Correlation between urine anion gap and urine ammonia-creatinine ratio in healthy cats and cats with kidney disease.

BACKGROUND: Ammonium excretion decreases as kidney function decreases in several species, including cats, and may have predictive or prognostic value in patients with chronic kidney disease (CKD). Urine ammonia measurement is not readily available in clinical practice, and urine anion gap (UAG) has been proposed as a surrogate test. OBJECTIVES: Evaluate the correlation between urine ammonia-to-creatinine ratio (UACR) and UAG in healthy cats and those with CKD and determine if a significant difference exists between UAG of healthy cats and cats with CKD. ANIMALS: Urine samples collected from healthy client-owned cats (n = 59) and those with stable CKD (n = 17). METHODS: Urine electrolyte concentrations were measured using a commercial chemistry analyzer and UAG was calculated as ([sodium] + [potassium]) - [chloride]. Urine ammonia and creatinine concentrations had been measured previously using commercially available enzymatic assays and used to calculate UACR. Spearman's rank correlation coefficient between UAG and UACR was calculated for both groups. The UAG values of healthy cats and cats with CKD were assessed using the Mann-Whitney test (P < .05). RESULTS: The UAG was inversely correlated with UACR in healthy cats (P < .002, r0 = -0.40) but not in cats with CKD (P = .55; r0 = -0.15). A significant difference was found between UAG in healthy cats and those with CKD (P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: The UAG calculation cannot be used as a substitute for UACR in cats. The clinical relevance of UAG differences between healthy cats and those with CKD remains unknown.

Establishment of an RI for the urine ammonia-to-creatinine ratio in dogs.

BACKGROUND: Ammonia is produced and excreted by the kidney, contributing to systemic acid-base homeostasis through the production of bicarbonate. Disorders of acid-base balance can lead to many clinical problems and measuring ammonia excretion helps in determining if the kidneys are responding to acid-base challenges appropriately. Reference intervals are integral to clinical decision-making, and there is no current RI for the urine ammonia-to-creatinine ratio (UACR) in dogs. OBJECTIVE: This study aimed to generate an RI for the UACR in healthy adult dogs. METHODS: The study used adult, client-owned dogs that were presented to the University of Florida Primary Care and Dentistry service (n = 60). Physical examinations were performed and serum chemistry and urinalysis samples were obtained. Urine ammonia and creatinine concentrations were determined. Dogs were excluded if there were significant abnormalities in either their urinalysis or serum chemistry results. The RI for the UACR was calculated according to the recommendation of the American Society for Veterinary Clinical Pathology. Data were evaluated for correlation with serum bicarbonate, weight, age, and sex. RESULTS: The RIs for the UACR were 0.16-23.69 with 90% confidence intervals for the lower and upper limits of (0.13-1.17) and (20.50-23.75), respectively. No significant impact of age, sex, or weight was found. There was no discernable relationship between serum bicarbonate and UACR. CONCLUSIONS: Establishing an RI for UACR in healthy adult dogs will allow for further studies to determine if alterations are observed during specific disease states.

Role of the renal androgen receptor in sex differences in ammonia metabolism.

There are sex differences in renal ammonia metabolism and structure, many of which are mediated by testosterone. The goal of the present study was to determine the role of renal expression of testosterone's canonical receptor, androgen receptor (AR), in these sexual dimorphisms. We studied mice with kidney-specific AR deletion [KS-AR-knockout (KO)] generated using Cre/loxP techniques; control mice were Cre-negative littermates (wild type). In male but not female mice, KS-AR-KO increased ammonia excretion, which eliminated sex differences. Although renal structural size typically parallel ammonia excretion, KS-AR-KO decreased kidney size, cortical proximal tubule volume density, and cortical proximal tubule cell height in males-neither were altered in females and collecting duct volume density was unaltered in both sexes. Analysis of key protein involved in ammonia handling showed in male mice that KS-AR-KO increased both phosphoenolpyruvate carboxykinase (PEPCK) and Na+-K+-2Cl- cotransporter (NKCC2) expression and decreased Na+/H+ exchanger isoform 3 (NHE3) and electrogenic Na+-bicarbonate cotransporter 1 (NBCe1)-A expression. In female mice, KS-AR-KO did not alter these parameters. These effects occurred even though KS-AR-KO did not alter plasma testosterone, food intake, or serum Na+, K+, or [Formula: see text] significantly in either sex. In conclusion, AR-dependent signaling pathways in male, but not female, kidneys regulate PEPCK and NKCC2 expression and lead to the sexual differences in ammonia excretion. Opposing effects on NHE3 and NBCe1-A expression likely limit the magnitude of ammonia excretion changes. As AR is not present in the thick ascending limb, the effect of KS-AR-KO on NKCC2 expression is indirect. Finally, AR mediates the greater kidney size and proximal tubule volume density in male compared with female mice.NEW & NOTEWORTHY Sexual dimorphisms in ammonia metabolism involve androgen receptor (AR)-dependent signaling pathways in male, but not female, kidneys that lead to altered proximal tubule (PT), phosphoenolpyruvate carboxykinase, and thick ascending limb Na+-K+-2Cl- cotransporter expression. Adaptive responses in Na+/H+ exchanger 3 and electrogenic Na+-bicarbonate cotransporter 1-A expression limit the magnitude of the effect on ammonia excretion. Finally, the greater kidney size and PT volume density in male mice is the result of PT androgen signaling through AR.