Menoufia Medical Journal

ORIGINAL ARTICLE
Year
: 2019  |  Volume : 32  |  Issue : 1  |  Page : 323--328

C-reactive protein as a marker of pediatric hemodilaysis adequacy


Ghada M El-Mashad1, El S. I. El-Gebally1, Tarek H Mohamed Afifi2,  
1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Department of Pediatrics, Abo Hammad Central Hospital, Sharkia, Egypt

Correspondence Address:
Tarek H Mohamed Afifi
Abo Hammad, Sharkia 173347
Egypt

Abstract

Objective To compare the C-reactive protein (CRP) levels with the delivered dose of dialysis in terms of index of hemodialysis adequacy (Kt/V) in patients undergoing maintenance hemodialysis (HD). Background According to different studies, the target Kt/V should be 1.2 per session, while weekly Kt/V should be 4.5 for thrice-weekly HD patients to maintain adequate HD. Patients and methods This is a comparative, cross-sectional survey study. Patients who fulfilled the inclusion and exclusion criteria were enrolled in the present study. The delivered dose of HD, Kt/V was assessed by online clearance module (OCM) in Fresenius machines at the end of every session of dialysis and the weekly Kt/V was determined by adding all the three Kt/V values. On the other hand, serum CRP was determined after each session of HD. Both weekly Kt/V and CRP values were entered in a predesigned proforma. Results Of 30 patients on maintenance HD, high serum CRP level (>6 mg/dl) was found in nine patients. When the Kt/V was compared with the CRP level, there was a negative correlation between the two parameters (r = −0.4, P < 0.001). Low Kt/V means dialysis inadequacy, which is associated with CKD state, resulting in high CRP levels. Conclusion Low Kt/V means dialysis inadequacy, and is associated with chronic inflammatory state resulting in high CRP levels. To reduce the rate of morbidity and mortality, we concluded that the quality of life of dialysis patients can be improved by offering an adequate dose of HD reflected by Kt/V of at least 4.5 per week in all patients with end-stage renal disease.



How to cite this article:
El-Mashad GM, El-Gebally ES, Mohamed Afifi TH. C-reactive protein as a marker of pediatric hemodilaysis adequacy.Menoufia Med J 2019;32:323-328


How to cite this URL:
El-Mashad GM, El-Gebally ES, Mohamed Afifi TH. C-reactive protein as a marker of pediatric hemodilaysis adequacy. Menoufia Med J [serial online] 2019 [cited 2019 Aug 23 ];32:323-328
Available from: http://www.mmj.eg.net/text.asp?2019/32/1/323/256130


Full Text



 Introduction



Chronic hemodialysis (HD) is technically feasible in children of all ages, and even in very small neonates. There are technical aspects of the procedure and complications that are unique to the pediatric population. It is crucial that these differences are recognized and addressed in order to effectively and safely perform pediatric HD, thereby reducing complications in children who are facing a lifetime of renal replacement therapy (RRT) [1].

Adequate dialysis dose is one of the most important goals in HD treatment and appropriately prescribed. Achieving a minimum dialysis dose is the responsibility of nephrologists and represents an area open to improvement. Because age, sex, and comorbidity cannot change, and dialysis parameters adjusted to ensure that the patient receives the optimal treatment [2]. Dialysis adequacy is assessed by clinical and laboratory data along with solute clearance. These are blood pressure control, nutritional status, uremic symptoms, inflammatory markers, serum phosphate levels, metabolic acidosis, urea reduction ratio, time average concentration of urea and Kt/V [3].

The dose of weekly delivered dose of Kt/V is an index of dialysis adequacy and defined as the fractional clearance of urea as a function of its distributional volume. According to different studies, the target Kt/V should be 1.2 per session, while weekly Kt/V should be 4.5 for thrice-weekly HD patients to maintain adequate HD [4].

An adequate amount of dialysis results in reversal of uremic symptoms and helps to improve the patient's nutritional and functional status as well as increasing patient survival [5]. Therefore, the goal of this study was to compare the CRP levels with the delivered dose of dialysis in terms of Kt/V in patients undergoing maintenance HD.

 Patients and Methods



The comparative cross-sectional survey studied 30 stable children with ESRD on regular maintenance HD for more than 6 months at the HD Unit of the Menoufia University Hospital, for 6 month from June 2016 to December 2016. Their ages ranged from 3 to 15 years with male to female ratio of 1:1. They were dialyzed three times a week for 4 h duration of each dialysis session using Fresenius 4008B machines (Fresenius Medical Care AG, Homburg, Germany). Blood flow 300 ml/min; and dialysate flow rate 500 ml/min.

Patients who were malnourished with serum albumin less than 3 g/dl, having tunnel dialysis catheters or functional or failed grafts and critically ill patients due to multiple comorbidities like malignancies, advanced cirrhosis, septicemia and chronic inflammatory diseases were excluded from our study. This study approved by the Ethical Committee of Menoufia University Hospital. Verbal and written consent obtained from all patients.

A brief history taking and clinical examination performed from all patients included in the study. Demographic information was collected from the database: age, sex, type of admission, ICU admission, use of mechanical ventilation, use of RRT, admission units, length of hospital stay and hospital mortality.

Fasting blood samples taking from the arterial line immediately before the mid-week dialysis session before heparin administration and obtained from the HD patients. The samples were then centrifuged at 1700g for 15 min or into serum separator tubes and frozen at −70°C before the measurements.

Biochemical determinations included levels of serum albumin, blood urea nitrogen (BUN) and serum creatinine (predialysis and postdialysis), lipid profile, and hemoglobin (Hb) level. Dialysis adequacy assessed by kinetically determined Kt/V and urea reduction ratio measurements at each study time point.

The delivered dose of HD (Kt/V) assessed by the OCM at the end of every dialysis session and weekly Kt/V was determined by adding all three Kt/V values. Serum CRP measured by the agglutination method after each session of HD, and reported as mg/dl. The mean CRP was calculated and considered elevated if it was more than 6 mg/dl. The CRP human ELISA kit was purchased from Abcam (Cambridge, UK) according to the manufacturer's protocols provided with each kit. Values of weekly Kt/V and mean CRP were entered in a predesigned proforma. The present study was statistically analyzed using statistical program for the social sciences (version 22.0; IBM, Armonk, New York, USA) [6]. Frequencies; calculated for variables like sex. Mean ± SD was calculated for numerical variables like age, Kt/V and CRP. The χ2-test used to compare the Kt/V and CRP levels. The Wilcoxon signed-rank test used to evaluate the association between variables compared with the paired t-test, while the Mann–Whitney U-test used for variables compared with the unpaired t-test. The correlation between Kt/V and CRP was determined by applying Pearson's correlation coefficient. For all above-mentioned statistical tests, P value was up to 0.05 taken as a significant [Figure 1].{Figure 1}

 Results



Thirty patients on regular HD, 15 were males and 15 were females, with a mean age of 13.2 ± 3.9 years and ranged from 3 to 15 years. On the other hand, in predialysis the mean ± SD of serum BUN level found to be 49.1 ± 14.7 g/dl. The mean serum creatinine level found to be 9.5 ± 2.5 mg/dl. Serum albumin, levels decrease as glomerular filtration rate (GFR) declines, even prior to the start of dialysis. The patients included in the project had average albumin levels from 3.3 to 4.9 g/dl. The mean ± SD of albumin was 3.9 ± 0.2 g/dl. In addition, the mean ± SD of serum CRP level found to be 7 ± 10.2 mg/l, and the mean weekly delivered dose of Kt/V was 1.4 ± 0.5, with a proposed target dose of 1.5 per dialysis session. However, the mean ± SD of ultrafiltration found to be 1.2 ± 0.7. However, the average Hb values for study group who conducted in the present study ranged from 11.1 to 11.7 g/dl; the mean ± SD of Hb was 10.9 ± 1.6. Finally, the mean ± SD of dialysis time was 3.9 ± 0.2 h and ranged from 3 to 4 h with median 4 h. In addition, the mean onset of dialysis was 3.4 ± 3.5 h and ranged from 0.25 to 15 years with median 2 years. On the other hand, the blood flow rates (>300 ml/min; 16.7%) was noted and differences for both variables as shown in [Table 1].{Table 1}

The mean weekly delivered dose of Kt/V the minimum dose being 1.2 and the maximum dose being 4.5. The patients were divided into two groups according to Kt/V (high and low Kt/V), and compared with their CRP levels. Group 1 (nine patients) had achieved the target weekly delivered dose of Kt/V of at least 1.2, whose mean CRP was 2.4 ± 0.07 mg/dl; 21 subjects did not achieve the target dose of Kt/V were included in group 2, whose mean CRP was 8.9 ± 1.8. The difference was highly significant (t = 6.1; P < 0.001). Also, all patients were divided into two groups according to CRP high level more than 6 mg/dl and CRP low level less than 6 mg/dl, and compared for their weekly delivered dose of Kt/V. Group 1 (10 patients) had CRP more than 6 mg/l whose mean Kt/V of at least 1.2 was 0.9 ± 0.3. Group 2 (20 patients) had CRP less than 6 mg/l whose mean Kt/V up to 1.2 was 3.04 ± 1.1. The difference was highly significant (t = 4.6; P < 0.001) as shown in [Table 2].{Table 2}

The result demonstrated that there was highly significant negative correlation between Kt/V and height, weight, SBP, and DBP between studied groups (r = −0.5, P = 0.002; r = −0.4, P = 0.02; r = −0.4, P = 0.02; r = −0.3, P = 0.04; r = −0.5, P = 0.002, respectively). Otherwise, there is no significant correlation between Kt/V and other variables. However, there was highly significant negative correlation between CRP and dialysis time (r = −0.6, P < 0.001). Otherwise, there is no significant correlation between CRP levels and other variables as shown in [Table 3].{Table 3}

There was highly significant negative correlation between Kt/V and BUN and creatinine level in postdialysis (r = −0.5, P < 0.001; r = −0.6, P < 0.001, respectively). Otherwise, there is no significant correlation between Kt/V and other variables. However, there was no significant correlation between CRP levels among laboratory investigations of the studied patients (P > 0.05) as shown in [Table 4].{Table 4}

 Discussion



At present, HD dose quantified by the Kt/V, which measures urea removal during treatment and a single pool Kt/V of 1.2, considered as adequate dose [7]. The primary data from the National Cooperative Dialysis Study showed that Kt/V less than 0.8 was associated with a high morbidity, whereas Kt/V values between 1.0 and 1.2 were associated with better outcome [8].

The presence of elevated CRP more than 6 mg/l in dialysis patients should prompt a search for immediately treatable causes of acute or chronic inflammation [9].

In total, 30 HD children were included in our study (mean ± SD of age, 13.2 ± 3.9 years) and ranged from 3 to 15 years with median 13 years. The male to female ratio was 1:1.

In predialysis patients, the present study demonstrated that the mean BUN level found to be 49.1 ± 14.7 g/dl. Amin et al. [10] demonstrated that, in ESRD patients, predialysis serum urea level was significantly higher than normal range (20–40 mg/dl). Most of the patients (53%) had serum urea level between 200–300 mg/dl. After dialysis, there was a clear reduction in serum urea levels; in most of the patients it reduced to 1–100 mg/dl (26%) and 101–200 mg/dl (40%). Mustafa and Khalaf [11], pointed that the rise in urea concentration reflects occurrence of uremia in patients that represent the ESRD.

The present study findings demonstrated the mean serum creatinine levels between our patients found to be 9.5 ± 2.5 mg/dl. Amin and colleagues demonstrated that, serum creatinine level was higher than normal range (≤1.4 mg/dl) in ESRD patients undergoing dialysis. Most of the patients have serum creatinine level between 7.6–12 mg/dl (57%) and 12–15 mg/dl (27%) before dialysis. Dialysis has positive impact on serum creatinine level and reduced its level towards normal value [9]. GFR or creatinine clearance is the based method for the estimation of kidney functioning. Factors like age, sex and physical status of person also effect serum creatinine level [12].

Alain et al. [13] pointed that the increase the urea concentration in the blood serum depends not only on renal function. In all cases of pre-renal above, the level of creatinine concentration in serum is normal, therefore urea does not reflect the renal function.

The mean albumin in the present study in predialysis was 3.9 ± 0.2 g/dl, and ranged from 3.3 to 4.9 g/dl with median 4.4 g/dl. On the other studies Daniel et al. [14] and Kaysen [15], were found low serum albumin concentration in HD children. In addition, Lowrie and Lew [16] showed that the low pre-HD serum albumin levels were associated with an increased likelihood of death and suggested that the established relationship between hypoalbuminemia and mortality would be mainly due to protein-energy malnutrition.

In the present study, serum CRP was assayed as a marker of chronic inflammation; our study found that 100% of patients on regular HD had high CRP, with mean CRP was 7 ± 10.2 mg/dl; this in agreement with Honda et al. [17], who reported a significant increase in CRP levels in maintenance HD patients. However, the mean Kt/V was 1.4 ± 0.5, with a proposed target dose of 1.5 per dialysis session [18].

The present study findings demonstrated that, the mean Hb was 10.9 ± 1.6 patients of the present study. This value is lower than the recommended DOQI guideline that recommends an Hb of 11–12 g/l. In the current study, mean Hb was lower as compared to other countries. Mean Hb levels were 12 g/dl in Sweden; 11.6–11.7 g/dl in the USA, Spain, Belgium, and Canada; and our results agreement with several studies such as Australia, New Zealand, Germany, Italy, the UK, France, and Egypt, the mean level was 11.1–11.5 g/dl [18],[19]. These factors responsible for the low Hb levels in our patients compared to the DOQI guidelines. In agreement with our results Mahan and Warady [19], stated that anemia is almost invariable feature of ESRD and usually becomes manifest at a GFR less than 35 ml/min/1.73 m 2.

The result of our study show the mean ± SD of dialysis time was 3.9 ± 0.2 h and ranged from 3 to 4 h with median 4 h. In addition, the onset of dialysis was 3.4 ± 3.5 h and ranged from 0.25 to15 years with median 2 years. On the other hand, the blood flow rates (>300 ml/min; 16.7%) was noted and differences for both variables. In agreement with our results, Malekmakan et al. [20] study has shown no significant differences between their patients concerning the duration of dialysis.

In the current study, subjects were divided into two groups according to CRP levels and their Kt/V value (high and low). High serum CRP more than 6 mg/dl was found in 10 patients; and high Kt/V more than 1.2 was found in nine patients. As regard dialysis adequacy, results of this study revealed that about 70% of the study population had Kt/V less than 1.2, indicating that patients were receiving inadequate dose. In study of Lotfy et al. [21], included 50 Egyptian children below 18 years with ESRD on regular HD for at least three months and being followed up, they demonstrated that the dialysis efficiency, as measured by Kt/V, had a mean of 1.8 ± 0.4. All patients had Kt/V more than 1.2. According to CRP levels (high and low) and compared with their Kt/V. In accordance with other study, the present study showed patients had CRP more than 6 mg/l whose mean Kt/V was 0.9 ± 0.3; and patients had CRP less than 6 mg/l whose mean Kt/V was 3.04 ± 1.1 (P < 0.001); the difference was highly significant [22].

According to Kt/V (high and low Kt/V) and compared with their CRP levels, in the present study; our subjects divided into two groups. Group I (nine patients) had achieved the target weekly delivered dose of Kt/V of at least 1.2, whose mean CRP level was 2.4 ± 0.7 mg/l; group 2 (21 patients) did not achieve the target dose of Kt/V of at least 1.2, whose mean CRP was 8.9 ± 1.8 mg/l (P < 0.001). The difference was highly significant which is in concordance with other Egyptian studies [14],[21],[22].

The present study findings demonstrated a significantly higher negative correlation between Kt/V and height, weight, SBP, and DBP between studied groups (r = −0.5, P = 0.002; r = −0.4, P = 0.02; r = −0.4, P = 0.02; r = −0.3, P = 0.04; r = −0.5, P = 0.002, respectively). Otherwise, there is no significant correlation between Kt/V and other variables. These results were in agreement with the study of Panagoutsos et al. [23], who found out that a reduction in blood pressure with increased dialysis dose suggesting a central role of increased dialysis dose [23]. Others have also reported similar findings with corresponding increase of dialysis dose. On the other hand, the results of the present study were in disagreement with McGregor et al. [24] and El-Sheikh and El-Ghazaly [25], who did not ascertain any correlation between Kt/V and blood pressure, and the study of Rahman et al. [26], who found out strong correlation between blood pressure and interdialytic weight gain.

In addition, there was a significantly higher negative correlation between CRP level and dialysis time (r = −0.6, P < 0.001). Otherwise, there is no significant correlation between CRP levels and other variables. These results were in agreement with the study of Elshamaa et al. [22]. However, Lotfy et al. [21] demonstrated that, the duration of HD showed a significant negative correlation with height CRP levels.

The present study shows highly significant negative correlation between Kt/V and BUN and creatinine level in postdialysis (r=−0.5, P < 0.001; r = 0.6, P < 0.001, respectively). Otherwise, there is no significant correlation between Kt/V and other variables. These results were in agreement with the study of Eknoyan et al. [7] and Nilsson et al. [2].

The present study shows that there was no significant correlation between CRP levels and patients investigations. These finding was in agreement with the study of Elshamaa et al. [22] and Gheissari et al. [27].

 Conclusion



CRP has an inverse correlation with Kt/V in chronic HD patients. Low Kt/V means dialysis inadequacy, and is associated with chronic inflammatory state resulting in high CRP levels. We suggest that the quality of life of dialysis patients who can be improved by offering an adequate dose of HD reflected by Kt/V of at least 4.5 per week in all patients with ESRD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1Ibrahim N, Wong IC, Tomlin S, Sinha MD, Rees L, Jani Y. Epidemiology of medication-related problems in children with kidney disease. Pediatr Nephrol 2015; 30:623–633.
2Nilsson LG, Bosch JP, Alquist M. Quality control in haemodialysis delivery. Eur Nephrol 2011; 5:132–137.
3Anees M, Ahmed AM, Rizwan SM. Evaluation of nutritional status of patients on haemodialysis. J Coll Physicians Surg Pak 2004; 14:665–669.
4Goldau R, Kuhlmann U, Samadi N, Gross M, Graf T, Orlandini G, et al. Ionic dialysance measurement is urea distribution volume dependent: a new approach to better results. Artif Organs 2002; 26:321–332.
5Korevaar JC, van Manen JG, Dekker FW, de Waart DR, Boeschoten EW, Krediet RT, et al. Effect of an increase in C-reactive protein level during a hemodialysis session on mortality. J Am Soc Nephrol 2004; 15:2916–2922.
6Nuzzo R. Scientific method: statistical errors. Nature 2014; 506:150–152.
7Eknoyan G, Beck GJ, Cheung AK, Daugirdas JT, Greene T, Kusek JW, et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 2002; 347:2010–2019.
8Gotch FA, Sargent JA. A mechanistic analysis of the National Cooperative Dialysis Study (NCDS). Kidney Int 1985; 28:526–534.
9Rashid H, Ul-Haq R, Rehman AU. Comparison of C-reactive protein levels with delivered dose of Kt/V in patients with end-stage renal disease on maintenance hemodialysis. Saudi J Kidney Dis Transpl 2015; 26:692–696.
10Amin N, Mahmood RT, Asad MJ, Zafar M, Raja AM. Evaluating urea and creatinine levels in chronic renal failure pre and post dialysis: a prospective study. J Cardiovasc Dis 2014; 2:2.
11Toborek M, Wasik T, Drózdz M, Klin M, Magner-Wróbel K, Kopieczna-Grzebieniak E. Effect of hemodialysis on lipid peroxidation and antioxidant system in patients with chronic renal failure. Metabolism 1992; 41:1229-32.
12Prasad N, Barai S, Gambhir S, Parasar DS, Ora M, Gupta A, et al. Comparison of glomerular filtration rate estimated by plasma clearance method with modification of diet in renal disease prediction equation and gates method. Indian J Nephrol. 2012; 22:103–7.
13Alain F, Nathalie G, Ilan S, Stephan S. Use of spent dialysate analysis to estimate blood levels of uremic salutes without blood sampling: urea. Nephrol Dial Transplant 2010; 25:873–879.
14Daniel Ski M, Izizler TA, McMonagle E, Kane JC, Pupin L, Morrow J. Linkage of hypoalbumiunia, inflammation, and oxidative stress in patients receiving maintenance hemodialysis therapy. Am J Kidney Dis 2003; 42:286–294.
15Kaysen GA. Disorders in high-density metabolism with insulin resistance and chronic kidney disease. J Ren Nutr 2010; 17:4–8.
16Lowrie EG, Lew NL. Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 1990; 15:458–482.
17Honda H, Ueda M, Kojima S, Mashiba S, Suzuki H, Hosaka N, et al. Oxidized high-density lipoprotein is associated with protein-energy wasting in maintenance hemodialysis patients. Clin J Am Soc Nephrol 2012; 5:1021–1028.
18Snit M, Gawlik R, Łącka-Gaździk B, Kuźniewicz R, Dwornicki M, Owczarek A, et al. Substance P and intensity of pruritus in hemodialysis and peritoneal dialysis patients. Med Sci Monit 2013; 19:723–732.
19Mahan JD, Warady BA. Assessment and treatment of short stature in pediatric patients with chronic kidney disease: a consensus statement. Pediatr Nephrol 2006; 21:917–930.
20Malekmakan L, Malekmakan A, Sayadi M, Pakfetrat M, Sepaskhah M, Roozbeh J. Association of high-sensitive C-reactive protein and dialysis adequacy with uremic pruritus. Saudi J Kidney Dis Transpl 2015; 26:890–895.
21Lotfy HM, Sabry SM, Ghobrial EE, Abed SA. The effect of regular hemodialysis on the nutritional status of children with end-stage renal disease. Saudi J Kidney Dis Transpl 2015; 26:263–270.
22Elshamaa MF, Sabry S, Nabih M, Elghoroury EA, El-Saaid GS, Ismail AA. Oxidative stress markers and C-reactive protein in pediatric patients on hemodialysis. Ann Nutr Metab 2009; 55:309–316.
23Panagoutsos SA, Yannatos EV, Passadakis PS, Thodis ED, Galtsidopoulos OG, Vargemezis VA. Effects of hemodialysis dose on anemia, hypertension, and nutrition. Ren Fail 2002; 24:615–621.
24McGregor DO, ButtimoreAL, NichollsMG, LynnKL. Ambulatory blood pressure monitoring in patients receiving long, slow home haemodialysis. Nephrol Dial Transplant 1999; 14:2676–2679.
25El-Sheikh M, El-Ghazaly G. Assessment of hemodialysis adequacy in patients with chronic kidney disease in the hemodialysis unit at Tanta University Hospital in Egypt. Indian J Nephrol 2016; 26:398–404.
26Rahman M, Fu P, Sehgal AR, Smith MC. Interdialytic weight gain, compliance with dialysis regimen, and age are independent predictors of blood pressure in hemodialysis patients. Am J Kidney Dis 2000; 35:257–265.
27Gheissari A, Mehrasa P, Merrikhi A, Madihi Y. Acute kidney injury: a pediatric experience over 10 years at a tertiary care center. J Nephropathol 2012; 2:101–108.