PATHO-MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL STUDIES OF EARLY AND LATE CONSEQUENCES OF ACUTE KIDNEY INJURY IN SD MALE RATS

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Date
2012
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AAU, Anand
Abstract
The present study was conducted to investigate the early and late consequences of acute kidney injury after the episode of 35 minutes of bilateral renal ischemia. The progressive changes in serum, urine and kidney structure were studied at day 1 to day 28 of reperfusion period. Serum and urine samples were analyzed for creatinine, urea, protein and electrolytes (sodium & potassium). 24 hr urinary output and its solutes were measured at each reperfiasion period. Paraffin section of kidneys stained with H&E, PAS and Masson's trichrome stains were microscopically evaluated for pathological and morphological analysis. Kidney was also assessed for special markers of endothelium (CD31) and immature renal tubules (vimentin) by Immunohistochemistry and image analysis. All experimental rats survived till the end of experimental period. Day 1 after the reperfiision period, serum creatinine and BUN rose to 5-8 folds of sham control or their baseline value. Anuria/oligouria with completely abolished glomerular filtration rate (creatinine clearance <2%), decreased urinary solutes (< 600 against the 1367 mOsm/KgH20) and increased excretion rate of sodium (FeNa >1), potassium (FeK >40) were striking features of day 1 after ischemic AKI. Similar scenario was also present on day 2 of reperfusion period while showing the recovery trend. Urine volume was exceptionally high (~3 folds) than the sham control on day 2 of reperfusion period. By day 7 of VR most of the functional parameters became comparable to the sham control except urine volume which remained ~2 fold higher than the sham till the end of day 28 of experimental period. Histopathologically, ischemic insult caused the severe necrosis of renal tubules at outer stripe of medulla within 24 hr of injury. By day 4 of reperfusion these cells were replaced by basophilic regenerating cell as hyperplastic islets of cells. Further these cells were differentiated in the fonn of renal tubules. At the end of 28 days of experimental period most of tubules restored their normal fiinction but 2-3 foci of tubulointerstitial lesions were present. These foci had dilated renal tubules surrounded by Masson's trichrome positive fibrous tissue. Tubular luminal index was increased by day 4 onwards, highest at day 7 (15399 vs 1679 µm2). Increased interstitial index recorded day 7 of reperfusion period onwards, and 47% area of interstitium noticed in tubulointerstitium foci at day 28. Increased vimentin index was present on day 4 (85.95%), day 7 (52.09%), day 14 (43.55%) and day 28 (36.18%). However, no remarkable change noticed on capillary density in Our experimental condition. Results of this study indicate that 35 minutes bilateral renal ischemia caused the moderate to severe acute kidney injury and pronounced early functional and structural changes to the kidney. Though the functional abnormalities got restored within a week time, the morphological recovery was not complete. Existence of tubulointerstitial fibrosis and undifferentiated tubules noticed even after the 28 days of reperfusion period, which may initiate the down streaming events causing chronic alteration in renal structure and function at a later stage.
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VETERINARY PATHOLOGY, A STUDY
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