Serum Concentrations of Symmetric Dimethylarginine and Creatinine in Dogs with Naturally Occurring Chronic Kidney Disease

Abstract

Background: Serum concentrations of symmetric dimethylarginine (SDMA) detected chronic kidney disease (CKD) in cats an average of 17.0 months before serum creatinine (Cr) concentrations increased above the reference interval.

Objectives: To report on the utility of measuring serum SDMA concentrations in dogs for detection of CKD before diagnosis by measurement of serum Cr.

Animals: CKD dogs (n = 19) included those persistently azotemic for ≥3 months (n = 5), dogs that were azotemic at the time of death (n = 4), and nonazotemic dogs (n = 10). CKD dogs were compared with healthy control dogs (n = 20).

Methods: Retrospective study, whereby serum Cr concentrations were determined by enzymatic colorimetry and serum SDMA concentrations were determined by liquid chromatography-mass spectrometry in dogs with necropsy confirmed CKD.

Results: Serum SDMA increased before serum Cr in 17 of 19 dogs (mean, 9.8 months; range, 2.2-27.0 months). Duration of elevations in serum SDMA concentrations before the dog developed azotemia (N = 1) or before the dog died (N = 1) was not determined. Serum SDMA and Cr concentrations were linearly related (r = 0.84; P < .001). Serum SDMA (r = -0.80) and serum Cr (r = -0.89) concentrations were significantly related to glomerular filtration rate (both P < .001).

Conclusion and clinical importance: Using serum SDMA as a biomarker for CKD allows earlier detection of kidney dysfunction in dogs than does measurement of serum Cr. Earlier detection might be desirable for initiating renoprotective interventions that slow progression of kidney disease.

Keywords: Canine; Endogenous; Pet foods; Predictor.

Figure 1

Relationship between serum symmetric dimethylarginine (SDMA; μg/dL) and serum creatinine (Cr; mg/dL) concentrations in 20 healthy dogs (mean age, 10.5 years; range, 8.2–13.3 years; circles) and 19 dogs with chronic renal disease (CKD). CKD dogs are shown at 3 time points: before serum SDMA concentrations were elevated (≥14 μg/dL; mean age, 11.7 years; range, 5.9–15.3 years; diamonds), at the time serum SDMA concentrations were first detected as elevated (mean age, 12.8 years; range, 6.5–15.8 years; squares), and when serum Cr concentrations were first detected as elevated (≥1.4 mg/dL) or at death (mean age, 13.6 years; range, 8.6–16.1 years; triangles). There is a positive linear relationship between serum SDMA and serum Cr concentrations (r = 0.84; P < .001). No dogs with serum Cr concentrations above the reference interval (≥1.4 mg/dL) had normal serum SDMA concentrations (<14 μg/dL).

Figure 2

Representative dog (neutered male) with serum symmetric dimethylarginine (SDMA; red bars) and serum creatinine (Cr; blue bars) concentrations indicated across time. Serum SDMA was increased at 8.0 years (15 μg/dL). Glomerular filtration rate was measured at 8.7 years and found to be 1.45 mL/min/kg, which was 67% below the mean of 4.38 mL/min/kg for the healthy control dogs. The dog became azotemic at 9.9 years (serum Cr, 1.60 mg/dL), approximately 22 months after serum SDMA was increased. The dog died at 10.7 years. Renal histopathology revealed lymphocytic/plasmacytic interstitial nephritis with interstitial and periglomerular fibrosis, glomerulosclerosis, and tubular proteinosis. The horizontal line represents the upper limit of the reference intervals for serum Cr and SDMA concentrations.