Potassium-sparing Diuretics Research Articles

Hypertension Editors' Picks: Hyperaldosteronism.

Hypertension Editors' Picks: Hyperaldosteronism.

The association between diuretic class exposures and enteral electrolyte use in infants developing grade 2 or 3 bronchopulmonary dysplasia in United States children's hospitals.

To evaluate the association between chronic diuretic exposures and enteral electrolyte use in infants developing severe bronchopulmonary dysplasia (sBPD). Retrospective longitudinal cohort study in infants admitted to United States children's hospitals. We identified diuretic exposures and measured enteral NaCl and KCl use during pre-defined exposure risk-interval days. We used mixed-effects logistic regression to model the association between diuretic exposures and electrolyte use. We identified 442,341 subject-days in 3252 infants. All common diuretic classes and class combinations were associated with increased NaCl and KCl use. Thiazide monotherapy was associated with greater electrolyte use than loop monotherapy. The addition of potassium-sparing diuretics was associated with a limited reduction in KCl use compared to thiazide monotherapy. Chronic diuretic exposures are associated with increased NaCl and KCl use. Presumptions about the relative impact of different diuretic classes on electrolyte derangements may be inaccurate and require further study.

COVID-19-The Potential Beneficial Therapeutic Effects of Spironolactone during SARS-CoV-2 Infection.

In March 2020, coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO). The clinical course of the disease is unpredictable but may lead to severe acute respiratory infection (SARI) and pneumonia leading to acute respiratory distress syndrome (ARDS). It has been shown that pulmonary fibrosis may be one of the major long-term complications of COVID-19. In animal models, the use of spironolactone was proven to be an important drug in the prevention of pulmonary fibrosis. Through its dual action as a mineralocorticoid receptor (MR) antagonist and an androgenic inhibitor, spironolactone can provide significant benefits concerning COVID-19 infection. The primary effect of spironolactone in reducing pulmonary edema may also be beneficial in COVID-19 ARDS. Spironolactone is a well-known, widely used and safe anti-hypertensive and antiandrogenic medication. It has potassium-sparing diuretic action by antagonizing mineralocorticoid receptors (MRs). Spironolactone and potassium canrenoate, exerting combined pleiotropic action, may provide a therapeutic benefit to patients with COVID-19 pneumonia through antiandrogen, MR blocking, antifibrotic and anti-hyperinflammatory action. It has been proposed that spironolactone may prevent acute lung injury in COVID-19 infection due to its pleiotropic effects with favorable renin–angiotensin–aldosterone system (RAAS) and ACE2 expression, reduction in transmembrane serine protease 2 (TMPRSS2) activity and antiandrogenic action, and therefore it may prove to act as additional protection for patients at highest risk of severe pneumonia. Future prospective clinical trials are warranted to evaluate its therapeutic potential.

Short review of SEC, a potential dexamethasone-sparing regimen for glioblastoma: Spironolactone, ecallantide, clotrimazole

This paper presents a short review of data supporting a dexamethasone sparing regimen, SEC, to reduce glioblastoma related brain edema. The conclusion of the reviewed data is that the rationale and risk/benefit ratio favors a pilot study to determine if the three drug regimen of SEC can reduce need for corticosteroid use during the course of glioblastoma. Details of how selected pathophysiological aspects of brain edema occurring during the course of glioblastoma and its treatment intersect with the established action of the three old drugs of SEC indicate that they can be repurposed to reduce that edema. Current first-line treatment of this edema is dexamethasone or related corticosteroids. There are multiple negative prognostic implications of both the edema itself and of dexamethasone, prime among them shortened survival, making a dexamethasone sparing regimen highly desirable. SEC uses spironolactone, an antihypertensive potassium-sparing diuretic acting by mineralocorticoid receptor inhibition, ecallantide acting to inhibit kallikrein activation marketed to treat hereditary angioedema, and clotrimazole, an old antifungal drug that inhibits intermediate conductance Ca++ activated K+ channel (KCa3.1). These three old drugs are well known to most clinicians, have a well-tolerated safety history, and have a robust preclinical database showing their potential to reduce the specific edema of glioblastoma. Additionally, these three drugs were chosen by virtue of each having preclinical evidence of glioblastoma growth and/or migration inhibition independent of their edema reduction action. A clinical study of SEC is being planned.

Spironolactone hyaluronic acid enriched cerosomes (HAECs) for topical management of hirsutism: in silico studies, statistical optimization, ex vivo, and in vivo studies

Spironolactone (SP) is a potassium sparing diuretic with antiandrogenic properties. This study aimed at formulating SP into hyaluronic acid enriched cerosomes (HAECs) for topical management of hirsutism. HAECs were prepared by ethanol injection method, according to D-optimal design, after a proper in silico study. HAECs were evaluated by measuring their entrapment efficiency (EE%), particle size (PS), and polydispersity index (PDI). Optimal hyaluronic acid enriched cerosomes (OHAECs) were subjected to further in vitro and ex-vivo and in-vivo studies. The in silico study concluded better interactions between SP and phosphatidyl choline in presence of hyaluronic acid (HA) and high stability of their binding in water. The prepared HAECs had acceptable EE%, PS, and PDI values. The statistical optimization process suggested OHAEC containing 10.5 mg ceramide III and 15 mg HA, utilizing Kolliphor® RH40. OHAEC had EE% and PS of 89.3 ± 0.3% and 261.8 ± 7.0 nm, respectively. OHAEC was stable for up to 3 months. It also showed a mixed tubular and vesicular appearance under transmission electron microscope. The ex vivo and in vivo studies concluded better skin deposition and accumulation of SP from OHAEC. The histopathological study demonstrated the safety of OHAEC for topical application. Therefore, OHAEC could be considered as effective system for topical application of SP to manage hirsutism, with prolonged action, coupled with minimized side effects.

The effect of hyperkalemia and long inter-dialytic interval on morbidity and mortality in patients receiving hemodialysis: a systematic review

Background Patients with chronic kidney disease, especially those receiving hemodialysis (HD), are at risk of hyperkalemia (HK). This systematic review aimed to evaluate the prevalence of HK in patients with renal disease receiving HD and collate evidence on the effect of HK and differing HD patterns (i.e., long vs. short inter-dialytic intervals [LIDI and SIDI, respectively] in a thrice weekly schedule) on mortality. Methods Comprehensive searches were conducted across six databases and selected conference proceedings by two independent reviewers up to September 2020. A hundred and two studies reporting frequency of HK, mortality, or cardiovascular (CV) outcomes in adult patients with acute, chronic or end-stage renal disease in receipt of HD were included. Narrative synthesis of results was undertaken with key findings presented in tables and figures. Results Median prevalence of HK in patients with renal disease receiving HD was 21.6% and increased in patients receiving concomitant medications – mainly renin–angiotensin–aldosterone system inhibitors and potassium-sparing diuretics. Associations between elevated potassium levels and increased risk of both all-cause and CV mortality in the HD population were consistent across the included studies. In addition, there was a rise in all-cause and CV mortality on the day following LIDI compared with the day after the two SIDIs in patients on HD. Conclusions Evidence identified in this systematic review indicates a relationship between HK and LIDI with mortality in patients with renal disease receiving HD, emphasizing the need for effective monitoring and management to control potassium levels both in emergency and chronic HD settings.

Abstract 15811: Prevalent Pharmacotherapy in United States Children and Adolescents After Fontan Completion

Background: Patients who have undergone Fontan palliation are at life-long risk of significant morbidities including thrombosis, heart failure, and arrhythmia. At present there is limited evidence to guide pharmacotherapy and no recent studies have evaluated US pharmaceutical practice in this population. Methods: A retrospective observational study evaluating the prevalent use of prescription medications in children and adolescents with hypoplastic left heart syndrome or tricuspid atresia after Fontan completion (identified using ICD9/10 codes) was performed using data from the Marketscan® Commercial and Medicaid databases. Cardiac pharmaceuticals were divided by class and function. Anticoagualants, other than aspirin, which is not uniformly a prescription medication, were also studied. Associations between increasing age and the likelihood of a filled prescription for each class of drug were evaluated. Results: A cohort of 4056 subjects [median age 12 years (IQR: 8-16), 61% male, 60% commercial insurance] was identified. The most common medication classes were angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB), diuretics, cardiac glycosides, and pulmonary vasodilators (Table), although 50% received no prescription medications. Older age was associated with increased likelihood of receiving anticoagulants (p=0.008), antiarrhythmic agents, digoxin, ACEI/ARB, and beta blockers (each p <0.0001 ), but also lower likelihood of receiving pulmonary vasodilators, diuretics (both p <0.0001), and potassium sparing diuretics ( p =0.02). Conclusion: Pharmacotherapy typically used to treat adult heart failure and pulmonary hypertension are the most commonly prescribed medications following Fontan palliation. Determining the optimal regimen for individual patients and the population at large is an important knowledge gap for future research.

Abstract 15924: Identification of Gender- and Age-specific Top Predictors of Hospitalization Due to Heart Failure Using Machine Learning in TOPCAT

Background: NHLBI supported Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist trial (TOPCAT) (NCT00094302) investigated whether treatment with spironolactone reduces hospitalization due to heart failure (hHF) in 3,445 adults with prior heart failure and a left ventricular ejection fraction over 45%. We reused publicly available individual patient-level data from NHLBI Data Repository (BioLINCC) to perform hypothesis-generating secondary analyses by machine learning (ML) on the American TOPCAT cohort (n=1767) to identify gender and age groups specific baseline (bl) predictors of hHF. Methods: The subjects were stratified into subgroups based on gender (male and female) and age (50-59, 60-69, 70-79, 80-90). Random Survival Forest (RSF), a non-parametric ML approach, evaluated 172 bl variables as predictors of hHF. Top 10 predictors were subsequently included in a multivariate Cox proportional hazards model. Results: The top 10 predictors of hHF are shown in Figure 1. Overall, renal and hematological biomarkers appeared prominently in the top 10 predictors for these patients. While liver markers were among top predictors for hHF in males, diabetes treatment and diabetic complications were top predictors for females. Also, diabetic treatment was a top predictor among age group 50-59, diabetic complications were top predictors among age groups 50-59 and 70-79, liver markers were top predictors among age groups 70-79, and race and years of smoking were top predictors among age group 60-69. Importantly, the use of potassium sparing diuretic at bl was the top predictor among age group 80-90. Conclusion: Using ML, we uncovered in an unbiased fashion, otherwise overlooked bl predictors of hHF in a large, international, multi-center trial like TOPCAT. Thus, ML can help to identify similarities and differences of disease and treatment outcomes among gender, race, ethnicity, and age specific subgroups and advance precision medicine.

Using genetics to understand the role of antihypertensive drugs modulating angiotensin‐converting enzyme in immune function and inflammation

AimAngiotensin‐converting enzyme 2 (ACE 2) is the binding domain for severe acute respiratory syndrome coronavirus (SARS‐CoV) and SARSCoV‐2. Some antihypertensive drugs affect ACE2 expression or activity (ACE inhibitors and angiotensin II receptor blockers [ARBs]), suggesting use of other hypertensives might be preferable, such as calcium channel blockers (CCBs). Given the limited evidence, the International Society of Hypertension does not support such a policy.MethodsWe used a Mendelian randomization study to obtain unconfounded associations of antihypertensives, instrumented by published genetic variants in genes regulating target proteins of these drugs, with immune (lymphocyte and neutrophil percentage) and inflammatory (tumour necrosis factor alpha [TNF‐α]) markers in the largest available genome‐wide association studies.ResultsGenetically predicted effects of ACE inhibitors increased lymphocyte percentage (0.78, 95% confidence interval [CI] 0.35, 1.22), decreased neutrophil percentage (−0.64, 95% CI −1.09, −0.20) and possibly lowered TNF‐α (−4.92, 95% CI −8.50, −1.33). CCBs showed a similar pattern for immune function (lymphocyte percentage 0.21, 95% CI 0.05 to 0.36; neutrophil percentage −0.23, 95% CI −0.39 to −0.08) but had no effect on TNF‐α, as did potassium‐sparing diuretics and aldosterone antagonists, and vasodilator antihypertensives. ARBs and other classes of hypertensives had no effect on immune function or TNF‐α.ConclusionVarying effects of different classes of antihypertensives on immune and inflammatory markers do not suggest antihypertensive use based on their role in ACE2 expression, but instead suggest investigation of the role of antihypertensives in immune function and inflammation might reveal important information that could optimize their use in SARSCoV‐2.

Spironolactone in Dermatology: Uses in Acne, Hidradenitis Suppurativa, Female Pattern Hair Loss, and Hirsutism

Spironolactone is an economical potassium-sparing diuretic with an anti-androgenic effect and a good safety profile. Our experience suggests that this diuretic is underexploited in dermatology even though there is evidence supporting its use in several skin conditions. When prescribed for acne in female patients (level 1–2 evidence; strength of recommendation, B), for example, it can reduce the need for antibiotics and possibly isotretinoin. Other diseases in which spironolactone is potentially useful are hidradenitis suppurativa and female pattern hair loss. We discuss the indications for spironolactone, dosing in dermatology, precautions to consider, and adverse effects. We also review new evidence that stresses the safety of long-term therapy and supports the use of this drug without the need for complementary testing in young women. We think that spironolactone merits a place among the medications commonly used in routine clinical practice.

An evaluation of sodium zirconium cyclosilicate as a treatment option for hyperkalemia

ABSTRACT Introduction Hyperkalemia, defined as serum potassium level > 5.0 mEq/l, is associated with serious cardiac dysrhythmias, sudden death and increased mortality risk. It is common in patients with chronic kidney disease (CKD), diabetes (DM) and heart failure (HF), particularly in those treated with the renin-angiotensin-aldosterone system (RAAS) inhibitors or potassium-sparing diuretics. Although these drugs have documented renal and cardiac protective benefits, frequent hyperkalemia associated with their use often dictates administration of suboptimal doses or their discontinuation altogether. Treatment for chronic hyperkalemia in these settings has been challenging; however, the recent introduction of two new potassium-binding resins has revolutionized our approach to treating hyperkalemia. Areas covered We review key clinical data relating to the pharmacokinetics, efficacy and safety of sodium zirconium cyclosilicate (SZC) as a treatment option for hyperkalemia Expert opinion SZC and Patiromer are promising new agents for lowering serum potassium in hyperkalemic patients, including those with CKD, with and without DM or HF, facilitating the use of the RAAS inhibitors for renal and cardiac protection. Recent randomized clinical trials have shown that SZC effectively lowers serum potassium and maintains normokalemia in most hyperkalemic patients. Clinical trials showed that SZC lowers serum potassium within 1 h, although it is not approved for treating acute hyperkalemia. SZC was well tolerated and associated with minimal adverse effects.

Dyskalemias in patients with acute kidney injury presenting to the emergency department are common and independent predictors of adverse outcome.

No data concerning the prevalence and risk factors of dyskalemia in acute kidney injury (AKI) exist. We investigated (a) prevalence rates, (b) risk factors and (c) outcome of hypo- and hyperkalemia in emergency patients. In this cross-sectional analysis, all patients admitted to the emergency department of a large public hospital in Switzerland between January 1st 2017 and December 31st 2018 with measurements of creatinine and potassium were included. Baseline characteristics, medication and laboratory data were extracted. Chart reviews were performed to identify patients with a diagnosis of chronic kidney disease (CKD) and to extract their baseline creatinine. For all other patients, the ADQI backformula was used in order to calculate baseline creatinine. AKI was graduated using creatinine criteria of the acute kidney injury network. Binary logistic regression analysis was used to identify risk factors for appearance of hyperkalemia and outcome. AKI was found in 8% of patients. Hyperkalemia was present in 13% and hypokalemia in 11% of patients with AKI. AKI stage, potassium-sparing diuretics, ACE inhibitors and underlying CKD were the strongest risk factors for hyperkalemia. Hyperkalemia as well as profound hypokalemia were independently associated with prolonged length of stay and in-hospital mortality. The study is limited by its dependency on chart review data in order to identify patients with chronic kidney disease and by limitations of the ADQI backformula to calculate baseline creatinine. Dyskalemias are common in emergency patients with AKI and are independent risk factors for adverse outcomes. Potassium-sparing diuretics, ACE-inhibitors, AKIN stage and CKD are predictors of hyperkalemia in AKI.

Spironolactone: A promising anti-schistosomal drug as revealed by scanning electron microscopy of adult worms

Background: Schistosomiasis mansoni is still a widespread parasitic infection especially among poor developing countries. Depending on praziquantel (PZQ) as a single medication for treatment and control, causes the emergence of isolates resistant to this drug. Continuous efforts are needed for the introduction of new effective therapies. Some diuretics including spironolactone, showed promising anti-parasitic effects. Objectives: In this study, spironolactone, a potassium-sparing diuretic, was evaluated regarding its in vitro lethal effect on Schistosomamansoni (S. mansoni) adult worms using scanning electron microscopy (SEM). Material and Methods: A total of 144 worms; 72 males and 72 females were exposed to a concentration of 10 μg/ml of spironolactone for 5 days at 37±0.5°C in 5% CO2 incubator. A pure medium and a medium containing 0.5% of dimethyl sulfoxide (DMSO) (vehicle) were used as negative controls, while PZQ at 10 μg/ml was used as a reference drug. The compound was then retested using the same technique by successive descending dilutions of the solution. Mortality rate of 50% (lethal concentration) (LC50) and 100% (lethal concentration) (LC100) were calculated after 72 h and 5 days exposure. Results: Our results highlighted the potent anti-schistosome effect of spironolactone as it showed 100% mortality of worms at 6.4 μg/ml and 5 μg/ml after 72 h and 5 days exposure, respectively. While 50% mortality of worms was obtained at 4.5 μg/ml and 3 μg/ml after 72 h and 5 days exposure, respectively. Moreover, SEM of male and female S. mansoni worms exposed to spironolactone in vitro, showed disintegration and sloughing of the tubercles on the dorsal surface of males, erosion of the tegument with exposure and appearance of the sub-tegumental tissue in males and females. Conclusion: Being a safe, oral, inexpensive, and well tolerated drug, spironolactone is capable of being a potent future anti-schistosome drug.

Trimethoprim-associated electrolyte and acid-base abnormalities.

The antimicrobial trimethoprim is structurally related to potassium-sparing diuretics and may consequently lead to derangements in electrolyte and acid-base balance. Since no report so far analyzed the literature documenting individual cases with electrolyte and acid-base derangements induced by trimethoprim, a systematic review was carried out. We retained 53 reports documenting 68 cases (42 males and 26 females 23 to 96 years of age) of electrolyte or acid-base derangements occurring on trimethoprim for about 5 days. One hundred five electrolyte imbalances were detected in the 68 patients: hyperkalemia (>5.0 mmol/L) in 62 (91%), hyponatremia (<135 mmol/L) in 29 (43%) and metabolic acidosis (pH<7.38 and bicarbonate <19 mmol/L) in 14 (21%) cases. Following possible predisposing factors for electrolyte and acid-base abnormalities were found in 54 (79%) patients: high-dose trimethoprim, comedication with drugs that have been associated with electrolyte and acid-base derangements, preexisting kidney disease, age ≥80 years and diabetes mellitus. High-dose trimethoprim, comedicated with drugs that have been associated with electrolyte and acid-base derangements, poor kidney function, age ≥80 years and diabetes mellitus predispose to trimethoprim-associated electrolyte and acid-base abnormalities. Clinicians must recognize patients at risk, possibly avoid drug combinations that may worsen the problem and monitor the laboratory values.

Syndromes de Bartter–Gitelman

Bartter–Gitelman syndromes are rare inherited autosomal recessive salt-losing tubulopathies characterized by severe and chronic hypokalemia associated with metabolic alkalosis and secondary hyperaldosteronism. Bartter syndrome results from a furosemide-like defect in sodium reabsorption in the Henle's loop leading to hypercalciuria and defect in urinary concentration capacity. The antenatal Bartter syndrome is defined by polyhydramnios and an infantile polyuria with severe dehydration whereas classic Bartter syndrome appears during childhood or adulthood. Gitelman syndrome is a thiazide-like salt-losing tubulopathy. It is associated with hypomagnesemia, hypocalciuria without defect in urinary concentration capacity. The diagnosis is most often made in adolescents or adults. Clinical symptoms include tetany, delay in the height-weight growth curves, chronic tiredness, muscle weakness, myalgia and vertigo. Nephrocalcinosis in Bartter syndrome could lead to chronic kidney disease. Antenatal Bartter syndrome requires hospitalization in intensive care unit to manage the severe newborn dehydration. Chondrocalcinosis is the major complication in the Gitelman syndrome. The corner stones of treatment is the fluid and electrolyte management Bartter and Gitelman syndromes need lifelong oral supplementations of potassium, salt (Bartter) and magnesium (Gitelman). Indomethacin is efficient to reduce water and electrolyte loss in Bartter. In Gitelman, potassium-sparing diuretics may be helping for severe hypokaliemia but they will reinforce hypovolemia.

Diuretic Effect of Prosopis farcta in Comparison with Spironolactone and Hydrochlorothiazide in Hypertensive Rats

Prosopis farcta has been used traditionally for several diseases as cardiovascular, kidney, diabetes, bacterial infection and it has diuretic activity. This study was designed to evaluate the diuretic effects of P. farcta extract in comparison with spironolactone and hydrochlorothiazide in normal and hypertensive rats.Forty eight rats, were divided into Two groups. The First group was consist of Twelve normotensive rats, to represent the control group and normal treated group receiving 50 mg/Kg of P. farcta extract; Six rats in each group.&#x0D; The Second group involved 36 hypertensive rats, were divided into six subgroups, each of six rats. The First subgroups served as a positive control, the Second, Third and Fourth sub-groups were received 25, 50, 100 mg/Kg of P. farcta fruit extract respectively. The Fifth and Sixth subgroups were received 5 mg/kg spironolactone, and 25 mg/Kg thiazide orally for a week. P. farcta extract produced a significant increase in urine flow, Sodium excretion rate, eGFR and urinary creatinine level. In addition there were significant reduction in heart rate, and serum creatinine and blood urea.&#x0D; Conclusion: P. farcta fruit extract has mild diuretic activity in normal and hypertensive rats that resemble the potassium sparing diuretics.&#x0D; Keywords: Prosopis farcta, Diuretics, Thiazide, Spironolactone, Antihypertensive.

Uso de la espironolactona en dermatología: acné, hidradenitis supurativa, alopecia femenina e hirsutismo

Spironolactone is an economical potassium-sparing diuretic with an anti-androgenic effect and a good safety profile. Our experience suggests that this diuretic is underexploited in dermatology even though there is evidence supporting its use in several skin conditions. When prescribed for acne in female patients (level 1–2 evidence; strength of recommendation, B), for example, it can reduce the need for antibiotics and possibly isotretinoin. Other diseases in which spironolactone is potentially useful are hidradenitis suppurativa and female androgenetic alopecia. We discuss the indications for spironolactone, dosing in dermatology, precautions to consider, and adverse effects. We also review new evidence that stresses the safety of long-term therapy and supports the use of this drug without the need for complementary testing in young women. We think that spironolactone merits a place among the medications commonly used in routine clinical practice.

Acute hyperkalemia in the emergency department: a summary from a Kidney Disease: Improving Global Outcomes conference.

Hyperkalemia is a common electrolyte disorder observed in the emergency department. It is often associated with underlying predisposing conditions, such as moderate or severe kidney disease, heart failure, diabetes mellitus, or significant tissue trauma. Additionally, medications, such as inhibitors of the renin-angiotensin-aldosterone system, potassium-sparing diuretics, nonsteroidal anti-inflammatory drugs, succinylcholine, and digitalis, are associated with hyperkalemia. To this end, Kidney Disease: Improving Global Outcomes (KDIGO) convened a conference in 2018 to identify evidence and address controversies on potassium management in kidney disease. This review summarizes the deliberations and clinical guidance for the evaluation and management of acute hyperkalemia in this setting. The toxic effects of hyperkalemia on the cardiac conduction system are potentially lethal. The ECG is a mainstay in managing hyperkalemia. Membrane stabilization by calcium salts and potassium-shifting agents, such as insulin and salbutamol, is the cornerstone in the acute management of hyperkalemia. However, only dialysis, potassium-binding agents, and loop diuretics remove potassium from the body. Frequent reevaluation of potassium concentrations is recommended to assess treatment success and to monitor for recurrence of hyperkalemia.

P0740HYPERKALEMIA, CKD AND RAAS INHIBITION: A TRIAD WITH A FINE BALANCE TO PREVENT MORTALITY

Abstract Background and Aims Hyperkalemia (HK) is a common and dangerous complication of CKD because of impaired kidneýs ability for potassium elimination. On the other hand, HK is a common complication of extremely beneficial therapeutic agents acting on the renin–angiotensin–aldosterone system (RAAS). Its initiation at early CKD stages is even more benefic but HK could lead to stop it. We wonder if there is a possible relation between HK, therapeutic changes in RAAS inhibition (not initiating or stopping it) and mortality. Our goal was to investigate incidence, prevalence and clinical outcomes of at least one episode of HK in a CKD population outpatient setting. Additionally, we investigated the association of HK with changes in RAAS inhibition and mortality risk. Method We conducted a patient-level, retrospective, cohort analysis of all adult patients referred to a nephrology clinic over a 6 years period. We included CKD stage 3 patients with at least 24 months of follow up and three or more serum potassium determinations. The prevalence of HK (blood potassium level ≥ 5,5mmol/L) at first consultation and incidence during follow up were accessed. Patients were spited in two groups prior to analysis: A) Patients without any HK episode and B) Patients with at least one HK episode. Baseline and follow up covariates included demographics, comorbid conditions, laboratory values, HK-associated drugs [ACEis, ARBs, potassium-sparing diuretics and diuretics]. The impact of HK and therapeutic changes on mortality was evaluated through a logistic regression. Results Out of the 3008 patients referred to the nephrology clinic, 575 (19.1%) met the inclusion criteria (mean age: 70.4 years; 63.7% male and 94.0% caucasians). Mean follow-up was 4.1±1.8 years. Important cardiovascular comorbidities included hypertension (HTN) (90.3%); overweigh (67.4%), DM (49.0%) and Heart Failure (31.4%). CKD stage progression was present in 122 (21.2%). The prevalence of HK at first consultation was 8.7% and follow up incidence 21.7%. From this cohort, 164 (28.5%) had at least on episode of HK (Group B) and 101 (17.6%) died. During the follow up, RAAS inhibition drugs was removed or not started in 200 (34.8%) patients and diuretic was initiated in 165 (28.7%). In univariate analysis, at least one HK episode was associated with Diabetes (65.9 vs 42.3%, p&amp;lt;0.001), Heart failure (36.6 vs 28.0%, p=0.007), Macroalbuminuria (34.1 vs 21.2%, p=0.001), CKD progression (33.5 vs 16.3. p&amp;lt;0.001) higher frequency of diuretic initiation (38.4 vs 24.8%, p&amp;lt;0.001) and higher mortality (27.6 vs 13.7%, p&amp;lt;0.001). In multivariate logistic regression analysis, the independent predictors of mortality were: At least one HK episode (OR 1.82, 95% CI 1.08-3.04, p=0.02); Heart Failure (OR 1.97, 95% CI 1.16-3.35, p=0.01); Older age (OR per 1 year increase 1.04, 95% CI 1.02-1.07, p=0.001); CKD progression (OR 4.18, 95% CI 2.43-7.19, p&amp;lt;0.001). Predictors of lower mortality risk were: Patients who maintained RAAS inhibition during follow up (OR 0.50, 95% CI 0.26-0.96, p=0.03); Patients who started RAAS inhibition during follow up (OR 0.38, 95% CI 0.16-0.88, p=0.02). Conclusion Our study confirms that RAAS inhibition had a protector and independent impact in mortality when prescribed in CKD early stages. On the other hand, patients with at least one episode of HK have a higher risk of mortality. All efforts should be made to maintain these therapeutic agents, looking for other ways to control hyperkalemia rather than stop it.

P0581HIPERKALEMIA IN COMMUNITY-ADQUIRED ACUTE KIDNEY INJURY. ASSOCIATED FACTORS AND CLINICAL CONSEQUENCES

Abstract Introduction and Aims Hyperkalemia (hyperK) is an analytical alteration that frequently occurs in the context of acute kidney injury (AKI) adding morbidity to the patient. We know little about the associated factors and the clinical consequences of this complication in patients with community-acquired acute kidney injury (CA-AKI). The aim of present study was to analyze the predisposing factors and the clinical consequences of the hiperK in patients with CA-AKI. Method The present study is based on a cohort of patients with CA-AKI admitted to the Nephology Service of a third level hospital from January 2010 to February 2015. Hyperkalemia was defined by the laboratory of our hospital as potassium levels above 5.1 meq / L Results A total of 308 patients were included in the final analyses. The mean age was 73,22±13,95 years. 58,4% were men. Charlson comorbidity index (CCI) was 7,16 ±2,7 points. The mean of drugs ingested daily was 7,81±3,66 and the length of stay 12,25±11,69 days. In view of the Etiology of AKI, 69,5% prerenal AKI and 30,5% non-prerenal ones. 212 patients had a history of previous chronic kidney disease (CKD) (68.8%). Hemodialysis (HD) was required in 54 patients (17.15%). 38 patients (12.3%) died during hospital stay. HyperK occurred in 173 cases (56,2 %). Mean potassium was 5,45±1,41 meq/L (95% IC 5,29-5,61) (range 2.65-9.70). There was a significant correlation between potassium and pH (r = - 0.328; p &amp;lt;0,001) as well as between K and CCI (r= 0,284; p &amp;lt;0,001). There was an association between hyperK and intake of potassium-sparing diuretics (p&amp;lt;0,001); ACEI/ARB (p=0,003) and beta blocker (p&amp;lt;0,001). There was no association with CKD nor NSAID intake. Using a multiple linear regression model the equation that predicted serum potassium level was: K = 36,44 – (4,4 x pH) + 0,98 (if intake of potassium-sparing diuretics) + (0.10 x CCI). Potassium level did not influence the length stay. Patients with HyperK required HD in a higher proportion (23.7 vs. 9.6%; p 0.01) and also had higher mortality during hospital stay (15.6 vs. 8.1%; p 0.048). After a follow-up of 971±702 days after hospital discharge, Kaplan-Meier survival curves showed a significant difference (Log Rank (Mantel-Cox): Chi-square 20,1; p&amp;lt; 0,001) between patients with hyperK and patients that did not present it. Conclusion HyperK occurred in just over half of our patients. The potassium level was significantly determined by the previous comorbidity, pH and the intake of potassium-sparing diuretics. HyperK patients required HD and died in a greater proportion during hospital stay than the others. Mortality after discharge was higher in patients who presented hyperK during hospital stay. Appropriate measures must be taken to correct hyperK early in patients with CA-AKI.