Classical and alternative renin-angiotensin-aldosterone systems in a feline remnant kidney model.

Objective: To characterize classical and alternative circulating renin-angiotensin-aldosterone system (RAAS) activities in cats with chronic kidney disease (CKD) induced by 11/12th functional nephrectomy.

Methods: This was a prospective study performed from September 9, 2022, through August 16, 2023. Serum was collected at 2 time points 6 months apart from young-adult purpose-bred cats with remnant kidney model-induced CKD (n = 15; 6 hypertensive, chronically treated with amlodipine besylate) and at a single time point from young-adult community-owned healthy cats (n = 15). Equilibrium concentrations of angiotensin I, II, III, IV, 1-5, and 1-7 and aldosterone as well as angiotensin-converting enzyme 2 activity were measured using LC-MS/MS. Kidney function was assessed 10 months after baseline RAAS evaluation in amenable CKD cats (n = 12) to identify progression (ie, 25% increase in serum concentration[s] of creatinine, symmetric dimethylarginine, or both). Linear mixed models were used for intergroup comparisons, accounting for blood pressure and amlodipine therapy.

Results: Serum aldosterone concentrations were higher in the CKD group than the healthy group; however, no angiotensin peptide concentrations differed significantly between groups. Amlodipine-treated CKD cats had higher concentrations of all RAAS markers than their nonhypertensive, amlodipine-naïve counterparts. Concentrations of RAAS markers at baseline in cats that experienced CKD progression (n = 3) were among the lowest of all CKD cats.

Conclusions: Evidence of RAAS activation at the level of circulating angiotensin peptides was not found in cats with induced CKD.

Clinical relevance: Although circulating aldosterone was increased in cats with induced CKD, this was not likely driven by an increase in other circulating RAAS components.