• A2 kidney allocation;
  • ABO barrier;
  • anti-A titer;
  • A antigen expression


  1. Top of page
  2. Abstract
  3. Acknowledgments
  4. References

Fifteen blood group O and B recipients have been transplanted with kidneys from subtype A2 living donors since April 1992. ABO red cell grouping was performed by local licensed blood banks with A2 subtype determined using an anti-A1 lectin and, retrospectively, by a polymerase chain reaction (PCR)-based molecular method. All grafts functioned immediately and no patient has required dialysis. Three patients each experienced one reversible rejection episode. With the exception of one cardiac death at 9 months and one patient with profound toxicity to calcineurin inhibitors, all allografts continue to function normally. One donor, mistyped as a group A2 using lectin, was by PCR typing an A1O1 nonsecretor; the graft continues to function normally at 30 months. Transplantation of living donor A2 renal allografts into non-A recipients produces excellent long-term allograft survival and expands the potential living donor pool for nonblood group A recipients.

In 1997, the median waiting time for blood group O renal transplant recipients was 1012 d, and that for blood group B recipients was 1320 d. These are more than double the 545 and 283 d for blood groups A and AB, respectively (1). Strategies to increase the potential donor pool for blood group O and B patients can decrease the morbidity and possibly the mortality associated with longer waiting times. Reports of transplanting A2 and A2B kidneys into O and B patients have produced encouraging results (2–8). A meta-analysis of these studies showed that A2 kidneys can be successfully transplanted into O and B recipients, yet concern over the possibility for early accelerated rejection continues to be expressed because of several early allograft failures (9–12).

Of the two distinct blood group A phenotypes (A1 and A2), A2 is observed to have a lower cell surface expression than the A1 phenotype. This is due to the fact that the A2 transferase is less efficient than the A1 transferase in converting the H (precursor) antigen to the A antigen (13). Moreover, since synthesis of H antigen is determined by H and secretor (Se) genes, the presence of the Se gene (in contrast to the recessive, sese nonsecretor genotype) can have further influence on the extent of A antigen expressed (14).

Transplantation of kidneys from living donors allows the patient to optimize the timing of the operation, reduce waiting time and benefit from the greatly shortened cold ischemia of the organ. Thus, the use of A2 kidneys from living donors placed in blood group O and B recipients should expand the pool of potential living donors for these patients and reduce their dependence on cadaver donors. Ultimately, this should reduce the number of O and B recipients on cadaver waiting lists.

From 1992 through April 2000, 275 cadaveric and 256 living donor renal transplants were performed at our center. Twelve of the living donor allografts were blood group A2O and three donors were A2B, transplanted into O or B recipients, respectively. Of these 15, five donors were genetically unrelated to the recipients (three spouses, one friend, and one adopted son). All donors underwent a standard evaluation, which included a complete history and physical examination, renal function screening and renal angiography. Red blood cell grouping was performed by FDA (BoB) licensed blood banks using certified commercial reagents. Donors were designated A2 on the basis of negative agglutination using the anti-A1 lectin, Dolichos biflorus. Retrospective molecular ABO typing and determination of donor secretor status were performed with a rapid, PCR-based SSP molecular typing method (12). Recipient anti-A agglutination titers were not used prospectively to determine suitability for transplant (2). However, retrospective serologic titers were performed as described by Nelson et al. (2) using washed, A1 red cells and patient sera collected prior to transplant. All sera were titrated with and without pretreatment with dithiothreotol (DTT) so that differentiation of total (IgG + IgM) and IgG anti-A isoagglutinins could be obtained; no Coombs titrations were performed. Several representative sera from our studies were confirmed with regard to titer in Dr Bryan's laboratory in Kansas City (2,4).

HLA typing was performed using conventional technologies. Matching ranged from HLA identical in two patients to a complete mismatch in one; seven recipients had a one haplotype match with their donor. HLA class I alloantibody screens and donor cross-matching were performed using the T-cell antiglobulin cytotoxicity procedure and B-cell cytotoxicity procedures as described extensively in the past (15). Specifics of these histocompatibility data are detailed in Table 1.

Table 1. : Histocompatibility data on 15 cases of renal transplant performed across the A2 blood group
Case no.Donor relationHLA matchRecipient PRA (%)Donor molecular ABO typeDonor secretor statusRecipient ABORecipient anti-A titer (IgM + IgG)Recipient IgG anti-A titer (+ DTT)
  • a

    Not tested as no serum available.

  • b A 2 determined solely by serology as no historical samples were available for molecular typing.

  • PRA, panel-reactive (HLA) alloantibodies; DTT, dithiothreotol;

1Daughter1 haplo2A2O1SeSeONTaNT
2Brother2 A, 1 B0A2O1SeSeO1:128< 1:2
3Son1 haplo0NT(A2)bNTO1:2541:16
4Father1 haplo14A2O1SeseONTNT
5Brother1 haplo0A2O1SeseONTNT
7Father1 haplo0A1O1seseO1:16< 1:2
8Adopted son1 A, 2 DR0A2O1SeseB1:4< 1:2
9Friend1 B, 1 DR9A2O1SeseO1:81:4
11Spouse3 antigen0A2O1SeseO1:81:2
12BrotherIdentical0A2BSeseB1:16< 1:2
13Mother1 haplo0A2BSeSeB1:2< 1:2
14Sister1 haplo0A2BSeseB1:8< 1:2
15Spouse1 B, 1 DR0A2O1SeseO1:641:8

Kidneys were procured using standard surgical technique and flushed on the back table with ice-cold Ringer's lactate solution. Preservation time for all grafts was less than 1 h. Primary immunosuppression consisted of tacrolimus or cyclosporine started postoperatively by mouth. Azathioprine or mycophenolate mofetil was given in standard doses to all but the two patients with a zero mismatch. All received 500 mg of methylprednisolone at surgery and a 2-d taper, which was then converted to prednisone initially at 30 mg/d. No patient received antibody induction therapy, plasmapheresis or splenectomy. Follow-up was managed according to our routine kidney transplant protocol for ABO-compatible living donor transplants.

All blood group O or B recipients were transplanted with A2 or A2B kidneys according to the blood bank serotyping. Retrospective DNA-based molecular typing for the A2 subgroup confirmed the serologic results in 14 out of the 15 patients, all of whom were secretors (Se) (Table 1). However, one donor (case 7) was repeatedly mistyped for the A2 subgroup by a local blood bank. The donor, who was the father of the recipient, was found to have the A1O1 genotype and was a nonsecretor (sese).

All ABO-incompatible A2 renal allografts functioned immediately following revascularization and no patient has required dialysis since the transplant. One patient died with a functioning graft 9 months after his transplant of a myocardial infarction. There have been no other deaths or graft failures (Table 2). Three patients (20%) have each had one episode of rejection. Two patients each had a rejection episode (10 d and 8 months after transplant) that responded to OKT3. The third occurred 2 weeks after transplantation in a patient receiving her third allograft. This was successfully treated with a course of antithymocyte globulin. Unfortunately, this patient has subsequently developed an extreme sensitivity to both cyclosporine and tacrolimus, leading to nephrotoxicity and a progressive elevation in her creatinine. Her renal function later stabilized with a creatinine in the 5.2–5.6 range when she was switched to sirolimus. Since her initial rejection 3.5 years ago, none of her subsequent biopsies has shown evidence of rejection. Currently, all remaining recipients have recent serum creatinine measurements within the normal range.

Table 2. : Clinical data following transplantation of ABO A2 mismatched living donor renal allografts
Case no.Months of follow-upOnset of rejectionRejection therapyPrevious no. of transplantsCreatinine at 1 week (mg/dL)Current creatinine (mg/dL)
  • a

    Patient died 9 months after transplant from a myocardial infarction.

  • ATG, antithymocyte globulin.

2912 weeksOKT301.51.5
398 monthsOKT301.3Deceaseda
6482 weeksATG22.65.4

Several previous reports (2,7) suggest that high IgG anti-A isoagglutinins (titers ≥1: 8) are detrimental to allograft survival. Of the 12 recipients in our series who had serum available for retrospective testing, three (cases 3, 10, and 15) fit these criteria. Only one developed rejection, 8 months after transplantation, which was successfully reversed with OKT3. Additionally, of the three patients who were treated for rejection (case 2, 3, and 6), only one had a high titer of IgG anti-A antibody. While we were unable to identify a clear association between IgG anti-A antibody titer and acute rejection, larger numbers of patients will be required to more fully understand the relationship.

Of definite interest in our series is case 7, wherein the donor was mistyped and found in retrospect actually to be A1O1. The post-transplant course was uneventful and the recipient's creatinine is in the normal range 35 months after transplantation. Importantly, the recipient had an anti-A titer of less than 1:2 and was a nonsecretor (sese). This finding raises the intriguing possibility of prospectively identifying another acceptable scenario (contrary to current practice) of utilizing blood group A1 allografts from nonsecretor donors in O and B recipients who have low IgG anti-A1 titers. This case should be considered in light of the rather remarkable experience of the Japanese who have successfully transplanted fully ABO-incompatible living renal allografts (16) in situations of low-titered ABO isoagglutinins. Obviously, more research is necessary to improve our understanding of the risks involved in transplanting A1 kidneys across the ABO barrier. Yet, if successful, ≈ 25% of Caucasian blood group A1 individuals would be classified as nonsecretors and could possibly be considered as universal donors.

Finally, caution should continue to be exercised with regard to transplantation of A2 allografts, especially from living donors. While absolute cause and effect of high-titered A isoagglutinins has not been established (7,11,12), the recommendation for plasmapheresis (7,16) may be warranted until further clarification of the role of anti-Acommon titer (10), secretor status, glycosyl-transferase specificity and the accompanying antigen site density of the ABO A substance are established in a larger series. As illustrated by our experience, serologic misassignment of the A2 blood group when in fact the donor is an A1 is possible using lectin agglutination techniques; this could explain some of the early failures reported in the literature (11,12). The initiation of a national registry to monitor these cases, most likely under the auspices of The United Network for Organ Sharing (UNOS), would advance our understanding of these interactions, and should be recommended by the Histocompatibility Committee.

In summary, transplantation of A2 living donor renal allografts into non-A recipients produces excellent results and expands the donor pool for blood type O and B recipients similar to that reported for mismatched cadaveric recipients. Moreover, utilization of A2 kidneys from living donors is particularly attractive because it not only offers more kidneys to O and B recipients, but also accomplishes this goal by bringing kidneys into the donor pool which would otherwise be unavailable for transplantation. The use of DNA-based molecular typing for ABO A1 and A2 subgroups and secretor status is straightforward and reliable; certainly these procedures should be used to confirm A2 subtype before elective transplantation.


  1. Top of page
  2. Abstract
  3. Acknowledgments
  4. References

The authors recognize the following individuals for their efforts in collecting and organizing the clinical and laboratory data: Joan Arata RN, Clinical and Research Manager, LDS Hospital Transplant Section; Michelle Taylor BS, Laboratory Manager, and Lisa Ewing BS, Medical Technologist, H & I Laboratory, University of Utah Health Sciences Center.


  1. Top of page
  2. Abstract
  3. Acknowledgments
  4. References
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  • 2
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  • 3
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