Severe symptomatic hyponatremia associated with the use of polyethylene glycol-based bowel preparation

Summary Colonoscopy is a useful tool in modern medicine and is increasingly employed for both diagnostic and treatment reasons. However, its effectiveness is highly reliant on the quality of bowel cleansing. Among different bowel-cleansing agents available, PEG (polyethylene glycol) is considered to be the safest cleansing agent, especially in relation to fluid and electrolyte problems. We present here a case of severe symptomatic hyponatremia that developed after the use of PEG for an elective colonoscopy. This case highlights that despite the use of PEG-based preparations, life-threatening fluid and electrolyte disturbances can still occur in patients with risk factors, such as old age, use of thiazide diuretics and SSRIs, chronic kidney disease, heart failure and a history of electrolyte problems. These patients should be closely monitored when undertaking bowel cleansing and should receive prompt care in the event of complications, to avoid permanent neurological sequelae and death. Rapid correction of sodium levels in patients requiring treatment of hyponatremia should be avoided to prevent complications such as osmotic demyelination syndrome. Learning points: PEG is considered to be the safest bowel-cleansing agents among different options available, but it can still cause significant side effects in susceptible individuals. Those at risk of developing adverse events include elderly individuals, patients with chronic kidney disease, heart failure or previous history of electrolyte problems and those taking thiazide diuretics and SSRIs. All such patients should be closely monitored i.e. have their metabolic profile checked prior to the commencement of bowel cleansing and a low threshold should be kept for the initiation of investigations and treatment in case of development of symptoms. Medications with a potential of causing fluid and electrolytes such as thiazide diuretics and SSRIs should be withheld while patient is undertaking bowel preparation. Hyponatremia in a hospitalized patient can be multifactorial, and the treatment principles are based on duration of onset, presence of symptoms and patients volume status. Overzealous correction of sodium levels during treatment of hyponatremia can result in serious complications such as osmotic demyelination syndrome.

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Osmotic demyelination syndrome in a normonatremic patient of chronic kidney disease

Indian Journal of Critical Care Medicine ◽

10.4103/0972-5229.140153 ◽

2014 ◽

Vol 18 (9) ◽

pp. 609-611 ◽

Cited By ~ 3

Author(s):

Atul Abhishek Jha ◽

Vineet Behera ◽

Anantharam Jairam ◽

Krishna Venkatesh Baliga

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Osmotic Demyelination Syndrome ◽

Osmotic Demyelination

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Abstract TP138: Chronic Kidney Disease in Heart Failure Patients is Associated with Increased Prevalence of Atrial Fibrillation or Atrial Flutter as well as CVA/TIA

Stroke ◽

10.1161/str.51.suppl_1.tp138 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Christopher Lu ◽

Jack Chan ◽

Zejia Yu ◽

Paula Anzenberg ◽

Mikhail Torosoff

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Risk Assessment ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Atrial Flutter ◽

Stroke Risk ◽

Multivariate Logistic Regression Analysis ◽

History Of ◽

Get With The Guidelines

Background: The CHADS-VASC score does not incorporate renal dysfunction in stroke risk assessment in patients with atrial fibrillation and the prevalence of atrial fibrillation, atrial flutter, and cerebrovascular accidents (CVA) in patients with concurrent CHF and CKD is not well investigated. Objective: Evaluate the prevalence of history of stroke, atrial fibrillation, atrial flutter in patients with CHF and CKD. Methods: Data from the single institution Get With The Guidelines- Heart Failure (GWG-HF) cohort of 2938 consecutive inpatients with known GFR was utilized. CHADS-VASC score was calculated from the GWG-HF variables. Chronic kidney disease (CKD) was defined as GFR <60 ml/min. Results: An overwhelming majority (95%) of GWG-HF patients had elevated >1 CHADS-VASC score, which was also significantly more common in patients with CKD (97.6% vs. 91.7% in patients without CKD, p<0.0001). Average CHADS-VASC score was also significantly increased in patients with CKD (4+/-1.3 vs. 3.3+/-1.4, p<0.0001). Furthermore, CKD was associated with increased prevalence of atrial fibrillation and/or flutter (45.6% vs. 35.3%, p<0.0001) and stroke history (17.5% vs. 12.3%, p=0.002). When stroke and TIA histories were removed from the CHADS-VASC score ("CHAD-VASC score"), the remaining variables were strongly predictive of stroke or TIA (14.2% vs. 3.8%, p<0.0001). In multivariate logistic regression analysis, both CHAD-VASC score (OR 2.6, 95%CI 1.3-5.4, p=0.009) and CKD (OR 1.5, 95%CI 1.2-1.8, p=0.001) were associated significantly increased odds of prior stroke or TIA. Conclusions: In patients admitted with heart failure, CKD is associated with increased prevalence of atrial fibrillation or atrial flutter as well as increased prevalence of CVA/TIA. Further prospective studies are warranted to examine whether CKD history should be included in stroke risk assessment in patients with atrial fibrillation or atrial flutter, in conjunction with existing risk assessment frameworks.

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Abstract 15407: Comorbidities and the Associated Long-term Utilization of Transthoracic Echocardiography Among Medicare Beneficiaries at a Large Academic Center

Circulation ◽

10.1161/circ.142.suppl_3.15407 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Patrick M Hyland ◽

Jiaman Xu ◽

Changyu Shen ◽

Lawrence Markson ◽

Warren J Manning ◽

...

Keyword(s):

Myocardial Infarction ◽

Heart Failure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Transthoracic Echocardiography ◽

Medicare Beneficiaries ◽

Female Sex ◽

History Of

Introduction: The association between baseline patient characteristics and the long-term utilization of transthoracic echocardiography (TTE) is unknown and may help focus value-based care initiatives. Methods: TTE reports from patients with ≥ 2 TTEs at our institution were linked to 100% Medicare Fee-for-service inpatient claims, 1/1/2000 – 12/31/2017. To avoid inclusion of individuals with short-interval follow-up, TTEs with < 1 year between studies were excluded. Validated claims algorithms were used to create 12 baseline cardiovascular comorbidities. Multivariable Poisson regression was used to estimate adjusted rates of TTE intensity according to baseline comorbidities. Results: Over a median (IQR) follow-up of 5.8 (3.1 – 9.5) years, 18,579 individuals (69.3 ± 12.8 years; 50.5% female) underwent a total of 59,759 TTEs (range 2 – 59). The median TTE intensity was 0.64 TTEs/patient/year (IQR 0.35 – 1.24; range 0.11 – 22.02). The top five contributors to TTE intensity were heart failure, chronic kidney disease, history of myocardial infarction, smoking, and hyperlipidemia ( Figure ). Female sex was associated with decreased TTE utilization (adjusted RR 0.95, 95% CI 0.94-0.96, p < 0.0001). Atrial fibrillation, hypertension, and history of ischemic stroke or transient ischemic attack were not significantly related to TTE intensity after multivariable adjustment (all p > 0.05). Conclusions: Among Medicare beneficiaries with ≥ 2 TTEs at our institution, the median TTE intensity was 0.64 TTEs/patient/year but varied widely. Heart failure, chronic kidney disease, and history of myocardial infarction were the strongest predictors of increased utilization. Female sex was associated with decreased utilization, reflecting broader disparities in utilization of cardiovascular procedures. Further research is needed to clarify reasons for this sex disparity and associations with cardiovascular outcomes.

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Finerenone and Cardiovascular Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes

Circulation ◽

10.1161/circulationaha.120.051898 ◽

2020 ◽

Cited By ~ 1

Author(s):

Gerasimos Filippatos ◽

Stefan D. Anker ◽

Rajiv Agarwal ◽

Bertram Pitt ◽

Luis M. Ruilope ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Renin Angiotensin System ◽

Mineralocorticoid Receptor Antagonist ◽

Angiotensin System ◽

Renin Angiotensin ◽

History Of

Background: The FIDELIO-DKD trial evaluated the effect of the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone on kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) with optimized renin-angiotensin system blockade. Compared with placebo, finerenone reduced the composite kidney and CV outcomes. We report the effect of finerenone on individual CV outcomes and in patients with and without history of atherosclerotic CV disease (CVD). Methods: This randomized, double-blind, placebo-controlled trial included patients with T2D and urine albumin-to-creatinine ratio 30-5000 mg/g and an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m 2 , treated with optimized renin-angiotensin system blockade. Patients with a history of heart failure with reduced ejection fraction were excluded. Patients were randomized 1:1 to receive finerenone or placebo. The composite CV outcome included time to CV death, myocardial infarction, stroke, or hospitalization for heart failure. Prespecified CV analyses included analyses of the components of this composite and outcomes according to CVD history at baseline. Results: Between September 2015 and June 2018, 13,911 patients were screened and 5674 were randomized; 45.9% of patients had CVD at baseline. Over a median follow-up of 2.6 years (interquartile range, 2.0-3.4 years), finerenone reduced the risk of the composite CV outcome compared with placebo (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.99; P=0.034), with no significant interaction between patients with and without CVD (HR, 0.85; 95% CI, 0.71-1.01 in patients with a history of CVD; HR, 0.86; 95% CI, 0.68-1.08 in patients without a history of CVD; P-value for interaction, 0.85). The incidence of treatment-emergent adverse events was similar between treatment arms, with a low incidence of hyperkalemia-related permanent treatment discontinuation (2.3% with finerenone vs 0.8% with placebo in patients with CVD and 2.2% with finerenone vs 1.0% with placebo in patients without CVD). Conclusions: Among patients with CKD and T2D, finerenone reduced incidence of the composite CV outcome, with no evidence of differences in treatment effect based on pre-existing CVD status. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02540993 (Funded by Bayer AG)

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Effect of Dapagliflozin on Clinical Outcomes in Patients with Chronic Kidney Disease, With and Without Cardiovascular Disease

Circulation ◽

10.1161/circulationaha.120.051675 ◽

2020 ◽

Cited By ~ 2

Author(s):

John J.V. McMurray ◽

David C. Wheeler ◽

Bergur V. Stefánsson ◽

Niels Jongs ◽

Douwe Postmus ◽

...

Keyword(s):

Heart Failure ◽

Cardiovascular Disease ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Secondary Prevention ◽

Cardiovascular Death ◽

Composite Outcome ◽

Primary And Secondary Prevention ◽

History Of ◽

End Stage

Background: Dapagliflozin reduces the risk of end-stage renal disease in patients with chronic kidney disease. We examined the relative risk of cardiovascular and kidney events in these patients and the effect of dapagliflozin on either type of event, taking account of history of cardiovascular disease. Methods: In the DAPA-CKD trial (Dapagliflozin And Prevention of Adverse Outcomes in Chronic Kidney Disease), 4304 participants with chronic kidney disease were randomized to dapagliflozin 10 mg once daily or placebo. The primary endpoint was a composite of sustained decline in estimated GFR ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The secondary endpoints were a kidney composite outcome (primary endpoint, minus cardiovascular death), the composite of hospitalization for heart failure or cardiovascular death and all-cause death. In a prespecified subgroup analysis, we divided patients into primary and secondary prevention subgroups according to history of cardiovascular disease. Results: Secondary prevention patients (n=1610; 37.4%) were older, more often male, had a higher blood pressure and body-mass index, and were more likely to have diabetes. Mean estimated glomerular filtration rate and median urinary albumin-to-creatinine ratio was similar in the primary and secondary prevention groups. The rates of adverse cardiovascular outcomes were higher in the secondary prevention group, but kidney failure occurred at the same rate in the primary and secondary prevention groups. Dapagliflozin reduced the risk of the primary composite outcome to a similar extent in both the primary (HR, 0.61 [95% CI, 0.48-0.78]) and secondary (0.61, 0.47-0.79) prevention groups (P-interaction=0.90). This was also true for the composite of heart failure hospitalization or cardiovascular death (0.67, 0.40-1.13 versus 0.70, 0.52-0.94, respectively, P-interaction=0.88), and all-cause (0.63, 0.41-0.98 versus 0.70, 0.51-0.95, respectively, P-interaction=0.71). Rates of adverse events were low overall and did not differ between patients with and without cardiovascular disease. Conclusions: Dapagliflozin reduced the risk of kidney failure, death from cardiovascular causes or hospitalization for heart failure, and prolonged survival, in people with chronic kidney disease, with or without type 2 diabetes, independently of the presence of concomitant cardiovascular disease Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT03036150

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30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Mineralocorticoid receptor antagonists: 60 years of research and development

Journal of Endocrinology ◽

10.1530/joe-16-0600 ◽

2017 ◽

Vol 234 (1) ◽

pp. T125-T140 ◽

Cited By ~ 68

Author(s):

Peter Kolkhof ◽

Lars Bärfacker

Keyword(s):

Heart Failure ◽

Chronic Kidney Disease ◽

Clinical Trials ◽

Kidney Disease ◽

Research And Development ◽

Mineralocorticoid Receptor ◽

Clinical Use ◽

Patients With Heart Failure ◽

History Of

The cDNA of the mineralocorticoid receptor (MR) was cloned 30 years ago, in 1987. At that time, spirolactone, the first generation of synthetic steroid-based MR antagonists (MRAs), which was identified in preclinical in vivo models, had already been in clinical use for 30 years. Subsequent decades of research and development by Searle & Co., Ciba-Geigy, Roussel Uclaf and Schering AG toward identifying a second generation of much more specific steroidal MRAs were all based on the initial 17-spirolactone construct. The salient example is eplerenone, first described in 1987, coincidentally with the cloning of MR cDNA. Its launch on the market in 2003 paralleled intensive drug discovery programs for a new generation of non-steroidal MRAs. Now, 30 years after the cDNA cloning of MR and 60 years of clinical use of steroidal MRAs, novel non-steroidal MRAs such as apararenone, esaxerenone and finerenone are in late-stage clinical trials in patients with heart failure, chronic kidney disease (CKD), hypertension and liver disease. Finerenone has already been studied in over 2000 patients with heart failure plus chronic kidney disease and/or diabetes, and in patients with diabetic kidney disease, in five phase II clinical trials. Here, we reflect on the history of the various generations of MRAs and review characteristics of the most important steroidal and non-steroidal MRAs.

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Finerenone Reduces Risk of Incident Heart Failure in Patients With Chronic Kidney Disease and Type 2 Diabetes: Analyses from the FIGARO-DKD Trial

Circulation ◽

10.1161/circulationaha.121.057983 ◽

2021 ◽

Author(s):

Gerasimos Filippatos ◽

Stefan D. Anker ◽

Rajiv Agarwal ◽

Luis M. Ruilope ◽

Peter Rossing ◽

...

Keyword(s):

Heart Failure ◽

Type 2 Diabetes ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Lower Risk ◽

Cardiovascular Death ◽

History Of ◽

The Impact ◽

New Onset

Background: Chronic kidney disease (CKD) and type 2 diabetes (T2D) are independently associated with heart failure (HF), a leading cause of morbidity and mortality. In the FIDELIO-DKD and FIGARO DKD trials, finerenone (a selective, nonsteroidal mineralocorticoid receptor antagonist) improved cardiovascular outcomes in patients with albuminuric CKD and T2D. These prespecified analyses from FIGARO-DKD assessed the impact of finerenone on clinically important HF outcomes. Methods: Patients with T2D and albuminuric CKD (urine albumin-to-creatinine ratio [UACR] ≥30 to <300 mg/g and estimated glomerular filtration rate [eGFR] ≥25 to ≤90 ml/min/1.73 m 2 , or UACR ≥300 to ≤5000 mg/g and eGFR ≥60 ml/min/1.73 m 2 ,), without symptomatic HF with reduced ejection fraction, were randomized to finerenone or placebo. Time-to-first event outcomes included: new-onset HF (first hospitalization for HF [HHF] in patients without a history of HF at baseline); cardiovascular death or first HHF; HF-related death or first HHF; first HHF; cardiovascular death or total (first or recurrent) HHF; HF-related death or total HHF; and total HHF. Outcomes were evaluated in the overall population and in prespecified subgroups categorized by baseline HF history (as reported by the investigators). Results: Overall, 7352 patients were included in these analyses; 571 (7.8%) had a history of HF at baseline. New-onset HF was significantly reduced with finerenone versus placebo (1.9% versus 2.8%; hazard ratio [HR], 0.68 [95% CI 0.50-0.93]; P =0.0162). In the overall population, the incidences of all HF outcomes analyzed were significantly lower with finerenone than placebo, including a 18% lower risk of cardiovascular death or first HHF (HR, 0.82 [95% CI 0.70-0.95]; P =0.011), a 29% lower risk of first HHF (HR, 0.71 [95% CI 0.56-0.90]; P =0.0043) and a 30% lower rate of total HHF (rate ratio, 0.70 [95% CI, 0.52- 0.94]). The effects of finerenone on improving HF outcomes were not modified by a history of HF. The incidence of treatment-emergent adverse events was balanced between treatment groups. Conclusions: The results from these FIGARO-DKD analyses demonstrate that finerenone reduces new-onset HF and improves other HF outcomes in patients with CKD and T2D, irrespective of a history of HF.

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Abstract 12683: Combined Assessment of High-Sensitive Troponin I and N-Terminal Pro-B-Type Natriuretic Peptide Levels Improves the Prediction of Future Admission for Heart Failure in Outpatients With Chronic Kidney Disease

Circulation ◽

10.1161/circ.130.suppl_2.12683 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Junnichi Ishii ◽

Hiroshi Takahashi ◽

Midori Hasegawa ◽

Ryuunosuke Okuyama ◽

Hideki Kawai ◽

...

Keyword(s):

Heart Failure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Natriuretic Peptide ◽

Troponin I ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Estimated Gfr ◽

History Of ◽

High Sensitive Troponin

Background: Heart failure (HF) is a common consequence of chronic kidney disease (CKD), and it portends high risk for mortality. We prospectively investigated the predictive value of a combination of high-sensitive troponin I (hsTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for HF admission in outpatients with CKD. Methods: Baseline hsTnI and NT-proBNP levels were measured in 451 stable outpatients with CKD (estimated GFR < 60 mL/min/1.73 m 2 ) on not dialysis (mean age, 69.7 years). Using echocardiography with tissue Doppler imaging, left ventricular ejection fraction (EF) and E/e’ ratio were estimated. Among these patients, 41% had a history of cardiovascular disease, and 48% had a history of diabetes. Results: During a mean follow-up period of 924 days, there were 70 HF admissions. Patients who admitted for HF had higher hsTnI levels (22.4 vs. 10.5 pg/mL, p < 0.0001), NT-proBNP levels (1726 vs. 310 pg/mL, p < 0.0001), and E/e’ ratio (15.3 vs. 10.3, p < 0.0001), and displayed lower values of EF (55 vs. 59%, p < 0.0001) and estimated GFR (23.7 vs. 30.6 mL/min/1.73 m 2 , p = 0.009) than those who did not. Using multivariate Cox regression analysis including 11 clinical variables, increased hsTnI (relative risk, 1.98 per 10-fold increment, p = 0.02) and NT-proBNP (3.18 per 10-fold increment, p = 0.003) levels were shown to be independent predictors of HF admission. When patients were stratified into four groups according to NT-proBNP levels > a median value of 397 pg/mL and/or hsTnI levels > a median value of 11.6 pg/mL, HF admission rates were 3.1%, 7.5%, 11.8%, and 33.1%, respectively (p < 0.0001). Furthermore, when hsTnI and NT-proBNP levels were combined, the predictive values for HF admission were increased, as shown by the C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI; Table 1). Conclusions: The combined assessment of hsTnI and NT-proBNP levels can improve the prediction of HF admission in outpatients with CKD.

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