Serum Potassium and Outcomes in CKD

Korgaonkar, Sonal; Tilea, Anca; Gillespie, Brenda W.; Kiser, Margaret; Eisele, George; Finkelstein, Fredric O.; Kotanko, Peter; Pitt, Bertram; Saran, Rajiv

doi:10.2215/cjn.05850809

Cited by 195 publications

(181 citation statements)

References 39 publications

(32 reference statements)

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“…Current Kidney Disease Outcomes Quality Initiative guidelines recommend that base be given when serum bicarbonate levels are ,22 mEq/L and to maintain a level $22 mEq/L, and Kidney Disease Improving Global Outcomes guidelines also recommend administering base when serum bicarbonate is ,22 mEq/L to maintain the value within the normal range of 22-29 mEq/L (25-29). Use of guideline-recommended alkali therapies and/or increased intake of fruit and vegetables reflects current clinical practice; however, these interventions have the potential to introduce large amounts of sodium or potassium to patients with CKD who often have hypertension, fluid overload, and hyperkalemia (28)(29)(30)(31)(32)(33)(34)(35)(36)(37).…”

Section: Introductionmentioning

confidence: 99%

Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD

Bushinsky

Hostetter

Klaerner³

et al. 2017

CJASN

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Background and objectives Metabolic acidosis is common in patients with CKD and has significant adverse effects on kidney, muscle, and bone. We tested the efficacy and safety of TRC101, a novel, sodium-free, nonabsorbed hydrochloric acid binder, to increase serum bicarbonate in patients with CKD and metabolic acidosis.Design, setting, participants, & measurements One hundred thirty-five patients were enrolled in this randomized, double-blind, placebo-controlled, multicenter, in-unit study (designated the TRCA-101 Study). Patients had a mean baseline eGFR of 35 ml/min per 1.73 m 2 , a mean baseline serum bicarbonate of 17.7 mEq/L, and comorbidities, including hypertension (93%), diabetes (70%), and heart failure (21%). Patients ate a controlled diet and were treated for 14 days with placebo or one of four TRC101 dosing regimens (1.5, 3, or 4.5 g twice daily or 6 g once daily). After treatment, patients were discharged and followed for 7-14 days.Results All TRC101 treatment groups had a mean within-group increase in serum bicarbonate of $1.3 mEq/L (P,0.001) within 72 hours of the first dose and a mean increase in serum bicarbonate of 3.2-3.9 mEq/L (P,0.001) at the end of treatment compared with placebo, in which serum bicarbonate did not change. In the combined TRC101 treatment group, serum bicarbonate was normalized (22-29 mEq/L) at the end of treatment in 35% of patients and increased by $4 mEq/L in 39% of patients. After discontinuation of TRC101, serum bicarbonate decreased nearly to baseline levels within 2 weeks. All adverse events were mild or moderate, with gastrointestinal events most common. All patients completed the study.Conclusions TRC101 safely and significantly increased the level of serum bicarbonate in patients with metabolic acidosis and CKD.

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Section: Introductionmentioning

confidence: 99%

Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD

Bushinsky

Hostetter

Klaerner³

et al. 2017

CJASN

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“…Fifth, extremes of serum K + were associated with greater rates of discontinuation of RAAS blockers. Prior studies have reported the prevalence of hyperkalemia and hypokalemia (9)(10)(11). However, the generalizability of these studies to the CKD population is limited by small sample sizes and a disproportionate representation of patients with very advanced CKD (10,11); the largest of these studies focused on clinical trial participants with concomitant heart failure, further limiting generalizability (11).…”

Section: Discussionmentioning

confidence: 99%

“…Prior studies have reported the prevalence of hyperkalemia and hypokalemia (9)(10)(11). However, the generalizability of these studies to the CKD population is limited by small sample sizes and a disproportionate representation of patients with very advanced CKD (10,11); the largest of these studies focused on clinical trial participants with concomitant heart failure, further limiting generalizability (11). In another study, a U-shaped association between serum K + and mortality was observed among patients with CKD who had a mean eGFR,25 ml/min per 1.73 m 2 (9); however, risk estimates for higher K + categories did not achieve statistical significance, possibly because of a small sample size: Only 65 hyperkalemic patients were included in the analysis.…”

Section: Discussionmentioning

confidence: 99%

Association between Serum Potassium and Outcomes in Patients with Reduced Kidney Function

Luo

Brunelli

Jensen

et al. 2016

Clinical Journal of the American Society of Nephrology

231

208

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Background and objectives Patients with CKD are more likely than others to have abnormalities in serum potassium (K + ). Aside from severe hyperkalemia, the clinical significance of K + abnormalities is not known. We sought to examine the association of serum K + with mortality and hospitalization rates within narrow eGFR strata to understand how the burden of hyperkalemia varies by CKD severity. Associations were examined between serum K + and discontinuation of medications that block the renin-angiotensin-aldosterone system (RAAS), which are known to increase serum K + .Design, setting, participants, & measurements A cohort of patients with CKD (eGFR,60 ml/min per 1.73 m 2 ) with serum K + data were studied (n=55,266) between January 1, 2009, and June 30, 2013 (study end). Serum K + , eGFR, and covariates were considered on a time-updated basis. Mortality, major adverse cardiovascular events (MACE), hospitalization, and discontinuation of RAAS blockers were considered per time at risk.Results During the study, serum K + levels of 5.5-5.9 and $6.0 mEq/L were most prevalent at lower eGFR: they were present, respectively, in 1.7% and 0.2% of patient-time for eGFR of 50-59 ml/min per 1.73 m 2 versus 7.6% and 1.8% of patient-time for eGFR,30 ml/min per 1.73 m 2 . Serum K + level ,3.5 mEq/L was present in 1.2%-1.4% of patient-time across eGFR strata. The median follow-up time was 2.76 years. There was a U-shaped association between serum K + and mortality; pooled adjusted incidence rate ratios were 3.05 (95% confidence interval, 2.53 to 3.68) and 3.31 (95% confidence interval, 2.52 to 4.34) for K + levels ,3.5 mEq/L and $6.0 mEq/L, respectively. Within eGFR strata, there were U-shaped associations of serum K + with rates of MACE, hospitalization, and discontinuation of RAAS blockers.Conclusions Both hyperkalemia and hypokalemia were independently associated with higher rates of death, MACE, hospitalization, and discontinuation of RAAS blockers in patients with CKD who were not undergoing dialysis. Future studies are needed to determine whether interventions targeted at maintaining normal serum K + improve outcomes in this population.

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“…Serum potassium >5.0 mmol/L was associated with increased mortality in non-dialysis dependent CKD patients [28]. A secondary analysis of the Renal Research Institute study CKD cohort also showed an increased risk of the composite of death or cardiovascular events requiring hospitalization but no increase in overall mortality with serum potassium >5.5 mmol/L [29]. These studies are limited to CKD subjects only.…”

Section: Archives Of Medicine Issn 1989-5216mentioning

confidence: 85%

Long-term Mortality Outcomes of Hyperkalemic Patients in the Emergency Department Setting: A Case Control Study

Velagapudi¹,

O’Horo²,

Glinskii³

et al. 2017

Arch Med

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Background: The impact of an episode of hyperkalemia on long term mortality is not well studied. Such a study is vital for development of a utilization strategy for new drugs for the treatment of hyperkalemia. To study the long term impact of hyperkalemia on mortality, we conducted a retrospective, observational casecontrol study in a tertiary care emergency department. We compared cases of non-hemolyzed serum potassium >5.3 mEq/L with normokalemic controls. Allcause mortality and causes of death were determined from social security death index, national death index, and medical record review over a follow-up period of 490 patient years. Methods and Findings:A total of 287 consecutive subjects (223 cases, 64 controls) were identified among 14,483 patients. Cox proportional hazard regression showed that for each 1 mEq/L increase in admit potassium, all-cause mortality Hazard Ratio was 1.54, 95% Confidence Interval: 1.22-1.96. Subgroup analyses showed higher mortality in acute kidney injury and heart failure patients. Conclusion:Hyperkalemia predicted all-cause mortality, when adjusted for age, sex, Charlson comorbidity index, and significant covariates (heart failure and end stage renal disease). The deleterious effect of admit hyperkalemia persisted in survivors from index episode throughout the study period. Cardiovascular mortality was statistically more prevalent. Future studies are needed for risk stratification strategies and mortality impact of newer drugs.

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Serum Potassium and Outcomes in CKD

Cited by 195 publications

References 39 publications

Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD

Randomized, Controlled Trial of TRC101 to Increase Serum Bicarbonate in Patients with CKD

Association between Serum Potassium and Outcomes in Patients with Reduced Kidney Function

Long-term Mortality Outcomes of Hyperkalemic Patients in the Emergency Department Setting: A Case Control Study

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