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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 21  |  Issue : 3  |  Page : 144-147

Successful kidney transplantation of a patient with thalassemia major: case report and review of literature


1 Department of Internal Medicine and Nephrology, Hamed Alessa Organ Transplant Center, Kuwait
2 Department of Internal Medicine and Nephrology, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt
3 MRCP-E Internal Medicine and Nephrology, Hamed Alessa Organ Transplant Center, Kuwait
4 MRCP-I Internal Medicine and Nephrology, Hamed Alessa Organ Transplant Center, Kuwait

Date of Submission06-Feb-2021
Date of Acceptance24-Feb-2021
Date of Web Publication09-Aug-2021

Correspondence Address:
Dr. Osama Gheith
Internal Medicine and Nephrology, Consultant Nephrologist, Urology and Nephrology Center, Mansoura University; Working in Hamed Alessa Organ Transplant Center, Kuwait; Hamed Al-Essa Organ Transplant Center, Ministry of Health, Ibn Sina Hospital, P.O. Box 25427, Safat (13115), Kuwait
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jesnt.jesnt_5_21

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  Abstract 


Thalassemia minor has a good prognosis, whereas thalassemia major (TM) is a severe disease, and the long-term prognosis depends on the treatment adherence to transfusion and iron chelation therapies. To our knowledge, there are no reported thalassemia cases that underwent kidney transplant. We aimed to highlight a successful kidney transplant in a patient with TM with stable graft function after 16 months of follow-up. In our case, repeated blood transfusions were inevitably associated with iron overload despite iron chelating agents. Moreover, she developed anti-HLA antibodies, but fortunately, there were no donor-specific antibodies, which facilitated the procedure of renal transplant that was performed on 17/3/2019. After 6 weeks of transplant, she started follow-up in the clinic and resumed iron chelation using deferasirox along with much less frequent blood transfusion. After more than 20 months of follow-up, she is enjoying stable graft function, hemoglobin around 9.2 g/dl, and with occasional trace proteinuria. This is a case report showing a β-TM case can undergo renal transplant with no contraindications under special circumstances, and it is the first case in the literature.

Keywords: iron chelating agent, outcome, renal transplantation, thalassemia


How to cite this article:
Emam M, Moneem MA, Gheith O, Mahmoud T, Nagib AM, Abdultawab K, Elsayed Z, Nair P, Al-otaibi T. Successful kidney transplantation of a patient with thalassemia major: case report and review of literature. J Egypt Soc Nephrol Transplant 2021;21:144-7

How to cite this URL:
Emam M, Moneem MA, Gheith O, Mahmoud T, Nagib AM, Abdultawab K, Elsayed Z, Nair P, Al-otaibi T. Successful kidney transplantation of a patient with thalassemia major: case report and review of literature. J Egypt Soc Nephrol Transplant [serial online] 2021 [cited 2021 Oct 17];21:144-7. Available from: http://www.jesnt.eg.net/text.asp?2021/21/3/144/323530




  Introduction Top


Thalassemia is an autosomal recessive disorder that results from a decreased synthesis of alpha or β chains of hemoglobin (Hb) owing to a genetic mutation − more than 200 mutations identified − or a deletion of certain gene fragments. One of the parents must be a carrier for the disease. Depending upon the frequency of blood transfusion, thalassemia can be classified into transfusion requiring and nontransfusion requiring [1],[2],[3]. Alpha-thalassemia is caused by deletions of alpha-globin genes, whereas β-thalassemia is caused by a point mutation in splice site and promoter regions of the β-globin gene on chromosome 11 [4]. Alpha-thalassemia is prevalent in Asian and African populations, whereas β-thalassemia is more prevalent in the Mediterranean population [4]. The prevalence of β-thalassemia carriers varied from 5.4% in Egypt to 8.5% in UAE and 2.9% in Bahrain. In Kuwait, α-thalassemia carriers ranged from 5 to 10% versus 49 and 24.2% in UAE and Bahrain, respectively [5].

Thalassemia treatment depends on the type and severity of the disease. Thalassemia minor (with Hb: 6–10 g/dl) is usually asymptomatic and requires no treatment. Occasionally, patients may need a blood transfusion, particularly after surgery, following childbirth, or to help manage thalassemia complications. In moderate to severe thalassemia (Hb <5–6 g/dl), frequent blood transfusions are often required, possibly every few weeks. The goal is to maintain hemoglobin between 9 and 10 mg/dl, which improves the sense of well-being and suppresses extramedullary hematopoiesis. To reduce transfusion-related complications, washed, packed red blood cells (at 8–15 ml cells/kg of body weight) over 1–2 h are recommended. Owing to chronic transfusions, iron starts to get deposited in various organs of the body. Iron chelating agents are given concomitantly to remove extra iron from the body [6]. However, adverse effects from iron chelating agents are not uncommon, and it can cause renal and cardiac adverse effects [7]. Bone marrow transplant is a potential option in selected cases, especially pediatrics with severe thalassemia. It can eliminate the need for lifelong blood transfusions [8]. However, such procedure has its own complications, which include graft-versus-host disease, chronic immunosuppressive therapy, graft failure, and transplantation-related mortality [9]. Gene therapy is the latest advancement in severe thalassemia management. It involves harvesting the autologous hematopoietic stem cells from the patient and genetically modifying them with vectors expressing the normal genes. Genome editing technique is another recent approach that involves editing genomic libraries, targeting specific mutation sites, and replacing them with the normal sequence [10].

Patients with thalassemia major (TM) often undergo splenectomy to limit the number of required transfusions. Splenectomy is usually recommended when the annual transfusion requirement increases to more than 200–220 ml red blood cells/kg/year. Postsplenectomy immunizations are compulsory to prevent bacterial infections, including Pneumococcus, Meningococcus, and Haemophilus influenzae. Postsplenectomy sepsis is possible in children, so this procedure is deferred until 6–7 years of age, and then penicillin is given for prophylaxis until they reach a certain age. Thalassemia minor has a good prognosis, whereas TM is a severe disease, and the long-term prognosis depends on the treatment adherence to transfusion and iron chelation therapies [11]. To our knowledge, the is no reported thalassemia cases that underwent kidney transplant.


  Aim Top


We aimed to highlight a successful kidney transplant in a patient with TM with stable graft function after 16 months of follow-up.


  Case presentation Top


The patient is a 44-year-old Kuwaiti women who had β-TM on regular blood transfusions since 1980 (average twice per month). She developed secondary hemochromatosis (arthralgia, prediabetes, weight loss, and fatigue) due to iron overload. Therefore, she was maintained on iron chelation by deferasirox since 2005. Deferasirox was held as she planned to get pregnant 2012 without any reportable complications. She developed hypersplenism (splenomegaly, pancytopenia, and hyperplastic bone marrow) for which she underwent splenectomy that reduced the frequency of blood transfusion (once every 2 months). Moreover, she was managed by postsplenectomy routine vaccination and prophylaxis against pneumococci. By the age of 40 years, she planned for in vitro fertilization but she discovered that she had chronic kidney disease with proteinuria and renal dysfunction. Her biopsy showed chronic tubule-interstitial nephritis that was proven by kidney biopsy on September 2015. Ovulatory drugs or iron chelating agent were mostly the cause for such chronic kidney disease. On March 2018, she was declared end-stage kidney disease and was started hemodialysis program via left brachial arteriovenous fistula. She was prepared for renal transplant with nearly normal echocardiography. We planned to proceed for renal transplant with target Hb around 10 g/dl and to consider modified dose of chelating agent according to the renal function. She had live renal transplant on 17/3/2019 with smooth perioperative course. She had four human leucocyte antigen (HLA) mismatches (2 : 2;0) with panel reactive antibody (PRA) against DQ locus 2 and 4 but without donor specific antibody (DSA). She received thymoglobulin as induction and she was maintained on steroid, tacrolimus, and mycophenolate mofetil (MMF). After 6 weeks of transplant, she started follow-up in the OPD and resumed iron chelation using deferasirox (500 mg per day orally) along with much less frequent blood transfusion (with Hb level around 9 g/dl). After more than 20 months of follow-up ([Figure 1]), she is enjoying stable graft function with creatinine level around 66 μmol/l, Hb around 9.2 g/dl (supported by darbepoetin and occasional transfusion), and with occasional trace proteinuria (0.25 g/day).
Figure 1 Posttransplant follow-up laboratory parameters of the reported case.

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  Discussion Top


Patients with β-TM usually present early in life with profound anemia that necessitates regular blood transfusions to survive. Repeated blood transfusions are inevitably associated with iron overload that leads to multiple organ dysfunctions, namely, heart, liver, and endocrine glands [7] and immunological adverse reactions, specifically the development of anti-HLA antibodies [12]. This observation was matched with our case as she developed hemochromatosis despite her iron chelation. Moreover, she was sensitized against multiple HLA antigens as she developed anti-HLA antibodies, but fortunately, there were no donor-specific antibodies that would have deferred the procedure of renal transplantation.

The advances in the care of cases with β-TM, especially with the advent of effective chelating agents that can reduce iron burden and its consequences, had translated into better patient survival. This success has allowed previously unrecognized complications to emerge, including several renal abnormalities [9],[13],[14], maintenances on dialysis, and even renal transplant.

A major important issue is the cardiotoxicity of iron overload which is usually found among such group of patients and was responsible for premature early deaths. Fortunately, cardiac assessment of our patient before transplant was satisfactory. Borgna-Pignatti and colleagues reported that renal diseases have not been a major issue in patients with β-TM because of short survival. Severe cardiac iron loading secondary to chronic transfusion therapy lead to premature mortality, and simply patients did not live long enough to develop conditions that necessitate renal replacement therapies.

Several major factors are responsible for functional abnormalities found in β-TM that induce comorbidities associating rapid iron turnover, and tissue deposition of excess iron. Moreover, the uses of specific iron chelating agents are not without harm to the kidney [10]. This is partially matched with our case that revealed biopsy-proven chronic tubule-interstitial mostly owing to drugs.

The increased awareness of the kidney and understanding of the potential mechanisms of kidney injury led to increase in the frequency of monitoring of the kidney function, especially in patients who are receiving chelating agents. Particular attention should be given to monitor renal function in patients at risk of complications as patients with diabetes, those who have preexisting renal conditions [or glomerular filtration rate (GFR) <60 ml/min/1.73 m2 and proteinuria], and those who have comorbidities or are on medications which may affect kidney function, although there is no strong evidence about the ideal way of monitoring these patients. A 3 monthly serum creatinine/measurements, a simple urine dipstick to detect nonvisible blood, and a protein/creatinine ratio (in a morning urine sample) should be performed. More frequent measurements (monthly) in patients who are receiving chelating agents should be performed. A more frequent monitoring program − including the previously mentioned biomarkers − was implemented routinely after kidney transplant in our center. This might explain the excellent outcome of the graft in such a high-risk patient. On the contrary, many investigators suggest that cystatin C is a poor biomarker of renal function in patients with thalassemia, though these data need to be validated [12],[13],[15],[16].


  Conclusion Top


To our knowledge, this is the first reported case in the literature with β-TM who underwent successful kidney transplant. With special precautions, such cases can be transplanted.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
He LN, Chen W, Yang Y, Xie YJ, Xiong ZY, Chen DY et al. Elevated prevalence of abnormal glucose metabolism and other endocrine disorders in patients with β-thalassemia major: a meta-analysis. Biomed Res Int 2019; 2019:6573497.  Back to cited text no. 1
    
2.
Vichinsky E, Cohen A, Thompson AA, Giardina PJ, Lal A, Paley C et al. Epidemiologic and clinical characteristics of nontransfusion-dependent thalassemia in the United States. Pediatr Blood Cancer 2018; 65:e27067.  Back to cited text no. 2
    
3.
Ahmadpanah M, Asadi Y, Haghighi M, Ghasemibasir H, Khanlarzadeh E, Brand S. In patients with minor beta-thalassemia, cognitive performance is related to length of education, but not to minor beta-thalassemia or hemoglobin levels. Iran J Psychiatry 2019; 14:47–53.  Back to cited text no. 3
    
4.
Jalil T, Yousafzai YM, Rashid I, Ahmed S, Ali A, Fatima S, Ahmed J. Mutational analysis of beta thalassaemia by multiplex arms-Pcr in Khyber Pakhtunkhwa, Pakistan. J Ayub Med Coll Abbottabad. 2019; 31:98–103.  Back to cited text no. 4
    
5.
Kim S, Tridane A. Thalassemia in the United Arab Emirates: why it can be prevented but not eradicated. PLoS One 2017; 12:e0170485.  Back to cited text no. 5
    
6.
Brittenham GM, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE et al. Efficacy of deferoxamine in preventing complications of iron overload in patients with thalassemia major. N Engl J Med 1994; 331:567–573.  Back to cited text no. 6
    
7.
Cappellini MD, Cohen A, Piga A, Bejaoui M, Perrotta S, Agaoglu L et al. A phase 3 study of deferasirox (ICL670), a once-daily oral iron chelator, in patients with beta-thalassemia. Blood 2006; 107:3455–3462.  Back to cited text no. 7
    
8.
Jariwala K, Mishra K, Ghosh K. Comparative study of alloimmunization against red cell antigens in sickle cell disease & thalassaemia major patients on regular red cell transfusion. Indian J Med Res 2019; 149:34–40.  Back to cited text no. 8
    
9.
Sarkar SK, Shah MS, Begum M, Yunus AM, Aziz MA, Kabir AL et al. Red cell alloantibodies in thalassaemia patients who received ten or more units of transfusion. Mymensingh Med J 2019; 28:364–369.  Back to cited text no. 9
    
10.
Darvishi Khezri H, Emami Zeydi A, Sharifi H, Jalali H. Is vitamin C supplementation in patients with β-thalassemia major beneficial or detrimental? Hemoglobin 2016; 40:293–294.  Back to cited text no. 10
    
11.
Zhang H, Zhabyeyev P, Wang S, Oudit GY. Role of iron metabolism in heart failure: from iron deficiency to iron overload. Biochim Biophys Acta Mol Basis Dis 2019; 1865:1925–1937.  Back to cited text no. 11
    
12.
Weinstock C, Schnaidt M. Human leucocyte sensitization and its impact on transfusion practice. Transus Med Hemother 2019; 46:356–368.  Back to cited text no. 12
    
13.
Musallam KM, Taher TA. Mechanisms of renal disease in β-thalassemia. J Am Soc Nephrol. 2012; 23:1299–1302.  Back to cited text no. 13
    
14.
Ponticelli C, Musallam KM, Cianciulli P, Appellini MD. Renal complications in transfusion-dependent beta thalassemia. Blood Rev 2010; 24:239–244.  Back to cited text no. 14
    
15.
Borgna-Pignatti C, Cappellini MD, De Stefano P, Del Vecchio GC, Forni GL, Gamberini MR et al. Cardiac morbidity and mortality in deferoxamine-or deferiprone-treated patients with thalassemia major. Blood 2006; 107:3733–3737.  Back to cited text no. 15
    
16.
Papassotiriou I, Margeli A, Hantzi E, Delaporta P, Sergounioti A, Goussetis E et al. Cystatin C levels in patients with beta-thalassemia during deferasirox treatment. Blood Cells Mol Dis 2010; 44:152–155.  Back to cited text no. 16
    


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