What is your approach to GDMT uptitration (particularly dosing for ARBs/ARNIs/MRA) if there is further evidence of renal dysfunction, especially in situations with worsening AKI on CKD?  

Titration of RAAS inhibitors in the setting of AKI on CKD is challenging. First, look at the patient: if they have an increase in Cr after an increase in the RAAS inhibitor but no/stable HF symptoms and appear euvolemic on examination, then I will decrease diuretic therapy and see if the Cr improves/stabilizes. If, however, they have worsening HF symptoms and/or symptomatic hypotension after the increase in the RAAS inhibitor, I will reduce back to the prior tolerated dose. The latter situation may be a marker of advanced HF requiring a discussion of therapies such as heart transplantation/LVAD in eligible patients.

I completely agree with Dr. @Dr. First Last's approach. Correlating the data with blood pressure and volemia is key to making the decision. It's important to point out that defaulting to reduce the doses may harm the patient in the long term as these patients can easily be labeled "intolerant" or at max dose when they may not be.

I think the approach by Dr. @Dr. First Last is great. Additionally, you must consider the role of cardiac output and venous congestion when assessing the true renal congestive pathway and RAAS effect. Patient Stevenson Profiles are important to understand if the worsening renal function results from poor cardiac output or increased venous congestion in combination with poor cardiac output. Hemodynamic assessment is important in patients with recurrent admission or refractoriness to GDMT optimization, irrespective of their LVEF. The cardiac index is an important prognostic marker for patients in which GDMT withdrawal occurs and should be aggressively managed or considered for advanced therapies (Grinstein et al., PMID 37352965).