Thrombotic microangiopathy following renal ischaemia and revascularization: apoptosis of endothelial cells in action

Jean-François Cailhier, Linda Nolin and Marie-Josée Hébert

Nephrology Division, Maisonneure-Rosemont Hospital, Montreal, Quebec, Canada

Sir,

We report a case implicating long-term renal ischaemia as an initiating event for development of thrombotic microangiopathy (TM). Recent advances in the fields of apoptosis and coagulation disturbances are discussed as possible pathophysiological hypotheses [1].

Case.

A 50-year-old woman presented with uncontrolled blood pressure and a history of sudden left flank pain of 24 h duration that occurred 6 weeks prior to admission. Renovascular hypertension was suspected and an angiogram confirmed thrombosis of the left renal artery, with patent collaterals. In the following days, revascularization was attempted with local thrombolysis using urokinase (500 000 IU) followed by PTRA and stenting of the left renal artery. Within hours following renal revascularization, evidence of a TM developed with progressive thrombopenia, schistocytes and elevation of serum creatinine. A screen for Escherichia coli O157:H7, auto-immune disorders, anti-phospholipid syndrome and other causes of secondary TM was negative. Fresh frozen plasma infusion and plasmapheresis were instituted. Within 2 weeks, haematological signs of TM disappeared with plasmapheresis and renal function stabilized (Table 1Go). On follow-up visits, hypertension was controlled and no evidence of TM was found. Seven months after placement, the stent was still permeable as confirmed by renal scintigraphy.


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Table 1. Evolution of patient's laboratories

 

Comment.

According to new evidence in the literature, we propose the following sequence of events to explain the occurrence of TM in this patient. Prolonged ischaemia has been recently shown to be a pro-apoptotic factor for endothelial cells in vitro [2]. Various investigators have shown that endothelial cells acquire procoagulant properties upon activation of apoptosis [3,4]. Following revascularization, contact between apoptotic microvascular renal endothelial cells and blood constituents was re-established, causing intra-renal activation of platelets [5], formation of microthrombi and rapid development of TM. Upon regeneration of the renal microvascular endothelium the microangiopathic process abated and did not recur.

In patients with renal ischaemia of weeks duration, signs of TM should be monitored after renal revascularization.

References

  1. Laurence J, Mitra D. Apoptosis of microvascular endothelial cells in the pathophysiology of thrombotic thrombocytopenic purpura/sporadic haemolytic uremic syndrome. Semin Hematol 1997; 34: 98–105[ISI][Medline]
  2. Stempien-Otero A, Karsan A, Cornejo CJ et al. Mechanisms of hypoxia-induced endothelial cell death. Role of p53 in apoptosis. J Biol Chem 1999; 274: 8039–8045[Abstract/Free Full Text]
  3. Bombeli T, Karsan A, Tait JF, Harlan JM. Apoptotic vascular endothelial cells become procoagulant. Blood 1997; 89: 29–42
  4. Greeno EW, Bach RR, Moldow CF. Apoptosis is associated with increased cell surface tissue factor procoagulant activity. Lab Invest 1996; 75: 281–289[ISI][Medline]
  5. Bombeli T, Schwartz BR, Harlan JM. Endothelial cells undergoing apoptosis become proadhesive for nonactivated platelets. Blood 1999; 93: 3831–3838[Abstract/Free Full Text]




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