Higher Urinary Potassium Excretion Research Articles

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

Apolipoprotein L1 Genotypes and the Association of Urinary Potassium Excretion with CKD Progression.

Progressive CKD in Black individuals is strongly associated with polymorphisms in the APOL1 gene, but it is unknown whether dietary risk factors for CKD progression vary in high- versus low-risk APOL1 genotypes. We investigated if APOL1 genotypes modify associations of dietary potassium and sodium with CKD progression and death. We analyzed 1399 self-identified Black participants enrolled in the Chronic Renal Insufficiency Cohort from April 2003 to September 2008. Exposures were calibrated 24-hour urine potassium and sodium excretion. The primary outcome was CKD progression defined as the time to 50% decline in eGFR or kidney failure. The secondary outcome was CKD progression or death. We tested for an interaction between urinary potassium and sodium excretion and APOL1 genotypes. Median 24-hour urinary sodium and potassium excretions in Black participants were 150 mmol (interquartile range, 118-188) and 43 mmol (interquartile range, 35-54), respectively. Individuals with high- and low-risk APOL1 genotypes numbered 276 (20%) and 1104 (79%), respectively. After a median follow-up of 5.23 years, CKD progression events equaled 605, and after 7.29 years, CKD progression and death events equaled 868. There was significant interaction between APOL1 genotypes and urinary potassium excretion with CKD progression and CKD progression or death (P=0.003 and P=0.03, respectively). In those with high-risk APOL1 genotypes, higher urinary potassium excretion was associated with a lower risk of CKD progression (quartiles 2-4 versus 1: hazard ratio, 0.83; 95% confidence interval, 0.50 to 1.39; hazard ratio, 0.54; 95% confidence interval, 0.31 to 0.93; and hazard ratio, 0.50; 95% confidence interval, 0.27 to 0.93, respectively). In the low-risk APOL1 genotypes, higher urinary potassium excretion was associated with a higher risk of CKD progression (quartiles 2-4 versus 1: hazard ratio, 1.01; 95% confidence interval, 0.75 to 1.36; hazard ratio, 1.23; 95% confidence interval, 0.91 to 1.66; and hazard ratio, 1.53; 95% confidence interval, 1.12 to 2.09, respectively). We found no interaction between APOL1 genotypes and urinary sodium excretion with CKD outcomes. Higher urinary potassium excretion was associated with lower versus higher risk of CKD progression in APOL1 high-risk and low-risk genotypes, respectively.

Urinary potassium excretion and mortality risk in community-dwelling individuals with and without obesity

ABSTRACTBackgroundPotassium intake has been shown to be inversely associated with blood pressure and premature mortality. Previous studies have suggested that the association between potassium intake and blood pressure is modified by obesity, but whether obesity similarly influences the association between potassium intake and mortality is unclear.ObjectivesWe investigated whether potassium intake, reflected by 24-h urinary excretion, is associated with all-cause mortality, and explored potential effect modification by obesity.MethodsWe performed a prospective cohort study in community-dwelling individuals. The association between urinary potassium excretion and all-cause mortality was investigated by using multivariable Cox regression. We performed multiplicative interaction analysis and subgroup analyses according to BMI and waist circumference.ResultsIn 8533 individuals (50% male), the mean age was 50 ± 13 y, mean urinary potassium excretion was 71 ± 21 mmol/24 h, median BMI (in kg/m2) was 25.6 (IQR: 23.1, 28.4) and mean waist circumference was 89 ± 13 cm. During median follow-up of 18.4 (IQR: 13.5, 18.8) y, 1663 participants died. Low urinary potassium excretion (first compared with third sex-specific quintile) was associated with an increased mortality risk (fully adjusted HR: 1.38; 95% CI: 1.18, 1.61), P < 0.001, irrespective of body dimensions (HR range for all body dimensions: 1.36–1.70, all P < 0.05). High urinary potassium excretion (fifth compared with third quintile) was associated with increased mortality risk in participants with obesity (BMI ≥30; HR: 1.52; CI: 1.00, 2.30), but not in participants without obesity (BMI: <25; HR: 0.89; 95% CI: 0.62, 1.26; P-interaction = 0.001).ConclusionsLow potassium intake was associated with increased mortality risk in community-dwelling individuals. In individuals with obesity, high potassium intake was also associated with increased mortality risk.

Dietary potassium and the kidney: lifesaving physiology.

Potassium often has a negative connotation in Nephrology as patients with chronic kidney disease (CKD) are prone to develop hyperkalaemia. Approaches to the management of chronic hyperkalaemia include a low potassium diet or potassium binders. Yet, emerging data indicate that dietary potassium may be beneficial for patients with CKD. Epidemiological studies have shown that a higher urinary potassium excretion (as proxy for higher dietary potassium intake) is associated with lower blood pressure (BP) and lower cardiovascular risk, as well as better kidney outcomes. Considering that the composition of our current diet is characterized by a high sodium and low potassium content, increasing dietary potassium may be equally important as reducing sodium. Recent studies have revealed that dietary potassium modulates the activity of the thiazide-sensitive sodium-chloride cotransporter in the distal convoluted tubule (DCT). The DCT acts as a potassium sensor to control the delivery of sodium to the collecting duct, the potassium-secreting portion of the kidney. Physiologically, this allows immediate kaliuresis after a potassium load, and conservation of potassium during potassium deficiency. Clinically, it provides a novel explanation for the inverse relationship between dietary potassium and BP. Moreover, increasing dietary potassium intake can exert BP-independent effects on the kidney by relieving the deleterious effects of a low potassium diet (inflammation, oxidative stress and fibrosis). The aim of this comprehensive review is to link physiology with clinical medicine by proposing that the same mechanisms that allow us to excrete an acute potassium load also protect us from hypertension, cardiovascular disease and CKD.

Association between urinary potassium excretion and blood pressure: A systematic review and meta-analysis of observational studies.

Background:The evidence base regarding the association between urinary potassium and blood pressure (BP), or risk of hypertension, is inconsistent. Therefore, we sought to conduct a qualitative and quantitative literature review on the association between potassium excretion and BP.Materials and Methods:Medline, Scopus, Web of Science, Science Direct, and Google Scholar were searched up to June 2020. All observational studies that reported BP and measured potassium excretion in overnight or 24-h urine samples were included. Correlation coefficients, mean urinary potassium excretion, and odds ratio (ORs) of hypertension were extracted from the included studies. There were no language or publication date restrictions.Results:Overall, twelve observational studies, including 16,174 subjects, were identified for inclusion in the present meta-analysis, and 21 effect sizes were extracted. Pooled mean potassium excretion was 3.46 mmol/24 h higher in normotensive individuals compared with hypertensive subjects (95% confidence interval [CI]: 0.61, 6.31). High urinary potassium excretion was not associated with the risk of hypertension (OR: 0.95; 95% CI: 0.79, 1.13). The pooled correlation coefficient between BP and urinary potassium was not significant (ES: 0.01; 95% CI: −0.03, 0.05). However, a subgroup analysis by age indicated a significant positive correlation between urinary potassium and systolic BP in children (ES: 0.12; 95% CI: 0.04, 0.19).Conclusion:24 h urinary potassium excretion was not correlated to BP and risk of hypertension. In contrast, mean urinary potassium excretion was higher in normotensive individuals compared with hypertensive counterparts. Future studies should focus on the association between different sources of dietary potassium and BP.

Bartter syndrome-like phenotype in a patient with diabetes: a case report

BackgroundBartter’s syndrome is a rare genetic tubulopathy affecting the loop of Henle leading to salt wasting. It is commonly seen in utero or in early neonatal period. Rare cases of acquired Bartter’s syndrome are reported in association with infections like tuberculosis, granulomatous conditions like sarcoidosis, autoimmune diseases, and drugs. The mainstay of management includes potassium, calcium, and magnesium supplementation.Case presentationWe report the case of a 62-year-old Sri Lankan Sinhalese man with diabetes and hypertension presenting with generalized weakness with clinical evidence of proximal myopathy. He was severely hypokalemic with high urinary potassium excretion and hypochloremic metabolic alkalosis. He poorly responded to intravenously administered potassium supplements. A diagnosis of idiopathic Bartter-like phenotype was made. He responded well to spironolactone and indomethacin.ConclusionsPatients presenting with body weakness need serum potassium estimation. Acquired Bartter’s syndrome although rare, should be ruled out in those with hypokalemia and metabolic alkalosis with increased urinary potassium loss with poor response to potassium replacement.

Continuum of Renin-Independent Aldosteronism in Normotension.

Primary aldosteronism is a severe form of autonomous aldosteronism. Milder forms of autonomous and renin-independent aldosteronism may be common, even in normotension. We characterized aldosterone secretion in 210 normotensives who had suppressed plasma renin activity (<1.0 ng/mL per hour), completed an oral sodium suppression test, received an infusion of angiotensin II, and had measurements of blood pressure and renal plasma flow. Continuous associations between urinary aldosterone excretion rate, renin, and potassium handling were investigated. Severe autonomous aldosterone secretion that was consistent with confirmed primary aldosteronism was defined based on accepted criteria of an aldosterone excretion rate >12 μg/24 hours with urinary sodium excretion >200 mmol/24 hours. Across the population, there were strong and significant associations between higher aldosterone excretion rate and higher urinary potassium excretion, higher angiotensin II-stimulated aldosterone, and lower plasma renin activity, suggesting a continuum of renin-independent aldosteronism and mineralocorticoid receptor activity. Autonomous aldosterone secretion that fulfilled confirmatory criteria for primary aldosteronism was detected in 29 participants (14%). Normotensives with evidence suggestive of confirmed primary aldosteronism had higher 24-hour urinary aldosterone excretion rate (20.2±12.2 versus 6.2±2.9 μg/24 hours; P<0.001) as expected, but also higher angiotensin II-stimulated aldosterone (12.4±8.6 versus 6.6±4.3 ng/dL; P<0.001) and lower 24-hour urinary sodium-to-potassium excretion (2.69±0.65 versus 3.69±1.50 mmol/mmol; P=0.001); however, there were no differences in age, aldosterone-to-renin ratio, blood pressure, or renal plasma flow between the 2 groups. These findings indicate a continuum of renin-independent aldosteronism and mineralocorticoid receptor activity in normotension that ranges from subtle to overtly dysregulated and autonomous. Longitudinal studies are needed to determine whether this spectrum of autonomous aldosterone secretion contributes to hypertension and cardiovascular disease.

Urinary Potassium Excretion and Renal and Cardiovascular Complications in Patients with Type 2 Diabetes and Normal Renal Function.

We investigated the association of urinary potassium and sodium excretion with the incidence of renal failure and cardiovascular disease in patients with type 2 diabetes. A total of 623 Japanese type 2 diabetic patients with eGFR≥60 ml/min per 1.73 m(2) were enrolled in this observational follow-up study between 1996 and 2003 and followed-up until 2013. At baseline, a 24-hour urine sample was collected to estimate urinary potassium and sodium excretion. The primary end point was renal and cardiovascular events (RRT, myocardial infarction, angina pectoris, stroke, and peripheral vascular disease). The secondary renal end points were the incidence of a 50% decline in eGFR, progression to CKD stage 4 (eGFR<30 ml/min per 1.73 m(2)), and the annual decline rate in eGFR. During the 11-year median follow-up period, 134 primary end points occurred. Higher urinary potassium excretion was associated with lower risk of the primary end point, whereas urinary sodium excretion was not. The adjusted hazard ratios for the primary end point in Cox proportional hazards analysis were 0.56 (95% confidence interval [95% CI], 0.33 to 0.95) in the third quartile of urinary potassium excretion (2.33-2.90 g/d) and 0.33 (95% CI, 0.18 to 0.62) in the fourth quartile (>2.90 g/d) compared with the lowest quartile (<1.72 g/d). Similar associations were observed for the secondary renal end points. The annual decline rate in eGFR in the fourth quartile of urinary potassium excretion (-1.3 ml/min per 1.73 m(2)/y; 95% CI, -1.5 to -1.0) was significantly slower than those in the first quartile (-2.2; 95% CI, -2.4 to -1.8). Higher urinary potassium excretion was associated with the slower decline of renal function and the lower incidence of cardiovascular complications in type 2 diabetic patients with normal renal function. Interventional trials are necessary to determine whether increasing dietary potassium is beneficial.

Renal outcomes and dietary potassium: the overshadowed electrolyte?

Smyth et al. examined the association between urinary sodium and potassium excretion and adverse renal outcomes in adults at high cardiovascular risk. They found no association between urinary sodium excretion and adverse renal outcomes, but a reduced odds of adverse renal outcomes with higher urinary potassium excretion. This finding is quite interesting and a major advancement from this study. It will be important to ascertain whether this finding holds true in individuals free from vascular disease and diabetes, as well as in patients with chronic kidney disease.

Association d’une hypertension artérielle rénovasculaire et d’un hyperaldostéronisme primaire

IntroductionRenal artery stenosis is rarely associated with Conn adenoma. Case reportWe report a 27-year-old male patient who presented in 2001 with a severe high blood pressure associated with hypokaliemia. Radiologic investigations showed a left renal artery stenosis with agenesis of left kidney. A left nephrectomy was performed and blood pressure returned to normal with a single antihypertensive drug. Five years later, the patient again presented with severe high blood pressure. Laboratory studies revealed a low serum potassium level at 2.8mmol/L associated with high urinary potassium excretion (84 mmol/24h) and a very high aldosterone/renin ratio (>462). Abdominal CT scan demonstrated a right adrenal mass. The patient underwent a right adrenalectomy (adenoma). Blood pressure returned to normal with a single antihypertensive. Serum potassium levels as well as aldosterone/renin ratio normalized. ConclusionWe discussed whether the association between these two entities is merely fortuitous or conversely based on a causal relationship.

Chronic hypokalaemia and nephrocalcinosis.

Unravelling chronic hypokalaemia can be a clinical challenge in some patients. History and physical examination can be misleading or inaccurate. Diagnostic steps usually involve assessing urinary potassium excretion, transtubular potassium gradient (TTKG) and concomitant acid–base disturbances. In those patients with low urinary potassium excretion, a gastrointestinal cause for the hypokalaemia would come to mind. In patients with a high urinary potassium excretion, the kidneys themselves are implicated. In any event, acid–base status is extremely helpful and generally indicates which end of the gastrointestinal tract or which level of the nephron is responsible. In patients with high urinary potassium with metabolic alkalosis, the urinary chloride concentration can be particularly helpful in separating surreptitious vomiting from Bartter's syndrome or Gitelman's syndrome. Diuretic abuse may be a confounder; however, metabolic breakdown products and the temporal course of chloride excretion generally solve the mystery. We recently encountered a patient who taxed our diagnostic skills.

Corticosteroid-dependent hypertension: environmental influences.

Hypertension is a major disease of later life affecting 25% of the adult population in the industrialized world with most hypertensive individuals diagnosed as having essential hypertension. Approximately one third of these patients have elevated blood pressure due to increased sodium and water retention by the kidney resulting in suppressed plasma renin and aldosterone concentrations with high urinary potassium excretion and low plasma potassium levels. Monogenic forms of corticosteroid-dependent hypertension are rare. However, the discovery of these disorders has revealed genes whose proteins play a key role in the regulation of sodium homeostasis. The impaired function of these proteins, due to altered protein expression or the presence of inhibitors, contributes to the development of corticosteroid-dependent hypertension. This article focuses on the potential impact of environmental influences on corticosteroid-dependent regulation of sodium homeostasis and the development of hypertension.

Corticosteroid-dependent hypertension: environmental influences.

Hypertension is a major disease of later life affecting 25% of the adult population in the industrialized world with most hypertensive individuals diagnosed as having essential hypertension. Approximately one third of these patients have elevated blood pressure due to increased sodium and water retention by the kidney resulting in suppressed plasma renin and aldosterone concentrations with high urinary potassium excretion and low plasma potassium levels. Monogenic forms of corticosteroid-dependent hypertension are rare. However, the discovery of these disorders has revealed genes whose proteins play a key role in the regulation of sodium homeostasis. The impaired function of these proteins, due to altered protein expression or the presence of inhibitors, contributes to the development of corticosteroid-dependent hypertension. This article focuses on the potential impact of environmental influences on corticosteroid-dependent regulation of sodium homeostasis and the development of hypertension.

Respiratory symptoms and bronchial responsiveness are related to dietary salt intake and urinary potassium excretion in male children

To investigate whether dietary salt intake and urinary sodium and potassium levels are related to respiratory symptoms and bronchial responsiveness, a cross-sectional study among 2593 subjects aged 9 to 16 was conducted in four communities of the Latium region (Italy). Questionnaires were administered to the parents, urine samples were collected, lung function, methacholine challenge tests and prick tests were performed. Information about familial and personal dietary salt use and respiratory health was collected from the parents of 2439 (94%) subjects. A total of 2020 methacholine challenge tests and 916 urinary sodium and potassium levels were available for analysis. Personal table salt use was strongly related to cough and phlegm apart from colds (adjusted odds ratios, OR, 1.87, 95% confidence intervals, CI, 1.20-2.90), wheezing apart from colds (OR, 2.19, 95% CI, 1.27-3.77), wheezing with dyspnoea (OR, 1.45, 95% CI, 0.98-2.12) and wheezing after exercise (OR, 2.16, 95% CI, 1.35-3.44). These associations were mainly found in boys. Use of familial table salt and canned food showed no relation to respiratory symptoms. Increased bronchial responsiveness was associated with a higher urinary potassium excretion in boys, but not with urinary sodium. In conclusion, personal table salt use is related to an increased prevalence of bronchial symptoms; an increase in bronchial responsiveness among those with higher potassium excretion also seems to be implied. Although it is difficult to interpret the results of this study in causal terms, the findings might be relevant to the distribution of bronchial symptoms and diseases in the population.

Mechanism of potassium depletion during chronic metabolic acidosis in the rat.

Pair-fed rats on a normal K diet were given either 1.5% NH4Cl or water for 4 days. The acid-fed animals developed metabolic acidosis, negative K balance, and K depletion. Urinary Na excretion and urinary flow were not different between the groups beyond the first day. After the 4 days, isolated kidneys from animals in each of these groups were perfused at normal pH and bicarbonate concentrations. Urinary K excretion was similar between the groups despite the potassium depletion in the acid-fed animals. In contrast, isolated kidneys from animals with comparable K depletion induced by dietary K restriction readily conserved K (fractional excretion 0.35 +/- 0.04 vs. 0.83 +/- 0.09 by the kidneys from acid-fed animals, P less than 0.01). Sodium excretion and urinary flow were similar among the three groups of isolated kidneys. Plasma aldosterone concentrations were greater in the acid-fed rats after the 4 days of NH4Cl ingestion than in the control animals (43 +/- 10 vs. 10 +/- 2 ng/dl, P less than 0.01). Adrenalectomized rats were treated with either normal (4 micrograms/day) or high (22 micrograms/day) aldosterone replacement while ingesting NH4Cl for 4 days. Only in the presence of high aldosterone replacement did the acid-fed adrenalectomized animals develop K depletion. We conclude that chronic metabolic acidosis stimulates aldosterone secretion, and that aldosterone maintains the inappropriately high urinary potassium excretion and K depletion seen in this acid-base disorder.

Urinary sodium and blood pressure in vegetarians

Urinary sodium, potassium, urea, creatinine, uric acid, plasma urea, creatinine, cholesterol, blood pressures, height, weight, and skinfold thickness were measured in some or all of 106 matched pairs of vegetarians (mainly Seventh-Day Adventists) and nonvegetarians. Mean blood pressures were lower in vegetarians (141.9/88.9 mm) than nonvegetarians (148.0/90.9 mm) but the urinary excretion of sodium was higher, although not significantly, in the vegetarians (mean of 169.7 compared with 161.2 mmole/day). The vegetarians also had a higher urinary potassium excretion (62.9 mmole/day) than the nonvegetarians (54.8 mmole/day) thus giving them a lower mean sodium to potassium ratio (3.0 compared with 3.3). Both systolic and diastolic blood pressures correlated positively with plasma cholesterol levels which were less in vegetarians (6.0 mmole/liter) than nonvegetarians (6.6 mmole/liter). They also correlated positively with the urinary sodium to potassium ratio, but only in nonvegetarians. It was concluded that dietary sodium does not explain the blood pressure differences between vegetarians and nonvegetarians.

Improved processing technique for renal biopsies for light microscopy.

<h3>Background and objectives</h3> Progressive CKD in Black individuals is strongly associated with polymorphisms in the <i>APOL1</i> gene, but it is unknown whether dietary risk factors for CKD progression vary in high- versus low-risk <i>APOL1</i> genotypes. We investigated if <i>APOL1</i> genotypes modify associations of dietary potassium and sodium with CKD progression and death. <h3>Design, setting, participants, &amp; measurements</h3> We analyzed 1399 self-identified Black participants enrolled in the Chronic Renal Insufficiency Cohort from April 2003 to September 2008. Exposures were calibrated 24-hour urine potassium and sodium excretion. The primary outcome was CKD progression defined as the time to 50% decline in eGFR or kidney failure. The secondary outcome was CKD progression or death. We tested for an interaction between urinary potassium and sodium excretion and <i>APOL1</i> genotypes. <h3>Results</h3> Median 24-hour urinary sodium and potassium excretions in Black participants were 150 mmol (interquartile range, 118–188) and 43 mmol (interquartile range, 35–54), respectively. Individuals with high- and low-risk <i>APOL1</i> genotypes numbered 276 (20%) and 1104 (79%), respectively. After a median follow-up of 5.23 years, CKD progression events equaled 605, and after 7.29 years, CKD progression and death events equaled 868. There was significant interaction between <i>APOL1</i> genotypes and urinary potassium excretion with CKD progression and CKD progression or death (<i>P</i>=0.003 and <i>P</i>=0.03, respectively). In those with high-risk <i>APOL1</i> genotypes, higher urinary potassium excretion was associated with a lower risk of CKD progression (quartiles 2–4 versus 1: hazard ratio, 0.83; 95% confidence interval, 0.50 to 1.39; hazard ratio, 0.54; 95% confidence interval, 0.31 to 0.93; and hazard ratio, 0.50; 95% confidence interval, 0.27 to 0.93, respectively). In the low-risk <i>APOL1</i> genotypes, higher urinary potassium excretion was associated with a higher risk of CKD progression (quartiles 2–4 versus 1: hazard ratio, 1.01; 95% confidence interval, 0.75 to 1.36; hazard ratio, 1.23; 95% confidence interval, 0.91 to 1.66; and hazard ratio, 1.53; 95% confidence interval, 1.12 to 2.09, respectively). We found no interaction between <i>APOL1</i> genotypes and urinary sodium excretion with CKD outcomes. <h3>Conclusions</h3> Higher urinary potassium excretion was associated with lower versus higher risk of CKD progression in <i>APOL1</i> high-risk and low-risk genotypes, respectively.