Supratherapeutic International Normalized Ratio causing Nephropathy: A Rare Adverse Effect of Warfarin

Abstract

There are many common causes of nephropathy (abnormal pathology of kidneys) such as diabetes, hypertension, autoimmune, and drugs. Amongst the drugs, warfarin has recently been recognized to cause nephropathy in rare cases. Warfarin-related nephropathy (WRN) is clinically defined as an increase in serum creatinine of 0.3 mg/dl within one week of international normalized ratio (INR) being greater than 3.A 61-year-old male was referred by his primary care physician (PCP) for having complaints of elevated creatinine associated with hematuria for one month. On evaluation with computed tomography (CT) of the abdomen/pelvis, it was revealed that he had small non-obstructing stones. The creatinine had increased from a baseline of 2.03 mg/dl to 6.8 mg/dl. Hemoglobin (Hb) had decreased from a baseline of 12.8 gm/dl to 8.1 gm/dl, the INR was 3.52. On subsequent days, the patient's renal function did not improve with fluids and supportive measures. Workup was unremarkable; therefore, a kidney biopsy was done. The biopsy specimen concluded the diagnosis of WRN. The patient was started on prednisone without any effect and then intermittent hemodialysis.Our case highlights the rare instance in which the cause of nephropathy is warfarin. If an early diagnosis had been made, the patient might have had a better prognosis; therefore, it is essential to have a high index of clinical suspicion when a patient presents with supratherapeutic INR and acute kidney injury (AKI) not getting better.

Warfarin-Related Nephropathy: Unveiling the Hidden Dangers of Anticoagulation

“…The renal biopsy reveal the presence of renal tubular red blood cell castsin both cases, WRN was diagnosed through typical clinical and pathological evidence. In terms of clinical characteristics, similar to the cases of WRN patients documented in the literature review [7][8][9][10][11][12][13], the two patients in the present study also exhibited gross hematuria and creatinine progression. WRN was initially characterized as AKI that occurs following excessive anticoagulation, with INR > 3 commonly regarded as indicative of excessive anticoagulation.…”

“…In previous literature, a total of ten cases of WRN con rmed by renal biopsy in patients with prosthetic valves were summarized [7][8][9][10][11][12][13]. The age range of the cases was between 50 and 76 years, with a time interval of 11 months to 26 years from the initiation of oral warfarin administration to the onset of WRN.…”

IgA Nephropathy Is the Most Common Underlying Disease in Patients With Anticoagulant-Related Nephropathy

“…We found 3 case series ( n = 63) 1 , 3 , 4 and 29 case reports describing histologic findings in patients with ARN. 2 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 Of 92 cases, 37 (40%) were compatible with IgAN. The main characteristics and outcomes of patients with ARN and IgAN available in the literature are summarized in Supplementary Table S1 .…”

“…To the best of our knowledge, at the present time, only 3 case series ( n = 63) 1 , 3 , 4 and 29 case reports have described histologic information on patients with ARN. 2 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 Of note, 37 of 92 (40%) cases were compatible with IgAN, comprising by far the most common underlying kidney disease associated to ARN. Moreover, in the largest series published to date of biopsy-proven ARN, IgA-predominant immune complexes in the glomeruli were observed in 34% of the patients (without specifying how many of them met IgAN criteria), representing the most frequent histologic lesion in kidney biopsies.…”

“…We used the search terms “anticoagulant-related nephropathy,” “warfarin-related nephropathy,” “hematuria and anticoagulant treatment,” “IgA nephropathy and anticoagulation,” OR “acute kidney injury” in combination with the terms “anticoagulation,” OR “anticoagulant therapy,” OR “anticoagulant treatment,” OR “warfarin,” OR “vitamin K antagonists,” OR “novel oral anticoagulants,” OR “hematuria,” OR “gross hematuria,” OR “macrohematuria.” Only English language papers were reviewed. This search revealed 3 case series 1 , 3 , 4 and 29 case reports, 2 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 comprising a total of 92 further cases of adult patients with biopsy-proven ARN.…”