Changes In Urinary Potassium Excretion Research Articles

Abstract P643: Potassium Differential Stress Response with Angiotensin II Blockade in Blacks

Background: In youths, we demonstrated stress increases systolic blood pressure (SBP) with decreased urinary sodium excretion (UNaV) and no change in urinary potassium excretion (UKV) in retainers (retain sodium during stress) but increased UNaV and UKV in excreters (excrete sodium during stress). Angiotensin receptor blockers (ARBs) are known to increase UNaV, yet are not commonly used in blacks. Purpose: This study sought to determine if angiotensin II plays a role in the Na/K imbalance in retainers. The tested hypothesis was angiotensin II (Ang II) blockade stabilizes the urinary sodium/potassium (UNa/KV) excretion ratio during stress. Methods: Impact of Ang II on changes in SBP, UNaV, UKV and UNa/KV ratio in response to stress was tested in blacks after three day sodium/potassium controlled diet in a double-blind, placebo-controlled crossover design using irbesartan. Results: Excreters (n=84) and retainers (n=25) were identified and compared on placebo versus ARB. In response to Ang II blockade, excreters reduced their UNa/KV ratio and increased UNaV. Conversely, retainers did not change UNaV while sustaining their UNa/KV ratio. However, both groups increased SBP and UKV with a greater effect in excreters. Conclusion: These data suggest Ang II plays a significant role in the UNa/KV ratio homeostasis, through its impact on UNaV. Specifically, retainers are able to maintain their UNa/KV ratio during stress with Ang II blockade, whereas excreters are unable to maintain their UNa/KV ratio under the same treatment. Identification of this stress response pattern may be a critical need in providing personalized and effective treatment.

Changes in urinary potassium excretion in patients with chronic kidney disease

BackgroundHyperkalemia is one of the more serious complications of chronic kidney disease (CKD), and the cause of potassium retention is a reduction in urinary potassium excretion. However, few studies have examined the extent of the decrease of urinary potassium excretion in detail with respect to decreased renal function. MethodsNine hundred eighty-nine patients with CKD (CKD stages G1 and G2 combined: 135; G3a: 107; G3b: 170; G4: 289; and G5: 288) were evaluated retrospectively. Values for urinary potassium excretion were compared between CKD stages, and the associations between urinary potassium excretion and clinical parameters, including diabetes mellitus status and use of renin–angiotensin–aldosterone system inhibitors, were analyzed using a multivariable linear regression analysis. ResultsUrinary potassium excretion gradually decreased with worsening of CKD (G5: 24.8 ± 0.8 mEq/d, P < 0.001 vs. earlier CKD stages). In contrast, the value of fractional excretion of potassium at CKD G5 was significantly higher than that at the other stages (30.63 ± 0.93%, P < 0.001). Multivariable linear regression analysis revealed that urinary potassium excretion was independently associated with urinary sodium excretion (standardized coefficient, 0.499), the estimated glomerular filtration rate (0.281), and serum chloride concentration (–0.086). ConclusionThis study demonstrated that urinary potassium excretion decreased with reductions in renal function. Furthermore, urinary potassium excretion was mainly affected by urinary sodium excretion and estimated glomerular filtration rate in patients with CKD, whereas the presence of diabetes mellitus and use of renin–angiotensin–aldosterone system inhibitors were not associated with urinary potassium excretion in this study.

Effect of potassium supplementation on renal tubular function, ambulatory blood pressure and pulse wave velocity in healthy humans

Background. Potassium is the main intracellular cation, which contributes to keeping the intracellular membrane potential slightly negative and elicits contraction of smooth, skeletal and cardiac muscle. A change in potassium intake modifies both cardiovascular and renal tubular function. The purpose of the trial was to investigate the effect of dietary potassium supplementation, 100 mmol daily in a randomized, placebo-controlled, crossover trial of healthy participants during two periods of 28 days duration. The participants (N = 21) received a diet that was standardized regarding energy requirement, and sodium and water intake. Methods. 24-hour ambulatory blood pressure (ABP) and applanation tonometry were used to assess blood pressure, pulse wave velocity (PWV), augmentation index (AIx) and central blood pressure (CBP). Immunoassays were used for measurements of plasma concentrations of vasoactive hormones: renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP), vasopressin (AVP), pro-brain natriuretic peptide (pro-BNP),endothelin (Endo), urinary excretions of aquaporin 2 (AQP2), cyclic AMP (cAMP), and the β-fraction of the epithelial sodium channel (ENaCß). Results. AQP2 excretion increased during potassium supplementation, and free water clearance fell. The changes in urinary potassium excretion and urinary AQP2 excretion were significantly and positively correlated. Aldo increased. GFR, u-ENaC- β, PRC, Ang II, ANP, BNP, Endo, blood pressure and AI were not significantly changed by potassium supplementation, whereas PWV increased slightly. Conclusions. Potassium supplementation changed renal tubular function and increased water absorption in the distal part of the nephron. In spite of an increase in aldosterone in plasma, blood pressure remained unchanged after potassium supplementation.ClinicalTrials.Gov Identifier: NCT00801034

The effect of potassium supplementation in persons with a high-normal blood pressure: Results from phase I of the Trials of Hypertension Prevention (TOHP)

We conducted a randomized, double-blind, placebo-controlled trial oral potassium chloride supple mentation (60 mmol/d) in 353 men and women with an initial average diastolic blood pressure between 80 and 89 mm Hg. In the active (n = 178) campared to the placebo (n = 175) treatment group, the urinary potassium level was significandy (p < 0.001) increased by an average of 44.0 and 42.3 mmol/24 h following 3 and 6 months of therapy, respectively. Compared to placebo, active treatment was associated with a small (mean = 1.8 mm Hg) but significant (p = 0.04) reduction in diastolic blood pressure following 3 months of therapy. Following 6 months, however, this apparent treatment effect had virtually disappeared (mean reduction in diastolic blood pressure = 0.3 mm Hg). There was no significant effect of potassium supplementation on systolic blood pressure at either follow-up visit. There was a significant, independant, dose-response relationship between change in both 24-hour urinary potassium excretion and urinary sodium-potassium ratio and the corresponding change in diastolic blood pressure (−1.49 mm Hg for the highest versus the lowest quartile of change in urinary potassium excretion).

Renal actions of the angiotensin AT 2 receptor ligands CGP 42112 and PD 123319 after blockade of the renin-angiotensin system

The purpose of this study was to investigate whether the selective angiotensin AT 2 receptor ligands, CGP 42112B (NicTyr-( N α -benzoylocarbonyl-Arg)LysHisProIleOH) and PD 123319 (( s)-1-[[4-(dimethylamino)- 3-methyl-phenyl]methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1 H-imidazo[4,5,- c]-pyridine-6-carboxylic acid) are agonists at angiotensin receptors influencing blood pressure and renal function in the enalaprilat-treated anesthetized rat. The agonist angiotensin II significantly increased blood pressure and renal vascular resistance. Glomerular filtration rate was unchanged by angiotensin II. Effective renal blood flow decreased significantly in response to angiotensin II leading to a significant increase in filtration fraction. Angiotensin II did not induce significant change in urinary potassium excretion or free water formation but significantly increased both urine volume and urinary sodium excretion. At doses up to 3 orders of magnitude greater than angiotensin II, CGP 42112B also significantly increased blood pressure, filtration fraction, glomerular filtration rate, urine volume and urinary sodium excretion, but did not significantly affect effective renal blood flow or renal vascular resistance. The selective angiotensin AT 2 receptor ligand PD 123319 had no significant effects on blood pressure nor any measured parameter of renal function. The changes in blood pressure and renal function produced by angiotensin II and CGP 42112B could be completely blocked by the angiotensin AT 1 receptor antagonist losartan. The result therefore only support a role for angiotensin AT 1 receptors and not angiotensin AT 2 receptors in the control of renal function in the rat and demonstrate that at high dose the angiotensin AT 2 selective ligand CGP 42112B behaves as an agonist at angiotensin AT 1 receptors.

Digoxin amplifies the effects of deoxycorticosterone acetate (DOCA) in intact water-drinking rats

An increase in digitalis-like substances has been reported in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. We hypothesized that the role of saline and unilateral nephrectomy in DOCA hypertension may be due to stimulation of endogenous digitalis-like substances. We investigated the effects of digoxin and DOCA alone and in combination in intact rats drinking water. Forty male Sprague-Dawley rats were used (body weight 223-298 g). Neither digoxin (40 micrograms/kg per day, by gavage, for 35 days, n = 10) nor DOCA (30 mg/kg twice a week, subcutaneously, for 5 weeks, n = 10) caused a consistent increase in blood pressure in intact rats drinking water. In contrast, combined digoxin and DOCA administration (n = 10) increased systolic blood pressure from day 18 of treatment onwards, to a maximum at day 34 compared with sham-treated rats (n = 10). There were no consistent changes in water intake, urine volume, urinary sodium or potassium excretion, or plasma sodium or potassium concentration with digoxin treatment. DOCA increased water intake and urine volume, and caused an initial decrease in urinary sodium excretion, but no change in urinary potassium excretion or plasma sodium concentration. Plasma potassium excretion was lower in DOCA- than sham-treated rats. Combined digoxin and DOCA administration in intact rats drinking water increased blood pressure significantly compared with either drug alone, raising the possibility that the mechanism by which nephrectomy and salt loading contribute to DOCA hypertension in the rat might be through stimulation of endogenous digitalis-like substances.

The effect of medetomidine, an α2‐adrenoceptor agonist, on plasma atrial natriuretic peptide levels, haemodynamics and renal excretory function in spontaneously hypertensive and Wistar‐Kyoto rats

1. The effects of the selective alpha 2-adrenoceptor agonist, medetomidine, were assessed on plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP), haemodynamics and on urine water and solute excretion in conscious, chronically cannulated, 7 month-old spontaneously hypertensive (SHR) and age-matched Wistar-Kyoto (WKY) rats, in order to examine the role of alpha 2-adrenoceptors in the control of ANP secretion. 2. A 60 min i.v. infusion of medetomidine (0.2 or 0.6 microgram kg-1 min-1) decreased heart rate dose-dependently in both strains. Medetomidine infusion (0.6 microgram kg-1 min-1) resulted in an increase in mean arterial pressure in WKY, whereas both doses decreased blood pressure in SHR. There was a slight increase in the right atrial pressure in both strains (WKY: +1.18 +/- 0.26 mmHg; SHR: +1.64 +/- 0.64 mmHg, NS) in response to infusion of 0.6 microgram kg-1 min-1 of medetomidine. 3. No differences were found in resting plasma IR-ANP levels between WKY (114 +/- 8 pg ml-1, n = 19) and SHR (117 +/- 10 pg ml-1, n = 21). Infusion of equibradycardic doses of medetomidine increased dose-dependently plasma IR-ANP levels in WKY, but did not affect the plasma IR-ANP concentration in SHR rats. 4. Despite the different effect of medetomidine on ANP release in WKY and SHR rats, i.v. administration of medetomidine affected renal excretory functions similarly in both strains; urine flow and sodium excretion increased and urine osmolality decreased significantly, while there was no consistent change in urinary potassium excretion. Urine osmolality decreased to hypo-osmotic levels during the infusion of 0.6 yg kg-1 min1 of medetomidine, suggesting a possible interaction between alpha 2-adrenoceptor stimulation and the vasopressin system. 5. These results show that the alpha 2-adrenoceptor agonist medetomidine increased plasma levels of ANP in WKY rats, probably through an increase in mean arterial and right atrial pressures, whereas the SHR had attenuated ANP release to alpha 2-adrenoceptor stimulation. Our findings, that medetomidine caused marked natriuretic and diuretic effects in both strains and that these effects on the excretory functions of the kidneys were not related to changes in plasma levels of IR-ANP, demonstrate that changes in plasma ANP levels alone do not account for the diuretic and natriuretic effect of alpha 2-agonists.

Renal sensitivity to angiotensin II in the conscious dog.

Local formation of angiotensin II (AII) within the kidney has been demonstrated. Changes in renal function induced by inhibitors of the renin-angiotensin system have been the basis for the postulate that AII may act as a paracrine substance in the kidney. We studied the renal action of chronic intrarenal infusions of AII at doses between 2 and 2000 fmol/kg X min in uninephrectomized conscious dogs monitored on 80 meq daily sodium intake. Exogenous AII was confined to the kidney, as demonstrated by the absence of systemic pressor and adrenal cortical responses during the intrarenal infusion. After 2 control days, each dose of AII was infused intrarenally for a period of 3 days. The smallest intrarenal dose of AII that caused significant antinatriuresis and antidiuresis was 20 fmol/kg X min. A significant reduction in urinary volume and sodium excretion occurred during the first 24 h of the infusion period and was proportionate to the amount of peptide infused. Renal escape from the antinatriuretic and antidiuretic effects of the peptide ensued on the second and third days of infusion. There were no significant changes in urinary potassium excretion, plasma renin activity (PRA), plasma aldosterone concentration, or blood pressure throughout the period of intrarenal AII administration. These data demonstrate dose-dependent direct antinatriuretic and antidiuretic actions of low AII concentrations. Escape from the sodium-retaining action of intrarenal AII occurred by 48 h and was independent of suppression of endogenous renin-angiotensin. These results indicate that AII alters renal function by direct intrarenal mechanisms.

Acute hypokalemic effect of gossypol.

Clinical trials had demonstrated that chronic ingestion of gossypol induced infertility in males. Hypokalemia of various severities were reported in volunteers taking gossypol. The purpose of this study is to investigate the effects of acute gossypol infusion into alkalotic rats. Plasma potassium concentration decreased from 4.08 to 2.87 mM after gossypol infusion with minimal change in urinary potassium excretion. The hypokalemic effect of gossypol was also observed in nephretomized rats. Some of the factors that are known to affect potassium distribution between the extracellular and intracellular fluid compartment have been investigated in these rats. Plasma glucose concentration was not significantly altered. Gossypol induced hypokalemia was not blocked in rats treated with propranolol. It is therefore believed that the acute hypokalemic effect of gossypol is a direct shifting of potassium into cells.

Bioavailability of potassium from controlled-release tablets with and without water loading.

The relative availability of potassium from a controlled-release multiple-units tablet (Kalinorm) and a single-unit tablet (Slow-K) were compared in 13 volunteers on a low potassium diet (less than 30 mmol), by observing changes in urinary potassium excretion after administration of a single dose of 32 mmol potassium, either with or without water loading. Irrespective of procedure, the two products had the same extent of availability. The use of water loading, and special precautions about the level of dietary potassium and its composition when studying urinary potassium excretion, are discussed. It is suggested that water loading should be avoided when investigating the rate of potassium excretion.