The Interaction between Orally Administered Non-Steroidal Anti-Inflammatory Drugs and Prednisolone in Healthy Dogs
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The interaction between oral non-steroidal anti-inflammatory drugs (NSAIDs) and prednisolone administered concurrently for 30 days was studied in 18 healthy dogs divided into 3 groups of 6 dogs each: a drug-free negative control group (NC group) given 2 gelatin capsules; a group given meloxicam (0.1 mg/kg) and prednisolone (0.5 mg/kg) (MP group); and a group given a reduced dosage of ketoprofen (0.25 mg/kg, PO) and prednisolone (0.5 mg/kg, PO) (KP group). The dogs were periodically monitored by physical examinations, blood analyses, endoscopic examinations, fecal occult blood tests, renal function tests [effective renal plasma flow (ERPF) and glomerular filtration rate (GFR)], urinalyses [urinary sediments, and urinary micro-albumin to creatinine ratio (UAlb/Cre)], urinary enzyme indices, and haemostatic function tests [buccal mucosa bleeding time (BMBT), cuticle bleeding time (CBT)]. Significant changes were observed in the KP group, including a decrease of ERPF and GFR, an increased UAlb/Cre ratio, prolonged BMBT and CBT, as well as the presence of more severe grades of endoscopic lesions and fecal occult blood. In both the MP and KP groups, abnormal enzymuria with exfoliation of renal tubular epithelial cells in the urine was found. However, no significant changes in any of the other tests were observed in the MP group compared with the NC group. These findings suggest that the combination of NSAIDs, even selective COX-2 inhibitors, with prednisolone may be contraindicated due to the potential for serious adverse effects on the kidneys, the platelets, and the gastrointestinal tract.Keywords:
Prednisolone
Meloxicam
To compare the conventional creatinine clearance measured on 24-h urine collection with the estimated Glomerular Filtration Rate by Cockcroft & Gault (CG) and Modification of Diet in Renal Disease (MDRD) prediction equations in adults aged 20 years and above in Pakistani population.All the patients, including inpatient admitted in hospital and outpatients, more than 20 years of age, reporting for the test of creatinine clearance in clinical chemistry department of Dr. Ziauddin Hospital clinical laboratory from 1st January to 31st December 2006 were studied.Comparison was made between conventional creatinine clearance and Cockcroft & Gault (CG) and Modification of Diet in Renal Disease (MDRD) prediction equations on 369 cases which revealed strong correlation with conventional creatinine clearance, MDRD equation has better correlation as compared with Cockcroft- Gault creatinine clearance. Statistical correlation was better in cases where serum creatinine was more than 1.50 mg/dl (r = 0.625 for Cockcroft- Gault creatinine clearance and r = 0.724 for MDRD equation) as compared when serum creatinine levels were less than 1.50 mg/dl (r = 0.608 for Cockcroft- Gault creatinine clearance and r = 0.596 for MDRD equation). There was positive bias in both calculated GFRs from conventional creatinine clearance in healthy as well as diseased population.The creatinine based formulas with their inherent property of convenience and cost effectiveness can be a useful tool for monitoring the progression of disease. They can be applied in clinical practice on our population but they should be interpreted with caution as they over estimate the GFR.
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PICO question
In cats with feline interstitial cystitis, which therapy brings a faster resolution of clinical signs: meloxicam or prednisolone?
Clinical bottom line
Category of research question
Treatment
The number and type of study designs reviewed
Two papers evaluated as relevant to the PICO question were critically reviewed. Both were double-blinded randomised controlled trials.
One paper not related to the PICO question, a single-blinded randomised controlled trial, was also reviewed as it is touched upon in the discussion section
Strength of evidence
Appraisal of the literature reveals weak evidence that meloxicam and prednisolone are of equivalent effectiveness when treating feline interstitial cystitis, also known as feline idiopathic cystitis (FIC)
Outcomes reported
There is no statistically significant difference in the reduction of clinical signs when meloxicam is compared with a placebo for the treatment of FIC. There is no statistically significant difference in reduction of clinical signs when prednisolone is compared with a placebo for the treatment of FIC. No studies were available for review which directly compared meloxicam against prednisolone as treatment options for FIC
Conclusion
In cats with FIC, insufficient evidence exists to truly conclude whether meloxicam or prednisolone is the most efficacious therapy for the reduction of clinical signs. Two double-blinded randomised controlled trials were evaluated – one compared the efficacy of meloxicam against a placebo; the other compared the efficacy of prednisolone against a placebo. Neither study found a statistically significant difference between the assessed treatment modality and the placebo used in reducing the clinical signs of FIC. As such, weak evidence exists that there is no significant difference between the use of meloxicam and a placebo, and prednisolone and a placebo in the reduction of clinical signs of FIC. Additionally, it could therefore be hypothesised that no significant difference exists in the reduction of clinical signs when comparing meloxicam against prednisolone as treatments for FIC however, no study was discoverable which was able to substantiate this claim
How to apply this evidence in practice
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.
Meloxicam
Prednisolone
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We evaluated cystatin C concentration as a marker of glomerular filtration rate in renal transplant recipients, and its correlation with creatinine-based glomerular filtration rate by urinary creatinine clearance, and the Cockroft-Gault and Modification of Diet in Renal Disease formulas.In this cross-sectional study, we measured serum cystatin C levels and its correlation with serum creatinine, creatinine clearance, and glomerular filtration rate using the Cockroft-Gault formula and Modification of Diet in Renal Disease formulas.One hundred two recipients between June and December 2012, were examined. The mean subject age was 31.87 ± 8.37 years; the male:female ratio was 4.3:1. Mean serum creatinine concentration was 141.44 ± 43.31 mol/L (1.60 ± 0.49 mg/dL) and serum cystatin C 122.09 ± 38.95 nmol/L (1.63 ± 0.52 mg/L). Serum cystatin C was significantly correlated with serum creatinine (r=0.90; P<.001), creatinine clearance (r=0.77; P<.001), and the Cockroft-Gault (r=0.73; P<.001) and the Modification of Diet in Renal Disease formulas (r=0.82; P<.001). We assessed the correlation among serum cystatin C with serum creatinine, creatinine clearance, the Cockroft-Gault and Modification of Diet in Renal Disease at 1, 2-3, 4-5, and more than 5 years after transplant. The correlation between serum cystatin C and serum creatinine ranged from 0.8 to 1.0; cystatin C and creatinine clearance ranged from 0.8 to 0.85; serum cystatin C and the Cockroft-Gault Formula ranged from 0.7 to 0.8; and serum cystatin C and the Modification of Diet in Renal Disease formulas ranged from 0.8 to 0.84.Our results show that serum cystatin C is a reliable marker for estimating glomerular filtration rate among renal transplant recipients. This test can determine the glomerular filtration rate of renal transplant recipients on follow-up. Further studies are required to establish serum cystatin C as a standard test for monitoring glomerular filtration rate in transplanted patients.
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Creatinine-based equations are used as standard ways to estimate glomerular filtration rate and kidney function. Unfortunately, serum creatinine varies based on factors such as age, gender, and muscle mass. Overestimation of renal function by creatinine-based equations can be dangerous for renally dosed medications, such as enoxaparin. We present a patient who developed spontaneous bleeding on enoxaparin where kidney function was significantly overestimated by creatinine-based equations. The use of cystatin C levels, which are creatinine independent, can provide a better prediction of renal function.
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We compared creatinine concentrations in serum and urine and creatinine clearances determined by two Jaffé (Beckman's "Astra," Boehringer Mannheim Diagnostics) and two enzymatic (Kodak, Boehringer Mannheim Diagnostics) methods. Serum creatinine and creatinine clearances determined by each method were also compared with the glomerular filtration rate as measured with use of sodium [125I]iothalamate in patients with a wide range of renal function. Results between methods correlated excellently, but we saw clear method-dependent biases of up to 2.9 mg/L for serum. The highest serum creatinine values and the lowest creatinine clearances were obtained with Boehringer Mannheim Diagnostics' Jaffé method. The reciprocal of the serum creatinine and the creatinine clearance also correlated well with the glomerular filtration rate, but all methods over-estimated the glomerular filtration rates to varying degrees. Appropriate standardization of methods appears to be as important as method principle for establishing an accurate relationship between creatinine determinations and glomerular filtration rate.
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Creatinine concentration is commonly used to verify the authenticity of urine specimens submitted for illicit drug screening. This study evaluated creatinine screening of donor urine specimens as a tool for detecting substituted and/or tampered specimens. The study carried out creatinine assay of animal urine, fruit juices, and urine from creatine-supplemented subjects by a modified version of the Jaffe reaction. All specimens were analyzed for creatinine concentration in a chemistry-immuno analyzer. Results showed that urine specimens from common domestic pets, including cats, dogs, and horses, have creatinine values similar to normal human values. Most fruit juices tested contained no detectable creatinine, and the few that did showed poor "urine" chemical integrity. Creatine supplementation by donors was found not to provide an effective means of elevating creatinine concentration in urine when attempting to flush out water-soluble drugs in the body. Thus, the assay for creatinine proved useful for the detection of some but not all adulterated urine specimens.
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Objective To evaluation of endogenous clearance marker glomerular filtration rate(GFR) in patients with various types of renal diseases.Methods We determined the serum cystatin C,urea,creatinine,and creatinine clearance levels in 57 patients with renal diseases,and 39 healthy controls,and compared the concentrations of patients with of healthy controls.Results The concentratons of serum urea,creatinine,and creatinine clearance was found to be significantly higher in the patients with renal diseases in comparison to the healthy controls(P0.01).Correlation was observed between cystatin C and creatinine clearance levels(P0.05),and between cystatin C and creatinine levels(P0.01).However,there were not correlation between creatinine and urea concentrations(P0.05),and between creatinine and creatinine clearance lenels(P0.05).Conclusion Serum cystatin C is probably more attractive for estimation of renal function than urea,creatinine,and creatinine clearance for detection of GFR in patients with early kidney diseases.
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Creatinine is a metabolite excreted mainly by glomerular filtration, which makes it an important endogenous indicator of kidney function. Creatinine clearance is defined as the ratio of the concentration of creatinine in serum and urine. It assesses glomerular filtration. Creatinine and creatinine clearance have the leading role in the early diagnosis, monitoring and classification of chronic kidney disease. The routine method for determining the concentration of creatinine is the Jaffé photometric method. A newer version is the compensated method. Furthermore, the recommended equation for the estimation of glomerular filtration rate (GFR) is the one based on the MDRD study (eGFR) intended for people over 18 years. The aim of the study was to evaluate how the introduction of the compensated method would affect the clinical use and influence the assessment of GFR in the interpretation of findings and treatment monitoring for people over 20 years. The study group included 130 men and 142 women whose requested laboratory test was creatinine clearance. Data were collected over 20 days at Sestre milosrdnice University Hospital. Serum creatinine concentration and eGFR were determined by the compensated and uncompensated Jaffé method. In conclusion, the compensated creatinine method is not statistically comparable with the uncompensated method, but is clinically fully applicable to the general population above the age of 20, given that the reference intervals are changed. Comparison of eGFR as estimated by the compensated and uncompensated methods to determine creatinine concentration showed the same results as the comparison of clearance. Using the compensated method yielded statistically incomparable results in GFR estimation. However, in clinical practice, patient classification according to stages of chronic kidney disease (CKD) was comparable in the male group according to clearance and eGFR (pi=0.922 and pi=0.230, respectively), while the female group was classified significantly different according to clearance and eGFR (pi<0.016 and pi<0.001, respectively). Switching to the compensated creatinine method while simultaneously applying the eGFR formula was shown to be valid, as patient classification according to CKD stages was comparable (pi=0.921); thus, the methods are reliable for use instead of creatinine clearance in the general population with various diagnoses, which can be noted in all laboratories and which is, although inhomogeneous, routinely used to measure daily creatinine clearance.
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