| Abstract|| |
Pulmonary function tests can differentiate between obstructive and restrictive lung diseases and assess the severity of the disease in children. The aim of work was to study pulmonary function tests in children with end-stage renal disease (ESRD) undergoing hemodialysis (HD) and its correlation with dialysis duration. This study was conducted on 40 patients with ESRD on regular HD for at least six months selected from the Pediatric Nephrology unit of Pediatric Department of Tanta university hospital and 40 healthy children as a control group. All participants were subjected to full history taking, thorough clinical examination, laboratory investigation: arterial blood gases and pulmonary function tests, including resting spirometry included measurement of lung volumes. There were significantly lower forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC ratio, peak expiratory flow rate, and forced expiratory flow in patients compared with controls and significant positive correlations between dialysis duration and both of FVC and FEV1 in studied patients. There were restrictive spirometric pattern in 30 patients (75%) with ESRD under regular HD and mixed obstructive and restrictive pattern in 10 patients (25%) with highly significant differences between patients and controls regarding patterns of spirometry. There was impairment of lung function in patients with chronic renal failure undergoing HD predominantly of the restrictive pattern. Children with ESRD under regular HD should undergo pulmonary function tests as follow-up investigation to detect associated pulmonary complications included obstructive, restrictive, or mixed patterns of impaired pulmonary function.
|How to cite this article:|
El-Gamasy MA. Study of some pulmonary function tests in Egyptian children with end-stage renal disease under regular hemodialysis in correlation with dialysis duration. Saudi J Kidney Dis Transpl 2019;30:119-28
|How to cite this URL:|
El-Gamasy MA. Study of some pulmonary function tests in Egyptian children with end-stage renal disease under regular hemodialysis in correlation with dialysis duration. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2020 Jun 1];30:119-28. Available from: http://www.sjkdt.org/text.asp?2019/30/1/119/252901
| Introduction|| |
Acute or chronic pulmonary complications may occur in patients with end-stage renal disease (ESRD) under regular hemodialysis (HD), and represent one of the common causes of death., The reduction in functional capacity of lung can be influenced by physical deconditioning, muscle disuse atrophy, weakness, fatigue, lower-limb edema, and back pain, hindering the performance of daily living activities by these children.,
Several mechanisms may impair pulmonary function and alter bronchial responsiveness in patients on long term regular HD treatment, some of which are trapping of neutrophils, increased extra-vascular lung water, left ventricular hypertrophy, metastatic lung calcification, and iron deposition.,,
In addition, other lung tissue impairments, compromises the functioning of the pulmonary system, thus resulting in decreased lung capacity.,
| Aim of the work|| |
The aim of this work was to study pulmonary function tests in children with ESRD under regular HD and its correlation with dialysis duration.
| Patients and Methods|| |
This study was carried out after approval from the research ethical committee center in Tanta University Hospital (TUH) and informed written parental consents from every subject that participates in this research and was carried out on 40 children with ESRD under regular HD, as group 1 (HDG) selected from the Pediatric Nephrology unit of Pediatric Department of TUH including 24 males and 16 females with their age ranging from nine to 15 years and mean age value of 12.7 ± 2.2 years and 40 healthy children as a control group (CG) including 22 males and 18 females with their age ranging from seven to 15 years and mean age value of 10.3 ± 2.36 years.
All patients were undergoing regular HD for at least six months. They were clinically stable, without anemia as unstable general condition and/or anemia may negatively affect pulmonary function and thus result in false results of pulmonary function tests. All patients and controls were under clinical follow-up. Dialysis was started when GFR is ≤15 mL/min/1.73 m,3 three times per week, with each dialysis session lasting for 3–4 h. Patients were dialyzed on Fresenius 4008B dialysis machine (Germany) at blood flow rate = 2.5 × weight (kg) + 100 vmL/ min, using polysulfane hollow fiber dialyzers suitable for the surface area of the patients (Fresenius F3 = 0.4 m2, F4 = 0.7 m2, F5 = 1.0 m2 and F6 = 1.2 m2). Bicarbonate dialysis solutions were used. Dry weight adjusted according to clinical assessment each visit. All patients were receiving supportive therapy in the form of subcutaneous erythropoietin in a dose of 50 IU/Kg/session, IV iron dextran 100 mg/kg/week, oral folic acid 1 mg/day, oral calcium 1000 mg/day, oral Vitamin D (one alpha) in a dose of 0.01–0.05 μg/kg/day and oral antihypertensive medications for hypertensive patients.
Children and adolescents with ESRD and treated by regular maintenance HD at least six months before the study.
Children with unstable general conditions such as anemia, history of bronchial asthma, other lung diseases, complex congenital heart disease, cardiac insufficiency, current respiratory infections, musculoskeletal disorders, children of smoker parents, those who were unable to cooperate.
All patients and controls were subjected to:
- Full history taking: including the patient data (age in years, weight in kilograms, height in centimeters and sex), child's previous growth and development
- Thorough clinical examination including:
- Anthropometric measurements for assessment of nutritional and developmental status which include (a) weight in kilograms which was recorded with minimal clothing using electronic weight scale, (b) height in centimeters measuring the distance from the vertex to the base of the heel by using a stadiometer in standing position, (c) body mass index (BMI) which was calculated by formula BMI = weight (kg)/ (height [m]), and mid-arm circumference (MAC) which measures the circumference of the left upper arm at the mid-point between the tip of the shoulder (olecranon process) and the tip of the elbow (the acromium process) in centimeters
- Vital signs especially temperature and arterial blood pressure which was measured by an auscultatory method using a mercury sphygmomanometer, in the semi setting position after 10 min of rest, in the nonfistula arm using an appropriately-sized cuff and was taken as the mean value of three successive readings in three different days
- Laboratory investigations including complete blood count (CBC) by an automated analyzer, blood urea, blood urea nitrogen (BUN), serum creatinine, serum albumin and serum electrolytes (ionized calcium, potassium, and phosphorus). Arterial blood was analyzed for pH, PaO2 and PaCO2 with an instrumentation laboratory blood gas analyzer, RAPID Lab 248/348 Systems
Specimen collection and handling: morning venous blood samples were withdrawn just before dialysis sessions. Two milliliters of venous blood were collected using sterile needles through gentle venipuncture after sterilization of the puncture site with alcohol, and collected samples in 20 L ethylenediaminetetraacetic acid solution for CBC including differential white blood cells count which was done on a Leishman stained peripheral blood smear with evaluation using an ERMA PCE-210 N cell counter (fully automated blood cells, counter from ERMA. Inc., Japan).
- Plain chest X-ray (PA view) before each inclusion, and if it was abnormal, the patient was eliminated from the study.
- Pulmonary function tests which were measured on the day of HD. The time interval between the end of HD session and the postdialysis study was 8–16 h.
Lung function assessment was performed by spirometry using a digital spirometer. One flow model (Clement Clarke International; Harlow, UK) and technical procedures, criteria for acceptability, and reproducibility followed the guidelines of the American Thoracic Society and European Respiratory Society. The forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), and FEV1/FVC ratio, PEF rate (PEFR) and forced expiratory flow (FEF) were determined. The maneuver was performed three times and the highest value was used, and all results were calculated as percent of predicted except for FEV1/FVC%.
Data were collected and analyzed using the Statistical Package for Social Science (SPSS) version for Windows version 12.0 (SPSS Inc., Chicago, IL, USA). All data were expressed as in terms of mean values ± standard deviation (SD). Comparisons of parameters among groups were made using the paired t-test. Two-group comparisons were performed nonparametrically using the Mann–Whitney U-test. All statistical tests were two-tailed, and P <0.05 was considered statistically significant.
| Results|| |
Of the total 64 children and adolescents with CKD treated at the Pediatric Nephrology Unit of TUH, 40 were included in the study and 24 were excluded (11 due to difficulties in understanding how to perform the respiratory tests, and five for having complex heart disease and eight for having severe chronic lung disease).
[Table 1] summarizes demographic and clinical data of the studied patients and CGs as regard age, anthropometric measurements, blood pressure, and dialysis duration. Of the 40 eligible patients, 24 (60%) were male, 16 (40%) were female.
The age ranged from 7 to 16 years with mean 12.7 ± 2.2 in patients group and 10.3 ± 2.36 in CG. There were no statistically significant differences between patients and controls as regards age and sex, but there were statistically significant differences as regards anthropometric measurements including weight, height, BMI, and MAC where the mean values of patients group were significantly lower than that of CG. Both systolic and diastolic blood pressures of the patient's group were significantly higher than that in CG (P<0.05). Duration of dialysis in patients group ranged from three to 12.3 years with mean 7.2 ± 2.51 [Table 1].
[Table 2] summarizes laboratory data of the studied patients and CGs; there was significant increase in levels of blood urea, BUN, serum creatinine, serum potassium, and serum phosphorus levels in patients group when compared to CG (P <0.05). However, there was a significant decrease in levels of hemoglobin percent, hematocrit values, platelet count, total leukocyte count, serum albumin, and serum ionized calcium in patients group when compared to CG (P<0.05) [Table 2].
|Table 2: Routine investigations of the cases group and the control group.|
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[Table 3] summarizes the studied pulmonary function tests of the studied patients and CGs. There were significantly lower FVC, FVC%, FEV1, FEV1%, FEV1/FVC ratio, PEFR, PEFR% and FEF in patients when compared with CG [Table 3].
|Table 3: Comparison of pulmonary function tests between patients and control group.|
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[Table 4] shows that there were significant negative correlations between the FVC, FEV1, FEV1/FVC ratio and the dialysis duration in the patient's group where (P <0.001) [Figure 1], [Figure 2] and [Table 4]).
|Figure 1: Correlation between FVC and dialysis duration (in days).|
FVC: Forced vital capacity.
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|Figure 2: Correlation between FEV1 and dialysis duration (in days).|
FEV1: Forced expiratory volume in 1 s.
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|Table 4: Correlation between the dialysis duration and pulmonary function tests in the studied patents group.|
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[Table 5] shows that there was a restrictive pattern of spirometry in 30 patients with ESRD (75%) and mixed obstructive and restrictive pattern in 10 patients (25%) with highly significant differences between patients and CG regarding different patterns of spirometry.
|Table 5: Pattern of spirometry in the studied patients and control group.|
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| Discussion|| |
Chronic renal failure (CRF) may affect respiratory function. Pulmonary dysfunction may be the direct consequence of circulating uremic toxins or may result indirectly from volume overload, anemia, immune suppression, extra osseous calcification, malnutrition, electrolyte disorders, and/or acid-base imbalances.
Patients with CKD may have muscle dysfunction due to interrelated factors, such as decreased protein-calorie intake, muscle disuse atrophy, and protein imbalance. These factors lead to changes in type II muscle fibers and reduction of the capillary vascular bed, intravascular presence of calcification, and reduction of local blood flow, thus contributing to muscle alterations.
In the present study, we evaluated pulmonary function tests in 40 patients with ESRD who were under regular HD in the Pediatric Nephrology Unit of Pediatric Department of TUH, compared to 40 healthy individuals of same age and sex as CG.
In our study, comparison between the different studied groups as regards arterial blood gases (ABG). Although all values were within normal levels, PaO2 in HDG was less than that in CG (P <0.001, mean ± SD of HDG was 80.45 ± 3.63 and for CG was 85.65 ± 2.62).
Our results regarding ABG were in accordance with Ahluwalia et al who studied pulmonary functions during peritoneal dialysis and found no significant differences in PaO2, PaCO2, or PH during any phase of the study.
Our results were also in accordance with Herrero et al. who studied pulmonary diffusion capacity in chronic dialysis patients and found that PaO2 and PaCO2 were similar in all the groups with no significant differences. PH and bicarbonate were within normal values in all groups; although, it is less in the group without dialysis than in the group with HD.
The present study demonstrates that children and adolescents with CKD have a significant reduction in lung functional capacity. In our study, we found that there was a significant difference between HDG and CG regarding FVC % of predicted (P <0.001, mean ± SD of HDG was 54.4 ± 13 and for CG was 93.5 ± 3.8), FEV1% of predicted (P = 0.001, mean ± SD of HDG was 47.1 ± 10.9 and for CG was 93.3 ± 5.4), FEV1/FVC % of predicted (P = 0.001, mean ± SD of HDG was 74.3 ±21.4, and for CG was 89.46 ±9.1), PEFR% of predicted (P <0.001, mean ± SD of HDG was 26.9 ±14.1 and for CG was 92.5 ± 4.3).
This was in agreement with Paul and Mavirdi who studied 45 patients with CRF which were classified as six under conservative treatment, 11 under regular HD, eight under continuous ambulatory peritoneal dialysis (CAPD) and 20 postkidney transplantation. They showed that their children with CRF had significantly lower FEV1 and FVC than controls who were matched for sex, race, and height (P >0.05) and added in their study that there was no significant correlation between hemoglobin % and FEV1 in their CRF patients (P >0.05). Our results were also in agreement with Bush et al who concluded reduced spirometric values in 71 out of 80 studied adult patients with ESRD.
Our results were also in accordance with Rev Bras Fisioter who reported reduced spirometric measures including FVC, FEV1 in their 42 studied ESRD patients (32 under dialysis and 10 underwent kidney transplantation) when compared to their 30 healthy controls (P <0.05) and added that they were not improved after kidney transplantation. These results are also in agreement with those of Kovacević et al, Teixeira et al, and de Medeiros et al who found that patients who were on long term HD showed a significant decline in FVC.
We found also FEF was less than normal in HDG and was within the normal range in CG (FEF mean ± SD in HDG was 1.2 ± 0.53 and for CG was 3.7 ± 0.36), this means that there was a small airway obstruction in HDG.
Our results are in agreement with those of Karacan et al who found significantly lower residual volume and total lung capacity in the HD and peritoneal dialysis groups than in the transplantation group. FEF between 25% and 75% of vital capacity was slightly below normal in the dialysis patients.
Kalender et al studied the effect of renal transplantation on pulmonary function and found that PEF was decreased in the uremic group than that in the transplant group. Furthermore, Bush and Gabriel concluded that patients with CKD undergoing dialysis and kidney transplant patients have limitations to their ventilatory capacity.
They believed that the likeliest cause of this is subclinical pulmonary edema or interstitial fibrosis secondary to recurrent pulmonary edema which would be favored by increased vascular permeability, fluid overload, and a low-serum albumin concentration.
Cury et al studied the pulmonary function and the functional capacity among patients with CKF undergoing dialysis and among kidney transplant patients and found that individuals in the HDG had worse results than did those in the CG.
Our results were not in agreement with Morales et al who studied the lung function pre- and postrenal transplantation on 21 patients and determined spirometry including lung volumes, ABG, before and 3, 6, and 12 months after transplantation. They concluded that spirometric and blood gases data remained within reference levels during the follow-up.
In this study, there were significant negative correlations between the duration of HD and both FVC and FEV1 in ESRD patients. This was in agreement also with Senatore et al but our results are not in agreement with Abdalla et al who reported that pulmonary function in their HD patients was not completely improved in the kidney transplant patients. Our results were not in agreement also with Paul and Mavirdi. who reported a significant positive correlation between HD and FEV1 in their CRF patients. Our results were not in agreement also with Bush and Gabriel who reported no significant correlation between duration of renal replacement therapy and spirometric values in their studied adult patients with ESRD (included 4 groups; before renal replacement therapy, after HD, after CAPD and after cadaveric renal transplant).
Variation between the study and previous studies may be explained by different locality, different number of studied patients, variations in ages of studied patients, variations in the severity of disease, variations in the degree of efficacy of therapy and compliance with dialysis therapy.
In the present work, there were restrictive spirometric pattern in 75% of studied patients with ESRD and mixed obstructive and restrictive pattern in 25% of patients which was consistent with Dujić et al. who reported that in their children with CKD, a decrease in spirometric variables was related to reversible airway obstruction and air trapping caused by accumulation of fluid near the small airways.
A French study revealed that children with CKD may have airflow limitations, where the reduction in FEV1 may be associated with decreased muscle strength, responsible for the delay in skeletal muscle fiber contraction.
The restrictive pattern may be attributed to lung injury resulting from repeated episodes of pulmonary damage as acute chest syndrome secondary to associated thromboembolism, pneumonia, fat embolization, or pulmonary hypertension.,
| Conclusions|| |
According to our findings, it can be concluded that pulmonary function tests decrease significantly in patients with ESRD undergoing HD compared with controls of matched age with significant negative correlation with dialysis duration. Most ESRD patients presented with abnormal pulmonary functions, being predominant of restrictive pattern.
| Recommendations|| |
Patients with ESRD under regular HD should undergo pulmonary function tests using spirometry as follow-up investigation to detect associated pulmonary complications included obstructive, restrictive, or mixed patterns of impaired pulmonary function.
Conflict of interest:
| References|| |
Rodriguez-Roisin R, Barbera JA. Pulmonary complications of abdominal disease. In: Mason RJ, Broaddus VC, Murray JF, Nadel JA, editors. Murray and Nadel's Textbook of Respiratory Medicine. Philadelphia: Elsevier Saunders; 2005. p. 2223-41.
Harambat J, van Stralen KJ, Kim JJ, Tizard EJ. Epidemiology of chronic kidney disease in children. Pediatr Nephrol 2012;27:363-73.
Goldstein SL, Rosburg NM, Warady BA, et al. Pediatric end stage renal disease health-related quality of life differs by modality: A PedsQL ESRD analysis. Pediatr Nephrol 2009;24:1553-60.
Johansen KL. Exercise and chronic kidney disease: Current recommendations. Sports Med 2005;35:485-99.
Igarashi H, Kioi S, Gejyo F, Arakawa M. Physiologic approach to dialysis-induced hypo-xemia. Effects of dialyzer material and dialysate composition. Nephron 1985;41:62-9.
Senatore M, Buemi M, Di Somma A, Sapio C, Gallo GC. Respiratory function abnormalities in uremic patients. G Ital Nefrol 2004;21:29-33.
Tarasuik A, Heimer D, Bark H. Effect of chronic renal failure on skeletal and diaphragmmatic muscle contraction. Am Rev Respir Dis 1992;146:1383-8.
Kemp GJ, Crowe AV, Anijeet HK, et al. Abnormal mitochondrial function and muscle wasting, but normal contractile efficiency, in haemodialysed patients studied non-invasively in vivo
. Nephrol Dial Transplant 2004;19:1520-7.
Sakkas GK, Sargeant AJ, Mercer TH, et al. Changes in muscle morphology in dialysis patients after 6 months of aerobic exercise training. Nephrol Dial Transplant 2003;18: 1854-61.
Romero-Corral A, Somers VK, Sierra-Johnson J, et al. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J Obes (Lond) 2008;32:959-66.
George-Gay B, Parker K. Understanding the complete blood count with differential. J Perianesth Nurs 2003;18:96-114.
ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: Guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002;166:111-7.
Khothari CR. Research Methodology, Methods and Techniques. 2nd
ed. New Delhi: New Age International; 2012. p. 95-7.
Pierson DJ. Respiratory considerations in the patient with renal failure. Respir Care 2006; 51:413-22.
Adey D, Kumar R, McCarthy JT, Nair KS. Reduced synthesis of muscle proteins in chronic renal failure. Am J Physiol Endocrinol Metab 2000;278:E219-25.
Ahluwalia M, Ishikawa S, Gellman M, Shah T, Sekar T, MacDonnell KF. Pulmonary functions during peritoneal dialysis. Clin Nephrol 1982; 18:251-6.
Herrero JA, Alvarez-Sala JL, Coronel F, et al. Pulmonary diffusing capacity in chronic dialysis patients. Respir Med 2002;96:487-92.
Paul K, Mavridis G, Bonzel KE, Schärer K. Pulmonary function in children with chronic renal failure. Eur J Pediatr 1991;150:808-12.
Bush A, Gabriel R. Pulmonary function in chronic renal failure: Effects of dialysis and transplantation. Thorax 1991;46:424-8.
Cury JL, Brunetto AF, Aydos RD. Negative effects of chronic kidney failure on lung functions and capacity. Braz J Physiother 2010; 14:91-8.
Kovacević P, Stanetic M, Rajkovaca Z, Meyer FJ, Vukoja M. Changes in spirometry over time in uremic patients receiving long-term hemo-dialysis therapy. Pneumologia 2011;60:36-9.
Teixeira CG, Duarte Mdo C, Prado CM, Albuquerque EC, Andrade LB. Impact of chronic kidney disease on quality of life, lung function, and functional capacity. J Pediatr (Rio J) 2014; 90:580-6.
de Medeiros AIC, Fuzari HKB, Rattesa C, Brandão DC, de Melo Marinho PÉ. Inspiratory muscle training improves respiratory muscle strength, functional capacity and quality of life in patients with chronic kidney disease: A systematic review. J Physiother 2017;63:76-83.
Karacan O, Tutal E, Colak T, Sezer S, Eyüboğlu FO, Haberal M. Pulmonary function in renal transplant recipients and end-stage renal disease patients undergoing maintenance dialysis. Transplant Proc 2006;38:396-400.
Kalender B, Erk M, Pekpak MA, et al. The effect of renal transplantation on pulmonary function. Nephron 2002;90:72-7.
Cury JL, Brunetto AF, Aydos RD. Negative effects of chronic kidney failure on lung function and functional capacity. Rev Bras Fisioter 2010;14:91-8.
Morales P, Cremades MJ, Pallardó L, Pastor A, Macián V. Effect of cyclosporin on lung diffusing capacity in renal transplant patients. Transpl Int 1995;8:481-4.
Abdalla M, AbdElgawad M, Alnahal A. Evaluation of pulmonary function in renal transplant recipients and chronic renal failure patients undergoing maintenance hemodialysis. Egypt J Chest Dis Tuberc 2013;62:145-50.
Dujić Z, Tocilj J, Ljutić D, Eterović D. Effects of hemodialysis and anemia on pulmonary diffusing capacity, membrane diffusing capacity and capillary blood volume in uremic patients. Respiration 1991;58:277-81.
Siafakas NM, Argyrakopoulos T, Andreopoulos K, Tsoukalas G, Tzanakis N, Bouros D. Respiratory muscle strength during continuous ambulatory peritoneal dialysis (CAPD). Eur Respir J 1995;8:109-13.
Mohamed A El-Gamasy
Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta City, Gharbia Governate
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]