Background
The aim of this study was to report the prevalence and mortality associated with anticoagulant-related nephropathy (ARN) through a systematic review of the literature.
Methods
Electronic searches were conducted in the Medline and EMBASE databases, and manual searches were performed in the reference lists of the identified studies. The studies were selected by two independent researchers, first by evaluating the titles and abstracts and then by reading the complete texts of the identified studies. Case series, cross-sectional studies, cohort studies and case–control studies reporting the prevalence and factors associated with ARN were selected. The methodological quality was assessed using the Newcastle–Ottawa scale. Meta-analyses of the prevalence of ARN and 5-year mortality using the random effects model were performed when possible. Heterogeneity was assessed using the I2 statistic.
Results
Five studies were included. Prevalence of ARN ranged from 19% to 63% among the four included cohort studies. Meta-analysis of these resulted in high heterogeneity [I2 96%, summary effect 31%; 95% confidence interval (CI) 22–42%]. Subgroup meta-analysis yielded an ARN prevalence of 20% among studies that included patients with fewer comorbidities (I2 12%; 95% CI 19–22%). In a direct comparison, meta-analysis of the 5-year mortality rate between anticoagulated patients who had experienced ARN and anticoagulated patients without ARN, patients with ARN were 91% more likely to die (risk ratio = 1.91; 95% CI 1.22–3; I2 87%). Risk factors for ARN that were reported in the literature included initial excessive anticoagulation, chronic kidney disease, age, diabetes, hypertension, cardiovascular disease and heart failure.
Conclusions
ARN studies are scarce and heterogeneous, and present significant methodological limitations. The high prevalence of ARN reported herein suggests that this entity is underdiagnosed in clinical practice. Mortality in patients with ARN seems to be high compared with patients without this condition in observational studies.
Carbonic anhydrase inhibitors, such as acetazolamide, are widely used in the treatment of open-angle glaucoma. Severe metabolic acidosis is a rare complication of acetazolamide use, and life-threatening acidosis occurs most commonly in elderly patients, in patients with advanced renal failure, and in patients with diabetes. We describe an unusual case of an elderly patient with diabetic nephropathy and chronic renal failure who presented to the emergency department with severe metabolic acidosis and coma after exposure to high doses of acetazolamide in the postoperative period of ophthalmic surgery. As symptoms of acetazolamide intoxication and uremia are similar, high suspicion is required to detect excessive plasma drug concentrations and intoxication in patients presenting with concomitant uremia. Clinical symptoms are potentially reversible with prompt diagnosis and treatment, including supportive treatment, bicarbonate therapy, and renal replacement therapy. Hemodialysis is particularly helpful in the management of acetazolamide overdose as the medication is dialyzable.
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