In the Limelight: November 2022 - Mayo Clinic Proceedings

Salient considerations in the management of patients with proteinuric chronic kidney disease (CKD) include blood pressure (BP) control; optimizing salt and water balance; correcting metabolic complications; and retarding the rate of decline of kidney function such that arrival of endstage kidney disease (ESKD) is delayed or, optimally, averted. As regards the latter, there is compelling evidence that angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) effectively delay the progression of CKD by actions that lower BP, proteinuria, and renal inflammation and fibrosis. However, as emphasized by the KDIGO 2021 Clinical Practice Guidelines for the Management of BP in CKD (https://www.kidney-international.org/article/S0085-2538(20)31270-9/fulltext), the efficacy of these agents in retarding the progression of proteinuric CKD requires that their doses be escalated to ones maximally approved and to the extent that such doses are tolerated; the rationale for this guideline is that such doses of these agents were generally employed in clinical trials that established their efficacy. The current study by Chu et al shows that in proteinuric CKD, ACEi/ARBs are often submaximally dosed. These authors used the database of the OptumLabs Data Warehouse to examine how ACEi/ARBs were dosed in over 100,000 adult patients in whom these medications were prescribed between January 1, 2017, and December 31, 2018. In these patients, overall, less than one third (29.8%) were administered maximal doses of ACEi/ARBs. The authors also defined criteria that may proscribe increasing the dose of ACEi/ARBs; these criteria included systolic BP less than 120 mmHg, serum potassium (K⁺) greater than 5.0 mEq/L, an eGFR lower than 15 ml/min per 1.73 m², and the occurrence of acute kidney injury (AKI) within the preceding year. In patients without these criteria (approximately 75,000), the percentage of patients who received maximal doses of ACEi/ARBs marginally increased to 32.3%. Submaximal ACEi/ARB dosing was more likely to occur in patients who were less than 40 years old, female, Hispanic, or those patients exhibiting a lower BP, a higher serum K⁺, a prior episode of AKI, less albuminuria, concomitant heart failure, or absence of diabetes. It should be noted that while some of these proscriptions against dose escalation may be absolute (for example, low BP), others are relative and can be safely managed (for example, marginally elevated serum K⁺ which can be controlled by increased doses of loop diuretics and/or by newer K⁺-binding agents). The progression of CKD to ESKD markedly increases morbidity and mortality, necessitates new therapies, and significantly alters the life of a patient with CKD. Delaying this outcome can be achieved by ACEi/ARBs, but the full efficacy of these agents is dose-dependent.

Chu CD, Powe NR, Estrella MM, et al. Submaximal angiotensin-converting enzyme inhibitor and angiotensin receptor blocker dosing among persons with proteinuria. Mayo Clin Proc. 2022;97(11):2099-2106. doi.org/10.1016/j.mayocp.22.07.010