Postoperative Bilateral Renal Cortical Necrosis Secondary to Antiphospholipid Syndrome: A Case Report and Literature Review

Abstract

French

We report a case of biopsy-proven renal cortical necrosis in a 42-year-old man after bioprosthetic aortic valve replacement despite prophylactic anticoagulation. He had antiphospholipid syndrome with chronic thrombotic microangiopathy and triple-positive antibodies, leading to renal cortical necrosis manifested as severe non-reversible dialysis-dependent acute kidney injury. We identified 13 previously published reports of renal cortical necrosis due to antiphospholipid syndrome: 3 occurred postpartum, 2 after kidney transplantation, and 1 following salpingectomy for ectopic pregnancy.

Keywords

antiphospholipid syndrome renal cortical necrosis renal thrombotic microangiopathy acute kidney injury triple-positive antiphospholipid antibody

Introduction

Renal cortical necrosis (RCN) is a rare etiology of severe acute kidney injury (AKI).¹ The leading cause of renal cortical necrosis in developing countries is obstetric complications.² We report a case of severe renal cortical necrosis in a patient with antiphospholipid syndrome (APS) following bioprosthetic aortic valve replacement. We also reviewed reported cases of diffuse renal cortical necrosis secondary to antiphospholipid syndrome in the literature.

Case Report

Presenting Concerns

A 42-year-old man with a history of antiphospholipid syndrome (APS), hypertension, epilepsy, thrombocytopenia, and severe aortic valve stenosis underwent a bioprosthetic aortic valve replacement. He also had chronic kidney disease (CKD) stage G3bA2 secondary to biopsy-proven thrombotic microangiopathy (TMA). The patient had been on aspirin, ramipril, amlodipine, lacosamide, and clobazam prior to admission. Immediately postoperatively, he experienced transient hypotension, which resolved with intravenous fluids. On postoperative day (POD) 1, he was noted to have developed acute kidney injury (AKI).

With regard to his chronic kidney disease course, his serum creatinine had slowly progressed from 140 to 220 µmol/L over the preceding decade, with proteinuria ranging between 1 and 3 g/day based on 24-hour urine collections. At age 40, he underwent a diagnostic kidney biopsy to evaluate the cause of progressive proteinuric chronic kidney disease (CKD). The biopsy demonstrated features of thrombotic microangiopathy (TMA) with both acute and chronic changes (Figure 1A and B). On light microscopy, the renal cortex contained 15 glomeruli, five of which were globally sclerosed. The remaining glomeruli showed moderate to marked mesangial matrix expansion, segmental mesangial hypercellularity, mesangiolysis, and perihilar segmental scarring. Glomerular capillaries remained patent without endocapillary hypercellularity; however, there was diffuse glomerular endothelial cell swelling with segmental double contouring, and glomerular capillary wall thickening. Some glomeruli appeared retracted with periglomerular fibrosis. There were moderate interstitial fibrosis and tubular atrophy, mild interstitial inflammation, severe hyaline arteriosclerosis, and moderate-to-severe arteriosclerosis with mucoid intimal changes. A possible fibrin thrombus was also noted. Immunofluorescence revealed global sclerosis in 34 out of 40 glomeruli, with nonsignificant staining for IgG, IgA, C3, C1q, kappa, and lambda. On electron microscopy, three of nine glomeruli were globally sclerosed. The mesangium was expanded by frequent hyaline electron densities, without immune-type deposits or tubuloreticular inclusions. Subendothelial widening, cellular interposition, and segmental endothelial cell swelling and hypertrophy were observed, consistent with ongoing acute and chronic endothelial injury. The glomerular basement membranes appeared thickened and segmentally duplicated, with segmental podocyte foot process effacement.

Figure 1.

Kidney biopsy findings at initial diagnosis of thrombotic microangiopathy (A, B) and postoperative renal cortical necrosis (C, D, E). Initial kidney biopsy reflecting thrombotic microangiopathy: (A) Glomerulus showing features of acute thrombotic microangiopathy: dilated capillary loops, mesangiolysis (white star) and fibrin thrombus (white arrow). In addition, periglomerular fibrosis due to chronic hypoperfusion. PAS 40×. (B) Ultrastructural features of chronic microangiopathy: subendothelial widening by fluffy proteinaceous material separating the endothelial cell from the GBM (white star) and forming double contours (white arrow). Endothelial cell hypertrophy (orange star) (TEM 20000×). Postoperative kidney biopsy: (C) Extensive necrosis (coagulative) with interstitial hemorrhage (white arrows). (H&E 20×). (D) Coagulative necrosis, interstitial inflammation (white arrows) in areas of reperfusion (H&E, 20×). (E) Extensive cortical necrosis (H&E 4×).

Further work-up to determine the underlying cause of thrombotic microangiopathy revealed triple-positive antiphospholipid antibodies: anticardiolipin IgG >160 GPL-U/mL (reference <20), anticardiolipin IgM 32 MPL-U/mL (reference <20), β2-glycoprotein 1 (β2GP1) IgG >160 U/mL (reference <20), β2GP1 IgM 98 U/mL (reference <20), positive Dilute Russell’s Viper Venom Time (DRVVT) test, and positive lupus sensitive PTT assay. Hemoglobin was 138 g/L, and platelet count was mildly reduced at 139 ×10⁹/L. Lactate dehydrogenase (LDH) was elevated at 5.5 ukat/L (reference 2-3.6), while INR and PTT were within normal limits. Total bilirubin was 6 µmol/L (reference < 22), and haptoglobin was 0.4 g/L (reference 0.3-2). Complement levels were suppressed, with C3 at 0.67 g/L (reference 0.90-1.80) and C4 at 0.08 g/L (reference 0.10-0.40). Autoimmune serologies, including antinuclear antibodies (ANA), anti-double-stranded DNA, and extractable nuclear antigen (ENA) antibodies, were negative. Genetic testing for atypical hemolytic uremic syndrome (aHUS) did not reveal any known pathogenic mutations in C3, CD46, CFB, CFH, CFHR5, CFI, or THBD.

Given the absence of clear evidence supporting anticoagulation in antiphospholipid syndrome with chronic thrombotic microangiopathy without arterial or venous thrombotic event, he was treated with aspirin only. With better control of his blood pressure, his proteinuria decreased to below 0.5 g per day and his serum creatinine stabilized around 195 µmol/L.

Clinical Findings

His serum creatinine began rising on postoperative day one despite hemodynamic stability. His serum creatinine immediately prior to operation was stable around baseline of 195 µmol/L. By day seven, serum creatinine had increased to 485 µmol/L, accompanied by bilateral flank pain, gross hematuria, and livedo reticularis. Blood tests showed low platelets 50 × 10⁹/L (142 × 10⁹/L preoperative), low hemoglobin 80 g/L (145 g/L preoperative), elevated LDH 8.3 ukat/L, and high-normal total serum bilirubin 16 µmol/L, with no schistocytes on blood smear. By day 10, his serum creatinine reached 850 µmol/L.

Diagnostic Focus and Assessment

Transthoracic echocardiogram demonstrated normal left ventricular ejection fraction (55%-60%) with a well-seated bioprosthetic valve and no intracardiac thrombus. Kidney ultrasound showed echogenic kidneys without hydronephrosis. Renal magnetic resonance angiography revealed normal arteries and veins.

A repeat kidney biopsy showed extensive coagulative cortical necrosis, severe interstitial fibrosis and tubular atrophy, severe arteriolar hyalinosis, and arterial sclerosis (Figure 1C and E).

Therapeutic Focus and Assessment

Postoperatively, he received prophylactic low molecular weight heparin. In light of the extensive cortical necrosis, escalation to full-dose anticoagulation was not pursued.

Follow-up and Outcomes

Platelet counts gradually improved and normalized 1 month postoperatively, reaching 163 × 10⁹/L. Hemoglobin levels improved more slowly, eventually reaching 110 g/L at three months post-op. Despite supportive measures, the patient remained dialysis-dependent six months postoperatively.

Discussion

In this report, we describe a case of postoperative severe bilateral renal cortical necrosis secondary to antiphospholipid syndrome. Antiphospholipid syndrome is an autoimmune thrombophilic disease that is diagnosed based on the development of venous, arterial, or microvascular thrombosis and/or obstetrical morbidity in the presence of persistent circulating antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibody, and/or B2 glycoprotein I antibody).³ The presence of antiphospholipid antibodies is not sufficient to provoke vascular thrombosis. Another precipitating factor like surgery, pregnancy, or infection usually represents the second hit at the time of thrombosis.⁴

Antiphospholipid syndrome can affect the kidneys targeting renal vessels of different sizes. This usually manifests as renal vein thrombosis, renal arterial thrombosis or stenosis, renal infarction, and renal small vessel disease also known as antiphospholipid syndrome nephropathy.³ Renal cortical necrosis is a rare manifestation of antiphospholipid syndrome. We conducted a comprehensive review of the literature by searching PubMed and Google Scholar using the terms “antiphospholipid syndrome” and “renal cortical necrosis.” Only English-language, peer-reviewed publications were included in the review. In addition to our report, there are 13 other reports in the literature of diffuse renal cortical necrosis secondary to antiphospholipid syndrome.

Table 1 summarizes the 14 reports. While cortical necrosis could be attributed to perioperative hypotension, the hypotensive episode was mild, transient, and rapidly responsive to intravenous fluid resuscitation, without requiring vasopressor support. Furthermore, the patient’s hematologic profile showed features suggestive of active thrombotic microangiopathy (TMA), including worsening anemia, thrombocytopenia, and elevated levels of lactate dehydrogenase (LDH) and total bilirubin. Although schistocytes were not observed on peripheral smear, which limits a definitive diagnosis of active hematologic TMA, the overall clinical and laboratory picture remains concerning for ongoing microvascular injury.

Table 1.

Reported Cases of Renal Cortical Necrosis Secondary to Antiphospholipid Syndrome.

	Age (y)	Gender	Renal necrosis (unilateral vs bilateral)	APS (Primary, secondary, catastrophic)	Pre-existing diagnosis vs newly diagnosed APS at presentation	Clinical setting	APS serology (+)	Presenting features	AC at presentation	Imaging diagnosis	Kidney biopsy/ Pathology findings	Acute management	Outcome	Long-term AC
Gude et al⁵	25	F	Bilateral	Primary	Newly diagnosed at presentation	Postpartum	aPL IgM	Anuria, Scr 371 µmol/L	No	Enhanced abdominal CT	Yes Diffuse loss of cellular architecture of glomeruli (ghostlike glomeruli)	HD	Dialysis dependent	Not specified
Haaskjold et al⁶	24	M	Unilateral	Primary	Newly diagnosed at presentation	NA	LA	Abdominal pain, fever, hematuria, proteinuria, AKI Scr 123 µmol/L	No	Enhanced abdominal CT + contrast-enhanced ultrasound	No	LMWH	CKD Scr 97 µmol/L	Warfarin
Laban et al⁷	38	F	Kidney graft	Primary	Pre-existing	Recurrence of APS post kidney transplant	History of triple + aPL; only LA + at transplant	Post-transplant AKI despite peri-transplant eculizumab, anemia, thrombocytopenia	Yes	Allograft MRI and contrast echocardiography.	No	Eculizumab, CS, PLEX, tacrolimus-to-belatacept switch, and warfarin	Serum creatinine 328 µmol/L at 1 year post-kidney transplant	Yes
Khan et al⁸	25	F	Unspecified	Primary, Obstetric	Newly diagnosed at presentation	Postpartum	LA and aCL IgM	Fever, oliguria, proteinuria, hematuria, AKI Scr 221 µmol/L	No	No	Yes 9 of the 11 glomeruli showed marked coagulative necrosis of the mesangium and capillaries, with preserved ghost cell outlines	HD and PLEX	Lost to follow up	Lost to follow up
Kim et al¹	16	F	Bilateral	SLE associated APS	Newly diagnosed at presentation	NA	LA	Dyspnea, anuria, Scr 984 µmol/L	No	Enhanced abdominal CT	No	CS, HD and AC	Dialysis dependent	Yes
Moreno-Torres et al⁹	27	F	Bilateral	Primary	Known aPL +	Post BNT162b2 mRNA COVID-19 vaccine	aB2GP-1 IgM, aCL IgM	Fever, digital ischemia, abdominal pain, AKI, hemodynamic instability, DIC	No	Enhanced abdominal CT	No	Antibiotics, CS and LMWH	Dialysis dependent	LMWH
Park et al¹⁰	40	M	Unspecified	Catastrophic primary	Newly diagnosed at presentation	NA	LA and aCL IgM	Oliguria, hematuria, abdominal pain, fever, Scr 530 µmol/L needing HD	No	MRI	No	HD	Kidney function improved, details unspecified.	Yes
Vellanki et al²	24	F	Bilateral	SLE associated APS	Newly diagnosed at presentation	Postpartum	aCL IgM	Anuria, kidney failure	No	Enhanced CT	No	Dialysis	Dialysis dependent	Not specified
Vigneau et al¹¹	46	M	Bilateral	Paraneoplastic (lung epidermoid cancer)	Newly diagnosed at presentation	NA	aCL IgG	Fever, anuria, Scr 1662 µmol/L	No	Renal arteriography	Yes Cortical necrosis with arterial thrombi predominant on small vessels and glomeruli	Lung tumor surgery, AC and HD	Dialysis dependent	Yes, then discontinued after few years
Vivaldi et al¹²	46	F	Unspecified	Primary	Pre-existing	NA	aCL IgG	Occlusion of the left subclavian and femoral arteries, AKI Scr 460 µmol/L requiring HD.	Yes	No	Yes 20 glomeruli: ischemic collapse; arterioles were thickened with fibrin thrombi. Extensive tubular necrosis and interstitial inflammatory infiltrates (Acute cortical necrosis)	Aspirin, dipyridamole, CS, cyclophosphamide, and PLEX	Deceased 26 days postadmission	Deceased 26 days postadmission
Yelnik et al¹³	46	F	Unspecified	Catastrophic primary	NA	NA	Triple + aPL	Kidney failure, MAHA thrombocytopenia, livedo reticularis, colic and splenic infarct	Yes	No reported	Not reported	AC, CS, Eculizumab and HD	Dialysis dependent	Yes
	54	F	Kidney graft	Catastrophicprimary	Pre-existing	Post kidney transplant	Triple +aPL	Thrombocytopenia,MAHA, kidney failure	Yes	Not reported	Not reported	AC, CS, Eculizumab and HD	Dialysisdependent	Yes
Zaafrane et al¹⁴	35	F	Bilateral	Primary	Pre-existing	Post salpingectomy for ectopic pregnancy	aCLantibodies	Sudden blurred vision(choroidal occlusion),AKI	Yes	MRI	No	CS, PLEX, IV immunoglobulins,Rituximab, dialysis, andAC	End stage kidney disease needing dialysis	Yes,Apixaban
Jdiaa et al (Current Case)	40	M	Bilateral	Primary	Pre-existing	Postoperative	LA, aB2GP-1 IgM andIgG, aCLIgM andIgG	Bilateral flank pain, gross hematuria, AKI	No	No	YesExtensive coagulative cortical necrosis	HD	Dialysis dependent	No

Note. AC: anticoagulation, aCL: anticardiolipin, AKI: acute kidney injury, aPL: anti-phospholipid antibody, APS: antiphospholipid syndrome, CKD: chronic kidney disease, CS: Corticosteroids, CT scan: computerized tomography scan, DIC: disseminated intravascular coagulation, F: female, HD: hemodialysis, LA: Lupus anticoagulant, LMWH: low molecular weight heparin, M: male, MAHA: microangiopathic hemolytic anemia, MRI: Magnetic resonance imaging, NA: not available, PLEX: plasma exchange, RCN: renal cortical necrosis, Scr: serum creatinine, SLE: systemic lupus erythematous.

There is no clear guidance regarding the optimal treatment for antiphospholipid syndrome induced chronic renal limited thrombotic microangiopathy and antiphospholipid syndrome nephropathy.³ Postoperatively, patients with antiphospholipid syndrome are considered high risk for both thrombosis and bleeding which can occur simultaneously. There is a knowledge gap in the best approach to manage antiphospholipid syndrome perioperatively. Meroni et al described successful eculizumab prophylaxis therapy prior to arterial bypass surgery in a patient with antiphospholipid syndrome and recurrent arterial thrombosis. Meroni et al¹⁵ also demonstrated the immunofluorescence positivity for b2GPI, b2GPI co-localizing IgG, C3, C4, and C1q on the endothelium of occluded femoral artery proposing classical pathway complement activation in the pathophysiology of antiphospholipid syndrome induced thrombotic event. Also, eculizumab has been used to prevent vascular thrombotic events and thrombotic microangiopathy in patients with catastrophic antiphospholipid antibody syndrome undergoing kidney transplantation.³ Since surgical intervention can be the second hit for thrombotic event in patients with high-risk antiphospholipid antibodies, clear guidance is needed for perioperative management of this population with and without prior large or small vessel thrombotic event.

Footnotes

ORCID iDs

Sara S. Jdiaa

Arenn Jauhal

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Informed Consent

Patient provided informed consent to publish this case.

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