|Year : 2019 | Volume
| Issue : 3 | Page : 615-627
|Evaluation of dialysis practice patterns in children having end-stage renal disease on maintenance hemodialysis at a pediatric nephrology unit
Ghada M El-Mashad1, Zein Abdellatif Omar1, Eman Salah Seif2
1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt
2 Department of Pediatrics, El-Helal Health Insurance Hospital, Shebin El-Kom, Menoufia, Egypt
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|Date of Submission||07-Mar-2018|
|Date of Decision||15-May-2018|
|Date of Acceptance||02-Jul-2018|
|Date of Web Publication||26-Jun-2019|
| Abstract|| |
Hemodialysis (HD) involves purifying the blood of waste products through diffusion through a semipermeable membrane. We aimed to evaluate dialysis practice patterns among children with end-stage renal disease (ESRD) on maintenance HD (MHD). This cross-sectional study was conducted on 30 children with ESRD on MHD at the pediatric nephrology unit of Menoufia University and 18 age- and sex-matched children who served as the control group. Consent was obtained from children more than seven years old and their parents and from parents of younger children. They were all subjected to full history, complete physical examination, efficiency measures estimation (for cases), and laboratory investigations. Risk factors for death were determined using the logistic regression model; data were analyzed using the Statistical Package for the Social Sciences software. The study showed that the causes of ESRD in children were unknown in 43.3%; about 73.3% of cases were short-statured and 53.3% were underweight. About 40% of the cases were hypertensive showing a significant difference from controls (P <0.01). A double-lumen jugular catheter (DLJC) was the initial access in 80% of cases. The urea reduction ratio and Kt/V were significantly higher in children with arteriovenous fistula (AVF) than those with DLJC (P <0.0001 and 0.004), respectively. About 66.7% of cases had anemia showing a significant difference from controls (P <0.01). Hypoalbuminemia, anemia, elevated C-reactive protein, and left ventricular hypertrophy were the significant risk factors resulting in death (P <0.0001). Although the most common initiating vascular access used for HD patients was a DLJC, the efficiency of dialysis was significantly higher in patients who had AVF. Stature was affected more than weight in HD patients in the study group.
|How to cite this article:|
El-Mashad GM, Omar ZA, Seif ES. Evaluation of dialysis practice patterns in children having end-stage renal disease on maintenance hemodialysis at a pediatric nephrology unit. Saudi J Kidney Dis Transpl 2019;30:615-27
|How to cite this URL:|
El-Mashad GM, Omar ZA, Seif ES. Evaluation of dialysis practice patterns in children having end-stage renal disease on maintenance hemodialysis at a pediatric nephrology unit. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Jul 23];30:615-27. Available from: http://www.sjkdt.org/text.asp?2019/30/3/615/261334
| Introduction|| |
Chronic kidney disease (CKD) is an abnormality in renal structure (detected by histology or inferred by imaging) or function (detected by proteinuria, albuminuria) which is persistent for three months or longer. As regards the pathophysiology of CKD, the Brenner hypothesis postulated that any critical loss of functioning renal nephrons, regardless of the cause of the initial injury, leads to glomerular hyperfiltration with an increased single-nephron glomerular filtration rate. The remaining nephrons lose their ability to autoregulate glomerular pressure, resulting in direct transmission of systemic hypertension to the glomerulus. Elevated intra-glomerular pressure induces glomerular and tubular hypertrophy besides endothelial and podocyte cell injury, resulting in vasculotoxic and inflammatory insults, which, in turn, are involved in progressive glomerular damage, inducing local inflammation and fibrosis., Furthermore, proteinuria is induced by increased intra-glomerular pressure and permeability; angio-tensin II is the primary stimulator of the renin-angiotensin system and is involved in most of the pathways described above. Angiotensin II is produced both systemically and locally in the kidney and exerts multiple endocrine, autocrine, and paracrine effects. Intrarenal angiotensin II concentrations are three-folds higher than in the circulation, angiotensin II is a potent vasoconstrictor that augments the level of intra-glomerular pressure by preferentially increasing the efferent arteriolar tone. The general management guidelines of CKD patient include the following components: treat reversible kidney dysfunction (treatment of renal hypoperfusion, avoid nephrontoxic drugs); prevent or slow down the progression of kidney disease, treat complications of CKD such as hypertension by using drugs, (angiotensin-converting enzyme inhibitor, angiotensin-receptor blocker, dual renin-angiotensin aldosterone system blockade and diuretic therapy); treatment of other complications such as glycemic control, anemia, mineral bone disorder, metabolic acidosis, cardiovascular disease, lipid management, and nutritional management. In addition, identify and adequately prepare the child/family in whom renal replacement therapy will be required. Finally, when indicated, transition to end-stage renal disease (ESRD) therapies are required and include hemodialysis (HD), peritoneal dialysis, and renal transplantation.
HD involves purifying the blood of a patient having nonfunctioning kidneys of waste products; it offers a higher rate of molecular transfer than peritoneal dialysis and other continuous renal replacement therapies and this qualifies it to be the most effective artificial renal support. Although HD is not a curative measure, it alleviates many serious and sometimes lethal adverse outcomes of CKD. HD patients have a higher hospitali-zation rate than the general population which, in turn, trigger another set of problems such as anemia, CKD mineral bone disease, vascular access-related complications, and hypertension. Chronic complications involving HD access include thrombosis, infection, ischemic steal syndrome, aneurysms, venous hypertension, hematomas, heart failure, and prolonged bleeding and result in frequent interventions together with increased morbidity and mortality. In addition, access interventions are often expensive, challenging and may require specialized surgical expertise.
In Europe and Japan, the reported five-year mortality rate of patients with ESRD was 20%–35% which was lower than reports from the United States. This observation was independent of age and comorbidities. Dialysis outcomes are practice dependent and this has been confirmed in several studies which have demonstrated a better patient survival on using a higher dialysis dose and different types of dialysis membranes., The dialysis outcomes and practice patterns study offer up-to-date, comprehensive data on HD practice and patient outcomes worldwide.
Assessment of predialysis blood pressure (BP), regular physical examination, and inter-dialytic weight gain (IDWG) are currently the mainstay of fluid assessment in pediatric dialysis patients. Clinical nephrologists routinely counteract the positive phosphate balance in dialysis patients through nutritional counseling, stronger phosphate removal by dialysis, and prescription of phosphate binders.
The general aim of dietary prescription includes: providing enough energy, protein, vitamins, minerals, dietary fiber and reduce intake of salt (sodium), potassium, and phosphate. Oliguric patients have to reduce intake of liquids.
Left ventricular hypertrophy (LVH) is an increase in the left ventricular (LV) mass in response to a disease state, either due to increase in LV wall thickness or an increase in cavity size, or both. These changes of LV diameter represent adaptive responses to pathologic overload due to HTN or valvular disease. Methods of the detection of LVH include: electrocardiogram, echocardiography (ECHO) M-mode (M-mode, motion over time mode), for superior endocardial definition, two-dimensional ECHO, which is more accurate than the M-mode, and 3D ECHO and cardiac magnetic resonance which is the gold standard in the selected population.
The rationale of the present study is that unlike adults, children on HD need extra care as well as special evaluation and monitoring to ensure a successful HD. Thus, this study was designed to evaluate dialysis practice patterns in order to provide better care for children with ESRD on maintenance HD (MHD).
| Materials and Methods|| |
This cross-sectional study was performed at Menoufia university hospital over a one-year period from December 2016 to December 2017. It included 30 children on MHD and 18 control children meeting eligibility criteria:
- They were age- and sex-matched
- They were admitted to the hospital for causes other than kidney disease
- They had normal kidney function tests.
The study protocol was approved by the Ethics Committee of the Menoufia University, and written consents were obtained from children >7 years old and their parents, and from parents of younger children. Patients aged between two and 18 years and on MHD for six months at least using the same HD technique during the past three months were included while patients aged >18 years, not on regular HD or suffering comorbidity such as malignancy or vasculitis were excluded from this study.
All patients included in the study were subjected to full history-taking, stressing on the etiology of renal disease, and vascular access. The patients were classified according to the type of vascular access used in their first HD session: Arteriovenous fistula (AVF) or central venous catheter (CVC), the current vascular access, drugs used, diet, erythro-poietin use, survival on HD, and causes of death.
For vascular access-related complications, classification of data was based on the following definitions:
Initial vascular access is the primary access which was used in the first HD sessions. Infection: Because it is impossible to identify the infection-confirming results of the blood cultures in the records, a CVC infection was considered to exist when it is removed due to fever, and/or when antibiotics were started with no evidence of other infectious focus. Thrombosis: When no blood flow was achieved from AVF or CVC, in spite of attempts to overcome the obstruction. Primary failure: If the AVF did not provide adequate flow since its creation or, an interrupted flow in a previously unused AVF within the first four weeks after its creation.
Complete physical examination stressing on BP and pulse and, systolic BP (SBP) of cases and controls plotted on BP charts, were made. Laboratory investigations including serum albumin and alkaline phosphatase (ALP), complete blood count, C-reactive protein (CRP), serum calcium (Ca), phosphorus (PO4), and parathyroid hormone (PTH) were performed. LVH was detected using 2D ECHO.
The adequacy of HD was assessed using the urea reduction ratio (URR) and the single-pool Kt/V (sp Kt/V). URR was calculated using the following formula: URR = (Predialysis BUN- Postdialysis BUN) ÷ Predialysis BUN. The Sp Kt/V was calculated using the second-generation Daugirdas formula:  Sp Kt/v = -In (R -0.008 × t) + (4 -3.5 × R) xUF/W, where: In = the natural logarithm, R = predialysis BUN/postdialysis BUN, t = dialysis session length (hrs), UF = the ultra-filtration volume (l) and W = postdialysis weight (kg).
To determine the parameters associated with mortality in our nephrology unit, patients who died during the year of the study (dead) were compared with those who survived (survivors). All continuous variables are presented as a mean ± standard deviation and percentage. Variables associated with mortality with P < 0.25 in univariate analysis were entered into the multivariate stepwise logistic regression model. Adjusted odds ratios and 95% confidence intervals were calculated. Level of significance was set at P < 0.05.
| Statistical Analysis|| |
The data accumulated were tabulated and analyzed using the Statistical Package for the Social Sciences (SPSS) software version 15.0 (SPSS, Chicago, Illinois, USA). Results are presented as the mean ± SD, Chi-square test, Mann–Whitney test, /-test, P-values, and odds ratio. Value of P < 0.05 was considered as significant, whereas P < 0.01 was considered highly significant. Pearson’s correlation analysis was used to demonstrate the strength and direction of the association between two quantitative variables, whereas Spearman correlation was used for qualitative and quantitative variables not following the normal distribution.
Ca, PO4, and ALP were measured using Synchron Cx9 (Beckman Instrument. Inc., Fullerton, California USA). PTH was measured using PTH immunoassay (Ibl Gesellschaft, Hamburg, Germany).
| Results|| |
The current study included 30 children with ESRD on MHD: there were 15 males (50%) and 15 females (50%) with a mean age of 12.9 years. Eighteen controls including 55.6% of males and 44.4% of females with a mean age of 10.7 years were also studied. No statistically significant differences were detected among cases and controls regarding age and gender. The etiology of ESRD was unknown in 43.3% of cases. Congenital abnormalities of the kidney and urinary tract (CAKUT) were the cause in 26.6%, glomerulonephritis (GN) in 20%, and cystic kidney in 10% of the patients [Figure 1].
At our nephrology unit, fluid overload assessment was performed through regular physical examination (neck veins-lower limb edema-chest auscultation) together with the measurement of the predialytic BP and IDWG, which was <5% of the total body weight in 100% of the cases that met the target level.
According to body mass index (BMI) Z score, 46.7% of the cases were underweight in contrast to only 5.5% of the control group. The mean value of the body weight of the patients was 27.7 kg, while the controls had a mean body weight of 35.8 kg, demonstrating a significant difference. According to the height Z score, 73.3% of the cases were short in contrast to only 5.5% of the control group. The mean height of the cases was 126.2 cm, whereas the mean height of controls was 136.9 cm showing a significant difference between both groups [Figure 2].
|Figure 2: Distribution of height and BMI Z score centiles among cases and controls.|
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There was a significantly high difference between cases and controls regarding systolic and diastolic BP; the SABP and DABP were high in the study patients compared with controls. Both groups were plotted on BP charts (systolic centile); accordingly, 100% of the controls were within the normal range (5th–<90th). The case group showed that 13.3% were prehypertensive, 26.7% were hypertensive, 13.3% were hypotensive, and 46.7% were normotensive. The heart rate was statistically higher among cases than that of controls [Table 1].
|Table 1: Statistical comparison among cases and controls regarding blood pressure and heart rate.|
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Three patients (25%) with SBP >90th percen-tile did not receive anti-hypertensive medications and were controlled with regular HD only, whereas nine of them (75%) received anti-hypertensive medications in the form of Ca channel blocker, B-blocker, and angiotensin-converting enzyme inhibitor; two (16.7%) of the patients received all three types of medications, three (25%) received two types, and four (33.3%) received only one type.
Phosphate imbalance in HD patients was treated by diet, adequate dialysis including hemodiafiltration in five of the patients (16.7%), and use of phosphate binders (100% of cases received Ca carbonate during the meal as a phosphate binder). The mean PO4 level among cases was 5.05 ± 1.1 mg/dL, 56.7% of cases had normal range of PO4 (3.4–5.3 mg/dL), whereas 36.7% of cases had hyper-phosphatemia.
The initial access was AVF and temporary femoral catheter in 3.3% of patients each, a permanent catheter was used in 13.3% and a double-lumen jugular catheter (DLJC) was used in 80% of patients, which suggested that emergency HD was more frequent than programmed HD. The current access was AVF in 90% of the patients. The cause of failure of the previous fistulas was thrombosis in 50% of patients, hypotension in 20%, trauma in 3.3%, and primary failure in 6.6%. Only 20.1% of the patients had no failure and the most common reason for removal of CVC was infection in 44%, followed by AVF creation in 36%, thrombosis in 12%, and exteriorization in 8% of cases [Table 2].
|Table 2: Initial, current vascular access, type of arteriovenous shunt, causes of failure of previous shunt, and causes of removal of central venous catheters in studied cases.|
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The association between the efficiency of dialysis and access showed that the URR and Kt/V were significantly higher in patients with AVF than DLJC with a value of P < 0.0001 and 0.004, respectively [Table 3].
|Table 3: Association between current vascular access and efficiency measures in the studied cases.|
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No significant differences were detected between cases and controls regarding the total protein, albumin, and CRP. However, there was a significant difference between them regarding hemoglobin (HB) and hematocrit (HCT). The latter was within the normal range in 100% of controls in contrast to only 50% of the cases [Table 4].
|Table 4: Statistical comparison between cases and control regarding biochemical parameters.|
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There were insignificant differences between cases and control regarding serum PO4, but showed highly significant differences between cases and controls regarding serum Ca, ALP, and PTH [Table 5]. Seven cases (23.1%) had LVH detected using 2D ECHO.
|Table 5: Statistical comparison between cases and controls regarding serum calcium, phosphorus, alkaline phosphatase, and parathyroid hormone (mineral bone disease parameters).|
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Nutritional management of children in our nephrology unit, included high protein, low salt, and low potassium fluid intake was advised depending on the urine volume and the amount that is removed by dialysis. Specific daily multivitamin supplement was recommended. Multivitamins-containing large amount of vitamin A were avoided.
In our unit, only one patient (3.3%) received recombinant human growth hormone therapy.
During the year of the study, there were five deaths (16.66%); the causes of death were: arrhythmia in three (10%), septic shock in one (3.33%), and sudden death at home in one (3.33%).
By doing the binary logistic regression analysis to detect the independent predictors for the studied variables among the studied cases, we concluded that decreased HB level, hypoalbuminemia, +ve CRP, and arrhythmia were independent predictors for HD outcome represented by death with a value of P < 0.0001. Patients were divided into survivors, 25 (83.3%) and dead, five (16.66%). Patients having +ve CRP were 34 times more likely to die, anemic patients were more exposed to death than nonanemic patients with odds ratio 14.5. LVH was one of the significant risk factors with odds ratio 8 and finally, patients with hypoalbuminemia were five times more likely to die [Table 6].
|Table 6: Univariate and multivariate logistic regression model between risk factors and the hemodialysis outcome (death).|
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| Discussion|| |
According to the current study, the cause of ESRD was unknown in 43.3%, CAKUT in 26.6%, GN in 20%, and cystic kidney in 10% of cases. This was in concordance with the results of an old Egyptian study where no definite causes were detected.
Lotfy et al, studied 50 Egyptian children <18 years with ESRD on regular HD for at least three months and being followed up at the Pediatric Nephrology and Transplantation Center, Cairo University. They reported urolo-gical disorders (32%), followed by hypoplastic (28%), unknown (20%), and glomerular disease as the most frequent causes of CKD. Among the patient group of the present study, weight and height were the most affected anthro-pometric parameters, 73.3% of patients had short stature and 53.3% were underweight, whereas 94.4% of the controls were of average height and 88.9% had average BMI.
Similar results were reported in studies conducted in developing countries as Egypt. For instance, Lotfy et al found that 90% of patients were short according to standard deviation charts. Furthermore, Elshafie et al reported that 80% of cases had short stature. On the other hand, studies conducted in developed countries generally showed less severely affected anthropometric measurements, some studies reported that only 36.6%, 47.0%, and 43% of children with chronic renal insufficiency, dialysis, and transplantation, respectively, were short. This evident discrepancy could be attributed to the delayed diagnosis and management of the current study cases.
BP is a critical determinant of the severity of the renal failure in children, and the incidence of cardiovascular mortality in childhood-onset renal failure. Thus, efficient control of BP of such patients ensures a better prognosis and longer survival of adults with childhood-onset CKD. Many studies have confirmed that hypertension is a major issue facing dialysis children. They reported that anti-hypertensive drugs were used in >50% of the assessed cases, yet <50% of cases met the criteria for controlled SBP (<90th percentile) after 6 months of dialysis, and 34% of patients with SBP >90th percentile did not receive anti-hypertensive drugs. Similarly, another study also reported that only 39% of the CKD children had controlled BP despite not receiving anti-hypertensive medications, but in our study, only 25% of patients with SBP >90th percentile did not receive anti-hypertensive drugs.
According to the current study, the initial access was AVF in only one patient. Previous studies reported a consistent finding that most patients were initiated on HD using uncuffed dual lumen catheters and only a few patients had a mature AVF at the time of presen-tation.
The majority of patients of the present study needed emergency HD, allowing no time for the insertion of an internal jugular catheter as vascular access and this is consistent with many previous reports.
Only a few patients of the present study presented for the first time with a readily available AVF, which is also consistent with many previous studies. This could be explained on the grounds that most CKD patients receive conservative treatment without creating an AVF at first saving the dialysis as the last option when the condition advances.
The guidelines of the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) necessitates the creation of primary AVF in at least 50% of all new kidney failure patients suspected to receive HD and that 40% of all prevalent patients should have a native AVF. In addition, catheters should be the permanent vascular access for <10% of patients on MHD. Late referral and poor awareness are the major reasons for using temporary catheters for the initiation of dialysis. Thus, early referral and patient education are essential.
A recent study reported that 33% of patients had failure of the AVF and thrombosis was the most common cause accounting for 51%, followed by infection (33%).
According to the KDOQI, a thrombosis rate of 0.25 episodes per patient-year in native fistulae is possible and the infection incidence should not exceed 1% in primary AVF. This emphasizes the need for more fistula surveillance and infection control measures in dialysis programs.
The association between the current vascular access and efficiency measures showed that the URR and Kt/V were significantly higher in AVF than the DLJC. Another study reported similar results of a significantly higher URR in dialysis children using AVF than other vascular accesses.
The mean HB in the current study population was lower than that demonstrated by Elshafie et al in 2016, who reported a mean HB level of 11.9 g/dL. It was lower than that reported from other countries including Sweden (12 g/dL), USA, Spain, Belgium, and Canada (11.6–11.7 g/dL), Australia, New Zealand, Germany, Italy, UK, and France (11.1–11.5 g/dL).
In this study, 63.4% of patients had HB <11 g/dL and 50% of patients had HCT value <33% which is consistent with another study that reported a <33% (target level) HCT value in 54% of patients, and an HB level <11 g/dL in 66% of patients. The KDOQI guidelines of 2006 for the management of anemia in pediatric dialysis patients attributed the low HB level of these patients to the inadequate administration of recombinant erythropoietin as a result of the poor finances as well as the resistance to the administered recombinant erythropoietin due to iron deficiency. This could be absolute or functional deficiency resulting from insufficient dietary intake, blood loss during the dialysis process or from the gastrointestinal tract, too frequent blood tests, insufficient absorption of iron from the intestine and inhibition of iron release from macrophages (anemia of chronic disease), and finally, heightened iron needs during administration of erythropoiesis-stimulating agents.
Recent study results reported serum albumin <3.5 g in the majority of patients, unlike the results of the current study, that indicates malnutrition of these patients.
Consistent results have also shown a significant decrease in Ca in HD patients. Observational studies have indicated that values of Ca, PO4, Ca x PO4 product and PTH outside current guidelines are associated with poor outcomes in HD patients.
A recent study examining early mortality among incident HD patients during the 1st four months versus the subsequent four to 12 months shows cardiovascular diseases were still the most common cause of death during the entire 1st year.
Bradbury showed that the most important risk factors raising the risk of mortality during the 1st year of HD included: CVC, albumin <3.5, PO4 >3.5, congestive heart failure and, cancer. The study was in concordance with a study which showed that C-reactive protein was the strongest risk factor; the reason could be the study population, which included patients with acute kidney injury of various causes, and showed that a low serum albumin level is reported to be a predictor of mortality in dialysis patients.
| Conclusion|| |
Although the most common initial vascular access used for HD patients was the DLJC, dialysis efficiency was significantly higher in patients who had AVF. Undetermined causes of CKD were the main finding in our study, less than half of the patients were in the hypertensive zone, and stature was affected more than weight in HD patients. It is noteworthy that hypoalbuminemia, anemia, +ve CRP, and arrhythmia were the significant risk factors for death in our unit.
| Acknowledgment|| |
This research project has been supported by the pediatric nephrology unit, Pediatric Hospital, Menoufia University hospital, Egypt.
Conflict of interest: None declared.
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Zein Abdellatif Omar
Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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