Relationship between Serum Symmetric Dimethylarginine Concentration and Glomerular Filtration Rate in Cats

Background Liver‐type fatty acid‐binding protein (L‐FABP) is a biomarker for early detection of renal disease in humans. Liver‐type fatty acid‐binding protein is cytotoxic oxidation products secreted from proximal tubules under ischemia and oxidative stress. Objective To examine renal expression and quantify urinary excretion of L‐FABP in catswith renal disease. Animals One hundred and thirty‐four client‐owned cats including 34 cats with serum creatinine (sCre) values >1.6 mg/dL and 10 other cats that died in clinics. Methods Tissue expressions of L‐FABP were examined by reverse transcription polymerase chain reaction and Western blotting. Urinary L‐FABP (uL‐FABP) and serum L‐FABP (sL‐FABP) levels were determined by enzyme‐linked immunosorbent assay. Anti‐liver‐type fatty acid‐binding protein antibody immunostained renal sections. Results Feline kidneys express L‐FABP. Strong L‐FABP signals were observed in the lumens of proximal tubular cells in 5 cats with high uL‐FABP excretion, but not in 5 cats with low uL‐FABP excretion. In 9 normal cats, uL‐FABP index was <1.2 μg/g urinary creatinine (uCre). High uL‐FABP indexes (>10.0 μg/g uCre) were detected in 7 of 100 cats with low sCre (<1.6 mg/dL) and 18 of 44 cats with high sCre (>1.6 mg/dL). There was a weak correlation between L‐FABP index and sCre, serum symmetric dimethylarginine (SDMA), or blood urea nitrogen (BUN), and these correlation coefficients were increased by analyzing only data of cats with sCre >1.6 mg/dL. There was a weak correlation between u L‐FABP index and sL‐FABP in all tested cats, but not in cats with high sCre. Conclusions and Clinical Importance This study demonstrates correlations between L‐FABP and current renal biomarkers for chronic kidney disease in cats, such as sCre and SDMA. Liver‐type fatty acid‐binding protein may be a potential biomarker to predict early pathophysiological events in feline kidneys.

Section: Discussionmentioning

confidence: 85%

Renal expression and urinary excretion of liver‐type fatty acid‐binding protein in cats with renal disease

Katayama

Ohata

Miyazaki

et al. 2020

“…Previous studies have demonstrated a strong relationship between serum SDMA and creatinine concentrations . Serum SDMA concentrations increase above normal when GFR decreases by approximately 40% below the normal rate, much earlier than the 75% decrease in GFR typically required for creatinine concentrations to increase above reference limits .…”

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confidence: 94%

“…Symmetric dimethylarginine is not protein‐bound in plasma, is eliminated primarily via renal excretion (>90%), is freely filtered by the glomerulus, and is not secreted or re‐absorbed by the tubules . In cats, SDMA concentrations correlate with GFR in an inverse linear relationship, with SDMA increasing as GFR decreases . All of these factors make SDMA a useful marker for GFR.…”

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confidence: 99%

Evaluation of Serum Symmetric Dimethylarginine Concentration as a Marker for Masked Chronic Kidney Disease in Cats With Hyperthyroidism

Peterson

Fv²,

Rishniw

et al. 2018

BackgroundHyperthyroidism can complicate (mask) the diagnosis of chronic kidney disease (CKD) because it increases glomerular filtration rate and decreases body muscle mass, both of which can lower serum creatinine concentrations. Currently, there is no clinical test that can reliably predict which hyperthyroid cats have concurrent azotemic CKD that will become apparent after treatment of the hyperthyroidism.ObjectivesTo investigate serum symmetric dimethylarginine (SDMA) concentration as a potential marker of masked azotemia in untreated hyperthyroid cats.AnimalsTwo hundred and sixty‐two hyperthyroid cats and 206 aged‐matched, clinically normal cats.MethodsProspective study. We measured creatinine, urea nitrogen, SDMA, T4, and TSH concentrations before and 1, 3, and 6 months after treatment with radioiodine (131I) and classified 131I‐treated cats as azotemic or nonazotemic based on persistent, post‐treatment creatinine concentrations >2.1 mg/dL. Groups were compared via nonparametric tests, and diagnostic accuracy was determined by receiver operating characteristic analysis and logistic regression.ResultsNo hyperthyroid cats were azotemic before treatment, but 42 (16%) became azotemic when rechecked at 4–8 months (median, 6 months) after 131I treatment; of these, 14 had high SDMA concentrations before treatment. As a diagnostic test for pre‐azotemic (masked) CKD in untreated hyperthyroid cats, SDMA showed a sensitivity of 33.3% and specificity of 97.7%.Conclusions and Clinical ImportanceFinding a high serum SDMA concentration in a hyperthyroid cat can help predict development of azotemia after treatment. The test has high diagnostic test specificity (few false‐positive results) but relatively low sensitivity (fails to predict azotemia in most hyperthyroid cats).

“…Recent studies determined that SDMA correlates strongly with GFR in cats with and without evidence of decreased renal function . Importantly, SDMA consistently increased months to years earlier than sCr in cats with naturally occurring CKD .…”

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confidence: 99%

Symmetric Dimethylarginine Assay Validation, Stability, and Evaluation as a Marker for the Early Detection of Chronic Kidney Disease in Dogs

Nabity

Lees

Boggess

et al. 2015

Self Cite

175

236

BackgroundSymmetric dimethylarginine (SDMA) is a small molecule formed by methylation of arginine, and released into blood during protein degradation. SDMA is primarily eliminated by renal excretion and is a promising endogenous marker of glomerular filtration rate (GFR).ObjectivesTo validate an assay for SDMA measurement, determine stability of SDMA in blood, and compare SDMA with serum creatinine concentration (sCr) and GFR for early detection of decreasing kidney function in dogs with chronic kidney disease (CKD).AnimalsEight male dogs affected with X‐linked hereditary nephropathy and 4 unaffected male littermates.MethodsProspective study validating SDMA measurement using liquid chromatography‐mass spectrometry, assessing stability of SDMA in serum and plasma, and serially determining sCr, SDMA, and GFR (using iohexol clearance) in dogs during progression from preclinical disease to end‐stage renal failure. Correlations were determined using linear regression. Timepoints at which sCr, SDMA, and GFR identified decreased renal function were compared using defined cutoffs, trending in an individual dog, and comparison with unaffected littermates.ResultsSymmetric dimethylarginine was highly stable in serum and plasma, and the assay demonstrated excellent analytical performance. In unaffected dogs, SDMA remained unchanged whereas in affected dogs, SDMA increased during disease progression, correlating strongly with an increase in sCr (r = 0.95) and decrease in GFR (r = −0.95). Although trending improved sCr's sensitivity, SDMA identified, on average, <20% decrease in GFR, which was earlier than sCr using any comparison method.Conclusions and Clinical ImportanceSymmetric dimethylarginine is useful for both early identification and monitoring of decreased renal function in dogs with CKD.