Vol 13 No 04 July-August 2016 2744 REVIEW Evaluation of Dialysis Adequacy in Hemodialysis Patients: A Systematic Review Hengameh Barzegar1, Mahmood Moosazadeh2, Hedayat Jafari3, Ravanbakhsh Esmaeili4* Purpose: Hemodialysis is the common kidney replacement therapy in Iran. Doing an adequate and effec- tive dialysis can improve patients’ quality of life and reduce kidney failure complications. Additionally, dialysis quality is an important factor in reducing mortality in patients with chronic kidney failure. This sys- tematic review has investigated the adequacy of dialysis in studies done on hemodialysis patients of Iran. Materials and Methods: All articles related to the dialysis adequacy in hemodialysis patients in English and Farsi (contemporary Persian) were identified by searching the related keywords in various electronic databases. Accord- ing to the inclusion criteria, 21 studies were identified. The results were analyzed using Stata software version 11. Results: A number of 6677 patients had been enrolled in 21 studies that were chosen for this systematic review. Based on the random effects model, the overall dialysis adequacy (KT/V) (K: clearance of urea, T: duration of dialysis, V: distri- bution of urea) more than 1.2 and its confidence interval were 36.3% and 26.4-46.2, respectively. Also, based on random effects model more than 65% urea reduction ratio in all studies was 28.8% and the confidence interval was 14.4-43.3. Conclusion: KT/V and urea reduction ratio were much less desirable in hemodialysis patients and the dialysis quality was also undesirable. It seems that inadequate dialysis prescription, use of inappropriate filters, low pump speed (blood flow speed), and the short duration and few times of dialysis are the major causes of this inadequacy. Keywords: dialysis adequacy; hemodialysis; systematic review; kidney failure INTRODUCTION Increased burden of chronic diseases is an existing challenge in the health systems worldwide.(1) Chronic kidney failure is a progressive and irreversible disorder in the kidney function in which the body's ability to main- tain fluid and electrolyte balance and metabolic waste excretion is lost, ultimately leading to uremia.(2) The ad- vanced stage of the disease is known as end stage kidney disease.(3) Until the middle of twentieth century, people who suffered from the kidney failure were helpless people who were waiting for their fate, but not death.(4) Today, in Iran and many countries, the most common treatment method is hemodialysis. The purpose of dialy- sis is to remove the excess material and stabilize body’s internal environment as well as removing the toxins that cause permanent injury.(5) By the end of 2014, 70% of patients with chronic kidney failure were on hemo- dialysis. Also by that time the number of dialysis pa- tients in Iran was around 27,457 people, of which about 25,934 patients (94%) were treated by hemodialysis.(6) Several factors affect the survival in end-stage kidney disease patients including the cause of disease, alter- native medicine, synchronism of other diseases such as cardiovascular disease and dialysis adequacy.(7) Dialysis quality is a predictor of mortality in dialysis patients. Evidences suggest that when there is enough 1 School of Nursing and Midwifery, Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran. 2 Health Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran. 3 Department of Medical-Surgical Nursing, Mazandaran University of Medical Sciences, Sari, Iran. 4 Department of Medical-Surgical Nursing, Orthopedic Research Center, Mazandaran University of Medical Sciences, Sari, Iran. *Correspondence: Department of Medical-Surgical Nursing, Orthopedic Research Center, Mazandaran University of Medical Sciences, Farahabad Road, Sari, Iran. Tel: +98 113 336 7341. Fax: +98 113 336 7341. E-mail: r.esmaeili90@gmail.com. Received December 2015 & Accepted February 2016 effective hemodialysis treatment, there is less mor- tality in patients with kidney disease.(8) By improving the dialysis adequacy, uremic complications and their effects on different organs will be reduced. Therefore, increasing dialysis quality is effective on various as- pects of life in patients with chronic kidney failure. If it is improved, a lot of physical health problems and subsequent psychosocial problems will be solved.(9) The most accepted methods for determining dialy- sis adequacy are the KT/V standard (K: clearance of urea, T: duration of dialysis, V: distribution of urea) and urea reduction ratio (URR).(10) According to Re- nal Physicians Association and the National Kidney Foundation’s disease outcomes quality initiative, the dialysis quality results using KT/V and URR are pre- ferred because they reflect urea removal more accurate- ly. Several studies have shown that if the rate of KT/V reaches 1.2 or URR is more than 65%, this is effective in improving dialysis patients’ prognosis.(11) Today, do- ing a correct and reasonable dialysis can prevent many complications and also by preventing repeated hospital stays and applying the savings on healthcare costs, it can provide better quality of life for dialysis patients.(12) There are different statistics about dialysis adequacy in Iran and there is still no general estimation. According to electronic searches, several studies with different Vol 13 No 04 July-August 2016 2744 number of patients have investigated dialysis adequa- cy in different dialysis centers of Iran. The rising trend of chronic kidney disease and absence of adequate di- alysis are the main causes of death in kidney patients. Thus, determining dialysis adequacy in hemodialysis patients can help to develop better healthcare. This study has systematically reviewed the studies which had been conducted on dialysis adequacy in Iran. MATERIALS AND METHODS The dialysis adequacy (KT/V and URR) in hemodi- alysis patients of Iran was estimated by a systematic literature review. The indexed articles in the available databases, including Magiran, scientific information database of Iran (SID), Google Scholar, Iranmedex, and Pubmed central, were used to find published studies on the subject. All studies were published in English and Farsi (contemporary Persian) between October 2000 and October 2014. The search was undertaken mainly using keywords of dialysis adequacy in these two lan- guages including hemodialysis adequacy, hemodialysis efficiency, and Iran with all possible combinations. The search with essential keywords was done using ‘and’ and ‘or’. The search was carried out from 24 to 28 Oc- tober 2014 by two researchers independently. Search evaluation was done by a member of the research team. The reference list of published studies was also stud- ied to increase sensitivity and find the more articles. Inclusion and exclusion criteria The full text or abstracts of all papers and documents from the search were extracted. First the articles were evaluated based on title, author name, year and publica- tion place and duplicates were removed. Then, the ar- ticles were carefully studied by researchers and the re- lated articles were selected. Then irrelevant cases were removed. All studies were evaluated by the checklist. The list was designed using the contents of strengthen- ing the reporting of observational studies in epidemiolo- Dialysis adequacy in hemodialysis patients- Barzegar et al. Table 1. Characteristics of studies included in this systematic review First Author Year Journal Title Language Number of patients KT/V > 1.2 URR > 65% Percentage Percentage 1 Lesanpezeshki M 2001 CE(1380 H) Feyz Persian 37 18.9 - 2 Delavari A.R 2001 CE (1380 H) Sci J Kurdistan Persian 62 21.1 - Univ Med Sci 3 Shahbazian H 2002 CE (1381 H) Sci Med J Persian 74 - - 4 Taziki O 2003 CE (1382 H) J Mazandaran Persian 50 - - Univ Med Sci 5 Mozafari N 2005 CE(1383 H) Res Sci J Ardabil Persian 70 10 - Univ Med Sci 6 Afshar R 2006 CE(1385 H) Iran J Pathol English 54 33.3 11.1 7 Mousavi Movahed T 2007 CE(1386 H) Qom Univ Med Sci J Persian 238 44.5 21 8 Monfared A 2008 CE(1387 H) J Guilan Univ Med Sci Persian 139 76.3 72.7 9 Pourfarziani V 2008 CE (1387 H) Saudi J Kidney English 338 - - Dis Transpl 10 Hojat M 2009 CE(1388 H) J Crit Care Nurs Persian 68 - - 11 Raiesifar A 2009 CE(1388 H) J Crit Care Nurs Persian 45 2.3 6.6 12 Malekmakan L 2010 CE(1388 H) Iran J Kidney Dis English 632 32.1 - 13 Shariati A.R 2010 CE (1389 H) J Gorgan Univ Med Sci Persian 113 77.9 - 14 Moghareb M 2010 CE(1389 H) J Birjand Univ Med Sci Persian 50 5 6 15 Amini M 2011 CE(1389 H) Iran J Kidney Dis English 4004 43.3 - 16 Mohseni R 2011 CE(1390 H) Hayat Persian 50 14 10 17 Shasti S 2011 CE (1390 H) Ebnesina Persian 100 50.5 46 18 Hashemi M 2012 CE(1391 H) J North Khorasan Persian 63 47.5 36.1 Univ Med Sci 19 Shariati A.R 2012 CE(1391 H) JHPM Persian 389 57.9 56.3 20 Abedi Samakoosh M 2013 CE(1392 H) J Mazand Med Sci Persian 60 41.7 20 21 Roozitalab M 2013 CE(1392 H) Life Sci J English 41 41.5 31.7 Abbreviation: URR, urea reduction ratio. Review 2745 Vol 13 No 04 July-August 2016 2746 gy (STROBE) list. The checklist included 12 questions that covered aspects of study design, sample size, age groups, sampling, objectives, study population, inclu- sion and exclusion criteria, matching samples method, analysis method, and presenting findings appropriately. Each questions had one point and any study that had at least eight points entered our systematic review. All Far- si and English articles that determined dialysis adequacy in hemodialysis patients with KT/V standard > 1.2 and URR > 65% between 2000 and 2014 in Iran were select- ed. Studies which access to their full text was not possi- ble, had insufficient data, were publish before 2000, and were related to dialysis adequacy with variables such as quality of life and quality of sleep were excluded. Data extraction Data were obtained for each of the original studies by re- searchers based on the title, name of the first author, publi- cation year, place of study, study design, sample size, av- erage age of the population, KT/V > 1.2, and URR > 65%. Statistical Analysis Data were transferred to the Stata software version 11 for analysis. The standard error for dialysis adequacy of patients in each study was calculated on the basis of a binomial distribution. The index of dissimilarity or heterogeneity between the studies was determined using Cochran (Q). According to the heterogeneity using the Meta command (Meta) in the meta-analy- sis the random effects model was used to assess dial- ysis adequacy. Additionally, to minimize the random distribution of studies’ point estimates, all studies’ findings were adjusted using the Bayesian analysis. The point estimate of the dialysis adequacy with 95% confidence interval was calculated in the accumu- lation graph (forest plots) that was the square size in this chart and it represented the weight of each study and for both sides with 95% confidence interval. RESULTS By searching in the databases including SID (68 cas- es), Magiran (55 cases), Pubmed (74 cases), Iranmedex (55 cases), Scopus (40 cases), Science direct (45 cases) and Google scholar (347 cases), a total number of 684 studies were found. By limiting the search with ‘and’ and ‘or’ operators, the number of articles was decreased to 342. In the initial review of the studies, 134 articles were excluded because they were duplicates, 145 stud- ies were also excluded due to being non-relevant to the topic. In the second review after reading the abstracts and texts of 63 articles, 41 studies were again exclud- ed. Two articles with a review of relevant articles were included in the study. Three researches were excluded after evaluating their full texts and lack of sufficient data. Finally, 21 articles that had the required crite- ria for a systematic review were included (Figure 1). Among the 21 articles in our systematic review, 20 stud- ies were analytical and descriptive and only one study was a comparative study. 16 articles were in Farsi and five were in English. The details of the included studies are illustrated in Table 1.Thus, in this systematic review the dialysis adequacy was studied in 6677 hemodial- ysis patients. Optimal dialysis adequacy (KT/V more than 1.2) was from 2.3% in Raisifar et al. study with 45 patients to 77.9% in Shariati et al. study with 113 pa- tients. The overall dialysis adequacy was also estimat- ed using a random effects model (I-squared = 98.1%, Q = 822.6, P < 0.001), (26.4-46.2, 36.3%) (Figure 2). URR was between 5% in Moghareb’s study and 72.7% in Monfared’s study. Additional- ly, the URR of all studies was estimated using random effects model (I-squared = 97.5%, Q = 396.5, P < 0.001), (14.4-43.3, 28.8%) (Figure 3). The secondary objectives were also evaluated in the studies including: sex, age, dialysis times per week and its duration. The relationship between gender and dialy- sis adequacy was assessed in the reviewed studies. Nine studies showed significant differences.(8, 11-18) Dialysis ad- equacy was higher in women than men and also no signif- icant difference was observed in seven researches.(9, 19-24) The average ages of the studied populations in all studies were from 47.07 years in the Ruzitalab’s study in Yasouj to 62.27 years in Shasti’s study in Tehran. A significant difference was observed in two studies which had investigated the relation- ship between age and dialysis adequacy. Thus dial- Figure 2. Frequency of KT/V > 1.2 in hemodialysis patients in each study and the overall estimate. Abbreviations: CI, confidence interval; ES, effect size. Figure 1. Flow chart of selecting studies for review. Dialysis adequacy in hemodialysis patients- Barzegar et al. ysis adequacy had reduced with increase of age.(11,25) The relationship between dialysis times per week and dialysis adequacy was significant in three studies.(11,12,23) The studies showed that patients who were on dialysis three times a week had a higher dialysis adequacy. Also, there was no significant relationship between dialysis ad- equacy and dialysis history in any of the reviewed studies. DISCUSSION In this systematic review 6677 hemodialysis patients were studied from 21 studies. About ⅓ of population had KT/V and URR more than 1.2 and 65%, respective- ly. Their dialysis adequacy was optimal. Survey results have shown that being women, having an older age and dialysis times per week can affect dialysis adequacy. In Malekmakan and colleagues’ study in Shiraz, 32.1% had KT/V at the optimal level.(18) In Egypt, a study showed that 45% of patients had optimal level of di- alysis adequacy on the basis of KT/V and URR crite- ria, while 44% of people had dialysis adequacy at an optimal level.(26) But the results in Great Britain and other European countries have been much better. The percentage of patients in Britain who had good URR has increased from 56% in 1998 to 86% in 2010.(27) Although national standards, internal investigations, and disease specific guidelines of the Ministry of Health of Iran have determined KT/V > 1.2 as the minimum acceptable quality of dialysis, the interna- tional standards are higher. For example, the Associ- ation of American Nephrologists has announced the KT/V level of 1.4 to 1.7.(28, 29) Therefore, obtaining the minimum acceptable quality in Iran is difficult. In studies in various countries including Egypt, Spain, Poland, Thailand, and Sweden, the acceptable KT/V level have been 1.5, 1.9, 1.4, 1.8, and 1.3, respective- ly,(30- 34) all of which are higher than standards in Iran. Therefore the results of Iranian studies on dialysis qual- ity of hemodialysis patients are weaker compared to for- eign studies. It seems that inadequate dialysis prescrip- tion, inappropriate use of filters, pumps with low speed (blood flow speed) and lack of time for dialysis are major causes of this inadequacy. There were significant differences in dialysis adequacy between developed countries and Iran, to some extent that may result in re- peated use of high- flux filter. Blood flow rate is higher in these countries compared to Iran. Rapid reduction of blood urea in the dialysis process with high blood flow may show the extracted urea level higher than the real rate because cells’ urea does not have the adequate time to exit the cell and adjust with the extracellular fluids.(18) In a review article in London, the average age of patients who did hemodialysis was from 45 to 64 years. This was 60.7 years in a study in Spain, 57.5 years in Abbas and colleagues’ study in Egypt, and 61.7 years in Tyne and colleagues’ study in China. (30,35-37) These are consistent with our results. Since the patients’ mean age in these studies was close, it is a guideline which shows the population at risk. Patients’ age is an issue which should be considered in particular. Because chronic kidney failure patients are elderly with special conditions and needs of living, they need emotional and educational support. The results showed that as age increases, KT/V reduces. Therefore some decisions should be made to improve the quality of older patients’ dialysis such as increasing hours of dialy- sis according to patient's tolerance, filter type, number of dialysis times per week, nutrition and physical activity. The results of our study showed that in some studies the dialysis adequacy in women was higher than men. This may be because of the using similar dialysis filters in both genders. Therefore it is better for women due to the smaller size, less weight and urea distribution. In this research the dialysis quality in patients who underwent dialysis, three times a week was more than those who did it twice a week. It seems that with changing treat- ment plans intended for dialysis patients from two to three times a week, the dialysis quality can be increased. CONCLUSIONS Most Iranian patients have KT/V and URR much low- er than the desirable level. They also have undesirable dialysis qualities. The prevalence of this condition in- creases mortality in these patients. Due to the increase of chronic diseases such as diabetes and high blood pressure as a result of an increase in hemodialysis pa- tients, it is necessary to increase dialysis adequacy. This can be done with a review of confounding factors such as nutrition diet, filter type, dialysis device, dialysis du- ration, patient education, and underlying disease. Thus, the medical costs can be reduced further and eventually the quality of life in hemodialysis patients can increase. ACKNOWLEDGMENTS The authors thank deputy of research of Mazandaran University of Medical Sciences who funded this study (Grant no: 1327). The authors would like to thank Seyed Muhammed Hussein Mousavi- nasab for his sincere cooperation in editing this text. CONFLICT OF INTEREST None declared. REFERENCES 1. Karimi S, Javadi M, Jafarzadeh F. Economic burden and costs of chronic diseases in Iran and the world. Director General. 2012;8(7):996. Figure 3. The frequency of hemodialysis patients in each study and the estimated URR. Abbreviations: CI, confidence interval; ES, effect size. 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