Topic Discussion: Anticoagulation related nephropathy(ARN)

Anticoagulation-related nephropathy (ARN) is a significant but under-diagnosed complication of anticoagulation  We have heard of cases of warfarin nephropathy but why can't this happen with any anti coagulation.  A recent review illustrates the data for us.  Check out this review here.  ARN is currently defined as acute kidney injury (AKI) without obvious etiology in the setting of an International Normalized Ratio (INR) of > 3.0. Prior investigations into ARN have almost universally focused on anticoagulation with warfarin; however, recent case reports and animal studies

suggest that it can also occur in patients taking novel oral anticoagulants. 
It is important to consider this entity in our differential. Biopsy is not always possible as most of the cases present with high INR levels and risk of bleeding could be high. But in certain cases, perhaps possible too make a more distinct diagnosis.  The authors make some interesting and important recommendations for patients at risk for ARN

1. INR and renal function to be monitored every 3-4 weeks in first 3 months of starting anticoagulation as most of the ARN happens in 6-8 weeks following therapy.
2. Rapid increases in INR can cause AKI
3. Patients with moderate to severe CKD should have their renal function checked even more frequently.
4. If INR is supratheurapeutic, renal function should be checked more closely
5. Workup should include Urinalysis, urine electrolytes, renal sonogram and if negative and only finding is hematuria- ARN should be in the differential diagnosis. 
6. The data on the newer direct oral AC is minimal in CKD patients.  Renal function should be monitored in those patients closely as well as dosing might depend on crcl as well for those agents.

While the data is mostly in warfarin, the newer agents and the kidney might be at risk. Thus far only 1 case report as I linked earlier is noted with dabigatran but was also clouded with hx of IgA nephropathy and warfarin use.  Some of the complications of dabigatran related bleeding are due to the AKI or low clearance. Which came first? 

Regardless, AKI can be seen with glomerular bleeding and I have noted crt rising with INR rising and considered it in many cases.  Let's see if the newer oral ACs have this complication.  Uptodate even has a section on this now listed under ARN. 
My prior post on WRN in 2011 when it was first described.
Check out this other review as well
http://www.krcp-ksn.com/article/S2211-9132(14)00131-4/abstract

Topic Discussion: Warfarin Related Nephropathy

A commonly used agent is warfarin for anticoagulation.  Recently there have been some published case reports of warfarin induced nephropathy(WRN). More recent, an original article on the incidence and prevalence of this entity in CKD has also been mentioned.

What is this entity? High INR was associated with a rise in crt in biopsy of patients showed glomerular hemorrahge and renal tubular obstruction with red blood cell casts.  A recent retrospective review of over 15000 patients who were on warfarin and had an INR >3 and creatinine at the same time were reviewed.  A presumptive diagnosis of warfarin induced toxicity in the kidney was made if crt increased by 0.3mg/dl in 1 week after INR was >3.  WRN occurred in 20.5%,and 33% of the patients with CKD.  The mortality was also higher with people with this entity.  Other diagnosis that could have cause an acute renal injury were considered in those 4006 patients and carefully ruled out by looking at the chart.

The study highlighted few important points:
1. This entity should be considered in the differential diagnosis with AKI on warfarin
2. The risk factors to make this risk higher were age, DM, HTN and CVD but most important risk factor that doubled the risk was CKD.
3. Average INR to show this entity was only 4
4. The higher risk of WRN in CKD patients maybe be more likely due to having a sub therapeutic INR
5. There is no correlation of WRN and level of INR
6. WRN has substantial decreased survival rate but unclear if this is purely from WRN or other co morbid conditions.
7. Glomerular hemorrhage leading to tubular cast obstruction leading to ATN is the most likely mechanism
RFN also blogged about this in 2010 at
http://renalfellow.blogspot.com/2010/08/warfarin-induced-aki.html
Read more at the following references:
http://www.ncbi.nlm.nih.gov/pubmed/21389969
http://www.ncbi.nlm.nih.gov/pubmed/20413993
http://www.ncbi.nlm.nih.gov/pubmed/19577348