Renal transplantation is the preferred treatment for chronic kidney disease. The dire shortage of organs fuels a constant effort to expand the donor organ pool. One focus of this effort is to retrieve more organs from donors who die with acute kidney injury (AKI). In this issue of Transplantation, Heilman et al report successful transplantation of 1313 kidneys obtained from donors with varying degrees of AKI staged using AKI Network (AKIN) criteria and followed for up to 6 years.1 In this commendable study, 5-year graft survival was 78.5%, 77.8%, 83.8%, and 84.6% for AKIN donor stages 0, 1, 2, and 3, respectively. Delayed graft function occurred in 44.6% and 75.4% of AKIN stages 2 and 3, compared with 33.9% and 33.5% in stages 0 and 1. Similar studies have been reported before but generally with shorter follow-up times and not always with accompanying pathology data. Indeed, an important strength of this study is that a preimplantation biopsy was available, and in most cases reviewed on site by a transplant surgeon, nephrologist, and pathologist, to rule out significant histologic chronicity. Organs with >10% cortical necrosis, moderate or severe glomerulosclerosis, interstitial fibrosis, arteriosclerosis, or arteriolar hyalinosis were not used, but the actual number of organs discarded because of biopsy findings is not clear.
The use of histology-based screening in this study raises the controversial question of the utility of preimplantation biopsies in donor selection. Some transplant surgeons and physicians use them religiously in conjunction with clinical parameters (age, diabetes mellitus, vascular disease, and cold ischemia time), whereas others state that biopsies only increase the rate of organ discard. It is not often appreciated that finding only mild histologic changes can have reassuring value when there are clinical questions about organ viability. Biopsies can promote organ usage and prevent inappropriate discard if used as a part of an overall clinicopathologic assessment. The widely quoted problem of poor reproducibility of histologic findings does not apply to extremes of pathology. Most pathologists can recognize a nearly normal kidney and a completely infarcted one. Low statistical kappa values reported in many studies reflect clinically insignificant disagreements such as absent versus mild chronicity. Most donor biopsy series do not have sufficient number of moderate or severe pathology to accurately measure corresponding kappa values.2 Indeed, the kappa statistic is not intended to be used with for conditions with low prevalence.3 It bears pointing out that that similarly, low kappa values do not detract from the unquestionable utility of histopathology in posttransplant monitoring of the renal allograft and staging of medical renal diseases such as systemic lupus erythematosus and IgA nephropathy.4-6
Certainly, biopsies can be and have been inappropriately used. Insufficient recognition of sampling problems, technical artifacts, conclusions based on inadequate biopsies, and rigidly applied histologic criteria (eg, 20% glomerulosclerosis) have likely contributed to higher organ discard rates in the United States compared with Europe. However, this should not be a reason to abandon donor biopsies; rather, it should act as an incentive to use them more rationally. There is significant need for education and training to accomplish this. As in other areas of medical practice, an initial learning curve, availability of round-the- clock specialty expertise, and experience are important for obtaining optimal results.7
Another important contribution of the biopsy to this study was to clarify that all donors referred to as AKI were actually subjects with acute tubular injury. Without a biopsy, AKI defined in terms of a rising serum creatinine cannot be distinguished from acute glomerulonephritis, acute interstitial nephritis, or thrombotic microangiopathy. The latter condition is of particular relevance to evaluating organ donors. Young and otherwise healthy donors dying of motor vehicle accident or gunshot trauma to the head can develop disseminated intravascular coagulation. A donor biopsy can exclude extensive thrombosis and infarction and prevent implantation of organs destined to primary nonfunction. Of course, milder forms of organ involvement should not be a contraindication to transplantation, since thrombi can resolve spontaneously after transplantation.
A pathologist can help in revealing the extent of thrombosis in an organ being considered for transplantation. However, a yes/no decision with regard to accepting or discarding an organ cannot be based on arbitrary histologic thresholds alone. Importantly, the degree of pathologic damage in an organ should not be gauged simply by reading a biopsy report or looking up information available in DonorNet. Personal review of the biopsy with a pathologist, or review of a whole slide scan made available for telepathology consultation, may, for example, indicate that a biopsy described as having thrombi in 50% of the glomeruli has only an occasional capillary thrombus in the individual glomeruli.8 Such a kidney is potentially usable if serum creatinine is normal or has shown a significant downward trend before donor death.
Where do we go from here? I think we need to try and push the envelope further. For stage 3 AKIN, the mean terminal serum creatinine in the study by Heilman et al was 4.60 mg/dL. To put this in perspective, current Organ Procurement Transplant Network policy lists a serum creatinine of 4.0 mg/dL as an exclusion criterion for organ donors. One could argue that this criterion is too conservative. On the other hand, one might expect that there will be an upper limit to the degree of AKI that is acceptable in a donor organ. Already, Table 4 demonstrates that progressive AKI is associated with a nonsignificant upward trend in the incidence of estimated glomerular filtration rate <30 minutes at 12 months. In Table 5, the interstitial fibrosis score in the 1-year biopsy is higher in AKI stages 1–3 compared with stage 0 (P = 0.06). In the native kidney, AKI is a risk factor for the development of chronic kidney disease. It is possible that larger series of transplant patients with stage 3 donor AKI may also show a similar outcome. The function of a donor kidney with AKI will also depend on recipient’s characteristics such as age, degree of HLA matching, sensitization status, and dialysis time.
1. Heilman RL, Smith MJ, Smith BJ, et al. Long-term outcomes following transplantation from donors with acute kidney injury. Transplantation. 2019; 103:e263–e272
2. Liapis H, Gaut JP, Klein C, et al; Banff Working Group. Banff histopathological consensus criteria for preimplantation kidney biopsies. Am J Transplant. 2017; 17:140–150
3. Chen G, Faris P, Hemmelgarn B, et al. Measuring agreement of administrative data with chart data using prevalence unadjusted and adjusted kappa. BMC Med Res Methodol. 2009; 9:5
4. Furness P, Assmann KJ, Cosyns JP, et al. International variation in histologic grading is large and persistent feedback does not improve reproducibility. Kidney Int. 2013; 13:805
5. Restrepo-Escobar M, Granda-Carvajal PA, Jaimes F. Systematic review of the literature on reproducibility of the interpretation of renal biopsy in lupus nephritis. Lupus. 2017; 26:1502–1512
6. Roberts SD, Cook HT, Troyanov S, et al. The Oxford classification of IgA nephropathy: pathology, definitions, correlations and reproducibility. Kidney Int. 2009; 76:546–556
7. Azancot MA, Moreso F, Salcedo M, et al. The reproducibility and predictive value on outcome of renal biopsies from expanded criteria donors. Kidney Int. 2014; 85:1161–1168
8. Sood P, Randhawa PS, Mehta R, et al. Donor kidney microthrombi and outcomes of kidney transplant: a single-center experience. Clin Transplant. 2015; 29:434–438