In order to decrease the time on the deceased donor kidney wait list and to have more organs available, criteria for acceptable organs for transplant could be made less stringent. There are reports of successful recipient outcomes using kidney donors presenting with disseminated intravascular coagulation (DIC). We report a unique circumstance where two patients received kidneys from the same deceased donor who had DIC; one patient developed thrombotic microangiopathy (TMA) while the other did not. This difference in outcome may indicate that both donor and recipient factors contribute to the development of posttransplant TMA.
Kidney transplantation is the treatment of choice for end stage kidney disease (ESKD). Unfortunately, the wait time for a deceased donor kidney continues to increase every year as the number of potential recipients on the waiting list has far surpassed the number of kidney donors available for transplantation [
The donor was a 24-year-old African American male with no significant medical history who sustained a gunshot wound to the head and subsequently developed DIC and multiorgan failure. The terminal serum creatinine was 6.0 mg/dL. Preimplantation biopsy of the donor's right kidney showed 27 glomeruli with no sclerosis; fibrin thrombi were present in 8 glomeruli; there was no interstitial fibrosis and tubular atrophy (IFTA), acute tubular necrosis (ATN), or infiltrates; mild (<25%) arterial sclerosis was identified but there was no arteriolar hyalinosis. Preimplantation biopsy of the left donor kidney revealed 34 glomeruli with 1 sclerosed glomerulus (2.9%); fibrin thrombi were present in 1 glomerulus; no IFTA, ATN, infiltrate, arterial, or arteriolar hyalinosis were observed.
The first recipient was a 55-year-old Caucasian male with ESKD secondary to hypertension who had been on hemodialysis for 6 years. There were 4 HLA mismatches with the donor, and the panel reactive antibody (PRA) titer at the time of transplant was 0%. He received the donor’s right kidney. The cold ischemia time (CIT) was 18 hours and 10 minutes. The patient was induced with antithymocyte globulin and maintained on tacrolimus, mycophenolate sodium, and prednisone. He had an uncomplicated postoperative course with a serum creatinine of 3.1 mg/dL at time of discharge. A month later, the serum creatinine improved to 1.2 mg/dL.
The second recipient was a 39-year-old African American, nonobese female with body mass index of 28.7, with ESKD presumed to be due to hypertension, and had been on peritoneal dialysis for 9 years. She received the donor’s left kidney and there were 4 HLA mismatches and the PRA was 0%. The CIT was 22 hours and 17 minutes. She was also induced with antithymocyte globulin. She had delayed graft function (DGF) requiring peritoneal dialysis for about 10 days after transplant.
As shown in Table
Pertinent laboratory values of the second patient describing the postoperative clinical course.
Labs | Before surgery | 48 hours after transplant | 4 weeks later/at discharge | 2 years after transplant |
---|---|---|---|---|
WBC (×1000/L) | 10 | 8.6 | 5.2 | 6 |
Hemoglobin (gm/dL) | 8.6 | 7.1 | 11 | 11.2 |
Platelets (×1000/L) | 289 | 35 | 239 | 188 |
Prothrombin time (sec) | 14 | 16 | ||
Partial thromboplastin time (sec) | 30 | 32 | ||
Lactate dehydrogenase (mg/mL) | 622 | |||
Haptoglobin (mg/dL) | <20 | |||
Coombs’ test | Negative | |||
ADAMTS13 activity | 59% | |||
HIT antibody PF-4 assay* | Negative | |||
Creatinine (mg/dL) | 14 | 12.5 | 1.4 | 1.3 |
She was treated with daily therapeutic plasma exchanges (total of 11 treatments) and four doses of rituximab (375 mg/m2 of body surface area or 700 mg per dose) on postoperative days 14, 21, 28, and 35. Her blood parameters improved with subsequent recovery of her kidney allograft as noted in Table
TMA refers to blood vessel wall thickening (mainly arterioles or capillaries) with swelling or detachment of the endothelial cell from the basement membrane, accumulation of fluffy material in the subendothelial space, intraluminal platelet thrombosis, and partial or complete obstruction of the vessel lumina [
The recurrence rate of TMA after kidney transplantation is reported between 25 and 50 percent [
De novo TMA after kidney transplantation is far less common with a reported incidence of only 0.8% in the analysis of United States Renal Data Systems [
DIC is characterized by activation of the coagulation pathway which results in the intravascular formation of fibrin [
Supporting this approach were findings from a retrospective cohort of 162 kidney transplants in which donor DIC was not associated with suboptimal graft function in the short term [
The role of ADAMTS13 deficiency for identifying patients who have a clinical diagnosis of TTP has not been well defined. In one study, the presenting features and clinical outcomes of 16 patients with idiopathic TTP-HUS who had severe ADAMTS13 deficiency were variable and not distinctively different from the 32 patients with idiopathic TTP-HUS who did not have ADAMTS13 deficiency [
Our report indicates that both donor and recipient factors are important in posttransplant TMA as the first recipient did not manifest the disease while the second recipient did. Since the underlying cause of ESKD was reported as hypertension in the second recipient, donor DIC perhaps played an important role in causing TMA.
Organ transplantation by itself can cause microvascular injury in numerous ways and thus may trigger TMA [
In general, the prognosis of de novo TMA is better than that of recurrent TMA. However, it may depend on the severity of clinical features and histological lesions. Patients with isolated glomerular TMA usually have a good outcome while patients with systemic signs and symptoms of TMA are more likely to need renal replacement therapy with associated loss of allograft function [
While there are no guidelines for treatment of de novo TMA after kidney transplantation, withdrawal of the offending agent is mandatory. Switching from a CNI based immunosuppressive regimen to a non-CNI based regimen can be helpful in some cases [
Our second patient developed posttransplant TTP-HUS even before the initiation of CNI. The syndrome was recognized early and with aggressive treatment her clinical course improved. She was maintained on mycophenolate mofetil and prednisone and was started on tacrolimus after completion of plasma exchange with close monitoring of her clinical course. A biopsy was not performed after the intervention as the patient’s kidney function remained stable. She did not have any subsequent episodes of TTP/HUS and her serum creatinine at 4 years after transplant was stable at 1.3 mg/dL.
More recently, there is evidence that eculizumab (anti-C5a) may be effective in treating and preventing recurrence of aHUS after kidney transplantation [
TMA in either the kidney recipient or the donor is generally associated with a poor prognosis. While donor kidneys with TMA should not be automatically discarded, reasonable caution should be exercised as to whom these kidneys should be transplanted into. For example, they should not be used in recipients who have had previous episodes of TMA needing therapy or those who currently have thrombocytopenia for unknown reasons. Needless to say, informed consent is critical. Recipients should be informed about the potential risk of developing TMA after transplant with associated loss of the allograft. Patients should be monitored closely after transplant and therapy instituted as soon as possible if there are signs or symptoms of TMA, either clinically or on the allograft biopsy. While conventional therapies of plasma exchange, IVIg and rituximab, are frequently used, the anti-C5a antibody eculizumab offers promise.
The authors attest that an informed consent was obtained from the patient prior to submitting the report.
The authors report no conflict of interests related to this paper.