Figure - available from: Rheumatology International
This content is subject to copyright. Terms and conditions apply.
Source publication
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 “antiphos...
Citations
... Oaks et al described how treatment with sirolimus in lupus-prone mice selectively blocked mTORC1 activation and antiphospholipid antibody (aPL) production. 22 Previous studies have described how aPLs are a major source of cardiovascular and renal disease in patients with SLE with or without nephritis, 23 suggesting that such mechanisms may represent a treatment target in patients with SLE. Likewise, Lai et al described the protective effects of sirolimus, a well-known mTOR inhibitor, in patients with SLE. ...
Objective
Systemic lupus erythematosus (SLE) is characterized by widespread organ inflammation. Metformin, commonly used for diabetes mellitus type 2, has been explored for its anti‐inflammatory potential in SLE. This study investigates the association of metformin use on renal and cardiovascular outcomes in patients with SLE.
Methods
This is a retrospective study. We used the multicenter research network (TriNetX) database from 88 health care organizations globally. Patients with SLE aged 18 and above, admitted between January 1, 2014, and April 21, 2024, were included. Propensity score matching compared patients with SLE on metformin with those not on metformin, considering demographics, laboratory results, comorbidities, and baseline medication use. The study assessed outcomes, including lupus nephritis (LN), chronic kidney disease (CKD), and major adverse cardiovascular events (MACEs) at one and five years after SLE diagnosis.
Results
We identified 9,178 patients with SLE on metformin and 78,983 patients with SLE not on metformin. After propensity score matching, patients with SLE on metformin had higher levels of hemoglobin A1C, whereas patients not on metformin had higher levels of urea nitrogen. When comparing both groups, the risk of developing LN (risk ratio [RR] = 1.70 [1.17–2.41]; P = 0.004), CKD (RR = 1.27 [1.07–1.52]; P = 0.007), and MACEs (RR = 1.21 [1.00–1.46]; P = 0.04) was significantly higher among patients not on metformin at one year after SLE diagnosis. After five years, the risk of LN and CKD was also higher in patients with SLE not on metformin. MACE risk was no longer significant after five years of diagnosis between both groups.
Conclusion
Patients with SLE not on metformin have a higher risk of developing LN, CKD, and MACEs compared with patients treated with metformin. Metformin's anti‐inflammatory potential offers promise as a complementary therapy for SLE. Nonetheless, further research and clinical trials are needed to clarify its mechanisms, optimal dosage, and long‐term effects.
... Las manifestaciones clínicas del síndrome antifosfolípidos primario son muy diversas, aún no se conoce por completo el mecanismo de afectación renal, el cual representa una de las manifestaciones más comunes y catastróficas de esta patología. La exacerbación de la nefropatía por autoanticuerpos, la enfermedad renal crónica progresiva, así como la pérdida temprana de la función del injerto renal forman parte del espectro de manifestaciones 6 . ...
... El diagnóstico de nefropatía por síndrome antifosfolípidos requiere la presencia de una o más lesiones intrarrenales típicas agudas o crónicas en la histología, después de descartar otras causas de microangiopatía renal. En el síndrome antifosfolípidos secundario a lupus eritematoso sistémico, la lesión renal se produce por una combinación de dos procesos fisiopatológicos: depósito de inmunocomplejos y microangiopatía trombótica 6 . ...
... Al confirmarse el diagnóstico de síndrome antifosfolípidos, se inició tratamiento para esta patología, el cual según la literatura puede iniciarse mediante anticoagulación, manteniendo un INR (International Normalized Ratio) entre 3 y 4.5, para restablecer la función renal. Desafortunadamente, nuestra paciente se presentó de forma tardía para recibir atención médica, lo que derivó en requerir tratamiento quirúrgico definitivo para la resolución de la patología 6 . ...
... In the literature, studies evaluated lupus patients with APS and, apart from lupus nephritis (LN), APS nephropathy was also frequently observed and was diagnosed in 63-67% [3,4]. Double or triple-positive patients for aPLs are at higher risk for renal involvement [5]. ...
... Acute form is represented by the presence of thrombotic microangiopathy (TMA) in glomerular capillaries with mesangiolysis and/or TMA in arteries and arterioles manifested by thrombotic lesions, intimal mucoid thickening and medial hyperplasia, while the chronic form of APS nephropathy is characterized by fibrous intimal hyperplasia, focal cortical atrophy and focal segmental glomerulosclerosis. Clinical manifestation of APS nephropathy is non-specific with hypertension (from moderate to malignant hypertension), sub-nephrotic range of proteinuria, hematuria, and acute kidney injury in 20-50%, but nephrotic syndrome is relatively rare [5][6][7]. ...
Unlabelled:
Antiphospholipid syndrome (APS) is a devastating autoimmune disease and in renal transplant recipients may result in allograft thrombosis or in extra-renal manifestation, mostly venous thromboembolism. There are many non- and immune risk factors affecting renal allograft in recipients with APS. However, renal allograft outcome in recipients with APS without APS nephropathy remains unknown.
Aim:
The aim of the study was to assess renal allograft function and survival in recipients with APS.
Methods:
Retrospective, multicenter study included 19 adult renal recipients with definite APS (primary or lupus-related) from three Polish transplant centers. Renal allograft function was assessed using serum creatinine concentration (SCr1) at 3rd month post-transplant and at the end of the observation (SCr2) and glomerular filtration rate (GFR) was estimated based on modification of diet in renal disease (MDRD) formula. General linear model was used to assess 12 month GFR change over time. Kaplan-Meier curves and restricted mean survival time were used for allograft survival. Matched control group consisted of 21 stable renal recipients without history of thrombosis and without anticoagulation/antiplatelet treatment.
Results:
The study group differs in induction therapy (p = 0.019), high-urgency procedure (p = 0.04), proteinuria (p = 0.0058), primary disease (lupus) (p < 0.0001), re-transplantation in primary APS (p = 0.0046) and shorter time since engraftment to SCr2 (p = 0.016). Primary APS was more often diagnosed post-transplant (p = 0.0005). Allograft biopsy revealed thrombotic microangiopathy (TMA) with acute rejection (AR) or isolated AR vs AR or chronic rejection in controls but did not reach significance (p = 0.054). Renal allograft function was inferior in the study group but did not reach significance: mean SCr2 (mg/dL) was 2.18 ± 1.41 and 1.5 ± 0.68 in controls, respectively, p = 0.27; mean GFR2 (ml/min/1.73m2) was 39.9 ± 20.83 and 51.23 ± 19.03, respectively, p = 0.102. Renal allograft duration was inferior in patients with APS and was (in years) 11.22 ± 1.44 vs. 14.36 ± 0.42, respectively, p = 0.037, in patients with primary APS (p = 0.021), in patients with APS diagnosed post-transplant (p = 0.012) but not in lupus-related APS (p = ns). Fifteen year renal allograft survival was inferior in APS vs. controls (73,86% vs. 90.48%, respectively, p = 0.049).
Conclusions:
Recipients with APS are at higher risk for allograft loss due to immune and non-immune causes. Renal allograft survival was inferior in recipients with APS and renal function remains impaired but stable.
... La hipertensión arterial sistémica es una de las principales manifestaciones asociadas a la presencia de aFL y es particularmente frecuente en pacientes con SAFP y embarazadas con aFL positivos. 20,21 La nefropatía por SAF se diagnostica con mayor frecuencia en un contexto agudo, y se manifiesta como lesión renal aguda, anemia hemolítica microangiopática (MAHA) y urgencia hipertensiva. 22 Algunos pacientes son asintomáticos, con proteinuria leve y función renal conservada, mientras que otros desarrollan insuficiencia renal aguda con proteinuria incluso en rango nefrótico, sedimento urinario activo con cilindros, e hipertensión arterial sistémica. ...
... 22 Algunos pacientes son asintomáticos, con proteinuria leve y función renal conservada, mientras que otros desarrollan insuficiencia renal aguda con proteinuria incluso en rango nefrótico, sedimento urinario activo con cilindros, e hipertensión arterial sistémica. 20 La Microangiopatía trombótica (MAT) ha sido descrita como la lesión vascular aguda intrarrenal más frecuente en pacientes con aFL positivo. 23 Las manifestaciones clínicas dependen del sitio y el tamaño de la vasculatura comprometida. ...
El Síndrome Antifosfolípido (SAF) es una enfermedad sistémica autoinmune caracterizada por la presencia de anticuerpos antifosfolípidos (aFL) y al menos una manifestación clínica de trombosis o historia de pérdida fetal según criterios de Sydney 2006. Se han descrito anticuerpos no convencionales y manifestaciones clínicas “extra criterio”, que si bien sugieren el diagnóstico de SAF, no son considerados parte de los criterios hasta la fecha. El diagnóstico tardío o la falta de un tratamiento adecuado y oportuno podría ocasionar secuelas graves para el paciente. Describimos manifestaciones clínicas extra criterio de SAF y anticuerpos no convencionales que permitan realizar un tratamiento correcto ante una sospecha de SAF.
... Patients with nephropathies may be asymptomatic with only mild proteinuria. They may have hypertension, nephrotic range proteinuria and active urinary sediment [10]. The most common renal manifestation of patients with secondary APS is the noninflammatory occlusion of the small renal vessels, which occurs in 63-67% of patients [4]. ...
... Our patient had an increase in creatinine, proteinuria and active sediment and the kidney biopsy showed lupus nephritis. The prevalence of valve lesions in patients with SLE and APS is of 40-50%, but it is lower (20%) in patients with SLE without APS on echocardiogram [2,10]. In contrast, up to 70% of patients with primary APS have at least one valvular lesion: it is characterized by thickening, stenosis, regurgitation and LSE, mainly in the mitral and aortic valves [11,12]. ...
... This is a case of APS associated with SLE that debuted with catastrophic APS where early diagnosis and medical treatment played a decisive role in the patient's survival. 10.2217/fca-2020-0145 Future Cardiol. ...
... APS nephropathy (APSN) is the result of thrombosis in renal arteries or veins, intraparenchymal arteries, and glomerular capillaries. Histologically, APSN is characterised by TMA, but chronic vaso-occlusive lesions are also commonly observed (fibrous intimal hyperplasia, focal cortical atrophy, fibrous occlusion of arteries) [48]. ...
A common criticism of the classification of lupus nephritis is the relative scarcity of information regarding tubular, interstitial, and vascular changes compared to the available information regarding glomerular changes, even though their potential for independent progression is known. This study reviewed the importance of less explored lesions by the current and widely used 2003 classification of lupus nephritis of the International Society of Nephrology/Renal Pathology Society (ISN/RPS), with emphasis on the tubulointerstitial, podocyte, and vascular lesions, increasingly recognised as being important in the pathogenesis and prognosis of the disease. Recognition of these lesions can help with therapeutic decision-making, thereby allowing better results for patients with systemic lupus erythematosus.
... [108][109][110] Secondly, if patients complain of acute back pain, haematuria, or uncontrolled hypertension, then acute nephropathy due to renal artery thrombosis or thrombotic microangiopathy may be suspected; in these cases, doppler US or abdominal CT may be helpful for differential diagnosis, with the addition of urinalysis, renal function tests, and biopsies. 111 Treatments include anticoagulation therapy, percutaneous angioplasty, and occasionally nephrectomy, and plasma exchange with anticoagulation is a firstline therapy in the case of thrombotic microangiopathy. 111,112 Thirdly, livedo reticularis (reticular-or mottled-patterned skin lesions that appear as persistent, nonreversible, and purplish discoloration of the skin), is the most frequent dermatologic manifestation of APS, and there are several case reports of livedo reticularis following surgery. ...
... 111 Treatments include anticoagulation therapy, percutaneous angioplasty, and occasionally nephrectomy, and plasma exchange with anticoagulation is a firstline therapy in the case of thrombotic microangiopathy. 111,112 Thirdly, livedo reticularis (reticular-or mottled-patterned skin lesions that appear as persistent, nonreversible, and purplish discoloration of the skin), is the most frequent dermatologic manifestation of APS, and there are several case reports of livedo reticularis following surgery. 113,114 Since livedo reticularis is also associated with a high risk for arterial thrombosis and cerebrovascular events in APS, patients with APS and livedo reticularis may require close follow-up. ...
Antiphospholipid syndrome (APS) is an acquired thrombotic autoimmune disorder that is clinically characterized by the development of thrombosis and obstetric morbidities in patients with antiphospholipid antibodies. Due to hypercoagulability, the focus of management is anticoagulation for the prevention of thrombosis and its recurrence. When such patients undergo surgery, however, the underlying risk of thrombosis increases as a result of anticoagulant withdrawal, immobilization, and/or intimal injury. Conversely, there is also an increased risk of bleeding due to thrombocytopaenia, possible disseminated intravascular coagulation, or progression to catastrophic APS, as a result of excessive anticoagulation, surgery, and infection. Measures for appropriate perioperative anticoagulation are discussed in this review, as well as anaesthetic considerations for preventing perioperative complications in patients with APS undergoing non-cardiac surgery.
... The major non-thrombotic manifestations of antiphospholipid syndrome included valvular heart disease, livedo reticularis, antiphospholipid syndrome nephropathy, thrombocytopenia and hemolytic anemia. Antiphospholipid antibodies [aPL] are a heterogeneous group of antibodies directed against anionic phospholipids or protein-phospholipid complexes and are composed of antibodies against cardiolipin, β2-glycoprotein 1 and lupus anticoagulant [4]. ...
... The most frequently observed histological findings are ischaemic features at the level of the glomerulus, tubular atrophy and interstitial fibrosis [4]. Although renal infarction is not a classic clinical manifestation of APS, aPL testing should be performed in young people who present with this disorder to tailor treatment if necessary, aPL tests Laboratory criteria for definite antiphospholipid syndrome include one coagulation test, lupus anticoagulant (LAC), and two immunological assays to detect antiphospholipid antibodies (aPL), that is, anticardiolipin antibodies (aCL) immunoglobulin G (IgG) and IgM isotypes and anti-β2 -glycoprotein I (aβ2GPI) antibodies IgG and IgM isotypes those tests should be repeated after 3 months to confirm the diagnosis [14]. ...
... Arterial hypertension affects many patients with primary and secondary APS and has been proposed as a sensitive sign of potential renal involvement [11]. The high rate of hypertension is suggested to be due to severe vascular lesions, including fibrous intimal hyperplasia (in most of the cases), arteriosclerosis, arterial and arteriolar fibrous and fibrocellular occlusions and TMA [4] [5] [11]. ...
... У механізмах її розвитку значну роль відіграє активація судинного ендотелію і тромбоцитів, зумовлена взаємодією АФЛ з ендотеліальними клітинами капілярів. АФС-нефропатія, зумовлена тромботичною мікроангіопатією судин, призводить до порушення внутрішньониркової мікроциркуляції з розвитком ішемії нирок і ниркової недостатності [2, 4,5]. ...
Вступ. Антифосфоліпідний синдром (АФС) належить до найактуальніших мультидисциплінарних проблем сучасної медицини. Частота ураження нирок при АФС становить 25–78 %. Мета дослідження – вивчити вплив комбінованої дії L-аргініну й аміногуанідину на стан показників вільнорадикального окиснення та тканинного дихання в нирках при експериментальному АФС і на тлі вагітності у тварин із цією патологією. Методи дослідження. Дослідження виконано на мишах-самках лінії BALB/с, в яких моделювали АФС. Для корекції використовували L-аргінін (25 мг/кг) та аміногуанідин (10 мг/кг). Досліджували в нирках тварин з АФС до вагітності й на 18-й день вагітності активність та вміст компонентів антиоксидантної системи (супероксиддисмутази, каталази, відновленого глутатіону), вміст гідропероксидів ліпідів і ТБК-активних продуктів, активність сукцинатдегідрогенази та цитохромоксидази. Результати й обговорення. У нирках мишей лінії BALB/с з АФС активувалися процеси пероксидного окиснення ліпідів, порушувалася рівновага в системі прооксиданти – антиоксиданти. При проведенні досліджень на 18-й день вагітності в нирках тварин з АФС спостерігали достовірне збільшення вільнорадикального окиснення, зменшення активності ензимів антиоксидантного захисту та дихального ланцюга мітохондрій порівняно з показниками контрольної групи вагітних мишей. При комбінованому введенні L-аргініну та аміногуанідину тваринам з АФС у нирках знижувалися вміст ТБК-активних продуктів (на 33 %) та активність супероксиддисмутази (на 15 %), зростали активність каталази (на 12 %), сукцинатдегідрогенази (на 16 %), цитохромоксидази (на 13 %) і вміст відновленого глутатіону (на 23 %) порівняно з показниками мишей з АФС. На фоні комбінованого застосування L-аргініну та аміногуанідину реєстрували послаблення активності процесів вільнорадикального окиснення та активацію системи антиоксидантного захисту в тканині нирок вагітних тварин з АФС. Встановлено достовірне підвищення активності сукцинатдегідрогенази на (18 %) та цитохромоксидази (на 75 %) порівняно з показниками вагітних самок з АФС. Висновки. При експериментальному АФС у тканині нирок невагітних та вагітних мишей лінії BALB/c відбуваються активація вільнорадикального окиснення, порушення рівноваги в системі прооксиданти – антиоксиданти. На фоні комбінованого введення L-аргініну та аміногуанідину в тканині нирок тварин з АФС (вагітних і невагітних) зменшуються прояви оксидативного стресу.
... But perhaps all TMA in SLE is related to a specific cause that is only found if it is meticulously sought after. In a vast proportion of lupus nephritis, TMA will occur in the presence of aPL, raising the question whether these patients have both lupus nephritis and antiphospholipid nephropathy 15 as comorbidities. Following this line of argument, other causes of TMA in lupus nephritis biopsies ...
