A 52-year-old woman with end-stage kidney disease on manual peritoneal dialysis (PD) was wait-listed in the deceased-donor kidney transplantation program. After about 3 years, she was offered an ABO-compatible deceased-donor kidney from centralized allocation system. Donor was 24 years, male, with no comorbidities, who suffered from brain death due to a road traffic accident. Family of deceased-donor was consented to donate multiple organs. One kidney was allocated to our patient. Pretransplant complement-dependent cytotoxicity crossmatch was negative. Warm and cold ischemia times were around 10 min and 12 h, respectively. She received rabbit antithymocyte globulin induction. Intraoperatively, she had hypotension (probably induced by an induction agent) requiring vasopressor support for about 12 h. Postoperatively, she remained anuric and affected with delayed graft function (DGF) requiring bedside automated PD. She was started on steroids and mycophenolate mofetil. Serial Doppler examination showed normal waveforms with good vascularity initially. However, at the end of 1 week, there was a loss of diastolic flow with raised resistive index (0.98) in segmental and interlobar arteries. The blood flow was normal in the main renal vessels. The patient remained anuric and an allograft biopsy was performed, which showed widespread areas of patchy cortical necrosis with ghost outlines of necrotic tubules in the affected areas. The intervened areas showed significant acute tubular necrosis (ATN) with vacuolization, flattening, and denudation of the lining epithelium of tubules [Figure 1]. There was no evidence of rejection or thrombotic microangiopathy (TMA) and C4d staining was negative. Retrospectively, we found that the recipient of another kidney from the same donor also had DGF and the biopsy showed severe ATN. Our patient required PD for about 2 weeks, thereafter urine output gradually improved to around 1.8 l/day and creatinine stabilized at 2.8 mg/dl at the end of 4 weeks. Currently, she is maintained on triple-drug immunosuppression with tacrolimus added to the regimen.
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Figure 1: Light microscopy examination of the kidney allograft biopsy specimens showing areas of patchy cortical necrosis with ghost outlines of necrotic tubules (long and thin arrows). The intervened areas show acute tubular necrosis with vacuolization, flattening, and denudation of lining epithelium of tubules (short and thick arrows) (H and E; A: low-power; B: ×10)
Posttransplant cortical necrosis (PTCN) is characterized by patchy or diffuse ischemic necrosis of all the elements of the renal cortex resulting from significantly diminished renal arterial perfusion due to vascular spasm and microvascular injury. It is commonly encountered in deceased-donor transplantation and can affect both the recipients of donor kidneys as noted in our case. The common predisposing factors for PTCN are severe and prolonged ischemia and hypotension, vascular insults (vascular thrombosis, thromboembolism, vasculitis, and surgical factors), disseminated intravascular coagulation, infections (sepsis and angioinvasive infections such as Aspergillus and Mucormycosis), immunological (systemic lupus erythematosus and antiphospholipid antibody syndrome), TMA, and severe vascular rejection (usually as a part of antibody-mediated rejection). The factors that could have contributed to PTCN in our patient are poor deceased-donor management, prolonged warm ischemia due to the harvesting of multiple organs, and significant hypotension in the recipient intraoperatively. Although we could not perform, preimplantation or procurement biopsy can be a valuable tool in some of these cases at the time of organ harvesting.
Cortical necrosis is associated with complete necrosis involving glomeruli, tubules, and vessels, identified with only ghost outlines (washout appearance with no nuclear details) of glomeruli and tubules in the areas involved. It is irreversible, heals with fibrosis, and then calcification. Bilateral cortical necrosis is a marker of the generalized Schwartzman reaction. In contrast, ATN is actually a misnomer, usually associated with variable tubular injury rather than necrosis. Injury may vary from loss of brush border, vacuolization, and flattening with dilated lumina to completely denuded epithelium, but the basement membrane is intact, which leads to regeneration after few weeks. If PTCN is bilateral and diffuse, it can lead to graft loss. Sometimes, it may require graft nephrectomy, especially in the presence of vascular thrombosis.
The incidence of PTCN seems to be declining due to better immunological evaluation with the availability of more sensitive and specific donor-specific antibody assays, advances in surgical techniques, and deceased-donor management. The individualization of induction therapies, adoption of desensitization techniques, and screening for prothrombotic states in high-risk patients (those with a history of multiple access failures while on hemodialysis, frequent miscarriages, spontaneous or recurrent deep vein thrombosis, and pulmonary embolism) might have also helped in reducing its incidence in the transplant setting. This case illustrates that proper management of deceased-donor at the time of organ harvesting can prevent devastating complications such as PTCN. Due to the patchy nature of PTCN in our patient, the graft function has recovered partially which was enough to stop dialysis.
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