Antiphospholipid syndrome and kidney damage

Antiphospholipid syndrome (APS) is a clinical and laboratory symptom complex associated with the synthesis of antibodies to phospholipids (aPL) and characterized by venous and/or arterial thromboses, habitual miscarriage, and thrombocytopenia. The disease antiphospholipid syndrome was first described by G. Hughes in 1983 in patients with systemic lupus erythematosus, and in the late 90s of the 20th century it was named "Hughes syndrome" in recognition of the scientist's role in studying this pathology.

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Epidemiology

Antiphospholipid syndrome, like systemic lupus erythematosus, develops predominantly at a young age, in women 4-5 times more often than in men, however, recently a tendency towards an increase in the incidence of primary antiphospholipid syndrome in the latter has been noted. The true prevalence of antiphospholipid syndrome in the population has not yet been fully established. The frequency of detection of antibodies to phospholipids in healthy people is on average 6 (0-14)%, however, their high titer, associated with the development of thrombosis, is recorded in less than 0.5% of healthy people.

In women with recurrent obstetric pathology, these antibodies are detected in 5-15% of cases. In patients with systemic lupus erythematosus, the frequency of detection of antibodies to phospholipids is on average 40-60%, however, clinical manifestations of antiphospholipid syndrome develop less frequently: the frequency of thrombotic complications in patients with the presence of antibodies to phospholipids in systemic lupus erythematosus reaches 35-42%, while in their absence it does not exceed 12%.

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Causes antiphospholipid syndrome

The causes of antiphospholipid syndrome are unknown. Most often, antiphospholipid syndrome develops in rheumatic and autoimmune diseases, mainly in systemic lupus erythematosus.

An increase in the level of antibodies to phospholipids is also observed in bacterial and viral infections ( streptococci and staphylococci, mycobacterium tuberculosis, HIV, cytomegalovirus, Epstein-Barr viruses, hepatitis C and B and other microorganisms, although thrombosis in such patients rarely develops), malignant neoplasms, and the use of certain medications (hydralazine, isoniazid, oral contraceptives, interferons).

Anti-phospholipid antibodies are a heterogeneous population of antibodies to antigenic determinants of negatively charged (anionic) phospholipids and/or to phospholipid-binding (cofactor) plasma proteins. The family of anti-phospholipid antibodies includes antibodies that cause a false-positive Wasserman reaction; lupus anticoagulant (antibodies that prolong in vitro blood clotting time in phospholipid-dependent coagulation tests); antibodies that react with cardiolipin aPL and other phospholipids.

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Symptoms antiphospholipid syndrome

The symptoms of antiphospholipid syndrome are quite diverse. The polymorphism of clinical manifestations is determined by the localization of thrombi in veins, arteries or small intraorgan vessels. As a rule, thromboses recur either in the venous or arterial bed. The combination of thrombotic occlusion of peripheral vessels and vessels of the microcirculatory bed forms a clinical picture of multiple organ ischemia, leading to multiple organ failure in some patients.

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Forms

Currently, secondary antiphospholipid syndrome is distinguished, associated mainly with systemic lupus erythematosus, and primary, developing in the absence of any other disease and, apparently, being an independent nosological form. A special variant of antiphospholipid syndrome is considered to be catastrophic, caused by acute thrombo-occlusive damage mainly to the vessels of the microcirculatory bed of vital organs (at least three at a time) with the development of multiple organ failure in a period from several days to several weeks. Primary antiphospholipid syndrome accounts for 53%, secondary - 47%.

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Diagnostics antiphospholipid syndrome

Characteristic features of antiphospholipid syndrome are thrombocytopenia, usually moderate (platelet count is 100,000-50,000 in 1 μl) and not accompanied by hemorrhagic complications, and Coombs-positive hemolytic anemia. In some cases, a combination of thrombocytopenia and hemolytic anemia (Evans syndrome) is noted. In patients with nephropathy associated with antiphospholipid syndrome, especially in catastrophic antiphospholipid syndrome, the development of Coombs-negative hemolytic anemia (microangiopathic) is possible. In patients with the presence of lupus anticoagulant in the blood, an increase in activated partial thromboplastin time and prothrombin time is possible.

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Treatment antiphospholipid syndrome

Treatment of antiphospholipid syndrome and renal damage is not clearly defined, since to date there are no large controlled comparative studies assessing the effectiveness of different treatment regimens for this pathology.

• In the treatment of patients with secondary antiphospholipid syndrome in the context of systemic lupus erythematosus, glucocorticoids and cytostatic drugs are used in doses determined by the activity of the disease. Suppression of the activity of the underlying disease, as a rule, leads to the disappearance of signs of antiphospholipid syndrome. In primary antiphospholipid syndrome, glucocorticoids and cytostatic drugs are not used.
• Despite the fact that treatment with glucocorticoids and cytostatic drugs leads to normalization of the aPL titer and disappearance of lupus anticoagulant in the blood, it does not eliminate hypercoagulation, and prednisolone even enhances it, which maintains conditions for recurrent thrombosis in different vascular pools, including the renal vascular bed. In this regard, when treating nephropathy associated with antiphospholipid syndrome, it is necessary to prescribe anticoagulants as monotherapy or in combination with antiplatelet agents. By eliminating the cause of renal ischemia (thrombotic occlusion of intrarenal vessels), anticoagulants are able to restore renal blood flow and lead to an improvement in renal function or slow the progression of renal failure, which, however, requires confirmation in the course of studies assessing the clinical effectiveness of both direct and indirect anticoagulants in patients with antiphospholipid syndrome-associated nephropathy.