| Background and Purpose of this StudyObstructive uropathy due to calculi in the urinary tract is being diagnosed with an increasing frequency in dogs and cats. In case of unilateral ureteral involvement, the condition often passes by unnoticed, because of the presence of non-specific findings such as malaise or abdominal pain. If the condition is not diagnosed at an early stage, it can be devastating to the kidney and pave way for the state of post-renal azotemia, which leads to irreversible renal damage, and the degree of which depends directly on the duration and extent of the obstruction.Modern clinical diagnostic modalities have revolutionized the diagnosis of urological disorders. B-mode Ultrasonography is amongst the first diagnostic tool which is relied upon, for directly visualizing and demonstrating the abnormalities of the internal architecture of soft tissues such as cysts, abscesses and hydronephrosis. Furthermore, because of the added benefits of least invasiveness and accurate localization of the lesions, ultrasonography augments collection of safer biopsy or fluid samples. Due to these benefits, it outshines the alternative diagnostic techniques of conventional and contrast radiography, which have limited uses. Besides these, histopathological findings, as determined through biopsy of the renal tissue, can further confirm early reduction in renal function by detecting changes at cellular level. In addition to these, direct quantitative measurement of renal function and hence pattern of progression of the disease can easily be ascertained by biochemistry, hematology, urinalysis and kinetic studies for plasma clearance of renal markers. These latter kinetic studies hold high specificity and sensitivity in direct quantification of the renal function, since these enable detection and extent of renal damage early in the course of renal disease.The present study thus emphasizes the need for routine implementation of modern diagnostic aids for early detection and successful monitoring of progressive renal disease in pets.Results of the Experimental StudyThis experimental study was accomplished on24healthy mongrel dogs of either sex, aged between6months-6yrs and ranging in weight between6-11kg. The dogs were divided into4groups with6animals in each group; qualitative and quantitative tests of renal function were applied on each animal on Day0(i.e. before ureteral ligation), and Days1,3,5,7,11,15and20post-ligation. Day0animals served as control. Before launching the experiments, appropriate preparations were made beforehand, for direct and indirect quantitative assessment of renal dysfunction (i.e. for kinetic studies of test markers, urinalysis and urine protein quantification). Preparations included sterilization of surgical instruments for use during the surgeries, preparation of chemical solutions required during the experimental study, surgeries performed on the experimental dogs, i.e. jugular catheter insertion (for convenient blood sampling), devocalization and subsequent laparotomies for ligation of the left ureter in each animal, for creating models of hydronephrosis.The experimental data was statistically analysed by application of ANOVA. The normal range of GFR value measured in this experimental study was2.769-7.705mL. min-1. kg-1, while the normal range of ERPF values measured was11.4～22.5mL. min-1. kg1. In hydronephrotic animals, the significant decrease in GFR values was recorded from a normal value of2.582±0.399mL. min-1. kg-1on Day0, to1.483±0.303mL. min-1. kg-1on Day3(P<0.01);1.32±0.123mL. min-1. kg-1on Day8(P<0.01);1.21±0.076mL. min-1. kg-1on Day11(P<0.01), and0.752±0.455mL. min-1. kg-1on Day20(P<0.05). Renal reserve was also seen to decrease likewise, from a normal value of100%on Day0to57.4%on Day3;51.1%on Day8;46.86%on Day11, and29.12%on Day20.The ERPF values were also seen to decrease significantly by Day3after ureteral ligation, from a mean normal value of17.2±1.74mL. min-1. kg-1to a mean value of10.23±1.06mL. min-1. kg-1(P<0.01). Later, on days5,8, and11post-ligation, the values were found to fluctuate, however, values remained significantly lower (i.e. P<0.05) than the normal mean value, and were indicative of a reduced ERPF than on Day0.Quantitative assessment of renal dysfunction was also checked through hematology, biochemistry, and urinalysis and urine protein quantification.Regarding hematology, the leukogram of the experimental dogs was suggestive of marked leukocytosis, with a highly significant value only on Day1(45.92±4.8x109. L-1; P<0.01), with no further profound changes in the later days. Moderate lymphocytosis (11.7±1.5x109. L-1. P<0.01) and marked granulocytosis (28.92±2.85x109. L-1; P<0.01) were also observed on Day1, immediately after the ureteral ligation and granulocytosis was insignificant during the rest of the experimental period. The thrombograms depicted severe and significant thrombocytopenia (53±9.6x109. L-1. P<0.05) on Day11of the experimental period; while the hemograms depicted a severe regenerative, normocytic (normal MCV), normochromic (normal MCHC) anemia. By Day15, RBC count was seen significantly to drop to4.47±0.45x1012.L-1, HGB to93.8±8.35g. L-1, and HCT to29.3±2.74%(P<0.01).Besides this, various serum analytes depicted the chronic pattern of the hyronephrosis lesion. The biochemical profile was hence, clearly indicative of a highly significant hypoproteinemia (28.72±3.85g. L-1-Day11, P<0.01) and hypoalbuminemia (15.36±3.62g. L-1, Day11and18.88±2.91g. L-1, Day15; P<0.01) in the experimental animals. Highly significant uric acid indices (145.30±69.20mmol. L-1-Day20, P<0.01), hyperchloremic acidosis (126.65±7.05mmol. L-1-Day20, P<0.01) and recurrent hyperaatremia (167.98±1.35mmol. L-1-Day11, and169.55±26.05mmol. L-1-Day20; P<0.01) were the most conspicuous findings, suggestive of the progressive devastating pattern of the renal diseaseSince urinalysis does not yield prominent changes in urine till most of the kidney tissue has become destroyed, thus mostly, the derangements in urine specific gravity were also negligible and insignificant, except on days2,6,8,10and12(P<0.05). These results indicated lowered tubular concentrating ability, due to extensive cellular damage produced as a result of hydronephrosis. Urine protein did not vary significantly; the quantity of urine proteins was usually found to be in the normal range. It was inferred that due to compensation by the intact contra-lateral kidney, changes in urine specific gravity largely remained subtle.Amongst the qualitative tests performed for assessing renal dysfunction in experimental animals, B-mode ultrasonography was the most sensitive, least invasive one, enabling direct visual assessment of the condition of the kidney tissue. Measurements taken for left renal pelvis depicted an enormously dilation in size, from a mean normal value of7.37±0.32mm on Day0, significantly to11.78±0.61mm on Day3(P<0.05),22±1.43mm on Day12(P<0.01),24.1±1.66mm on Day14(P<0.01), and26.1±3.4mm on Day20(P<0.01), respectively. Likewise, due to the increased intra-renal pressure of accumulated urine, the left renal cortex also showed a significant decrease in thickness, from a mean normal value of5.5±0.5mm, to4±0.13mm on Day10(P<0.05),3.27±0.24mm on Day14(P<0.01), and3±0.31mm on Day20(P<0.01), respectively. Left renal length simultaneously increased significantly on all days post-ligation, from a mean normal value of51.6±1.2mm on Day0, to64.45±1.93on Day10, and68.45±2.63mm on Day14, respectively,(P<0.01). Left renal width and depth also depicted similar significant enlargements on all days post-ligation. Changes recorded in left renal width included a mean normal value of28±0.88mm on Day0, to34.42±0.77mm on Day10and35.91± 1.77mm on Day14, respectively,(P<0.01). Depth of the left kidney also showed significant increases from a mean normal value of25.87±0.65mm on Day0, to35.1±1.2mm on Day10, and40.28±2.8mm on Day20, respectively,(P<0.01). Besides this, the change in diameter of the left ureter depicted the most enormous significant enlargement, specifically due to the increased intra-pelvic and ureteral pressure, with progression of the renal lesion. Hence, from a mean normal value of1.0±1.0mm on Day0, the opening of the left ureter increased to17.2±0.77mm on Day10, and23.28±2.44mm on Day20, respectively,(P<0.01).Contrast radiography (intravenous urography) was clearly indicative of a dilated ureter-filled pelvis with thinning and fibrosis of the renal parenchyma (cortex and medulla). Due to pressure atrophy, the pseudo-diverticulae of the renal pelvis was visualized as thin cords extending towards the cortex. Histopathology was suggestive of tissue necrosis and apoptosis. The long-standing ureteral obstruction was seen to induce an increase in the number of apoptotic renal tubular cells. Besides this, the sections were characterized with severe tubular dilatation, tubular atrophy, widened interstitial space with a greater number of interstitial cells and infiltrating mononuclear cells. Hemorrhage was also noticed in various sections, and tubulointerstitial fibrosis was evident in the later stages of the experimental study.ConclusionThis present study, comprising of experimental models of hydronephrosis by complete ureteral ligation, was hence, conducted in order to assess the pattern of renal dysfunction, as may be produced in natural conditions by usual blockage of the ureter due to some reason, such as calculi. We have also tried to develop an easier method for direct renal function tests, by assessing plasma clearance of Inulin for GFR determination and plasma clearance of Para-aminohippurate for ERPF determination. This multi-directional study may, thus, prove a beacon-light for future research and development of more efficacious methods for direct determination of renal function, in veterinary clinical patients, for early detection of reduced renal function. |
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