#3232 ANTICOAGULANT RELATED NEPHROPATHY – AN UNDERDIAGNOSED COMPLICATION
Authors: Islami Tefik , Gregorini Marilena , D'ambrosio Gioacchino , Vino Paolo Del , Pattonieri Eleonora Francesca , Fusi Miriam , Canu Pietro , Montecucco Carlo Maurizio , Rampino Teresa 
Published: June 2023

Abstract

Background and Aims
Anticoagulant-related nephropathy (ARN) is an underdiagnosed complication of anticoagulant therapy (AT).

Method
We report 3 cases of ARN.
Patient 1: 31 year-old male (M), kidney transplanted for reflux nephropathy, with normal renal function (Rfx) and urinalysis (U), on therapy with tacrolimus (FK), everolimus and mycophenolate. He started edoxaban (E) (60 mg od) for deep vein thrombosis (DVT). After 10 days he developed hematuria and Acute Kidney Injury (AKI). Ruled out urological and infectious causes, we performed kidney biopsy (KB) which showed extensive tubular necrosis (TN), erythrocyte casts (cRBC) and glomerular hemorrhage (EG). Perl's stain (PS) showed iron deposits in tubular cells released by erythrocytes lysis (Fig. 1). Although E posology was adequate the concomitant intake of FK by reducing CYP3A4 metabolism of E resulted in over anticoagulation (OAC), demonstrated by the dosage of the factor Xa (FXa) at peak. Upon withdrawal of AT, Rfx and U normalized.
Patient 2: 73-year-old M with hypertension and mild chronic kidney disease (CKD) on antiplatelet therapy (ASA 100 mg od) for biological valve prosthesis and AT with Enoxaparin sodium (Es) (4000UI od) for DVT prophylaxis. He was admitted to the hospital for fever and hypotensive episodes. Microbiological, neoplastic and immune investigations were negative. A progressive worsening of Rfx associated with macro-hematuria was observed, requiring renal replacement therapy (RRT). KB showed a post-infectious glomerulonephirits, but in the hypothesis that tubular damage was enhanced by antiplatelet/AT, PS was performed and resulted positive. OAC was confirmed by the dosage of the factor Xa (FXa) at peak. After withdrawal of therapy, progressive improvement of the Rfx and hematuria were observed, such as to allow the suspension of the RRT.
Patient 3: 54 year-old M with kidney and lung involvement of ANCA-associated vasculitis. After rituximab induction therapy he showed marked improvement on lung and renal function and antibody titer (c-ANCA PR3 positive). He experienced an unusual worsening of Rfx and hematuria after starting a AT (Es 6000 UI BID) to treat a DVT. A KB was performed in the suspicion of ARN. The histology revealed an extensive TN, numerous cRBC with extracapillary glomerulonephritis and PS positive. IF was negative. OAC was confirmed and adjustment of anticoagulation dose for glomerular filtration rate resulted in improvement of Rfx.

Results
ARN is a not uncommon occurrence in cases of OAC and glomerular fragility (Table 1).

Conclusion
ARN should be suspected in predisposed patients in whom glomerular hyperfiltration or preexisting GN during OAC facilitate EG. Attention should be given to drug interactions that can induce an unrecognized OAC. The cases described underline the need for careful monitoring of U, RFx and FXa activity to promptly treat this complication, avoiding permanent damage.