Low Serum Potassium Levels Increase the Infectious-Caused Mortality in Peritoneal Dialysis Patients: A Propensity-Matched Score Study

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Abstract

Background and Objectives

Hypokalemia has been consistently associated with high mortality rate in peritoneal dialysis. However, studies investigating if hypokalemia is acting as a surrogate marker of comorbidities or has a direct effect in the risk for mortality have not been studied. Thus, the aim of this study was to analyze the effect of hypokalemia on overall and cause-specific mortality.

Design, Setting, Participants and Measurements

This is an analysis of BRAZPD II, a nationwide prospective cohort study. All patients on PD for longer than 90 days with measured serum potassium levels were used to verify the association of hypokalemia with overall and cause-specific mortality using a propensity match score to reduce selection bias. In addition, competing risks were also taken into account for the analysis of cause-specific mortality.

Results

There was a U-shaped relationship between time-averaged serum potassium and all-cause mortality of PD patients. Cardiovascular disease was the main cause of death in the normokalemic group with 133 events (41.8%) followed by PD-non related infections, n=105 (33.0%). Hypokalemia was associated with a 49% increased risk for CV mortality after adjustments for covariates and the presence of competing risks (SHR 1.49; CI95% 1.01-2.21). In contrast, in the group of patients with K <3.5mEq/L, PD-non related infections were the main cause of death with 43 events (44.3%) followed by cardiovascular disease (n=36; 37.1%). For PD-non related infections the SHR was 2.19 (CI95% 1.52-3.14) while for peritonitis was SHR 1.09 (CI95% 0.47-2.49).

Conclusions

Hypokalemia had a significant impact on overall, cardiovascular and infectious mortality even after adjustments for competing risks. The causative nature of this association suggested by our study raises the need for intervention studies looking at the effect of potassium supplementation on clinical outcomes of PD patients.

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Most cited references 13

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Do observational studies using propensity score methods agree with randomized trials? A systematic comparison of studies on acute coronary syndromes.

Georgios Kitsios, Vasileia Varvarigou, Thomas A Trikalinos … (2012)

Randomized controlled trials (RCTs) are the gold standard for assessing the efficacy of therapeutic interventions because randomization protects from biases inherent in observational studies. Propensity score (PS) methods, proposed as a potential solution to confounding of the treatment-outcome association, are widely used in observational studies of therapeutic interventions for acute coronary syndromes (ACS). We aimed to systematically assess agreement between observational studies using PS methods and RCTs on therapeutic interventions for ACS. We searched for observational studies of interventions for ACS that used PS methods to estimate treatment effects on short- or long-term mortality. Using a standardized algorithm, we matched observational studies to RCTs based on patients' characteristics, interventions, and outcomes ('topics'), and we compared estimates of treatment effect between the two designs. When multiple observational studies or RCTs were identified for the same topic, we performed a meta-analysis and used the summary relative risk for comparisons. We matched 21 observational studies investigating 17 distinct clinical topics to 63 RCTs (median = 3 RCTs per observational study) for short-term (7 topics) and long-term (10 topics) mortality. Estimates from PS analyses differed statistically significantly from randomized evidence in two instances; however, observational studies reported more extreme beneficial treatment effects compared with RCTs in 13 of 17 instances (P = 0.049). Sensitivity analyses limited to large RCTs, and using alternative meta-analysis models yielded similar results. For the treatment of ACS, observational studies using PS methods produce treatment effect estimates that are of more extreme magnitude compared with those from RCTs, although the differences are rarely statistically significant.

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Serum potassium and cause-specific mortality in a large peritoneal dialysis cohort.

Klara Torlén, Kamyar Kalantar-Zadeh, Miklos Z Molnar … (2012)

Unlike hemodialysis (HD), peritoneal dialysis (PD) is a continuous therapy and does not induce myocardial stunning. Yet, the death risk in HD and PD patients is similar. This study tested the hypothesis that serum potassium abnormalities contribute more to the death risk in PD patients than in HD patients. Data from patients treated in DaVita facilities between July 1, 2001 and June 30, 2006 (n=10,468 PD patients; n=111,651 HD patients) were used to determine association of serum potassium with mortality. PD patients were significantly more likely to have serum potassium < 4 mEq/L, with an adjusted odds ratio of 3.30 (95% confidence interval [95% CI], 3.05, 3.56). There was a U-shaped relationship between time-averaged serum potassium and all-cause and cardiovascular mortality of PD patients, with adjusted hazards ratios of 1.51 for all-cause mortality for potassium < 3.5 mEq/L (95% CI, 1.29, 1.76) and 1.52 for potassium ≥ 5.5 mEq/L (95% CI, 1.32, 1.75). The population-attributable risks for all-cause mortality for serum potassium < 4.0 and ≥ 5.5 mEq/L were 3.6% and 1.9%, respectively, in PD patients, and 0.8% and 1.5%, respectively, in HD patients. Abnormalities in serum potassium contribute disproportionately to the high death risk in PD patients. This may, in part, account for the equivalent cardiac risk seen with the two therapies.

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The analysis of competing events like cause-specific mortality--beware of the Kaplan-Meier method.

Marion Verduijn, Diana C. Grootendorst, Friedo W Dekker … (2011)

Kaplan-Meier analysis is a popular method used for analysing time-to-event data. In case of competing event analyses such as that of cardiovascular and non-cardiovascular mortality, however, the Kaplan-Meier method profoundly overestimates the cumulative mortality probabilities for each of the separate causes of death. This article provides an introduction to the problem of competing events in Kaplan-Meier analysis. It explains cumulative incidence competing risk analysis and demonstrates on a cohort of elderly dialysis patients that, in contrast to the Kaplan-Meier method, application of this method yields unbiased estimates of the cumulative probabilities for cause-specific mortality.

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Author and article information

Contributors

Abelardo I Aguilera: Role: Academic Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 19 June 2015

Publication date Collection: 2015

Volume: 10

Issue: 6

Electronic Location Identifier: e0127453

Affiliations

[1 ]School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil

[2 ]Graduate Program in Medicine and Health Sciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil

[3 ]School of Medicine, UNESP, Botucatu, Brazil

Hospital Universitario de La Princesa, SPAIN

Author notes

Competing Interests: AF has received consulting fees and a speaker honorarium from Baxter Healthcare. PB has received consulting fees and a speaker honorarium from Baxter Healthcare. RPF has received research grants, consulting fees and speaker honorarium from Baxter Healthcare. TPM has received consulting fees and speaker honorarium from Baxter Healthcare. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Conceived and designed the experiments: SCR RPF TPM. Performed the experiments: SCR AEF PB RPF TPM. Analyzed the data: SCR TPM. Contributed reagents/materials/analysis tools: SCR AEF PB RPF TPM. Wrote the paper: SCR AEF PB RPF TPM.

¶ Centers that contributed to the BRAZPD II are provided in the Acknowledgments.

* E-mail: thyago.moraes@ 123456pucpr.br

Article

Publisher ID: PONE-D-14-57656

DOI: 10.1371/journal.pone.0127453

PMC ID: 4474697

PubMed ID: 26091005

SO-VID: 585aeb3f-c3d1-4d6e-9607-6fa65c3fbd8c

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

History

Date received : 23 December 2014

Date accepted : 15 April 2015

Page count

Figures: 5, Tables: 2, Pages: 13

Funding

This study was funded by Baxter Healthcare. The sponsor had no participation in the study design, data analysis or preparation of the manuscript.

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Data Availability Due to ethical restrictions and patient privacy requirements, data are available upon request and held at the Pontifícia Universidade Católica do Paraná. Any person can ask for additional information or submit a project to use data from BRAZPD II for analysis, under the supervision of the Steering Committee. The administrative structure of the BRAZPD II comprises a steering committee with 3 members, one project manager, one project coordinator and one biostatistician. The study leader is currently Dr. Roberto Pecoits-Filho and he may be contacted at r.pecoits@ 123456pucpr.br .

Low Serum Potassium Levels Increase the Infectious-Caused Mortality in Peritoneal Dialysis Patients: A Propensity-Matched Score Study

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Abstract

Background and Objectives

Design, Setting, Participants and Measurements

Results

Conclusions

Related collections

PLOS Climate

Most cited references 13

Do observational studies using propensity score methods agree with randomized trials? A systematic comparison of studies on acute coronary syndromes.

Serum potassium and cause-specific mortality in a large peritoneal dialysis cohort.

The analysis of competing events like cause-specific mortality--beware of the Kaplan-Meier method.

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