Adequacy of Hemodialysis and Its Associated Factors among Patients Undergoing Chronic Hemodialysis in Dar es Salaam, Tanzania

The worldwide prevalence of maintenance hemodialysis continues to rise. An adequate delivery of hemodialysis dose as measured by Kt/V or urea reduction ratio is a crucial determinant of clinical outcome for chronic hemodialysis patients. The aim of this study was to assess the adequacy of hemodialysis and its associated factors among patients undergoing chronic hemodialysis in Dar es Salaam. This was a cross-sectional study done on patients undergoing chronic hemodialysis in four dialysis centers in Dar es Salaam. Sociodemographic information and treatment characteristics were collected. Urea reduction rate and single-pool Kt/V were calculated to determine the adequacy of hemodialysis. The data were analyzed and any associated factors for inadequate hemodialysis were determined using a chi-square test and a logistic regression analysis. A total of 143 patients participated in the study. Males represented 65.7% of the study population. The mean age (±SD) was 51.7 ± 1.2 years. Only 34.3% (based on urea reduction ratio (URR)) and 40.6% (based on Kt/V) of patients received adequate hemodialysis. The univariate analysis showed that males were more likely to have inadequate dialysis (65.6% versus 48.0%, p=0.048 based on Kt/V). Patients using hemodialyzers with dialyzer surface area less than 1.4 m2 received significantly less hemodialysis dose than those with more than 1.4 m2 (69.0% versus 41.2%, p=0.02, by URR) (62.7% versus 35.3%, p=0.03, by Kt/V criteria). Patients who had hemoglobin <10 g/dl received significantly inadequate hemodialysis dose as compared to patients with hemoglobin ≥10 g/dl by Kt/V criteria (69.8% versus 51.3%, p=0.03). None of the factors acquired significance in the multivariate analysis. The proportion of patients receiving an adequate hemodialysis dose is low (34.3% based on URR and 40.6% based on Kt/V). Male gender, dialyzer surface area of <1.4 m2, and hemoglobin level of <10 g/dl were associated with an inadequate delivered dose of hemodialysis in the univariate analysis but not in the multivariate analysis. This study can increase awareness about the importance of measuring hemodialysis adequacy and giving the correct hemodialysis dose to achieve the intended benefit.


Introduction
Chronic kidney disease (CKD) has nearly doubled as a cause of death worldwide between 1990 and 2010 and was the 18 th highest cause of death worldwide in 2010 [1]. It is estimated that by 2030 more than 70% of patients with end-stage renal disease will be living in low-income countries, such as those in Sub-Saharan Africa. In Kinshasa, the prevalence of CKD was found to be 12.4% among adults in the general population. In Uganda, 20% of HIV/AIDS patients had CKD [2,3]. ere are many potential causes of CKD in Sub-Saharan Africa which makes kidney disease burdensome in the region. In addition to noncommunicable diseases, communicable diseases such as infectious glomerulonephritis, schistosomiasis, leishmaniasis, and HIV infection are common and can cause CKD [4,5].
Patients with end-stage renal disease (ESRD) are unable to sustain life without dialysis support. Hemodialysis is the transport process by which a solute passively diffuses down its concentration gradient from one fluid compartment (either blood or dialysate) into the other [6]. e goal of hemodialysis is exiting of the toxins from the body and preservation of its intracellular and extracellular composition in normal range as much as possible.
e worldwide prevalence of long term dialysis continues to rise [7,8] driven in part by strong trends towards the initiation of dialysis earlier in the natural history of CKD than was the practice previously [9]. e adequacy of hemodialysis refers to how well toxins and waste products are removed from the patient's blood and has a major impact on their well-being. Dialysis delivery should be adequate to improve adequacy of life and to prolong survival [10]. Studies have indicated an increase in morbidity and mortality among patients with inadequate dialysis [11]. e urea removal indexes help to calculate the adequacy of hemodialysis. e urea removal indexes include urea reduction ratio (URR), single-pool (spKt/V), equilibrated (eKt/V), and the weekly standard index (std Kt/V). is study used URR and spKt/V to calculate hemodialysis adequacy.

Urea Reduction Ratio (URR) Index.
e URR can be assessed by measuring the blood urea nitrogen (BUN) level before and after dialysis (8). It is calculated as follows: (1)

Single-Pool Index (spKt/V).
e spKt/V index is defined as the amount of serum that is cleared from urea via the distribution volume, in relation to the urea reduction ratio during hemodialysis. Parameter K is the dialyzer blood water urea clearance that is provided by the filter (measured as liters per hour), t is the duration of the hemodialysis session in hours, and V is the volume of urea distribution in combination with the body water in liters. e parameters spKt/V and URR are connected mathematically as follows: where ln stands for natural logarithm. In addition, the spKt/V index counts the ultrafiltration and the urea production. However, none of the parameters surpass the other as a denouement criterion (9)(10)(11)(12).
e National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) 2006 guidelines recommend spKt/V > 1.2 or URR ≥ 65% for maintenance hemodialysis, when a three times per week hemodialysis program is applied. ese values constitute the lowest possible values and not the target values, which are 1.4 for spKt/V and 70% for URR.
No previous studies have been done to determine the adequacy of hemodialysis in Dar es Salaam. Since the cost of hemodialysis is high and entails significant patient time, it is important that hemodialysis should be done adequately.
ere are approximately 300 patients who are undergoing hemodialysis in Dar es Salaam.
is study was aimed at determining the adequacy of hemodialysis and its associated factors in patients undergoing chronic hemodialysis in Dar es Salaam. Findings from this study will provide important feedback information to the dialysis centers in Dar es Salaam which can serve to improve dialysis services in the region. Furthermore, this study built awareness among the dialysis centers who were not already measuring the adequacy of hemodialysis for their patients.

Materials and Methods
is was a cross-sectional study carried out in four dialysis centers in Dar es Salaam, which included Muhimbili National Hospital, TMJ Hospital, Aga Khan Hospital, and Tumaini Hospital. e finite sample size was 143. Data were collected over a period of seven months. e study population included all consenting adults ≥18 years of age undergoing chronic hemodialysis who were in a steady state at the time of data collection. All patients had an average dialysate flow rate of 500 ml/min. e measurement of blood urea before and after dialysis was done for previous month in the first week of the next month. e calculation of URR and spKt/V was done using the formulas described above. Relevant data on sociodemographics and treatment characteristics were collected using structured questionnaires and patient's hospital records.
Urea after dialysis was taken following KDOQI guidelines as follows: (1) e ultrafiltration rate was set to zero.
(2) e blood pump was slowed to 100 ml per minute for 10-20 seconds. (3) e pump was then stopped. (4) A sample was drawn, either from arterial blood line sampling port or from the tubing attached to arterial needle.
Data were analyzed using SPSS 23. Relevant frequencies and appropriate tables were generated for different variables. Means and proportions were calculated for appropriate variables. All associated factors for inadequate dialysis were analyzed using Chi-squared test. A logistic regression analysis was done to find out independent associating factors for inadequate hemodialysis. Statistical significance was set at p value < 0.05.
Permission to conduct the study was sought from relevant ethical committees at MNH and Muhimbili University of Health and Allied Sciences (MUHAS) (Ref no. MU/PGS/SAEC/Vol. XIV). Permission from the dialysis centers was also sought.
All patients were entered into the study after an informed consent, either given by the patients themselves or their guardians in the case where patients were not able to. e data obtained during the study were kept anonymous. (Table 1). A total of 143 participants were enrolled in the study. About two-thirds (65.7%) were males. e mean age (±SD) was 51.7 ± 1.2 years.  (Table 3).

Proportion of Patients
By Kt/V criteria, patients who had hemoglobin of <10 g/ dl in the last month had significantly more inadequate hemodialysis as compared to those who had hemoglobin of ≥10 g/dl.
is association was not seen when using URR criteria (71.4% versus 61.3%, p � 0.203, by URR criteria) (69.8 versus 51.3%, p � 0.029, by Kt/V criteria) ( Table 3). e logistic regression analysis was done to find independent association of factors with inadequate hemodialysis in patients undergoing chronic hemodialysis in Dar es Salaam. Factors that showed association in univariate analysis were included in the regression model. None of the factors showed independent association with inadequate hemodialysis in patients undergoing chronic hemodialysis by both URR and Kt/V (Table 4).

Discussion
is was a cross-sectional study looking at the prevalence of inadequate dialysis and its associated factors.
In this study, the mean Kt/V was 1.1 and URR was 60.9%. is indicated that generally patients achieve less than the hemodialysis target therapy as per NKF-KDOQI 2006 recommendations [16]. ese values were however better than the values reported in Iran (Kt/V � 0.93, 1.17 and URR � 53%) [17,18]. is study revealed similar findings to those carried out in other developing countries such as Brazil, Nigeria, Nepal, and Pakistan [19][20][21][22][23] but they differed from those reported from developed countries such as the United States [24] and from other five European countries as part of the DOPPS study where the mean delivered Kt/V varied from 1.28 to 1.50 [25].
In this study, it was found that about one-third (34.3%) and 40.6% receive target URR (≥65%) and Kt/V (>1.2), respectively. Similar values for URR and Kt/V were found in studies done in Sari [26] and Rasht states and in Qom [27,28]. A study in Ardabil showed that only 10% of patients received adequate hemodialysis [29]. is was in contrast to studies done in developed countries (DOPPS study and in the United States) where URR ranged from 60-90% and Kt/ V was more than 1.2 [24,25]. e substantial discrepancy in hemodialysis adequacy between developed and developing regions may be resulting from the more frequent use of highflux dialysis and higher blood flow rates in the developed countries than in the developing regions like Dar es Salaam (19-60% versus 0.0%, and 251-322 ml/min versus 269 ml/ min, respectively) [24,25]. Some centers in Dar es Salaam do not adequately follow the KDOQI guidelines and this could have resulted in the lower proportion of adequate hemodialysis.
is study found three factors that were significantly associated with inadequate dialysis in the univariate analysis.
Males were more likely to have inadequate hemodialysis than females. ese results were similar to a study done in Iran where they found that males had three times more inadequate hemodialysis as compared to females [17]. Since the dialysis efficiency is inversely proportional to the urea distribution volume (V), it is expected that patients with higher values of height will have less dialysis efficiency and this may at least in part explain the difference as men are generally taller than women. It may also be due to less muscular mass, less body activity, and better diet observance among females [28].
is study also found that patients using hemodialyzers with surface area less than 1.4 m 2 received significantly less hemodialysis dose than those who used dialyzers with surface area of more than or equal to 1.4 m 2 . Hemodialyzers with smaller surface area are known to give less adequate hemodialysis than those having larger surface area. is was shown in a study done in Bangladesh where they found that increasing the surface area of a dialyzer membrane (from 1.2 to 1.3 m 2 ) increased the adequacy of hemodialysis by 10.4% (by URR criteria) and 19.7% (by Kt/V criteria) [30]. Similarly, Panagoutsos et al. showed that increasing the surface area of the dialyzer membrane from 1.15 m 2 ± 0.1 to 1.7 m 2 increased the Kt/V from 0.93 ± 0.19 to 1.55 ± 2.9 (p < 0.05) and URR from 52 ± 8% to 71 ± 7% (p < 0.05); that is, there was 66.7% and 36% increment in Kt/V and URR, respectively [31].
is study also found that patients with hemoglobin of less than 10 g/dl had more inadequate hemodialysis as compared to those who had hemoglobin of 10 g/dl. A study in South Africa showed that increasing the dose of International Journal of Nephrology hemodialysis from a Kt/V of 0.8 to 2 increased the hemoglobin level from 8.5 g/dl to more than 10 g/dl [32]. e inadequate urea clearance by hemodialysis can result in malnutrition, anemia, and functional impairment with an increased risk of hospitalization, morbidity, and mortality. Anemia could also be a marker for inflammation and malnutrition, which can influence Kt/V, but this was not evaluated in this study.  International Journal of Nephrology e logistic regression analysis failed to show any significant association between the above factors with hemodialysis adequacy. is probably indicates that hemodialysis adequacy is not dependent on one variable alone, but rather it is a function of different factors.
Strengths of this study were that it was a multicenter study which enabled participants from different backgrounds to be included. Many factors were evaluated for them associated with hemodialysis adequacy. Furthermore, hemodialysis adequacy was assessed using both Kt/V and URR.
e study had a few limitations. Firstly, the investigations for different patients were done at their respective centers which may have brought some variability in the results. Data on some confounding factors for Kt/V were not collected in this study such as albumin, inflammatory markers (CRP and ferritin), residual renal function, and other comorbidities unrelated to CKD.

Conclusion
Hemodialysis inadequacy is frequent in Dar es Salaam and is associated with male gender, dialyzer surface area, and hemoglobin level. Giving the correct hemodialysis dose could help improve hemodialysis adequacy.
Data Availability e data that support the findings of this study are available from the Muhimbili University of Health and Sciences, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission from the Muhimbili University of Health and Allied Sciences.

Conflicts of Interest
e authors declare that there are no conflicts of interest regarding the publication of this paper. International Journal of Nephrology 5