ABSTRACT. The serum cystatin C (Cys-C) concentration is a better filtration marker than plasma creatinine (Cre) concentration in humans. In veterinary medicine, a few studies have shown that the serum Cys-C concentration in dogs is also a better marker than the plasma Cre concentration. The purpose of this study is to evaluate the applicability of measuring the serum Cys-C concentration by an enzymelinked immunosorbent assay (ELISA) as a marker of the glomerular filtration rate in dogs with various renal dysfunctions. The serum Cys-C concentration in dogs with chronic kidney disease (CKD) was significantly higher (1.23  0.21 mg/L) than that in 76 control dogs (0.85  0.15) (P<0.001). The reference range of the serum Cys-C concentrations in samples from the 76 control dogs was 0.55-1.15 mg/l. Serum Cys-C concentration was more strongly correlated with plasma iohexol clearance (r=-0.704, P<0.001) than plasma Cre concentration in dogs (r=-0.598, P<0.001). In a receiver operating characteristics analysis, significant differences between the serum Cys-C and plasma Cre concentrations were found with regard to their AUC (0.949, [SE, 0.019] and 0.849 [SE, 0.029]) and diagnostic sensitivity (90.3% and 73.6%) for detecting decreased PCio (P<0.05). Therefore, the measurement of serum Cys-C concentration by ELISA is more useful for the detection of early CKD than measuring the plasma Cre concentration.KEY WORDS: chronic kidney disease, cystatin C, glomerular filtration rate.

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ABSTRACT. Chronic kidney disease is one of the most common disorders in dogs and cats. The plasma urea nitrogen (P-UN) and creatinine (P-Cre) concentrations are not sufficiently sensitive for early diagnosis of renal dysfunction. Although urine and plasma clearance methods allow earlier detection of reductions in the GFR, it is difficult to estimate a mildly reduced GFR from the values obtained by these methods, as they are also affected by physiological factors, such as body weight (BW) and age. The present study is a retrospective survey designed to assess the factors that affect markers of kidney function and to revaluate the clinical utility of the markers, including P-UN, P-Cre and GFR determined by plasma iohexol clearance (PCio) in dogs and cats. The P-UN, P-Cre and PCio values in dogs and the P-Cre and PCio values in cats were significantly correlated with BW (P<0.001). PCio in smaller dogs (15.0 kg) was significantly and inversely correlated with age. In smaller dogs, increase of P-UN alone might warrant a suspicion of a decreased GFR, but in contrast, P-Cre may be inefficient for detecting renal dysfunction or determining the severity of CKD compared with that in larger dogs ( 15.1 kg). P-Cre in larger dogs correlated better with PCio than in smaller dogs, suggesting that P-Cre in larger dogs was a more sensitive marker of reduced GFR.KEY WORDS: body weight, plasma creatinine, plasma iohexol clearance, plasma urea nitrogen.J. Vet. Med. Sci. 72(9): 1129-1136, 2010 Chronic kidney disease (CKD) is one of the most common disorders and is a common cause of death in dogs and cats. The prevalence of renal diseases has been reported to range from 0.5 to 7% in dogs and from 1.6 to 20% in cats [29,43]. Although CKD occurs in dogs and cats of all ages, the mortality of CKD commonly increases with age. In human and veterinary medicine, CKD is diagnosed by detecting chronic decreases in the glomerular filtration rate (GFR) or the presence of chronic renal damage [4,36]. GFR can be evaluated indirectly from the concentrations of plasma and urine markers, which are dependent on the amount eliminated by the kidneys. The plasma urea nitrogen (P-UN) and creatinine (P-Cre) concentrations are widely used as endogenous markers to evaluate renal function in dogs and cats because they can be easily, rapidly and cheaply measured. GFR is measured directly by urine or plasma clearance methods using inulin, creatinine or iohexol [7,14,15,20,21,33,34]. Although the urinary clearances of inulin and creatinine are considered to be the gold standards for measuring GFR in humans and animals, these methods are impractical in clinical settings because they require insertion of a bladder catheter, which is associated with a risk of developing a urinary tract infection or urethral injury; complete collection of a timed urine sample; and continuous infusion of the marker. The single injection technique can be used to determine plasma clearance from the elimination curve of a marker in plasma after a bolus injection. Plasma clearance ca...

ABSTRACT. The diagnostic significance of the plasma concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) was evaluated in 72 dogs with mitral valve insufficiency and 36 control dogs. In the controls, the plasma NT-proBNP concentration was 163.9  114.7 (SD) pmol/l. The values in those with International Small Animal Cardiac Health Council (ISACHC) functional classification of heart failure class Ia, Ib, II and IIIa mitral valve insufficiency were 302.8  257.1 (n=21), 634.2  642.5 (n=23), 1,277.9  756.2 (n=18) and 1,908.9  538.8 (n=10) pmol/l, respectively; those in the class Ib or severer groups were significantly higher than that in the controls. In dogs in which the intensity of cardiac murmurs was Levine 3, 4, 5 and 6, plasma NT-proBNP concentrations were 647.6  577.3 (n=27), 1,184.7  841.0 (n=18), 1,532.4  784.2 (n=10) and 1,461.8  932.2 (n=4) pmol/l, respectively, and were significantly higher than that in the controls. The plasma NT-proBNP concentration was significantly correlated with the cardiac size (VHS) and LA/Ao (r=0.611, n=89, p<0.01; and r=0.705, n=91, p<0.01, respectively). When dogs with ISACHC class II or IIIa were regarded as heart failure, the cut-off value was 713.5 pmol/l, and the sensitivity and specificity were 0.913 and 0.857, respectively. These findings could indicate that plasma NT-proBNP concentration was significantly associated with the severity of heart failure due to mitral valve insufficiency in dogs. Further investigation is required to determine factors other than heart failure affecting plasma NT-proBNP concentration.KEY WORDS: canine, mitral valve insufficiency, NT-pro BNP.

ABSTRACT. Plasma iohexol clearance (PCio) is a practical method for measuring the glomerular filtration rate (GFR) in clinical settings. However, it is too time-consuming for routine application and requires hospitalization for at least half a day. Therefore, the development of a simpler procedure for plasma clearance is necessary to allow the frequent measurement of GFR in clinical settings. The purpose of the present study was to evaluate a single sampling method for estimation of PCio in dogs and cats with various kidney functions. The PCio determined by the 1-compartment model using 3 samples (PCio 3samples ) was used as a reference for the evaluation of the single sampling method (PCio single ). Plasma iohexol concentration was determined by a cerium arsenite colorimetric method.

ABSTRACT. We evaluated the diagnostic significance of the N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration in asymptomatic cats with cardiac enlargement. The plasma NT-proBNP concentration was measured in 21 clinically healthy control cats, and 67 asymptomatic cats with cardiac enlargement defined as end-diastolic interventricular septum thickness (IVSd) and/or diastolic left ventricular posterior wall thickness (LVPWd) >0.6 cm, vertebla heart scale (VHS) >7.8, and/or left atria/aorta ratio (LA/Ao) >1.5. The plasma NT-proBNP concentration in the asymptomatic cats with cardiac enlargement (median: 662.0, range: 24.0-2,449.0 pmol/l) was significantly higher than that in the controls (24.0, 24.0-95.0 pmol/l, P<0.001). The plasma NT-proBNP concentration was significantly correlated with the VHS, LA/Ao, IVSd and LVPWd (r=0.578, P<0.001; r=0.462, P<0.001; r=0.563, P<0.001; and r=0.764, P<0.001, respectively). Receiver operating characteristic analysis showed a cut-off value of 95.0 pmol/l for the detection of asymptomatic cats with cardiac enlargement, sensitivity and specificity of 88.1 and 100%, respectively, and an area under the curve of 0.971. These results suggest that the determination of the plasma NT-proBNP concentration can be a useful screening test for asymptomatic cats with cardiac enlargement.

Objectives To examine the relationship between fibroblast growth factor‐23 levels, chronic kidney disease severity and mineral metabolic disorders associated to chronic kidney disease in dogs. Materials and Methods Fifteen control and 75 chronic kidney disease dogs were retrospectively included. Serum fibroblast growth factor‐23 concentration and other phosphate metabolite parameters were compared between controls and each International Renal Interest Society stage. Multiple regression analysis was performed to determine the predictors of fibroblast growth factor‐23. Results Serum fibroblast growth factor‐23 concentrations were significantly higher in dogs with IRIS stages 2, 3 and 4 chronic kidney disease than those in dogs in control group and with stage 1 and increased along with the severity of chronic kidney disease. Compared with control dogs, serum intact parathyroid hormone significantly increased from stage 2 and serum phosphorus concentrations increased in dogs with stage 4. In dogs with stage 2, fibroblast growth factor‐23 levels significantly increased in those with hyperphosphatemia compared with those with normophosphatemia. While eight of 26 (30.8%) dogs with stage 2 developed hyperparathyroidism (intact parathyroid hormone>8.5 ng/L), 19 (73.1%) dogs with stage 2 had elevated fibroblast growth factor‐23 levels above the reference range (>528 pg/mL). Log creatinine, log intact parathyroid hormone and log product of total calcium and phosphorus were independent predictors of log fibroblast growth factor‐23. Clinical Significance This preliminary study suggests that canine fibroblast growth factor‐23 might be involved in mineral metabolic disorders associated to chronic kidney disease in dogs, and this factor could be potentially used as an early marker for this condition.

Objectives The aim of this study was to investigate serum fibroblast growth factor (FGF)-23 concentrations in young and mature adult cats with chronic kidney disease (CKD). Methods The present study retrospectively investigated the serum samples and medical records of 1–8-year-old clinically healthy cats (control group, n = 7) and cats with CKD (n = 54). Cats with CKD were divided into four stages based on serum creatinine concentrations, according to the International Renal Interest Society (IRIS) CKD guidelines. Serum FGF-23 concentrations were compared between cats in the control group, IRIS stages 1, 2 and 3–4 CKD. Continuous variables were analysed using correlations and multiple linear regression. Results Serum FGF-23 concentrations were significantly higher in cats with IRIS stages 1, 2 and 3–4 CKD, compared with those in the control group ( P = 0.02, P = 0.002 and P = 0.002, respectively). Additionally, serum FGF-23 concentrations in cats with IRIS stages 3–4 CKD had higher serum FGF-23 concentrations than those with IRIS stages 1 and 2 CKD ( P = 0.04 and P = 0.02, respectively). In the multiple linear regression analysis, serum urea nitrogen concentration, serum phosphorus concentration and blood ionised calcium concentration were independent variables predicting serum FGF-23 concentration. Conclusions and relevance Serum FGF-23 concentrations in younger cats with CKD increased in early-stage CKD and were associated with mineral metabolic markers, as also occurs in geriatric cats.