Friday, August 7, 2015

Drug induced renal injury:- a consensus classification.

A recent article in KI 2015 discusses categorizing all drug induced AKI based on certain types and following few strict guidelines.  This ensures that the effect was clearly to a culprit drug and gives an idea of type of injury.
1.       Phenotype description: Glomerular, tubular dysfunction, AKI and nephrolithiasis/crystalluria
2.       Tubular dysfunction refers to RTA, Fanconis, SIADH, DI, phosphate wasting
3.       AKI refers to ATN, AIN or osmotic nephrosis. While not discussed in article- pre renal insult from pharmacologic agents might be under this category as well
4.       The mechanism then is divided in two types A and B.  Type A reaction are dose dependent toxicities and that are predictable based on drug exposure and pharmacology of agent for example aminoglycoside.  Type B reaction is unpredictable such as AIN from PPI or any agent for the matter.  A Type B reaction in glomerular category would be hydralazine or PTU induced lupus nephritis.
5.       Same drug can cause Type A or B reaction.
6.       Time course:  Acute ( 1-7 days),  sub acute (8-90 days) and chronic(>90 days).
7.       Setting: Hospitalized vs outpatient setting.  Outpatient setting drug injury is the most missed type as not easy to recognize as compared to inpatient setting as more reliable and easily visible data by consultants.
8.       The authors propose that drug induced kidney injury meet the following criteria:
a.       The drug exposure must be 24 hours before renal event
b.      Reasonable evidence for biological plausibility for the casual drug
c.       Complete data( full medication list, biomarker comparison)
d.      Strength of the relationship between attributable drug and phenotype should be based on drug exposure and duration, extent of primary and secondary criteria met and the time course of injury.
9.       Transient factors that affect change is important to know- BP trends, infections, and medications that can alter hemodynamics
10.   Kidney biopsy should be used to define ATN vs AIN or Gn to better get the phenotype.
11.   In patients with CKD, reference baseline crt might be used to use as value to which crt might return back to.  In cases of AIN, the crt may take much longer to return to baseline—making it a sub acute injury.
12.   Tools such as the Naranjo scale can be used to help guide but sometimes with multi drug exposure and other events, this might be not that helpful.

13.   This is an interesting start to a common problem we face. Sometimes biopsies are not that easy in the sick patient and guidance tools as this paper might be useful.    

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