Histological Examination Of Renal Tissue Research Articles

Investigation of the nephroprotective activity of Moringa peregrina leaves aqueous extract in mice

Traditional remedies for Moringa peregrina leaves have a variety of uses with confirmed biological and therapeutic effects, as per published reports. The current study aims to evaluate the ability of the leaves aqueous extract to protect from nephrotoxicity in gentamicin-treated mice. Phytochemical analysis for the aqueous extract was performed using DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay for antioxidants, Folin-Ciocalteu, AlCl3 and HPLC- MS/MS analysis, focusing on phenol and flavonoid content. The nephroprotective activity of the prepared extract was evaluated by means of variable biochemical parameters including Creatinine (Cr), Uric Acid (UA), and Urea (Ur). In addition, histological examination of renal tissues was performed in all mice groups (control, gentamicin-induced (150 mg/Kg i.p) and aqueous extract-orally treated groups (500 and 1000 mg/Kg)). Findings reveal that the prepared extract has total phenols (555.57±0.92mg/g, equivalent to gallic acid), flavonoids (40.08±1.56 mg/g, equivalent to quercetin), and DPPH IC50 (3.10 µg/ml). HPLC-MS/MS analysis revealed the presence of 10 phenols and flavonoids compounds. In vivo studies showed a significant (P < 0.05) reducing effect for the high-dose treatment, on serum and urine concentrations for UA, Cr, and U, among the nephrotoxicity induced mice. Low-dose treated group showed significant reduction on serum concentration of UA, Cr and U, but only for Cr concentration in urine. The histological examination showed an improvement in the image of the renal tissue among the induced-nephrotoxicity mice, which was treated with high-dose extract. In conclusion, leaves aqueous extract of M. peregrina have shown potential protective effect to counteract some of the gentamicin consequences on kidney functions.

Evaluation of renoprotective potential of Ficus religiosa in attenuation of diabetic nephropathy in rats

BackgroundDiabetic nephropathy (DN) is a major complication associated with diabetes and more than 25% of people suffering with diabetes eventually develop several problems related to renal system. The plant Ficus religiosa (Moraceae) is widely used traditional medicine amongst plants for the therapy of pain, inflammation, neuroprotection, diabetes, uterine tonic and disorders related to urinary system. ObjectiveThe aim of current study is to evaluate the effect of hydroalcoholic extract of aerial part of Ficus religiosa on DN in male wistar rats. MethodThe diabetic nephropathy induced by single injection of streptozotocin (STZ) (65 mg/kg, i.p.). Elevated levels of glucose, renal and lipid parameters & altered renal tissue histology suggested development of diabetic nephropathy. ResultAfter 30 days of diabetes induction, treatment with hydro alcoholic extract (HAE) of aerial part of Ficus religiose (50, 100 & 200 mg/kg, p.o.) and standard drug glimepride (10 mg/kg, p.o.) was continued for next 45 days. Histological examination of renal tissue was done after treatment to evaluate the renoprotective effect of Ficus religiosa, Administration of different doses of hydroalcoholic extract of aerial part of Ficus religiosa produced significant antidiabetic activity by decreasing the elevated glucose level. Moreover, levels of renal & lipid parameters along with oxidative stress parameters were also found to be normalized along with renal histology. ConclusionCurrent study concluded that HAE of Ficus religiosa possess significant renoprotective activity in streptozotocin STZ-induced diabetic rats.

Comparative amelioration of renal histomorphology by ascorbic acid and Camellia sinensis extract in Wistar rats exposed to Lead-induced nephropathy

Aim: To compare the ameliorative effects of ascorbic acid and Camellia sinensis extract on renal histomorphology of lead-induced nephropathic rats. Material and methods: Twenty four rats were randomly grouped into four groups (I–IV) as follows: Normal control group I administered distilled water (5 ml/kg), Test control group II administered lead acetate (2 mg/ml), Treated group III administered lead acetate (2 mg/ml) + ascorbic acid (100 mg/kg), Treated group IV administered lead acetate (2 mg/ml) + Camellia sinensis extract (10 mg/kg). All administrations were done through oral route and lasted for 30 days. Results: Body and renal tissue weight of study animals were significantly reduced (p 0.05) in test control relative to normal control while treated groups showed non-significant reduction. Histological examination of renal tissue showed significant prominence of histopathological features such as inflammation, necrosis and glomerular congestion in test control group while treated groups showed marked reduction.Conclusion: According to the findings of this study, treatment with ascorbic acid or Camellia sinensis extract comparatively exert ameliorative effects on lead-induced nephropathy in Wistar rats which in turn culminates into reparative influence on their renal histomorphology.

Nrf2 signaling attenuates epithelial-to-mesenchymal transition and renal interstitial fibrosis via PI3K/Akt signaling pathways

BackgroundNrf2 constitutes a therapeutic reference point for renal fibrosis and chronic kidney diseases. Nrf2-related signaling pathways are recognized to temper endothelial-to-mesenchymal transition (EMT) in fibrotic tissue. Nevertheless, the mechanism by which Nrf2 mitigates renal interstitial fibrosis is imprecise. MethodsThe relationship between Nrf2 and renal interstitial fibrosis was investigated using the unilateral ureteral obstruction (UUO) model of Nrf2−/− mice. The mice were separated into four groups, based on the treatment and intervention: Nrf2−/− + UUO, Nrf2−/− + Sham, WT + UUO and WT + Sham. Histological examination of renal tissue following the hematoxylin-eosin and Masson staining was carried out, as well as immunohistochemical staining. Additionally, to confirm the in vivo discoveries, in vitro experiments with HK-2 cells were also performed. ResultsThe Nrf2−/− + UUO group showed more severe renal interstitial fibrosis compared to the WT + UUO, Nrf2−/− + Sham and WT + Sham groups. Furthermore, the manifestations of α-SMA and Fibronectin significantly increased, and the manifestation of E-cadherin considerably decreased in kidney tissues from the group of Nrf2−/− + UUO, compared to the WT + UUO group. The Nrf2 protein level significantly decreased in HK-2 cells, in reaction to the TGF-β1 concentration. In addition, the overexpression of Nrf2 presented contradictory results. What is more, the PI3K/Akt signaling pathway was discovered to be activated in the proteins extracted from cultured cells, and treated with Nrf2 siRNA and kidney tissues from the Nrf2−/− + UUO group. ConclusionsThe results we obtained demonstrate that Nrf2 signaling pathway may perhaps offset the development of EMT, prompted by TGF-β1 and renal interstitial fibrosis. Likewise, the anti-fibrotic effect of Nrf2 was imparted by the inactivation of PI3K/Akt signaling. From our discoveries, we deliver new insight related to the prevention and treatment of kidney fibrosis.

Schisandrin B alleviates diabetic nephropathy through suppressing excessive inflammation and oxidative stress

Diabetic nephropathy (DN) is a progressive kidney disease due to glomerular capillary damage in diabetic patients, with inflammation and oxidative stress implicated as crucial pathogenic factors. There is an urgent need to develop effective therapeutic drug. Natural medicines are rich resources for active lead compounds. They would provide new opportunities for the treatment of DN. The present study was designed to investigate the protective effects of Schisandrin B (SchB) on DN and to delineate the underlying mechanism. Oral administration of SchB in the diabetic mouse model significantly alleviated hyperglycemia-induced renal injury, which was accompanied by maintenance of urine creatinine and albumin levels at similar to those of control non-diabetic mice. Histological examination of renal tissue indicated that both development of fibrosis and renal cell apoptosis were dramatically inhibited by SchB. The protective effect of SchB on DN associated with suppression of inflammatory response and oxidative stress. These results strongly suggested that SchB could be a potential therapeutic agent for treatment of DN. Moreover, our findings provided a fuller understanding of the regulatory role of NF-κB and Nrf2 in DN, indicating that they could be important therapeutic targets.

Heat stress-induced renal damage in poultry and the protective effects of HSP60 and HSP47.

The present study investigates the effects of heat stress on the kidney in broilers, based on previous findings which showed that heat stress caused cardiac damage in broilers. Further, the possible renoprotective role of aspirin and the heat shock proteins HSP60 and HSP47 was also investigated. The enzyme levels of urea and uric acid, which are indicators of renal damage, and lactate dehydrogenase, an indicator of oxidative damage, were measured in chickens that were only exposed to heat stress, chickens that were pretreated with aspirin before heat stress, and chickens that were only treated with aspirin. Further, histological examination of renal tissue from the three groups was also performed. Finally, expression of HSP60 and HSP47 was also examined. In the heat stress group, the enzyme measurements were indicative of renal dysfunction and oxidative damage, and the histological findings were indicative of renal ischemia and damage. Aspirin seemed to have a protective effect against the renal damage caused by the stress, based on the enzyme measurements and histopathological findings in the aspirin-treated group. The findings also indicate that aspirin may induce HSP60 and HSP47 expression in renal cells. Finally, the expression patterns of HSP60 and HSP47 indicated that they may play a renoprotective role, as their expression was higher in the aspirin-treated groups. In conclusion, the present findings show that heat stress causes renal damage in poultry and that aspirin may play a protective role against this damage via pathways that involve HSP60 and HSP47.

Hepatic and renal histology and mercury concentrations of North West and North East Greenland narwhals (Monodon monoceros)

ABSTRACTNarwhals (Monodon monoceros) are at the top of the Arctic food web and therefore might biomagnify high total mercury (Hg) concentrations in organs and tissues. The aim of this study was to determine histopathology and Hg concentrations in liver and kidneys from 15 North East Greenland narwhals (3 subadult females, 8 adult females, 3 subadult males, and 1 adult male) and compare data with previous observations of 12 North West Greenland specimens (1 subadult female, 4 adult females, 1 subadult male, and 6 adult males). The zoological length was significantly larger and hepatic and renal concentrations significantly higher in adults compared to subadults. When comparing tissues, the Hg levels were significantly the highest in liver, while a correlation between metal levels in liver and kidneys was positive and significant. Histological examination of renal tissues presented four types of glomerular lesions (capillary dilatation [0–100%], membrane thickening [0–100%], dilatation of space [0–80%], and sclerosis [0–70%]) and two tubular lesions (atrophy/hyalinization [0–40%] and casts [0–60%]). Hepatic tissues exhibited three portal lesions (fibrosis [0–33%], cell infiltrates [0–40%], and bile duct proliferation [0–40%]) and two parenchymal lesions (steatosis [83–100%] and lipid-filled Ito cells [0–33%]). All 12 lesions were found in adult whales from North West Greenland while eight were present in adult whales from North East Greenland. Six lesions were detected in subadults from North East Greenland and four in subadults from North West Greenland. A significantly higher frequency of dilatation and hyalinization of Bowman’s space and capsule and glomerular capillary dilatation was found in adult narwhals from West Greenland. There was no marked difference in Hg concentrations in whales with and without histological lesions. In conclusion, the prevalence of histological changes and Hg levels were the highest in adults and therefore both age and metal are important factors to include when evaluating liver and kidney lesions in narwhals.

Candidate Urine Peptide Biomarkers for IgA Nephropathy: Where Are We Now?

Early detection, prognosis, and management of IgA nephropathy (IgAN) remain a challenge. Histological examination of renal tissue still comprises the only way to confirm an IgAN diagnosis. It is of great importance to establish noninvasive diagnostic, prognostic, and predictive biomarkers that would improve the clinical care and outcome of patients suffering from IgAN. This review summarises the findings from previous mass spectrometry- (MS-) based studies dedicated to the discovery of urinary peptide profiles specific to IgAN. There is a substantial number of urinary peptides that have been discovered to date, which show promise as biomarkers of IgAN; however, all of them require further, rigorous validation in well-planned studies, involving a large number of subjects who represent diverse and numerous populations.

Effect of erythropoietin on the expression of dynamin-related protein-1 in rat renal interstitial fibrosis

This study aimed to observe the expression of dynamin-related protein-1 (Drp-1) in the renal interstitium in a rat model of renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). In addition, the renoprotective effect of erythropoietin in this model was investigated. A total of 81 rats were randomly assigned to sham surgery, UUO model and treatment groups. Following surgery, the rats in the treatment group were subcutaneously administered erythropoietin at a dose of 3,000 IU/kg once a week until the time of sacrifice. Rats in the sham surgery and UUO model groups were administered an identical volume of normal saline. In each group, nine rats were chosen randomly for sacrifice on days 7, 14 and 21 after surgery for histological examination of renal tissue. Renal tissue specimens were examined by hematoxylin and eosin and Masson's trichrome staining. Immunohistochemical analysis was performed to determine the expression of Drp-1 in the renal interstitium. Renal function damage, as evaluated by the measurement of serum creatinine (Cr) and blood urea nitrogen (BUN) levels, was less severe in the treatment group compared with that in the model group at day 21 (P<0.01). Compared with the UUO model group, the renal interstitial injury score and fibrotic area of the treatment group were decreased markedly at the three time points (P<0.05). The expression level of Drp-1 in the treatment group was decreased markedly at the three time points compared with that in the model group (P<0.05). In conclusion, the expression of Drp-1 is increased in rat renal interstitial fibrosis, and erythropoietin may alleviate the degree of renal interstitial fibrosis by downregulating the expression of Drp-1.

Effect of Morin against Gentamicin-Induced Nephrotoxicity in Young Male Rats

Background: Morin, a bioflavonoid with antioxidant properties, is a constituent of many herbs and fruits that are used as herbal medicines. It exhibits many biological activities and possibly even has protective effects against chronic diseases. The present study was conducted to determine the protective effect of morin against gentamicin-induced nephrotoxicity in young male rats. Material and Methods: Young male rats (n=24) were divided into four groups as follow; (1): control group, (2): gentamicin (GM) group; rats injected intraperitioneally (i.p.) with GM at a dose of 100 mg /kg body weight (b.w.) for five consecutive days to induced nephrotoxicity, (3): morin group; rats administered morin daily at a dose of 30 mg/ kg b. w. via gavage, and (4) GM group pretreated with morin; rats were orally received morin at the same dose and route in group (3) up to two weeks followed by injected i.p. with GM as in group (2). Separated serum samples were used for determination of protein metabolism parameters, kidney functions, malondialdehyde (MDA), and ionic sodium (Na+) and potassium (K+). Results: GM injection induced marked nephrotoxicity as evidenced by significant elevation in serum levels of albumin, creatinine, urea, uric acid, MDA and K+, with significant reduction in serum levels of total protein, Na+ and albumin/creatinine ratio (ACR). Pretreatment with morin protected the rats from GM- induced nephrotoxicity as evidenced by significant improvement of these investigated parameters. Histological examination of renal tissues showed marked glomerular thickening, vacuolations of the wall of blood vessels associated with necrobiotic changes in GM injected group, meanwhile there were amelioration in rats group received morin pre-GM injection. Conclusion: Morin exert potential antioxidant activity and offer nephroprotective effect against GM- induced nephrotoxicity in young rats.

Aldosterone, but not angiotensin II, increases profibrotic factors in kidney of adrenalectomized stroke-prone spontaneously hypertensive rats

An increase in angiotensin II (ANG II) under conditions of high salt intake can result in renal damage. The extent to which ANG II does this directly or by way of stimulating aldosterone (Aldo) secretion is a subject of some debate. In the present study, we sought to determine the separate effects of Aldo and ANG II on the expression of plasminogen activator inhibitor-1 (PAI-1) and other factors related to renal fibrosis in the stroke-prone spontaneously hypertensive rat (SHRSP). Saline-drinking male SHRSPs underwent adrenalectomy (ADX) or sham operation (Sham). Treatment groups consisted of ADX + ANG II (25 ng/min sc) and ADX + Aldo (40 microg.kg(-1).day(-1) sc). After 2 wk of treatment, circulating Aldo levels were reduced to the limit of detection, renal PAI-1, transforming growth factor-beta1 (TGF-beta1), and osteopontin expression, and phospho-Smad2 (p-Smad2) level were decreased severalfold, and Smad7 (an inhibitory regulator of TGF-beta1 action) expression was increased in ADX compared with Sham rats. Infusion of Aldo into ADX SHRSPs restored the renal mRNA expression of PAI-1, TGF-beta1 (along with restored p-Smad2 level), and osteopontin and reduced that of Smad7, whereas ANG II had no or a lesser effect. The findings were confirmed by histological examination of renal tissue. In summary, in the saline-drinking SHRSP, Aldo increased renal profibrotic factors and produced renal injury whereas ANG II in the absence of the adrenals had no effect.

Carvedilol Protects against Cyclosporine Nephropathy in Rats

The aim of our experimental work was to study whether carvedilol is able to protect renal tissue from cyclosporine toxic effect in animal model of cyclosporine nephropathy. The study was performed on twenty Wistar rats divided in two experimental groups: control (treated with placebo) and carvedilol (treated with p.o. dose 10mg/kg/day in 1 ml solution). Cyclosporine in oral dose of 15 mg/kg/day was administered to all animals during 15 days of experiment. Urine was collected daily for the assessment of diuresis, proteinuria, and determination of urea and creatinine levels. Serum collected at the end of the experiment (day 15) was used for the determination of urea and transferrin levels. The level of renal tissue damage was evaluated by the Jones method for basal membranes, glomeruli and tubuli impregnation, and by the Kossa method for calcium impregnation. For the determination of paranuclear inclusions presence we used chromanilinblue (CAB) method. Statistically significant differences between total protein levels in urine on day 7 of the experiment and urea levels in serum at the end of the experiment in the control group and the carvedilol-treated group indicate a protective effect of carvedilol on renal tissue, which is supported also by the results of a histological examination of renal tissue. Significant increase in the serum transferrin level was registered in the carvedilol-treated group and no significant changes were noted in ceruloplasmin serum levels. In conclusion, our pilot study showed that carvedilol has the ability to protect renal tissue from cyclosporine induced nephropathy in rats.

Use of pamidronate disodium to reduce cholecalciferol-induced toxicosis in dogs.

To determine whether pamidronate disodium can reduce cholecalciferol-induced toxicosis in a dose-related manner. 20 clinically normal, 8- to 12-month-old male Beagles. All dogs were given 8 mg of cholecalciferol (CCF)/kg of body weight once orally, then were randomly assigned to 4 groups of 5 dogs each. Dogs were treated with IV administration of 0.9% NaCl solution (SC group), 0.65 mg of pamidronate/kg in 0.9% NaCl solution (LP group), 1.3 mg of pamidronate/kg in 0.9% NaCl solution (MP group), or 2.0 mg of pamidronate/kg in 0.9% NaCl solution (HP group) on days 1 and 4 after administration of CCF. Dogs were observed for 14 days, and serial blood samples were collected for serum biochemical, electrolyte, and 25-hydroxyvitamin D3 analyses. Urine samples were collected for determination of specific gravity. Glomerular filtration rate (GFR) was determined by plasma iohexol clearance. Histologic examination of renal tissue was performed. One dog in the SC group was euthanatized 3 days after administration of CCF because of severe clinical signs of toxicosis. Dogs in the HP group had significantly higher mean GFR (day 3), serum potassium concentrations (day 14), and urine specific gravity (days 7 and 14) and significantly lower mean serum creatinine concentrations and total calcium X phosphorus concentration product (days 4 and 7) than dogs in the SC group. Dogs in the HP group had no abnormal findings on histologic examination of renal tissue, dogs in the LP and MP groups had trace to mild mineralization of renal tissue, and dogs in the SC group had moderate mineralization and cellular necrosis of proximal renal tubules. Pamidronate disodium is a potentially useful drug to reduce CCF-induced toxicosis and other causes of hypercalcemia associated with increased bone resorption in dogs.

Histologic and functional renal alterations caused by Bothrops moojeni snake venom in rats.

Acute renal failure (ARF) is the main cause of death following snake bites by Bothrops species. In this study, we investigated the morphologic and functional renal disturbances caused by Bothrops moojeni venom in rats. Renal function was assessed based on creatinine and lithium clearances and on histologic examination of renal tissue 5 hr after the intravenous administration of 0.2 mg of venom/kg and 5 hr, 16 hr, and 48 hr after 0.4 mg of venom/ kg. A venom dose of 0.4 mg/kg produced renal tubule disturbances, including acute impairment of proximal and post-proximal tubule sodium handling associated with acute tubule necrosis. The glomerular filtration rate (GFR) decreased significantly and was accompanied by severe morphologic disturbances in the renal glomeruli. These functional and morphologic findings were observed in the absence of any change in mean arterial blood pressure. The decrease in GFR was not related to the presence of fibrin deposits in the glomerular capillary loops. These results suggest an early nephrotoxic action of B. moojeni venom involving significant morphologic and functional changes similar to those observed in snakebite-induced ARF in humans.

Renal amyloidosis in related English foxhounds.

Renal amyloidosis was diagnosed in six related English foxhounds from two separate hunting kennels. There was no apparent age or sex predilection. All the dogs had clinical and laboratory findings compatible with renal disease. The onset of clinical signs was acute in all cases with death or euthanasia in five of the six affected dogs occurring within one week of presentation. The remaining dog was treated with diuresis which produced a temporary improvement. Histological examination of renal tissue from affected dogs identified the presence of both glomerular and interstitial amyloid, which was confirmed by immunohistochemical staining to be of the reactive type (amyloid A). There were occasional sclerosed glomeruli or glomeruli with thickened Bowman's capsules, in addition to interstitial and periglomerular infiltration with a predominance of plasma cells and lymphocytes and secondary changes including tubular eosinophilic casts. Renal papillary necrosis was identified in three dogs. One hound had concurrent multicentric lymphoma. Pedigree analysis of the affected dogs revealed that four individuals shared a common great grandsire and that the same dog was the grandsire of a further case. Pedigree analysis of five additional dogs from one of the kennels, all of which had clinical signs of acute renal failure but from which renal tissue was not available, revealed a close relationship to those foxhounds with confirmed renal amyloidosis.

Idiopathic Focal Segmental Glomerulosclerosis in a Patient With Systemic Lupus Erythematosus: An Unusual Combination

Renal involvement is a major cause of morbidity in patients with systemic lupus erythematosus (SLE). Histologic examination of renal tissue using light microscopy, immunofluorescent staining, and electron microscopy permit identification of glomerular immune complex deposits in virtually all patients with SLE. We report a patient who fulfilled four American College of Rheumatology criteria for the classification of SLE whose clinical course was consistent with SLE, yet whose renal failure resulted from focal glomerulosclerosis that was not mediated by immune complexes. The characteristics of this case of focal glomerulosclerosis that differentiate it from healed focal proliferative glomerulonephritis are discussed.

Renal amyloidosis in a family of Beagles

Summary Renal amyloidosis was confirmed in 6 related male and female Beagles, ranging in age from 5 to 11 years. The most commonly reported signs of illness included lethargy, anorexia, vomiting, and weight loss. Common clinicopathologic abnormalities were normocytic, normochromic anemia; hypoalbuminemia; azotemia; hypercholesterolemia; proteinuria; and urine specific gravity values below the normal range. Histologic examination of renal tissue from the 6 Beagles revealed moderate to severe glomerular amyloidosis with inconsistently observed mild medullary interstitial amyloidosis. Congo red-stained kidney sections from 4 of 4 affected dogs were potassium permanganate-sensitive, suggestive of reactive amyloidosis. Hereditary predisposition for renal amyloidosis was suspected in these Beagles.

Acute renal failure due to viperine snake bite as seen in tropical western India.

A wide spectrum of clinicopathological changes have been described in 50 cases of ARF following viperine snake bite studied prospectively over a 15-year period. Disseminated intravascular coagulation (DIC) was seen in 24/50 cases (Russel's viper bite in 62% and Ecchis carinatus bite in 42% of subjects). Histological examination of renal tissue obtained 1.5 days to 8 weeks after the bite revealed proliferative glomerular changes in 17 cases. These were characterized by ballooning of the capillaries, thickening and splitting of glomerular basement membrane (GMB), fibrin thrombi in the capillaries, and mesangial cell proliferation most prominently seen in Ecchis carinatus bites resulting in ARF.

Arachidonate lipoxygenase products and renal allograft rejection in dogs.

The production of 12-hydroxyeicosatetraenoic acid (12-HETE) and leukotriene B4 (LTB4) was studied in renal tissue obtained from renal allografts and normal kidneys of nonimmunosuppressed dogs that had undergone unilateral renal allotransplantation. We have shown that allografted renal cortex undergoing rejection synthesizes significantly greater quantities of 12-HETE than normal or autotransplanted control renal cortex. There was no significant increase in 12-HETE production by allografted medulla undergoing rejection. Production of LTB4 was significantly greater in the rejecting renal cortex compared to control renal cortex but was not different in the rejecting compared to normal renal medulla. Production of 12-HETE and LTB4 was significantly inhibited by the lipoxygenase-cyclooxygenase inhibitor BW755C, suggesting that production of these compounds was enzyme catalyzed. Histologic examination of renal tissue undergoing rejecting revealed varying degrees of tissue destruction and cellular infiltration. These histologic parameters correlated with the magnitude of 12-HETE production in the allografts. Our findings therefore indicate that arachidonate lipoxygenase products are generated in increased amounts by renal cortical tissue undergoing rejection and suggest that these products may be involved in the rejection process.

Functional basis for the glomerular alterations in uranyl nitrate acute renal failure

We have examined the acute renal failure that occurs after uranyl nitrate administration in the rat and the specific effects of pretreatment of rats with angiotensin converting enzyme inhibitor (CEI), plasma volume expansion (PVE) after uranyl nitrate, and a combination of these treatments. We utilized a combination of micropuncture measurements of glomerular hemodynamics, cage studies, and histologic examination of renal tissue to evaluate the degree of acute renal failure in all groups studied. Uranyl nitrate (UN) (25 mg/kg body wt) administration caused a reduction in the nephron filtration rate (SNGFR) (39.4 +/- 1.6 to 24.8 +/- 2.9 nl X min-1 X g kidney wt-1, P less than 0.02) as a result of a major decrease in the glomerular ultrafiltration coefficient (LpA) from control values (greater than or equal to 0.085 +/- 0.008 to 0.035 +/- 0.007 nl X sec-1 X mm Hg-1 X g kidney wt-1, P less than 0.01). Treatments with CEI, PVE, and the combination of CEI and PVE in rats receiving UN restored 0.38 +/- LpA to normal values (greater than 0.061 +/- 0.009, 0.091 +/- 0.020, and 0.138 +/- 0.020 nl X sec-1 X mm Hg-1 X g kidney wt-1, respectively). Cage studies revealed that CEI treatment prevented oliguria and resulted in major volume losses and reduction in weight. However, rats died after a similar period after UN, but probably by different mechanisms. Analysis of renal ultrastructure revealed equivalent tubular damage in all experimental groups. Alterations in LpA after UN are functional in nature and are potentially preventable and reversible by a combination of treatments with CEI and PVE.