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Towards unbiased estimation of the optimal time for renal replacement therapy

Sileanu, Florentina Elena (2015) Towards unbiased estimation of the optimal time for renal replacement therapy. Master's Thesis, University of Pittsburgh. (Unpublished)

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Acute kidney injury (AKI), a sudden deterioration in renal function which occurs when the kidneys no longer remove waste products from the blood, is a challenging medical condition that affects intensive care unit patients worldwide. Patients with severe cases of AKI are placed on renal replacement therapy (RRT), a life-supporting treatment, and have been linked to mortality rates as high as 60%. Despite having guidelines with indications for RRT it is unclear what the optimal initiation time should be. Studies looking at the association between timing of initiation and mortality give contradictory results: some suggest a better outcome with early initiation while others with late initiation. There are four issues with current studies: 1) selection bias due to treatment status being driven by a patient’s baseline characteristics and the physician’s decision to treat; 2) the time from which survival is measured is different across studies causing lead-time or immortal-time biases; 3) results from the different statistical methods used are not always comparable; 4) patients never started on RRT are excluded from analyses.
The aim of this study is to determine the association between timing of initiation of RRT and mortality by addressing existing biases and limitations. Selection bias will be controlled for by a propensity score and 1-1 matching without replacement using the nearest neighbor Mahalanobis distance. Lead-time bias will be addressed by counting survival time from the same point for all patients. Immortal-time bias will be eliminated by using an expanded risk sets analysis in which patients are part of all three risk groups: early, late, and no RRT. Unlike current studies patients never started on RRT will also be analyzed. Cox proportional hazards will be used to test differences in the hazard of mortality at 1-year between groups.
Public Health Significance: To our knowledge, this is the largest observational study investigating the optimal time for initiating RRT. Our study shows the effect of different biases on the outcome and reinforces the importance of carefully designing an observational study. Future nephrology researchers can use this work as foundation in the quest of finding the optimal time for RRT initiation.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Sileanu, Florentina Elenaflorenti@pitt.eduFLORENTI
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorChang, Chung-Chou H.changj@pitt.eduCHANGJ
Committee MemberClermont, Gillescler@pitt.eduCLER
Committee MemberKellum, John
Committee MemberYouk, Adayouk@pitt.eduYOUK
Date: 29 June 2015
Date Type: Publication
Defense Date: 22 April 2015
Approval Date: 29 June 2015
Submission Date: 5 April 2015
Access Restriction: 3 year -- Restrict access to University of Pittsburgh for a period of 3 years.
Number of Pages: 45
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Biostatistics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: renal replacement therapy; propensity score; Mahalanobis matching; expanded risk sets; immortal-time bias
Date Deposited: 29 Jun 2015 14:41
Last Modified: 01 May 2018 05:15


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