Global Dialysis Perspective: North Macedonia

Introduction

North Macedonia is a small landlocked country located on the Balkan Peninsula in Southeast Europe with a population of around 2 million inhabitants (Figure 1).¹ The World Bank classifies North Macedonia as an upper–middle-income economy with a gross domestic product (GDP) of 13.88 billion US dollars in 2021.² The country has a social insurance–based health system operated by the Health Insurance Fund (HIF) which is responsible for the collection of contributions, allocation of funds, and supervision and contracting of providers. The Ministry of Health has a central role in the decision-making process in most health-related activities, whereas the Ministry of Finance determines the HIF budget. About 88% of the HIF's revenues come from health insurance contributions for salaries, and the other constituted percentage is transferred from the Ministry of Labor and Social Policy for maternity leaves.³ The number of insured persons in North Macedonia ranges from 85% to 96% and is comparable with other countries in the region (Bulgaria, Croatia, and Slovenia).⁴ People lacking health insurance in the country are predominantly individuals without regular employment or employees with delays in the payment of their salaries, individuals employed in international organizations who have international private health insurance, or individuals without documents.⁴ The HIF covers broad basic packages of emergency care, primary and secondary outpatient care, inpatient care, and preventive and rehabilitation services by providers contracted by the HIF. Health expenditures as a percentage of GDP fluctuated in the previous two decades from 6% to 10% and decreased from 8.9% in 2000 to 7.3% in 2019. Health expenditure per capita in 2018 amounted to 1.073 US dollars purchasing power parity and was below the average of neighboring European countries (US$ 1419 PPP).³

Figure 1: Location of North Macedonia and distribution of HD centers. SER, Serbia; GRE, Greece; TUR, Turkey; ITA, Italy; ROM, Romania; CRO, Croatia; BIH, Bosnia and Herzegovina.

Description of Renal Replacement Therapy in North Macedonia

CKD is an international health problem, and around three million patients are currently receiving RRT. This number is expected to increase from 5 to 10 million by 2030.⁵ In the past decade, as in other countries, the number of patients who required RRT in North Macedonia was continually increasing and reached nearly 926.5 per million population (pmp) by the end of 2019 (Figure 2). According to the annual reports from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) registry, from 80% to 85% of patients were treated with hemodialysis (HD) as one of the modalities of RRT in the last years. The mean age of patients was 59.2±9.5 years (median 60.4 years), and 60.2% were male. Half of the patients (50.0%) were in the age group of 45–64 years. Hypertension (25.8%) and diabetes mellitus (17.4%) were the leading causes of CKD in patients requiring RRT (Table 1). The annual register data of ERA-EDTA for 2019 showed that the number of patients on HD was 774.5 pmp, from which only one patient used home HD 0.5 pmp.⁶ The continual increase in the number of HD patients is primarily due to better quality of HD and longer patients' survival compared with the results in the year 2008 when the average 5-year survival of patients on HD was 60%.⁷ The incidence of patients with RRТ in 2016 was 249 pmp and followed an upward trend until 2020 when it dropped to 184 pmp.⁶ The decrease in the number of new patients is thought to be due to coronavirus disease 2019 (COVID-19) pandemic and the higher mortality of patients with CKD.⁸ Peritoneal dialysis (PD) was first initiated in 1995 in children and in 1996 in adults.⁷ In our country, PD is infrequently used and is usually reserved as a very last resort for patients with no vascular access. The poor development of PD is a consequence of the existence of a widespread network of HD centers, the absence of patients' motivation, and the lack of a national development program for promotion of PD. In 2021, only 17 adult patients (Figure 2) were treated with PD and four children on automated PD. The living donor kidney transplant (KTx) in our county was first indicated in 1977, but without a real continuum in the following years. In the period from 1985 to 1987, 15 cadaveric KTxs were made, followed by an average of 6.75 pmp living donor KTxs per year in the period 1996–2011.⁷ The involvement of North Macedonia in the South-Eastern Europe Health Network initiative and Regional Health Development Center on Organ Donation and Transplant Medicine form 2011 was shown to be successful for improvement of transplantation program and historic increase in the number of KTx in the next 3 years (from 12 pmp in 2012, 17.5 pmp in 2013, and 20 pmp in 2015) with 7.5 pmp cadaveric KTx.⁷ In the past few years, even during COVID-19 pandemic, the KTx program from living and deceased donors has retained the aforementioned success. The total number of KTx recipients alive with a functional graft reached 115.5 pmp patients in 2020.⁶

Figure 2: Number of patients with RRT per year for North Macedonia.

Table 1 - RRT trend in the past 6 years in North Macedonia

Years	Total	Men	Women	0–19	20–44	45–64	65–74	75+	Etiology of Renal Disease								Type of RRT
				Total	Total	Total	Total	Total	GN	PN	PKD	DM	HTA	RV	Mis	Unk	HD	PD	Tx
2020	1762	1085	677	10	238	816	448	250	263	124	166	312	473	6	171	247	1514	17	231
2019	1853	1114	739	8	245	849	489	262	284	141	176	329	483	19	183	238	1608	17	228
2018	1756	1061	695	12	256	850	405	233	296	168	157	304	454	3	144	230	1488	19	249
2017	1761	1048	713	9	256	852	396	248	297	160	166	200	446	2	142	248	1521	22	218
2016	1665	989	676	10	248	822	366	219	290	152	163	273	414	3	155	215	1433	25	207
2015	1598	929	669	10	265	790	343	190	253	125	165	245	389	2	216	202	1353	32	213

PN, pyelonephritis; PKD, polycystic kidney disease; HTA, hypertension; RV, renovascular disease; Mis, miscellaneous; Unk, unknown; HD, hemodialysis; PD, peritoneal dialysis; Tx, transplantation.

HD Centers in North Macedonia

Since 2014, HD management in North Macedonia has been provided in 90% through public-private partnerships by long-term collaboration, whereby private providers typically invest in physical and digital infrastructure and required human capital to provide service. The rest 10% are provided by public hospitals and clinics.⁹ North Macedonia has a total area of 25.713 km² (9928 sq mi) with an excellent coverage of 23 HD centers throughout the whole territory (Figure 1). The first HD in North Macedonia was performed in 1959 on a patient with AKI. In the beginning, HD was performed only on patients with AKI until May 1971 when the program of maintenance HD was started.⁷

HD Characteristics

HD dialysis session is an important factor for patients' survival. In our country, conventional HD sessions are usually performed for at least 4 hours, 3 days per week. In some patients with poor interdialysis compliance, HD sessions are performed more frequently or with longer duration than usual. All dialysis sessions for patients with health insurance are covered by the HIF, and patients do not have additional out-of-pocket expenses. In addition, patients who require additional dialysis during the week do not pay anything. The frequency and long duration of HD are in accordance with Kidney Disease Outcomes Quality Initiative guidelines.¹⁰

Dialysis Quality Indicators for Meeting Clinical Practice Guidelines

With regards to human resources in the health sector, there is a persistent lack of physicians and nurses in our country. However, in the past years, the number of physicians increased from 269 per 100,000 population in 2010 to 312 per 100,000 in 2019, approaching the endotoxin units average of 382 per 100,000 population. The number of nurses also increased, from 340 per 100,000 population in 2010 to 440 per 100,000 population in 2019.³ Regarding the current number of nephrologists, our country has 20 pmp including eight professors at the Faculty of Medicine, Ss. Cyril, and Methodius University in Skopje, North Macedonia. Similar data have been presented by International Society of Nephrology (ISN) for West Europe at 22.9 pmp (range 9.47–55.75 pmp). Most of the nephrologists in North Macedonia had successfully completed international education programs and fellowships organized by ERA-EDTA and ISN.¹¹ In clinical practice, there should be at least one dialysis nurse per every eight patients and one dialysis technician per every three patients.¹² In our dialysis centers, the patient-to-register nurses ratio is 4:1 which is in accordance with the recommendation. The entire medical staff involved in the process of dialysis is professionally educated and with great experience in this field. Patients also have regular nephrological control at least once a week. Almost all dialysis centers have a nephrologist or internist/specialist in nephrology or internal medicine who is in charge of patients' health condition but is also responsible to perform mandatory medical examinations. The adequacy of dialysis sessions is monitored by Urea Reduction Ratio and K×T/V performed every 3 and 6 months.

Vascular Access for HD

Vascular access is a gate of life for patients on HD. An arteriovenous fistula (AVF) is a golden standard as a first option, but central venous catheters (CVCs) are also widely used as another option. Interpreting data related to vascular access in the available literature is heterogeneous and lack standardization in outcomes.¹³ Therefore, the best vascular access for every patient depends on more factors such as health condition, life expectancy, etiology of renal disease, the diameter of blood vessels, HD vintage, and sex. In our country, the strategy for creating a permanent type of vascular access is AVF first. Therefore, almost 80% of patients use AVF, around 14% of patients use permanent CVC, and the rest use temporary CVC.¹⁴ The number of patients who use arteriovenous graft is <1%. On the other hand, most patients begin on HD with temporary CVC, and only a very small number of patients start with preventive AVF.

Cost and Funding of Dialysis Services

The treatment of patients with ESKD remains an international issue. There is a continuous increase in health expenditures worldwide, but still HD is the most frequently used and the most expensive treatment modality. Thus, in the United States, nearly 400,000 patients are currently treated with HD, with Medicare payments approaching $90.000 per patient per year of care in 2011.¹⁵ In addition, the result of Panama for 2015 showed that the total costs for dialysis in the public sector ranged from 7.9 million US$ for PD to 62 million US$ for HD. In accordance with the aforementioned and based on the annual report of HIF for 2021, North Macedonia spent a total of 21.561.314 US$, approximate cost for one patient being 13.793 US$ per year.⁹ The reimbursement rates from 2012 to the present day have minimally changed and amount to almost 95 US$ for HD and 133 US$ for hemodiafiltration (HDF) per session. It should be emphasized that HDF as a chronic modality is used in 10% of all patients with chronic HD. On the other side, the total cost for one patient for continual ambulatory PD is 1.420 US$ per month or 1.706 US$ for automated PD.⁹

In conclusion, ESKD is a significant and continually growing health and financial burden for many countries worldwide, including North Macedonia. HD is the most frequent modality of RRT used in our country. The network of HD centers is highly developed and provides HD treatment closest to the patients' place of residence. The chronic HD treatment of patients in North Macedonia is performed successfully, which provides long and good survival for the patients. They have normal lives and families. In the following years, the stakeholders in North Macedonia should make an effort to increase the number of patients with home HD and the number of KTxs, especially from a deceased donor. It is important to develop a national program for the promotion of PD to increase the number of patients.