Dialysis and kidney transplant practices and challenges in Thailand

Abstract

Thailand is a country in the heart of mainland Southeast Asia (SEA), divided into 5 regions (north, northeastern, south, eastern and central) and 77 provinces. As of 2023, the Thai population is estimated to be 70 million, with a population density of 137 habitants/km2 and a median age of 40 years.1 Half and one-sixth of the population live in urban areas and Bangkok (the capital city), respectively. According to World Bank records, Thailand is classified as an upper-middle-income country that has spent 6.5% of its gross domestic product on health.2, 3 Since 2008, kidney failure has been recognized as a ‘catastrophic disease’ by the government, meaning all kidney replacement therapy (KRT) costs related to kidney failure are covered by the Thai state. This kidney failure coverage includes active and passive workers contributing to the social insurance system, representing 20% of the Thai population. These patients attend The Social Security System (SSS) Office for treatment.4 Those who do not have a formal job and who do not contribute to social insurance, representing 68% of the population, receive Universal Health Coverage (UC) from the National Health Security Office (NHSO).3 The government officers receive health coverage from the Civil Servant Medical Beneficiary System (CSMBS), which covers, free of charge, all kidney failure expenses.5 This article aims to describe the current status of dialysis and kidney transplantation service deliveries in Thailand, reviewing the barriers to effective dialysis management and highlighting opportunities for improvement. According to the USRDS 2022 and Thai Renal Replacement Therapy Registry 2022 Preliminary reports,6-8 there were ~0.12 million Thai population on KRT, representing a local kidney failure prevalence of 2470 patients per million population (pmp) and an annual incidence of 339 pmp,6 causing >20 000 newly acquired KRT each year. Thailand ranks top 4 and 5 in the highest prevalence and incidence of treated kidney failure since 2010 and ranks the biggest average yearly change in both prevalence (174 pmp) and incidence (20 pmp) of treated kidney failure between 2010 and 2020.6 The peritoneal dialysis (PD) penetration in dialysis is 16%. The prevalence and incidence of kidney transplantation (KT) are 101 and 12 ppm, respectively. Deceased donor transplantation (DDKT) is 4 times more common than living-related donor transplants (LDKT). Only 6% of dialysis patients receive KT.9 The top 2 most common aetiologies of kidney failure are the same as those worldwide (diabetes 32% and hypertension 29%), and the most frequent cause of mortality is cardiovascular disease (Figures 1 and 2).6-8 Source: Special analysis, USRDS ESRD Database, data expresses as per million population Source: Special analysis, Databases of the Thailand Renal Replacement Therapy Registry (Nephrology Society of Thailand), Thai Transplant Society, and National Health Society Organization In 1960, PD was taking its first steps as a KRT, closely followed by haemodialysis (HD) in 1962, saving and prolonging the lives of Thai patients with acute kidney injury (AKI). With the creation of permanent vascular access for chronic patients by Cimino and Brescia, HD accelerated its development, enabling dialysis for Thai patients since 1964. However, during 1960–1970, PD in the intermittent modality could not keep up with HD. However, with the advent of the Tenckhoff catheter and the ‘Double-bag’ system using the ‘flush-before-fill’ concept, PD as maintenance dialysis finally took flight spreading the therapy at a slow speed since the 1980s and has rocketed up after the launch of the ‘PD-First’ policy in Thailand 2008.7 In February 2022, NHSO launched additional benefits of UC for KRT under the ‘Free Choice Dialysis’ policy, in which dialysis modality selection (either PD or in-centre HD) is a patient-centred care approach guided by patient's preference based on comprehensive information (e.g., medical illnesses, social and cultural factors, lifestyle, physical and psychological factors) and tailor to local resource limitation and infrastructure. HD patients who self-pay are the first group to benefit from this reformed policy immediately, causing a doubling in the number of HD patients in the first year subsequent, mainly in the metropolitans. In contrast, a gradual increase is observed in rural areas with limited resources for HD and vascular access services. However, HD transfer is lower than expected.3, 8, 10 KT set foot in Thailand in 1978 with LDKT. The technique of KT has evolved significantly over the years, with advancements in immunosuppressive medications and organ donation systems. The brain death donor act was passed in 1999, facilitating DDKT in the country. The Medical Council of Thailand ensures transplantation transparency by regulating medical professionals. The Thailand Organ Donation Center (OCD) was established in 1993 under the umbrella of the Thai Red Cross Society as an independent, not-for-profit organization. The ODC developed criteria for transplantation centre licences and authority to accredit centres to ensure transparency and compliance with the rules and regulations. Besides the regulator, ODC is federally designated by the law as the Organ Procurement and Allocation Organization (OPO) responsible for servicing the state of Thailand. KT was historically considered a high-cost treatment, with economic barriers limiting access to transplantation. However, thanks to the efforts of organizations like the Thai Transplant Society, The Kidney Foundation of Thailand and the Ministry of Public Health, reimbursement schemes have been established for all patients, and national treatment guidelines have been put in place (Figure 3). In 2022, HD patients receive haemodialysis services from 12 000 dialysis machines in 1009 dialysis centres (75% hospital-based and 25% outsourcing clinics) distributed throughout the country; about one-third are located in Bangkok metropolitan area. Dialysis centres are private (54%), public (44%) and charity (2%). Home HD in Thailand is considerably not available. The government reimbursed most HD patients through UC (30%), SSS (29%) and CSMBS (28%), while 12% were out-of-pocket payments. Six hundred fifty nephrologists and 3700 registered dialysis nurses deliver care to HD patients.8 Most centres use single-patient dialysis fluid delivery systems with reverse osmosis (RO) water treatment systems. HD prescription is typically 4 h per session, 2–3 times per week with bicarbonate dialysate, high-flux dialyzer reuse and disposable bloodline.10 Online haemodiafiltration (HDF) is available in large metropolitan hospitals. However, it is used in a few HD patients due to the high cost, acquired ultrapure water quality certification, not covered by UC, and required co-payment in SSS and CMBS. Dialyzers are reused in most HD units, except for subjects with positive serologies for hepatitis B, hepatitis C or HIV. Concerning the quality assurance of patient care and facility services, all HD units must get approval at the establishment and regular recertification by the HD Quality Assurance Audit Committee endorsed by the Medical Council of Thailand. Thai HD patients receive an adequate dose of HD and nutritional requirement, with an average single pooled KT/V of 1.9, a normalized protein catabolic rate of 1.2 g/kg per day, a serum albumin level of 3.7 g/dL, and a haemoglobin level of 10.8 gm/dL.8 The prevalence of chronic hepatitis B and hepatitis C virus infection among chronic HD patients have been stable at ~4.2% and 2.6%, respectively, and HIV infection is about 0.6%–0.8%. Cardiovascular disease was the leading cause of death, accounting for 44% of HD patients (cardiac cause 36%, cerebrovascular disease 8%), and infection, particularly catheter-related bloodstream infection (CRBSI), was the second most important cause of death (18%).8 The average cost per session of HD is 60 USD, but varies according to the patient's scheme coverage and facility affiliation. The CSMBS and SSS subsidies are 50–57 USD for each session, whereas the UCS subsidy is 40 USD/session.7 Most PD facilities (99%, 198/202) are affiliated with public/governmental hospitals. Thai PD facilities are crowded, with an average PD density of 102 (interquartile range: 48–208),11 and a low automated PD (APD) penetration (5%).12 The physician-to-patient ratio is 64:1, whereas the PD nurse-to-patient ratio is 39:1,12 causing a burgeoning workload for medical staff. Thai PD patients have an average age of 56 years and low education levels and household incomes (lower than $5000/year).13 These parameters are worse in patients located in rural areas. Continuous ambulatory PD (CAPD) is the dominant mode (95%); 82% of CAPD perform 2 L × 4 daily exchanges. The average daily CAPD prescribed, normalized to BSA, is 8.7 L/1.73 m2. While 81% of automated PD (APD) patients have no day dwell with an average total prescribed cycler volume per BSA of 11.0 L/1.73 m2.12 Icodextrin and Neutral pH low GDP solutions are not frequently used in Thailand, <5%.13, 14 The average weekly peritoneal KT/V is 1.73 and 1.75 in CAPD and APD patients, respectively.12 Hypokalemia and hypoalbuminemia are commonly observed in 37% and 67%, respectively.13 The average serum potassium, phosphate and albumin are 3.7 ± 0.6 mEq/L, 4.2 ± 1.5 mg/dL and 3.1 ± 0.8 gm/dL.13, 15, 16 The mean haemoglobin level is 10.2 gm/dL, and 42% have Hb levels below 10 gm/dL.13 Most Thai PD patients are on short-acting erythropoietin, 93% using Epoetin-alpha.7, 17 Over one-half of Thai PD patients require caregivers to assist with their PD exchanges (60%), which likely reflects the high prevalence of functional impairment in PD patients (47%).13, 18 Patients who persistently or subsequently require caregivers to assist with PD exchange are associated with increased mortality risk, but not with peritonitis or HD transfer risk, compared with patients who never need PD caregivers.19 Peritonitis is the leading cause of HD transfer and death in Thai PD patients. The crude peritonitis rate was 0.39 episodes/year and at the upper end of the range reported in PDOPPS (0.28–0.40 episodes/year)11 and complying with the 2022 International Society for PD (ISPD) guidelines target of below 0.4 episodes/year.20 The Gram-negative rate has overtaken the Gram-positive bacterial peritonitis rate (0.12 vs. 0.10 episodes/year),11 and there is a notably high culture-negative peritonitis rate in Thailand (0.11 episodes/year) accounting for 28% of all peritonitis episodes.13 Culture yields from PD effluent are greatly dependent on facility/laboratory practices. There is considerable variability in microbiology laboratories' capacity, capability and practices, with some needing formal accreditation. Deviation from the ISPD guidelines20 is associated with culture-negative peritonitis rates.21 Of interest, Streptococcus is the most common pathogen (12%), followed by Escherichia coli (8%), Staphylococcus aureus (7%) and coagulase-negative staphylococci (6%), possibly due to high prevalence (two-third) of fair-poor patients' oral health hygiene.13, 21, 22 However, the patient and technique survival rates have improved substantially. In 2016, the 1- and 5-year PD patient survival rates were 83% and 54%, respectively,23 compared with the 2012 rate with 1-year patient survival of 79%. These rates are comparable with those of Asia-Pacific countries, including Hong Kong (1-year, 91% and 5-year, 48%), China (1-year, 94% and 5-year, 64%), and Australia (1-year, 89% and 5-year, 39%).24 In addition, the technique survival rates (censored for death and KT) are 95% and 81% in the first and fifth years of PD, respectively.23 The technique survival rate is analogous to the previous reports, including China (1-year, 95% and 5-year, 86%), and Australia (1-year, 70% and 5-year, 10%).24, 25 Moreover, Thai patients have a slightly high health-related quality of life (HRQoL) by the European Quality of Life-5 Dimensions (EQ-5D) questionnaire and 12-item Short-Form (SF-12) of the original 36-item Kidney Disease Quality of Life (KDQOL-36)26, 27 and have moderate to high spiritual well-being score.27 During the past 10 years (2010–2020), the number of Thai patients who underwent KT has been doubled. There are 30 transplant centres in Thailand, currently handling more than 7000 cases with male predominant (60%) and a mean age of 47 ± 13 years.8 Most patients undergo induction therapy with interleukin-2 receptor antagonists (IL2 RA). Calcineurin inhibitor plus mycophenolic acid/mycophenolate mofetil and low-dose corticosteroid is the most common immunosuppression prescribed. Delayed graft function was found in 19% (DDKT) and 5% (LRKT) recipients. Most patients (83%) reimburse their direct KT-related costs from CSMBS (23%), SSO (31%) and UC (27%), while 17% are self-payment and perform their KT at private hospitals.8 Death with a functioning graft is the leading cause of graft loss, followed by transplant rejection. The primary cause of death is infection, followed by cardiovascular disease. Transplant outcomes are comparable to Japan and the US. Graft and patient survival have gradually improved over the past 2 decades. The 1-, 5-, and 10-year graft survival rates of DDKTs and LDKTs in 2022 were 97% versus 98%, 87% versus 95% and 63% versus 79%, respectively.9 Since the dialysis policy in Thailand was reformed last year, causing a rapid flood of HD patients and a rising death toll relating to CRBSI, many concerns are anticipated, including the readiness of the HD service system and access to vascular surgeons, mainly services in rural public hospitals. Currently, sizeable proportions of public HD facilities have to increase HD services to 3–4 treatment shifts per day to accommodate the inflating demand. This surge in demand might shortly create barriers to accessing HD care and increase unplanned HD initiation.28 The burgeoning workload and insufficient HD nurses may lead to burnout, ultimately affecting the quality and safety of HD care.29 In facing the dialysis flood, collective strategic plans must be in the act: (1) early detection and prevention of chronic kidney disease (CKD) progression, (2) promotion of KT and (3) starting dialysis in only suitable patients and implementation of a ‘conservative concept’ modality for those unsuitable. As a global trend, the Thailand dialysis population is continuously increasing and has slowly been overshadowed by non-communicable diseases. There are tremendous gaps between CKD prevention campaigns and KRT promotion policies. Although health stakeholders have promoted the CKD prevention program, it only targets diabetes, hypertension and obesity. The lack of local CKD registries and a limited number of kidney pathologists (as evidenced by unknown-aetiology kidney failure accounting for 25%) have prevented individuals at high risk of CKD from being identified accurately, and this crucial information is needed for more effective advocacy. Additionally, many CKD patients rely on alternatives, including buying medicines over the counter for symptom relief or purchasing alternative medicines marketed as curative, causing late referral to nephrologists. Our overarching goal is an integrated approach with the prevention, early detection and aetiology identification of CKD measures. At the same time, statewide promoting and improving health literacy and sustainable development are needed for more effective advocacy. The decision to KRT modality should be individualized in a timely shared decision-making process with unbiased information on KRT options to ensure a timely dialysis access preparation and avoid unplanned dialysis initiation.28, 30 Despite universal coverage, the residual financial burden remained high in dialysis patients. Of note, the expenditure from out-of-pocket HD spending was 2 times greater than those with PD, mainly related to travelling expenses.31 A recent cost–benefit study applying the concept of willingness to pay on current real-practice costs found that the ‘PD-First’ policy is more cost-effective than the ‘Free-Choice Dialysis’ policy given the willingness to pay threshold of 4766 USD.32 Home-based PD is more cost-effective than in-centre HD and should be promoted, especially in low-resource settings. KT, especially preemptive LDKT, should be offered in suitable patients since it provides better survival and quality of life and is more cost-effective than dialysis.30, 33 Although there is a notable increase in deceased donors (DD), the organ donation rate remains low at 4.5 pmp compared to Western countries. Most DDs come from upcountry, where most local hospitals need a designated donor care and retrieval team. Organ procurement is usually performed by a team travelling from the transplant centre, mainly in Bangkok. The transportation of the procurement team and organs over long distances requires commercial flights, which may only sometimes be available, resulting in the high prevalence of donor hypotension and relatively long cold ischemic time. Developing of regional retrieval team in upcountry public hospitals might solve this obstacle. Additionally, LDKTs have progressively declined over the last 6 years. Pretransplant donor biopsy-based marginal donor allocation system initiatives may expand the donor pool during the shortage. Since ageing is a global trend, there is a growing need to expand KT in the elderly population. An increasing number of transplants for the elderly may be necessary to meet the demand. Implementation of longevity matching is rolling to maximize the utilization of DD kidneys. Since PD is cost-wise, a tantalizing KRT option for countries with constrained kidney failure budgets, introducing the ‘PD-First’ policy in 2008 is an important initiative to close the access to health services gap between the and the after years the of between and solutions for kidney failure patients. it is to CKD and and patients KRT with a concept, and KT in suitable to annual KRT and this of KRT in the Thai population. the and of KRT in Thailand are by and there is for in the years to the of all health and from the centres who by in ‘PD-First’ policy, Thailand Renal Replacement Therapy and Thailand A thanks to the Society of Thailand, Thai Transplant Society, Kidney Foundation of Thailand, Thailand Organ Donation Center Red Cross and Thai has from and as country and is a current of the National Council of Thailand and from and The that the article was commercial or financial that could be as a of

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