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ORIGINAL ARTICLE
Year : 2015  |  Volume : 28  |  Issue : 4  |  Page : 986-990

Steroid-induced renal dysfunctions in children with immune thrombocytopenia


1 Department of Pediatrics, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt

Date of Submission14-Mar-2014
Date of Acceptance29-Mar-2015
Date of Web Publication12-Jan-2016

Correspondence Address:
Abd Elfatah A Khalaf
Ard Elgamiat, 41511 Ismailia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1110-2098.173697

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  Abstract 

Objectives
The study was designed to evaluate the effect of steroid therapy on renal functions in children with immune thrombocytopenia (ITP).
Background
ITP is usually a benign self-limiting condition. The most appropriate initial therapy for children with ITP remains controversial. When therapy is indicated, the primary method of treatment is steroid therapy.
Materials and methods
The study was conducted on 33 children newly diagnosed with ITP (19 male; 14 female). The patients were classified into two main groups: group I included patients who needed corticosteroid therapy (18 patients) and group II included patients who did not need corticosteroid therapy (15 patients). Fifteen healthy age-matched and sex-matched children were included in the study as controls. All individuals were subjected to history taking, thorough clinical examination, anthropometric measurements, complete blood count, complete urine analysis, and renal function tests [blood urea, serum creatinine concentrations, and estimated glomerular filtration rate (eGFR)]. Blood samples were taken before any treatment and after an accumulative dose of 350 mg/m 2 steroid therapy for group I.
Results
The study revealed that ITP children who received steroids had significant increase in serum creatinine and significant decrease in eGFR without difference in blood urea, compared with those who did not receive steroids and with controls. The same was true in paired analysis on comparing ITP patients after steroid therapy with their investigations before steroid therapy.
Conclusion
Patients with ITP under short course of corticosteroid therapy are at risk for impaired renal functions in the form of increased serum creatinine concentration and decreased eGFR.

Keywords: estimated glomerular filtration rate, immune thrombocytopenia, serum creatinine, steroids


How to cite this article:
Ragab SM, Helwa MA, Khalaf AA. Steroid-induced renal dysfunctions in children with immune thrombocytopenia. Menoufia Med J 2015;28:986-90

How to cite this URL:
Ragab SM, Helwa MA, Khalaf AA. Steroid-induced renal dysfunctions in children with immune thrombocytopenia. Menoufia Med J [serial online] 2015 [cited 2020 Feb 27];28:986-90. Available from: http://www.mmj.eg.net/text.asp?2015/28/4/986/173697


  Introduction Top


Immune thrombocytopenia (ITP) is a clinical syndrome in which a decreased number of circulating platelets (thrombocytopenia) manifest as a bleeding tendency, easy bruising (purpura), or extravasation of blood from capillaries into the skin and mucous membranes [1] .

ITP is characterized as isolated thrombocytopenia (platelet count <100 × 10 3 /mm 3 ) in the absence of other causes or disorders that may be associated with thrombocytopenia [2] .

The most appropriate initial therapy for children with ITP remains controversial [3] . Once the decision to treat a patient with ITP has been made, provided the patient's situation is not life-threatening, corticosteroids are the standard initial treatment [4] .

The potent anti-inflammatory and immunosuppressive properties of corticosteroids have led to their use in a variety of diseases. It has been recognized that corticosteroid therapy is associated with many undesirable side effects [5] .

In this study, we aimed to assess the incidence of renal dysfunction in children with ITP due to corticosteroid therapy.


  Materials and methods Top


This study was conducted on 33 children with ITP (19 male; 14 female), with a mean age of 8.03 years (range 1.3-18 years) during the period from March 2013 to April 2014. All children were newly diagnosed ITP patients. They were recruited from the Hematology unit, Pediatric Department, Menoufia University.

On the basis of the protocol applied in our unit [6] , the patients were classified into two main groups: group I included patients who needed corticosteroid therapy (18 ITP patients) and group II included patients who did not need corticosteroid therapy (15 ITP patients).

The study included 15 age-matched, sex-matched, and surface area-matched normal children as the control group (nine male; six female), with a mean age of 6.67 years (range 3-12 years). The study was approved by the ethical committee of Menoufia Faculty of Medicine. Formal consent was taken from the guardians of the children.

All individuals were subjected to the following:

  1. Full history taking (including onset, course, duration, bleeding tendency, fatigue, previous viral infections, treatment regimens, and response to treatment).
  2. Thorough clinical examination, with special emphasis on purpuric sites, number and distribution, mucous membranes, bleeding, petechiae, and organomegaly.
  3. Anthropometric measurements (weight in kilograms with light clothes, height in meters without shoes, and surface area using nomogram).
  4. Laboratory investigations:
    1. Complete blood count (CBC) by Pentra-80 automated blood counter (ABX diagnostics, B.P. 7290, Rue du caducée Parc Euromédecine 34184 Montpellier Cedex 04 - France.
    2. Bone marrow examination (for patients only) to confirm the diagnosis of ITP.
    3. Complete urine analysis.
    4. Renal function tests:
      1. Blood urea estimation using the Berthelot method [7] with Beckman Coulter AU480 (Japan).
      2. Serum creatinine concentration determination using kinetic Jaffe' method [8] with Beckman Coulter AU480.
      3. Glomerular filtration rate (GFR) calculated from serum creatinine, the patient's height, and a proportionality constant using the original Schwartz method gives an estimate in ml/min/1.73 m 2 . The original Schwartz formula is as follows:




where k is 0.55 for children and adolescent girls and 0.70 for adolescent boys [9] .

Renal function tests (blood urea, serum creatinine, and eGFR) in group I were performed before and after administering steroid at a dose of 350 mg/m 2 according to Bardi et al. [10] .

Statistical analysis

Statistical analysis was performed using SPSS-20 (SPSS Inc., Chicago, Illinois, USA). Data were expressed as mean ± SD. Continuous parametric variables were presented as means ± SD, whereas for categorical variables n (%) were used. The difference between the two groups was evaluated with Student's t-test for parametric continuous variables and with the Mann-Whitney U-test for nonparametric variables. For more than two groups, the one-way analysis of variance (ANOVA) test was used for parametric data and the Kruskal-Wallis test was applied to discriminate nonparametric variables. For paired analysis, the paired t-test and Wilcoxon signed-rank test were used for parametric and nonparametric variables, respectively.


  Results Top


At diagnosis, the two patient groups of ITP showed no significant difference as regards blood urea, serum creatinine, or estimated glomerular filtration rate (eGFR) in comparison with each other or with the control group ([Table 1]).
Table 1 Comparison between immune thrombocytopenia patients in group I, immune thrombocytopenia patients in group II (presteroid therapy), and the control group at diagnosis


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Compared with group II (which included ITP patients who did not require therapy) and with controls, group I ITP children after steroid therapy had significant increase in serum creatinine and significant decrease in eGFR without difference in blood urea ([Table 2]). The same was true in paired analysis on comparing ITP patients after steroid therapy with their investigations before steroid therapy ([Table 3]; [Figure 1], [Figure 2], [Figure 3]).
Figure 1 Comparison between blood urea before and after steroid therapy in group I. ITP, immune thrombocytopenia

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Figure 2 Comparison between serum creatinine before and after steroid therapy in group I. ITP, immune thrombocytopenia

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Figure 3 Comparison between eGFR before and after steroid therapy in group I. eGFR, estimated glomerular filtration rate; ITP, immune thrombocytopenia

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Table 2 Comparison between immune thrombocytopenia patients in group I, immune thrombocytopenia patients in group II (after steroid therapy), and the control group at diagnosis


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Table 3 Comparison as regards kidney functions between immune thrombocytopenia patients who received steroid therapy before and after steroid therapy


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  Discussion Top


Childhood ITP is a benign self-limiting condition without serious bleeding problems [11] .

The male-to-female ratio in this study was 1.3 : 1. This is in agreement with the results of Wilson [12] , who reported that there is a slight male predominance in children with ITP, with a male-to-female ratio of 1.2 : 1.

All children were newly diagnosed ITP patients: 10 patients (33.3%) became chronic ITP patients on follow-up. This result was slightly higher than that reported by Kalpatthi and Bussel [13] , who stated that 10-30% of diseased children develop chronic ITP.

The patients were classified into two main groups on the basis of the therapy needed as per the applied protocol [6] : group I included patients who needed corticosteroid therapy (18 patients) and group II included patients who did not need corticosteroid therapy (15 patients).

On the basis of the method of Imbach et al. [14] for grading episodes of bleeding, our studied ITP children were classified as follows: stage I, no bleeding (14 patients); stage II, mild bleeding (one patient); stage III, moderate bleeding (16 patients); and stage IV, severe bleeding (two patients). Accordingly, patients with moderate and severe bleeding (18 patients) required treatment in the form of oral prednisolone (16 patients) or IV methylprednisolone (two patients).

The most appropriate initial therapy for children with ITP remains controversial [3] .

Corticosteroids are considered the standard initial treatment for ITP children in most centers [4] .

Corticosteroids can exhibit a wide range of adverse effects. They are able to suppress the hypothalamic-pituitary-adrenal axis, and can also cause osteoporosis, increased infection, electrolyte disturbances, and a number of cardiovascular effects such as obesity, hypertension, hyperglycemia and dyslipidemia [5] .

To our knowledge, few data have been published on corticosteroid nephrotoxic side effects; therefore, we aimed to assess is the incidence of renal dysfunction in children with ITP due to corticosteroid therapy.

At diagnosis, the two patient groups of ITP showed no significant difference as regards blood urea, serum creatinine, or eGFR, in comparison with each other or with the control group; this means that all children with ITP involved in this study were free from any renal impairment at diagnosis.

In contrast, Horber et al. [15] reported that chronic glucocorticoid therapy results in decreased muscle mass and decreased urinary creatinine excretion, suggesting that creatinine production may be reduced secondary to the muscle wasting due to prolonged glucocorticoid administration.

Compared with group II (which included ITP patients who did not require therapy) and with controls, group I ITP children after steroid therapy showed significant increase in serum creatinine and significant decrease in eGFR without difference in blood urea. The same was true in paired analysis on comparing ITP patients after steroid therapy with their investigations before steroid therapy.

Hence, these results suggest that steroid therapy may have a deleterious impact on renal functions in ITP children.

In accordance with our results, Manetti et al. [16] reported significant increase in the levels of serum creatinine after 48 h medication use in patients with Graves ophthalmopathy treated with high doses methylprednisolone; therefore, it was supposed that such increase could be due to the change in GFR.

Although by definition none of our studied ITP children could be considered as having renal impairment on serum creatinine or GFR, the mean value of both parameters was significantly changed after steroid therapy.


  Conclusion Top


Patients with ITP under short course of corticosteroid therapy are at risk for impaired renal functions in the form of increased serum creatinine concentration and decreased eGFR.


  Acknowledgements Top


Conflicts of interest

None declared.

 
  References Top

1.
Butros LJ, Bussel JB. Intracranial hemorrhage in immune thrombocytopenic purpura: a retrospective analysis. J Pediatr Hematol Oncol 2003; 25 :660-664.  Back to cited text no. 1
    
2.
Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009; 113 :2386-2393.  Back to cited text no. 2
    
3.
Watts RG. Idiopathic thrombocytopenic purpura: a 10-year natural history study at the Childrens Hospital of Alabama. Clin Pediatr (Phila) 2004; 43 :691-702.  Back to cited text no. 3
    
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Stasi R, Evangelista ML, Stipa E, Buccisano F, Venditti A, Amadori S. Idiopathic thrombocytopenic purpura: current concepts in pathophysiology and management. Thromb Haemost 2008; 99 :4-13.  Back to cited text no. 4
    
5.
Maxwell SR, Moots RJ, Kendall MJ. Corticosteroids: do they damage the cardiovascular system? Postgrad Med J 1994; 70 :863-870.  Back to cited text no. 5
    
6.
Lanzkowsky P. Disorders of platelets. In: Lanzkowsky P, editor. Manual of pediatric hematology and oncology. 5th ed. (London, England): Churchil Livingstone 2011; 12 :321-377.  Back to cited text no. 6
    
7.
Allain CC, Poon LS, Chan CSG, Richmond W, Fu PC. Enzymatic determination of total serum urea. Clin Chem 1978; 20 :470-475.  Back to cited text no. 7
    
8.
Spencer K. Analytical reviews in clinical biochemistry: the estimation of creatiine [review]. Ann Clin Biochem 1986; 23 :1-25.  Back to cited text no. 8
[PUBMED]    
9.
Vogt BA, Avner ED. Renal failure. In: Kliegman RM. Nelson text book of pediatrics. 18th ed. Philadelphia, PA: Elsevier/Saunders, USA 2008; 535 :2206-2214.  Back to cited text no. 9
    
10.
Bardi E, Dobos E, Kappelmayer J, Kiss C. Differential effect of corticosteroids on serum cystatin C in thrombocytopenic purpura and leukemia. Pathol Oncol Res 2010; 16 :453-456.  Back to cited text no. 10
    
11.
Bolton-Maggs P. Severe bleeding in idiopathic thrombocytopenic purpura. J Pediatr Hematol Oncol 2003; 25 (Suppl 1):S47-S51.  Back to cited text no. 11
    
12.
Wilson D. Acquired platelet defects. In: Nathan D, Orkin S, Look A, Ginsburg D, editors. Nathan and Oski′s: hematology of infancy and childhood. 6th ed. Philadelphia: WB Saunders; 2003. 1544-1597.   Back to cited text no. 12
    
13.
Kalpatthi R, Bussel JB. Diagnosis, pathophysiology and management of children with refractory immune thrombocytopenic purpura. Curr Opin Pediatr 2008; 20 :8-16.  Back to cited text no. 13
    
14.
Imbach P, Kühne T, Zimmerman S. New developments in idiopathic thrombocytopenic purpura (ITP): cooperative, prospective studies by the Intercontinental Childhood ITP Study Group. J Pediatr Hematol Oncol 2003; 25 (Suppl 1):S74-S76.  Back to cited text no. 14
    
15.
Horber Fl′, Scheidegger J, Frey FJ. Overestimation of renal function in glucocorticosteroid-treated patients. Eur J Clin Pharmacal 1985; 28 :537-541.  Back to cited text no. 15
    
16.
Manetti L, Genovesi M, Pardini E, Grasso L, Lupi I, Linda Morse L, et al. Early effects of methylprednisolone infusion on serum cystatin C in patients with severe Graves′ ophthalmopathy. Clin Chim Acta 2005; 356 :227-228.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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