End-stage renal disease (ESRD) is a world-wide public health problem. The prevalence and incidence of ESRD are increasing both in the developed and the developing countries, and this will place an enormous financial burden for health-care systems due to the cost of the the management of these patients.123456 For example, in the United States (US), the number of patients enrolled in the ESRD Medicare-funded program has significantly increased in recent years from approximately 10,000 patients in 1973 to 527,283 patients in 2008.6
In addition, according to the Registry of the European Renal Association (EDTA-ERA), the number of ESRD patients receiving renal replacement therapy in Europe at the end of 1993 was 197,721 compared with 70,950 in 1981.3
Although the exact reasons of rising the prevalence of patients with ESRD are unclear, it can be attributed to the increased prevalence of diabetes mellitus (DM) and hypertension (HTN), which are the most common causes of ESRD, improved survival from non-renal diseases (particularly cardiovascular and malignant diseases), increased survival of patients with ESRD and relaxed criteria for entry into ESRD programs.7891011
Because of the rapid increase in the prevalence of ESRD, it is medically and economically imperative to have increased awareness for detection, management and planning prevention strategies to be introduced in developed and developing countries. This will require new updated epidemiologic data about the disease. In the past few decades, there have been significant changes in the epidemiologic aspects of ESRD across the world, particularly in the developing countries, and the aim of this review article is to evaluate the epidemiologic aspects of ESRD in Iran, a developing country.
Materials and Methods
For this review, a variety of sources were used by searching through PubMed, Embase, Scopus, Current Content and Iran Medex from January 1990 up to September 2011. The search was performed using several pre-defined combinations of the following key words and their equivalents: "hemodialysis," "dialysis," "peritoneal dialysis," "kidney transplantation" in combination with "epidemiology" and "Iran." Articles published in English language, as full-text manuscripts and as abstract form about the epidemiology of ESRD in Iran were included in the study, although we did not specifically hand search conference proceedings.
Demographic Data of ESRD in Iran
Iran is the most populous country in the Middle East, with a population of approximately 75,000,000 and covering an area of 1.65 million km2. Majority of the people (68%) in Iran are between 15 and 64 years, 14% are younger than 14 years and 4.9% are older than 64 years. The life expectancy and the population growth rate are 69.96 years and 0.86%, and the gross domestic product per capita is approximately US $12264 .1213
According to the report of the Management Center for Transplantation and Special Diseases (MCTSD) of Iran, the total number of patients with ESRD undergoing renal replacement therapy (RRT) in 2007 was 32,686, which denotes a prevalence of 435.8 per million population (pmp). This number is very high compared with 1997 and 2000, when the prevalence of ESRD was 137 pmp and 238 pmp, respectively. The incidence of ESRD patients also seems to be increased, from 13.82 pmp in 1997 to 49.9 pmp in 2000 and 63.8 pmp in 2006. It is possible that the increase is due to the increased recognition of the disease due to the increase in the number of hemodialysis centers (150 in 1997, 227 in 2000 and 316 in 2006), kidney transplantation centers, transplantations (22.8 pmp in 1997 to 26.5 pmp in 2006) and nephrologists in our country.12131415 Although the prevalence and incidence of ESRD are increasing in Iran in recent years, they are still low compared with the developed countries, which may suggest poor referral and the ensuing under-diagnosis of ESRD.
The mean age of men and women with ESRD has also increased in Iran in recent years compared with the past few decades. By use of data of the national registry of Iran's ESRD provided by the Ministry of Health, Aghighi et al retrieved detailed demographic data of 35,859 ESRD patients between 1997 and 2006. According to the results of this epidemiologic study, the mean age of men and women ESRD patients was 47.0 and 49.0 years in 1997, which increased to 52.5 and 53.0 years, respectively, in 2006. The male-female ratio of 1.3:1 during the period of study remained without significant changes.12
What is the Difference between Causes of ESRD in Iran and Developing Countries?
Although there are many studies about the etiology of ESRD in developed countries, there is lack of data in developing countries and also in Iran. In the past few decades, different forms of glomerulonephritis (GN) were the most common causes of ESRD in the world. However, possibly because of the increasing prevalence of obesity, diabetes and HTN, and because of more aggressive treatment of GN, it is being reported that type 2 diabetic nephropathy and hypertensive nephro-sclerosis are now the major causes of ESRD in developed countries.1617181920
Only a few studies have been performed to ascertain the primary causes of ESRD in Iran, and they have demonstrated that DM and HTN are the leading causes. For example, Beladi Mousavi et al have shown that these two diseases have in together 50 or more than 50% causative roles in the Khuzestan province of Iran.212223 Aghighi et al have also demonstrated that diabetic nephropathy and hypertensive nephrosclerosis are the most common causes of ESRD in Iran. The results of Aghighi et al's study showed that the percentage of ESRD patients attributed to DM increased from 16% in 1997 to 31% in 2006.24 Nobakht et al and Malekmakan et al have also reported similar results.1425
There is an important question about this issue now. Is there any difference between causes of ESRD in the above studies that were carried out in Iran and developed countries? The answer to that question is "YES," and there is an important difference between the causes of ESRD in Iran and developing countries. In contrast to the United States and other developed countries, the cause of ESRD in the significant percent of patients with ESRD in Iran, as we see in the results of the Beladi Mousavi et al study in 2010, is due to unknown etiology (27%).21 The results of Nobakht Haghighi et al's study in 2002,14 Salahi et al's study in 2004,26 Aghighi et al's study in 200920 and Malekmakan et al's study in 2009,25 which were carried out in Iran, also have similar findings.
In our country, and also in most of the developing countries like ours, patients with chronic kidney diseases present in the hospital only when they have severe symptoms of uremia, and, at this time, determining the primary cause of ESRD is not possible. The size of the kidney in most of the patients with ESRD is small and therefore kidney biopsy is associated with increment risk and histologic findings of kidney biopsy at the late stage of chronic renal failure shows glomerulosclerosis, interstitial fibrosis and tubular atrophy regardless of the etiology and therefore one cannot determine the cause of chronic kidney disease at late stages.2728
In conclusion, it appears that diabetic nephropathy and hypertensive nephrosclerosis are the most common causes of ESRD in Iran, similar to developed countries. But, possibly because of late presentation and late referral of patients with ESRD to the specialists, the cause of ESRD in the significant percent of patients in our country is due to unknown etiology, in contrast to the United States and other developed countries.
Renal Replacement Therapy in Iran
RRTs including hemodialysis, kidney transplantation and peritoneal dialysis were started in Iran in 1964, 1968 and 1975, respectively. At present, the most common RRT modalities in Iran are kidney transplantation (48.8%) and hemodialysis (47.7%). Peritoneal dialysis plays a marginal role, and the proportion of ESRD patients treated by peritoneal dialysis is approximately 3.5%.12131415
Hemodialysis is mainly performed in hospital centers in the presence of nursing staff, and home hemodialysis is not performed. In addition, almost all of ESRD patients undergoing hemodialysis are receiving conventional inter-mittent hemodialysis. Continuous arteriovenous or venovenous HD, hemofiltration and hemo-diafiltration were not being performed till recent years.
Almost all of the hemodialysis centers were using acetate as a buffer until 2000. After that, bicarbonate-based hemodialysis was started and according to the positive feedbacks of this program, the number of centers using bicarbonate increased gradually with a 63% coverage of all hemodialysis sessions in 2006. By use of bicarbonate, the prevalence of hypotension during hemodialysis has decreased, the increase of dialysis blood flow rate is better tolerated with a higher urea reduction ratio and better Kt/V values.
The majority of hemodialysis centers are using synthetic membranes (polysulfone membranes in 70% of patients and cuprophane in 30%). The use of high-flux dialyzers started in late 2006, and it has covered only 15% of patients on hemodialysis.12131415
The first renal transplantation was performed in Iran from a live donor in 1967 and, till 1998, the main source of kidney donations was living-related donors. Although kidney transplantation in Iran started from living-related donors, due to the large number of ESRD patients with no living-related donor, and absence of a national cadaveric transplantation program, a regulated living non-related donor renal transplant program was adopted in Iran in 1998.
After that, the rate of renal transplantations from non-related donor increased, which caused significant improvement of the renal transplant waiting list and, today, the main source of kidney donations is living non-related donors. According to the Ghods et al study, a total of 21,251 renal transplants have performed in Iran from 1967 to 2006, and most of them (78%) are from living non-related and only 17% and 5% are from living related and deceased donors. Currently, the rate of kidney transplantation in Iran is 24 pmp, which is comparable to developed countries (20-40 pmp).293031
Compared with hemodialysis and renal transplantation, peritoneal dialysis is a young modality of RRT and has a minor role in the treatment of patients with ESRD in Iran. At present, continuous ambulatory peritoneal dialysis (CAPD) is the only modality used and automated PD is not available.13
According to the report of the Iran dialysis center, the proportion of patients with ESRD treated by PD was less than 1% (2 pmp) in 2000; this number increased to approximately 2.5% (9.7 pmp) in 2005 and 3.6% (6.8% of total dialysis patients) in 2006.
The majority of ESRD patients are considered for CAPD because they are not to be accepted for other modalities (hemodialysis and transplantation) due to poor cardiac function, poor vascular access, etc. Therefore, they are undergoing peritoneal dialysis based on negative selection with the presence of much comorbidity. Thus, poor results could be expected and they have lower survival compared with those under other modalities.13
Survival of Patients with ESRD in Iran
Although maintenance dialysis prevents death from uremia, survival of patients with ESRD is much worse than the general population.2332333435363738 As an example, according to the report of the United States Renal Data System (USRDS), the survival of patients with ESRD undergoing maintenance dialysis is approximately eight years (varies with race) for those aged 40-44 years, and approximately 4.5 years for those 60-64 years of age. These values are far below those of the general population (wherein the range of the expected remaining life span is 30-40 years for individuals aged 40-44 years and 17-22 years for those aged 60-64 years).32
Although many studies on the survival of these patients have been carried out in developed countries, there are limited data from Iran. In our research, we found only a few articles that evaluated the long-term survival of patients on maintenance dialysis in our country. Beladi Mousavi et al analyzed the survival of 185 adult ESRD patients on maintenance hemodialysis. Overall, regardless of the cause of ESRD, the 1-, 3- and 5-year survival of patients was 89.2.0%, 69.2% and 46.80%, respectively, and there was no significant difference between males and females, blood groups and various insurance organizations in the survival of patients. In addition, there was no significant difference between diabetic and non-diabetic patients in 1-year survival. But, the 3-year survival of diabetic patients was significantly lower than that of non-diabetic patients (52.2% vs. 73.8%), and none of the diabetic patients had a 5-year survival in this study (0% vs. 56.9%).23
In the other article, Beladi Mousavi et al evaluated the long-term survival of 1312 ESRD patients referred to nine hemodialysis centers in southwest Iran. In this multicenter study, the 1-, 3-, 5-, 7- and 10-year survival of diabetic and non-diabetic patients were 70 vs. 82%, 26.9 vs. 50.7%, 9 vs. 28.6%, 3.3 vs. 13.6% and 0.6 vs. 4.5%, respectively. The survival of diabetic patients was also significantly lower than that of non-diabetic patients (P <0.001). As we see in the above two studies, the survival of ESRD patients, especially diabetic patients, is catastrophic and is much lower than that from many centers in the developed countries like UK, Europe, Japan and France. For example, the 5-, 10-, 15- and 20-year survival of ESRD patients on maintenance hemodialysis in Tassin, France was 87%, 75%, 55% and 43%, respectively, which is much longer than that of our country.34 However, the survival of patients in the Beladi Mousavi et al study was approximately similar to the report of the USRDS in 2009, where the 1-, 3-, 5- and 10-year survival of ESRD patients on maintenance hemodialysis in the US is 79%, 53%, 35%, and 11.2%, respectively.39
In conclusion, according to the report of the Management Center for Transplantation and Special Diseases (MCTSD) of Iran, the prevalence and incidence of ESRD have significantly increased in Iran in recent years; however, they are still lower compared with developed countries, which may suggest poor referral and under-diagnosis of ESRD patients and therefore it is safe to predict that the demand for RRT will increase in the future. The cause of ESRD in the significant percent of patients in Iran is unknown, and is possibly because of late referral of these patients to the specialists, which also points to the necessity of improved pre-ESRD work-up. In addition, kidney transplantation and hemodialysis is the most common RRT modality used in Iran, and the proportion treated by peritoneal dialysis is very low. It is very interesting to note that the main source of kidney donations is living non-related donors, and a negligible proportion of patients receive renal allograft from living related and deceased donors in Iran.
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