Anticoagulant-related nephropathy (ARN) is a form of acute kidney injury that mainly occurs in patients with previously unrecognized glomerular disease in addition to excessive anticoagulation. Since ...a renal biopsy is not performed in most cases, the diagnosis is often presumptive.
Here, we present the characteristics of a national Slovenian patient cohort with histologically verified ARN, from the first case in 2014 to December 2020, and a review of the current literature (Pubmed database).
In Slovenia, ARN has been detected in 13 patients, seven of whom were treated with coumarins, and others with direct oral anticoagulants. In seven patients, ARN appeared after excessive anticoagulation. As many as 11 patients had underlying IgA nephropathy. Similar to the global data presented here, the pathohistological impairment associated with pre-existing glomerulopathy was mild and disproportionate to the degree of functional renal impairment. The majority of our patients with ARN experienced severe deterioration of renal function associated with histological signs of accompanying acute tubular injury, interstitial edema, and occlusive red blood cell casts. These patients were treated with corticosteroids, which (in addition to supportive treatment and discontinuation of the anticoagulant drug) led to a further improvement in renal function.
Anticoagulant therapy combined with a pre-existing glomerular injury may lead to ARN. In addition to discontinuation of the anticoagulant and supportive care, corticosteroids, which are currently listed in only a few cases in the world literature, may have a positive influence on the course of treatment. However, the benefits of steroid treatment must be weighed against the risk of complications, especially life-threatening infections.
Background and objectives
Warfarin-related nephropathy is reported to occur with an INR >3.0 as a result of glomerular bleeding. There is a lack of prospective studies examining the effect of ...supratherapeutic warfarin anticoagulation on haematuria and acute kidney injury (AKI). Older patients may be susceptible due to greater warfarin use, prevalence of kidney disease and comorbidities. The objective of this study was to determine the incidence and nature of haematuria and AKI in older patients on warfarin and to determine any association with high INR levels.
Design, setting, participants and measurements
This was a prospective, observational study of 150 elderly patients receiving warfarin anticoagulation who were acutely hospitalised in a tertiary hospital. AKI was assessed using RIFLE criteria. Urinalysis was performed to quantify haematuria, characterise erythrocyte morphology and measure the albumin–creatinine ratio. Positive cases received follow-up at 4–6 weeks to determine resolution.
Results
An INR >3.0 was found in 54 % of patients. Pre-admission antibiotic use increased the risk of excessive anticoagulation. The incidence of isolated AKI, isolated haematuria and both was 18.7, 13.3 and 12 %, respectively. Factors associated with a higher risk of haematuria were an INR >4.0, non-urinary infection, catheterisation and albuminuria. Most cases of AKI were mild, and there was no demonstrable correlation between the admission INR and AKI. Admission with heart failure was significantly associated with an increased risk of persistent kidney impairment at follow-up.
Conclusions
Supratherapeutic warfarin anticoagulation was associated with an increased risk of haematuria, but not with AKI. The majority of cases of haematuria were transient.
Recent studies suggest that overanticoagulation impairs renal function in patients on warfarin therapy, due to renal tubular obstruction from glomerular hemorrhage.
Data from the Rotterdam Study (The ...Netherlands), a prospective population-based cohort study of patients 55 years and older, were used for this study. Information on vitamin K antagonist (VKA) therapy was obtained from the regional anticoagulation clinic, where prothrombin times were monitored every 1-6 weeks depending on target level and stability of the international normalized ratio (INR). Linear regression was performed to study the association between the cumulative number of instances of overanticoagulation (defined as a measurement of an INR >6.0) and the change in renal function between baseline and third examination round based on estimated glomerular filtration rate (CKD-EPI equation). Age, sex, baseline renal function, baseline and incident heart failure, and indication for VKA therapy were included as potential confounders.
Information was available for analysis on 2,802 study participants in whom overanticoagulation was significantly associated with a decline in renal function, after adjustment for confounding by age, sex, heart failure, baseline glomerular filtration rate and indication for VKA therapy (-0.180 ml/min per 1.73 m(2) per year per event for INR >6.0, p = 0.030).
Overanticoagulation (INR >6.0) is associated with a decline in renal function. Further studies are needed to evaluate the causal role of different degrees of overanticoagulation, including transient effects, in high-risk groups, and the association with the new oral anticoagulants.
PDF
