|Year : 2015 | Volume
| Issue : 6 | Page : 1154-1160
|Association of dialysis adequacy with nutritional and inflammatory status in patients with chronic kidney failure
Roya Hemayati1, Mahboub Lesanpezeshki2, Sepideh Seifi2
1 Department of Nephrology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2 Department of Nephrology, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
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|Date of Web Publication||30-Oct-2015|
| Abstract|| |
The number of patients with dialysis-dependent renal failure has increased in the past years worldwide. Several parameters have been introduced for the quantitative assessment of dialysis adequacy. The National Cooperative Dialysis Study results indicated that Kt/V and time-averaged concentration of urea (TAC) are predictors of mortality in patients who receive maintenance hemodialysis (HD). Also, the protein catabolic ratio (PCR), which is an indicator of nutritional status, can predict patients' mortality. Our aim was to assess the impact of parameters that show dialysis adequacy on indices of nutrition or inflammation. A total of 46 patients were included in the study; eight patients were excluded during the course of the study and 38 patients were enrolled in the final analysis. All patients were receiving HD for at least for three months. HD was administered three times per week and the study lasted for two months. Kt/V, TAC and PCR were assessed at the beginning of the study based on patients' urea and blood urea nitrogen in the first week of our study; these calculations were repeated at the end of the first and second months using the mean of the mentioned values in the month. Both adequacy indices significantly and positively correlated with changes in PCR (P <0.001). However, no significant correlation was detectable between Kt/V and TAC with either body mass index and albumin or C-reactive protein. Based on the Kt/V values, patients with adequate dialysis had slower decrease in the PCR (P <0.001). Our results indicate that adequacy of dialysis is correlated with patients' nutritional status. No correlation was observed between dialysis adequacy and inflammatory status.
|How to cite this article:|
Hemayati R, Lesanpezeshki M, Seifi S. Association of dialysis adequacy with nutritional and inflammatory status in patients with chronic kidney failure. Saudi J Kidney Dis Transpl 2015;26:1154-60
|How to cite this URL:|
Hemayati R, Lesanpezeshki M, Seifi S. Association of dialysis adequacy with nutritional and inflammatory status in patients with chronic kidney failure. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2019 Jul 21];26:1154-60. Available from: http://www.sjkdt.org/text.asp?2015/26/6/1154/168593
| Introduction|| |
The number of patients with dialysis-dependent renal failure has dramatically increased in the past years. In 1999, it was estimated that about 340,000 patients in the United States (US) were suffering from kidney failure. Soon this figure is expected to almost double with around 520,000 patients in need for regular dialysis.  According to the Third National Health and Nutrition Examination Survey, 4.7% of the US population (8.3 million) has chronic kidney disease (CKD), placing a substantial burden on the health-care system.  Similar prevalence and incidence rates for CKD have been reported from other countries worldwide. , In Iran, the prevalence of end-stage renal disease (ESRD) has risen from 238 to 357 patients per million population over a period of six years (2000-2006);  In 2008, about 12,000 ESRD patients were receiving hemodialysis (HD) on a regular basis. 
Evaluating the adequacy of HD is of critical importance in clinical practice. Available measures like blood urea nitrogen (BUN) are not suitable for the assessment of HD adequacy as the BUN values are largely influenced by diet and normal values can be achieved following a low protein diet despite inadequate HD.  For this reason, a number of indices of HD adequacy have been developed and used in research and clinical settings. The urea kinetic modeling of the dose of dialysis (Kt/V) proposed by Daugirdas is a measure of HD competence that can be individualized for each patient.  Previous studies have demonstrated that a Kt/V of lower than 1.2 is associated with a significant increase in the patient mortality rate. ,, Another factor that showed equivalent power to Kt/V for predicting the adequacy of dialysis is timed-averaged concentration of urea (TAC).  Based on the results of the National Cooperative Dialysis Study (NCDS), TAC is a predictor of morbidity among patients with kidney failure.  Another important predictor of morbidity and mortality in patients with CKD is poor nutritional status. In fact, initiation of dialysis is recommended to prevent malnutrition.  Several indicators and parameters have been used for the evaluation of nutritional status in patients who receive HD, including, among others, serum albumin, serum transferrin, body mass index (BMI) and skin fold thickness. , Dialysis adequacy can affect the nutritional status of patients, and it has been shown that Kt/V correlates with serum albumin and BMI.  Protein catabolic ratio (PCR) has been shown to be a reliable indicator of nutritional status in patients with CKD. , Also, the NCDS revealed that PCR is a major predictor of morbidity and mortality in patients with CKD. 
The aim of this prospective study was twofold. First, to evaluate the competence of HD in a group of Iranian patients receiving dialysis on a weekly schedule; and second, to investigate how HD adequacy affects parameters of nutritional and inflammatory status in dialysis-dependent ESRD patients.
| Materials and Methods|| |
Enrollment and assessment of patients
A prospective study was designed and initiated to assess the impact of adequacy of HD on patients' nutrition-and inflammation-related parameters in the Imam Khomeini Hospital in Tehran, Iran. From February to November 2009, all patients meeting the study criteria were enrolled in a consecutive manner. Eligibility for inclusion was ascertained if a patient was receiving HD on a regular schedule, three times a week, starting at least three months before study commencement. Patients with a history of malignancy and also those reported to have episodes of hemodynamic instability following HD were excluded. Upon enrolment, informed consent was obtained from each participant and was formally recorded. All procedures involving human subjects were performed in accordance with the guidelines laid down in the latest revision of the Declaration of Helsinki. The local ethics committee also approved the study protocol.
Dialysis was performed three times a week; overall, each patient underwent 24 HD sessions throughout the study period. Patients' weight was determined at baseline and then at the end of every month using a calibrated digital scale. BMI was calculated according to the Quetelet formula of weight in kilograms divided by height in square meters.
Laboratory evaluations and urea kinetic modeling
Laboratory evaluation was conducted at the beginning of the study and after the 24 th session of dialysis. Laboratory work-up included hemoglobin, ferritin, serum iron, total iron-binding capacity (TIBC), calcium, phosphorus, alkaline phosphatase (ALP), parathyroid hormone (PTH), uric acid, serum albumin and C-reactive protein (CRP). Additionally, the following markers and indices were determined at baseline and at the end of each month (three time points in total): Kt/V, TAC and PCR. Finally, serum urea concentrations were measured before and after each dialysis session.
Kt/V was calculated by the equation described by Daugridas: 
(U2, urea after dialysis; U1, urea before dialysis; W1, patients' weight before dialysis; W2, patients' weight after dialysis)
TAC indices were determined using the formulae that have been previously explained by Kloppenburg et al.  Normalized PCR was calculated using the equation described by Jindal et al.  PCR typically manifests the nutritional status of patients undergoing dialysis. CRP, an acute phase reactant, is believed to be tightly correlated with the level of chronic inflammation.
| Statistical Analysis|| |
Statistical analyses were performed using Software Package for Social Sciences (SPSS) version 19.0 (IBM Corporation, Armonk, NY, USA). In all tests, a P-value <0.05 was considered necessary to reject the null hypothesis. Continuous variables are depicted as mean ± standard deviation and categorical variables are depicted as proportions. Changes in continuous variables between baseline and after two months were evaluated using the paired t-test. Additionally, point-to-point changes in continuous variables were assessed using repeated measures analysis of variance (rANOVA). Correlation between changes in indices of HD adequacy (i.e., Kt/V and TAC) and nutritional and inflammatory markers (i.e., PCR, BMI, albumin and CRP) was investigated using the Pearson correlation coefficient.
Based on HD competence, patients were divided into two groups. For this purpose, a cut-off point of 1.2 was used to categorize patients into adequate (Kt/V ≥1.2) and inadequate (Kt/V <1.2) HD groups. The mentioned cut-off point has been recommended by several international guidelines. , rANOVA and independent t-test were employed to compare outcome variables between the two groups. In each rANOVA analysis, effect size was calculated using partial eta squared.
| Results|| |
A total of 46 patients were included in the study. During the course of the study, two patients died before the study end-point. Three patients refused to further cooperate and an additional three patients failed to complete the study protocol due to change of HD center. Therefore, final analyses were conducted on the remaining 38 patients. Study participants consisted of 25 males (65.8%) and 13 females (34.2%). The mean age of the patients was 50.2 ± 16.09 years (ranging from 23 to 80 years). Diabetic mellitus (DM) and hypertension were the leading causes of renal failure (70%), glomerulonephritis accounted for 20% of the cases and in 10% of our patients, the underlying cause was unknown.
Baseline and end-point assessment of study participants is summarized in [Table 1]. After 24 sessions of dialysis, a significant increase was observed in the serum calcium and phosphorus concentrations (0.003 and 0.016, respectively). Change in other parameters, however, did not reach statistical significance.
|Table 1: Baseline and end-point assessment of 38 ESRD patients undergoing regular hemodialysis.|
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Point-to-point changes in outcome variables are illustrated in [Table 2]. During the study period, Kt/V showed a slight decrease, but this difference did not reach statistical significance (P = 0.223). On the other hand, TAC significantly decreased over the course of the study (baseline: 47.77 ± 14.01, 2nd month: 39.23 ± 12.7, P = 0.006). The patients' BMI did not show an apparent change between the three time points (P = 0.816). On the contrary, in the other nutritional parameters PCR and albumin, a noticeable change was observed (P = 0.001 for both tests). CRP concentrations did not change significantly over the 24 HD sessions (P = 0.386).
|Table 2: Point-to-point changes in indices of hemodialysis adequacy, nutritional status and inflammation.|
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Correlation analysis between changes in indices of dialysis adequacy and parameters of nutrition and inflammation are delineated in [Table 3]. Both adequacy indices (ΔKt/V and ΔTAC) significantly and positively correlated with ΔPCR. However, no significant correlation was detectable between ΔKt/V and ΔTAC and either BMI and albumin, or CRP [Table 3].
|Table 3: Correlation between adequacy of hemodialysis and nutritional and inflammatory parameters.|
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Based on the mean Kt/V values during the study period, 15 patients (39.5%) received adequate dialysis. Although both groups experienced a decline in the PCR values, rANOVA showed a significant difference in the PCR decline rate between the two groups, suggesting that patients with inadequate HD suffered a steeper decline in PCR (F (1, 35) = 15.45, P <0.001, effect size = 30%) [Table 4]. Patients in both groups experienced an increasing trend in albumin levels, but the difference was not significant (P = 0.227). Changes in other factors such as BMI and CRP did not have any significant differences between the two groups (P = 0.153 and P = 0.760, respectively) [Table 4].
|Table 4: Comparison of nutritional parameters between groups with adequate and inadequate hemodialysis.|
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| Discussion|| |
Thirty-eight patients receiving regular HD in the Imam Khomeini Hospital for at least three months were enrolled in the present study. Kt/V and TAC were determined for all patients during the study period as indicators of HD adequacy. Additionally, PCR, BMI and albumin were also measured to reflect the overall nutritional status of the patient. We observed a significant and positive correlation between HD adequacy and PCR, suggesting that better HD efficacy is associated with better nutritional response in ESRD subjects. Moreover, patients with adequate dialysis had higher concentrations of serum albumin, although the difference between the two groups did not reach statistical significance.
A number of studies to date have been conducted to assess the relationship between inadequate dialysis and poor nutritional status. It is conceivable that diminished renal function leads to metabolic disturbances, consequently causing a fall in PCR. Kopple et al  investigated the correlation between glomerular filtration rate (GFR) and nutrition. Based on their observations, GFR significantly correlated with amount of dietary energy and protein as well as serum albumin, transferrin, urinary creatinine, percentage of body fat and skin fold thickness.  Another study in patients with progressive renal failure over a period of seven years clearly indicated that lower PCR is linked to impaired creatinine clearance. Of note, a steep decline in PCR, three months before initiation of dialysis was recorded.  Additionally, evaluation of Kt/V in patients who receive continuous ambulatory peritoneal dialysis showed a positive correlation between Kt/V and PCR.  Collectively, these findings are in accordance with our observation that insufficient dialysis leads to worsening nutritional status.
Increased albumin concentrations with adequate dialysis could be attributed to an ameliorated inflammatory condition or merely reflect an improved nutritional metabolism. It has been suggested that pro-inflammatory cytokines can cause hypoalbuminemia.  Jager et al  observed an increase in albumin levels in patients receiving HD; they proposed that it can be due to an increase in Kt/V. Iseki et al  claimed that dialysis dose has a positive correlation with serum albumin concentration and increased albumin level can lead to lower mortality. However, our data did not provide evidence in support of the former, as no correlation was found between changes in albumin and CRP (data not shown).
In the current study, a surprisingly high proportion of patients (60.5%) did not receive what is considered adequate HD; this was paralleled by a gradual but not significant decline of Kt/V over the study period. Our findings reflect the fact that most of our patients did not receive adequate dialysis.
In our study of two months' duration, no significant changes in BMI were noted. This probably reflects the short duration of the study conducted, as changes in BMI are more gradual and reflect nutritional status over longer periods of time.
It is unfortunate that dialysis centers in Iran do not assess dialysis adequacy based on pertinent indices such as Kt/V. The authors' observations from multiple dialysis centers in Iran indicate that HD efficacy is often evaluated solely by BUN and serum creatinine levels. In the past few years, the Management Center for Transplantation and Special Disease of Iran has endorsed multiple programs to place Kt/V assessment in dialysis centers' routine practice. 
In another multicenter study that cumulated the data of six dialysis centers across the country (two centers from Tehran, others from Shiraz, Ahvaz, Kermanshah and Mashhad), the mean Kt/V of 338 included patients was 1.17 ± 0.31, still lower than the accepted cutoff point of 1.2.  Similar results were reported in another recent study conducted by Mahdavi-Mazdeh et al, who included the entire HD population of Tehran.  A mean Kt/V of 0.97 ± 0.25 was reported, again confirming the notion that most ESRD patients in Iran are not being dialyzed using optimal conditions. Based on their assessment, inadequate dialysis in Iran largely stems from type of buffer used (acetate buffer, which results in low blood flow) and the lack of mandated equipments in dialysis facilities.
In conclusion, our findings suggest that dialysis adequacy can affect patient's nutritional status; patients with higher Kt/V values, as an indicator of dialysis adequacy, are benefited from improvements in PCR. Regarding the low mean Kt/V values in our study, which has been repeatedly reported in other multicenter studies as well, we recommend frequent assessment of dialysis adequacy using composite indices like Kt/V and TAC.
Conflicts of interest: None to declare.
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Department of Nephrology, Shahid Sadoughi University of Medical Sciences, Yazd
[Table 1], [Table 2], [Table 3], [Table 4]
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