EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: Transplant of kidneys from donors with acute kidney injury has shown favorable outcomes. We investigated the outcomes of kidney transplant recipients with deceased donors who developed acute kidney injury before organ procurement.
Materials and Methods: We retrospectively reviewed the medical records of recipients from January 2016 to December 2021 in a single center. Outcomes in recipients of kidney grafts from donors with and without acute kidney injury were compared.
Results: The mean follow-up time was 40 months. Our study included 129 (34%) kidneys transplanted from donors with acute kidney injury and 251 (66%) kidneys from donors without acute kidney injury. Delayed graft function rate in recipients was 33% in the acute kidney injury group and 25.5% in the group without acute kidney injury (P = .099). Readmission rate at 30 days was significantly higher among recipients of kidneys with acute kidney injury compared with recipients of kidneys without acute kidney injury (45% vs 33.5%; P = .02). The mean overall costs of transplant in the acute kidney injury group were comparable to the group without acute kidney injury ($253 865 vs $253 611; P = .97). The acute rejection rate was comparable between the 2 groups (4% in both groups; P = .96). Delayed graft function rate was increased with increased stage of acute kidney injury (18% stage 1, 45% stage 2, 36% stage 3; P = .03). However, the overall length of hospital stay and costs were comparable among recipients of different stages of acute kidney injury.
Conclusions: Our study showed that kidney transplants from donors with acute kidney injury have early and late outcomes comparable to kidney transplants from donors without acute kidney injury. Allografts from donors with acute kidney injury can be used safely and can expand the donor pool in kidney transplant without increasing perioperative resource utilization.

Key words : Expanded criteria grafts, Graft, Renal transplantation

Kidney transplant is the gold standard therapy for eligible patients with end-stage renal diseases.^1-4 There is currently an imbalance between the number of available donor kidneys and the number of recipients on wait lists. According to the Organ Procurement and Transplantation Network (OPTN), 22 742 patients had kidney transplants; meanwhile, 97 935 patients remained on wait lists in 2021.⁵ This discrepancy between the donor pool and patients on wait lists and the pressure on the health care system has resulted in a revision in donor kidney criteria.^6-9 The OPTN reported that nearly 5000 patients on wait lists become ineligible or expire annually.^10,11

One kidney risk profile index (KDPI) charac-teristic that recently grabbed the attention of many transplant centers in the United States is a kidney with acute kidney injury (AKI). Previously, the diagnosis of AKI led to disqualifying a kidney from being a potential transplant organ, which resulted in the discard of many viable organs. However, recent clinical trials have shown that AKI in many kidneys is reversible and that using a kidney with AKI can be an alternative for an ideal organ.^12-15

Although using a kidney with a high KDPI and AKI results in a higher rate of delayed graft function (DGF),^16-18 many studies reported that long-term results of recipients of kidneys with AKI, including patient and graft survival rates, were promising.^19-21 In contrast, other studies found a meaningful outcome difference between the 2 groups, so the relation between the AKI itself and the long-term outcomes of the transplanted kidney is still unclear and controversial.^13,22-24

Our study aimed to assess the short-term and long-term outcomes and complications of kidney transplants in patients who received a kidney with AKI, to compare them with outcomes and complications of non-AKI kidney recipients, and to assess the possibility of this application as an alternative way to expand the kidney donor pool.

Materials and Methods

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

We conducted a retrospective analysis of a prospectively collected database of all kidney transplant patients at the State University of New York (SUNY) Upstate Medical Hospital from January 1, 2016, to December 31, 2021. The data were collected from patients’ records from the electronic medical record system, with data collection approved by the hospital’s institutional review board committee. Our inclusion criteria were patients who received kidneys from deceased donors. Exclusion criteria were recipients of kidney transplants from living donors, simultaneous kidney-pancreas transplants, or other multiorgan transplants and recipients who died within the first 30 days posttransplant.

The total number of patients included in the study was 380, with patients divided into AKI and non-AKI groups. The AKI group (n = 129) included patients who received a kidney graft from a donor with AKI, and the non-AKI group (n = 251) included patients who received a kidney graft from a donor without AKI.

Acute kidney injury was defined and staged using the Acute Kidney Injury Network (AKIN) criteria.²⁵ Based on AKIN, AKI is defined as an increase in serum creatinine of ≥0.3 mg/dL or ≥50% within 48 hours or urine output of <0.5 mL/kg/hour for >6 hours. Stage 1 AKI is defined as an increase in serum creatinine of ≥0.3 mg/dL or to 150% to 200% of baseline or urine output of <0.5 mL/kg/hour for 6 to 12 hours. Stage 2 is defined as an increase in serum creatinine to 200% to 300% of baseline or urine output of <0.5 mL/kg/hour for 12 to 24 hours. Stage 3 is defined as an increase in serum creatinine to >300% of baseline or increase in serum creatinine by >0.5 mg/dL to ≥4.0 mg/dL or urine output of <0.3 mL/kg/hour for >24 hours or anuria for >12 hours or initiation of kidney replacement therapy.

We investigated donor and recipient clinical characteristics related to creatinine level, DGF, length of hospital stay, hospital costs, acute rejection rate, and allograft and patient survival rates. Acute rejection was defined as graft loss in the first year posttransplant. The mean duration of follow-up was 40 months. Cold ischemia time was defined as the period from the start of perfusion with cold preservation fluid after cessation of circulation, due to cardiac arrest or arterial clamping, until the start of the first vascular anastomosis at implantation. Delayed graft function was defined as failure of the renal transplant to function immediately, with the need for dialysis in the first week posttransplant.

Values are reported as means ± SD (for continuous data) or medians (ranges). Categorical data are reported as proportions and percentages. Our primary outcome was the comparison of baseline characteristics between the groups of interest. Secondary outcomes were comparisons of patient and graft survival rates. Incidences of mortality and death-censored graft loss were analyzed with Kaplan-Meier analysis. Univariate analysis was performed by the t-test, with analysis of variance for continuous variables and chi-square test for categorical variables. P < .05 was considered significant, and P < 0.1 was considered a trend toward significance.

Our study included 380 consecutive deceased donor kidney transplant recipients: 129 (34%) kidneys were transplanted from AKI donors and 251 (66%) kidneys were from non-AKI donors. Donor and recipient demographics were similar between groups (Table 1). The mean ages of recipients in the AKI and non-AKI groups were 52.69 ± 14.73 years and 48.84 ± 15.47 years (P = .02), respectively. Rate of DGF was 33% in the AKI group and 25.5% in the non-AKI group (P = .099). On the other hand, the 30-day readmission rate was significantly higher among the AKI group than the non-AKI kidney group (45% vs 33.5%; P = .02). The mean overall costs of transplant were $253 865 in the AKI group and $253 611 in the non-AKI group (P = 0.97). The mean length of hospital stay in the AKI group was 6 ± 3.94 days and 6.3 ± 6.3 days for the non-AKI group (P = .59). When we compared cold ischemic time between the 2 groups, time was significantly lower in the AKI group (P = .02). The acute rejection rate was also comparable between the 2 groups (4.6% vs 4.7% in the AKI vs non-AKI group; P = .96) (Table 2).

We also analyzed the data for different stages of AKI to see whether the stage of AKI can affect the patient’s posttransplant outcome. Rate of DGF was increased as the AKI stage got higher (P = .03), with DGF rate of 18% for kidneys with stage 1 AKI, 45% for stage 2 AKI, and 36% for stage 3 AKI; however, there was no significant difference when we compared the DGF rate between stage 2 and stage 3 (P = .38). The 30-day readmission rate was 36% for those with grafts with stage 1 AKI, 47% for stage 2 AKI, and 50% for stage 3 AKI (P = .39). The mean cost of transplant and hospital stay was $250 290 for those with grafts with stage 1 AKI, $254 892 for those with grafts with stage 2 AKI, and $255 832 for those with grafts with stage 3 AKI, with no significant difference (P = .91). Table 3 summarizes the data analysis in recipients with grafts of different stages of AKI.

The allograft and patient survival rates were comparable between both groups (Figure 1). Comparisons between different stages of AKI showed no significant difference in terms of patient and graft survival rates (Figure 2).

Kidney transplant is the gold standard treatment for patients with end-stage renal disease.^1-4 Compared with dialysis, kidney transplant enhances the patient’s quality of life and improves long-term morbidity and mortality.²⁶ According to the OPTN, 22 742 patients had kidney transplants; meanwhile, 97 935 patients were still on wait lists in 2021.⁵ This imbalance between the number of available donor organs and the number of patients on wait lists and the pressure on the health care systems due to higher long-term dialysis costs compared with kidney transplants have urged efforts to expand the donor pool.

Many efforts have been made during the past decades in terms of better organ assessment for transplant and organ preservation before transplant with the purpose of donor pool expansion.²⁷ Recently, donor kidneys with AKI have grabbed the attention of many centers around the United States. Acute kidney injury is a sudden loss of kidney function usually within a 7-day period; depending on the etiology, AKI can be corrected. Therefore, many studies and clinical trials have started to investigate donor kidneys with AKI. Growing evidence has shown that donor kidneys with AKI have similar long-term function and survival rates compared with so-called ideal kidneys without AKI. However, some controversy remains about the long-term results.^28-33

Hall and associates,³³ in an investigation of outcomes of 585 deceased donor kidneys with AKI, showed that using donor AKI kidneys was not associated with reduced allograft survival. Heilman and associates¹⁵ also found no difference in 1-year graft survival and 1-year glomerular filtration rate between the AKI and non-AKI groups.

Our study showed that overall outcomes of kidney transplant are nearly similar between kidney recipients who received AKI versus non-AKI kidneys. We did not see a meaningful difference between the 2 groups regarding costs, DGF rate, and length of hospital stay. Although 30-day readmission was higher in the AKI group, it did not significantly affect patient and graft survival rates, and patient and graft survival rates were comparable to those shown in the non-AKI group (Figure 1).

Farney and colleagues¹⁹ studied 84 deceased donors with AKI over 5 years, with AKI defined as doubling of the donor’s admission serum creatinine level and a terminal serum creatinine level of >2.0 mg/dL before organ recovery. The investigators concluded that kidney transplants from donors with AKI have similar 5-year patient and graft survival rates compared with kidney transplants from donors without AKI. Although they found that transplants from AKI donors had higher DGF rates, this had no effect on the graft survival rate. We also found a trend in DGF between AKI and non-AKI groups, but it did not significantly affect either graft or patient survival rate after 5 years of follow-up.

In a retrospective study from Zuckerman and associates¹⁸ of 100 patients divided into AKI and non-AKI kidney donors, 17 patients in the AKI group were compared with 83 in the non-AKI group. Acute kidney injury was defined as terminal creatinine (before organ extraction) of 2-fold or more than the baseline creatinine or values of terminal serum creatinine >2.0 mg/dL. The investigators reported no difference between the 2 groups relative to the outcomes analyzed in terms of 1-year graft and patient survival rates, acute rejection rate, days staying at the hospital, and renal function after 6 months. Although our outcomes were similar, we found a meaningful difference in terms of the 30-day readmission rate between the 2 groups (45% vs 33.5%;P = .02). Over the follow-up period, we observed that the 1-year graft and survival rates were comparable, and the higher 30-day readmission rate did not affect the final outcomes.

In a study from Lin and associates,³⁴ 25 recipients of deceased donors whose terminal serum creatinine was >2.0 mg/dL, with a mean level of 3.37 mg/dL, were assessed. Although the investigators reported a higher rate of DGF (80% vs 30%) in recipients of donors with high levels of terminal creatinine, the patient and graft survival rates and rate of acute rejection were comparable to those of the control group.

Delayed graft function is a risk factor that contributes to early acute kidney rejection, and studies have reported higher DGF among recipients of kidneys from AKI donors compared with kidneys from non-AKI donors.^35-39 However, they suggested that higher DGF does not have a negative effect on patient and graft survival rates, and the rate of acute rejection was not significantly higher.^13,14,40,41

Although recent evidence has grown in favor of including AKI kidneys in the donor pool, some controversial results have been shown. Schütte-Nütgen and colleagues¹⁶ observed a difference in estimated glomerular filtration rate between AKI and non-AKI kidney recipient groups of approximately 10 mL/min/1.73m² at 3 months and at 1 and 3 years posttransplant. The investigators also noticed a meaningful influence of DGF on short- and long-term kidney function. Yu and colleagues³² reported that the AKI kidney donors, even with higher stages of AKI, have promising graft survival rates compared with the non-AKI group and are suitable for transplant. Kolonko and colleagues30 found that AKI donor kidneys, especially those with higher stages of AKI, have higher graft loss compared with non-AKI donor kidneys (27.8% vs 7.1%; P = .02). Our findings were the opposite, as we found comparable graft rejection rates in both the long term and short term. We even found higher 1-, 3-, and 5-year graft survival rates in the AKI group compared with the non-AKI group, although it was not statistically significant (P = .15).

Boffa and colleagues¹³ reported that, depending on the severity of AKI, the outcome of graft survival would be influenced. They studied 1869 kidneys with AKI in the United Kingdom and found that recipients of AKI kidneys had only 2% lower graft survival than recipients of non-AKI kidneys, concluding that, compared with the annual death rate of 8.2% for patients on kidney transplant wait lists, AKI kidneys are still beneficial and lifesaving.

Our study has some limitations as it was a retrospective, single-center cohort study. In addition, the study cohort was over a period of 6 years and the number of cases was limited. During the study, selection biases were inevitable. Randomized clinical trials with a meaningful cohort size are needed to eliminate possible biases.

Our study provides more evidence that transplant of kidneys with AKI has a comparable result to transplant with non-AKI kidneys, and transplant centers may consider using AKI kidneys more often, which could result in kidney donor pool expansion, as it does not result in increased perioperative resource utilization.

Volume: 21 Issue: 2 February 2023

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