BACKGROUND/RATIONALE:
Chronic kidney disease (CKD) is a progressively debilitating, highly prevalent, and disproportionately costly disease. Initiation of long-term dialysis has significant financial and quality of life implications for the patient as well as costs to the health care system and society. Often, the decision to dialyze is based on declining levels of kidney function, as measured by the estimated Glomerular Filtration Rate (eGFR), and patient symptoms of uremia, such as fatigue and weight loss. However, optimal timing for dialysis is not well understood. There is little evidence to evaluate the benefits, if any, of referral to dialysis at higher levels of kidney function. A recently completed randomized trial found no mortality benefit to early dialysis, but this study was conducted in a highly select group of patients receiving mostly peritoneal dialysis. Observational studies outside the VA have found early hemodialysis was associated with greater mortality.

Nevertheless, data from the U.S. Renal Data System (USRDS) suggest that every year patients are initiating dialysis earlier, at ever higher levels of eGFR.


OBJECTIVE(S):
The objectives of this study were to assess the effects of early versus late dialysis for veterans with chronic kidney disease receiving care at the VA. Specific aims were to 1) determine if trends toward earlier dialysis apparent at the national level were also found within the VA; 2) estimate the potential health benefits for VA patients of earlier dialysis initiation compared to later; and 3) estimate the medical cost of earlier dialysis initiation for VA patients.

METHODS:
The study was a retrospective analysis of VA administrative and clinical data, and linked VA-USRDS data. For Aim 1, we identified Veterans and non-Veterans who initiated dialysis from 1999-2009 using the linked VA-USRDS databases. We compared trends in early initiation of dialysis (measured by eGFR>10) for VA versus non-VA patients. For Aims 2 and 3, we used a subset of VA patients who initiated dialysis between 1999 and 2009 to estimate the potential health benefits of early vs. late dialysis. We assessed differences in mortality, morbidity and costs. To address lead-time bias, we followed patients not from when they started dialysis, as was the case for all previous analyses using the USRDS, but from the time when a patient's eGFR first fell below 20 mL/min/1.73 m2. An eGFR of 20 mL/min/1.73 m2 was chosen because it is above the recommended threshold for renal replacement therapy (eGFR<15) but in the range where discussions about dialysis are considered. A detailed chart abstraction (n=1691 Veterans) was conducted to assess whether dialysis was being initiated earlier because patients were more frequently presenting with clinical signs and symptoms that indicate the need for dialysis but are not recorded in the USRDS. We estimated log gamma models of VA costs as a function of starting dialysis early and other confounders.

FINDINGS/RESULTS:
Aim 1: Trends toward earlier initiation of chronic dialysis within the VA from 2000-2009 parallel those observed in the wider population of dialysis patients; however, level of eGFR at initiation was markedly lower among Veterans who initiated dialysis within the VA (n=16,761) versus outside the VA (n=103,449). In 2000, 20% of Veterans cared for in the VA started dialysis at an eGFR >10, compared to 29% of Veterans cared for outside the VA. By 2009, the percent of these early initiations increased to 42% within VA and 51% outside the VA. The most pronounced differences in eGFR at initiation within versus outside the VA were observed among older patients and those with more limited life expectancy.

Chart abstraction found little evidence of an increase over time in the proportion of patients who were acutely ill at the time of initiation (49.8% in 2000 vs. 49.7% in 2009), or in the proportion of clinical signs and/or symptoms documented in the electronic medical record around the time of initiation, including gastrointestinal, cardiopulmonary, fatigue and/or weakness, electrolyte abnormalities, neurologic symptoms (p>0.20 for each symptom). We also found little evidence that clinicians were increasingly relying on eGFR measures to initiate dialysis: the proportion of patients for whom the decision to initiate dialysis was based only on level of kidney function did not increase significantly over time (4.5 vs. 5.8%, P=0.23),

Aim 2: Veterans who started dialysis at eGFR>10 (n=12,130) were older and more acutely ill than Veterans initiating at eGFR<=10 (n=11,961), and had higher all-cause mortality (hazard ratio 1.31; p<0.001). This higher mortality persisted after adjusting for variables that are available to researchers using only the USRDS (hazard ratio 1.10; p<0.001). However, when we augmented USRDS data with VA data on eGFR prior to dialysis to address lead-time bias, and accounted for the estimated trajectory of eGFR prior to dialysis to address omitted variables bias, the increased hazard associated with early dialysis was no longer apparent (hazard ratio 0.99; p=0.652).

Aim 3: We found little evidence that early dialysis was associated with higher VA dialysis costs (adjusted difference early dialysis versus timely= -$7.2; 95% CI (-$1013, $998), inpatient costs (adjusted difference -$3818, 95% CI (-$10,205, $2,568)), or total costs (adjusted difference $3315, 95% CI (-$5600, $1230)).

IMPACT:
Although the VA appears to be partially protecting Veterans from the more aggressive dialysis initiation practices outside the VA; VA nephrologists should consider whether these emerging practices are in the best interests of their patients, especially elderly patients and patients with limited life expectancy. Discussing dialysis options as part of advanced care planning should be considered.

Contrary to research conducted using USRDS data alone, we did not find that early dialysis was associated with increased mortality. We found that the trajectory of eGFR was a major confounding factor-it was the single most important factor in multivariate survival models-- and data on trajectory are not available in the USRDS. VA researchers studying dialysis and chronic kidney disease should include the trajectory of kidney function as a risk factor in future analyses.

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External Links for this Project

NIH Reporter

Grant Number: I01HX000125-01A2
Link: https://reporter.nih.gov/project-details/8004711

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PUBLICATIONS:

Journal Articles

1. Wong SPY, Yu MK, Green PK, Liu CF, Hebert PL, O'Hare AM. End-of-Life Care for Patients With Advanced Kidney Disease in the US Veterans Affairs Health Care System, 2000-2011. American journal of kidney diseases : the official journal of the National Kidney Foundation. 2018 Jul 1; 72(1):42-49. [view]

Conference Presentations

1. Hebert PL, Liu C, Wong ES, Hernandez S, Batten A, Lo S, Lemon JM. National Evaluation of the effects of healthcare utilization and costs of the VA patient centered Medical Home Initiative. Paper presented at: Society of General Internal Medicine Annual Meeting; 2013 Apr 25; Denver, CO. [view]
2. Hebert PL, Perkins M, Lemon JM, Liu C, O'Hare AM. Unexplained and Medically Unjustified Trend toward Starting Dialysis at Higher Levels of Kidney Function Found Outside and Inside the VA. Poster session presented at: VA HSR&D / QUERI National Meeting; 2012 Jul 19; National Harbor, MD. [view]

DRA: Health Systems
DRE: none
Keywords: none
MeSH Terms: none