normal route (caudal renal vein) by which blood exits the medial and ... Kidney function comparisons (urine flow rates, glomerular filtration rates, renal .... mained intact at the abdominal midline. ..... radioopaque fluid to trace blood flow patterns.
PHYSIOLOGY AND REPRODUCTION Kidney Function in Domestic Fowl with Chronic Occlusion of the Ureter and Caudal Renal Vein1 ROBERT F. WIDEMAN, JR. Department of Poultry Science, 206 William Henning Building, The Pennsylvania State University, University Park, Pennsylvania 16802 GARY LAVERTY
(Received for publication February 24. 1986) ABSTRACT A previously published technique for producing renal insufficiency in chicks involves ligating the caudal renal vein together with the ureter near the midpoint of the kidney. This ligation occludes the normal route (caudal renal vein) by which blood exits the medial and posterior kidney divisions. The present study was conducted to evaluate kidney function following chronic caudal renal vein and ureter occlusion. The ureters and caudal renal veins of 2 to 3-week-old chicks were clamped with hemostatic clips (Clamp Group), and kidney function evaluations were conducted when the birds reached 14 weeks of age. Plasma values [osmolality, Na, K,Ca, inorganic P (P;)] of control, sham, and clamp groups did not differ significantly. Plasma uric acid concentrations did not differ when the control and clamp groups were compared. Clamping the ureter near the midpoint of the kidney caused a significant reduction in the number of filtering glomeruli per kidney, but due to compensatory hypertrophy the kidney weights of the groups did not differ significantly. Kidney function comparisons (urine flow rates, glomerular filtration rates, renal plasma flow rates, urine pH, fractional excretion of Na, K, Ca, P i; and uric acid) revealed a significant reduction in Na and K excretion by the clamp group, but other renal function parameters did not differ significantly. These experiments demonstrate that chickens have a remarkable capacity to survive significant reductions in renal mass and to adapt to major disruptions of blood flow patterns. (Key words: uric acid, sodium, potassium, renal portal) 1986 Poultry Science 65:2148-2155 INTRODUCTION
A technique for producing renal insufficiency in chicks has been described by Hartenbower and Coburn (1972) and by Harvey et al. (1984). This technique involves ligation of both ureters. The right ureter is ligated near its junction with the cloaca, thereby completely preventing the right kidney from excreting urine. The left ureter is ligated along with the caudal renal vein near the midpoint of the left kidney, thereby preventing the left cranial renal division and a portion of the left medial renal division from excreting urine. The resulting renal insufficiency causes a significant increase in plasma uric acid levels within 1 to 2 days following surgery, but the uric acid levels begin to return toward normal values within 12 to 14 days after surgery. The gradual decrease in plasma uric acid has been
1 Paper Number 7348 in the journal series of the Pennsylvania Agricultural Experiment Station.
attributed to compensatory hypertrophy of the unobstructed portions of the left kidney (Hartenbower and Coburn, 1972; Harvey etal., 1984). It is not wholly unexpscted that chicks can recover from dramatic reductions in functional renal mass, as similar reductions can occur when kidney stones obstruct the ureters of domestic fowl during outbreaks of urolithiasis. Laying hens and pullets with urolithiasis can have completely normal external appearances and normal plasma uric acid, mineral, and electrolyte concentrations, whereas only one kidney division remains functional (Wideman etal., 1983,1986; Mallinson et al., 1984; Niznik et al., 1985). Due to compensatory hypertrophy of the undamaged kidney tissue, total kidney weights of chickens with urolithiasis often do not differ significantly from total kidney weights of chickens without urolithiasis (Niznik et al., 1985). The chick model of renal insufficiency described by Hartenbower and Coburn (1972) and Harvey et al. (1984) differs from urolithiasis in one very important feature. Urolithiasis involves
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School of Life and Health Sciences, University of Delaware, Newark, Delaware 19716
RENAL VEIN OCCLUSION
MATERIALS AND METHODS
Single Comb White Leghorn chicks, 2 to 3
weeks old, were allowed ad libitum access to feed (commercial chick starter) and water up to the time of surgery. They were anesthetized with an intramuscular injection of Allobarbital (DIAL, quarter strength, 1.5 ml/kg body weight, Ciba Pharmaceutical Co.). Lidocaine (2%) was injected intracutaneously as a supplemental anesthetic at surgical incision sites. Each chick was placed in a supine position on a surgical board with the wings taped securely to the board. Feet were taped together and retracted cranially. Feathers on the ventral and lateral abdominal regions were plucked. Both kidneys were exposed as described by Harvey et al. (1984); however a 1 cm strip of skin and peritoneum remained intact at the abdominal midline. McKenzie silver hemostatic clips (Arista Surgical Supply Co., New York, NY) were used to clamp together the ureter and caudal renal vein on the ventral surface of the medial renal division of each kidney. This is the same occlusion site used by Hartenbower and Coburn (1972) and Harvey et al. (1984). In the present study, two clips were used on each side to ensure successful occlusion, then a small drop of cyanoacrylate adhesive was applied on top of the clips to fix them in place. The kidneys of Sham chicks were exposed in an identical fashion, but clips were not placed on the ureter and renal vein. The abdominal incisions were closed using 9-mm Autoclip Wound Clips (Clay Adams). Furazolidone aerosol powder (Veterinary Products Industries, Phoenix, AZ) was applied as a tropical antibacterial agent. The chicks were placed under a heat lamp for 2 to 4 hr to recover from the surgery, then they were returned to their brooders. Three groups that were hatched and raised together were used for kidney function evaluations: a control group (three males and two females); a sham group (three males and one female); and a clamp group (four males and two females). Kidney function studies were conducted when the birds were 14 weeks of age. Each bird was anesthetized with an intramuscular injection of Allobarbital (3.5 ml/kg body weight). A brachial vein was cannulated with PE-50 tubing for systemic intravenous infusions. An anterior tibial vein was cannulated for unilateral infusion into the renal portal system. A carotid artery was cannulated for blood sample withdrawal. Ureters were prepared for urine collection as described previously (Wideman and Braun, 1982). A solution containing 2.5% mannitol, 100 mg% inulin, and 100 mg% PAH was infused
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obstruction of only the ureter, thereby triggering pressure-induced degeneration of any kidney tissue upstream from the site of blockage. In contrast, the renal insufficiency model involves ligation of both the ureter and the caudal renal vein near the midpoint of the left kidney (Hartenbower and Coburn, 1972; Harvey et al., 1984). This is necessary because it is extremely difficult to separate the caudal renal vein from the ureter. Caudal renal vein obstruction would be expected to have quite profound effects on blood flow patterns within the kidney. The medial and posterior divisions of the kidney receive arterial inflow from the medial and caudal renal arteries (Siller and Hindle, 1969; Kurihara and Yasuda, 1975a). These arteries branch several times until terminal afferent arterioles, glomerular capillary beds, and efferent arterioles are formed. Postglomerular blood flows from the efferent arterioles into peritubular sinuses surrounding the proximal and distal nephron segments (Johnson, 1979; Siller, 1981; Wideman et al., 1981). Renal portal blood from the posterior portions of the body also enters the peritubular sinuses, flowing from the terminal branches of the caudal renal portal vein. The peritubular sinuses coalesce to form intralobular central veins, which then converge to form branches of the caudal renal vein (Siller, 1981; Wideman et al., 1981). The caudal renal vein then exits the kidney to join the common iliac vein flowing into the caudal vena cava. Therefore, a mixture of renal portal blood and postglomerular arterial blood normally exits the medial and posterior kidney divisions through the caudal renal vein (Akester, 1967; Kurihara and Yasuda, 1975b). Ligating the caudal renal vein should prevent blood from flowing in its normal pattern through the peritubular sinuses and out of the kidney. The objectives of the present study were to confirm the long-term viability of chickens with ureters and caudal renal veins occluded and to evaluate kidney function after chronic clamping of the ureters and caudal renal veins. Chickens with symmetrically clamped kidneys should have profoundly altered blood flow patterns in the cortical areas. Presumably, the major route for postglomerular blood outflow after caudal renal vein ligation should be retrograde through the caudal renal portal vein, thereby restricting renal portal blood inflow.
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(FE) values (FE = Cx/CIn) to compensate for individual differences in GFR. In calculating the fractional excretion of Ca (CCa/Cln), it was assumed that plasma Ca is approximately 50% ultrafilterable (Wideman and Braun, 1981). Renal plasma flow rates were calculated as the clearance of PAH (CPAH) during systemic intravenous infusion of RAH (urine Samples 4, 5, 6 only), and were expressed as milliliters per kilogram body weight per minute. With the exception of CPAH, kidney function was consistent for individual birds during unilateral (Samples 1 to 3) and systemic (Samples 4 to 6) infusion periods. Consequently, overall mean values for the left and right kidneys of each bird were calculated for samples 1 to 6. Individual mean values then were used to calculate group means. Intragroup left vs. right kidney function comparisons were made using a paired t test. Student's t test was used for intergroup comparisons. Values of P
