Initiation of diuretics or calcium channel blockers on the top of renin-angiotensin system inhibitors on kidney outcome: which is better?

We appreciate the study performed by Faucon et al.1 Faucon A.-L. Fu E.L. Stengel B. et al. A nationwide cohort study comparing the effectiveness of diuretics and calcium channel blockers on top of renin-angiotensin system inhibitors on chronic kidney disease progression and mortality. Kidney Int. 2023; 104: 542-551 Abstract Full Text Full Text PDF Scopus (0) Google Scholar and have read it with great interest. The authors conducted a nationwide, well-matched cohort study involving 5875 patients with nondialysis chronic kidney disease (CKD) stage 3–5. The study found that using a diuretic rather than a calcium channel blocker on top of renin-angiotensin system inhibitor (RASi) might improve kidney outcomes (CKD progression) without compromising cardioprotection. RASi is widely recognized as the first-line antihypertensive drug for patients with CKD, 2 Cheung A.K. Chang T.I. Cushman W.C. et al. Executive summary of the KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021; 99: 559-569 Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar but there is no optimal recommendation for the choice of second-line antihypertensive therapy, such as diuretics or calcium channel blockers, in CKD. 2 Cheung A.K. Chang T.I. Cushman W.C. et al. Executive summary of the KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021; 99: 559-569 Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar ,3 Williams B. Mancia G. Spiering W. et al. ESC Scientific Document Group2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018; 39: 3021-3104 Crossref PubMed Scopus (5918) Google Scholar Although this study may provide valuable insights into the management of hypertension in patients with CKD, there are 2 concerns that should be addressed. First, it is well established that the dosage of RASi is significantly associated with renal and cardiovascular events. 4 Liu J.C. Hsu Y.P. Wu S.Y. Statins and renin angiotensin system inhibitors dose-dependently protect hypertensive patients against dialysis risk. PLoS One. 2016; 11e0162588 Google Scholar However, the article does not provide data on whether the doses of RASi used in the 2 groups were balanced at baseline. Consequently, it is challenging to determine whether the observed differences in kidney outcomes are attributable to variations in the use of diuretics or calcium channel blockers or differences in RASi dosage. To address this, we recommend incorporating the variable of RASi dosage into the propensity score weighting. Second, given that there may be frequent switching of second-line antihypertensive drugs, it would be beneficial to conduct a sensitivity analysis with switching as a censoring factor. Overall, the findings are constructive, and we believe that the study can further enhance its applicability and credibility with the suggested refinements. A nationwide cohort study comparing the effectiveness of diuretics and calcium channel blockers on top of renin-angiotensin system inhibitors on chronic kidney disease progression and mortalityKidney InternationalVol. 104Issue 3PreviewIt is unknown whether initiating diuretics on top of renin-angiotensin system inhibitors (RASi) is superior to alternative antihypertensive agents such as calcium channel blockers (CCBs) in patients with chronic kidney disease (CKD). For this purpose, we emulated a target trial in the Swedish Renal Registry 2007-2022 that included nephrologist-referred patients with moderate-advanced CKD and treated with RASi, who initiated diuretics or CCB. Using propensity score-weighted cause-specific Cox regression, we compared risks of major adverse kidney events (MAKE; composite of kidney replacement therapy [KRT], experiencing over a 40% eGFR decline from baseline, or an eGFR under 15 ml/min per 1.73m2), major cardiovascular events (MACE; composite of cardiovascular death, myocardial infarction or stroke), and all-cause mortality. Full-Text PDF Open AccessThe authors replyKidney InternationalVol. 104Issue 5PreviewWei et al.1 argue that the observed outcome differences in our study addressing use of diuretics and calcium channel blockers (CCBs) on top of renin-angiotensin system inhibitors2 might be explained by residual confounding. Although this is a limitation of any observational study, including ours, we do not believe their concerns are likely to invalidate our findings. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend maximum-tolerated renin-angiotensin system inhibitor dose for these patients. Full-Text PDF