Acute thrombosis of a transplanted renal artery after gastric ulcer bleeding in a patient with a long-term well-functioning renal allograft: A case report and literature review.

BACKGROUND: Acute thrombosis of a transplanted renal artery is a serious vascular complication following renal allograft transplantation, which usually occurs within the first month after transplantation and often results in graft loss. It rarely occurs beyond the first month, except in a rejected kidney or in a kidney with high-grade transplant renal artery stenosis. RESULT: A 65-year-old male with a history of type 2 diabetes mellitus, hypertension, pulmonary tuberculosis, and end-stage renal disease was previously treated with hemodialysis (HD). He received a kidney transplant and had a well-functioning graft for 2 years. He presented to our emergency department with gastric ulcer bleeding and received treatment involving an endoscopic submucosal epinephrine injection, a proton pump inhibitor, and blood transfusions. Nine days later, he complained of sudden lower abdominal pain and had acute anuric kidney failure. Renal ultrasonography revealed an absence of blood flow to the allograft kidney. Renal artery angiogram demonstrated complete occlusion of the transplanted renal artery. After thrombectomy and percutaneous transluminal angioplasty (PTA) with stent placement, 60% stenosis of the proximal renal artery with distal perfusion was noted. However, his graft function did not improve, and he received HD again. Histopathology of the transplanted kidney revealed ischemic tubular nephropathy with focal infarction without rejection.
CONCLUSION: This is the first case of acute thrombosis of the transplanted renal artery following gastric ulcer bleeding in a patient with a long-term well-functioning graft kidney.

Introduction

Arterial thrombosis in a transplanted kidney is a serious complication that often results in graft loss.[ It typically occurs within the first month following transplantation, and more than 90% of cases occur within the first year.[ The incidence of transplant renal artery thrombosis ranges between 0.2% and 3.5%. It is associated with technical surgical problems such as vessel kinking, torsion, and intimal injuries, drugs such as cyclosporine and orthoclone OKT3, hypercoagulable states, and hyperacute and acute rejection.[ Beyond the first month after transplantation, transplant renal artery thrombosis rarely occurs, except in a rejected kidney or in a kidney with high-grade arterial stenosis.

Here, we report the case of a patient with a long-term well-functioning renal allograft who suffered from acute graft loss because of transplant renal artery thrombosis after gastric ulcer bleeding.

Case report

A 65-year-old male with type 2 diabetes mellitus and hypertension had a history of pulmonary tuberculosis and end-stage renal disease. He had been on hemodialysis (HD) for 6 years before receiving a deceased donor kidney transplant. The transplanted renal artery was anastomized end-to-side to the recipient's external iliac artery. His graft function continued functioning appropriately under immunosuppression therapy for 2 years. His serum creatinine and tacrolimus levels were 0.9 mg/dL (reference range, 0.5–1.3 mg/dL) and 9.4 ng/mL (reference range, 5–20 ng/mL), respectively, in the half-year before admission. Type 2 diabetes mellitus and hypertension were in control, and his past medical regimen included gliquidone, barnidipine, carvedilol, and irbesartan.

He visited our emergency department because of tarry stool for 1 day. Physical examination revealed a blood pressure of 120/55 mm Hg, pulse rate of 88 beats/min, and temperature of 36.2°C. Hemogram revealed a hematocrit (Hct) of 20.3% (reference range, 35–48%), leukocyte count of 6.1 × 103/μL (reference range, 3.8–10 × 103/μL), and platelet count of 1.82 × 105/μL (reference range, 1.4–4.5 × 105/μL). Prothrombin time and activated partial thromboplastin time were 12 (range, 9.4–12.5 seconds) and 32 seconds (range, 26–38 seconds), respectively. Biochemistry assay revealed blood urea nitrogen (BUN) and serum creatinine levels of 36 (range, 7–25 mg/dL) and 1.3 mg/dL, respectively. Panendoscopy revealed a huge gastric ulcer with active bleeding, and 28 mL of diluted epinephrine (1:10,000) was injected locally. He was treated with proton pump inhibitors and transfused with 4 packed red blood units. He was hospitalized thereafter.

On hospital day 1, follow-up panendoscopy showed a giant ulcer 3 cm in diameter with little fresh blood oozing in the antrum; 16 mL of diluted epinephrine was injected locally, and 1 metallic clip was applied. After treatment, the Hct levels increased from 20.3% to 27.2%, and BUN and serum creatinine levels were 31 and 0.9 mg/dL, respectively. On hospital day 4, Hct increased to 31%.

On hospital day 9, he complained of sudden onset of lower abdominal pain followed by anuria and intermittent tarry stool. BUN and serum creatinine levels were 23 and 1.9 mg/dL, respectively, on hospital day 10, and they were 29 and 3.1 mg/dL, respectively, on hospital day 11. During this period, he had been anuric even after diuretic treatment. His tacrolimus level was 15.0 ng/mL. Renal duplex ultrasonography detected an absence of blood flow to the allograft kidney. Renal artery angiogram revealed complete occlusion of the transplant artery and no distal perfusion. After thrombectomy, 60% stenosis of the orifice of the transplanted renal artery was observed. Distal flow was subsequently detected after percutaneous transluminal angioplasty (PTA) with stent placement (Fig. 1).

Figure 1

Angiogram of the transplanted renal artery. (A) Thrombus in the anastomosis of the transplanted renal artery and external iliac artery (arrow), and complete occlusion of the transplanted renal artery (arrowheads) before thrombectomy. (B) Significant (60%) stenosis of the proximal transplant renal artery (arrow) after thrombectomy, and still thrombus in the distal transplant renal artery (arrow). (C) Perfusion of the transplanted renal artery after percutaneous transluminal angioplasty with stent placement.

After treatment, the daily urine output was 30 mL. BUN and serum creatinine levels increased to 40 and 4.7 mg/dL, respectively, on hospital day 12 and to 64 and 7.6 mg/dL, respectively, on hospital day 13. Other laboratory data revealed anticardiolipin concentration of 4.1 (range: 0–11) μL/mL and negative lupus anticoagulant. Histopathological examination of the transplanted kidney on hospital day 16 showed ischemic tubular nephropathy with focal infarction (Fig. 2) without antibody-mediated and T-cell mediated rejection. He returned to chronic HD subsequently.

Figure 2

Histopathology of the transplanted kidney. (A) Coagulative necrosis of the glomerulus. (B) Ischemic necrosis of tubules.

Discussion

Acute thrombosis of a transplanted renal artery beyond the first month after transplantation is distinctly uncommon, except in a rejected kidney or in a kidney with high-grade arterial stenosis. The histology of the transplanted kidney in our patient demonstrated ischemic tubular nephropathy with coagulative necrosis without rejection. In addition to no signs of acute rejection, our patient did not interrupt his immunosuppressive therapy because acute rejection usually develops in patients discontinuing immunosuppressive therapy.

An end-to-end anastomosis of the transplanted renal artery to the internal iliac artery and end-to-side anastomosis of the transplanted renal artery to the external iliac artery are the most common techniques for arterial anastomosis in kidney transplantation. The end-to-end anastomosis involves a higher incidence of stenosis compared with end-to-side anastomosis, although the procedure is easier and faster to perform and does not compromise circulation to the leg.[ Furthermore, more than 75% stenosis of the transplanted renal artery is called high-grade arterial stenosis.[ Here, the renal artery was anastomized end-to-side to the patient's external iliac artery. After thrombectomy, angiogram revealed 60% stenosis of the proximal transplant renal artery. These findings indicate that high-grade transplant renal arterial stenosis is not the etiology of transplant renal artery thrombosis.

Two case studies have reported that patients with long-standing renal transplant developed acute transplant renal artery thrombosis because of late hemolytic uremic syndrome (HUS)[ and had increased levels of antiphospholipid antibodies.[ A study on a patient with HUS revealed classic findings of renal failure, hemolytic anemia, schistocytes, and thrombocytopenia. Cyclosporin[ or tacrolimus-associated HUS[ following renal transplantation has been reported. Increased incidence of acute thrombosis of the transplanted renal artery is also associated with increased use of cyclosporin. The underlying mechanism for this may be the effect of this drug on endothelial cells, thus minimizing prostacyclin production and predisposing a patient to thrombosis. Our patient did not have thrombocytopenia, and Hct levels were maintained at approximately 27.2% to 31% before acute thrombosis of the transplanted renal artery. In addition, our patient did not receive cyclosporin treatment, and the tacrolimus dosage was adjusted according to the serum tacrolimus level. HUS seemed unlikely; therefore, we did not perform blood smear to confirm schistocytes.

Antiphospholipid syndrome (APS), which is diagnosed on the basis of the presence of antiphospholipid antibodies, is an acquired disorder associated with vascular thrombosis.[ The most commonly known antiphospholipid antibodies are the lupus anticoagulant and anticardiolipin antibody. Our patient was negative for lupus anticoagulant and IgM anticardiolipin antibody. Moreover, our patient had no history of an autoimmune disorder.

Except for HUS and APS, 4 studies have reported acute thrombosis in patients with long-standing renal transplant. In 2 of these reported cases, the event was associated with significant medical problems such as myocardial infarction and sepsis.[ In the third case of acute transplant renal artery thrombosis, the patient had severe hypertension.[ In the fourth case, the patient developed acute transplant renal artery thrombosis following hip surgery.[ We did not encounter the aforementioned situations in our patient.

However, risk factors for arterial thrombosis are not limited to antiphospholipid antibodies and lupus anticoagulants. Other hypercoagulable states include factor V Leiden mutation,[ antithrombin deficiency,[ and methylene tetrahydrofolate reductase mutation and hyperhomocysteinemia.[ Furthermore, infectious and inflammatory states such as polyarteritis nodosa,[ Takayasu arteritis,[ and Behcet disease[ are associated with renal artery thrombosis. These diseases might still possibly endanger acute thrombosis of a transplanted renal artery; hence, careful evaluation and screening of the aforementioned diseases should be required. Our patient did not present any cutaneous or musculoskeletal joint symptoms, and infectious and inflammatory states seemed unlikely. However, we did not perform an activated protein C resistance test or measure for antithrombin and total homocysteine levels in our patient.

One of the pathogenic mechanisms in our patient may be anemia, engendered by bleeding, that enhanced thrombosis because studies have reported a relationship between bleeding and cerebral infarction onset.[ Hypercatecholaminemia caused by the systemic absorption of submucosal epinephrine injected for gastric ulcer bleeding and acute stress may be another pathogenic mechanism in our patient that may have resulted in thrombosis through vasoconstriction and platelet aggregation.[ The patient had a history of hypertension, diabetes mellitus, and kidney disease, which indicated a high risk of a cardiovascular event. However, he was not taking acetylsalicylic acid. This event could be attributed to thrombosis formation of atherosclerotic lesions and plaque rupture.

The timing of diagnosis as well as the method of treatment are critical for renal infarction; therefore, previously reported cases of transplanted renal artery thrombosis, medical problems, timing of diagnosis, methods of treatment, and outcomes are reviewed, and are tabulated in Table 1. Graft thrombosis treatment is generally unsatisfactory, and only few cases were effectively rescued by surgical revascularization or intraarterial thrombolytic therapy.[

Table 1

Review of previous and present cases with late transplant renal artery thrombosis.

In summary, we report the first case of a patient with a long-term well-functioning renal allograft who suffered from acute thrombosis of the renal transplant artery after gastric ulcer bleeding.