"Black swan in the kidney": renal involvement in the antiphospholipid antibody syndrome

The antiphosphospholipid antibody syndrome (APS) describes a clinical entity with recurrent thrombosis, fetal loss, thrombocytopenia in the presence of lupus anticoagulant and/or antibodies to cardiolipin. These antibodies may be associated with connective tissue diseases such as systemic lupus erythematosus (secondary APS) or be found in isolation (primary APS). Renal syndromes increasingly being reported in association with these antibodies include thrombotic microangiopathy, renal vein thrombosis, renal infarction, renal artery stenosis and/or malignant hypertension, increased allograft vascular thrombosis, and reduced survival of renal allografts. Although much has been understood concerning the biology of these antibodies and the pathogenesis of thrombosis, the optimal therapy remains to be elucidated. This article presents a historical review of the renal involvement in the antiphospholipid syndrome and discusses therapeutic options. Further research is needed.     

Renal thrombotic microangiopathy in patients with systemic lupus erythematosus and the antiphospholipid syndrome.

Current studies indicate that a thrombotic microangiopathy (TMA) identifies patients with systemic lupus erythematosus (SLE) who are at high risk of progressing to end-stage renal disease. We have observed two patients with SLE and one patient with a primary antiphospholipid syndrome (APS) who developed acute renal insufficiency with thrombocytopenia. Renal biopsies showed a TMA characterized by thrombi or by cellular and mucoid intimal hyperplasia of small arteries and arterioles. No arterial or arteriolar immune-complex deposits were detected by immunofluorescent or electron microscopy. Biopsies from one SLE patient and the APS patient showed no immune-complex glomerular disease. Both had serum antiphospholipid antibodies (aPL). aPL were not detected in the serum of the other SLE patient who had an active lupus nephritis. Acute renal failure and thrombocytopenia resolved in each case following treatment by plasmapheresis or prednisone and heparin. None of the patients were initially treated with cytotoxic drugs. As more knowledge is gained, the accurate identification of renal vascular lesions in SLE or related diseases could influence renal prognosis and choice of therapy. The cases reported here provide further evidence that a TMA can cause acute renal failure independent of lupus nephritis. TMA should be distinguished from other forms of renal vascular disease, particularly a noninflammatory lupus microangiopathy, which is probably mediated by subendothelial immune-complex deposits. The absence of immunoglobulin deposits in vessels involved by a TMA indicates that microvascular thrombosis is promoted by mechanisms other than those usually attributed to immune-complex disease. Phospholipid reactive antibodies may be pathogenetic in some cases.     

抗磷脂综合征的肾损害

目的分析抗磷脂综合征(APS)致肾损害的临床特点,旨在提高对该类疾病的认识。方法回顾性分析北京协和医院1983年至2004年期间91例APS中肾损害的临床特点及其中8例的肾组织学表现。结果原发性APS(PAPS)13例(14.3%);继发性APS(SAPS)78例(85.7%),其中系统性红斑狼疮(SLE)55例(占SAPS的70.5%)。APS伴肾损害共82例(90.1%),男性20例、女性62例;PAPS肾损害发生率为76.9%,SAPS为92.3%;发生肾损害时年龄为(38±14)岁,肾损害前病程为(4.9±6.8)年。肾损害临床表现主要为蛋白尿(92.7%)、肉眼血尿(2.4%)、镜下血尿(76.8%)、高血压(33.0%)、肾功能不全(18.3%),其中12.2%为肾病综合征。14例(15.4%)出现急性肾功能不全,病因包括血栓性微血管病、肾动脉栓塞、肾静脉血栓形成等。肾组织学检查8例,均为SLE所致PAPS,APS肾病占62.5%,表现为肾小血管、肾小球毛细血管血栓形成以及肾小叶间动脉内膜增生、洋葱皮样改变。结论APS肾损害比较常见,临床上以蛋白尿最为多见,可伴血尿、高血压,可引起血栓性微血管病、肾动脉栓塞或肾静脉血栓形成,致肾功能急剧恶化。     

Anesthetic implications of the catastrophic antiphospholipid syndrome

The antiphospholipid antibody syndrome (or the anticardiolipin antibody syndrome) is characterized by the presence of autoantibodies. Its major association is with systemic lupus erythematosus. 'Catastrophic' antiphospholipid syndrome (CAPS) is defined as an accelerated form of APS usually resulting in multiorgan failure and can be precipitated by surgery. We present the case of a 12-year-old male child who presented for enucleation of his left eye for fungal endopthalmitis. This patient had a history of CAPS 2 months before surgery with myocardial, gastrointestinal, renal and laryngeal involvement that improved on aggressive treatment and was subsequently managed on an outpatient basis for 2 months before presenting for enucleation. To the best of our knowledge, this is the first case of CAPS in a child reported in the anesthetic literature. Further aspects of this puzzling condition and its anesthesia implications are discussed.     

Catastrophic antiphospholipid antibody syndrome

Antiphospholipid antibody syndrome (APS) is characterized by recurrent thrombosis with the presence of circulating antiphospholipid antibodies. A diagnosis of APS requires the presence of at least one clinical and one laboratory criteria (detection of aCL IgG or IgM antibodies or the presence of lupus anticoagulant on two or more consecutive occasions 6 weeks apart). A severe, rapidly progressive form characterized by clinical involvement of at least three different organ systems with histopathological evidence of small and large vessel occlusion is termed catastrophic antiphospholipid syndrome. Early recognition of APS is crucial since aggressive management can result in a favorable outcome. We present the case of a 12-year-old boy who presented with a devastating illness with multiple thrombotic episodes and rapidly progressive renal failure.     

Antiphospholipid syndrome nephropathy in systemic lupus erythematosus.

In the course of the antiphospholipid syndrome (APS), the existence of vaso-occlusive lesions capable of affecting numerous organs is now well established. The renal involvement attributable to primary APS, APS nephropathy (APSN), corresponds to vaso-occlusive lesions of the intrarenal vessels, associating side-by-side, acute thromboses with chronic arterial and arteriolar lesions, leading to zones of cortical ischemic atrophy. A retrospective study of 114 lupus patients undergoing renal biopsy was undertaken to determine the following: (1) if APSN can be found in the course of systemic lupus erythematosus (SLE); (2) if certain clinical and biologic factors can permit the prediction of the presence of APSN; and (3) if APSN is a superadded renal morbidity factor in lupus patients. This study shows the following: (1) APSN occurs in SLE (32% of patients with renal biopsies) in addition to, and independently of, lupus nephritis; (2) APSN is statistically associated with lupus anticoagulant but not with anticardiolipin antibodies; (3) APSN is associated with extrarenal APS, mainly arterial thromboses and obstetrical fetal loss, but not with the venous thromboses of APS; (4) APSN is an independent risk factor, over and above lupus nephritis, that contributes to an elevated prevalence of hypertension, elevated serum creatinine, and increased interstitial fibrosis. Thus, it seems likely that, because of its associations with hypertension, elevated serum creatinine, and increased interstitial fibrosis, APSN may worsen the prognosis in these patients. APSN may also have therapeutic significance in that its recognition should permit a better balance between immunosuppressor and antithrombotic and/or vasoprotective therapy. Finally, this study suggests that APSN should be considered as an element to be included in the classification criteria of APS.     

End-stage renal disease from glomerulonephritis associated with anti-phospholipid syndrome

Primary anti-phospholipid syndrome (APS) is perceived to be an uncommon disorder, infrequently recognized as a cause of renal disease in childhood. While renal involvement in APS classically manifests as thrombotic events, other renal diseases associated with APS have been reported in adults, including membranous nephropathy and minimal change disease. We report our experience of caring for a child who presented with acute anuric renal failure due to anti-neutrophilic cytoplasmic antibody-negative rapidly progressive glomerulonephritis (RPGN), with concomitant thrombotic microangiopathy (TMA). Recognition of the APS as a cause of the patients TMA facilitated institution of anticoagulation. Our patients renal failure did not improve and the patient remained dependent on dialysis until he was successfully transplanted. The purpose of our report is to make health-care professionals aware of the previously unreported association of pauci-immune RPGN and APS in children; early recognition of APS will allow initiation of anticoagulation to prevent recurrent thromboses and enable successful transplantation.     

Catastrophic antiphospholipid syndrome: report of 4 cases

Catastrophic antiphospholipid syndrome (CAPS), described by Asherson in 1992, is a rare form of antiphospholipid syndrome resulting in multiorgan failure with a mortality rate of about 50%. The syndrome occurs in patients with either systemic lupus erythematosus and other rheumatic diseases (systemic sclerosis, rheumatoid arthritis, primary Sjogren syndrome) or alone. Whereas in "classic" antiphospholipid syndrome (APS), medium-large vessels are involved, a diffuse small vessel ischemia and thrombosis (microangiopathic disease) leading to a severe multiorgan dysfunction is predominant in CAPS. "Trigger" factors have been demonstrated in 45% of patients, but in the majority, they remain unknown. Not infrequently, CAPS arises in patients without any previous thrombotic history. The kidney is the organ most commonly affected, followed by the lung, the central nervous system, the heart and the skin. Disseminated intravascular coagulation occurs in approximately 13% of patients. The present study reports the clinical and serological features of 4 patients affected by this rare form of antiphospholipid syndrome. Nephrologists should be aware of the possibility of this syndrome as a cause of multiorgan failure since prompt recognition is essential for effective treatment.     

Primary antiphospholipid antibody syndrome and mesangial IgA glomerulonephritis

The antiphospholipid antibody syndrome (APS) is characterized by recurrent thrombosis, fetal loss, multiorgan involvement, and the presence of lupus anticoagulant and/or anticardiolipin antibody. When not associated with systemic lupus erythematosus, other collagen diseases, or ingestion of medications, the condition is called primary APS. The kidney may be involved in the APS syndrome with acute nephritis and renal failure. The cases with renal biopsy studies have shown variable glomerular morphology, ranging from mild mesangial changes to a diffuse endocapillary proliferative glomerulonephritis. The most frequent lesion is thrombotic microangiopathy or features seen in the hemolytic uremic syndrome. Apart from fibrin thrombus deposition, only a few cases have shown focal and segmental deposits of IgG and/or IgM and/or C3. We describe a patient with primary APS who had thrombosis with lower limb amputation and acute renal failure. The renal biopsy specimen showed a focal proliferative glomerulonephritis with endothelial proliferation and damage, with diffuse heavy mesangial deposits of IgA and fibrinogen. This case with diabetes mellitus, but without diabetic nephropathy, represents the occurrence of primary APS and mesangial IgA nephropathy which potentiated the renal injury, leading to acute renal failure. The relationship to the Henoch-Sch?nlein syndrome is discussed.     

Primary antiphospholipid syndrome presented by total infarction of right kidney with nephrotic syndrome.

We report the case of a young woman with primary antiphospholipid syndrome (APS), which presented with acute renal failure, hypoproteinemia, hypoalbuminemia and nephrotic proteinuria. Investigations showed total infarction of right kidney by extensive arterial and vein thrombosis and presence of anticardiolipin antibodies IgG isotype (anti-beta2-glycoprotein I-positive). She was submitted to right nefrectomy and initiated anticoagulant therapy. After nefrectomy, the postoperative period was marked by the development of arterial hypertension and persistence of nephrotic syndrome. Hypertension was treated with antihypertensive drugs (IECA, beta-blocker and calcium antagonist). As the nephrotic syndrome persisted despite anticoagulant and antihypertensive therapy, the patient was treated with oral corticosteroids. Her renal function improved, hypoproteinemia and hypoalbuminemia corrected to normal values and proteinuria decreased to subnephrotic value. We discuss the unusual presentation of this case of primary antiphospholipid syndrome with total unilateral renal thrombosis and nephrotic syndrome that respond to anticoagulant, antihypertensive and corticosteroid therapy.     

Two cases of systemic lupus erythematosus accompanied by antiphospholipid syndrome nephropathy without immune complex nephritis

We report here two interesting cases of systemic lupus erythematosus(SLE) accompanied by antiphospholipid syndrome nephropathy(APSN). These cases satisfied the criteria for SLE established by the American College of Rheumatology 1997 and also satisfied the criteria for antiphospholipid syndrome (APS) established by the Sapporo International Workshop of APS 1998. Both cases had high blood pressure with elevated plasma renin activity, proteinuria and renal dysfunction. Their biopsied renal specimens showed the characteristic findings for APSN, such as mesangial proliferation, double contours, thickening of the capillary loops, and intimal hyperplasia, but there was no evidence for immune complexes in the glomeruli, which were examined by the indirect immunofluorescence methods and the electron microscopy method. These results indicated that their renal dysfunction was caused by APSN, but not by immune complex nephritis. In addition to treatment with prednisolone, they were administered anticoagulants(warfarin, or aspirin, or heparin) for APSN and an angiotensin II receptor blocker, candesartan, for the hypertension. Subsequently, their conditions recovered with the improvement of renal function and hypertension. Our experiences suggest that anticoagulant therapy in addition to corticosteroids offers advantages in the treatment of patients with SLE accompanied by APSN and renal dysfunction.     

Infarction of the right hemisphere in a patient with antiphospholipid antibody syndrome

Summary Hemicraniectomy as a surgical treatment for intracranial pressure following large ischemic lesions is widely practiced in selected patients. The antiphospholipid antibody syndrome (APS), a disorder characterized by recurrent arterial and venous thrombosis, is a very rare cause of space occupying ischemic lesions. We present a case of a 35 year old female diagnosed with APS who initially presented with small ischemic lesions and within days developed a massive near-total infarction of the right hemisphere. Because of central nervous system, skin and systemic manifestations Sneddon’s syndrome and catastrophic antiphospholipid antibody syndrome (CAPS) remained a possible diagnoses. Sneddon’s syndrome is a non-inflammatory occlusive arteriopathy of small and medium size arteries predominantly of the skin and brain, whereas the catastrophic antiphospholipid antibody syndrome is characterized by acute multi-organ system thrombosis of small and large vessels. In addition to the diagnostic criteria for APS a heterozygous factor V Leiden mutation was found in this patient, which may be a contributing risk factor for cerebral ischemia. When considering invasive decompressive procedures the neurosurgeon has to be aware of the poor prognosis of some forms of APS with systemic manifestations.These authors contributed equally to this work.     

The intrarenal vascular lesions associated with primary antiphospholipid syndrome

Even 10 yr after the identification of the antiphospholipid syndrome (APS), renal involvement in the course of APS is still relatively unrecognized, and is probably underestimated. The association of anticardiolipin antibodies and/or lupus anticoagulant with the development of a vaso-occlusive process involving numerous organs is now confirmed. In a multicenter study, 16 cases of "primary" APS (PAPS) were found and followed for 5 yr or more, all with renal biopsy. In all 16 cases of PAPS, there was a vascular nephropathy characterized by small vessel vaso-occlusive lesions associated with fibrous intimal hyperplasia of interlobular arteries (12 patients), recanalizing thrombi in arteries and arterioles (six patients), and focal cortical atrophy (10 patients). In combination, these led to progressive destruction of the kidney, accelerated by acute glomerular and arteriolar microangiopathy in five patients. Focal cortical atrophy is a distinctive lesion, present in 10 biopsies, and likely represents the histologic and functional renal analogue to the multiple cerebral infarcts detected on imaging studies. The clinical hallmark of this vascular nephropathy in PAPS is systemic hypertension, only variably associated with renal insufficiency, proteinuria, or hematuria. The ensemble of histologic renal lesions defined in this study should aid in the separation of the lesions found in cases of secondary APS, especially systemic lupus erythematosus, into those lesions related to APS and those related to the underlying disease.     

Severe Vascular Lesions and Poor Functional Outcome in Kidney Transplant Recipients with Lupus Anticoagulant Antibodies

The impact of antiphospholipid antibodies (APA) on clinical outcome and graft histology following renal transplantation remains poorly known and controversial. We retrospectively explored the functional and histological significance of APA, primarily lupus anticoagulant (LA), in kidney transplant recipients using a systematic evaluation of 3‐ and 12‐month posttransplant screening biopsies and glomerular filtration rate measurements (mGFR). During the study period, 37 patients had APA (2.7%), primarily LA, and 12 fulfiled antiphospholipid syndrome (APS) diagnostic criteria (0.8%) at the time of transplantation. Early after transplantion, 4 of the 12 APS patients died. Early thrombosis of graft vessels and deep venous thrombosis occurred more frequently in APA+ patients than in controls (27% vs. 7%, p < 0.05 and 35% vs. 14%, p < 0.05, respectively). The survival rate was significantly lower in patients with APS. Strikingly, the hallmark lesions of APS‐associated nephropathy (APSN) were found in most of screening graft biopsies in APA+ patients but not in the controls. Accordingly, APA+ patients had a dramatic increase in chronic vascular scores and a faster decline in mGFR at 1 year. In conclusion, renal transplantation may be life‐threatening in APS patients, and the presence of LA at the time of transplantation is associated with a high rate of allograft APSN and poor transplantation outcomes.     

Antiphospholipid syndrome in renal transplantation

Antiphospholipid syndrome (APS) may occur in isolation or in association with systemic lupus erythematosus (SLE), with the potential to cause renal failure via several distinct pathologies. Renal transplantation in the presence of APS carries a risk of early graft loss from arterial or venous thrombosis, or thrombotic microangiopathy (TMA). Whilst perioperative anticoagulation reduces the risk of large vessel thrombosis, it may result in significant haemorrhage, and its efficacy in preventing post‐transplant TMA is uncertain. Here, we report a patient with end‐stage kidney disease (ESKD) due to lupus nephritis and APS, in whom allograft TMA developed soon after transplantation despite partial anticoagulation. TMA resolved with plasma exchange‐based therapy albeit with some irreversible graft damage and renal impairment. We discuss the differential diagnosis of post‐transplant TMA, and current treatment options.     

Antiphospholipid antibody syndrome and renal disease

The antiphospholipid syndrome is a disorder of hypercoagulability in association with circulating antiphospholipid antibodies directed against epitopes on oxidized phospholipids complexed with a glycoprotein, beta 2-glycoprotein I, or against the glycoprotein itself. Disorders associated with antiphospholipid antibodies but not the antiphospholipid syndrome, such as HIV and hepatitis C infection, appear to lack antibodies to beta 2-glycoprotein I. Patients with systemic lupus erythematosus have a high incidence of antiphospholipid antibodies with a high risk of thrombosis, often associated with anticardiolipin antibodies, beta 2-glyocoprotein I antibodies, and the presence of the lupus anticoagulant. Antiphospholipid antibodies are a significant cause of morbidity and mortality in renal patients with and without systemic lupus erythematosus. Renal manifestations include thrombotic microangiopathy and large vessel thrombosis. In patients with end-stage renal disease, antiphospholipid antibodies are prevalent and may increase in frequency with time on dialysis, possibly as a result of oxidative stress incurred during dialysis. The presence of anticardiolipin antibodies have been associated with a high incidence of hemodialysis access clotting. In renal transplant recipients, the incidence of antiphospholipid antibodies is also elevated and may be associated with a higher incidence of primary graft non-function. Although patients with systemic lupus erythematosus have similar renal allograft survival rates to the general population, survival is worse for those patients who are also antiphospholipid antibody positive. Additionally, in hepatitis C positive renal transplant recipients, the presence of anticardiolipin antibodies confers an increased risk of thrombotic complications and the development of thrombotic microangiopathy. Treatment of antiphospholipid antibody syndrome remains centered around anticoagulation with warfarin. The use of immunosuppressive agents has had no dramatic effect on antiphospholipid antibody titers and little clinical effect on thrombotic events.     

Comparison of surgical methods in catastrophic antiphospholipid syndrome (CAPS)

Antiphospholipid syndrome (APS) is an autoimmune condition characterized by vascular thromboses and/or pregnancy morbidity in the presence of antiphospholipid antibodies. The variant "catastrophic" (CAPS) is defined as a potential life-threatening disease, characterized by multiple small vessel thromboses that can lead to multiple organ failure. Surgery is between precipitating factors in CAPS International Registry, but it's still unclear the relationship between surgery and syndrome. The present study reports two surgical procedures, performed on two patients with APS admitted with diagnosis of loss of substance of the lower limb needing of reconstructive treatment. We compared and analyzed aggressive and minimally invasive surgery.     

狼疮肾炎合并抗磷脂抗体综合征的中西医结合诊疗

抗磷脂抗体综合征(APS)是系统性红斑狼疮(SLE)常见继发病症。以循环中出现抗磷脂抗体、血栓形成和病态妊娠为特征性表现。合并APS的狼疮肾炎(LN)患者易出现更多并发症，预后较差，对治疗的敏感性降低。抗凝和(或)抗血小板是治疗LN合并APS的关键，血浆置换则对重症APS患者有一定疗效。近年来，新型药物与治疗方法如利伐沙班、美罗华及干细胞移植展现出了巨大的治疗潜力。中西医结合治疗是另一种极有希望的治疗方法，多位中医大家均认为活血化瘀法可有效治疗LN合并APS患者。现代临床与药理研究也发现了中药治疗LN合并APS的价值。     

Central retinal vein occlusion in a patient on hemodialysis secondary to antiphospholipid syndrome: Case report

Central retinal vein occlusion (CRVO) is one of the most common retinal vascular disease. Macular edema associated is responsible of the major decrease in visual acuity. The main causes often implicated are high blood pressure and diabetes. Other etiologies should be sought including CRVO secondary to antiphospholipid syndrome (APS). This rare etiology is associated with a poor prognosis when late diagnosed. Owing to the high associated mortality, early diagnosis and prompt treatment are necessary. We describe a case of APS complicated by a catastrophic antiphospholipid syndrome in a patient who presented a decrease visual acuity.