The impact of dialysis therapy on older patients with advanced chronic kidney disease: a nationwide population-based study

Older patients with chronic kidney disease (CKD) stage 5 comprise a rapidly growing emerging population that may face the dilemma of whether to undergo dialysis or receive conservative care [1]. Although patients with end-stage renal disease (ESRD) tend to choose dialysis therapy over conservative care, the use of dialysis to treat kidney failure peaks in patients who are 75 years old and declines thereafter [2],[3]. The perceived financial burden of dialysis, as well as a high comorbidity rate, uncertainty about the treatment’s long-term benefit, and sense of life completion and acceptance of death, leads many older patients to forego dialysis [4]. The most critical concern of older patients with CKD stage 5 is whether dialysis provides benefits such as increased life expectancy and improved functional ability at the end of life [5],[6]. The new guidelines of the Renal Physicians Association and the American Society of Nephrology on the initiation and withholding or withdrawal of dialysis emphasize shared decision making with patients, their family members and physicians in charge of their care [7]. Although comprehensive physician-patient communication may help to achieve treatment goals and avoid unnecessary medical expenditure [8],[9], independent and objective evidence of the comparative effectiveness of treatment options is still needed to guide older patients’ decision making about dialysis.

To date, very few studies have investigated the risks and benefits of dialysis therapy for older patients with advanced CKD. Previous studies examining this issue found that dialysis conferred a significant but small advantage over conservative care in older patients [10]-[12]. However, the statistical power of these studies was limited due to small samples, short follow-up periods and limitations of analytical methodologies. Because initiation of chronic dialysis commonly occurs during follow up in patients with advanced CKD, the use of appropriate statistical methods to calculate the fraction of mortality attributable to dialysis is essential. Accordingly, in this nationwide population-based cohort study based on Taiwan’s National Health Insurance Research Database (NHIRD), we utilized the initiation of chronic dialysis as a time-dependent covariate in Cox regression models to assess the real effect of dialysis on older patients with advanced CKD.

This nationwide population-based study provides novel evidence that dialysis therapy does not always provide a substantial survival advantage among older patients with advanced CKD. Most of these patients face the prospect of dialysis therapy for the remainder of their lives. Thus, an understanding of the survival benefit of dialysis for this population is important. Using the initiation of chronic dialysis as a time-dependent variable in a Cox regression model, we found that dialysis therapy was associated with a nearly 40% increase in mortality risk, in patients ?70 years old compared with those receiving conservative care. These increases remained significant in propensity score-matched analysis.

The risk of approaching dialysis was found to exceed that of mortality in most older patients with estimated GFR <15 ml/min/1.73 m²[26]. Some authors have argued that older patients may have no real choice in dialysis decision making due to the lack of comprehensive insurance coverage, which may prohibit access to dialysis through implicit or explicit dialysis rationing due to limited medical resources and financial barriers [27]-[29]. Our study results, however, suggest that NHI coverage of dialysis expenses eliminates financial barriers for patients who may benefit from the treatment. Furthermore, nephrologists in Taiwan cannot legally withdraw or withhold dialysis without patient agreement, even when they believe that the treatment will have no benefit or that any benefit is outweighed by the burdens of treatment. In other words, patients and their families take active roles in dialysis decision making. Thus, our findings provide unrestricted objective evidence that can be used to optimize the risk-benefit analysis of dialysis therapy in older patients with advanced CKD.

The survival of patients undergoing dialysis in Taiwan improved rapidly after the initiation of the NHI program in 1995. However, outcomes of older patients have not improved substantially despite public insurance benefits enabling free healthcare access and total coverage of medical expenses [30]. Furthermore, Wu and colleagues [31] found that incident dialysis has been associated with a 6.27- to 10.4-fold greater risk of mortality in patients ?70 years old compared with those <30 years old, even after adjusting for CCI. Among US nursing home residents, initiation of dialysis was related to substantial functional decline and up to 60% mortality within one year [32]. The cost of dialysis care also increases with age and the number of comorbidities [33]. In our study, the average annual per-patient cost of dialysis was much higher than that of conservative care among older patients; dialysis increased the total cost by US$5,742 per patient year. The healthcare cost was also significantly higher after initiation of chronic dialysis than in the pre-dialysis period (US$42,980 versus US$8,738 per patient year). In 2011, Medicare expenditures for dialysis in the US were $71,630 to $87,945 per patient year [1], at least double the costs calculated in the present study. Thus, ample opportunity exists to improve the outcomes of older patients after the initiation of dialysis therapy from a global standpoint. Alternatively, our findings support that robust conservative care was encouraged when considering opportunity cost principles. However, risk-benefit analysis in the present study is insufficient for decision making about dialysis for older patients; examination of this issue requires further long-term assessment.

Most previous small-scale studies [10]-[12],[34],[35] found that dialysis therapy conferred a modest (2 to 45.9 months) absolute survival advantage over conservative care in older patients, although this advantage was largely offset by high comorbidity rates. By contrast, our study demonstrated that dialysis therapy in older patients increased mortality risk by almost 40% compared with conservative care. This discrepancy may be due to differences in enrollment criteria and drawbacks of the statistical methods used in previous studies, such as the consideration of initiation of chronic dialysis as a dichotomous (non-time-dependent) variable in Cox proportional hazards models. This approach involves the examination of the relationship between survival and patient characteristics at the time of study enrollment, which may result in a false increase in survival rate in the dialysis group because patients who survived longer had an increased likelihood of receiving dialysis therapy. Several prognostic models have been developed to resolve this issue [36]-[38]. The definition of initiation of chronic dialysis as a time-dependent covariate in the present study allowed for the divergence of survival curves after this event had occurred. This type of model ensures that the risk of mortality increases only after dialysis initiation, which is more accurate and clinically relevant.

Our subgroup analyses showed that the risk of mortality was consistently elevated in older patients receiving dialysis therapy, regardless of age, sex, comorbidities or time cohort. Mortality risk was lower in patients >80 years old than in those 70 to 80 years old, implying that the impact of dialysis on increased mortality risk became less dominant with advanced age in patients with advanced CKD. The influence of dialysis on mortality in very old patients may be offset by competition between the risks of dialysis and death. The mortality risk associated with dialysis increased consistently, irrespective of specific comorbidities; however, the adjusted HR of mortality was lower in patients with, than in those without, hypertension. This result may be due to the vulnerability of older patients receiving dialysis to intradialytic hypotension, such that those with higher blood pressure targets may have a survival benefit [39]. Moreover, the effect of dialysis on mortality risk was smaller in the 2009 to 2010 cohort than in the 2000 to 2002 cohort. This finding may be attributed to advances in medical therapy and improvement in dialysis care over time.

Our study has several strengths. First, we present the largest currently available database for older patients with advanced CKD and their dialysis outcomes, with an extended follow-up period. Second, previous studies found that late or no referral to a nephrologist may be associated not only with an increased risk of short-term mortality, but also with incomplete understanding of dialysis in decision making [8],[34]. Subjects in our study were referred early to nephrologists, with a median interval of 192 days between enrollment and dialysis. This characteristic eliminated selection bias because patients were placed under nephrologists’ care with the intent of initiating dialysis.

Our results provide objective information to facilitate dialysis decision making among older patients, their family members and physicians; however, some limitations of this study should be acknowledged. First, decisions about whether to receive dialysis may depend on patient preferences (family support, financial constraints and the will to live), but examination of this complex process was beyond the scope of the current study. Second, information on several potential confounding factors, including obesity, nutritional condition, psychosocial function, performance status and indication for dialysis initiation, were not available in the NHIRD database. Estimated GFRs at dialysis initiation were also not recorded, whereas the Initiating Dialysis Early and Late (IDEAL) Study showed no significant survival difference between early initiation (estimated GFRs: 10.0 to 14.0 ml per minute) and late initiation (estimated GFRs: 5.0 to 7.0 ml per minute) of dialysis [40]. Third, our study was subject to the inherent limitations of its retrospective and observational design. However, randomized control trials investigating this issue are not possible because of the potential of violating medical ethics. Finally, we based the diagnosis of advanced CKD on ESA prescriptions, resulting in the exclusion of patients with advanced CKD who never received such prescriptions (that is, those who had no obvious renal anemia). The results of the study cannot be generalized to all older patients with advanced CKD.

Our findings provide novel information useful for the reconsideration of dialysis decision making that accounts for risk-benefit relationships in older patients with advanced CKD. For frail older patients with late-stage CKD, conservative care may be a viable treatment option, as dialysis may not prolong life expectancy.

DCT had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: CJS, YTC, SMO, DCT. Acquisition of data: CJS, YTC, SCK, DCT. Analysis and interpretation of data: CJS, YTC, SMO, DCT. Drafting of the manuscript: CJS, YTC, SMO, DCT. Statistical analysis: YTC, SCK, WCY. Obtained funding: DCT. Administrative, technical, or material support: SMO, SCK, WCY, DCT. Study supervision: DCT. All authors read and approved the final manuscript.