Health Economics of Renal Replacement Therapy

Abstract

The medical treatment of renal failure is increasingly being discussed in terms of medical economics against the background of disease mechanisms, treatment techniques, and related systems. Particularly, renal replacement therapy requires considerable medical resources and results in high medical costs; therefore, the interest in medical economics is increasing worldwide. This article discusses the cost-effectiveness of renal replacement therapy using macro- and micro-analyses. Based on the macroscopic analysis of international comparisons of renal replacement therapy systems based on medical expenses per patient with end-stage renal disease and a one-year mortality rate, Japan performed better than other developed countries. A clinical economic study of renal replacement therapy is significant because it quantitatively demonstrates the socioeconomic value of life-saving and health benefits (Hemodialysis: approximately 6.5 million JPY/Qaly). In other words, even with high annual medical expenses and a heavy financial burden, the level of medical fees is appropriate from the perspective of the public’s value judgment. A micro-analysis comparing the cost-effectiveness of marginal and standard donors revealed no statistically significant difference in their cumulative medical costs per long-term life expectancy. Thus, evidence and decision-making related to medical economics are required for the sustainable development of the medical system for end-stage renal disease.

1. Introduction

The estimated worldwide prevalence of chronic kidney disease (CKD) in 2017 was 9.1%, an increase of 29.3% since 1990 [1]. In Japan, the number of patients with CKD is increasing annually, with one in eight adults estimated to have CKD. Under these circumstances, the medical economics of renal replacement therapy for patients with end-stage renal disease (ESRD) are attracting global attention against the backdrop of medical system sustainability. Based on these trends, this paper discusses the medical economics of renal replacement therapy by combining theories of medical value assessment and clinical economic studies. These findings are presumed to contribute to the further development of CKD treatment.

2. Socio-economy and medical innovation

In general, since economic trends and the rate of the aging population affect the balance of social security payments that support medical care, recent circumstances have increased the severity of socioeconomic trends surrounding medical care, leading to discussions on increasing the national burden and improving productivity [2]. For example, medical expenditures in the areas of coronary and kidney diseases are growing faster than the gross domestic product (GDP) in Japan [3]. Against this background, the insurance premiums borne by beneficiaries cover only approximately half of the financial structure of the universal health insurance system, and public funds (compensation from general revenue sources with a debt of approximately 30%), which are widely borne by the public, account for nearly 40%.

When discussing health policy as a system, this situation (social income-expenditure imbalance) is regarded as one of the uncertainties concerning a stable supply of medical services in the future.

In other words, social security debt is problematic because whether it can be regarded as an “investment” that can be expected to increase social added value (return) is unclear. However, since the field of pediatric medicine targets the group that will become the working population in the future, it is relatively easy to discuss “investment and recovery” based on the above-mentioned perspective. Additionally, in the field of medical care for older adults, the socioeconomic added value can be discussed while creating new medical innovations and building social models that are beneficial for everyone. We hope that these perspectives will be discussed further in the future.

In recent years, themes related to the sustainability of systems and social harmony in the medical field have been emphasized, and concepts such as Sustainable Development Goals (SDGs) and Appropriate Use Criteria (AUC) have been introduced. Hence, even with the further development of artificial organs and transplantation medicine, socioeconomic perspectives are becoming increasingly significant. Therefore, it is important to realize the economic added value of these medical treatments and share them with the stakeholders. Particularly, it should be reaffirmed that a robust universal health insurance system is necessary to encourage related research and development [4].

For example, an analysis aimed at clarifying the preliminary interactions between Universal Health Coverage (UHC) and medical innovations regarding the security and continued progress of medical services showed that UHC levels and medical innovations (drug discovery) were positively correlated (r = 0.629, R² = 0.395, p < 0.05; Figure 1) through the health economic mechanism (value chain).

Figure 1.

An international comparison of correlations between medical innovation (drug discovery ability) and UHC levels.

This study conducted a correlation analysis using statistical data from 11 countries (World Bank and the Japanese government) on the relationship between UHC indicators and medical innovations. The UHC index was converted into an integral value of the UHC index (0–100 score) and the total population (in millions) while considering the contribution of each level to the population. Focusing on drug discovery as a major aspect of medical innovation, we selected the share of the top 100 ethical drugs worldwide according to the country of origin. Pearson’s correlation coefficient was used for the correlation analysis. The statistical significance level was set at 5%. Notably, this figure is represented by a logarithmic transformation.

A country’s UHC level is generally affected by its real economy (e.g., GDP) (Table 1) [5]. Particularly, the impact of fluctuations in public medical costs is significant. Additionally, the ratio of medical expenses per capita is considered to affect the spread of innovative medical technologies that have been developed [5]. Thus, economic growth is important for promoting medical innovation. Therefore, sustainable and equitable capital investment in medical care (i.e., the improvement of UHC) is crucial. Furthermore, the active expansion of public medical resources is essential to enhance the synergistic effect between medical innovation and UHC. In future, these factors should be systematically discussed as value chains (Figure 2).

UHC Index of Service Coverage (SCI)	Partial Regression Coefficient	Standardized Partial Regression Coefficient	S.E.	p-value	95% CI
Population (total: million people)	0.0049	0.1921	0.0012	0.0001	0.0025–0.0074
GDP per capita (current USD)	0.0017	1.6129	0.0002	<0.001	0.0013–0.0021
Health expenditure (% of GDP)	2.3481	0.4116	1.5748	0.136	−0.7386–5.4347
Government health expenditures (% of general government expenditures)	1.4511	0.6575	0.2804	<0.001	0.9015–2.0006
Unemployment rate (%: ratio of unemployed persons)	−1.4764	−0.2253	0.7105	0.0377	−2.8689−−0.0838
Poverty rate (%: poverty gap)	−1.6736	−0.2303	0.4674	0.0003	−2.5897−−0.7575

Table 1.

Panel data analysis of the impact of the economic level (GDP, health expenditure, unemployment, and poverty) on the UHC level (SCI). (source: Ref. [5]).

Model: R² = 0.991, F test: p < 0.001.

GDP, gross domestic product; UHC, universal health coverage; SCI, service coverage index; S.E., standard error; CI, confidence interval.

Figure 2.

Progress mechanisms of healthcare and socioeconomic factors associated with medical innovation: Value chain, including UHC. (source: Ref. [4]).

3. Life-saving value and cost-effectiveness

In the discussion on medical value that advocates the real-world economy, it is generally possible, albeit limited, to evaluate the value of medical services by applying cost-effectiveness analysis and marginal utility theory. The main theories are outlined below. Usually, in microeconomics, the efficiency of service provision is maximized through price convergence based on the supply and demand equilibrium, backed by the fundamental utility theory [6]. Additionally, the prices at which the supply and demand are in equilibrium represent this value.

On the other hand, in the medical field that has a high public interest, the perspective of equity (balance of well-being) is considered along with efficiency. It is necessary to discuss the value of public interest while considering the harmony between the patient’s medical care requests (preferences and willingness to pay) and the government’s medical finances (income redistribution and fiscal balance). Therefore, the value of medical care should be examined in terms of the balance between utility (health outcomes) and costs (resource consumption) per health program unit, while interweaving the relationship between individuals and society against the background of welfare economics (Figure 3) [7].

Figure 3.

The concept of medical valuation (application of the utility theory and cost-effectiveness). (source: Ref. [7]).

Consequently, when utility is maximized within a certain budget range, the higher the performance, the greater the utility of the group as a whole and the higher the “value” of stakeholders. Compared with other conceptual discussions, this approach to value assessment in medical care is relatively consistent with the values of the real economy and daily life (national consensus) (e.g., approximately 6 million yen per quality-adjusted life year [Qaly]). Therefore, it is suitable to examine the value of medical services in the public sector [8].

For example, a Japanese report assessed the value of renal replacement therapy (hemodialysis, HD) for ESRD, whose annual medical expenses are approximately 5 million JPY and the financial burden is approximately 1.6 trillion JPY (Figure 4) [9, 10]. This study is significant because it quantitatively demonstrates the socioeconomic value of life-saving and health (HD: approximately 6.5 million JPY/Qaly). In other words, even with high annual medical expenses and a heavy financial burden, the level of medical fees is appropriate from the perspective of the public’s value judgment. This is further supported by the macro analysis based on the international comparison shown below.

Figure 4.

Cost-effectiveness of dialysis intervention (artificial kidney): Hemodialysis versus peritoneal dialysis. (source: Ref. [9]).

In the previous section, it was stated that an increase in public medical expenses is necessary to promote innovative treatment technologies and improve treatment outcomes. The next point of contention is whether the amount of medical resource consumption is appropriate to improve medical outcomes. Part of the answer to this question derives from cost-effectiveness. For example, ESRD treatment costs and public healthcare budget were positively correlated (Figure 5). Based on this, when a macro cost-effectiveness analysis was performed on the annual total medical expenses and one-year life prognosis of ESRD, Japan had the best performance compared to other countries (Figure 6). Thus, renal replacement therapy in Japan is highly valuable to the general public.

Figure 5.

The relationship between patients’ medical expenses in the field of end-stage renal disease (ESRD) and medical expenses per capita. Data source: Refs. [11, 12].

Figure 6.

An international comparison of the cost-effectiveness of the clinical system for end-stage renal disease (ESRD). (note) U.S., United States. Data source: Refs. [11, 13].

Since the medical insurance system that advocates UHC includes a stable supply as one part of the system, its sustainable development is considered as the most significant medical value to the public. Although there may be variations in the national culture and disease characteristics, it can be inferred that saving lives is the most common value. It is essential to remember that lifesaving not only results in opportunities for other medical interventions (opportunities for disease improvement) but also provides assurance of the quality of life (QOL) in the long run, which is of considerable significance in due course. Therefore, the potential value of renal replacement therapy (HD) is significant.

However, the assessment of medical value involves stakeholders’ interests and is affected by the application of subjective outcomes and the macro real economy. Therefore, there are some restrictions on its use, along with difficulties in data analysis and direct recognition. However, against the background of tight medical finances and progress in innovation, cost-effectiveness analysis, which is a part of health technology assessment (HTA), is being actively introduced globally. Based on this trend, medical value assessments are expected to increase.

4. Cost-effectiveness of renal replacement therapy

Although the disease and economic burden associated with kidney diseases are increasing worldwide, there have been few international reports evaluating the cost-effectiveness of renal replacement therapy in recent years. Several recent reports have systematically reviewed the cost-effectiveness of dialysis. This section briefly introduces the contents of this study and discusses a research report on the cost-effectiveness evaluation of renal replacement therapy in Japan.

The main report [14] conducted a systematic review of the costs and health outcomes of dialysis modalities between January 2000 and December 2017. The survey sources included the MEDLINE, National Health Service Economic Evaluation Database, Health Technology Assessment Database from the Center of Reviews and Dissemination, Cochrane Library, and Econlit. They identified 16 health economic evaluation reports that compared dialysis modalities from both high- and low-income countries. Two similar review papers have also been published [15, 16].

These studies examined the cost and health outcomes of multiple dialysis modalities and reported average cost-effectiveness rather than incremental cost-effectiveness (ICER). Nearly all evaluations suggest that home dialysis is less costly and provides similar or better health outcomes than institutional dialysis, which is the mainstay intervention. Therefore, home dialysis, which includes both hemodialysis (HD) and peritoneal dialysis (PD), is generally more cost-effective than institutional dialysis (Table 2). However, there are few reports with high-quality study designs.

Author (year)	ICER/main results	Authors’ conclusions
Moradpour et al. (2020)	PD was dominant over HD; ICER for KT vs. PD: $1446/Qaly.	KT is cost-effective compared with PD at a WTP threshold of $12,400, and HD was dominated.
Rosselli et al. (2015)	KT was a cost-effective alternative from the second year and became the dominant alternative after the fourth year.	KT improves the overall survival rates and quality of life and is a cost-saving alternative compared with dialysis.
Jensen et al. (2014)	KT holds a dominant position over dialysis with both lower costs (810,516 DKK versus 1,032,934 DKK) and higher effects (4.4 Qaly versus 1.7 Qaly).	KT was the dominant treatment when compared with dialysis.
Shimizu et al. (2012)	Base scenario (current composition of KRT) was dominated by Scenario 2 (likelihood of a preemptive LT increased by 2.4 times), Scenario 3 (likelihood of a LT increased by 2.4 times), and Scenario 4 (likelihood of a DT increased by 22 times).	Increased rate of KT and PD can reduce costs and improve health outcomes.
	The ICER of Scenario 1 (likelihood of starting with PD increased by 2.3 times) over Base scenario was $5458/Qaly.
Villa et al. (2012)	Scenario 1 (57% of scheduled incident patients on any RRT modality) was dominated by all the proposed scenarios: Scenario 2 (increased proportion of overall scheduled incident patient to 75% from 57%), Scenario 3 (increased proportion of scheduled patients on PD to 30% from 10%) and Scenario 4 (combined scenarios 2 and 3)	An increase in the overall scheduled incidence of KRT on PD should be promoted.
Haller et al. (2011)	Scenario 1 (current policy of assigning 90.6% of incident ESKD patients to HD, 7.2% to PD, 0.1% to LT, and 2.1% to DT) was dominated by Scenario 2 (increasing PD to 20%), and Scenario 3 (increasing PD to 20% and increasing KT to 10%)	KT and PD are more cost-effective than HD.

Table 2.

Example of the cost-effectiveness of renal replacement therapy: A systematic review. (source: Ref. [14]).

NR, not reported; QALY, quality-adjusted life year; ESKD, end-stage kidney disease; KRT, kidney replacement therapy; HD, hemodialysis; PD, peritoneal dialysis; CAPD, continuous ambulatory peritoneal dialysis; KT, kidney transplantation; LT, living-donor transplantation; DT, deceased-donor transplantation; ICER, incremental cost-effectiveness ratio; SA, sensitivity analysis; PAS, probabilistic sensitivity analysis; WTP, willingness-to-pay.

In Japan, some studies have preliminarily evaluated the cost-effectiveness of HD, PD, and kidney transplantation (KT) for renal replacement therapy. The results are summarized in Table 3. Although both reports were observational studies, and the level of evidence was not high, it is possible to estimate the level of performance of renal replacement therapy in Japan. Particularly, the analytical approach was unified using a cost-utility analysis, which is suitable for mutual comparison of the medical economics of each modality.

Renal replacement therapy	Kidney transplant	Peritoneal dialysis	Hemodialysis	Hemodialysis (Online-HD)
Publication year	2017	2019	2015	2013
Research design	Prospective observational study, Multicenter study (Added: Model calculation for 3 years)	Prospective observational study, Multicenter study	Prospective observational study, Multicenter study	Prospective observational study, Multicenter study
Number of patients (n)	25	179	29	24
Observation period (months)	12	36	437 dialysis sessions (average: 15 months)	4
Evaluation index	Health-related QOL, Life year, Medical fee claim (Including donor medical expenses)	Health-related QOL, Life year, Medical fee claim	Health-related QOL, Life year, Medical fee claim	Health-related QOL, Life year, Medical fee claim
Result of the analysis
ICUR (Kidney death as nonintervention)	66,000 (USD/Qaly; 12 months), 51,600 (USD/Qaly; Model calculation for 3 years)	55,019 (USD/Qaly)	68,800 (USD/Qaly)	65,700 (USD/Qaly)
ICUR (Other control therapy)		126,034 (USD/Qaly; APD vs. CAPD)
Reference number	14	9	10	15

Table 3.

Japanese report on the cost-effectiveness of renal replacement therapy.

(Note) Exchange rates were averages for the publication year or observation period. ICUR, incremental cost-utility ratio.

The most cost-effective renal replacement therapy has been PD [9]. The reason for this is a good quality of life in home care, as found in a previous study. However, the PD selection rate in Japan is approximately 9%, which is lower than that of other countries. There are several reasons for this, but the previous paper has discussed the socioeconomic significance of “PD first for older adults” based on the characteristics of bacterial peritonitis, which is one of the reasons for limiting the duration of PD. Thus, there is a perspective on the sustainability of the medical system in the selection of renal replacement therapy.

KT is approximately at the same level as PD and tends to be more cost-effective [17]. Particularly, KT has the best incremental cost-utility ratio (ICUR) for renal death at 51,600 (USD/Qaly) when converted to medical costs using the exchange rate of the year of publication. Furthermore, it should be noted that the results of this study did not reflect the superiority of the treatment mechanism or the cumulative cost of transplantation medicine because of a short observation period (analysis period) of 3 years. Thus, it can be inferred that KT outperforms other modalities in terms of long-term clinical and economic performance.

HD, which accounts for the majority of renal replacement therapy in Japan, has almost the same results as the cost-effectiveness judgment criteria in the medical insurance system set by the government authorities, and as described in the previous section, its socioeconomic usefulness is significant [10]. Additionally, online HD with improved dialysate quality significantly improves the QOL and function [18]. In Japan, HD is advantageous in terms of facility access and medical management. Therefore, it is essential to select a therapy suitable for the condition and lifestyle of each patient to further develop a treatment system for ESRD.

5. Health economics evaluation of marginal donors

As discussed in the previous section, KT, as a therapy for ESRD, is generally considered economically superior. Therefore, although the widespread use of KT is desired, a solution to the limitations of therapy selection (e.g., securing a donor) has long been expected. As the burden of renal failure increases in Japan, the use of marginal donors in kidney transplantation medicine is expanding. Therefore, based on the definition of a marginal donor developed in a research project, we introduce a preliminary report that verifies its medical economic usefulness through a cost-effectiveness analysis.

This study [19] utilized renal transplant registry data from the Japan Society for Transplantation and Tokyo University Health Economy Big Data (TheBD). The evaluation group included marginal donors, while the control group included standard donors. The eGFR cut-off of 70 mL/min/1.73 m² was used to separate the two. Clinical results (engraftment rate, mortality rate, etc.) were analyzed from the renal transplant registry data, and the cost elements (hospitalization and outpatients by disease) of the medical economic big data were extrapolated to the obtained results. In the cost-effectiveness analysis, total medical costs (kidney transplantation medical costs and related disease treatment costs) were used as cost indicators and life-years (LYs) were used as effect indicators. Survival analysis was performed using the Kaplan-Meier method and Wilcoxon rank-sum test.

There were 3336 marginal donors and 7960 standard donors (Table 4). There was no significant difference (p = 0.681) in survival between the two groups (Figure 7). Regarding cost-effectiveness, the standard donor group tended to be slightly better in each observation period, but there was no statistically significant difference between the two (overall:2.59 million JPY/LY/year vs. 2.48 million JPY/LY/year, p = 0.849). Multiple regression analysis revealed that donor eGFR at transplantation, recipient age at transplantation, and dialysis duration were statistically significant factors influencing cost-effectiveness (Table 5). No statistically significant difference was observed in the analysis in which the conditions for setting the standard donor group were stricter and the age at transplantation and dialysis history were the same for both groups (Table 6).

Item	(parameter)	Unit	Standard donor			Marginal donor			p-value
Number of samples	Whole population	N	7960			3336
Observation period		year	4.1	±	2.4	3.8	±	2.3	NS
Donor type		%
	Living donor		100.0			100.0
	Deceased donor		0.0			0.0
Sex		Male ratio (%)
	Recipient		63.6			62.3
	Donor		36.0			38.3
Age		year
	Recipient		44.7	±	16.0	47.3	±	14.7	NS
	Donor		54.9	±	11.2	61.8	±	8.7	NS
Primary disease	(top 50%)	%
	IgA nephropathy		16.2			15.6
	Diabetic Nephropathy (NIDDM)		15.0			14.3
	Not clear		17.8			21.5
Dialysis history	(recipient prior treatment)
	Hemo/Peritoneal/Combination	%	80.1			78.9
	Introduction period	year	3.4	±	4.7	3.4	±	5.0	NS
Recipient comorbidity	(at the time of transplantation: overlap)	%
	Cardiovascular complications		83.8			82.7
	Diabetic complications		12.5			23.2
Donor test value
	BMI	kg/m^2	22.8	±	9.8	23.2	±	9.0	NS
	Blood pressure (systolic)	mmHg	123.2	±	14.7	125.6	±	15.1	NS
	Serum creatinine	mg/dL	0.64	±	0.12	0.82	±	0.15	< 0.05
	eGFR	mL/min/1.73m^2	85.9	±	12.9	62.2	±	6.7	< 0.05
Donor history		%
	Diabetes		4.8			3.9
	Heart disease		1.5			2.2

Table 4.

Composition of the target population.

(Note) NIDDM, non-insulin-dependent diabetes mellitus. (Source: Ref. [19])

Figure 7.

Comparison of survival rates between marginal and standard donor groups (Kaplan-Meier curve).

Item	Standard partial regression coefficient	F-value	p-value	Standard error	VIF
d_eGFR at transplantation	−0.033	6.164	< 0.05	0.181	1.02
d_Postoperative hospital stay	0.003	0.044	NS	0.559	1.02
d_BMI value	0.002	0.026	NS	0.916	1.05
d_Systolic blood pressure	0.014	1.145	NS	0.189	1.06
d_Diabetes	0.011	0.654	NS	5.288	1.01
r_Age at transplantation	0.031	5.134	< 0.05	0.199	1.08
r_Duration of dialysis	0.054	16.375	< 0.01	0.587	1.05
r_Diabetes	0.007	0.270	NS	5.976	1.13
r_Cardiovascular disease	0.020	2.220	NS	3.380	1.06
Constant term		0.131	NS	43.281

Table 5.

Factors affecting cost-effectiveness (multiple regression analysis).

Model: p < 0.01.

(Note) d_, donor; r_, recipient.

Item	Standard donor			Marginal donor			p-value
Standard donor’s conditions (cut-off) and patient’s background conditions (age, dialysis)	Donor eGFR>80			Donor eGFR<70
	Donor age<70			Recipient age: adjusted
	Donor complications: None			History of dialysis introduction: adjustment
	Donor BMI<25			Pediatric exclusion
Recipient age (years)	44.4	±	16.5	44.3	±	12.7	NS
History of dialysis introduction (years)	3.6	±	4.9	3.3	±	4.7	NS
Donor eGFR (mL/min/1.73m^2)	88.4	±	14.2	62.2	±	6.8	< 0.05
Cost-effectiveness (10,000 JPY/LY/year)	199.7	±	191.1	215.7	±	453.5	NS

Table 6.

Cost-effectiveness analysis with more detailed conditions for standard donors. (source: Ref. [19]).

(Note) Units in the table are eGFR: mL/min/1.73m², age: years old, and BMI: kg/m².

Supplement: SD notation.

The results of this study showed that the survival and cost-effectiveness in the marginal donor group were not significantly lower than those in the standard donor group. These results are generally valid in the clinical settings in Japan, where the practice of marginal donors is expanding while maintaining the clinical results of kidney transplantation. In the future, along with a robust evaluation by non-inferiority trials, continuous (prospective) verification of long-term results using high-quality research designs, such as randomized trials, will be essential.

6. Conclusions

This study first explored the relationship between UHC and medical innovations. The results suggested that expansion of the real economy and public investment is necessary for the progress of the medical system. Next, the method of explaining the medical and socioeconomic value of lifesaving was explained using HD research reports as examples. Based on the findings of previous studies, we highlighted case studies on the cost-effectiveness of renal replacement therapy and clarified that the performance of KT was generally better than that of other therapies. Finally, research on the medical economics of marginal donors against the backdrop of considering measures to promote KT was introduced. In the future, it will be important to select an appropriate therapy to further increase its clinical value for patients with ESRD.

Acknowledgments

We gratefully acknowledge the work of the past and present members of our study. This manuscript received significant help from Dr. Yoshiko Yamamoto. Section 5 of this chapter was funded by the Japan Agency for Medical Research and Development (research project title: Investigating new evidence to understand the safety of kidney transplantation from marginal donors).

Conflict of interest

The authors declare no conflict of interest.

Other declarations

It was ensured that articles in other languages cited in this paper were acceptable secondary publications.