Potassium Concentration Gradient Research Articles

Blocking Aδ- and C-fiber neural transmission by sub-kilohertz peripheral nerve stimulation.

We recently showed that sub-kilohertz electrical stimulation of the afferent somata in the dorsal root ganglia (DRG) reversibly blocks afferent transmission. Here, we further investigated whether similar conduction block can be achieved by stimulating the nerve trunk with electrical peripheral nerve stimulation (ePNS). We explored the mechanisms and parameters of conduction block by ePNS via ex vivo single-fiber recordings from two somatic (sciatic and saphenous) and one autonomic (vagal) nerves harvested from mice. Action potentials were evoked on one end of the nerve and recorded on the other end from teased nerve filaments, i.e., single-fiber recordings. ePNS was delivered in the middle of the nerve trunk using a glass suction electrode at frequencies of 5, 10, 50, 100, 500, and 1000 Hz. Suprathreshold ePNS reversibly blocks axonal neural transmission of both thinly myelinated Aδ-fiber axons and unmyelinated C-fiber axons. ePNS leads to a progressive decrease in conduction velocity (CV) until transmission blockage, suggesting activity-dependent conduction slowing. The blocking efficiency is dependent on the axonal conduction velocity, with Aδ-fibers efficiently blocked by 50-1000 Hz stimulation and C-fibers blocked by 10-50 Hz. The corresponding NEURON simulation of action potential transmission indicates that the disrupted transmembrane sodium and potassium concentration gradients underly the transmission block by the ePNS. The current study provides direct evidence of reversible Aδ- and C-fiber transmission blockage by low-frequency (<100 Hz) electrical stimulation of the nerve trunk, a previously overlooked mechanism that can be harnessed to enhance the therapeutic effect of ePNS in treating neurological disorders.

Positron emission tomography imaging of the sodium iodide symporter senses real-time energy stress in vivo

BackgroundTissue environment is critical in determining tumour metabolic vulnerability. However, in vivo drug testing is slow and waiting for tumour growth delay may not be the most appropriate endpoint for metabolic treatments. An in vivo method for measuring energy stress would rapidly determine tumour targeting in a physiologically relevant environment. The sodium-iodide symporter (NIS) is an imaging reporter gene whose protein product co-transports sodium and iodide, and positron emission tomography (PET) radiolabelled anions into the cell. Here, we show that PET imaging of NIS-mediated radiotracer uptake can rapidly visualise tumour energy stress within minutes following in vivo treatment.MethodsWe modified HEK293T human embryonic kidney cells, and A549 and H358 lung cancer cells to express transgenic NIS. Next, we subjected these cells and implanted tumours to drugs known to induce metabolic stress to observe the impact on NIS activity and energy charge. We used [18F]tetrafluoroborate positron emission tomography (PET) imaging to non-invasively image NIS activity in vivo.ResultsNIS activity was ablated by treating HEK293T cells in vitro, with the Na+/K+ ATPase inhibitor digoxin, confirming that radiotracer uptake was dependent on the sodium–potassium concentration gradient. NIS-mediated radiotracer uptake was significantly reduced (− 58.2%) following disruptions to ATP re-synthesis by combined glycolysis and oxidative phosphorylation inhibition in HEK293T cells and by oxidative phosphorylation inhibition (− 16.6%) in A549 cells in vitro. PET signal was significantly decreased (− 56.5%) within 90 min from the onset of treatment with IACS-010759, an oxidative phosphorylation inhibitor, in subcutaneous transgenic A549 tumours in vivo, showing that NIS could rapidly and sensitively detect energy stress non-invasively, before more widespread changes to phosphorylated AMP-activated protein kinase, phosphorylated pyruvate dehydrogenase, and GLUT1 were detectable.ConclusionsNIS acts as a rapid metabolic sensor for drugs that lead to ATP depletion. PET imaging of NIS could facilitate in vivo testing of treatments targeting energetic pathways, determine drug potency, and expedite metabolic drug development.

Ian Michael Glynn. 3 June 1928—7 July 2022

In the mid 1950s the convergence of crucial discoveries on nerve and muscle physiology brought to centre stage the question of how sodium and potassium concentration gradients needed for nerve conduction and muscle contraction are maintained. This was the subject Ian Glynn set out to investigate when he returned to Cambridge as a Trinity College graduate student in 1953. His initial results on the sodium and potassium permeabilities of the human red blood cell membrane, published in 1956–1967, established these cells as an ideal experimental system for studying the transport properties of the ‘sodium pump’ because of the ease with which the ionic composition of intra- and extracellular environments could be controlled, cell metabolism managed and ionic fluxes measured using isotopes. This work was followed by ground-breaking contributions from his research group over the next decades in a long series of brilliantly designed experiments, setting the foundations of our current understanding of the molecular mechanism of the sodium/potassium pump. Ian became a Trinity College fellow in 1960, advanced rapidly to a professorship in the Department of Physiology after being elected Fellow of the Royal Society in 1970, and was appointed head of department in 1986 until his retirement in 1995.

Urine osmolality predicts worsening renal function and poor prognosis in acute decompensated heart failure

Abstract Background/Purpose Worsening renal function (WRF) can sometimes occur in the patients with acute decompensated heart failure (ADHF) and increase the risk of morbidity and mortality (1). In a previous study, it was reported that fractional excretion of sodium (FENa) reflects net sodium reabsorption from nephron segments and predicts WRF during treating ADHF (2). On the other hand, recently the new drugs which approach urine concentration mechanism and affect urine osmolality (U-OSM), such as tolvaptan and sodium-glucose cotransporter-2 inhibitor, have begun to be widely used as treatment of heart failure. Thus, we focused on U-OSM, which reflects not only sodium handling but also water excretion controlled by the collecting duct, and evaluated the association between WRF and U-OSM. Moreover, previous studies have demonstrated that FENa, fractional excretion of urea nitrogen and transtubular potassium concentration gradient are markers for long-term prognosis in patients with ADHF (3–5). Therefore, we also studied whether U-OSM can predict prognosis in ADHF. Methods A total of 157 patients admitted to our hospital because of a primary diagnosis of ADHF from February 2020 through July 2021 were retrospectively reviewed. U-OSM in the spot urinary samples were examined within 72 hours after admission. U-OSM was calculated based on the following validated formula (6): U-OSM = 1.07 × {2 × [urine sodium (mEq/L)] + [urine urea nitrogen (mg/dL)]/2.8 + [urine creatinine (mg/dl)] × 2/3} + 16.2. The primary outcome was the occurrence of WRF during hospitalization. WRF was defined as increased serum creatinine ≥0.3 mg/dL from baseline (7). The secondary outcome was the occurrence of ADHF readmission and all-cause death within 180 days after discharge. Results Primary Outcome. WRF developed in 46% of all patients. In the patients that developed WRF during hospitalization, U-OSM was significantly lower than in the patients without WRF (366±106 mOsm/L versus 430±128 mOsm/L; P&amp;lt;0.001). Receiver operating characteristic curve analysis revealed the optimal cutoff values of U-OSM was 403 mOsm/L (AUC 0.64; 95% CI: 0.56–0.72; P&amp;lt;0.001) to predict the WRF (Figure 1). On multivariable logistic regression analysis, U-OSM (OR, 1.99, 95% CI: 1.27–3.12; p=0.003) and serum creatinine (OR, 1.00, 95% CI: 0.99–1.00; P=0.009) were independent predictors of WRF. Secondary Outcome. There were 34 patients (22%) readmitted and 9 patients (6%) died within 180 days after discharge. ROC curve analysis revealed the optimal cutoff values of U-OSM as 349 mOsm/L (C-statistic 0.74; 95% CI: 0.65–0.83; P&amp;lt;0.001) to predict ADHF readmission and all-cause death within 180 days (Figure 2A). On Kaplan-Meier analysis, the secondary outcome was significantly higher in patients with U-OSM&amp;lt;349 mOsm/L (u-OSM≥349, 57%, U-OSM&amp;lt;349, 43%; HR, 0.99; 95% CI: 0.99–1.00, P&amp;lt;0.001) (Figure 2B). Conclusion U-OSM on admission may be a predictor of WRF and a prognostic marker in ADHF patients. Funding Acknowledgement Type of funding sources: None.

Early role for a Na+,K+-ATPase (ATP1A3) in brain development

Osmotic equilibrium and membrane potential in animal cells depend on concentration gradients of sodium (Na+) and potassium (K+) ions across the plasma membrane, a function catalyzed by the Na+,K+-ATPase α-subunit. Here, we describe ATP1A3 variants encoding dysfunctional α3-subunits in children affected by polymicrogyria, a developmental malformation of the cerebral cortex characterized by abnormal folding and laminar organization. To gain cell-biological insights into the spatiotemporal dynamics of prenatal ATP1A3 expression, we built an ATP1A3 transcriptional atlas of fetal cortical development using mRNA in situ hybridization and transcriptomic profiling of ∼125,000 individual cells with single-cell RNA sequencing (Drop-seq) from 11 areas of the midgestational human neocortex. We found that fetal expression of ATP1A3 is most abundant to a subset of excitatory neurons carrying transcriptional signatures of the developing subplate, yet also maintains expression in nonneuronal cell populations. Moving forward a year in human development, we profiled ∼52,000 nuclei from four areas of an infant neocortex and show that ATP1A3 expression persists throughout early postnatal development, most predominantly in inhibitory neurons, including parvalbumin interneurons in the frontal cortex. Finally, we discovered the heteromeric Na+,K+-ATPase pump complex may form nonredundant cell-type-specific α-β isoform combinations, including α3-β1 in excitatory neurons and α3-β2 in inhibitory neurons. Together, the developmental malformation phenotype of affected individuals and single-cell ATP1A3 expression patterns point to a key role for α3 in human cortex development, as well as a cell-type basis for pre- and postnatal ATP1A3-associated diseases.

High-magnesium exposure to bullfrog heart causes ST segment elevation.

Hypermagnesemia occurs in elderly people or patients with renal insufficiency after excessive ingestion of magnesium-containing laxatives. In addition to typical electrocardiogram (ECG) findings caused by conduction defects, changes in the ST segments and T waves are also observed in patients with severe hypermagnesemia. This suggested the involvement of similar pathophysiology to acute myocardial infarction, as we previously demonstrated using burn-induced subepicardial injury model in frog hearts. In the present study, by exposing the bullfrog heart to high-magnesium solution, we reproduced prominent ST segment changes in ECG as actually observed in patients with severe hypermagnesemia. In addition to the great increase in the T waves, the ECG showed a marked elevation of the ST segments and the cardiac action potential demonstrated a marked shift of the resting membrane potential to the depolarized side. High-magnesium exposure did not affect the abundance of Na+/K+-ATPase proteins. However, the pharmacological stimulation of Na+/K+-ATPase activity by insulin quickly retrieved the elevated ST segments in ECG. From these results, the functional blockade of Na+/K+-ATPase activity by magnesium ions was thought to be responsible for generating the potassium concentration gradient and the subsequent ST segment changes.

Mechanisms of formation of tubulointerstitional renal impairment at the initial stages of experimental diabetes mellitus

Tubulointerstitial disorders were studied in 11-day long experimental alloxan-induced diabetes mellitus. We concluded that changes in the concentration gradients of sodium and potassium are already observed at the early stages of pathology and indicate the initiation of tubular dysfunction accompanied by intensification of natriuresis and kaliuresis. Despite regulatory control of the renal countercurrent multiplication system and intensification of sodium and potassium reabsorption at the level of the ascending Henle loop, further progression of tubulopathy, in addition to the relative insufficiency of the proximal and distal tubules, will result in the disturbance of hormonal-dependent reabsorption of cations, inhibition of aldosterone- and vasopressin-dependent mechanisms of interstitial osmolarity regulation with the development of tubulointerstitial disorders that unable adequate osmotic concentration of urine. Keywords: experimental diabetes mellitus, alloxan, concentration gradient of sodium and potassium, tubulointerstitial renal impairment.

Effect of empagliflozin as add-on therapy on transtubular potassium concentration gradient in patients with type 2 diabetes hospitalized for acute decompensated heart failure

Abstract Background The transtubular potassium concentration gradient (TTKG) has been reported to be a marker of renal aldosterone bioactivity, and has been shown to be a surrogate of arterial underfilling in patients with acute decompensated heart failure (ADHF). Moreover, high TTKG at discharge has been shown to be associated with poor prognosis in ADHF patients. Empagliflozin, one of the sodium glucose cotransporter 2 inhibitors, has been shown to reduce the risk of cardiovascular mortality in patients with type 2 diabetes mellitus (T2D) and cardiovascular disease. However, little is known about the effect of empagliflozin as add-on therapy on TTKG in T2D patients with ADHF. Purpose We sought to elucidate the effect of empagliflozin as add-on therapy on TTKG in T2D patients with ADHF. Methods We enrolled 58 consecutive T2D patients admitted for ADHF. On admission, enrolled patients were randomly assigned in a 1:1 ratio to either empagliflozin add-on therapy (EMPA(+)) or conventional glucose-lowering therapy (EMPA(−)). All patients in EMPA(+) group received empagliflozin (10 mg/day) throughout the study period. Left ventricular ejection fraction (LVEF) was measured at baseline using echocardiography. Body weight and vital signs, such as blood pressure and heart rate, were measured, and blood and urine samples were collected at baseline and 1, 2, 3 and 7 days after randomization. The TTKG was measured using the first morning urine samples collected on each day. TTKG was calculated according to the following equation: TTKG = (Ku/Ks)×(plasma osmolality/urine osmolality), where Ku is urine potassium concentration and Ks is serum potassium concentration, as previously reported. Results Thirty patients were assigned to the EMPA(+) group, and 28 patients were assigned to the EMPA(−) group. There were no significant baseline differences in LVEF, plasma B-type natriuretic peptide (BNP) level, body mass index, or serum creatinine level between the EMPA(+) and EMPA(−) groups. TTKG did not significantly differ between the two groups at baseline. However, seven days after randomization, plasma BNP level was significantly lower in the EMPA(+) group than in the EMPA(−) group (median 227 [IQR 114–381] pg/mL vs 362 [227–554] pg/mL, p=0.0294). Furthermore, TTKG of the EMPA(+) group was significantly lower at 2, 3 and 7 days after randomization (Figure). Conclusions This study demonstrated that empagliflozin as add-on therapy can lower TTKG in T2D patients with ADHF. Figure 1 Funding Acknowledgement Type of funding source: None

Diagnostic value of parameters from a spot urine sample for renal potassium loss in hypokalemia

BackgroundWe assessed the value of 1) a spot urine test for diagnosing hypokalemia caused by renal potassium loss, and 2) actual 24-hour urine potassium excretion (24 hUK-actual) for diagnosing hypokalemia caused by renal potassium loss in patients treated with potassium supplementation. The study population was from Southwest China. MethodsPatients with hypokalemia were divided into 2 groups: hypokalemia caused by renal potassium loss (n = 67) and hypokalemia caused by extrarenal potassium loss (n = 63). Urine potassium concentration (UK), urine creatinine concentration (UCr), urine potassium-creatinine ratio (UK/UCr), fractional excretion of potassium (FEK), transtubular potassium concentration gradient (TTKG), and 24-h urine potassium excretion (24 hUK-calculated) were derived from spot urine samples collected on admission, before initiation of therapy. Patients received intravenous potassium chloride 0.4 or 0.6 g/h. 24 hUK-actual was detected in patients whose serum potassium did not return to normal after 24 h of therapy. ResultsPatients with hypokalemia caused by renal potassium loss had significantly higher UK, UK/UCr, FEK, TTKG and 24 hUK-calculated compared to patients with hypokalemia caused by extrarenal potassium loss (P < 0.05). FEK predicted renal potassium loss in hypokalemia with high accuracy at a cut-off of 9.29% (sensitivity, 80.6%; specificity, 85.7%). The area under the curve for 24 hUK-actual in predicting renal potassium loss in patients with hypokalemia treated with low or high-dose potassium chloride infusion were 0.939 or 0.956, respectively. On the spot urine test, FEK showed the highest correlation with 24 hUK-actual during low or high dose potassium chloride infusion (r = 0.831, p < 0.001 or r = 0.764, p < 0.001). ConclusionsFEK from a spot urine sample represents a convenient and reliable parameter to predict renal potassium loss in patients with hypokalemia.

Efficacy, potency and kinetics of activation process of Kv7.4 and Kv7.5 channel with novel pharmacological activators targeted for Lower Urinary Tract Syndrome (LUTS)

Among several types of Kv7 (KCNQ) voltage gated potassium channel family, Kv7.4 (KCNQ4) and Kv7.5 (KCNQ5) channels show prominent expression in smooth muscle, cardiac tissues and vasculature. In general, activation of the channel would mediate strong efflux of potassium and lead membrane potential to hyperpolarization, though the extent may depend on established potassium concentration gradient and membrane potential. Once membrane potential is hyperpolarized, it would decrease the excitability of excitable cells. Decreased excitability may reduce calcium spikes and Ca‐CaM mediated activation of myosin light chain kinase (MLCK) in smooth muscle cells. Recently, it was reported that Kv7.4 channels are highly expressed in corpus cavernosum smooth muscle cells and Kv7.5 channels in prostate smooth muscle cells, respectively. Since smooth muscle relaxation of corpus cavernosum and smooth muscle tension in prostate are in the center of pathophysiology of erectile dysfunction and LUTS, we examined the effect of novel Kv7.4 and Kv7.5 activators to the channel activation process.In HEK293 cells expressing human Kv7.4 or Kv7.5 channels, we performed whole‐cell patch clamp technique with two different voltage protocols in order to measure specific activity of the channel. For kinetic analysis of the activation process, voltage steps from –100 mV to +100 mV with 10 mV of step interval was applied. For each step, pulse duration was 3 seconds for activation process of Kv7.4 and Kv7.5 channels is rather slow. Intersweep duration was 10 seconds and holding potential was –80 mV. For measurement of time‐dependent action of the drug, 10 seconds single step with +50 mV was applied in every 30s with holding potential of –80 mV. The composition of internal solution is as following; 120 KCl, 5.37 CaCl2, 1.75 MgCl2, 10 EGTA, 10 HEPES, 4 ATP, 0.2 GTP. pH was adjusted to 7.3 using KOH and [Ca2+]free = 100 nM. Normal tyrode solution was used for external solution and drugs stocked with DMSO was diluted to corresponding concentrations with the Normal tyrode solution.We have found that URO‐K10, a novel activator, increases not only maximum conductance of the channel but also time constant of activation gate. In comparison to positive control, ML‐213, a well‐known Kv7.4 channel activator, URO‐K10 showed significant supremacy. EC50 of URO‐K10 was 0.304 ± 0.058 μM for Kv7.4 channel which is smaller than EC50 of ML‐213 (0.8 ± 0.3 μM). URO‐K10 not only increased the maximum conductance of the channel but also left‐shifted activation curve in terms of Boltzmann distribution. Half‐maximal voltage (V1/2) of Kv7.4 channel without any of the drugs was −43.03 mV whereas V1/2 of URO‐K10 activated channel was −67.65 mV, which is near the resting membrane potential of smooth muscle cells. ML‐213 activated channels showed V1/2 of −51.91 mV.Support or Funding InformationThis work was supported by the National Research Foundation of Korea, which is funded by the Ministry of Science, ICT (Information &amp; Communication Technology), and Future Planning (MSIP) of the Korean Government (2018R1A41023822 to I. So) and by the Education and Research Encouragement Fund of Seoul National University Hospital (I. So). Jung Eun Lee was supported by the BK plus program from the MSIP.

Influence of potassium concentration gradient on stable caesium uptake by Calla palustris

The effect of potassium (K) concentration gradient on stable caesium (Cs) uptake by Calla palustris was studied under hydroponic conditions after eight-day exposure in a greenhouse experiment. The plants were exposed to two different concentrations of Cs (provided as 0.5 and 1 mM CsCl) and five different concentrations of K (provided as K2SO4 in 0.5, 1, 2, 5, and 10 mM). The results indicate negative dependence of Cs uptake on K concentrations for both Cs treatments. The application of K reduced the transfer of stable Cs from water to plant by about 44–72% for 0.5 mM CsCl and 56–74% for 1 mM CsCl. The highest efficiency of Cs removal from water was observed for plants in K+ deficient solutions (plants starving), with an efficiency 8.0% for plants cultivated in 0.5 mM CsCl and 9.4% for plants in 1 mM CsCl. An increasing concentration of K also supported translocation of Cs from roots to leaves. Higher translocation was observed for the treatments with lower level of Cs, where the concentration of Cs in leaves became higher than that in roots. The Cs uptake and translocations were affected not only by the external concentration of K, but also the external concentration of stable Cs. A high concentration of K in the environment protects the food chain from Cs uptake by plants, but lowers the efficiency of phytoremediation techniques.

A Practical Approach for Pathophysiological Diagnosis of Refractory Hypokalemia

Hypokalemia is a common finding in hospitalized patients. In most cases the cause will be obvious. However, in a subgroup of patients the cause is occasionally uncertain and establishing the diagnosis may present difficulties and can become a challenge. In such cases, measurement of urinary indices e.g. trans-tubular potassium gradient [TTKG] and random urine potassium/creatinine concentrations along with blood acid/base parameters and assessment of urinary excretion of potassium, chloride, calcium and creatinine have been employed in the differential diagnosis. TTKG and urine potassium/creatinine ratio are used as a rapid appropriate index of potassium excretion and to establish a proper diagnosis and management in this medical emergency. It helps to differentiate between hypokalemia caused by redistribution or renal potassium wasting. Urinary chloride excretion and urinary calcium/creatinine ratio in conjunction with plasma acid/base values, aldosterone, renin and cortisol values are used for narrowing the differential diagnosis of refractory hypokalemia. Conclusions: Calculating the trans-tubular potassium concentration gradient, urinary potassium/creatinine ratio, urinary chloride excretion and urinary calcium/creatinine ratio in conjunction with plasma acid/base values provided simple and reliable tests for differential diagnosis of causes of refractory hypokalemia and to provide a proper management in the intensive care unit and in the emergency until advanced further tests to be done.

144The transtubular potassium concentration gradient as a predictive index of clinical tissue hypoperfusion in patients with acute decompensated heart failure

144The transtubular potassium concentration gradient as a predictive index of clinical tissue hypoperfusion in patients with acute decompensated heart failure

Surface modification of ion-exchanged float aluminosilicate glass during deposition of amorphous alumina coatings by e-beam evaporation

The main objective of this study was to investigate the physico-chemical and mechanical properties of ion-exchanged float aluminosilicate glasses deposited the Al2O3 films. The concentration gradients of potassium (K), sodium (Na), aluminum (Al) and oxygen (O) elements near Al2O3 film/ion-exchanged glass interface were analyzed by electron probe X-ray micro-analyser (EPMA). Compared with the ion-exchanged glasses, the peak of potassium concentration profile in the ion-exchanged glasses deposited Al2O3 films decreases and moves from glass surface to the inner part. Potassium ion diffusion is accompanied by aluminum (Al) and oxygen (O) diffusion from Al2O3 film into the ion-exchanged glass during deposition. In-depth analyses are performed using micro-Raman spectroscopy on sample cross sections in the aim to investigate the microstructure variation of the ion-exchanged glasses after deposited Al2O3 film on it. The results show that the change of chemical composition throughout ion-exchanged glass surface region can cause a gradual change in microstructure and physical properties.

Potassium: friend or foe?

The kidney plays an essential role in maintaining homeostasis of ion concentrations in the blood. Because the concentration gradient of potassium across the cell membrane is a key determinant of the membrane potential of cells, even small deviations in serum potassium level from the normal setpoint can lead to severe muscle dysfunction, resulting in respiratory failure and cardiac arrest. Less severe hypo- and hyperkalemia are also associated with morbidity and mortality across various patient populations. In addition, deficiencies in potassium intake have been associated with hypertension and adverse cardiovascular and renal outcomes, likely due in part to the interrelated handling of sodium and potassium by the kidney. Here, data on the beneficial effects of potassium on blood pressure and cardiovascular and renal outcomes will be reviewed, along with the physiological basis for these effects. In some patient populations, however, potassium excess is deleterious. Risk factors for the development of hyperkalemia will be reviewed, as well as the risks and benefits of existing and emerging therapies for hyperkalemia.

A case report of distal RTA presenting as hypokalaemic periodic paralysis in young male

A 21-year-old normotensive male presented with acute onset flaccid paralysis with the history of a similar episode a few months back. Clinical and laboratory evaluation revealed lower motor neuron type of flaccid quadriparesis with hypokalaemia, normal anion gap metabolic acidosis, bicarbonaturia, and transtubular potassium concentration gradient (TTKG) more than 7. Subsequently urine acidification test (by NH4CI challenge test) was done and diagnosis of distal renal tubular acidosis was established. The patient responded to conservative management (Sohl's solution).

A case report of recurrent hypokalaemic periodic paralysis in a young male patient

A 21-year-old normotensive male patient presented with acute-onset flaccid paralysis with the history of a similar episode a few months back. Clinical and laboratory evaluation revealed lower motor neuron type of flaccid quadriparesis with hypokalaemia, normal anion gap metabolic acidosis, bicarbonaturia and transtubular potassium concentration gradient more than 7. Subsequently, urine acidification test (by ammonium chloride challenge test) was performed and diagnosis of renal tubular acidosis was established. The patient ultrasound did not show nephrocalcinosis, and history of recurrent diarrhoea preceding the attack revealed that the patient also had coeliac disease. The patient responded to conservative management (Sohl’s solution) and gluten-free diet.

P114 – 2576: Hypokalemic periodic paralysis: A case report based on clinical and genetic findings

Objectives Hypokalemic periodic paralysis (HPP) is a rare channelopathy characterized by episodes of acute muscle weakness associated with hypokalemia. The classification of this disorder is based on anamnesis, biochemical study and molecular genetic testing. Our aim is to present a patient with HPP confirmed by genetic study. Methods Case description providing the results of complementary tests. Results A 14-year-old male presented with several episodes of sudden weakness of all four limbs that prevents him from walking, always on waking and without any triggers. No relevant personal or familial history, except for delayed tooth eruption and oligodontia. During the attack the examination revealed weakness predominantly in lower limbs with hyporeflexia; laboratory tests showed severe hypokalaemia (1.8 mmol/l) and increased creatinine kinase levels; blood gases, biochemical analysis of urine and thyroid hormones where normal; electrocardiogram showed a slight flattening of the T wave with no other abnormalities. Admission to the PICU was necessary twice in order to receive intravenous potassium infusion. Other episodes where satisfactorily treated with oral supplements. Genetic investigations showed a heterozygous mutation in the SCN4A gene (c.1582C>G), compatible with HPP diagnosis. The patient is currently being treated with oral potassium supplements and acetazolamide, achieving a reduction in the number of episodes. Conclusion HPP is a condition in which affected individuals may experience flaccid paralytic episodes with concomitant hypokalemia. In primary HPP caused by a genetic ion channel defect (CACNA1S gene for the majority of cases), hypokalemia is caused by intracellular muscular shift of potassium, so transtubular potassium concentration gradient and potassium-creatinine ratio during paralytic attack is key to distinguish primary HPP from hypokalemia caused by urinary losses. Associated hyperthyroidism must be ruled out. It's important to differentiate between the acute and preventive treatment. The response varies depending on the type of mutation.

Circadian rhythm of urinary potassium excretion during treatment with an angiotensin receptor blocker

We have reported that the circadian rhythm of urinary potassium excretion (U(K)V) is determined by the rhythm of urinary sodium excretion (U(Na)V) in patients with chronic kidney disease (CKD). We also reported that treatment with an angiotensin receptor blocker (ARB) increased the U(Na)V during the daytime, and restored the non-dipper blood pressure (BP) rhythm into a dipper pattern. However, the circadian rhythm of U(K)V during ARB treatment has not been reported. Circadian rhythms of U(Na)V and U(K)V were examined in 44 patients with CKD undergoing treatment with ARB. Whole-day U(Na)V was not altered by ARB whereas whole-day U(K)V decreased. Even during the ARB treatment, the significant relationship persisted between the night/day ratios of U(Na)V and U(K)V (r=0.56, p<0.0001). Whole-day U(K)V/U(Na)V ratio (p=0.0007) and trans-tubular potassium concentration gradient (p=0.002) were attenuated but their night/day ratios remained unchanged. The change in the night/day U(K)V ratio correlated directly with the change in night/day U(Na)V ratio (F=20.4) rather than with the changes in aldosterone, BP or creatinine clearance. The circadian rhythm of U(K)V was determined by the rhythm of UNaV even during ARB treatment. Changes in the circadian U(K)V rhythm were not determined by aldosterone but by U(Na)V.

Persistent Hyperkalemia Associated with Hypotension Due to Relative Hyporeninemic Hypoaldosteronism: Recognition is Key

Introduction: Persistent hyperkalemia in adults can be caused hyporeninemic hypoaldosteronism (HH), which typically occur in diabetic patients with chronic kidney dysfunction and is associated with hypertension and a mild degree of hyperchloremic acidosis. Rarely, HH may occur and be featured by persistent hyperkalemia and renal salt wasting. Case presentation: A 49-year-old female developed unexplained lightheadedness and hyperkalemia several months following unilateral nephrectomy for a renal cell carcinoma. She was treated by her local physician with dietary potassium restriction, salt tablets and regular dosage of sodium polystyrene sulfonate. Two years later, her symptoms progressed to episodes of near syncope and supraventricular tachycardia. On presentation to our clinic, her blood pressure (BP) was 95/49 mmHg and laboratory studies showed serum potassium of 6.7 mmol/L, creatinine 0.8 mg/dL, renin activity 1.4 ng/mL/hour, and aldosterone 6.2 ng/dL (reference range <21 ng/dL). Serial transtubular potassium concentration gradients (TTKGs) were obtained. Upon administration of a single 0.1 mg of oral fludrocortisone, her TTKG raised sharply to 6.91 from a baseline of 3.87. She was diagnosed with relative HH; fludrocortisone 0.1 mg daily was initiated. On return visits two week later, she denied any lightheadedness, her BP rose to 108-125/65-80 mmHg (6 measurements), serum potassium normalized to 5.1 mmol/L (4.4 mmol/L at three-month follow-up). Conclusion: Although rare in adults, HH can develop and present with hypotension and persistent hyperkalemia. As illustrated in this case, recognizing such an occurrence is critical for correct management to avoid serous complications.