Warp Speed Drugs for Kidney diseases 2021

 In ASN Kidney News 2021, Feb issue, I created this figure that gives a sense of the amazing rapid development for kidney disease therapeutics. The figure appears in the Feb issue of kidney news. Created using biorender.com 

Topic Discussion: ACEI/ARB ( hold em or keep them going)

 The COVID19 pandemic has ignited an ongoing saga of holding ACEi/ARB when someone is hospitalized. Normally a consult note in nephrology would include holding of these agents before a cardiac cath, CABG, or major procedure ( with little data on doing it).

A recent study in JASN done using a novel methodology showed no real benefit in stopping these agents in late stage CKD patients in the Swedish Renal Registry for the last 10 years.  Advanced CKD ( GFR<30) on these agents were evaluated. A target trial emulsion technique was used on risk of stopping these agents for 6 months and their outcomes on 5 year mortality, and MACE and KRT. So while KRT risk increased, the MACE and mortality decreased. MACE was mainly driven by mortality. In this nationwide observational study of people with advanced CKD, stopping RAS inhibition was associated with higher absolute risks of mortality and major adverse cardiovascular events, but also with a lower absolute risk of initiating KRT.

Meanwhile, in the COVID19 world,  REPLACE COVID published in Lancet was published. This trial began on March 31, 2020, within a few months of COVID-19 hitting North America and in the thick of the first wave. All COVID19 patients hospitalized , already on chronic ACEi or ARB  were randomized to either continue or stop their ACEi or ARB. In terms of the results, there was absolutely no difference in any of the outcomes, all cause death and length of stay. There was also no difference in the exploratory outcomes of ICU admission, ventilation, or hypotension requiring hemodynamics support. These findings are also bolstered by the similar findings from the BRACE CORONA trial published in JAMA in a slightly less sick cohort of 659 patients showing similar results. The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression.  The study found that in patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These two trial (RCTs done in pandemic)  findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with COVID19.  Check out this nice editorial on this in ASN kidney news 2021

There is an ongoing trial called STOP-ACEi. Do we really need that trial? Given we were able to do an RCT in a middle of a pandemic with sick patients with COVID19 and that showed no real difference in terms of outcomes of holding ACEi or ARBs, my guess is that STOP-ACEi will show the same. Unless there is hyperkalemia, or hypotension, no real strong indication to hold or stop these life saving cardiac medications.

Culture change will take time:  It is hard to convince nephrologists to start ACEi/ARB in late stage CKD, let alone convincing hospitalists or internists. It is hard to NOT to hold ACEi/ARB when creatinine is rising during an acute cardio-renal syndrome- convincing will take time. Hope these trials will help us continue these life saving agents in hospitalized patients( and ok to even stop them) but sometimes- nobody restarts them on discharge...