Consult Rounds: Novel Sofosbuvir based Hep C agents and AKI

Can the novel agents used to treat hepatitis C cause AKI?

Most of the novel agents used to treat Hep C now in the current era are Sofosbuvir based. It has low rate of drug-drug interaction but kidney excretes over 70% of it’s major metabolite. This metabolite know as GS-331007 increases by ten fold in patients with renal dysfunction.

To my knowledge, no initial trials had any cases of AKI reported with this agent. Based on some recent trials using this agent, AKI might happen in 1-15% of patients treated with this agent.  Higher incidences were seen ( 45%) in liver transplant patients getting this agent. 

https://www.ncbi.nlm.nih.gov/pubmed/26923436

https://onlinelibrary.wiley.com/doi/full/10.1111/apt.14117

When?- 9-22 weeks of treatment.
Risk factors:- CKD, NSAID use, other nephrotoxic agent, DMII and ascites

Pathology:- what is the mechanism? There are only 4 published cases of kidney biopsy findings. We had published the first case of this in 2016 that showed AIN.  Subsequently, 3 other cases with AIN have been published and in one case ATN was also reported. It appears that the most likely mechanism is interstitial disease. In 2 of the 4 cases, 8 weeks was the time frame of injury, in remaining was 14 and 22 weeks of injury. It seems to be reversible in most cases.

https://accpjournals.onlinelibrary.wiley.com/doi/abs/10.1002/phar.1803

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496585/

https://europepmc.org/abstract/med/28656492

This is an interesting trend to watch. As we see less and less of Hep C induced renal disease, it is more likely we may see more treatment induced renal disease now.

A recent review of this topic is a good read.

Live from the consensus conference on "Optimal Testing of Live Donors to Prevent Transmission of Infectious Diseases"

What is the optimal testing strategy for testing live donors?

In a lecture given by Dr. Michael Ison, we can see that this is an area of great debate. We all agree that potential donors should have serology done for hepatitis b, hepatitis c, and HIV on initial visit. But should we repeat testing? Should we do repeat testing for everyone or should we repeat testing for high risk donors only? And what would this repeat testing mean? When is the optimal time to repeat this testing?
A suggestion was that possibly we can do repeat hepatitis B core and surface antigen testing, and nucleic acid testing for hcv and HIV. 7-14 weeks prior to surgery may be a good time to do these repeat testing.

Again, these tests can result in false positives, more costs, more patient anxiety, more visits and time spent to get blood drawn which can be looked at negatively.
More experience and studies are needed to tell us what exactly should be done. For now we need to follow our instincts and do what is best for the donor and recipient.