There have been concerns about using kidneys from potential donors with sickle cell trait because kidneys from these donors may not concentrate urine properly. We report a case of living-related renal transplant, in which both the recipient and the donor had sickle cell trait, and the postoperative course for both was uneventful.
Key words : Renal transplantation, Hemoglobin S disease, Sickle cell anemia
Sickle cell trait is a benign carrier condition that may present with mild hypochromic and microcytic anemia and rarely, may be associated with renal abnormalities. Prevalence of sickle cell trait is 8% to 10% in African Americans and as high as 25% in certain parts of west Africa (1). Hemoglobinopathies are among the most common genetic disorders in Saudi Arabia, especially in the eastern region (2). In 1 study, the incidence of sickle cell trait in Saudi neonates was 23.4% (3). Among US soldiers with sickle cell trait, a 30-fold increased risk of unexplained sudden death during basic military training was reported, apparently related to exercise-induced vaso-occlusion and rhabdomyolysis (4, 5).
A few clinical presentations of sickle cell trait (ie, splenic infarction at high altitudes in an unpressurized airplane and during mountain climbing) have been reported. Recognized complications include increased risks of bacteruria and pyelonephritis during pregnancy. In addition, sickle cell trait is a common cause of hyposthenuria (ie, impaired urine concentrating ability) and microhematuria (4, 5). Sickle cell trait is a common cause of microhematuria among African Americans. In addition, the impaired ability of those with sickle cell trait to properly concentrate urine is directly related to the intraerythrocyte concentration of hemoglobin (Hgb) S (6).
In some reports, using donor kidneys from persons with sickle cell trait has been linked to negative outcomes, although no clear association between sickle cell trait and increased morbidity and mortality, or even decreased graft survival, exists (7).
There is a paucity of data regarding patients with sickle cell trait undergoing renal transplant or regarding patients who receive a kidney from a donor with sickle cell trait. Here, we report the case of living-related kidney transplant between siblings in which both the donor and the recipient have sickle cell trait.
A 22-year-old woman with end-stage renal disease secondary to chronic glomerulonephritis was placed on maintenance hemodialysis in December 1999. A renal ultrasound revealed small kidneys with increased echogenicity and poor corticomedullary differentiation. She was also found to be hypertensive; a regimen of antihypertensive drugs was initiated. There was a history of tuberculosis peritonitis, for which she had been treated for 1 year; otherwise, there was no significant medical or family history. A pretransplant echocardiography revealed mild left ventricular hypertrophy with a left ventricular ejection fraction of 50% with evidence of severe tricuspid and moderate mitral regurgitation. Hemoglobin electrophoresis using high-performance liquid chromatography (showing Hgb A1, 63.1%; HbS, 31.1%; HbF < 1%; Hgb A2; and glycated Hgb S, 5.8%) confirmed that she had sickle cell trait.
The donor was her brother, a healthy 35-year-old man, with no significant medical history, whose laboratory results showed Hgb of 144 g/L and mean corpuscular volume of 66 fL. Hemoglobin electrophoresis revealed the following: Hgb A1, 68.2%; HbS, 26.3%; HbF, < 1%; Hgb A2; and glycated Hgb S, 5.5%, consistent with sickle cell trait and most likely a coexisting alpha thalassemia trait. The results of a preoperative donor’s morning urine analysis were normal, with a specific gravity of 1.010. Renal tubular function assessment was not performed. The results of his blood and urine chemistries were as follows: glucose, 5.0 mmol/L; urea, 2.5 mmol/L; creatinine, 65 µmol/L; Na, 135 mmol/L; K, 3.6 mmol/L; Cl, 105 mmol/L; tCO2, 26 mmol/L; and serum albumin, 40 g/dL. The results of renal imaging studies (ultrasound and DTPA scan) also were normal.
HLA antigen match showed 1 haplo match. HLA antigen results were as follows: recipient A23, A24, B7 (Bw6), B50 (Bw6), DRB1*15, DRB5*01/02, while the donor HLA antigen was A2, A24; B7 (Bw6), B51 (Bw4), DRB1*01, DRB1*15, DRB5*01/02.
Our patient received a kidney from her brother on August 27, 2002; the postoperative course was uneventful for both. The recipient was started on an immunosuppressive regimen that included prednisolone, mycophenolate mofetil, and tacrolimus. The recipient’s serum creatinine level returned to the normal range within 5 days after the transplant; since then, she has been regularly followed-up in the nephrology clinic. At her last follow-up, 4 years after the transplant, she had a serum creatinine level of 79 µmol/L. The results of a urine analysis were normal; the specific gravity was 1.005, and the creatinine clearance was 72 mL/minute. She currently is on a regimen that includes tacrolimus (3 mg daily), azathioprine (50 mg daily), and prednisolone (5 mg daily). The donor is living a normal life 4 years after the transplant, with a serum creatinine level of 84 µmol/L and normal results of a urine analysis with a specific gravity of 1.025.
Sickle cell anemia is an autosomal recessive disorder resulting in structurally abnormal hemoglobin, sickling, and increased adhesiveness of sickle cells, leading to endothelial cell injury in microcirculation and subsequently, end-organ damage. End-organ damage is an exceedingly rare complication of sickle cell trait (8).
The natural history of renal allografts in recipients who have sickle cell trait or sickle cell disease has not been adequately studied. Although sickle cell trait is considered a benign condition as compared with homozygous sickle cell disease, there remains concern about the safety and feasibility of kidney donation for both the donor and the recipient. In the past, sickle cell trait was considered unsuitable for kidney donation (9).
The defect in concentrating the urine is well known in sickle cell trait likely due to vaso-occlusion of the vasa recta as a consequence of sickling in the relatively low-oxygen tension environment of the medulla. Since it is a recipient-related factor, this defect is expected to persist after renal transplant.
A survey of 106 transplant centers in the United States found that 88 centers had no experience performing transplants on recipients with sickle cell disease or sickle cell trait. The remaining 18 centers reported a total of 34 transplants in 30 patients, 9 of whom had sickle cell disease and 21 of whom had sickle cell trait. Overall graft survival was 67% at 1 year for both deceased-donor and living-related transplants, albeit this graft survival rate is considered to be lower than the transplant rate in patients without sickle cell disease. Unfortunately, that survey did not include a question about the sickle cell status of the donors (10).
There is a reported case of failed renal allografts in 2 renal transplants in succession in a patient with sickle cell trait. The first graft failed on the 21st day after surgery despite treatment for rejection. The histopathology of the removed graft showed mild-to-moderate cellular rejection with extensive intravascular sickling of the red blood cells. The second allograft failed 7 to 8 weeks after the transplant despite the successful treatment of 2 episodes of acute rejection. The histopathology of the second graft revealed an essentially similar picture to that of the first graft, except that the evidence of rejection was much milder. It has been hypothesized that those earlier rejection episodes made the tissue hypoxic, leading to sickling of red blood cells and thus, further aggravation of the condition (11).
An updated national experience, published by Chatterjee and associates, showed that 20 out of 110 transplant centers reported their experience with 45 transplants in 40 patients in whom 13 had sickle cell disease and 27 had sickle cell trait. The 1-year graft survival rate was 82% in living-related and 62% in deceased-donor transplant recipients (12).
In a donor-recipient pair in which both persons have sickle cell trait, the difficulty in concentrating urine, which is usually insignificant, could affect the transplanted kidney and may negatively affect the donor’s remaining kidney. Complications secondary to transplanting a structurally compromised kidney might occur. Therefore, such potential donations should be thoroughly assessed. Since patients with sickle cell trait excrete diluted urine, significant proteinuria is unusual, albeit microalbuminuria is frequently associated with sickle cell trait. Therefore, proteinuria exceeding 0.3 g warrants further investigation in potential donors. In fact, the specific gravity in our patient’s urine was low, suggesting dilute urine (although no formal testing to examine the concentrating ability of the donated kidney was made). Intermittent hematuria has been reported and may present either as macroscopic or microscopic blood loss (13). Most cases of hematuria represent benign findings; however, rare cases of urinary tract malignancies mandate full evaluation prior to transplant (9, 14). In fact, the urine analysis in our donor-recipient pair revealed no evidence of micro- or macro-hematuria, and the long-term follow-up showed no clinical or biochemical abnormalities
To the best of our knowledge, this report is the first to address the issue of kidney transplant in a donor-recipient pair, in which both have sickle cell trait. The favorable and uneventful postoperative courses for the recipient and the donor are reassuring in a clinical area with little existing data. The normal kidney functioning in the donor 4 years after the transplant encourages using a donor with this trait. We believe that sickle cell trait in the donor and the recipient is not a contraindication for kidney transplant. More data are needed to confirm this conclusion.
Volume : 5
Issue : 2
Pages : 698 - 700
From the Departments of 1Medicine, 2Hematology, and 3Surgery, King Faisal Specialist Hospital and Research Center- Jeddah, Saudi Arabia, and 4Brigham and Women’s Hospital, Boston, MA, USA
Address reprint requests to: Saeed M G Al-Ghamdi, MD, FRCPC, FACP, Consultant Nephrologist, Chairman Department of Medicine, J-46, King Faisal Specialist Hospital and Research Center, PO Box 40047, Jeddah 21499, Kingdom of Saudi Arabia
Phone: +966 2 667 77 77 ext 5814
Fax: +966 2 667 77 77 ext 5817