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1.
Ann Clin Biochem ; 57(6): 444-455, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33016076

RESUMEN

BACKGROUND: Differentiating between true and pseudohyperkalaemia is essential for patient management. The common causes of pseudohyperkalaemia include haemolysis, blood cell dyscrasias and EDTA contamination. One approach to differentiate between them is by checking the renal function, as it is believed that true hyperkalaemia is rare with normal function. This is logical, but there is limited published evidence to support it. The aim of this study was to investigate the potential role of the estimated glomerular filtration rate in differentiating true from pseudohyperkalaemia. METHODS: GP serum potassium results >6.0 mmol/L from 1 January 2017 to 31 December 2017, with a repeat within seven days, were included. Entries were retrospectively classified as true or pseudohyperkalaemia based on the potassium reference change value and reference interval. If the initial sample had a full blood count, it was classified as normal/abnormal to remove blood cell dyscrasias. Different estimated glomerular filtration rate cut-points were used to determine the potential in differentiating true from pseudohyperkalaemia. RESULTS: A total of 272 patients were included with potassium results >6.0 mmol/L, with 145 classified as pseudohyperkalaemia. At an estimated glomerular filtration rate of 90 ml/min/1.73 m2, the negative predictive value was 81% (95% CI: 67-90%); this increased to 86% (95% CI: 66-95%) by removing patients with abnormal full blood counts. When only patients with an initial potassium ≥6.5 mmol/L were included (regardless of full blood count), at an estimated glomerular filtration rate of 90 ml/min/1.73 m2, the negative predictive value was 100%. Lower negative predictive values were seen with decreasing estimated glomerular filtration rate cut-points. CONCLUSION: Normal renal function was not associated with true hyperkalaemia, making the estimated glomerular filtration rate a useful tool in predicting true from pseudohyperkalaemia, especially for potassium results ≥6.5 mmol/L.


Asunto(s)
Tasa de Filtración Glomerular , Hiperpotasemia/sangre , Hiperpotasemia/orina , Potasio/orina , Recuento de Células Sanguíneas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
2.
Hormones (Athens) ; 19(2): 223-232, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31863347

RESUMEN

Mild hyperkalemia is a common side effect of mineralocorticoid receptor antagonist (MRA) treatment of patients with primary aldosteronism (PA), which can be worsened by instructions to minimize salt intake. Our objective was to evaluate the effect of salt consumption on serum potassium levels and mean, mean minimal, and mean maximal systolic and diastolic blood pressure (BP) in MRA-treated hyperkalemic PA patients under relative salt restriction. Seventeen consecutive mildly hyperkalemic MRA-treated PA patients aged 66.3 ± 8.37 years were recruited. Body mass index (BMI) and BP were assessed, and serum and 24-h urinary sodium and potassium levels, plasma renin, and serum aldosterone were measured, while patients followed a relatively salt-restricted diet, after 1 month of controlled salt supplementation (usual salt-restricted diet plus 4 g salt/day) and after 6 months on instructions for free dietary salt consumption. Baseline salt consumption was additionally evaluated in two more patient groups (normotensive subjects and normokalemic MRA-treated PA patients). One month of controlled salt supplementation (24-h urine sodium (median, min, max): 195.2 (120.30-275.20) vs 110.13 (34.30-139.20) mEq/day, p < 0.001) resulted in increased kaliuresis (62.25 (40.69-97.0) vs 54.0 (23.28-79.60) mEq/day, p = 0.001) and a decrease of serum potassium (5.2 (5-5.70) vs 4.6 (3.8-5.1) mEq/L, p < 0.001), while serum sodium (139 (133-141) vs 1 39 (135-144) mEq/L) and mean systolic (130 (105-141 vs. 130 (106-141) mmHg) and diastolic (76 (53-85) vs75 (53-84) mmHg) BP remained stable. These findings were unchanged after 6 months of free salt consumption. BMI remained constant, while plasma renin and serum aldosterone decreased following salt repletion. Adequate salt consumption attenuates MRA-induced hyperkalemia in relatively salt-restricted PA patients without affecting BP or BMI.


Asunto(s)
Presión Sanguínea , Hiperaldosteronismo/sangre , Hiperaldosteronismo/tratamiento farmacológico , Hiperpotasemia/sangre , Hiperpotasemia/fisiopatología , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Potasio/sangre , Cloruro de Sodio Dietético/administración & dosificación , Sodio/sangre , Anciano , Femenino , Estudios de Seguimiento , Humanos , Hiperpotasemia/inducido químicamente , Hiperpotasemia/orina , Masculino , Persona de Mediana Edad , Potasio/orina , Sodio/orina
4.
BMC Nephrol ; 20(1): 104, 2019 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-30909873

RESUMEN

BACKGROUND: Guidelines for general hypertension treatment do not recommend the combined use of renin-angiotensin-aldosterone system (RAAS) inhibitors due to the risk of hyperkalemia. However, a recent clinical trial showed that polycystic kidney disease (PKD) patients had infrequent episodes of hyperkalemia despite receiving combined RAAS inhibitors. Because intrarenal RAAS is a main component for renal potassium handling, we further investigated the association between intrarenal RAAS activity and serum potassium level in patients with chronic kidney disease, particularly in PKD patients, and examined whether intrarenal RAAS activity has a prognostic role in patients with PKD. METHODS: A total of 1788 subjects from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) were enrolled in this study. Intrarenal RAAS activity was assessed by the measurement of urinary angiotensinogen (AGT). The primary outcome was the composite of all-cause mortality and renal function decline. RESULTS: Patients with PKD had a significantly lower serum potassium level in chronic kidney disease stages 1 to 3b than non-PKD patients. In logistic regression analysis, after adjusting for multiple confounders, PKD patients had a significantly lower risk of hyperkalemia than non-PKD patients. In multivariable linear regression analysis, the urinary AGT/creatinine (Cr) ratio was negatively correlated with the serum potassium level (ß = - 0.058, P = 0.017) and positively correlated with the transtubular potassium gradient (TTKG, ß = 0.087, P = 0.001). In propensity score matching analysis, after matching factors associated with serum potassium and TTKG, PKD patients had a significantly higher TTKG (P = 0.021) despite a lower serum potassium level (P = 0.004). Additionally, the urinary AGT/Cr ratio was significantly higher in PKD patients than in non-PKD patients (P = 0.011). In 293 patients with PKD, high urinary AGT/Cr ratio was associated with increased risk of the composite outcome (hazard ratio 1.29; 95% confidence interval, 1.07-1.55; P = 0.007). CONCLUSIONS: High activity of intrarenal RAAS is associated with increased urinary potassium excretion and low serum potassium level in patients with PKD. In addition, intrarenal RAAS activity can be a prognostic marker for mortality and renal function decline in these patients.


Asunto(s)
Angiotensinógeno/orina , Homeostasis/fisiología , Enfermedades Renales Poliquísticas/sangre , Enfermedades Renales Poliquísticas/orina , Potasio/sangre , Adulto , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Estudios de Cohortes , Femenino , Humanos , Hiperpotasemia/sangre , Hiperpotasemia/diagnóstico , Hiperpotasemia/orina , Masculino , Persona de Mediana Edad , Enfermedades Renales Poliquísticas/diagnóstico , Estudios Prospectivos , Resultado del Tratamiento , Adulto Joven
5.
Am J Physiol Renal Physiol ; 313(1): F62-F73, 2017 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-28356292

RESUMEN

We assessed effects of acute volume reductions induced by administration of diuretics in rats. Direct block of Na+ transport produced changes in urinary electrolyte excretion. Adaptations to these effects appeared as alterations in the expression of protein for the distal nephron Na+ transporters NCC and ENaC. Two hours after a single injection of furosemide (6 mg/kg) or hydrochlorothiazide (HCTZ; 30 mg/kg) Na+ and K+ excretion increased but no changes in the content of activated forms of NCC (phosphorylated on residue T53) or ENaC (cleaved γ-subunit) were detected. In contrast, amiloride (0.6 mg/kg) evoked a similar natriuresis that coincided with decreased pT53NCC and increased cleaved γENaC. Alterations in posttranslational membrane protein processing correlated with an increase in plasma K+ of 0.6-0.8 mM. Decreased pT53NCC occurred within 1 h after amiloride injection, whereas changes in γENaC were slower and were blocked by the mineralocorticoid receptor antagonist spironolactone. Increased γENaC cleavage correlated with elevation of the surface expression of the subunit as assessed by in situ biotinylation. Na depletion induced by 2 h of furosemide or HCTZ treatment increases total NCC expression without affecting ENaC protein. However, restriction of Na intake for 10 h (during the day) or 18 h (overnight) increased the abundance of both total NCC and of cleaved α- and γENaC. We conclude that the kidneys respond acutely to hyperkalemic challenges by decreasing the activity of NCC while increasing that of ENaC. They respond to hypovolemia more slowly, increasing Na+ reabsorptive capacities of both of these transporters.


Asunto(s)
Diuréticos/farmacología , Canales Epiteliales de Sodio/efectos de los fármacos , Hiperpotasemia/metabolismo , Hipovolemia/metabolismo , Nefronas/efectos de los fármacos , Potasio/metabolismo , Sodio/metabolismo , Amilorida/farmacología , Animales , Diuréticos/toxicidad , Canales Epiteliales de Sodio/metabolismo , Femenino , Furosemida/farmacología , Hidroclorotiazida/farmacología , Hiperpotasemia/sangre , Hiperpotasemia/inducido químicamente , Hiperpotasemia/orina , Hipovolemia/sangre , Hipovolemia/inducido químicamente , Hipovolemia/orina , Masculino , Modelos Biológicos , Nefronas/metabolismo , Fosforilación , Potasio/sangre , Potasio/orina , Ratas Sprague-Dawley , Eliminación Renal/efectos de los fármacos , Sodio/sangre , Sodio/orina , Miembro 3 de la Familia de Transportadores de Soluto 12/efectos de los fármacos , Miembro 3 de la Familia de Transportadores de Soluto 12/metabolismo , Espironolactona/farmacología
6.
Am J Physiol Renal Physiol ; 313(3): F641-F656, 2017 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-27440776

RESUMEN

(Pro)renin receptor (PRR) is highly expressed in the distal nephron, but it has an unclear functional implication. The present study was conducted to explore a potential role of renal PRR during high K+ (HK) loading. In normal Sprague-Dawley rats, a 1-wk HK intake increased renal expression of full-length PRR and urinary excretion of soluble PRR (sPRR). Administration of PRO20, a decoy peptide antagonist of PRR, in K+-loaded animals elevated plasma K+ level and decreased urinary K+ excretion, accompanied with suppressed urinary aldosterone excretion and intrarenal aldosterone levels. HK downregulated Na+-Cl- cotransporter (NCC) expression but upregulated CYP11B2 (cytochrome P-450, family 11, subfamily B, polypeptide 2), renal outer medullary K+ channel (ROMK), calcium-activated potassium channel subunit α1 (α-BK), α-Na+-K+-ATPase (α-NKA), and epithelial Na+ channel subunit ß (ß-ENaC), all of which were blunted by PRO20. After HK loading was completed, urinary, but not plasma renin, was upregulated, which was blunted by PRO20. The same experiments that were performed using adrenalectomized (ADX) rats yielded similar results. Interestingly, spironolactone treatment in HK-loaded ADX rats attenuated kaliuresis but promoted natriuresis, which was associated with the suppressed responses of ß-ENaC, α-NKA, ROMK, and α-BK protein expression. Taken together, we discovered a novel role of renal PRR in regulation of K+ homeostasis through a local mechanism involving intrarenal renin-angiotensin-aldosterone system and coordinated regulation of membrane Na+- and K+-transporting proteins.


Asunto(s)
Hiperpotasemia/metabolismo , Riñón/metabolismo , Potasio en la Dieta , ATPasas de Translocación de Protón/metabolismo , Receptores de Superficie Celular/metabolismo , Sistema Renina-Angiotensina , Adrenalectomía , Aldosterona/metabolismo , Animales , Citocromo P-450 CYP11B2/metabolismo , Modelos Animales de Enfermedad , Canales Epiteliales de Sodio/metabolismo , Homeostasis , Hiperpotasemia/sangre , Hiperpotasemia/genética , Hiperpotasemia/orina , Riñón/efectos de los fármacos , Subunidades alfa de los Canales de Potasio de Gran Conductancia Activados por Calcio/metabolismo , Masculino , Antagonistas de Receptores de Mineralocorticoides/farmacología , Fragmentos de Péptidos/farmacología , Canales de Potasio de Rectificación Interna/metabolismo , ATPasas de Translocación de Protón/antagonistas & inhibidores , ATPasas de Translocación de Protón/genética , Ratas Sprague-Dawley , Receptores de Superficie Celular/antagonistas & inhibidores , Receptores de Superficie Celular/genética , Renina/farmacología , Sistema Renina-Angiotensina/efectos de los fármacos , Transducción de Señal , Miembro 3 de la Familia de Transportadores de Soluto 12/metabolismo , Espironolactona/farmacología , ATPasas de Translocación de Protón Vacuolares
7.
Magnes Res ; 28(4): 126-35, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26878252

RESUMEN

Magnesium-deficient patients show dysfunctional calcium (Ca(2+)) metabolism due to defective parathyroid hormone (PTH) secretion. In mice and rats, long-term magnesium (Mg(2+)) deprivation causes hyperphosphaturia and increases fibroblast growth factor 23 (FGF23) secretion, despite normal serum phosphate (Pi) and Ca(2+). Electrolyte disturbances during early hypomagnesemia may explain the response of mice to long-term Mg(2+) deprivation, but our knowledge of electrolyte homeostasis during this stage is limited. This study compares the effect of both short- and long-term Mg(2+) restriction on the electrolyte balance in mice. Mice were fed control or Mg(2+)-deficient diets for one to three days, one week, or three weeks. Prior to killing the mice, urine was collected over 24 h using metabolic cages. Within 24 h of Mg(2+) deprivation, hypomagnesemia, hypocalcemia and hyperphosphatemia developed, and after three days of Mg(2+) deprivation, serum potassium (K(+)) was increased. These changes were accompanied by a reduction in urinary volume, hyperphosphaturia, hypocalciuria and decreased Mg(2+), sodium (Na(+)) and K(+) excretion. Surprisingly, after one week of Mg(2+) deprivation, serum K(+), Pi and Ca(2+) had normalized, showing that mineral homeostasis is most affected during early hypomagnesemia. Serum Pi and K(+) are known to stimulate secretion of FGF23 and aldosterone, which are usually elevated during Mg(2+) deficiency. Thus, the hyperphosphatemia and increased serum K(+) concentration observed during short-term Mg(2+) deprivation may help our understanding of adaptation to chronic Mg(2+) deficiency.


Asunto(s)
Calcio/sangre , Hiperpotasemia/etiología , Hiperfosfatemia/etiología , Hipocalcemia/etiología , Deficiencia de Magnesio/complicaciones , Magnesio/sangre , Fosfatos/sangre , Potasio/sangre , Adaptación Fisiológica , Animales , Biomarcadores/sangre , Biomarcadores/orina , Peso Corporal , Calcio/orina , Modelos Animales de Enfermedad , Factor-23 de Crecimiento de Fibroblastos , Hiperpotasemia/sangre , Hiperpotasemia/fisiopatología , Hiperpotasemia/orina , Hiperfosfatemia/sangre , Hiperfosfatemia/fisiopatología , Hiperfosfatemia/orina , Hipocalcemia/sangre , Hipocalcemia/fisiopatología , Hipocalcemia/orina , Magnesio/orina , Deficiencia de Magnesio/sangre , Deficiencia de Magnesio/fisiopatología , Deficiencia de Magnesio/orina , Masculino , Ratones Endogámicos C57BL , Fosfatos/orina , Potasio/orina , Factores de Tiempo , Equilibrio Hidroelectrolítico
8.
Am J Physiol Renal Physiol ; 306(9): F1059-68, 2014 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-24598799

RESUMEN

Dietary potassium loading results in rapid kaliuresis, natriuresis, and diuresis associated with reduced phosphorylation (p) of the distal tubule Na(+)-Cl(-) cotransporter (NCC). Decreased NCC-p inhibits NCC-mediated Na(+) reabsorption and shifts Na(+) downstream for reabsorption by epithelial Na(+) channels (ENaC), which can drive K(+) secretion. Whether the signal is initiated by ingesting potassium or a rise in plasma K(+) concentration ([K(+)]) is not understood. We tested the hypothesis, in male rats, that an increase in plasma [K(+)] is sufficient to reduce NCC-p and drive kaliuresis. After an overnight fast, a single 3-h 2% potassium (2%K) containing meal increased plasma [K(+)] from 4.0 ± 0.1 to 5.2 ± 0.2 mM; increased urinary K(+), Na(+), and volume excretion; decreased NCC-p by 60%; and marginally reduced cortical Na(+)-K(+)-2Cl(-) cotransporter (NKCC) phosphorylation 25% (P = 0.055). When plasma [K(+)] was increased by tail vein infusion of KCl to 5.5 ± 0.1 mM over 3 h, significant kaliuresis and natriuresis ensued, NCC-p decreased by 60%, and STE20/SPS1-related proline alanine-rich kinase (SPAK) phosphorylation was marginally reduced 35% (P = 0.052). The following were unchanged at 3 h by either the potassium-rich meal or KCl infusion: Na(+)/H(+) exchanger 3 (NHE3), NHE3-p, NKCC, ENaC subunits, and renal outer medullary K(+) channel. In summary, raising plasma [K(+)] by intravenous infusion to a level equivalent to that observed after a single potassium-rich meal triggers renal kaliuretic and natriuretic responses, independent of K(+) ingestion, likely driven by decreased NCC-p and activity sufficient to shift sodium reabsorption downstream to where Na(+) reabsorption and flow drive K(+) secretion.


Asunto(s)
Hiperpotasemia/sangre , Riñón/metabolismo , Natriuresis , Potasio/sangre , Sodio/orina , Animales , Modelos Animales de Enfermedad , Canales Epiteliales de Sodio/metabolismo , Hiperpotasemia/inducido químicamente , Hiperpotasemia/fisiopatología , Hiperpotasemia/orina , Infusiones Intravenosas , Riñón/fisiopatología , Masculino , Fosforilación , Potasio/administración & dosificación , Potasio/orina , Canales de Potasio/metabolismo , Potasio en la Dieta/sangre , Potasio en la Dieta/orina , Proteínas Serina-Treonina Quinasas/metabolismo , Ratas , Ratas Sprague-Dawley , Sodio/sangre , Intercambiador 3 de Sodio-Hidrógeno , Intercambiadores de Sodio-Hidrógeno/metabolismo , Miembro 3 de la Familia de Transportadores de Soluto 12/metabolismo , Factores de Tiempo
9.
J Aerosol Med Pulm Drug Deliv ; 27(3): 200-8, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23905576

RESUMEN

BACKGROUND: Inhaled epithelial sodium channel (ENaC) blockers are designed to increase airway surface liquid volume, thereby benefiting cystic fibrosis patients. This study evaluated the safety, tolerability, and pharmacokinetics of multiple doses of ENaC blocker GS-9411, in healthy participants. METHODS: This randomized, double-blind, placebo-controlled, parallel-group, residential, Phase 1 study evaluated inhaled GS-9411 (2.4, 4.8, and 9.6 mg) or placebo, dosed twice daily for 14 days. RESULTS AND CONCLUSIONS: GS-9411 was well tolerated; 86.1% of treated participants completed dosing (n=31/36). Cough and dizziness (27.8% participants each; most of mild severity) were the most commonly reported adverse events and occurred in both placebo and GS-9411 treatment groups. Arrhythmias were not observed for GS-9411-treated participants, and electrocardiographic changes were not considered clinically significant. Serum potassium levels exceeded the upper limit of normal (>5 mmol/L), 4 hr after the morning dose in GS-9411 (n=16/24) and placebo (n=4/12) treatment groups (38 incidences total). Retesting revealed levels had returned to normal within 2-3 hr. In urine electrolyte analyses, obtained 0-6 hr after the Day 1 morning dose, mean sodium/potassium ratios significantly increased from values 0-6 hr before dosing. Increased urine sodium/potassium ratios corresponded with high urine concentrations of active GS-9411 metabolites, which inhibited sodium reabsorption in the kidney, leading to the observed transient hyperkalemia in these participants. Inhaled GS-9411 was well tolerated except for the emergence of transient clinically significant hyperkalemia; this finding resulted in termination of further clinical development of this drug and will necessitate development of a new generation of ENaC blockers, which provide a sustained improvement in mucociliary clearance, while reducing renal exposure to ENaC blockade. Transient increases in mean urine sodium/potassium ratios appeared to be the first signal of electrolyte imbalances resulting from drug-induced block of ENaC in the kidney. The results of this study strongly suggest that clinical trials of novel ENaC blockers will require intensive measurement of plasma and urine electrolyte levels.


Asunto(s)
Bloqueadores del Canal de Sodio Epitelial/administración & dosificación , Bloqueadores del Canal de Sodio Epitelial/efectos adversos , Hiperpotasemia/inducido químicamente , Potasio/sangre , Enfermedad Aguda , Administración por Inhalación , Adulto , Australia , Biomarcadores/sangre , Biomarcadores/orina , Método Doble Ciego , Esquema de Medicación , Bloqueadores del Canal de Sodio Epitelial/farmacocinética , Femenino , Voluntarios Sanos , Humanos , Hiperpotasemia/sangre , Hiperpotasemia/diagnóstico , Hiperpotasemia/orina , Masculino , Potasio/orina , Medición de Riesgo , Adulto Joven
10.
Ross Fiziol Zh Im I M Sechenova ; 99(3): 372-82, 2013 Mar.
Artículo en Ruso | MEDLINE | ID: mdl-23789440

RESUMEN

Ion-regulating renal function and influence of vasopressin and its analogues on the rate and selectiveness of the urinary potassium excretion were investigated after short-term parenteral and oral potassium loading. In experiments with Wistar rats it was shown that increase in volume of orally administrated 1.25% KCl solution from 1 to 5 ml per 100 g body weight led to the proportional rise in potassium excretion. Hyperkalemia was already observed at 5 min after parenteral potassium loading, potassium excretion reached the maximum after administration of 2 ml of KCl solution per 100 g body weight. Kaliuresis induced by oral potassium load was higher and faster than after parenteral load and was followed by increase in diuresis, urinary sodium and magnesium excretion. Desmopressin and 1-deamino-Arg4-vasotocin prevented rise of diuresis, natriuresis and magniuresis under these conditions; 1-deamino-Arg4-vasotocin and vasopressin stimulated urinary potassium excretion during first 30 min after loading. After parenteral potassium load vasopressin analogues did not affect urinary potassium and sodium excretion. The data obtained suggest the participation of the gut in regulatory signal transduction to the kidney after potassium entering and prevention of significant changes in the internal environment.


Asunto(s)
Fármacos Antidiuréticos/farmacología , Desamino Arginina Vasopresina/farmacología , Riñón/fisiología , Natriuresis/fisiología , Potasio/metabolismo , Sodio/metabolismo , Vasotocina/análogos & derivados , Administración Oral , Animales , Femenino , Hiperpotasemia/orina , Inyecciones Intraperitoneales , Mucosa Intestinal/metabolismo , Riñón/efectos de los fármacos , Potasio/farmacología , Ratas , Ratas Wistar , Transducción de Señal , Vasotocina/farmacología , Equilibrio Hidroelectrolítico/efectos de los fármacos
11.
Aust Fam Physician ; 38(5): 307-9, 2009 May.
Artículo en Inglés | MEDLINE | ID: mdl-19458800

RESUMEN

BACKGROUND: Persistent hyperkalaemia in elderly patients caused by hyporeninaemic hypoaldosteronism is relatively common and often under recognised in the general practice setting. OBJECTIVE: This article highlights the importance of suspecting hyporeninaemic hypoaldosteronism in any elderly patient with persistent hyperkalaemia and provides an outline of investigation and management of the condition. DISCUSSION: Elderly patients with persistent hyperkalaemia may have hyporeninaemic hypoaldosteronism. The diagnosis is made by calculating the transtubular potassium concentration gradient, and then measuring the serum aldosterone level. Hyporeninaemic hypoaldosteronism is managed with a low potassium diet and a low dose loop or thiazide diuretic.


Asunto(s)
Hiperpotasemia/etiología , Hipoaldosteronismo/complicaciones , Hipoaldosteronismo/diagnóstico , Anciano de 80 o más Años , Aldosterona/sangre , Femenino , Humanos , Hiperpotasemia/sangre , Hiperpotasemia/diagnóstico , Hiperpotasemia/terapia , Hiperpotasemia/orina , Hipoaldosteronismo/sangre , Hipoaldosteronismo/terapia , Hipoaldosteronismo/orina , Potasio/sangre , Potasio/orina
12.
Am J Perinatol ; 25(3): 193-7, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18425722

RESUMEN

Our objective was to compare the efficacy and safety of rectal cation-exchange resin (Kayexalate) versus salbutamol infusion for the treatment of nonoliguric hyperkalemia (NOHK) in preterm infants. Data of all neonates born with NOHK during the study period of 6 years and 8 months were recorded. Diagnostic criteria of NOHK included serum potassium (SK) concentration > or = 7 mmol/L during the first 72 hours of life with urine output > or = 1 mL/kg/hour. This before-after study was divided according to the date of admission; the first 15 patients were treated with Kayexalate enema 1 g/kg every 4 hours, and the remaining 30 patients were treated with intravenous salbutamol infusion as 4 mug/kg every 4 hours. Treatment discontinued when SK became < 6 mmol/L. SK was measured every 4 hours. Daily urine was collected. Fluid intake and output, serum electrolytes, urea, creatinine, and glucose concentrations were obtained in all infants every 12 hours. All infants were observed with a cardiorespiratory monitor and oxygen saturation and blood pressure measurements. Perinatal characteristics in both groups were comparable. Mean gestational age was 26 and 28 weeks for salbutamol and Kayexalate, respectively. The peak of SK ranged between 7 and 9.3 mmol/L in the Kayexalate group and between 7 and 8.7 mmol/L in the salbutamol group ( P = 0.64). At 12 hours of treatment, SK became normal in only 4 patients (26%) in the Kayexalate group compared with 18 patients (60%) in the salbutamol group ( P = 0.003). The number of doses of Kayexalate administration was significantly higher than the doses of salbutamol ( P = 0.003). No significant side effects were detected in the salbutamol-treated infants. In contrast, there were two cases of severe ventricular tachycardia and one case of intestinal obstruction in the cation-exchange resin group. We concluded that salbutamol infusion is more effective with faster action and safer than cation-exchange resin (Kayexalate) for the treatment of NOHK in preterm infants.


Asunto(s)
Agonistas Adrenérgicos beta/uso terapéutico , Albuterol/uso terapéutico , Resinas de Intercambio de Catión/uso terapéutico , Hiperpotasemia/tratamiento farmacológico , Enfermedades del Prematuro/tratamiento farmacológico , Poliestirenos/uso terapéutico , Femenino , Humanos , Hiperpotasemia/sangre , Hiperpotasemia/orina , Recién Nacido , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Masculino , Potasio/sangre , Resultado del Tratamiento
13.
J Nutr Health Aging ; 12(2): 152-5, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18264644

RESUMEN

OBJECTIVES: Sustained hyperkalaemia usually indicates a defect in renal potassium (K+) excretion and can be due to severe impairment of glomerular filtration rate (GFR). The major determinants of renal K+ secretion were studied in hyperkalaemic and normokalaemic elderly subjects to probe the major determinants of hyperkalaemia in this setting. DESIGN: The transtubular potassium gradient (TTKG) provides an index of tubular K+ secretion and normally rises in patients with significant hyperkalaemia. Both GFR(glomerular filtration rate) and TTKG were assessed at baseline and repeated after 3 hours following ingestion of 0.1mg of fludrocortisone in three groups. SETTING: An acute general hospital in the West of Ireland. PARTICIPANTS: 23 subjects in total; 8 older patients with unexplained hyperkalaemia (OHK), 8 older patients with normokalaemia (ONK) and 9 young normokalaemic controls (YNK). MEASUREMENTS: The GFR was either measured by 24 hour creatinine clearance estimation or calculated using the Cockroft and Gault formula.TTKG was calculated using a specific formula. RESULTS: Mean baseline TTKG was similar in all three groups and consequently inappropriately low in hyperkalaemic subjects. Three hours post fludrocortisone, the TTKG had risen significantly from baseline levels in the young subjects only (from 7.5+/-0.09 to 11.6+/-1.1, p<0.05). No significant increase was noted in either older group at this timepoint. CONCLUSIONS: The inappropriately low baseline TTKG in the OHK group as well as the absence of a response to fludrocortisone indicate tubular insensitivity to aldosterone. GFR values in both OHK (40.06+/-2.31) and ONK (55.58+/-6.1) groups were significantly lower than those in the YNK group (101.66+/-6.9). In aggregate, these findings indicate that older hyperkalaemic patients typically have both impairment of glomerular filtration and renal tubular K+ secretion and highlights the requirement for vigilance in elderly patients when using medications which interfere with tubular function.


Asunto(s)
Tasa de Filtración Glomerular/fisiología , Hiperpotasemia/metabolismo , Túbulos Renales/metabolismo , Potasio/metabolismo , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Creatinina/metabolismo , Femenino , Humanos , Hiperpotasemia/orina , Riñón/metabolismo , Masculino , Concentración Osmolar , Potasio/análisis , Potasio/orina
14.
J Am Soc Nephrol ; 19(3): 424-6, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18216310

RESUMEN

The transtubular potassium gradient (TTKG) is used to gauge renal potassium secretion by the cortical collecting duct, indirectly assessing mineralocorticoid bioactivity in patients who have hypo- or hyperkalemia. TTKG values <6 indicate an inappropriate renal response to hyperkalemia, whereas values >2 during hypokalemia point to renal loss. Hypokalemia is not addressed here. Studies supporting the usefulness of the TTKG in hyperkalemia are limited to case series. This calculation may be most useful in distinguishing hyperkalemic patients who have mineralocorticoid deficiency versus resistance by observing a change in TTKG values after physiologic or pharmacologic doses of mineralocorticoids.


Asunto(s)
Hiperpotasemia/sangre , Hiperpotasemia/orina , Potasio/sangre , Potasio/orina , Humanos , Túbulos Renales Colectores/metabolismo , Concentración Osmolar
15.
Nephrol Dial Transplant ; 23(2): 492-6, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17951312

RESUMEN

BACKGROUND: Familial hyperkalaemia and hypertension (FHH), also termed pseudohypoaldosteronism type II, is a rare monogenic form of hypertension caused by mutations in the WNK1 or WNK4 kinases. In vitro expression of WNK4 reduces surface abundance and activity of coexpressed NaCl cotransporter (NCCT). This effect is lost in disease-producing WNK4 mutants. In two mice models of FHH, one expressing two extra copies of mutant WNK4 (Q562E) and another in which a mutant (D561A) WNK4 replaced wild-type WNK4, renal distal tubule hyperplasia with overexpression of NCCT was found. Currently no FHH human renal tissue is available to test for increased distal tubule surface abundance of NCCT. The availability of a unique large family with FHH and the Q565E WNK4 mutation enabled us to investigate this issue in an indirect manner. METHODS: Assuming that shedding of NCCT to the urine reflects its abundance in the distal tubule epithelium, we measured urinary NCCT protein in eight subjects of the FHH family and in eight unrelated controls by western blotting. RESULTS: Urinary NCCT protein was about four times higher in FHH than in controls [111.1 +/- 40.5 versus 26.1 +/- 16.4 densitometry units (P < 0.0001)]. No significant difference in urinary sodium and potassium concentrations was seen between FHH and controls. CONCLUSIONS: The increased urinary NCCT in FHH most probably reflects increased NCCT abundance in the apical membrane of distal tubule cells in patients with FHH and the WNK4 mutation and points to the pathogenetic mechanism for the clinical phenotype of FHH and the WNK4 mutation, supporting results in transgenic mice with the same mutation and in knockin mice with another mutation.


Asunto(s)
Hiperpotasemia/orina , Hipertensión/orina , Seudohipoaldosteronismo/orina , Simportadores del Cloruro de Sodio/orina , Adulto , Femenino , Humanos , Hiperpotasemia/genética , Hipertensión/genética , Masculino , Persona de Mediana Edad , Mutación , Proteínas Serina-Treonina Quinasas/genética , Seudohipoaldosteronismo/genética
16.
Anesth Analg ; 105(3): 780-5, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17717240

RESUMEN

BACKGROUND: Hyperkalemia poses serious hazards to patients undergoing orthotopic liver transplantation (OLT), and its predictors have not been thoroughly examined. METHODS: We retrospectively studied 1124 consecutive adult patients who underwent OLT. Hyperkalemia was defined as serum K+ > or =5.5 mmol/L. A total of 47 recipient, donor, intraoperative, and laboratory variables were initially analyzed in univariate analyses. Independent predictors of hyperkalemia in three periods of OLT (prereperfusion, early postreperfusion, and late postreperfusion) were determined in multivariate logistic regression analyses. RESULTS: Of 1124 patients, 10.2%, 19.1%, and 7.9% had hyperkalemia in the prereperfusion, early postreperfusion, and late postreperfusion periods, respectively. Higher baseline K+ and red blood cell transfusion were independent predictors of prereperfusion hyperkalemia. Higher baseline K+ (or prereperfusion K+) and donation after cardiac death donor were independent predictors of early postreperfusion hyperkalemia. Higher baseline K+, longer warm ischemia time, longer donor hospital stay, lower intraoperative urine output, and the use of venovenous bypass were independent predictors of late postreperfusion hyperkalemia. CONCLUSIONS: Several laboratory, intraoperative, and donor variables were identified as independent predictors of hyperkalemia in the different periods. Such information may be used for more targeted preemptive interventions in patients who are at risk of developing hyperkalemia during adult OLT.


Asunto(s)
Hiperpotasemia/etiología , Trasplante de Hígado/efectos adversos , Potasio/sangre , Reperfusión , Donantes de Tejidos , Adulto , Factores de Edad , Creatinina/sangre , Femenino , Humanos , Hiperpotasemia/sangre , Hiperpotasemia/epidemiología , Hiperpotasemia/orina , Tiempo de Internación , Trasplante de Hígado/estadística & datos numéricos , Modelos Logísticos , Los Angeles/epidemiología , Masculino , Persona de Mediana Edad , Transfusión de Plaquetas/efectos adversos , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Donantes de Tejidos/estadística & datos numéricos , Procedimientos Quirúrgicos Vasculares/efectos adversos , Isquemia Tibia/efectos adversos
17.
Pathophysiol Haemost Thromb ; 32(3): 107-10, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12372922

RESUMEN

BACKGROUND: Low-molecular-weight heparins (LMWHs) are being preferred to unfractionated heparin (UFH) because of their superior convenience and a comparable or slightly better toxicity profile. Whether LMWH has an inhibitory effect on aldosterone that causes hyperkalemia is yet uncertain. METHODS: Twenty-eight patients (all male; mean age: 70 years, range 52-87 years) placed on LMWH therapy (40 mg subcutaneously every 12 h) for deep venous thrombosis prophylaxis after an operation were included in the study. Transtubular potassium concentration gradient (TTKG) was calculated 1 day prior to LMWH therapy and again after 4 days of treatment. Of the 28 patients enrolled in the study, we were able to calculate the TTKG in only 19 patients: 9 had a urinary osmolarity (either before or after LMWH therapy) less than the serum osmolarity, making the TTKG calculation unreliable. The Wilcoxon signed-rank test was used to analyze differences in the median serum potassium levels and TTKG before and after LMWH therapy. RESULTS: All patients had adequate renal function (creatinine clearance >90 ml/min). Mean (+/- SD) serum potassium concentration before LMWH was 4.25 (+/- 0.40) mmol/dl. It increased to 4.35 (+/- 0.41) mmol/dl after initiating LMWH therapy (p = 0.09). Similarly, the mean (+/- SD) TKKG calculated was 5.52 (+/- 2.33) before and 5.97 (+/- 3.06) after 4 days of LMWH (p = 0.54). CONCLUSIONS: Unlike UFH, LMWH (Lovenox in doses used for postoperative prophylaxis against deep venous thrombosis does not seem to have a significant effect on potassium homeostasis.


Asunto(s)
Aldosterona/fisiología , Heparina de Bajo-Peso-Molecular/farmacología , Potasio/metabolismo , Anciano , Anciano de 80 o más Años , Creatinina/metabolismo , Heparina de Bajo-Peso-Molecular/efectos adversos , Homeostasis/efectos de los fármacos , Humanos , Hiperpotasemia/sangre , Hiperpotasemia/inducido químicamente , Hiperpotasemia/orina , Túbulos Renales/efectos de los fármacos , Túbulos Renales/metabolismo , Masculino , Persona de Mediana Edad , Procedimientos Ortopédicos , Concentración Osmolar , Complicaciones Posoperatorias/prevención & control , Trombosis de la Vena/prevención & control , Zona Glomerular/efectos de los fármacos
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