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.