Potassium Clearance Research Articles

Impact of convective clearance on intra-dialytic potassium removal in chronic dialysis patients.

Hyperkalemia is frequently encountered and associated with cardio-vascular mortality in chronic hemodialysis (HD) patients. While online hemodiafiltration (OL-HDF) is thought to offer clinical benefit over high-flux HD, the impact of convective clearance on intra-dialytic potassium removal is unknown. Chronic dialysis patients undergoing outpatient HD or OL-HDF at a single center attached to a university hospital were recruited in a prospective observational study. Spent dialysate along with clinical and biological variables were collected during a single mid-week session. We included 141 patients, with 21 treated with HD and 120 with OL-HDF. Mean age was 65.7 ± 15.6 years with 87 (61.7%) men. Mean intra-dialytic potassium removal was 69.9 ± 34.2 mmol. Patients on OL-HDF and HD have similar intra-dialytic potassium removal, with mean values of 69.1 ± 34.2 and 74.3 ± 35.0, respectively. In multivariate analysis, factors associated with intra-dialytic potassium removal were (decreasing order of effect size): dialysate potassium (β -15.5, p < 0.001), pre-HD serum potassium (β 9.1, p < 0.001), and session time (β 7.8, p = 0.003). In OL-HDF patients, substitution flow was not associated with potassium removal. In chronic dialysis patients, convective therapy provided by OL-HDF does not affect potassium removal when compared with high-flux HD. Moreover, the importance of convective volume is not associated with potassium clearance in OL-HDF. Overall, session length and serum-to-dialysate potassium gradient are the main determinants of potassium clearance regardless of dialysis modality. Those results should inform clinicians on the optimal therapy in chronic dialysis patients in the era of OL-HDF.

Renal potassium regulation in a pig model of therapeutic hypothermia

Therapeutic hypothermia is increasingly utilized clinically to reduce tissue metabolism and protect against neurological damage in cases of cardiac arrest, traumatic brain injury or perinatal hypoxic ischemia. With even mild exposure to hypothermia, hypokalemia develops purportedly due to transcellular potassium shifts resulting in decreased circulating potassium levels. Renal dysfunction with body temperature cooling has also been postulated to potentially contribute to development of sustained hypokalemia. In this study, we used a pig model of controlled acute hypothermia without confounding hypotension and hypoxemia, to test the hypothesis that renal handling of potassium remains intact in hypothermia and is not the cause of decreased circulating plasma potassium seen with body cooling. Anesthetized, mechanically ventilated Duroc cross young pigs (n=25, body weight = 10.0 ± 0.4 kg, male or female) were catheterized for hemodynamic monitoring, regional blood flow assessment via colored microspheres, and urine collection. After baseline values were obtained, pigs were divided into a control normothermia group (n=12) with body temperature maintained at 38.4 ± 0.1 oC or a hypothermia group (n=13) with core body temperature cooled to 34.5 ± 0.1 oC and hypothermia sustained for 2 hours. Hypothermia reduced tissue metabolism as indicated by a decrease in oxygen consumption (VO2= 5.2 ± 0.2 ml/kg in normothermia vs 3.7 ± 0.3 ml/kg in hypothermia. Mean arterial pressure (68± 3 mm Hg) and cardiac output (199 ± 21 ml/min/kg) were not different between groups. Even with the short duration of cold exposure, plasma potassium was lower (p&lt;0.05) within 2 hours of hypothermia (4.1 ± 0.1 mEq/L) vs control (4.8 ± 0.1 mEq/L). Cold exposure caused redistribution of blood flow to the small intestines from other internal organs. Renal blood flow tended to decrease with cold, but glomerular filtration rate was suffcient to maintain urine flow, sodium excretion and free water clearance. Potassium clearance, however, was lower (p&lt;0.05) in hypothermia (0.70 ± 0.07 ml/min/kg) than in normothermia (1.04 ± 0.07 ml/min/kg), with lower potassium excretion (hypothermia = 2997 ± 331 mEq/min vs control = 4784 ± 393 mEq/min, p&lt;0.05) and fractional excretion of potassium. Reduced renal potassium excretion is consistent with renal compensation for lower circulating potassium induced by hypothermia. Interestingly, with relatively higher blood flow to the small intestines compared to decreased blood flow of other internal organs, potassium secretion in the early colon may contribute to further potassium wasting in hypothermia. The rapid initiation of decreased potassium circulating levels with hypothermia supports the thesis of temperature sensitive cell membrane potassium channels affecting extracellular to intracellular shifts of potassium. Results of this study indicate that renal potassium regulation is maintained in hypothermia and functions to decrease urinary potassium loss in the face of hypokalemia. The views expressed are those of the authors and do not necessarily reflect the offcial policy or position of the Defense Health Agency, Department of the Army, Department of Defense, or the U.S. Government. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

HPB O04 Segmental perfusion of ex-vivo human liver segments: A 3Rs compliant directly translatable model for pharmacological, bacteriological and genetic research

Abstract Background We have previously presented studies describing the development of a human ex-vivo segmental liver perfusion model (AUGIS 2022, Plenary Prize Session). Utilising surgically resected human liver segments which would otherwise be discarded, bacteriological studies examining host-pathogen interactions can be assessed in a controlled experimental setting. The aim of this study was to compare in a human model the conclusions of work published in the Journal of Experimental Medicine which suggested that in a murine model high-virulence serotypes of Streptococcus pneumoniae exhibited an extraordinary ability to evade capture by Kupffer cells (An et al., 2022). Methods Suitable patients undergoing elective liver resections at a single hepato-pancreato-biliary unit were recruited to the TIMOLD trial. Following hemi-hepatectomies, a healthy liver segment was resected from the specimen and flushed with one litre of heparinised CustodiolTM HTK solution on ice. A segmental branch of the hepatic artery (HA) and portal vein (PV) was identified and cannulated. Ten human liver segments were subjected to normothermic machine perfusion for six hours with OxyglobinTM. During perfusion, six segments were infected with different strains and serotypes of Streptococcus pneumoniae. Perfusate and biopsy specimen were analysed to evaluate bacterial clearance and co-localisation with Kupffer cells. Results Human liver segments exhibited normal histology during perfusion for both control and infected liver segments. Although infected segments had a longer warm and cold ischaemia time than controls (p=0.03 and p=0.01, respectively), there was no difference in PV or HA resistance. Furthermore, there was no difference in lactate clearance (p=0.55), glucose regulation (p=0.87), or potassium clearance (p=0.47). Perfusate culture assays demonstrated no bacterial elimination by the liver. Furthermore, immunofluorescent staining of Kupffer cells and bacteria found no co-localisation of high and low virulence serotypes to hepatic macrophages after 30 minutes (p=0.52) and five hours (p=0.14) of infection. Conclusions Human liver segments did not eliminate pneumococcal strains in a serotype-specific manner or demonstrate preferential co-localisation of bacteria with macrophages based on serotype. These findings highlight issues when extrapolating findings from small animal models as demonstrated with the response of the human liver to invading pathogens. The adoption and implementation of an ex-vivo human liver segmental perfusion model entirely eliminates the need for unethical and unnecessary animal experiments. Using perfused ex-vivo human liver from surgically resected specimens provides a metabolically and physiologically stable environment and is unique in providing results which can be directly translated to the clinical setting.

Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1

Regulation of the volume and electrolyte composition of the cerebrospinal fluid (CSF) is vital for brain development and function. The Na-K-Cl co-transporter NKCC1 in the choroid plexus (ChP) plays key roles in regulating CSF volume by co-transporting ions and mediating same-direction water movements. Our previous study showed ChP NKCC1 is highly phosphorylated in neonatal mice as the CSF K+ level drastically decreases and that overexpression of NKCC1 in the ChP accelerates CSF K+ clearance and reduces ventricle size [1]. These data suggest that NKCC1 mediates CSF K+ clearance following birth in mice. In this current study, we used CRISPR technology to create a conditional NKCC1 knockout mouse line and evaluated CSF K+ by Inductively Coupled Plasma Optical Emission spectroscopy (ICP-OES). We demonstrated ChP-specific reduction of total and phosphorylated NKCC1 in neonatal mice following embryonic intraventricular delivery of Cre recombinase using AAV2/5. ChP-NKCC1 knockdown was accompanied by a delayed perinatal clearance of CSF K+. No gross morphological disruptions were observed in the cerebral cortex. We extended our previous results by showing embryonic and perinatal rats shared key characteristics with mice, including decreased ChP NKCC1 expression level, increased ChP NKCC1 phosphorylation state, and increased CSF K+ levels compared to adult. Collectively, these follow up data support ChP NKCC1’s role in age-appropriate CSF K+ clearance during neonatal development.

Manual single lumen alternating micro-batch dialysis achieves reliable clearance via diffusion.

Acute kidney injury is a cause of preventable deaths in low resource settings due to lack of dialysis access and cost. A manual single lumen alternating micro-batch (mSLAMB) dialysis technique performs kidney replacement therapy using single lumen access, low-cost bags/tubing, intravenous fluids, anda filter without electricity, a battery, or a pump. We propose a protocol whereby mSLAMB can perform diffusive clearance simply and efficiently to bring dialysis to underserved populations. Expired packed red blood cells mixed with crystalloid solution were spiked with urea and anticoagulated with heparin. A Static diffusion Technique (with short flushes of fluid before each filter pass) was compared to a Dynamic diffusion Technique (with fluid running through the filter during the forward pass) to assess urea and potassium clearance. Passive ultrafiltration was the difference between the 200 mL batch volume and volume returned to the blood bag per cycle. Five cycles achieved urea reduction ratios (URR) between 17-67% and potassium clearance of 18-60%, with higher percentagesachieved from higher proportions of batch volume dialyzed to patient volume. Dynamic Technique increased clearance over the Static Technique. Passive ultrafiltration volumes were 2.5-10% of batch volume. mSLAMB dialysis performs diffusive clearance and passive ultrafiltration efficiently, while preserving resources and available manpower. mSLAMB is a dialysis technique that can perform efficient diffusive clearance and passive ultrafiltration without electricity, batteries, or a pump. With basic medical supplies and limited manpower, mSLAMB is a cost-effective means of providing emergency dialysis in low resource areas. We propose a basic algorithm for safe and cost-effective dialysis for people of different ages and sizes.

Casting a Wider Net When Fishing for Mechanisms of Anesthesia.

Casting a Wider Net When Fishing for Mechanisms of Anesthesia.

Plasticity of perisynaptic astroglia during ischemia-induced spreading depolarization.

High astroglial capacity for glutamate and potassium clearance aids in recovering spreading depolarization (SD)-evoked disturbance of ion homeostasis during stroke. Since perisynaptic astroglia cannot be imaged with diffraction-limited light microscopy, nothing is known about the impact of SD on the ultrastructure of a tripartite synapse. We used serial section electron microscopy to assess astroglial synaptic coverage in the sensorimotor cortex of urethane-anesthetized male and female mice during and after SD evoked by transient bilateral common carotid artery occlusion. At the subcellular level, astroglial mitochondria were remarkably resilient to SD compared to dendritic mitochondria that were fragmented by SD. Overall, 482 synapses in `Sham' during `SD' and `Recovery' groups were randomly selected and analyzed in 3D. Perisynaptic astroglia was present at the axon-spine interface (ASI) during SD and after recovery. Astrocytic processes were more likely found at large synapses on mushroom spines after recovery, while the length of the ASI perimeter surrounded by astroglia has also significantly increased at large synapses. These findings suggest that as larger synapses have a bigger capacity for neurotransmitter release during SD, they attract astroglial processes to their perimeter during recovery, limiting extrasynaptic glutamate escape and further enhancing the astrocytic ability to protect synapses in stroke.

Does the early aldosterone-induced SGK1 play a role in early Kaliuresis?

Urinary K+ potassium excretion rapidly increases after a potassium‐rich meal. The early aldosterone‐induced sgk1 gene (encoding serum and glucocorticoid‐induced kinase 1), activates potassium clearance, but the role of this kinase in the early activation of K+ secretion has not been clearly defined. Here, we challenged inducible renal‐tubule‐specific Sgk1Pax8 / LC1 knockout mice with an acute high‐potassium load (HK:5%K+) and compared the physiological and molecular responses to control mice. We observe that urinary excretion after a K+ load over the first 3 h is not dependent on SGK1 but is coincident with the rapid dephosphorylation of the Na+,Cl−‐cotransporter (NCC) to increase distal salt delivery. Molecular analyses indicate that whereas SGK1‐mediated phosphorylation of the ubiquitin‐protein ligase NEDD4‐2 begins to increase by 3h, SGK1‐dependent proteolytic activation of ENaC only becomes detectable after 6 h of HK intake. Consistent with SGK1‐dependent ENaC activation via inhibition of NEDD4‐2‐mediated ubiquitylation, Sgk1Pax8 / LC1 mice are unable to efficiently inhibit NEDD4‐2 or increase ENaC cleavage after 6 h of HK. Nevertheless, no defect in acute K+ balance was detected in the mutant mice after 6 h of HK. Moreover, we found that Sgk1Pax8 / LC1 mice reduce NCC phosphorylation and NCC‐mediated salt absorption to a greater extent than control mice after a K+ load, promoting increased amiloride‐sensitive Na+‐reabsorption via ENaC to maintain adequate kaliuresis. Together, these data indicate that: (a) during the early 3 h of HK intake, K+ excretion is SGK1‐independent even under an extreme K+ challenge, (b) shortly after, SGK1 inhibits NEDD4‐2 and activates ENaC to stimulate K+‐secretion, (c) SGK1‐dependent phosphorylation of NCC occurs, acting more likely as a brake pedal to prevent excessive K+ loss.

Kidney Replacement Therapy for Patients Requiring Cardiopulmonary Bypass Support during Cardiac Surgery.

Kidney Replacement Therapy for Patients Requiring Cardiopulmonary Bypass Support during Cardiac Surgery.

Astroglial asthenia and loss of function, rather than reactivity, contribute to the ageing of the brain.

Astroglia represent a class of heterogeneous, in form and function, cells known as astrocytes, which provide for homoeostasis and defence of the central nervous system (CNS). Ageing is associated with morphological and functional remodelling of astrocytes with a prevalence of morphological atrophy and loss of function. In particular, ageing is associated with (i) decrease in astroglial synaptic coverage, (ii) deficits in glutamate and potassium clearance, (iii) reduced astroglial synthesis of synaptogenic factors such as cholesterol, (iv) decrease in aquaporin 4 channels in astroglial endfeet with subsequent decline in the glymphatic clearance, (v) decrease in astroglial metabolic support through the lactate shuttle, (vi) dwindling adult neurogenesis resulting from diminished proliferative capacity of radial stem astrocytes, (vii) decline in the astroglial-vascular coupling and deficient blood-brain barrier and (viii) decrease in astroglial ability to mount reactive astrogliosis. Decrease in reactive capabilities of astroglia are associated with rise of age-dependent neurodegenerative diseases. Astroglial morphology and function can be influenced and improved by lifestyle interventions such as intellectual engagement, social interactions, physical exercise, caloric restriction and healthy diet. These modifications of lifestyle are paramount for cognitive longevity.

Exercise in patients on chronic hemodialysis: current evidence, knowledge gaps and future perspectives.

Physical inactivity is common in hemodialysis patients, and is associated with disability and poor outcomes. We summarize the effects of aerobic, resistance or mixed exercise training on aerobic capacity, muscle mass and strength, dialysis efficiency, quality of life and cardiovascular adaptation according to clinical studies on this population, also focusing on knowledge gaps as topics for future research. Finally, we put evidence into clinical context deriving practical indications for exercise implementation in these patients. In hemodialysis patients, aerobic or mixed exercise training increases predominantly aerobic capacity, whereas resistance training seems more effective in increasing muscle strength. Data concerning dialysis efficiency are equivocal, although phosphate and potassium clearances seem to be improved. There is also inconclusive evidence concerning changes in cardiovascular risk factors. All types of exercise improve patients' quality of life. However, there is a need for protocol standardization and selection of easily measurable endpoints. In clinical practice, it is advised that exercise implementation be performed gradually, and goals be tailored to individual pretraining fitness levels to maximize patient adherence and clinical benefits. The overall evidence suggests that exercise training is beneficial and well tolerated in hemodialysis patients, although heterogeneity across studies hinders generalization of results. In any case, a gradual and individualized approach should be used to implement exercise in these patients.

Serotonin, norepinephrine, and acetylcholine differentially affect astrocytic potassium clearance to modulate somatosensory signaling in male mice.

Changes in extracellular potassium ([K+ ]e ) modulate neuronal networks via changes in membrane potential, voltage-gated channel activity, and alteration to transmission at the synapse. Given the limited extracellular space in the central nervous system, potassium clearance is crucial. As activity-induced potassium transients are rapidly managed by astrocytic Kir4.1 and astrocyte-specific Na+ /K+ -ATPase, any neurotransmitter/neuromodulator that can regulate their function may have indirect influence on network activity. Neuromodulators differentially affect cortical/thalamic networks to align sensory processing with differing behavioral states. Given serotonin (5HT), norepinephrine (NE), and acetylcholine (ACh) differentially affect spike frequency adaptation and signal fidelity ("signal-to-noise") in somatosensory cortex, we hypothesize that [K+ ]e may be differentially regulated by the different neuromodulators to exert their individual effects on network function. This study aimed to compare effects of individually applied 5HT, NE, and ACh on regulating [K+ ]e in connection to effects on cortical-evoked response amplitude and adaptation in male mice. Using extracellular field and K+ ion-selective recordings of somatosensory stimulation, we found that differential effects of 5HT, NE, and ACh on [K+ ]e regulation mirrored differential effects on amplitude and adaptation. 5HT effects on transient K+ recovery, adaptation, and field post-synaptic potential amplitude were disrupted by barium (200µM), whereas NE and ACh effects were disrupted by ouabain (1µM) or iodoacetate (100µM). Considering the impact [K+ ]e can have on many network functions; it seems highly efficient that neuromodulators regulate [K+ ]e to exert their many effects. This study provides functional significance for astrocyte-mediated buffering of [K+ ]e in neuromodulator-mediated shaping of cortical network activity.

Citrus aurantium Ameliorates Cisplatin-Induced Nephrotoxicity.

We aimed to study the effects of Citrus aurantium (C. aurantium) on renal functions in cisplatin-induced nephrotoxicity in rats. The study involved male Wistar rats weighing 250–300 g that were fed and kept under standard conditions. Rats were randomly divided into control, cisplatin administered, C. aurantium 200 mg/kg, and C. aurantium 400 mg/kg groups. Cisplatin was administered at 5 mg/kg i.p. once at the start of study to induce nephrotoxicity. Blood and urine samples were obtained at alternative days for analysis. The body weight and urine output were monitored at regular intervals. Plasma and urinary sodium, potassium, and creatinine levels were measured at the end of study duration. Absolute excretion of sodium and potassium; sodium to potassium ratio; kidney weights; fractional excretion of sodium and potassium; and absolute creatinine clearance were determined to analyze the effects of C. aurantium. Histopathological changes of kidney tissues were studied to determine relevant effects. The results indicate that cisplatin lowered the total body weights while raising the urinary output and kidney weights, reversed by C. aurantium both dose and time dependently. Similarly, C. aurantium markedly normalized plasma, urinary sodium, potassium, and creatinine levels. Cisplatin-induced absolute sodium clearance, absolute potassium clearance, absolute creatinine clearance, sodium to potassium ratio, and fractional excretion of sodium and potassium were significantly reversed by C. aurantium. Histopathological analysis showed notable improvement in C. aurantium administered groups as compared to cisplatin-induced group. Study suggests that C. aurantium possesses excellent nephroprotective effects against cisplatin-induced toxicity.

The effect of a multidisciplinary weight loss program on renal circadian rhythm in obese adolescents.

Adolescent obesity is a serious health problem associated with many comorbidities. Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is also disrupted in obesity, though this has not yet been investigated. This study aimed to examine renal circadian rhythm in obese adolescents before and after weight loss.In 34 obese adolescents (median age 15.7years) participating in a residential weight loss program, renal function profiles and blood samples were collected at baseline, after 7months, and again after 12months of therapy. The program consisted of dietary restriction, increased physical activity, and psychological support. The program led to a median weight loss of 24kg and a reduction in blood pressure. Initially, lower diurnal free water clearance (- 1.08 (- 1.40-- 0.79) mL/min) was noticed compared with nocturnal values (0.75 (- 0.89-- 0.64) mL/min). After weight loss, normalization of this inverse rhythm was observed (day - 1.24 (- 1.44-1.05) mL/min and night - 0.98 (- 1.09-- 0.83) mL/min). A clear circadian rhythm in diuresis rate and in renal clearance of creatinine, solutes, sodium, and potassium was seen at all time points. Furthermore, we observed a significant increase in sodium clearance. Before weight loss, daytime sodium clearance was 0.72mL/min (0.59-0.77) and nighttime clearance was 0.46mL/min (0.41-0.51). After weight loss, daytime clearance increased to 0.99mL/min (0.85-1.17) and nighttime clearance increased to 0.78mL/min (0.64-0.93).Conclusion: In obese adolescents, lower diurnal free water clearance was observed compared with nocturnal values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity. Both before and after weight loss, clear circadian rhythm of diuresis rate and renal clearance of creatinine, solutes, sodium, and potassium was observed.What is Known:• Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is disrupted in obesity, though this has not been investigated yet.What is New:• In obese adolescents, an inverse circadian rhythm of free water clearance was observed, with higher nighttime free water clearance compared with daytime values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity.• Circadian rhythm in diuresis rate and in the renal clearance of creatinine, solutes, sodium, and potassium was preserved in obese adolescents and did not change after weight loss.

The effects of intradialytic exercise on hemodialysis adequacy: A systematic review.

Dialysis adequacy is an independent predictor of high mortality rates in hemodialysis patients. Intradialytic exercise is a potential strategy to increase uremic solute removal by increasing blood flow to low perfusion tissue beds. The purpose of this review is to establish the efficacy of intradialytic exercise for hemodialysis adequacy. Additionally, this review aims to provide practical information to aid health care professionals implement intradialytic exercise for dialysis adequacy. Database and hand searches identified 15 published interventional studies that implemented intradialytic exercise for dialysis adequacy as a primary outcome measure in adult maintenance hemodialysis patients. Data pertaining to dialytic solute clearance of urea, creatinine, beta2 microglobulin, phosphate, and potassium were extracted. Mean differences, normalized to percentages, and effect sizes were calculated and reported. The current data pertaining to the use of intradialytic exercise for improving dialysis adequacy in terms of Kt/Vurea or small molecule uremic toxin clearance are equivocal. Limited data showed that intradialytic exercise has no effect middle molecule toxin (beta2 - microglobulin) clearance. Intradialytic exercise favored increased phosphate removal showing medium to large effects for reduced serum concentrations, reduced rebound and increased clearance. In summary, supervised light to moderate intradialytic aerobic cycling appears to be beneficial for increasing phosphate removal and may be an adjunct therapy for patients failing to meet clinical phosphate targets. Further work is required to establish the effect of intradialytic exercise on Kt/Vurea and other middle molecule and protein bound solutes. Research aimed at establishing the most effective exercise prescription for improved solute clearance is warranted.

Neuro-Glial Network Model Of Postictal Generalized EEG Suppression (PGES).

Over the past couple of decades, glial cells have been highlighted as active agents in hyperexcitability of neuronal networks, specifically playing key roles in seizure onset and termination. In particular, microglia have been suggested to have both neuroprotective and neurotoxic effects on the brain. Investigation into seizure termination is of particular interest, as it is sometimes followed by a postictal generalized EEG suppression (PGES) - a low activity state that is potentially associated with sudden unexpected death in epilepsy. In this study, we attempt to link glial effects - synaptic pruning and astrocytic potassium clearance - to the duration of spontaneous epileptiform discharges (SEDs) as well as interSED intervals (iSEDs). We build upon an earlier model of a neuroglial network by translating it into the cortical paradigm and including microglial units. Preliminary findings of our model demonstrated that the duration of SEDs is largely determined by the astrocytic potassium clearance, whereas iSEDs significantly increased with microglial-driven synaptic pruning. In our model, astrocytic potassium clearance itself did not bring a PGES-like state, whereas microglial effects did, which suggests a potential biomarker for PGES phenomena.

Experience of cyclooxygenase inhibitor use for correction of urine overproduction in incontinent women

Hypothesis/aims of study. Questions of urine incontinence pathogenesis and ways of treatment are actively discussed by gynecologists, urologists and neuropathologists. Urine incontinence often has multifactor origin: the causes of urine incontinence are connected, as a rule, with violation of urine continence functional mechanisms, anatomical and topographical features of the lower urinary tract or an age failure of ovaries function. At the same time changes of kidneys function play part in urine incontinence pathogenesis. In some cases urine incontinence is combined with urine overproduction or inversion of circadian rhythm of renal function due to decrease in a reabsorption sodium ions in the thick ascending limb of a Henle’s loop. The reabsorption of Na+, K+, Ca2+, Mg2+, Cl– in this department of a nephron is increased by vasopressin activation of V2-receptors. In some patients we succeeded to normalize ions transport, diuresis, circadian rhythm of urine production by desmopressin administration, however in some cases significant decrease in a diuresis did not happen. The lack of therapy effect could be connected with local production of substances resisting to effect of this hormone, in particular prostaglandin E2. The current analysis was undertaken to evaluate the clinical efficiency of Diclofenac in incontinent patients with nocturnal polyuria and polyuria.&#x0D; Study design, materials and methods. A total of 44 patients with complaints of urinary incontinence, polyuria (24-urine volume of 40 mL/kg bodyweight or above) or nocturnal polyuria (nocturnal volume/24-h urine volume of 0.33 or above) (Van Kerrebroeck P., 2002) and 14 control subjects were included. Mean patient age was 42.8 ± 4.5 years, in control subjects 39.4 ± 6.3 (p &gt; 0.05). All participants performed 72h-urinecollection to determine the voided volumes and the levels of creatinine, osmolality, sodium, magnesium and potassium for each sample. A blood sample was taken during the 72-urinecollection to determine the levels of creatinine, osmolality, sodium, magnesium and potassium. The examination of patients with polyuria and nocturnal polyuria was performed twice: in the initial state and one month after the start of treatment with optimal dose of Diclofenac.&#x0D; Results. In patients with polyuria and nocturnal polyuria the glomerular filtration rate was normal, whereas diuresis and solute (sodium, magnesium, potassium) clearance in night samples in nocturnal polyuria and both in night and day samples was higher. Diclofenac use had the normalizing effect on transport of ions in a nephron.

Low-to-High Cross-Frequency Coupling in the Electrical Rhythms as Biomarker for Hyperexcitable Neuroglial Networks of the Brain.

One of the features used in the study of hyperexcitablility is high-frequency oscillations (HFOs, >80Hz). HFOs have been reported in the electrical rhythms of the brain's neuroglial networks under physiological and pathological conditions. Cross-frequency coupling (CFC) of HFOs with low-frequency rhythms was used to identify pathologic HFOs in the epileptogenic zones of epileptic patients and as a biomarker for the severity of seizure-like events in genetically modified rodent models. We describe a model to replicate reported CFC features extracted from recorded local field potentials (LFPs) representing network properties. This study deals with a four-unit neuroglial cellular network model where each unit incorporates pyramidal cells, interneurons, and astrocytes. Three different pathways of hyperexcitability generation-Na - ATPase pump, glial potassium clearance, and potassium afterhyperpolarization channel-were used to generate LFPs. Changes in excitability, average spontaneous electrical discharge (SED) duration, and CFC were then measured and analyzed. Each parameter caused an increase in network excitability and the consequent lengthening of the SED duration. Short SEDs showed CFC between HFOs and theta oscillations (4-8 Hz), but in longer SEDs the low frequency changed to the delta range (1-4 Hz). Longer duration SEDs exhibit CFC features similar to those reported by our team. First, Identifying the exponential relationship between network excitability and SED durations; second, highlighting the importance of glia in hyperexcitability (as they relate to extracellular potassium); and third, elucidation of the biophysical basis for CFC coupling features.

A population-based approach to assess the heritability and distribution of renal handling of electrolytes

The handling of electrolytes by the kidney is essential for homeostasis. However, the heritability of these processes, the first step in gene discovery, is poorly known. To help clarify this, we estimated the heritability of serum concentration, urinary excretion, renal clearance, and fractional excretion of sodium, potassium, magnesium, calcium, phosphate, and chloride in a population-based study. Nuclear families were randomly selected from the general population in Lausanne, Geneva, and Bern, Switzerland, and urine collected over 24-hour periods. We used the ASSOC program (S.A.G.E.) to estimate narrow sense heritability, including sex, age, body mass index, and study center as covariates in the model. The 1128 participants, from 273 families, had a mean age of 47 years, body mass index of 25.0 kg/m2, and an estimated glomerular filtration rate (CKD-EPI) of 98 mL/min/1.73 m2. The heritability of serum concentration was highest for calcium, 37% and lowest for sodium, 13%. The heritability of 24-hour urine clearances, excretions, and fractional excretions ranged from 15%, 10%, and 16%, respectively, for potassium to 45%, 44%, and 51%, respectively, for calcium. All probability values were significant. The heritability for phosphate-related phenotypes was lower than that for calcium. Thus, the serum and urine concentrations as well as urinary excretion and renal handling of electrolytes are heritable in the general adult population. The phenotypic variance attributable to additive genetic factors was variable and was higher for calcium. These results pave the way for identifying genetic variants involved in electrolyte homeostasis in the general population.

Comparison of hypotensive, diuretic and renal effects between cladodes of Opuntia ficus-indica and furosemide.

To investigate the diuretic, hypotensive and renal effect of Opuntia ficus-indica in two different species in oral and intravenous administration. Diuretic activity was evaluated in rats with the plant cladode gel and aqueous extract administrated orally, and was evaluated in rabbits with plant extract administered intravenously. Single and repeated doses of cladode gel or aqueous extract of cladode were tested. Urine volume and blood and urine creatinine, sodium and potassium were measured, and creatinine clearance was calculated. The hypotensive effect of lyophilized extract of cladode was evaluated in rabbits. Two polyethylene PE50 catheters were used: one in the jugular vein for the infusion of the plant extract and the other in the carotid for the evaluation of the arterial pressure. The cladode gel or aqueous extract increased urine volume, creatinine clearance and urinary excretion of sodium and potassium without significant effect on serum creatinine or blood urea. Furosemide, gel and aqueous extract of cladode insignificantly lowered plasma potassium in rats. Intravenous administration of the lyophilized extract caused a significant decrease in mean arterial pressure in rabbits with a significant increase in urine volume and urine sodium and potassium; the effect was dose dependent. Intravenous administration of lyophilized extract did not affect plasma sodium or potassium. Gel and aqueous extract of Opuntia ficus-indica cladode have a significant diuretic effect on rats, and the lyophilized extract has a diuretic and hypotensive effect on normotensive rabbits without deterioration in renal function test. Additional studies on active ingredients are essential to pave the way for clinical studies on diuretic and hypotensive effect of the plant.