The kidney in thrombotic thrombocytopenic purpura

Abstract

The kidney is commonly affected in thrombotic thrombocytopenic purpura (TTP), a multi-system disorder with microvascular thrombosis of the capillaries and arterioles. Nevertheless, due to difference in its diagnostic criteria, the frequency and severity of renal dysfunction in TTP remains controversial. Recent studies indicate that the severe deficiency of a von Willebrand factor (VWF) cleaving protease, ADAMTS13, is the main cause of platelet thrombosis in TTP; it is now possible to define TTP at the molecular level. Among patients with acquired TTP due to inhibitory antibodies of ADAMTS13, renal dysfunction is usually mild; oliguria, fluid overload, hypertension, and need of dialysis support are infrequent. When any of these complications occur, one must re-examine the diagnosis of TTP and consider the possibility that the patient has another cause for these complications. In a patient with hereditary TTP, acute renal failure may ensue. However, the renal dysfunction is mostly reversible if the patients are promptly treated with plasma to replenish ADAMTS13. Patients with TTP, particularly of the hereditary type, may develop chronic renal failure. This complication may be a consequence of repeated insults by overt or subclinical microvascular thrombosis to the kidney, or it may have a separate cause. Therapy of hereditary TTP should aim not only to prevent acute exacerbations but also to minimize the risk of irreversible renal injury.

Figure 1

SDS agarose gel electrophoresis comparing the multimeric compositions of endothelial and plasma VWF. VWF is visualized by probing with rabbit anti-VWF and ¹²⁵I-labeled goat anti-rabbit IgG. A: endothelial secreted VWF consists of a single band that is much larger than the largest forms in plasma VWF multimers. B: The VWF compositions in the plasma samples from a patient of TTP during remission (Rem) and the same patient during acute relapse (Acute) are compared with those in three normal plasma samples (NP). Both plasma samples have ultra large multimers because their ADAMTS13 activity levels are decreased (15% and <10% respectively). In acute TTP, the ultra and large multimers are decreased because they are consumed in the process of VWF-platelet binding.