Renal Involvement In Antiphospholipid Syndrome Research Articles

Clinical-Pathological Characteristics of Renal Injuries Identify Different Clusters in Patients With Antiphospholipid Antibodies

Significant heterogeneity still exists in the nomenclature of renal involvement in antiphospholipid syndrome (APS). We applied a hierarchical cluster analysis to determine subgroups of patients according to clinical, laboratory, and renal histology characteristics in a cohort of subjects with confirmed antiphospholipid antibodies (aPL) positivity and biopsy proven aPL-related renal injuries. Kidney outcomes were then assessed at 12 months. A total of 123 aPL-positive patients were included in the study (101 [82%] female, 109 [88.6%] with systemic lupus erythematosus [SLE], 14 (11.4%) with primary APS [PAPS]). Three clusters were identified. Twenty-three patients (18.7%) were included in the first cluster (cluster 1), characterized by a higher prevalence of glomerular capillary and arteriolar thrombi and fragmented red blood cells in the subendothelial space. Cluster 2 included 33 patients (26.8%) and showed a higher prevalence of fibromyointimal proliferative lesions as seen in hyperplastic vasculopathy. Cluster 3 was the largest (67 patients, mainly with SLE) and was characterized by higher prevalence of subendothelial edema, of both glomerular capillaries and arterioles. Three different clusters of patients with aPL and renal injuries emerged from our study as follows: the first, with the worst renal prognosis, was associated with features of thrombotic microangiopathy (TMA), thrombosis, triple aPL positivity and higher adjusted Global APS Score (aGAPSS) values; the second, characterized by hyperplastic vasculopathy with an intermediate prognosis, was seen more frequently in patients with cerebrovascular manifestations; and the third, more benign in terms of outcomes and with no overt association with thrombotic features, was characterized by endothelial swelling in concomitant lupus nephritis (LN).

Diversity of Renal Involvement in Antiphospholipid Syndrome Based on Pathological Findings and Treatment Responses.

Diversity of Renal Involvement in Antiphospholipid Syndrome Based on Pathological Findings and Treatment Responses.

Renal Involvement in Antiphospholipid Syndrome.

Antiphospholipid syndrome is a complex autoimmune disease, characterized by the presence of vascular thrombosis, obstetric, hematologic, cutaneous, and cardiac manifestations. Renal disease in patients with antiphospholipid syndrome was not recognized in the first descriptions of the disease, but later on, the renal manifestations of the syndrome have been investigated widely. Renal manifestations of antiphospholipid syndrome conform a wide spectrum of diverse renal syndromes. Hypertension is one of the most frequent, but less commonly recognized renal alteration. It can be difficult to control as its origin is renovascular. Renal vascular thrombosis can be arterial or venous. Other alterations are renal infarction and vascular thrombosis in arterial territories. Venous thrombosis can be present in primary and secondary antiphospholipid syndrome; it presents with worsening of previous proteinuria or de novo nephrotic syndrome, hypertension and renal failure. Antiphospholipid syndrome nephropathy is a vascular disease that affects glomerular tuft, interstitial vessels, and peritubular vessels; histopathology characterizes the renal lesions as acute or chronic, the classic finding is thrombotic microangiopathy, that leads to fibrosis, tubule thyroidization, focal cortical atrophy, and glomerular sclerosis. Antiphospholipid syndrome nephropathy can also complicate patients with systemic lupus erythematosus, and there is vast information supporting the worse renal prognosis in this group of patients with the classic histopathologic lesions. Treatment consists of anticoagulation, as for other thrombotic manifestations of antiphospholipid syndrome. There is some evidence of glomerulonephritis as an isolated lesion in patients with antiphospholipid syndrome. The most frequently reported glomerulonephritis is membranous; with some reports suggesting that immunosuppressive treatment may be effective. Patients with end stage renal disease commonly are positive for antiphospholipid antibodies, but it is not clear what is the role of aPL in this setting. Patients with vascular access may have complications in the presence of antibodies so that anticoagulation is recommended. Patients ongoing renal transplant with persistent antiphospholipid antibody positivity may have early and late graft failure.

Renal involvement in antiphospholipid syndrome.

This is a review of scientific publications on renal involvement in antiphospholipid syndrome (APS), with focus on clinical and histopathological findings and treatment. A search for English-language articles on renal involvement in APS covering the period 1980-2017 was conducted in Medline/PubMed and Scopus databases using the MeSH terms "antiphospholipid syndrome", "antiphospholipid antibodies", "glomerulonephritis" and "thrombotic microangiopathy" (TMA). APS nephropathy is primarily the result of thromboses in renal arteries or veins, intraparenchymatous arteries and glomerular capillaries. On histology, APS nephropathy is characterized by TMA, but chronic vaso-occlusive lesions are also commonly observed (fibrous intimal hyperplasia, focal cortical atrophy, fibrous occlusions of arteries). Anticardiolipin and lupus anticoagulant are the most prevalent antibodies in patients with APS nephropathy. The spectrum of renal manifestations includes renal vein thrombosis, renal artery thrombosis/stenosis, TMA, increased allograft vascular thrombosis and malignant hypertension. Anticoagulation is the standard treatment of thrombotic events. In systemic lupus erythematosus (SLE) patients with antiphospholipid antibodies (aPL), kidney failure due to SLE nephritis (immune-complex disease) should be clearly distinguished from kidney failure due to APS-related TMA. In such cases, renal biopsy is mandatory. SLE nephritis requires immunosuppressive therapy, whereas APS nephropathy is usually treated with anticoagulants. Recently, eculizumab and sirolimus have been proposed as a rescue therapy. Based on our review, APS nephropathy appears to be a distinct clinical condition. TMA is a characteristic histopathological finding in APS and is strongly associated with the presence of aPL. This has important therapeutic implications and allows distinguishing APS nephropathy from lupus nephritis.

Ultrasonographic Evaluation of Resistive Index and Renal Artery Stenosis in Patients with Anti-Phospholipid Syndrome: Two Distinct Mechanisms?

Renal involvement in anti-phospholipid syndrome (APS) is still relatively unknown and probably underestimated. The described lesions consist of renal artery stenosis (RAS), venous renal thrombosis and glomerular lesions. The resistive index (RI) of intra-renal arteries, expression of the degree of vascular resistance, has been analyzed in different nephropathies and observed to be associated with functional parameters and some histologic features. In contrast, there are no studies on patients with APS. We evaluated the presence of a pathologic RI and RAS in a cohort of patients with APS. The study protocol included ultrasonographic assessment to measure the RI (RIs >0.7 were considered pathologic) and to determine the presence of RAS. We enrolled 36 patients with APS, 13 with primary APS and 23 with the form associated with systemic lupus erythematosus (SLE, secondary APS). As controls, we enrolled 10 anti-phospholipid antibody carriers, 10 patients with SLE without renal involvement and 14 age- and sex-matched healthy patients. A pathologic RI was identified in five patients with APS (13.9%) and in none of the anti-phospholipid antibody carriers (p = 0.00007). Four of the five (80%) patients with a pathologic RI had secondary APS. Three patients, all with primary APS, had RAS. The almost exclusive association of a pathologic RI with secondary APS and of RAS with primary APS suggests the involvement of two pathogenic pathways in the development of these different manifestations. The hypercoagulability status driven by APS could play a central role in the determination of RAS in patients with primary APS, whereas the activation of mTORC (mammalian target of rapamycin complex) pathways could be the pathogenic mechanism inducing development of a pathologic RI.

Antiphospholipid Antibodies and APS Nephropathy

The presence of pathogenic antiphospholipid antibodies (aPL) is the characterizing feature of the antiphospholipid syndrome (APS), mediating the recurrent pregnancy loss and thrombosis typical of the disease through its action on various antigenic targets. APS nephropathy is the characteristic clinico-athological manifestation of renal involvement in APS and occurs as a result of vaso-occlusive disease in the intrarenal vasculature. The typical clinical features and morphological lesions of APS nephropathy have been well characterized and several studies have established a link between these features and the presence of various aPL. In this review, we outline the proposed pathophysiological mechanisms of aPL-mediated thrombosis, the characteristic clinical and morphological features of APS nephropathy and the evidence linking aPL action to the occurrence of APS nephropathy.

Antiphospholipid Antibodies and APS Nephropathy

The presence of pathogenic antiphospholipid antibodies (aPL) is the characterizing feature of the antiphospholipid syndrome (APS), mediating the recurrent pregnancy loss and thrombosis typical of the disease through its action on various antigenic targets. APS nephropathy is the characteristic clinico-athological manifestation of renal involvement in APS and occurs as a result of vaso-occlusive disease in the intrarenal vasculature. The typical clinical features and morphological lesions of APS nephropathy have been well characterized and several studies have established a link between these features and the presence of various aPL. In this review, we outline the proposed pathophysiological mechanisms of aPL-mediated thrombosis, the characteristic clinical and morphological features of APS nephropathy and the evidence linking aPL action to the occurrence of APS nephropathy.

Identification and treatment of APS renal involvement.

Renal involvement in antiphospholipid syndrome (APS), either primary or systemic lupus erythematosus (SLE)-related APS, includes renal artery stenosis or thrombosis, renal infarction, renal vein thrombosis and a small-vessel vaso-occlusive nephropathy defined as "antiphospholipid antibody (aPL)-associated nephropathy." aPL-associated nephropathy is characterized by acute lesions, thrombotic microangiopathy, and chronic lesions such as fibrous intimal hyperplasia, organizing thrombi with or without recanalization, fibrous occlusions of arteries or arterioles and focal cortical atrophy. Systemic hypertension, hematuria, proteinuria (ranging from mild to nephrotic level) and renal insufficiency represent the major clinical manifestations associated with aPL-associated nephropathy. Similar renal histologic and clinical characteristics have been described among all different groups of patients with positive aPL (primary APS, SLE-related APS, catastrophic APS and SLE/non-APS with positive aPL). In patients with aPL-associated nephropathy lesions in the absence of other causes associated with similar histological characteristics, aPL testing needs to be considered.

Renal involvement in antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for antiphospholipid antibodies (aPLs). APS can be isolated (known as primary APS) or associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE; known as secondary APS). The kidney is a major target organ in APS and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal arteries, glomerular capillaries and renal veins); events reflect the site and size of the involved vessels. Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal prognosis is affected by the presence of aPLs in patients with lupus nephritis and can be poor. In patients with SLE and aPLs, biopsy should be performed because inflammatory and thrombotic lesions require different therapeutic approaches. Renal involvement in patients with definite APS is treated by anticoagulation with long-term warfarin. The range of renal manifestations associated with APS is broadening and, therefore, aPLs have increasing relevance in end-stage renal disease, transplantation and pregnancy.

Renal Involvement in Antiphospholipid Syndrome

Renal involvement can be a serious problem for patients with antiphospholipid syndrome (APS). However, this complication has been poorly recognized and studied. It can be present in patients who have either primary or systemic lupus erythematosus-associated APS. Clinical and laboratory features of renal involvement in APS include hypertension, hematuria, acute renal failure, and progressive chronic renal insufficiency with mild levels of proteinuria that can progress to nephrotic-range proteinuria. The main lesions are renal artery stenosis, venous renal thrombosis, and glomerular lesions (APS nephropathy) that may be acute (thrombotic microangiopathy) and/or chronic (arteriosclerosis, arterial fibrous intimal hyperplasia, tubular thyroidization, arteriolar occlusions, and focal cortical atrophy). APS can also cause end-stage renal disease and allograft vascular thrombosis. This article reviews the range of renal abnormalities associated with APS, and their diagnosis and treatment options.

The kidneys and antiphospholipid syndrome

There are clinical observations and data from literature showing that kidney involvement is frequently found in antiphospholipid syndrome (APS). The clinical pictures of renal involvement in APS can be different: from modest to severe hypertension, nephritic or nephrotic syndrome and chronic kidney disease at all stages. There is no clear connection between the presence of a significant level of antiphospholipid antibodies (aPL) and advancing of nephropathy especially occurring in course of connective tissue diseases. In the paper the relations between APS, the presence of aPL and nephropathy have been discussed.

Renal Involvement in the Antiphospholipid Syndrome (APS)—APS Nephropathy

Although the kidney represents a major target organ in antiphospholipid syndrome (APS), renal involvement in APS was poorly recognized until recently. The most well-recognized renal manifestations of APS are the renal artery thrombosis/stenosis, renal infarction, hypertension, renal vein thrombosis, end-stage renal disease, increased allograft vascular thrombosis, some types of glomerular disease, and a small-vessel vaso-occlusive nephropathy, recently defined as APS nephropathy. APS nephropathy was first described in primary APS patients, characterized by acute thrombotic lesions in glomeruli and/or arterioles (thrombotic microangiopathy) and chronic vascular lesions such as fibrous intimal hyperplasia of arterioles and interlobular arteries, organized thrombi with or without recanalization, and fibrous arterial and arteriolar occlusions or focal cortical atrophy. APS nephropathy was also detected in further studies including patients with systemic lupus erythematosus (SLE)-related APS and SLE/non-APS patients with positive antiphospholipid antibodies, independently of lupus nephritis. The same histologic lesions, especially thrombotic mictroangiopathy, were also observed in patients with catastrophic APS. The most frequent clinical and laboratory characteristics of APS nephropathy in all the above groups of patients are hypertension (often severe), proteinuria (ranging from mild to nephrotic range), hematuria, and acute or chronic renal insufficiency.

The expanding spectrum of renal diseases associated with antiphospholipid syndrome

Background:The association of thrombotic events and/or pregnancy complications with circulating antiphospholipid antibodies defines antiphospholipid syndrome (APS). In previous reports, renal involvement in APS consisted mainly of thrombotic vascular complications involving large vessels or intrarenal small-sized vessels (APS nephropathy). We report 9 cases of glomerulonephritis associated with APS. These cases are characterized by predominant pathological features distinct from vascular APS nephropathy. Methods:We reviewed consecutive renal biopsies examined in 2 French university hospitals between 1980 and 2002 and identified renal biopsies performed in patients with primary APS. Results:We identified 29 biopsies performed in patients with APS. Twenty biopsies showed characteristic features of APS nephropathy. In 9 cases, predominant pathological features distinct from vascular APS nephropathy were noted: membranous nephropathy (3 cases), minimal change disease/focal segmental glomerulosclerosis (3 cases), mesangial C3 nephropathy (2 cases), and pauci-immune crescentic glomerulonephritis (1 case). In 7 cases, the presentation of renal symptoms was subacute or chronic. Two patients experienced episodes of acute renal failure. At referral, median creatinine clearance was 50 mL/min (0.83 mL/s) (range, 18 to 117 mL/min [0.30 to 1.95 mL/s]). Proteinuria was noted in all cases (range, 1.5 to 15 g/d), with nephrotic syndrome in 4 cases. Lupus anticoagulant was present in all cases, and anticardiolipin antibodies, in 8 cases. Anti-DNA antibodies repeatedly were negative in all cases. Treatment consisted of antihypertensive therapy (6 cases), anticoagulant drugs (5 cases), steroids (4 cases), and antiplatelet drugs (3 cases). At last follow-up, renal function remained stable in 7 patients. Of 2 patients presenting with acute renal failure, 1 patient recovered normal renal function, whereas the other patient progressed to end-stage renal failure. Conclusion:The cases reported here represent a new aspect of the expanding spectrum of renal diseases encountered in association with APS.

Renal involvement in antiphospholipid syndrome.

Renal involvement in antiphospholipid syndrome.