Serum cystatin C concentration can be used to evaluate glomerular filtration rate in small dogs

Serum cystatin C levels (CysC) are used in human medicine to document progressive kidney failure. Although CysC are not thought to be useful for the diagnosis of kidney dysfunction in dogs, there has been no specific consideration of body weight as a confounding issue. The aim of this study was to assess that the utility of CysC for the diagnosis of decreased glomerular filtration rate (GFR) in smaller vs. larger dogs. In clinically healthy dogs, serum creatinine (Cre) and CysC correlate directly with body weight; we found that dogs weighing <20 kg had significantly lower CysC than those weighing ≥20 kg (0.27 ± 0.07 vs. 0.34 ± 0.05 mg/l, respectively, P<0.001). In dogs weighing <20 kg, CysC had superior diagnostic accuracy for the detection of mildly decreased plasma iohexol clearance (PCio) (<1.8 ml/min/kg) compared with Cre (sensitivity 100% vs. 80.9% and specificity 100% vs. 85.7%); this was not true for dogs weighing ≥20 kg. Additionally, using a cut-off PCio of <1.8 ml/min/kg, the area under receiver-operating characteristics curve (AUC) of CysC was significantly higher than that of Cre in dogs weighing <20 kg (P<0.05); this was not true for dogs weighing ≥20 kg (P=0.695). In conclusion, CysC is a useful marker for the detection of a mild decreasing GFR compared with Cre in dogs weighing <20 kg.     

Relationship of glomerular filtration rate based on serum iodixanol clearance to IRIS staging in cats with chronic kidney disease

We examined the correlation between the glomerular filtration rate (GFR) estimated from an equation based on the serum iodixanol clearance technique and International Renal Interest Society (IRIS) stages of chronic kidney disease (CKD) in cats. The equation included the injection dose, sampling time, serum concentration and estimated volume of distribution (Vd) of the isotonic, nonionic, contrast medium iodixanol as a test tracer. The percent changes in the median basal GFR values calculated from the equation in CKD cats resembled those of IRIS stages 1–3. These data validate the association between the GFR derived from the simplified equation and IRIS stages based on the serum creatinine concentration in cats with CKD. They describe the GFR ranges determined using single-sample iodixanol clearance for healthy cats and cats with various IRIS stages of CKD.     

Assessment of glomerular filtration rate with dynamic computed tomography in normal Beagle dogs

The objective of our study was to determine individual and global glomerular filtration rates (GFRs) using dynamic renal computed tomography (CT) in Beagle dogs. Twenty-four healthy Beagle dogs were included in the experiment. Anesthesia was induced in all dogs by using propofol and isoflurane prior to CT examination. A single slice of the kidney was sequentially scanned after a bolus intravenous injection of contrast material (iohexol, 1 mL/kg, 300 mgI/mL). Time attenuation curves were created and contrast clearance per unit volume was calculated using a Patlak plot analysis. The CT-GFR was then determined based on the conversion of contrast clearance per unit volume to contrast clearance per body weight. At the renal hilum, CT-GFR values per unit renal volume (mL/min/mL) of the right and left kidneys were 0.69 ± 0.04 and 0.57 ± 0.05, respectively. No significant differences were found between the weight-adjusted CT-GFRs in either kidney at the same renal hilum (p = 0.747). The average global GFR was 4.21 ± 0.25 mL/min/kg and the whole kidney GFR was 33.43 ± 9.20 mL/min. CT-GFR techniques could be a practical way to separately measure GFR in each kidney for clinical and research purposes.     

犬药物性急性肾损伤模型的建立及评价

[目的]探讨建立犬药物性急性肾损伤模型。[方法]16只健康成年比格犬每8 h皮下注射20 mg/kg庆大霉素,注射前血肌酐浓度(SCr)作为基线,注射后每6 h采集血液检测SCr浓度,于SCr无明显升高、SCr升高临近正常值上限及SCr升高到基线1.5倍时观察肾组织病理形态学改变,确定犬药物性急性肾损伤模型。[结果]SCr在注射庆大霉素后78 h显著升高(P<0.05),实验犬SCr均在120～132 h达到基线的1.5倍;肾组织在SCr升高到基线1.5倍时肾皮质大面积的肾小管变性、坏死,管腔有较多的细胞碎片和颗粒管型,基底膜裸露明显,髓质损伤较轻;与健康对照组相比,注射后肾损伤评分差异有统计学意义(P<0.05),且肾损伤随用药时间延长评分逐渐增加。[结论]庆大霉素每8 h皮下注射20 mg/kg直至SCr浓度升高到基线1.5倍的方法可成功建立犬药物性急性肾损伤模型。     

Effects of administration of fluids and diuretics on glomerular filtration rate, renal blood flow, and urine output in healthy awake cats

OBJECTIVES: To determine effects of commonly used diuretic treatments on glomerular filtration rate (GFR), renal blood flow (RBF), and urine output (UO) and compare 2 methods of GFR measurement in healthy awake cats. ANIMALS: 8 healthy cats. PROCEDURE: In a randomized crossover design, cats were randomly allocated to 4 groups: control; IV administration of fluids; IV administration of fluids and mannitol; and IV administration of fluids, dopamine, and furosemide. Inulin and para-aminohippuric acid were used for determination of plasma clearance for GFR and RBF, respectively. Plasma clearance of technetium-Tc-99m-diethylenetriaminepentacetic acid (99mTc-DTPA) was also used for GFR determination. RESULTS: Furosemide-dopamine induced the largest UO, compared with other groups. Both mannitol and fluid therapy increased RBF, compared with the control group. Mannitol, and not fluid therapy, increased RBF, compared with furosemide-dopamine. There were significant differences in GFR values calculated from 99mTc-DTPA and inulin clearances between the 2 groups. In all groups, use of 99mTc-DTPA caused underestimation of GFR, compared with use of inulin. CONCLUSIONS AND CLINICAL RELEVANCE: In healthy awake cats, administration of furosemide-dopamine did not increase GFR or RBF despite increased UO. Fluid therapy and fluid therapy plus mannitol improved RBF. Determination of GFR by use of 99mTc-DTPA cannot always be substituted for inulin clearance when accurate measurement is required.     

Azotemia and glomerular filtration rate in dogs with chronic valvular disease

BACKGROUND: Little information is available about the prevalence of renal dysfunction in dogs with chronic valvular heart disease (CVD). HYPOTHESIS: Azotemia and a decrease in glomerular filtration rate (GFR) are more severe with increased severity of CVD. ANIMALS: 124 (study No. 1) and 24 (study No. 2) client-owned dogs with CVD. METHODS: A retrospective study (study No. 1) was performed to assess the prevalence of azotemia in the New York Heart Association (NYHA) classes of heart failure in dogs with CVD. A prospective study (study No. 2) was then designed to determine GFR in dogs with different degrees of CVD severity. Complete physical examination, electrocardiography, blood pressure measurement, thoracic radiographs, echocardiography, and plasma and urine analyses were also performed. RESULTS: In study No. 1, 50% of the dogs were azotemic and the percentage of azotemic dogs increased with functional class (up to 70% in NYHA class IV patients). In study No. 2, 8/24 dogs were azotemic. Plasma urea and creatinine were higher in NYHA class III-IV dogs compared with class I-II dogs. The GFR was lower (P < .001) in NYHA class III-IV dogs (1.7 +/- 0.7 mL/min/kg) than in class I to II dogs (3.1 +/- 0.8 mL/min/kg). Only 1 dog in class I-II had a GFR below 2 mL/min/kg and only 2/9 class III-IV dogs had a GFR above 2 mL/min/kg. CONCLUSION AND CLINICAL RELEVANCE: Azotemia and renal impairment increase with the severity of congestive heart failure and are frequent findings in dogs with CVD. It remains to be shown if deterioration of renal function is a direct result of progression of the heart disease.     

五苓注射液对家兔水钠和肌酐排泄及肾小球滤过率的影响

五苓散源于张仲景的《伤寒论》，此方由猪苓、泽泻、白术、茯苓、桂枝组成，主要用于治疗发热恶风、汗出、小便不利、少腹胀满、烦渴、水入即吐等证，现代多用于治疗水肿、胃肠炎、腹泻、传染性肝炎、泌尿系统感染等。本方原为散剂．现多作汤剂。但汤剂系采用自来水熬制，水中Ca^ 、Mg^ 会影响中药有效     

Renal biopsy and pathologic evaluation of glomerular disease

Presence of suspected primary glomerular disease is the most common and compelling reason to consider renal biopsy. Pathologic findings in samples from animals with nephritic or nephrotic glomerulopathies, as well as from animals with persistent subclinical glomerular proteinuria that is not associated with advanced chronic kidney disease, frequently guide treatment decisions and inform prognosis when suitable specimens are obtained and examined appropriately. Ultrasound-guided needle biopsy techniques generally are satisfactory; however, other methods of locating or approaching the kidney, such as manual palpation (e.g., in cats), laparoscopy, or open surgery, also can be used. Visual assessment of the tissue content of needle biopsy samples to verify that they are renal cortex (i.e., contain glomeruli) as they are obtained is a key step that minimizes the submission of uninformative samples for examination. Adequate planning for a renal biopsy also requires prior procurement of the fixatives and preservatives needed to process and submit samples that will be suitable for electron microscopic examination and immunostaining, as well as for light microscopic evaluation. Finally, to be optimally informative, renal biopsy specimens must be processed by laboratories that routinely perform the required specialized examinations and then be evaluated by experienced veterinary nephropathologists. The pathologic findings must be carefully integrated with one another and with information derived from the clinical investigation of the patient's illness to formulate the correct diagnosis and most informative guidance for therapeutic management of the animal's glomerular disease.     

Evaluation of cystatin C as an endogenous marker of glomerular filtration rate in dogs

Cystatin C is a cysteine protease inhibitor produced by all nucleated cells. It is freely filtered by the glomerulus and is unaffected by nonrenal factors such as inflammation and gender. Because of greater sensitivity and specificity, cystatin C has been proposed to replace creatinine as a marker of glomerular filtration rate (GFR) in humans. The aims of this study were to validate an automated assay in canine plasma and to evaluate the usefulness of cystatin C as a marker of GFR in dogs. Western blotting was used to demonstrate cross-reactivity of an anti-human cystatin C antibody. An immunoturbidimetric assay was used to detect cystatin C in 25 clinically healthy dogs and 25 dogs with renal failure. Mean cystatin C concentration in the healthy dogs and the dogs with renal failure was 1.08 +/- 0.16 mg/L and 4.37 +/- 1.79 mg/L respectively. Intra- and interassay variability was <5%. The assay was linear (r = .974) between 0.14 and 7.53 mg/L. Both cystatin C and creatinine concentrations were measured in banked, frozen serum from 20 remnant kidney model dogs and 10 volume-depleted dogs for which GFR measurements by exogenous creatinine clearance had been determined previously. In the remnant kidney model, cystatin C was better correlated with GFR than creatinine (r = .79 versus .54) but was less well correlated with GFR in volume-depleted dogs (r = .54 versus .95). GFR measurements were repeated in the remnant kidney model dogs 60 days after initial GFR measurements. At this time, cystatin C and creatinine concentrations correlated equally well with GFR (r = .891 versus .894, respectively). Cystatin C concentration is a reasonable alternative to creatinine for screening dogs with decreased GFR due to chronic renal failure.     

Glomerular filtration rate after tramadol, parecoxib and pindolol following anaesthesia and analgesia in comparison with morphine in dogs

ObjectiveTo compare the effects of morphine, parecoxib, tramadol and a combination of parecoxib, tramadol and pindolol on nociceptive thresholds in awake animals and their effect on glomerular filtration rate (GFR) in dogs subjected to 30 minutes of anesthesia.AnimalsEight adult mixed breed experimental dogs.Study designRandomized, controlled trial.MethodsDogs received 0.05 mg kg^?1 acepromazine subcutaneously (SC) as anaesthetic pre-medication. Thirty to sixty minutes later, they received either tramadol 3 mg kg^?1 intravenously, (IV), parecoxib (1 mg kg^?1 IV), a combination of tramadol 3 mg kg^?1 (IV), parecoxib 1 mg kg^?1 (IV) and pindolol 5 μg kg^?1 (SC), morphine (0.1 mg kg^?1 (IV) or 0.9% saline (2 mL). Anaesthesia was then induced with IV propofol to effect (2.9 ± 0.8 mg kg^?1) and maintained with halothane in oxygen for 30 minutes. Systolic arterial blood pressure was maintained above 90 mmHg with IV fluids and by adjusting the inspired halothane concentration. Post-treatment nociceptive thresholds to mechanical stimuli, expressed as percent of pre-treatment values, were compared between the treatments to assess the analgesic efficacy of the drugs. Plasma iohexol clearance (ICL), a measure of GFR, was estimated both before and 24 hours after induction of anaesthesia to study the drugs’ effects on renal perfusion. Nociceptive threshold and GFR data were compared using mixed model analysis in sas^®9.1.ResultsBoth tramadol and parecoxib produced similar analgesia, which was less than that of morphine. Their combination with pindolol produced analgesia comparable with morphine. None of the test drugs, either alone or in combination, reduced GFR.ConclusionTramadol and parecoxib (either alone or in combination) can increase nociceptive thresholds in awake dogs and have minimal effects on renal perfusion in normotensive dogs subjected to anaesthesia.     

Evaluation of urine specific gravity and urine sediment as risk factors for urinary tract infections in cats

Background: It has been suggested that diseases that promote isosthenuria predispose to urinary tract infections because of a lack of the common bacteriostatic properties present in concentrated urine. Objectives: The purpose of this study was to assess the clinicopathologic risk factors for positive urine culture outcome in cats with chronic kidney disease (CKD), diabetes mellitus (DM), uncontrolled hyperthyroidism (HT), or lower urinary tract disease (LUTD). Methods: For this retrospective study, medical records of all cats in which a urinalysis and aerobic bacterial urine culture were performed between January 1995 and December 2002 were reviewed. Signalment, body weight, and clinicopathologic data were recorded. Based on the medical records, cats were diagnosed with CKD, DM, HT, or LUTD. Prevalence odds ratios and 95% confidence intervals were calculated using logistic regression. Multivariate models were created for each variable of interest while controlling for the confounding effect of disease group. Results: Six hundred fourteen cats met the criteria for inclusion in the study. Overall, positive urine cultures were identified in 16.9% of cats with CKD, 13.2% of cats with DM, 21.7% of cats with HT, and 4.9% of cats with clinical signs of LUTD. Decreasing urine specific gravity was not associated with positive urine culture when controlled for disease but pyuria, bacteriuria, and hematuria were all associated with positive urine culture outcome. Persians, females, increasing age, and decreasing body weight were all associated with positive urine culture outcome. Conclusions: Performing a urine culture sample based solely on the presence of isosthenuria does not seem warranted. Further studies are warranted to help identify host predisposing factors for urinary bacterial colonization in cats with these diseases.     

Estimation of glomerular filtration rate in healthy cats using single-slice dynamic CT and Patlak plot analysis

Commonly used clinical indicators of renal disease are either insensitive to early dysfunction or have delayed results. Decreased glomerular filtration rate (GFR) indicates renal dysfunction before there is a loss of 50% of functional nephrons. Most tests evaluate global rather than individual kidney function. Dynamic computed tomography (CT) and Patlak plot analysis allows for individual GFR to be tested. Our objectives were to establish a procedure and provide reference values for determination of global GFR in 10 healthy cats using dynamic CT (CTGFR). This method of GFR determination was compared against serum iohexol clearance (SIC). A single CT slice centered on both kidneys and the aorta was acquired every fifth second during and after a bolus injection of iohexol (240 mgI/ml; 300 mgI/kg) for 115 s. Using data from this dynamic acquisition, Patlak plots were obtained, GFR was calculated, and results were compared to global GFR determined by iohexol clearance. The average global CTGFR estimate was 1.84 ml/min x kg (SD = 0.43; range = [1.22, 2.45]). The average global GFR measured using SIC was 2.45 ml/min x kg (SD = 0.58; range = [1.72, 3.69]). GFR measurements estimated by both dynamic CT and SIC were positively associated (estimated Spearman rank correlation coefficient = 0.72; P = 0.0234). The CTGFR method consistently underestimated GFR with a bias of -0.62 (SE = 0.1307) when compared to SIC (P = 0.0011). In healthy cats, CTGFR was capable of determining individual kidney function and appears clinically promising.     

Iron status and erythropoiesis response to darbepoetin alfa in dogs with chronic kidney disease

Iron metabolism, hepcidin and some blood profiles were investigated in 13 healthy and 31 chronic kidney disease (CKD) dogs. The study consisted of 2 experiments, experiment I included healthy dogs (CONT) and CKD dogs (stage 2, 3 and 4), while experiment II consisted of anemic CKD dogs subjected to 28-day darbepoetin alfa treatment. The response to darbepoetin alfa could divide anemic CKD dogs into responder (RP) and non-responder (NRP) subgroups. The results from experiment I showed that packed cell volume (PCV) and plasma albumin concentration were significantly lower in CKD dogs of all stages while the total iron binding capacity (TIBC) was lower in only CKD stage 3 and 4 compared with dogs in CONT group. The PCV was related to both TIBC and albumin when considering among all dogs or only in CKD dogs. The hepcidin concentration in CKD dogs with anemia was lower than those without anemia (P<0.05). In experiment II before darbepoetin alfa treatment, RP subgroup had significantly higher iron and TIBC compared with NRP subgroup (P<0.05), the iron concentration was decreased only in RP subgroup after darbepoetin alfa treatment (P<0.05). The percent increase in PCV was correlated with initial TIBC (P<0.01). Plasma hepcidin concentration was not different between CONT and CKD groups and between RP and NRP subgroups both before and after darbepoetin alfa treatment. It is concluded that TIBC and plasma iron concentration play role on anemia and erythropoietic response to darbepoetin alfa treatment in CKD dogs.     

Pharmacokinetics of levofloxacin after single intravenous,oral and subcutaneous administration to dogs

The pharmacokinetic properties of the fluoroquinolone levofloxacin (LFX) were investigated in six dogs after single intravenous, oral and subcutaneous administration at a dose of 2.5, 5 and 5 mg/kg, respectively. After intravenous administration, distribution was rapid (T_½dist 0.127 ± 0.055 hr) and wide as reflected by the volume of distribution of 1.20 ± 0.13 L/kg. Drug elimination was relatively slow with a total body clearance of 0.11 ± 0.03 L kg^?1 hr^?1 and a T_½ for this process of 7.85 ± 2.30 hr. After oral and subcutaneous administration, absorption half‐life and T_max were 0.35 and 0.80 hr and 1.82 and 2.82 hr, respectively. The bioavailability was significantly higher (p ? 0.05) after subcutaneous than oral administration (79.90 vs. 60.94%). No statistically significant differences were observed between other pharmacokinetic parameters. Considering the AUC_24 hr/MIC and C_max/MIC ratios obtained, it can be concluded that LFX administered intravenously (2.5 mg/kg), subcutaneously (5 mg/kg) or orally (5 mg/kg) is efficacious against Gram‐negative bacteria with MIC values of 0.1 μg/ml. For Gram‐positive bacteria with MIC values of 0.5 μg/kg, only SC and PO administration at a dosage of 5 mg/kg showed to be efficacious. MIC‐based PK/PD analysis by Monte Carlo simulation indicates that the proposed dose regimens of LFX, 5 and 7.5 mg/kg/24 hr by SC route and 10 mg/kg/24 hr by oral route, in dogs may be adequate to recommend as an empirical therapy against S. aureus strains with MIC ≤ 0.5 μg/ml and E. coli strains with MIC values ≤0.125 μg/ml.