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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2014  |  Volume : 25  |  Issue : 4  |  Page : 781-787
Effect of hemodialysis on pulmonary function tests and plasma endothelin levels

1 Chronic Kidney Disease Research Center, Department of Nephrology, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
2 Chronic Kidney Disease Research Center, Department of Nephrology, Sina Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
3 Department of Pulmonology, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
4 Department of Anesthesiology, Tehran University of Medical Sciences, Tehran, Iran
5 Tropical Diseases, Imam Reza Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
6 Department of Internal Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

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Date of Web Publication24-Jun-2014


End-stage renal disease (ESRD) is a complex illness that involves different organs including the lungs. We studied the pulmonary function tests, arterial blood gases (ABG) and plasma endothelin-1 (ET-1) levels to check whether there is any change in their levels after hemodialysis (HD) in patients with ESRD. In this cross-sectional study (from July 2009 to April 2010), 20 patients with ESRD were evaluated. ABG, spirometric parameters and plasma ET-1 were measured before and after HD in these patients. Student's t-test was performed to clarify the differences and Pearson's test was used for correlations. P <0.05 was considered statistically significant. Significant reduction was seen in oxygen saturation (O 2 sat), partial pressure of carbon-dioxide (PaCO 2 ) and oxygen (PaO 2 ) after a HD session (P <0.001). Also, improvement was seen in all spirometric parameters except forced expiratory volume (FEV1)/forced vital capacity (FVC) after HD. Plasma ET-1 levels decreased signi­ficantly after HD. Mean ET-1 before HD was 6.88 + 5.81 pg/mL while it was 3.91 + 2.76 pg/mL after HD (P = 0.009). Based on the plasma levels of ET-1, the patients were divided into two groups. The mean level of ET-1 was higher in the first group. Significant increase was seen in spirometric parameters in the second group. Our study suggests that, in patients with ESRD, plasma ET-1 level is higher than in the normal population, and this is closely related to deterioration of pulmonary function tests. Significant reduction of plasma ET-1 may be an important factor in the improvement of spiro­metry parameters after HD.

How to cite this article:
Safa J, Noshad H, Ansarin K, Nikzad A, Saleh P, Ranjbar A. Effect of hemodialysis on pulmonary function tests and plasma endothelin levels. Saudi J Kidney Dis Transpl 2014;25:781-7

How to cite this URL:
Safa J, Noshad H, Ansarin K, Nikzad A, Saleh P, Ranjbar A. Effect of hemodialysis on pulmonary function tests and plasma endothelin levels. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2021 Dec 3];25:781-7. Available from: https://www.sjkdt.org/text.asp?2014/25/4/781/135003

   Introduction Top

End-stage renal disease (ESRD), apart from causing impaired renal function alone, also affects other organs. The lungs are one of the most important organs affected. [1] Organs like the heart and lungs get affected due to pulmo­nary edema (increased permeability of pulmo­nary capillaries), increased intravascular and extracellular volume, elevated blood pressure and congestive heart failure. These alterations result in an increase in the resistance of the airways. [2]

When the blood urea level rises, its effects on the respiratory system become manifest [3] in the form of pulmonary edema, pleural effusion and acute respiratory distress syndrome as well as cardiovascular calcifications. Renal failure, directly or indirectly, affects mecha­nical and ventilatory functions of the lung and, on the other hand, drugs and hemodialysis (HD) also contribute to alterations in air flow. [2]

Many studies have been published on func­tional changes affecting the respiratory system in patients with ESRD. These studies have focused on changes in arterial oxygen and spirometric parameters. Reduction of arterial oxygen content has been shown in association with HD, although the etiology is not clarified. It is believed to be due to diffusion of carbon dioxide (CO 2 ) into the dialysate, which may cause alveolar hypoventilation and reduction of partial pressure of oxygen (PaO 2 ). [4],[5] On the other hand, because this phenomenon is seen in mechanically ventilated patients also, the effect of hypoventilation is doubtful. [6],[7],[8]

It has been suggested that ventilation-perfu-sion mismatch and activation of the com­plement system are responsible for the hypo-xia. [9],[10] In an earlier study, changes in spiro-metric parameters during HD were evaluated. Evaluation of 61 patients with ESRD on HD showed that the mean value of forced expi­ratory volume in 1 second (FEV 1 ) before HD was 91.68% and after HD was 98.3% (P <0.001). The mean value of FVC before HD was 87.4% and after HD was 95.87% (P <0.001). [11]

Endothelin-1 (ET-1) is a middle molecule and most of it is secreted in the lungs by the endo-thelium and smooth muscles of airway epithe-lium. ET-1 is also found circulating in the plasma. Since the discovery of ET-1, investi­gators from different parts of the world have performed numerous studies because of its prolonged vasoconstrictive effect even after a single-dose injection to rats. It has been shown that ET-1 has an important role in stabilizing the blood pressure. Also, ET-1 causes bron-choconstriction and pulmonary artery hyper-tension. [12],[13],[14] A recent study indicates that over­production of ET-1 is seen in patients on HD, [15],[16] but the reason is not clear. [17]

In this study, we attempted to show impair­ment of respiratory function in patients on HD and its relationship with ET-1 as an important factor affecting pulmonary function. [10],[18]

To study this, we analyzed changes in arterial blood gases (ABG), spirometric parameters as well as changes in the plasma levels of ET-1 in patients with ESRD.

   Methods Top

Twenty patients on HD for ESRD at the Imam Reza Hospital, Tabriz, Iran were enrolled ran­domly in this cross-sectional study, which was conducted from July 2009 to April 2010. All patients were dialyzed using an R5 cupro-phane, which is a synthetic fiber dialyzer. ET-1 is a middle molecule and its clearance is influenced by the flux and size of the dialyzer membrane; we therefore chose this filter for all the study patients. None of the patients had any apparent heart (ischemic and valvular heart disease and congestive heart failure), li­ver (cirrhosis or impaired liver function) or lung (asthma, interstitial or obstructive lung disease) disease. Patients with any heart, liver and underlying pulmonary disease were exclu­ded as these problems may lead to important bias. The study patients were selected from a total of 80 patients who were dialyzed in our center. In view of the strict inclusion criteria, our study sample was small.

All the study patients were non-smokers and were in the age range between 20 and 50 years. Spirometry was performed by an expert clinician exactly 30 min before and after a HD session, and blood sampling was performed from arterial dialysis line simultaneously and ABG and ET-1 levels were measured. The pa­tients' height as well as weight, before starting and after finishing HD, were measured. The body mass index (BMI) and changes in body weight were evaluated.

Blood samples were analyzed by an Advance AVL 995 analyzer at the Imam Reza Hospital. All collected blood samples were centrifuged for measuring blood levels of ET-1. Plasma samples were stored at -70°C and analysis was performed by a biochemist. The kit used was the Human Endothelin-1 (R&D Systems, Minnesota, USA).

Data were analyzed using SPSS 16.0 soft­ware. We used the Student t-test for calcu­lating differences and the Pearson test for calculating correlations, and results were re­ported as mean ± SD; P <0.05 was considered significant.

   Results Top

The ABG parameters were analyzed before and after HD. Plasma bicarbonate (HCO 3 ) and pH increased significantly after HD (P = 0.002 and P = 0.018, respectively), but PaCO 2 and O 2 saturation decreased (P = 0.011 and P = 0.001, respectively).

The ABG parameters before and after HD were not significantly different in males and females: HCO 3 , P = 0.081; pH, P = 0.096; PCO 2 , P = 0.929; PaO 2 , P = 0.251; O 2 sat, P = 0.547.

Following HD, spirometric parameters such as forced expiratory flow (FEF) 25-75%, forced expiratory volume in 1 second/forced vital capacity (FEV 1 /FVC), predicted percent of forced vital capacity (FVC%) pre, forced vital capacity (FVC), predicted forced expiratory volume in 1 second (FEV 1 %) pre and FEV 1 , showed differences. However, no change was observed in the FEV 1 /FVC levels before and after HD (P = 0.21). The differences noted in FEF 25-75%, FVC% pre, FVC, FEV 1 % pre and FEV 1 after HD treatment were significant (P = 0.002, P = 0.003, P = 0.004, P = 0.001 and P = 0.001, respectively). All values were lower before HD.

Changes observed in the spirometric para­meters measured were not significantly diffe­rent between males and females.

The serum ET-1 levels were different before and after HD. The mean value before HD was 6.88 ± 5.81 units and that after HD was 3.91 ± 2.76 (P = 0.009). The ET-1 levels were almost similar in males and females before and after HD; 3.06 ± 5.62 and 2.26 ± 3.04, respectively, P = 0.924.

The correlation between ABG parameters, height, weight, body mass index (BMI) and spirometric parameters, before and after HD, is shown in [Table 1]. Correlations between spirometric parameters and height, weight and BMI, before and after HD, are shown in [Table 2].
Table 1: Correlation between ABG parameters, height, BMI, weight and spirometric parameters before and after HD.

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Table 2: Correlation between spirometeric parameters, weight, height and BMI before and after HD.

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Based on the ET-1 levels, the patients were divided into high-level (10.67 ± 6.10) and low-level (3.10 ± 1.27) groups (P = 0.001). Spiro­metric parameters of FEF (P = 0.003) and FEV1 (P = 0.006) were lower in the low ET-1 group. Levels of spirometric parameters in the high- and low-level ET-1 groups are shown in [Table 3].
Table 3: Comparison of spirometric parameters in both groups before and after HD.

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The ABG parameters (HCO 3 , pH, PaCo 2 , PaO 2 and O 2 sat) were almost similar in the two groups (P = 0.594, P = 0.920, P = 0.564, P = 0.732 and P = 0.288, respectively).

   Discussion Top

In this study, ABG parameters were studied in 20 patients (11 males and nine females) with ESRD on chronic acetate buffer-based HD. The filter used was an R5 cuprophane, a kind of synthetic filter. We found a decrease in O 2 saturation and PaCO 2 ; the reduction seen in the mean PaCO 2 value may be caused by hyperventilation secondary to arterial hypo-xemia. It also may be related to diffusion of CO 2 into the dialysate and is exaggerated in acetate-based HD, as mentioned in previous studies. [19],[20]

No association was found between gender, height as well as changes that occur in the body weight during HD and PaO 2 , PaCO 2 and O 2 sat. It must be emphasized that our sample size was small, and this lack of association should be viewed with caution. In other studies, the role of hypoxia-inducing agents like micro-embolism, histamine release, serotonin, com­plement activation and neutrophil entrapment in the vascular bed were mentioned, but we did not study these interrupting factors. [21]

Spirometric parameters studied included FEV 1 , FEV 1 pre%, FVC pre%, FEV 1 /FVC and FEV 1 25-75%. We found an increase in all para­meters expect for FEV 1 /FVC after HD. In some earlier studies, FEV 1 /FVC was also found to increase. [1],[2] This finding is similar to the findings of Alves et al, who found an increase in FEV 1 and FVC and also found a correlation between these parameters and weight reduction during HD. [11] We could not find any such association.

Navari et al studied the spirometric changes in two groups of patients on HD (bicarbonate-and acetate-based) and found that only patients who were dialyzed with a bicarbonate-based dialysate showed an improvement in spiro-metric parameters. In their study, all spiro-metric parameters, except FEV 1 /FVC, signifi­cantly increased in bicarbonate-based HD patients. This improvement was seen more in males; decrease of weight after HD did not have any significant association with spiro-metric parameters. [2] , [22]

We studied only patients on acetate buffer-based HD and our results showed that all spi-rometric parameters changed and the changes were not significantly different between males and females. In the study of Kovelis et al, changes in body weight with HD had a re­markable relationship with changes in FVC. It seems that greater weight gain between dia­lysis sessions may be associated with wor­sening of pulmonary function, and these effects will be reversed with HD. [23] Our study results showed a negative correlation between change in weight after HD and FEV1; we could not find such a correlation with any other spirometeric parameters.

The serum ET-1 levels were high in almost all patients with ESRD. The mean serum ET-1 level before HD was 6.8 ± 5.8 pg/mL (normal value = 1.88 ± 0.6 pg/mL). The decrease of ET-1 level after HD, seen in our study, was significant and it was not affected by gender, height, weight changes and BMI. We found a reduction in serum ET-1 level after performing HD with acetate-based solution and poly-carbone membrane.

Based on the ET-1 levels, the patients were divided into two groups: High and low; the spirometric and ABG parameters were com­pared between the two groups. The mean ET-1 level in the high group was 10.67 ± 6.16 pg/mL and 4.86 ± 3.4 pg/mL before and after HD, respectively. On the other hand, it was 3.1 ± 1.27 pg/mL and 2.97 ± 1.58 pg/mL pre- and post-HD, respectively, in the low ET-1 group. When the two groups were compared, we found that the spirometric parameters were better after HD in the low-ET-1 group. Among those, the increase in FEV1 and FEF 25-75% was statistically significant. This suggested that high ET-1 levels were associated with poor pulmonary functions as assessed by the spirometric findings. Aytul Noyan et al in their study showed a reduction in serum ET-1 level after HD using bicarbonate-based buffer and polycarbone membrane as well as acetate-based buffer and polysulofan membrane. [21] Derayl et al reported elevated serum levels of ET-1 in patients with chronic renal damage and its level was higher, before and after HD, than in the normal population; however, they did not find any significant difference in ET-1 levels after HD. [18]

Noshad et al and Stockenhuber et al also revealed elevation of serum and tissue ET-1 levels in patients with chronic kidney disease compared with normal people. [24],[25] Stanetic et al studied the effects of ET-1 on pulmonary function in patients on HD and showed that patients with higher ET-1 levels had signi­ficant reduction in FVC, FEV 1 and FEF 25- 75% compared with patients with lower se­rum ET-1 level as well as the normal popu-lation. [26]

The ABG parameters were also compared bet­ween the two ET-1 groups. No significant difference was observed between the two groups before and after HD. Regarding the etiology of hypoxemia, we could not study the role of factors other than ET-1 levels; more studies with a larger sample size are required. Also, we could not find any published reports related to changes in ABG after HD and its correlation with blood levels of ET-1. Thus, our study is a trend setter.

We are presently in the process of conducting another study using a novel biocompatible synthetic, high-flux membrane dialyzer and bicarbonate-based dialysis.

   Conclusion Top

Hemodialysis with acetate and cuprofane membrane leads to significant reduction of PaO 2 , O 2 sat and PaCO 2 . There was no appa­rent correlation between ABG parameters and plasma ET-1 level. Spirometric parameters showed improvement after HD (except for FEV 1 /FVC), as also the plasma ET-1 levels. The mean values of all spirometric parameters in patients with lower plasma ET-1 level, before and after HD, were greater than in pa­tients with higher plasma ET-1 level. Based on these results, we believe that plasma ET-1 level in addition to uremia, volume expansion and drugs, may affect pulmonary function in patients on HD.

   References Top

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19.Kalmunkar SN, Hase NK, Billimoria FR, Chawla KP. Arterial oxygenation during acetate haemodialysis, sequential haemodialysis and isolated ultrafiltration. Indian J Clin Biochem 1993;8:16-9.   Back to cited text no. 19
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25.Stockenhuber F, Gottsauner-Wolf M, Marosi L, Liebisch B, Kurz RW, Balcke P. Plasma levels of endothelin in chronic renal failure and after renal transplantation: Impact on hyper­tension and cyclosporin A-associated nephro-toxicity. Clin Sci 1992;82:255-8.  Back to cited text no. 25
26.Stanetic M, Kovacevic P, Matavulja A, Rajkovaca Z, Huskic J, Veljkovic S. Effects of Endothelin-1 on respiratory function in hemodialyzed patients. Chest 2007;132:616s.  Back to cited text no. 26

Correspondence Address:
Hamid Noshad
Chronic Kidney Disease Research Center, Department of Nephrology, Sina Hospital, Tabriz University of Medical Sciences, Tabriz
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DOI: 10.4103/1319-2442.135003

PMID: 24969188

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  [Table 1], [Table 2], [Table 3]

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