warfarin is an oral vitamin k antagonist , which inhibits -carboxylation of clotting factors ii , vii , ix , and x. it is one of the most widely used drugs for treating and preventing thromboembolism . although very cheap and effective , warfarin use is potentially complicated by bleeding manifestations and over - anticoagulation . warfarin is mainly metabolized by cyp-2cp microsomal liver enzymes , which is affected by a multitude of different environmental factors , diet , drug interactions , and genetics , especially cyp2 complex mutations which can alter the pharmacokinetics and pharmacodynamics of warfarin metabolism leading to toxicity and prolonged international normalized ratio ( inr ) . the prothrombin time , standardized as the inr , is used to monitor warfarin anticoagulation . warfarin - related nephropathy ( wrn ) is a recently reported clinical entity , secondary to a prolonged inr . it can occur in patients with or without chronic kidney disease ( ckd ) and is associated with progression of ckd leading to a poor outcome . further studies also found that novel oral anticoagulants such as dabigatran also caused a similar syndrome and hence the term anticoagulant - related nephropathy is now used . a 33-year - old male , recently de - inducted from a high altitude area with no known prior comorbidities , was admitted to our center with breathlessness , dry cough , hemoptysis , and left - sided pleuritic chest pain of sudden onset . physical examination revealed tachypnea , tachycardia , and normal blood pressure . on systemic examination , the chest was clear and there were no cardiovascular localizing signs . the serum creatinine at admission was 0.9 mg / dl ( normal range - 0.81.1 mg / dl ) , blood urea was 20 mg / dl ( normal range - 2040 mg / dl ) , and urine examination was normal . chest x - ray , 2d echocardiography , and doppler scan of lower limbs and pelvic vessels were normal . a computed tomography pulmonary angiogram revealed acute pulmonary thromboembolism in the descending branch of the left pulmonary artery and the 2 order branch medial basal and superior segment of the right descending pulmonary artery ( modified well 's score - 4 ) . a serological workup including antineutrophil antibody , ds dna , complement c3/c4 levels , antineutrophil cytoplasmic antibody , and procoagulant studies was essentially normal . he was thrombolyzed with recombinant tissue plasminogen activator and thereafter started on low molecular weight heparin and bridged onto warfarin . on day 22 of the warfarin therapy , he again developed increasing left - sided chest pain and hematuria . his inr was 5.3 and his serum creatinine had also progressively risen to 2.6 mg / dl . his urine routine examination revealed albumin of 2 + , with numerous red blood cells ( rbcs ) and a 24 h urinary protein of 2292 mg / day . a pre- and post - renal cause for acute kidney injury ( aki ) was excluded , and a thorough drug history was also not contributory toward a cause for suspicion of acute interstitial nephritis . his warfarin was withheld and the coagulation parameters corrected with adequate blood component support . over the next few days , his azotemia showed a settling trend . as the inr normalized , a renal biopsy was done which showed the modest matrix expansion associated with vascular hyalinosis , glomerular congestion with rbcs [ figure 1 ] , and diffuse tubular damage with large and occlusive rbc casts in the tubules associated with interstitial hemosiderin laden macrophages suggestive of interstitial hemorrhage [ figure 2 ] . is maintained other than mild vascular hyalinosis ( h and e , 40 ) extensive and diffuse tubular damage . the interstitium shows focal areas of hemosiderin - laden macrophages suggestive of interstitial hemorrhage ( arrow ) pas stain ( 40 ) the patient was restarted on warfarin in escalating doses till a therapeutic inr was attained . at present , his renal functions have settled back to normal . warfarin can cause nephropathy by several mechanisms , namely acute interstitial nephritis , atheroembolism , direct mesangial damage , and the recently described wrn . wrn is defined as an acute increase in serum creatinine of > 0.3 mg / dl within 1 week of an inr > 3.0 . the cause of renal damage is glomerular hemorrhage and tubular rbc casts causing obstruction and inflammatory and oxidative damage to the tubular epithelial cells . warfarin is mainly metabolized by cyp-2cp microsomal liver enzymes , which is affected by a multitude of different environmental factors , diet , drug interactions , and genetics , especially cyp2 complex mutations which can alter the pharmacokinetics and pharmacodynamics of warfarin metabolism leading to toxicity and increase in the inr . in the pioneering study by brodsky et al . , wrn developed in 37.0% of patients with ckd , who had an inr > 3 and 20.5% of patients without ckd . there was no correlation between the inr increase and the rise in serum creatinine and the mean inr at which it occurred was around 4 . the major mechanisms for wrn are glomerular hemorrhage and tubular dysfunction by obstruction due to rbc casts . awareness of wrn is important because the subtle renal impairment can lead to long - term kidney damage and reduced gfr as seen in the study by brodsky sv et al . , where an episode of wrn - accelerated progression of ckd studied . studies revealed that this entity is also caused by other oral anticoagulants ; hence , the new term anticoagulant - related nephropathy . we suggest that wrn should always be considered a possible cause of aki occurring during episodes of over - anticoagulation and hence monitor the inr meticulously . it is usually a clinical diagnosis as biopsy is difficult due to the risk of bleeding ; however , a transvenous renal biopsy can be attempted in cases where it is felt obligatory by the treating nephrologist to rule out or confirm a diagnosis . early detection and timely intervention can go a long way in preventing renal damage leading to chronic kidney disease .
warfarin is an oral anticoagulant used extensively in clinical practice ; however , its side - effect of causing renal damage has been recently detected . 
 the mechanism leading to renal damage is glomerular hemorrhage and red blood cell tubular casts prothrombin time . 
 recently , it was found that warfarin causes renal damage in patients with chronic kidney disease and is also associated with progression of renal disease . 
 warfarin causing acute kidney injury in patients with normal renal function is a rare manifestation . 
 it is important to be aware of this condition as its innocuous presence can lead to chronic kidney disease if not corrected in time . 
 further studies have also found that novel oral anticoagulants such as dabigatran also cause a similar syndrome and hence a new term called anticoagulant - related nephropathy is now in vogue .