Successful kidney transplantation using organs from a donor with disseminated intravascular coagulation and impaired renal function: case report and review of the literature
Myriam Pastural1,
Benoît Barrou,1,
Annick Delcourt2,
Marc-Olivier Bitker1,
Saïda Ourahma3 and
François Richard1
1 Departments of Urology,
2 Histology and
3 Anesthesiology, Hôpital La Pitié-Salpêtrière, Paris, France
Keywords: disseminated intravascular coagulation; kidney transplant
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Introduction
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Disseminated intravascular coagulation (DIC) is characterized by the widespread activation of coagulation, which results in intravascular formation of fibrin and ultimately in thrombotic occlusion of small and midsize vessels [1]. DIC can lead to the failure of multiple organs, including kidneys. Incidence of DIC is estimated at 25% in cadaveric organ donors, and as high as 37% and 59% when the cause of death is a closed or open head trauma, respectively [2]. Many groups are reluctant to use kidneys from donors with DIC because primary non-function was reported to occur in 33% of cases [3]. However, only a few reports [29] are available in the literature to date. Patients with traumatic head injury represent a large source of organs, which are in many instances of better quality than those harvested from elderly donors who died from vascular disease. It is of most interest to determine the outcome of transplants using organs harvested from DIC donors, especially in these times of organ shortages. We report herein the outcome of two kidneys, harvested from a same DIC donor, with renal impairment and glomerular thrombi on the pre-transplant biopsy.
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Case
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The donor, a 25-year-old male, had an open head trauma following a suicide attempt by gunshot. After an initial short period of resuscitation, a stable haemodynamic state was achieved by the administration of noradrenaline (5 mg/h) and dobutamine (4 µg/kg/min). Over the next 12 h, he developed DIC evidenced by: a prothrombin rate of 62% (normal range: 70100%), an activated cephalin time of 56 s (control: 30 s), a platelet count of 75000/mm3 (normal range: 150400000), a fibrinogen level of 1 g/l (normal range: 2.54 g/l). Over the first 24 h, renal function deteriorated. The serum creatinine level peaked at 238 µmol/l and decreased to 203 µmol/l immediately before organ harvesting. Adequate urine output was maintained throughout the stay in the Intensive Care Unit as well as during surgery. During the last hour, urine output was 300 ml. Treatment for DIC consisted of 4 units of plasma and 6 units of packed red blood cells. After in situ flushing with EuroCollins solution, kidneys were harvested and a wedge biopsy was performed. Histopathological examination showed massive fibrin deposition on glomeruli. Of the twelve glomeruli seen on the biopsy, six were altered with multiple fibrin thrombi in glomerular capillaries, detected with usual colorations (Masson trichrom, haemateineosinsafran) and confirmed with adequate antiserum by immunofluorescence examination (Dr H. Beaufils). There were no midsize or large vessels on biopsy. Tubular necrosis was observed in
15% of the tubules (Figure 1
).

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Fig. 1. Pre-transplant kidney biopsy. Multiple fibrin thrombi in glomerular capillaries. (Color PAS, x160)
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Recipient 1 was a 46-year-old man from Japan with end-stage renal failure secondary to chronic glomerulonephritis. He had been on haemodialysis for 7 months. He had no panel reactive antibodies (PRA) and shared two antigens (DR4, A2) with the donor. Cold ischaemia time was 19 h. Induction immunosuppression consisted of administration of anti-thymocyte globulins (ATG) (Fresenius 20 mg/ml, 0.1 ml/kg/day) for 14 days, prednisone (20 mg/day) and mycophenolate mofetil (MMF) (1.5 g/day). He received no cyclosporin according to our immunosuppression protocol for low immunological risk patients. No anticoagulation treatment was given. Urine output resumed soon after surgery. The serum creatinine level was 964 µmol/l on day 0, 294 µmol/l on day 3, 161 µmol/l on day 10, and 117 µmol/l on day 30. Two minor complications were observed in the early post-operative period, namely thrombopenia and haemolytic anaemia. Platelet count decreased to 32 000/mm3 on day 3 (vs 244 000/mm3 prior to surgery), then spontaneously increased to 168 000 and 308 000/mm3, respectively, on days 7 and 10. Anaemia occurred simultaneously and persisted until day 10. Hematocrit decreased from 43% (normal range: 3652%) at admission to 35% on the first post-operative day, 28% on day 3 and 23% on day 6. Haptoglobin decreased to 0.06 g/l (normal range: 0.242 g/l) on day 3 and 0.17 g/l on day 7, and returned to normal on day 10. No schizocytes were found at any time. The patient was discharged on day 15, with a serum creatinine level of 115 µmol/l. At 1 year post-transplant, renal function was good with a serum creatinine level of 105 µmol/l and creatinine clearance of 52 ml/min/1.73 m2, with no proteinuria. Maintenance immunosuppression consisted of prednisone (10 mg/day) and MMF (1.5 g/day).
Recipient 2 was a 35-year-old woman from Mali with end-stage renal failure secondary to urinary schistosoma infection. She had been on haemodialysis for 9 months. She had no PRA and shared one antigen (DR4) with the donor. Cold ischaemia time was 27 h. Induction immunosuppression consisted of ATG (0.1 ml/kg/day) for 14 days, cyclosporine (CsA) (3.5 mg/kg/day), prednisone (20 mg/day) and MMF (0.75 g/day), according to our immunosuppression protocol for high immunological risk patients. No anticoagulation treatment was given. Urine output resumed soon after surgery. Serum creatinine level was 1066 µmol/l on day 0, 493 µmol/l on day 3, 140 µmol/l on day 10 and 123 µmol/l on day 30. No haemolytic anaemia occurred. A core renal biopsy was performed on day 16 (the same kidney had already been biopsed prior to transplantation) and showed no fibrin thrombi in the glomerular capillaries. The patient was discharged on day 20. At 1 year post-transplant, renal function was almost normal with a serum creatinine level of 130 µmol/l and creatinine clearance of 73 ml/min/1.73 m2, with no proteinuria. Maintenance immunosuppression consisted of CsA (3.5 mg/kg/day), prednisone (10 mg/day) and MMF (0.75 g/day).
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Discussion
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DIC is associated with histopathological evidence of microthrombi in several organs, particularly in the brain, liver, lung, kidney and pancreas. A combination of mechanisms, including release of fat, phospholipids and thromboplastin from tissueespecially brain tissueinto the circulation, haemolysis and endothelial damage may promote systemic activation of coagulation. Cytokines also may have a role in the development of DIC [1, 9]. Little is known about the outcome of kidneys harvested from DIC donors. To the best of our knowledge, this is the first report of successful kidney transplantation using grafts with temporarily impaired function and glomerular thrombi on the pre-transplant biopsy. It raises the question of acceptation criteria for kidneys harvested from DIC donors.
Reports available in the literature are listed in Table 1
. Among 63 reported cases of donors with biological evidence for DIC, renal function impairment occurred in only five cases. Kidney transplantation was performed in 118 recipients. Eight kidneys were not grafted (9.4%) for unexplained reasons. A renal biopsy was available in only 23 cases and glomerular thrombi were present in 50% of the cases. Among the 12 recipients with fibrin thrombi in glomerular capillaries, only nine (75%) had a good renal transplant outcome and the kidneys of three (25%) never functioned. In the last three cases, reported by Meyers et al. [3], kidneys looked dusky and flabby after vascular clamp release. Poor preservation conditions cannot be ruled out and could have played a role in primary non-function. Hefty et al. [2] compared 34 recipients of DIC donor kidneys with 81 from donors not meeting DIC criteria. Primary non-function, delayed graft function, and graft function at 1 month and 1 year were not different between the two groups. Leunissen et al. [4] showed massive fibrin deposition in glomeruli 1 h after kidney transplantation from a DIC donor with normal renal function. The histopathological study of biopsies performed at 7 days and 6 months post-transplantation showed normal glomerular capillaries. As in our cases, these authors did not use anticoagulation therapy, although others recommended it [2, 3]. Anticoagulation is not given after transplantation in our institution unless thrombosis risk factors are present. This suggests that glomerular fibrin thrombi can be resolved by the recipient's own fibrinolytic system [5]. A pre-transplant renal biopsy is probably helpful in making the decision of whether to use kidneys from DIC donors, but fibrin deposition in glomerular capillaries cannot be considered a contra-indication. The goal of histological examination is to rule out massive infarction or cortical necrosis.
Interestingly, only one of our recipients developed a transient thrombopenia and haemolytic anaemia, without schizocytes. This could have resulted from the DIC positive graft or from ATG administration, although haemolytic anaemia in such cases is rather infrequent in our experience. Hefty et al. [2] also observed a microangiopathic anaemia in their recipient during the early post-operative course.
The reasons we elected to transplant these two grafts were: (i) no irreversible lesion on pre-transplant biopsy; (ii) the age of donor (25 years) with no additional vascular risk; and (iii) maintenance of a good urine output and evolution of serum creatinine level during the pre-operative period.
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Conclusion
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DIC can lead to acute renal failure due to intrarenal microvascular thrombi, the ultimate effect being cortical necrosis. The good outcome of our cases suggests that kidneys from DIC donors can be accepted for transplantation, even in the case of renal function deterioration if there is no additional vascular risk factor and if the pre-transplant biopsy shows no lesions other than glomerular fibrin thrombi. These can be resolved by the recipient's own fibrinolytic system and do not preclude successful renal transplantation. However, there are no clear acceptation criteria in the literature, in part because histological patterns are not fully detailed. It would be of interest to learn more details of clinical and histological patterns to be able to define criteria for acceptation or refusal of kidneys from DIC donors.
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Notes
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Correspondence and offprint requests to: Dr Benoît Barrou, Department of Urology, Hôpital La Pitié-Salpêtrière, 4783 Boulevard de l'Hôpital, F-75013 Paris, France. 
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Received for publication: 4. 7.00
Revision received 2.10.00.