EXPERIMENTAL AND CLINICAL TRANSPLANTATION

In recent years, dual-kidney transplant (DKT) has become an established method to overcome the inferior quality of donor organs. This procedure has helped to treat more transplant patients by utilizing marginal kidneys that would otherwise be discarded.¹ Several studies have compared the performance of DKT with ideal single-kidney transplant (SKT), and the use of 2 marginal kidneys in the same recipient is becoming more widespread. It is worth noting that both transplant options demonstrate comparable data in terms of renal function retrieval and graft survival.^1,2

Donors can be classified as expanded criteria donors (ECD) based on age, hypertension, renal dysfunction, macroscopic examination, and preimplant biopsy, all of which may help to guide the decision to perform SKT or DKT.³ Most groups implement DKT strategy after considering the donor age, type of death, medical history, renal function, and histology score of preimplant kidney biopsy.^2,4 However, in some cases, if 1 of the ECD kidneys is discarded due to severe pathological changes, then the remaining marginal kidney is often discarded, regardless of whether it meets the criteria for DKT.

Here, we used 2 marginal kidneys from 2 different donors, both of whom had missed the transplant because of serious pathological changes in their contralateral kidney. Then, a DKT was performed on a recipient, and a favorable outcome was recorded.

Donor kidney selection process
In addition to the clinical evaluation of the donors, the Chinese guidelines have recommended a routine preimplant biopsy for histological evaluation. Based on the donor’s age, renal function, comorbidities, and histological score,⁵ the kidneys were allocated for SKT or DKT. Specifically, the histological scores (range, 0-12) were assessed using the scoring systems of Karpinski and colleagues⁶ and Remuzzi and colleagues^2,7 according to the degree of glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arterial and arteriolar narrowing. The ECD organs with renal scores of 3 or less were suitable for SKT, those with renal scores of 4 to 6 were recommended for DKT, and those with renal scores of 7 or more were discarded.^2,5,7

Donor 1
The first donor was a ~60-year-old man (A Rh+) who had an intracranial hemorrhage and became eligible after brain death. Donor risk factors were hypertension and multiple hepatic/renal cyst disease. The serum creatinine (sCr) level before organ procurement was 183 μmol/L (2.07 mg/dL), and the estimated glomerular filtration rate (eGFR) was 40.80 mL/min/1.73 m² (Table 1). Histological scores for the right kidney and left kidney were 6 and 11, respectively (Table 2). During back-table preparation, we found severe cystic lesions and almost no normal appearance in the left kidney (Figure 1, A and B), which was discarded directly. In contrast, the right kidney had a normal appearance (Figure 1B). Histological results showed that the right kidney was more suitable for DKT than for SKT. However, without the left kidney, the right kidney had to be discarded as well.

Donor 2
The second brain dead donor was a ~50-year-old man (blood type A Rh+) who died after a massive cerebral infarction. The organ procurement date was 1 day after procurement for donor 1 in August 2020. Donor risk factors were hypertension, hydronephrosis, and multiple renal calculi in the right kidney. The sCr before organ procurement was 91 μmol/L (1.03 mg/dL), and the eGFR was 87.87 mL/min/1.73 m² (Table 1). Histological score was 5 for both kidneys (Table 2). During back-table preparation, the right kidney had an irregular size with severe hydronephrosis and renal calculi (Figure 1, C and D), and so the kidney was discarded directly. Similar to the first donor, the left kidney of the second donor was more suitable for DKT. However, without the right kidney, the left kidney of the second donor had to be discarded as well.

Ethics approval
Our study followed the Declaration of Helsinki guidelines and was approved by the Human Organ Transplant Clinical Technology and Ethics Committee at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology. Written informed consent was obtained from patients for the publication of any potentially identifiable images or data included in this article.

After we obtained the emergency approval from the Human Organ Transplant Clinical Technology and Ethics Committee in our hospital and informed consent, we recalled the right kidney of the first donor (R1) and combined it with the left kidney of the second donor (L2). Subsequently, DKT was scheduled for the transplant patient. The patient had signed an informed consent document for DKT before enrollment and was chosen for only 3 of 12 mismatches in human leukocyte antigens (HLA) A, B, and DR loci of the 2 donors (Table 3). The patient was a primary transplant recipient with low immunological risk. The pretransplant panel reactive antibodies and complement-dependent cytotoxicity both yielded negative results.

Unilateral dual-kidney transplant
The recipient patient was a 41-year-old female patient (blood type A Rh⁺, 163 cm in height and 46 kg in body weight) with chronic renal failure due to nephroangiosclerosis. The hemodialysis time was more than 1 year, and the sCr level was 660 μmol/L (7.47 mg/dL) before transplant. In accordance with the standard procedure, DKT was performed without any complications. Both kidneys were implanted into the right iliac fossa after 13 hours 40 minutes of cold ischemia time for the left kidney (L2) and 30 hours 30 minutes for the right kidney (R1). Briefly, the surgical procedure began with a lateral incision above the right iliac fossa. The right external iliac artery and vein, as well as the proximal part of the internal iliac artery, were retroperitoneally exposed and prepared. The proximally placed kidney (R1) was implanted first. The renal artery was anastomosed end-to-end to the recipient internal iliac artery with 6-0 Prolene sutures, and the renal vein was anastomosed end-to-side to the external iliac vein with 5-0 Prolene sutures (Figure 1E). After recirculation of the proximally placed kidney, the distally placed kidney (L2) was implanted with vascular anastomoses to the recipient external iliac artery and vein (Figure 1E). The 2 ureters were implanted onlay to the bladder over double-J stents.

Patient outcome
No bacterial or fungal contaminations were detected from the microbiological cultures performed using both preservation solution and drainage fluid. Antibiotic (carbapenems) and antifungal (caspofungin) drugs were administered for 10 days. A complete regimen of thymoglobulin infusion, steroids, tacrolimus, and mycophenolate mofetil was followed according to the standard protocols.⁸ Briefly, as induction therapy, anti-T-lymphocyte globulin Fresenius (ATG-F) was given from day 0 to day 4 at a daily dose of 2 mg/kg. Methylprednisolone was given intravenously from day 0 to day 2 (500 mg/d), followed by oral doses of prednisone at 50 mg/d, which were then tapered every other day to a maintenance dose of 10 mg/d. Mycophenolate mofetil was administered at a dose of 10 mg/kg/d. Tacrolimus was started at day 3, with a targeted trough level of 7 to 10 ng/mL initially and 6 to 8 ng/mL at 1 month after transplant.

The recipient had immediate graft function, with sCr of 110 μmol/L (1.24 mg/dL) at 4 days after the operation and 4500 mL/d of diuresis (Figure 2A). At 15 days after DKT, magnetic resonance imaging examination showed good positioning of the 2 grafted kidneys (Figure 1F), and the GFR values measured by radionuclide dynamic renal imaging with ^99mTc-radiolabeled diethylenetriaminepentaacetic acid were 27.14 and 53.44 mL/min for the R1 (upper) and L2 (lower) kidneys, respectively (Figure 1F). Considering that the measurement areas of the 2 grafted kidneys were overlapping, the actual GFR value of each kidney may be varied, but the total calculated GFR value of 80.58 mL/min is correct and meaningful. On the day of discharge (26 days after DKT), the sCr level of the patient was 70 μmol/L (0.79 mg/dL); at the 1.5-year follow-up after transplant, the sCr levels ranged from 85 to 117 μmol/L (0.96 to 1.32 mg/dL) (Figure 2B). No positive donor-specific antibody (DSA) was detected in the 3 tests performed at 3, 4, 6, and 12 months after DKT (Figure 2B).

The dual transplant of marginal kidneys has shown positive results and can help to increase the number of available allografts. However, the use of marginal kidneys is complex and risky.^1,2 There are many aspects to consider in determining the eligibility for DKT.^1,5 Clinical algorithms have been proposed by some groups for the allocation of ECD organs (SKT, DKT, or discard) according to the donor characteristics such as age, renal function, histology, and/or comorbidities,^7,9 but no consensus has been reached so far. In our center, a routine preimplant biopsy was implemented with a scoring system based on the histological score from the studies of Karpinski and colleagues⁶ and Remuzzi and colleagues.^2,7 However, histology score alone is not the only aspect to consider for SKT or DKT assignment. In addition to biopsy data, we also considered the donor’s age, renal function, comorbidities, and macroscopic inspection during the back-table procedure. Severe multiple renal cysts, hydronephrosis, and renal calculi are the common reasons for organ discard,¹⁰ which are characteristics that have occasionally been found during back-table preparation.

In this report, multiple hepatic/renal cysts were found by routine ultrasonography in the first donor, and hydronephrosis/multiple renal calculi were found in the second donor, prior to organ procurement. However, because of the unstable status of the donors, no further risky examination was performed. During the back-table preparation, we found extremely severe renal cystic lesions in the left kidney of the first donor. Although the right kidney met the criteria for DKT, the status of the left kidney jeopardized the overall procedure. Fortunately, the same situation happened on the next day, for which the right kidney of the second donor was discarded because there was irreparable hydronephrosis/multiple renal calculi, and only the left kidney was eligible for DKT. After rigorous ethical review and risk assessment, we combined the marginal kidneys from the 2 different donors and successfully performed DKT in 1 recipient with favorable outcome. To our surprise, without hypothermic machine perfusion, the first donor kidney recovered quickly even with 30 hours of cold ischemia time. However, the long-term function remains to be seen.

Our greatest concerns with this procedure were the increased risks of donor-derived infection and both short-term and long-term immunologic challenges. Despite the lack of positive findings in microbiological cultures, we still chose to prescribe a strong antibiotic and antifungal regimen for 10 days to prevent potential infections. In addition, DKT with kidneys from 2 donors may increase the risk of immunological rejection, so the selection of the immunosuppressive strategies is another challenge. Fortunately, the number of HLA mismatches between the recipient and 2 donors was acceptable (only 3 of 12 mismatches). Given the balance of risk between infection and rejection, we still routinely used a complete regimen of induction therapy and regular maintenance therapy. Therefore, it is more important to closely monitor the occurrence of acute rejection and the appearance of DSA. To date, the transplant recipient has shown no acute rejection events and no positive DSA has been detected during the follow-up period.

To the best of our knowledge, this is the first case report to describe a favorable outcome of successful unilateral DKT of discarded kidneys from 2 ECDs.

Volume: 20 Issue: 11 November 2022

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