n = 5) housed in standard shoe box cages. Animals were placed into individual metabolic cages for urine collection. Urine output was significantly increased for 3 days following flight. Excretion rates of Na+ and K+ were increased, resulting in an increased osmotic excretion rate. Creatinine excretion rate increased over the first two postflight days. Glomerular filtration rate increased immediately following spaceflight without changes in plasma creatinine, Na+, K+, or osmolality. Increased excretion of solute was thus the result of increased delivery and a decreased percent reabsorption of the filtered load. Osmolal clearance was increased immediately postflight while free water clearance was decreased. In growing rats, the diuresis after short-duration spaceflight is the result of an increase in solute excretion with an accompanying reduction in free water clearance.

STS-58 Shuttle Project↗

Alterations in renal stone risk factors after space flight

Exposure to the microgravity environment of space produces a number of physiological changes of metabolic and environmental origin that could increase the potential for renal stone formation. Metabolic, environmental and physicochemical factors that influence renal stone risk potential were examined in 24-hour urine samples from astronauts 10 days before launch and on landing day to provide an immediate postflight assessment of these factors. In addition, comparisons were made between male and female crewmembers, and between crewmembers on missions of less than 6 days and those on 6 to 10-day missions. Results suggest that immediately after space flight the risk of calcium oxalate and uric acid stone formation is increased as a result of metabolic (hypercalciuria, hypocitraturia, pH) and environmental (lower urine volume) derangements, some of which could reflect residual effects of having been exposed to microgravity.

NASA Center JSC↗

Use of Potassium Citrate to Reduce the Risk of Renal Stone Formation During Spaceflight

Introduction: NASA s Vision for Space Exploration centers on exploration class missions including the goals of returning to the moon and landing on Mars. One of NASA s objectives is to focus research on astronaut health and the development of countermeasures that will protect crewmembers during long duration voyages. Exposure to microgravity affects human physiology and results in changes in the urinary chemical composition favoring urinary supersaturation and an increased risk of stone formation. Nephrolithiasis is a multifactorial disease and development of a renal stone is significantly influenced by both dietary and environmental factors. Previous results from long duration Mir and short duration Shuttle missions have shown decreased urine volume, pH, and citrate levels and increased calcium. Citrate, an important inhibitor of calcium-containing stones, binds with urinary calcium reducing the amount of calcium available to form stones. Citrate inhibits renal stone recurrence by preventing crystal growth, aggregation, and nucleation and is one of the most common therapeutic agents used to prevent stone formation. Methods: Thirty long duration crewmembers (29 male, 1 female) participated in this study. 24-hour urines were collected and dietary monitoring was performed pre, in, and postflight. Crewmembers in the treatment group received two potassium citrate (KCIT) pills, 10 mEq/pill, ingested daily beginning 3 days before launch, all inflight days and through 14 days postflight. Urinary biochemical and dietary analyses were completed. Results: KCIT treated subjects exhibited decreased urinary calcium excretion and maintained the levels of calcium oxalate supersaturation risk at their preflight levels. The increased urinary pH levels in these subjects reduced the risk of uric acid stones. Discussion: The current study investigated the use of potassium citrate as a countermeasure to minimize the risk of stone formation during ISS missions. Results suggest that supplementation with potassium citrate decreases the risk of stone formation during and immediately after spaceflight.

Whitson, P. A.↗

Renal Stone Risk during Spaceflight: Assessment and Countermeasure Validation

NASA's Vision for Space Exploration centers on exploration class missions including the goals of returning to the moon and landing on Mars. One of NASA's objectives is to focus research on astronaut health and the development of countermeasures that will protect crewmembers during long duration voyages. Exposure to microgravity affects human physiology and results in changes in the urinary chemical composition favoring urinary supersaturation and an increased risk of stone formation. Nephrolithiasis is a multifactorial disease and development of a renal stone is significantly influenced by both dietary and environmental factors. Previous results from long duration Mir and short duration Shuttle missions have shown decreased urine volume, pH, and citrate levels and increased calcium. Citrate, an important inhibitor of calcium-containing stones, binds with urinary calcium reducing the amount of calcium available to form stones. Citrate inhibits renal stone recurrence by preventing crystal growth, aggregation, and nucleation and is one of the most common therapeutic agents used to prevent stone formation. Methods: Thirty long duration crewmembers (29 male, 1 female) participated in this study. 24-hour urines were collected and dietary monitoring was performed pre-, in-, and postflight. Crewmembers in the treatment group received two potassium citrate (KCIT) pills, 10 mEq/pill, ingested daily beginning 3 days before launch, all in-flight days and through 14 days postflight. Urinary biochemical and dietary analyses were completed. Results: KCIT treated subjects exhibited decreased urinary calcium excretion and maintained the levels of calcium oxalate supersaturation risk at their preflight levels. The increased urinary pH levels in these subjects reduced the risk of uric acid stones. Discussion: The current study investigated the use of potassium citrate as a countermeasure to minimize the risk of stone formation during ISS missions. Results suggest that supplementation with potassium citrate decreases the risk of stone formation during and immediately after spaceflight.

Whitson, Peggy A.↗

Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 expression displays prognostic value. Single-nuclei RNA sequencing of the adverse sarcomatoid and rhabdoid phenotypes uncover gene signatures and potential insights into tumor evolution. In vitro cell line studies confirm the potential of inhibiting identified phosphoproteome targets. This study molecularly stratifies aggressive histopathologic subtypes that may inform more effective treatment strategies.

CPTAC↗

An outbreak of renal failure in asian dogs due to s-triazine adulteration of pet food raw material: Analysis of unique, green kidney stones formed as a result

Renoliths were removed at necropsy from dogs that had died from acute kidney injury in Asia in 2004 and submitted to our laboratories for analysis including elemental composition, mass spectrometry, and microprobe analysis. The presence of a mixed s-triazine matrix comprising melamine, cyanuric acid, and ammelide, but no detectable ammeline, was found in the stone samples we analyzed. The unusual and unique green coloration of these stones was determined to be due to the presence of biliverdin. The occurrence of these green stones distinguished the 2004 incident from another incident in 2007 in the USA and other reported cases. The presence of crystals was reported in renal tubules and collecting ducts in both outbreaks, but no stones were reported in the 2007 incident. Here, this difference suggested a variation in the disease process caused by mixed s- triazine ingestion. Careful monitoring of food additives is warranted to prevent future problems in animals and humans.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Patient-Specific Mathematical Model of the Clear Cell Renal Cell Carcinoma Microenvironment

The interactions between cells and molecules in the tumor microenvironment can give insight into the initiation and progression of tumors and their optimal treatment options. In this paper, we developed an ordinary differential equation (ODE) mathematical model of the interaction network of key players in the clear cell renal cell carcinoma (ccRCC) microenvironment. We then performed a global gradient-based sensitivity analysis to investigate the effects of the most sensitive parameters of the model on the number of cancer cells. The results indicate that parameters related to IL-6 have high a impact on cancer cell growth, such that decreasing the level of IL-6 can remarkably slow the tumor’s growth.

60 APPLIED LIFE SCIENCES↗