Renal dysfunction in horses can develop with primary renal diseases as well as a secondary complication of gastrointestinal tract disorders, dehydration, septicemia, endotoxemia and administration of nephrotoxic drugs like NSAIDs. Commonly used parameters in diagnosis of renal failure are serum creatinine and BUN. However concentrations of creatinine and BUN only start to increase when 70 to 75 % of nephrons of both kidneys become nonfunctional. Estimation of glomerular filtration rate is the best parameter to assess renal function as it estimates the numer of functional nephrons. GFR is the volume of fluid filtered out of the plasma per unit of time and mass.
Function tests to estimate the GFR are renal clearance tests and plasma clearance tests. Both techniques measure the disappearance of a marker substance, which is characterized as being exclusively excreted by glomerular filtration, from the plasma. The renal clearance tests additionally require the measurement of the marker substance in the urine, and the urine volume over a period of time. Renal clearance tests like inulin clearance, which is considered the gold standard, are accurate methods to asses renal function, but they are difficult to perform, time consuming and expensive.
Creatinine is constantly produced out of creatine by a non-enzymatic irreversible process in muscle tissue and may be used as an endogenous marker substance. The endogenous creatinine clearance tends to underestimate the GFR. In the exogenous plasma creatinine clearance, creatinine is administered as an i.v. bolus injection, followed by the measurement of its plasma concentration over a period of time.
In this study, blood and urine samples were collected from 8 horses, owned by the Clinic for Equine Internal Medicine of the University of Veterinary Medicine Vienna, to examine renal function based on plasma creatinine and BUN concentrations, and the fractional excretion of electrolytes. The exogenous plasma creatinine clearance test was performed twice on each horse to determine potential intra-individual differences. After inserting a catheter in one jugular vein, creatinine solution (80mg/ml) was administerd as a single bolus injection i.v. (50 mg/kg). In two experiments blood samples were collected 1; 2,5; 5; 10; 20; 30; 45; 60; 90; 120; 180; 240; 360; 540 and 720 minutes after the application in heparinized tubes. Clinical examinations were conducted at the beginning and at the end of each experiment; further, the vital functions (pulse, respiration). were checked continuously throughout the sampling time. Creatinine concentrations were determined via enzymatic method and the plasma disappearance curves were analysed leading to an improved experimental design; in the subsequent experiments the blood samples were taken 1; 2,5; 5; 10; 20; 30; 45; 60; 90; 120; 180; 250; 320; 390; 460; 530 and 600 minutes after the application. Bi- and tri-exponential equations were fit to the plasma concentration versus time profiles; the 3-compartment model provided the best fit.
The exogenous creatinine clearances were calculated by use of the 3-compartment modell (plasma clearance), modell-independent method (trapezoidal methode) and terminale clearance. The endogenous creatinine clearance was calculated by use of the method developed by BICKHARDT et al. (1996). As the terminal method usually overestimates clearance values, a correction formula, derived from regression analysis, was applied to deterimine the terminal clearance.
Clearance values obtained for the 3-comparment modell ranged from 1,55 to 2,42 ml/min/kg and for the trapezoidal method from 1,19 to 2,13 ml/min/kg. There was a significant correlation between terminal clearance values and plasma clearance values as well as between terminal clearance values and the other methods (trapezoidal and endogenous clearance). The terminal clearance values derived from the correction formula were not significantly different from the plasma clearance values.
The terminal clearance of exogenous creatinine is a good method for use in estimating the glomerular filtration in healthy horses. Further studies are necessary to ascertain the accuracy of the method, especially in horses with renal dysfunction.