Indian Journal of Transplantation

CASE REPORT
Year
: 2020  |  Volume : 14  |  Issue : 2  |  Page : 152--155

ABO-incompatible kidney transplantation in Chhattisgarh – Challenges and outcome


Prawash Kumar Chowdhary1, Sanjeev Anant Kale1, Ajay Parashar2, Sudha Trivedi3, Shruti Khatkhedkar3, Pratibha Sharma4,  
1 Department of Nephrology, Ramkrishan Care Hospital, Raipur, Chhattisgarh, India
2 Department of Urology, Ramkrishan Care Hospital, Raipur, Chhattisgarh, India
3 Department of Anesthesia, Ramkrishan Care Hospital, Raipur, Chhattisgarh, India
4 Department of Blood Transfusion Medicine, Ramkrishan Care Hospital, Raipur, Chhattisgarh, India

Correspondence Address:
Dr. Prawash Kumar Chowdhary
Department of Nephrology, Ramkrishan Care Hospital, Raipur, Chhattisgarh
India

Abstract

Patients with chronic kidney disease stage 5 are usually excluded from renal transplantation if they do not have a compatible blood group donor. Paired kidney donation and ABO-incompatible kidney transplantation are the only options for such patients. We describe the case of a 49-year-old male patient who had blood Group B positive and potential donor; his wife had blood Group nagative. The patients had an initial anti-A antibody titer of 1:32 and underwent antibody depletion with plasmapheresis (two sessions). He also received rituximab 200 mg on minus 14th days and was induced with basiliximab. At the time of transplant, his anti-A titer was 1:8. Postoperatively, the patient had delayed graft function and received one session of hemodialysis but no plasmapheresis. Postoperatively, anti-A titer was 1:8. He was discharged on the 14th postoperative day with normal renal function.



How to cite this article:
Chowdhary PK, Kale SA, Parashar A, Trivedi S, Khatkhedkar S, Sharma P. ABO-incompatible kidney transplantation in Chhattisgarh – Challenges and outcome.Indian J Transplant 2020;14:152-155


How to cite this URL:
Chowdhary PK, Kale SA, Parashar A, Trivedi S, Khatkhedkar S, Sharma P. ABO-incompatible kidney transplantation in Chhattisgarh – Challenges and outcome. Indian J Transplant [serial online] 2020 [cited 2020 Sep 19 ];14:152-155
Available from: http://www.ijtonline.in/text.asp?2020/14/2/152/289032


Full Text



 Introduction



In Chattissgarh, near about 33% of population live in tribal areas. The immunology and renal biopsy facility is not available in our state. We need to depend on other nearby states. Doing even an ABO-compatible renal transplantation is a challenge in Chhattisgarh. Due to a lack of ABO-compatible donors, most of the chronic kidney disease patients on dialysis are not able to undergo kidney transplantation. Hence, to increase the donor pool and to help the chronic kidney disease patients on dialysis in Chhattisgarh, we did our first ABO-incompatible kidney transplantation (ABOiKT) with great challenge and difficulties.

 Case Report



A 49-year-old male with Type 2 diabetes mellitus and hypertension for 11 years was on maintenance hemodialysis for 3 years. He was on follow-up with us for 1 year. Option for kidney transplantation was discussed.

The patient's blood Group was B positive and no family members had the same group. The patient's wife blood Group was AB positive. After discussing the pros and cons of ABOiKT, the wife was selected as the donor.

The baseline anti-A IgG antibody titer was 1:32 by column agglutination technology by the gel card method. A flow cytometry cross-match was negative. LumXm was performed to detect the preformed donor-specific antibody and was found to be negative (<500 mean fluorescence intensity) for both human leukocyte antigen (HLA) Class I and II.

HLA typing of the patient and donor (HLA-A, HLA-B, and HLA-DR) showed a 2/6 match [Table 1].{Table 1}

After obtaining negative cross-match report, he was posted for renal transplantation. His anti-A IgG titer was 1:32 [Figure 1].{Figure 1}

On day 14, he received 200 mg of rituximab. On minus 7 days, his anti-A titer was found to be 1:32. He received one session of plasmapheresis, following which mycophenolate mofetil 360 mg twice a day and prednisolone 20 mg was started. On day 5, tacrolimus was started at a dose of 0.1 mg/kg/day. On day 2, he received one more session of plasmapheresis, as his titer was 1:16. His tacrolimus trough level was 6.5 ng/dl.

On the day of transplantation, his anti-A titer was 1:8 [Figure 2]. Induction was given with injection basiliximab 20 mg on days 0 and 4 and methylprednisolone on 3 consecutive days (500 each) followed by oral prednisolone. Intraoperatively, there was severe arterial spasm while retrieving the kidney during open donor nephrectomy. Warm ischemic time was 4 min and cold ischemic time was 2 h and 39 min.{Figure 2}

Following transplantation, he had delayed graft function. His urine output was low. His postoperative maintenance immunosuppression were mycophenolate mofetil 720 mg twice a day and prednisolone 50 mg which was gradually tapered; on the 3rd postoperative day, he received one session of hemodialysis. Postoperatively, anti-A titers were monitored daily. Repeat donor-specific antibody was sent. Graft biopsy was done on the 5th postoperative day. From postoperative day 8, serum creatinine showed a declining trend along with an increase in urine output from 80 to 200–250 ml/h. His donor-specific antibody was negative. Graft biopsy was suggestive of patchy acute tubular injury and no rejection (Banff scores: I0, ti0, t0, v0, mm0, g0, cg0, ci0, ct0, cv1, ah2, and ptc0) [Figure 3]. Cd4 was negative. Gradually, tacrolimus was started from the 8th postoperative day. He was discharged on the 14th postoperative day with maintenance immunosuppresants as tacrolimus (2 mg twice a day), mycophenolate mofetil (720 mg twice a day), and prednisolone 20 mg. Prophylactic medication for pneumocystis carinii pneumonia (cotrimoxazole), fungal (fluconazole), and cytomegalovirus (valganciclovir) infection was advised. At the time of discharge, his serum creatinine was 1.1 mg/dl, 200–250 ml hourly urine output, and ABO anti-A titer was1:8 [Figure 4] and [Figure 5].{Figure 3}{Figure 4}{Figure 5}

 Discussion



ABOiKT is becoming an increasingly popular modality to tide over the crisis of shortage of organ donors even in developing countries like India. No studies or case report has been reported from the state of Chhattisgarh.

Pretransplant assessment along with effective desensitization strategies is the key factor for a successful renal transplantation in such patients. Desensitization protocol varies from center to center [1],[2],[3] and from clinical experience within a center. The desensitization protocol employed for our patient included rituximab, plasmapheresis, and triple immunosuppression.

Rituximab, anti-CD20 monoclonal antibody, has an added advantage over splenectomy that it effectively inhibits the B-cell proliferation and induces apoptosis by antibody-dependent cell-mediated cytotoxicity by complement.[4] The study done by Fuchinoue et al. reported that patients receiving rituximab pretransplant had a lower incidence of Antibody mediated rejection (AMR) along with better 5-year graft outcome.[5] Montgomery et al. have used rituximab, plasma exchange, and cytomegalovirus (CMV) intravenous immunoglobulin (IVIG) as preconditioning.[6] The dose of rituximab used in most centers is 375 mg/m2 of body surface area given 4 weeks prior to transplantation.[7],[8],[9],[10] In our study, we used rituximab 2 weeks prior to transplantation at a dose of 200 mg. Shirakawa et al.[7] decreased the dose to 200 mg/kg body weight in the later phase after using 500 mg/body initially. The graft and patients' survival rates were similar with both the dosages, suggesting that rituximab at the dose of 200 mg is sufficient for ABOiKT. A study done in Eastern India by Ray and Thukral [11] has used rituximab at a dose of 200 mg/kg body weight, 2 weeks prior to transplantation, and achieved good patient and graft survival.

An important issue is isoagglutinin titer method. In the USA, Kobayashi and Saito et al.[12] compared four antibody measurement techniques: the test-tube technique, BioVue column agglutination technique, DiaMed-ID microtyping system, and flow cytometry. The comparison revealed that flow cytometry had the best reproducibility. However, the flow cytometry technique is not available in all laboratories. AuBuchon et al.[13] study showed that the gel card technique showed reduced variance compared to tube-based techniques. In our study, antibody titer measurement was done by column agglutination technology by the gel card method.

Another issue is the lack of consensus with regard to a suitable level of anti-A/B IgG or IgM titers on the day of transplantation. In most centers, the acceptable target for isoagglutinin titer is <1:8 on the day of transplantation.[14],[15],[16] In other studies, the target acceptable isoagglutinin is <1:16.[9],[17],[18] In our patient, the acceptable isoaggultinin titer was 1:8, on the day of transplantation. Tydén et al.[19] aimed to achieve IgG titer of <1:8 and Tanabe et al.[20] had accepted an upper limit of 1:32. These studies reported good graft survival.

Antibody depletion technique remains the cornerstone of ABOiKT. Various techniques used are plasma exchange, double-filtration plasmapheresis, and antigen-specific immunoadsorption to achieve adequate antibody depletion. Each session removes 20% of anti-ABO antibodies. Some studies by Gloor et al.,[21] van Agteren et al.,[22] and Squifflet et al.[23] have shown successful use of therapeutic plasma exchange along with rituximab for antibodies depletion. In our patient, plasmapheresis was used along with rituximab for antibody depletion.

Most of the protocols have used IVIG after plasmapheresis. A study done in Eastern India by Ray and Thukral [11] used 10–25 g of IVIG. In a few other studies, a single dose of 0.5 g/kg IVIG was given pretransplantation.[14],[22],[24] We did not use IVIG after plasmapheresis because of economic constraint.

Accommodation is a process in which the recipient of an organ develops an acquired resistance to immune-mediated rejection.[25] It takes nearly 2 weeks for the graft to accommodate in the host body.[26] In our patient, graft biopsy was done on the 5th postoperative day; we did not get C4d positivity.

Ravichandran et al.[27] and Ray and Thukral [11] have started triple immunosuppression (tacrolimus, mycophenolic acid, and prednisolone) as preconditioning immunosuppression on minus 7 days of kidney transplantation. In our case, we started mycophenolic acid and prednisolone on minus 7 days, but tacrolimus was started on minus 5 days of kidney transplantation.

To our knowledge, this is the first case report from Chhattisgarh regarding ABOiKT. The facilities required for renal transplantation such as immunological laboratory to assess DSA level, renal pathologist to obtain timely biopsy report, and tacrolimus level assessment which takes nearly 2 days to get report make this case challenging. The immediate graft outcome was good, although he had delayed graft function requiring one session of hemodialysis due to acute tubular injury. We need to see long-term outcomes with our protocol.

 Conclusion



Immunological risk assessment and proper surgical planning have a great impact on ABOiKT outcome. Acute tubular necrosis is the leading cause of delayed graft dysfunction. Multidisplinary approach and good team effort play a major role in ABOi renal transplant outcome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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