The Effect of Cortex/Medulla Proportions on Molecular Diagnoses in Kidney Transplant Biopsies: Rejection and Injury Can Be Assessed in Medulla.

Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses. Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes (e.g. NPHS2, NPHS1, CLIC5, PTPRO, PLA2R1, PLCE1, PODXL, and REN). Using NPHS2 (podocin) to estimate proportion cortex, we examined whether proportion cortex influenced molecular assessment in the molecular microscope diagnostic system. In 1190 unselected kidney transplant indication biopsies (Clinicaltrials.govNCT01299168), only 11% had <50% cortex. Molecular scores for antibody-mediated rejection, T cell-mediated rejection, and injury were independent of proportion cortex. Rejection was diagnosed in many biopsies that were mostly or all medulla. Agreement in molecular diagnoses in paired cortex/medulla samples (23/26) was similar to biological replicates (32/37). We conclude that NPHS2 expression can estimate proportion cortex; that proportion cortex has little influence on molecular diagnosis of rejection; and that, although histology cannot assess medulla, rejection does occur in medulla as well as cortex.

Nebivolol prevents ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat kidney by regulating NADPH oxidase activation and expression.

We studied whether the ß1-adrenergic antagonist nebivolol would prevent ethanol-induced reactive oxygen species generation and lipoperoxidation in the rat renal cortex. Male Wistar rats were treated with ethanol (20% v/v) for 2 weeks. Nebivolol (10mg/kg/day; p.o. gavage) prevented both the increase in superoxide anion (O2-) generation and thiobarbituric acid reactive substances (TBARS) concentration induced by ethanol in the renal cortex. Ethanol decreased nitrate/nitrite (NOx) concentration in the renal cortex, and nebivolol prevented this response. Nebivolol did not affect the reduction of hydrogen peroxide (H2O2) concentration induced by ethanol. Nebivolol prevented the ethanol-induced increase of catalase (CAT) activity. Both SOD activity and the levels of reduced glutathione (GSH) were not affected by treatment with nebivolol or ethanol. Neither ethanol nor nebivolol affected the expression of Nox1, Nox4, eNOS, nNOS, CAT, Nox organizer 1 (Noxo1), c-Src, p47phox or superoxide dismutase (SOD) isoforms in the renal cortex. On the other hand, treatment with ethanol increased Nox2 expression, and nebivolol prevented this response. Finally, nebivolol reduced the expression of protein kinase (PK) Cδ and Rac1. The major finding of our study is that nebivolol prevented ethanol-induced reactive oxygen species generation and lipoperoxidation in the kidney by a mechanism that involves reduction on the expression of Nox2, a catalytic subunit of NADPH oxidase. Additionally, we demonstrated that nebivolol reduces NADPH oxidase-derived reactive oxygen species by decreasing the expression of PKCδ and Rac1, which are important activators of NADPH oxidase.

A case of penetrating glass foreign body within the renal cortex.

A 32-year-old patient sustained a penetrating injury to the left flank and kidney after a fall backward onto a glass table. On computed tomography imaging, a 12×10×4 cm glass shard was identified penetrating the renal cortex. The patient was taken to the operating room to remove the foreign object. A rubber-shodded clamp was used to successfully remove the glass shard without complication. Although we commonly encounter stab wounds at our trauma center, the penetrating object is rarely present. The presence of the glass object resulted in a technically challenging and rare case.

Efecto del extracto acuoso de la raíz de Ruellia Tuberosa L. sobre el daño renal en la diabetes. Papel del estrés oxidativo / Effect of the aqueous extract of the root of Ruellia Tuberosa L. on kidney damage in diabetes. Role of oxidative stress

La diabetes es una de los principales problemas de la salud pública mundial, en parte debido a su asociación con otras enfermedades cardiometabólicas. Las complicaciones tisulares de la diabetes es su principal causa de muerte, siendo la nefropatía diabética la que lidera la lista de daños inducidos por la hiperglicemia crónica. Se conocen varios mediadores celulares de la nefropatía: la angiotensina II, los productos de glicosilación avanzada, las kinasas activadas por mitógenos, las especies reactivas de oxígeno y nitrógeno, entre otras, cuya activación traen como consecuencia el aumento de la síntesis de proteínas de la matriz extracelular, el ensanchamiento del glomérulo, el daño tubular y la fibrosis. Esto se traduce en insuficiencia renal crónica, caracterizada por la proteinuria, el aumento de la diuresis, el desequilibrio electrolítico, el incremento de creatinina plasmática y del nitrógeno ureico en sangre (BUN), los cuales son considerados marcadores clínicos del daño renal en la diabetes. Muchos grupos de investigación están enfocados en la búsqueda de fármacos que sean capaces de abolir, disminuir o prevenir la nefropatía diabética. En el campo de la etnobotánica, la etnomedicina y la etnofarmacología existen diversos estudios que han aportado nuevas especies, fitofármacos y productos naturales para el tratamiento no sólo de la diabetes, sino también de sus complicaciones. Existen alrededor de 1200 plantas antidiabéticas en el mundo. En Venezuela son muy pocas las especies que han sido estudiadas, a pesar que goza de gran biodiversidad vegetal. Ruellia tuberosa L. (yuquilla) es una de estas plantas de uso etnomédico, la cual pertenece a la familia Acanthaceae y está distribuida en todo el país. Las partes aéreas de esta especie han sido estudiadas de manera exhaustiva, encontrándose actividad: antidiabética, antioxidante, antiinflamatoria y analgésica. Sin embargo, su raíz ha sido muy poco estudiada. Recientemente, reportamos la actividad analgésica y antiinflamatoria del extracto acuoso de la raíz de R. tuberosa (RT) en animales de experimentación. Con el fin de validar su uso tradicional como antidiabético y de conocer la capacidad protectora ante las complicaciones de la diabetes, en este trabajo se evaluó el efecto del RT sobre el daño renal en un modelo de ratas con diabetes inducida por la estreptozotocina (ETZ) e in vitro en células de epitelio renal (células Vero) sometidas a altas concentraciones de glucosa. Asimismo, se evaluó la relación de la actividad protectora del RT con su potencial antioxidante y con la inhibición de la vía de señalización de la PKC-NF-κB. Para ello fueron evaluadas las modificaciones de la glicemia, de los marcadores de daño renal, el daño oxidativo renal, el sistema antioxidante renal, la proliferación y muerte de las células de epitelio renal, en los modelos experimentales bajo diferentes condiciones de estrés. Asimismo la expresión del NF-κB inducida por un activador de la PKC (PMA) en células de cáncer de cuello uterino (HeLa), la actividad antioxidante y el contenido de polifenoles del extracto. Los resultados muestran que el RT contiene compuestos polifenólicos y que produce un efecto atrapador del anión superóxido, estableciéndose así su capacidad antioxidante. El RT disminuyó la glicemia, la proteinuria, la diuresis, el BUN la creatinina plasmática y la pérdida de peso en los animales diabéticos; disminuyó el contenido de grupos carbonilos en las proteínas, de malonildialdehido, de proteínas totales en la corteza renal y suprimió el incremento del peso del riñón en las ratas con diabetes inducida por la ETZ; contrarrestó el decremento de la actividad de la CAT, SOD total, CuZn-SOD, GPx y GR inducida por la glucosa in vivo e in vitro; protegió a las células Vero de la glucotoxicidad, del estrés oxidativo y del estrés nitrosativo, inducido por la alta glucosa, por el peróxido de hidrógeno y por el nitroprusiato de sodio respectivamente. Sin embargo, el peróxido, el nitroprusiato así como el PMA disminuyeron el efecto protector del RT sobre la glucotoxicidad. Este extracto previno el incremento de la actividad del NF-κB inducido por el PMA en las células HeLa. Todos estos hallazgos establecen al RT como un antioxidante con efecto protector sobre el daño renal en la diabetes, tanto in vivo como in vitro, a través de un mecanismo que involucra la disminución de la glicemia, del estrés oxidativo, del estrés nitrosativo, y de la vía de señalización de la PKC-NF-kB. Esto aporta, por primera vez, información acerca de los efectos farmacológicos de la especie, a la vez que contribuye tanto a la validación de su uso tradicional como a la caracterización farmacológica de su género, sentado así las bases para el estudio fitoquímico y tecnológico de este potencial fitofármaco.

Ultrastructural changes in the kidney cortex of rats treated with lead acetate / Cambios ultraestructurales en la corteza renal de ratas tratadas con acetato de plomo

The purpose of this study was to investigate the ultrastructural effects of lead on the kidney cortex of rats. Wistar Albino rats (180-200g body weight) were divided into a controlled and lead acetate-exposed group. Rats received lead acetate at 500 ppm in their drinking water for 60 days. Both groups were fed with the same standard food, but lead acetate was added to the drinking water. During the experimental period, blood samples were taken from the abdominal aorta of the anesthetised animals. At the end of exposure, body weight and blood lead levels were measured. The kidney tissue samples were prepared and analyzed by light and transmission electron microscopy. Cortical renal tubules show various degenerative changes with focal tubular necrosis invaded by inflammatory cells. The ultrastructural alterations found in lead acetate-treated rats were a diminution in the amount of filtration slits, increased fusion of foot processes in epithelial cells of the glomeruli, increase of lysosomal structures and pinocytic vesicles as well as large mitochondria in proximal tubule cells.

El propósito de este estudio fue investigar los efectos ultraestructurales del plomo en la corteza renal. Ratas Wistar albinas (180-200g de peso corporal) fueron divididas en grupo control y grupo experimental. Las ratas recibieron 500 ppm de acetato de plomo en el agua potable durante 60 días. Ambos grupos fueron alimentados con el mismo alimento estándar, pero acetato de plomo se le añadió al agua potable al grupo experimental. Durante el período experimental, se tomaron bajo anestesia muestras sanguíneas desde la parte abdominal de la aorta. Al final de la exposición, fueron medidos el peso corporal y los niveles de plomo en la sangre. Fueron preparadas las muestras de tejido renal y se analizaron mediante microscopía de luz y electrónica de transmisión. Los túbulos renales corticales mostraron varios cambios degenerativos con necrosis tubular focal invadida por células inflamatorias. Las alteraciones ultraestructurales encontradas en las ratas tratadas con acetato de plomo correspondieron a una disminución en la cantidad de ranuras de filtración, aumento de la fusión de los procesos podales en las células epiteliales de los glomérulos, aumento de la estructura lisosomal y las vesículas pinocíticas, así como grandes mitocondrias en las células del túbulo proximal.

Predictive factors for acute renal cortical scintigraphic lesion and ultimate scar formation in children with first febrile urinary tract infection.

PURPOSE: We assessed predictive factors for acute renal cortical scintigraphic lesion and ultimate scar formation in children with a first febrile urinary tract infection. MATERIALS AND METHODS: A total of 89 girls and 138 boys with a first febrile urinary tract infection were included in the study. We analyzed radiological (ultrasound, dimercapto-succinic acid scintigraphy, voiding cystourethrogram), clinical (age, gender, peak fever, therapeutic delay time) and laboratory (complete blood count with differential count, absolute neutrophil count, blood urea nitrogen, creatinine, urinalysis, Gram's stain, culture, C-reactive protein, erythrocyte sedimentation rate) variables. Dimercapto-succinic acid scintigraphy was performed within 5 days and at 6 months after diagnosis of urinary tract infection. Voiding cystourethrogram was performed after the acute phase of the urinary tract infection. Predictive factors for acute scintigraphic lesion and ultimate scar formation were assessed using logistic regression analysis. RESULTS: Of 227 patients enrolled 140 had a refluxing and 87 a nonrefluxing urinary tract infection. On logistic regression analysis therapeutic delay time (p = 0.001) and presence of reflux (p = 0.011) were predictive of acute scintigraphic lesion and ultimate scar formation (p = 0.001 and p = 0.0001, respectively) in children with a first febrile urinary tract infection. CONCLUSIONS: Since vesicoureteral reflux is the common risk factor for acute scintigraphic lesion and ultimate scar formation, voiding cystourethrogram must be considered as an initial study in patients with acute febrile urinary tract infection.

Analysis of microcracks caused by drop shatter testing of porcine kidneys.

Although kidney trauma is a relatively common injury, its microscopic biomechanics are poorly understood. Experimental low-grade trauma in pig kidneys was studied using optical microscopy. We observed ruptures in the cortex as well as in the medulla. Both parts of the renal parenchyma were damaged, even in areas of the kidneys that were free of macroscopic cracks on the surface. To determine which constituents of the renal cortex and medulla, i.e. tubular parts of the nephron or the interstitial connective tissue, were less resistant to injury during the drop shatter test, we applied a simple stereological method to discriminate between random and tissue-specific rupture propagation. The ruptures propagated predominantly through the interstitial connective tissue of the renal cortex and medulla. The volume fraction of the tubules assessed by the Cavalieri principle was 90.4% within the renal cortex and 52.4% within the medulla. The most frequently affected blood vessels were the arcuate and interlobular veins, followed by the arcuate and interlobular arteries. No disruptions of the renal calyces were found.

The repeated extracorporeal shock waves and the renal parenchyma injury on normal and diabetic rats

PURPOSE: To assess the effect of repeated extracorporeal shock waves (ESW) on renal parenchyma of normal and diabetic rats. METHODS: 40 normal rats (A) and 40 diabetic rats (B) were assigned for ESW (Direx Tripter X1® - 14 KVA) as follow: A1/B1 and A3/B3 no ESW; A2/B2 one ESW (2,000 SW); A4/B4 two ESW (4,000 SW) in an elapsed 14 days. All the animals were sacrificed 3 days after the ESW and samples of renal parenchyma were histological prepared, stained by H&E. For each animal the frequency of hemorrhage focus (HF) in the subcapasular, interstitial and glomerulus area was calculated (porcentage) on 20 randomly histological sections. RESULTS: No one HF was identified in all normal or diabetic animals without ESW (A1, A3 and B1, B3). In the normal rats the HF frequency was similar to one ESW (subcapsular =15 percent; interstitial =20 percent and glomerular =10 percent) or repetead ESW (subcapsular =25 percent; interstitial =20 percent; glomerular=10 percent). In diabetic rats the occurence of HF with repetead ESW was more frequent (subcapsular =40 percent; interstitial =30 percent and glomerular =10 percent) than with a single ESW (subcapsular =25 percent; interstitial =15 percent and glomerular =15 percent). CONCLUSION: A single ESW or a repeated ESW caused a mild and similar damage on renal cortex of normal rats. In diabetic rats the repetead ESW may result in an accumulated damage, especially with focus of hemorrhage in subcapsular and interstitial tissue and glomerulus edema.

RESUMO OBJETIVO: Avaliar o efeito de repetidas ondas de choque extracorpóreas (OCE) sobre o parênquima renal de ratos normais e diabéticos. MÉTODOS: 40 ratos normais e 40 ratos diabéticos foram distribuídos para aplicação de OCE (Direx Tripter X1® - 14 KVA) como segue: A1/B1 e A3/B3 sem OCE; A2/B2 uma sessão de OCE (2000 OC); A4/B4 duas sessões de OC (4000 OC) num intervalo de 14 dias. Todos os animais foram sacrificados no 3°. dia após a aplicação da OCE e amostras de parênquima renal foram histologicamente preparados e corados em H&E. Para cada animal foi calculado, em 20 campos aleatórios, a freqüência (em porcentagem) de focos hemorrágicos (FH) nas áreas subcapsular, intersticial e glomerular. RESULTADOS: Nenhum foco hemorrágico foi identificado nos animais normais ou diabéticos que não receberam nenhuma OCE (A1, A3 e B1, B3). Nos ratos normais a freqüência de FH foi similar com uma sessão de OCE (subcapsular =15 por cento; intersticial =20 por cento e glomerular =10 por cento) ou duas sessões de OCE (subcapsular =25 por cento; intersticial =20 por cento; glomerular =10 por cento). Nos ratos diabéticos a ocorrência de FH com duas sessões de OCE foi mais freqüente (subcapsular =40 por cento; intersticial =30 por cento e glomerular =10 por cento) do que com uma simples sessão de OCE (subcapsular =25 por cento; intersticial =15 por cento e glomerular =15 por cento). CONCLUSÃO: Uma única ou duas sessões de OCE causa um discreto e semelhante dano no parênquima renal de ratos normais. Nos ratos diabéticos a repetição da OCE pode resultar em acúmulo de danos, especialmente com FH nas áreas subcapsular e intersticial e no edema do glomérulo.

The repeated extracorporeal shock waves and the renal parenchyma injury on normal and diabetic rats.

PURPOSE: To assess the effect of repeated extracorporeal shock waves (ESW) on renal parenchyma of normal and diabetic rats. METHODS: 40 normal rats (A) and 40 diabetic rats (B) were assigned for ESW (Direx Tripter X1 - 14 KVA) as follow: A1/B1 and A3/B3 no ESW; A2/B2 one ESW (2,000 SW); A4/B4 two ESW (4,000 SW) in an elapsed 14 days. All the animals were sacrificed 3 days after the ESW and samples of renal parenchyma were histological prepared, stained by H&E. For each animal the frequency of hemorrhage focus (HF) in the subcapsular, interstitial and glomerulus area was calculated (percentage) on 20 randomly histological sections. RESULTS: No one HF was identified in all normal or diabetic animals without ESW (A1, A3 and B1, B3). In the normal rats the HF frequency was similar to one ESW (subcapsular =15%; interstitial =20% and glomerular =10%) or repeated ESW (subcapsular =25%; interstitial =20%; glomerular=10%). In diabetic rats the occurrence of HF with repeated ESW was more frequent (subcapsular =40%; interstitial =30% and glomerular =10%) than with a single ESW (subcapsular =25%; interstitial =15% and glomerular =15%). CONCLUSION: A single ESW or a repeated ESW caused a mild and similar damage on renal cortex of normal rats. In diabetic rats the repeated ESW may result in an accumulated damage, especially with focus of hemorrhage in subcapsular and interstitial tissue and glomerulus edema.

Investigation of the thermal and tissue injury behaviour in microwave thermal therapy using a porcine kidney model.

Minimally invasive microwave thermal therapies are being developed for the treatment of small renal cell carcinomas (RCC, d<3 cm). This study assessed the thermal history and corresponding tissue injury patterns resulting from microwave treatment of the porcine renal cortex. Three groups of kidneys were evaluated: (1) in vitro treated, (2) in vivo with 2-h post-treatment perfusion (acute) and (3) in vivo with 7-day post-treatment perfusion (chronic). The kidneys were treated with an interstitial water-cooled microwave probe (Urologix, Plymouth, MN) that created a lesion centered in the renal cortex (50 W for 10 min). The thermal histories were recorded at 0.5 cm radial intervals from the probe axis for correlation with the histologic cellular and vascular injury. The kidneys showed a reproducible 2 cm chronic lesion with distinct histologic injury zones identified. The thermal histories at the edge of these zones were found using Lagrangian interpolation. The threshold thermal histories for microvascular injury and stasis appeared to be lower than that for renal epithelial cell injury. The Arrhenius kinetic injury models were fit to the thermal histories and injury data to determine the kinetic parameters (i.e. activation energy and frequency factor) for the thermal injury processes. The resultant activation energies are consistent in magnitude with those for thermally induced protein denaturation. A 3-D finite element thermal model based on the Pennes bioheat equation was developed and solved using ANSYS (V7.0). The real geometry of the kidneys studied and temperature dependent thermal properties were used in this model. The specific absorption rate (SAR) of the microwave probe required for the thermal modelling was experimentally determined. The results from the thermal modelling suggest that the complicated change of local renal blood perfusion with temperature and time during microwave thermal therapy can be predicted, although a first order kinetic model may be insufficient to capture blood flow changes. The local blood perfusion was found to be a complicated function of temperature and time. A non-linear model based on the degree of vascular stasis was introduced to predict the blood perfusion. In conclusion, interstitial microwave thermal therapy in the normal porcine kidney results in predictable thermal and tissue injury behaviour. Future work in human kidney tissue will be necessary to confirm the clinical significance of these results.

Morphological changes induced in the pig kidney by extracorporeal shock wave lithotripsy: nephron injury.

While shock wave lithotripsy (SWL) is known to cause significant damage to the kidney, little is known about the initial injury to cells along the nephron. In this study, one kidney in each of six juvenile pigs (6-7 weeks old) was treated with 1,000 shock waves (at 24 kV) directed at a lower pole calyx with an unmodified HM-3 lithotripter. Three pigs were utilized as sham-controls. Kidneys were fixed by vascular perfusion immediately after SWL or sham-SWL. Three of the treated kidneys were used to quantitate lesion size. Cortical and medullary samples for light (LM) and transmission electron microscopy (TEM) were taken from the focal zone for the shock waves (F2), the contralateral kidney, and the kidneys of sham-SWL pigs. Because preservation of the tissue occurred within minutes of SWL, the initial injury caused by the shock waves could be separated from secondary changes. No tissue damage was observed in contralateral sham-SWL kidneys, but treated kidneys showed signs of injury, with a lesion of 0.2% +/- 0.1% of renal volume. Intraparenchymal hemorrhage and injury to tubules was found at F2 in both the cortex and medulla of SWL-treated kidneys. Tubular injury was always associated with intraparenchymal bleeding, and the range of tissue injury included total destruction of tubules, focal cellular fragmentation, necrosis, cell vacuolization, and membrane blebbing. The initial injury caused by SWL was cellular fragmentation and necrosis. Cellular vacuolization, membrane blebbing, and disorganization of apical brush borders appear to be secondary changes related to hypoxia.

Cholesterol ester accumulation: an immediate consequence of acute in vivo ischemic renal injury.

BACKGROUND: Cholesterol is a major constituent of plasma membranes, and recent evidence indicates that it is up-regulated during the maintenance phase of acute renal failure (ARF). However, cholesterol's fate and that of the cholesterol ester (CE) cycle [shuttling between free cholesterol (FC) and CEs] during the induction phase of ARF have not been well defined. The present studies sought to provide initial insights into these issues. METHODS: FC and CE were measured in mouse renal cortex after in vivo ischemia (15 and 45 minutes)/reperfusion (0 to 120 minutes) and glycerol-induced myoglobinuria (1 to 2 hours). FC/CE were also measured in (1) cultured human proximal tubule (HK-2) cells three hours after ATP depletion and in (2) isolated mouse proximal tubule segments (PTSs) subjected to plasma membrane damage (with cholesterol oxidase, sphingomyelinase, phospholipase A2, or cytoskeletal disruption with cytochalasin B). The impact of cholesterol synthesis inhibition (with mevastatin) and FC traffic blockade (with progesterone) on injury-evoked FC/CE changes was also assessed. RESULTS: In vivo ischemia caused approximately threefold to fourfold CE elevations, but not FC elevations, that persisted for at least two hours of reperfusion. Conversely, myoglobinuria had no effect. Isolated CE increments were observed in ATP-depleted HK-2 cells. Neither mevastatin nor progesterone blocked this CE accumulation. Plasma membrane injury induced with sphingomyelinase or cholesterol oxidase, but not with phospholipase A(2) or cytochalasin B, increased tubule CE content. High CE levels, induced with cholesterol oxidase, partially blocked hypoxic PTS attack. CONCLUSIONS: In vivo ischemia/reperfusion acutely increases renal cortical CE, but not FC, content, indicating perturbed CE/FC cycling. The available data suggest that this could stem from specific types of plasma membrane damage, which then increase FC flux via aberrant pathways to the endoplasmic reticulum, where CE formation occurs. That CE levels are known to inversely correlate with both renal and nonrenal cell injury suggests the potential relevance of these observations to the induction phase of ischemic ARF.

Modulation by cyclic AMP and phorbol myristate acetate of cephaloridine-induced injury in rat renal cortical slices.

Intracellular signaling pathways of cAMP and protein kinase C (PKC) have been suggested to modulate the generation of free radicals. We investigated the effects of cAMP and phorbol myristate acetate (PMA), a PKC activator, on cephaloridine (CER)-induced renal cell injury, which has been reported to be due to the generation of free radicals. Incubation of rat renal cortical slices with CER resulted in increases in lipid peroxidation and lactate dehydrogenase (LDH) release and in decreases in gluconeogenesis and p-aminohippurate (PAH) accumulation in rat renal cortical slices, suggesting free radical-induced injury in slices exposed to CER. A derivative of cAMP ameliorated not only the increase in lipid peroxidation but also the renal cell damage induced by CER. This amelioration by a cAMP derivative of lipid peroxidation and renal cell damage caused by CER was blocked by KT 5720, a protein kinase A (PKA) inhibitor. Lipid peroxidation and the indices of cell injury were increased by PMA. PMA also enhanced CER-induced lipid peroxidation and cell damage in the slices. This enhancement by PMA of CER-induced injury was blocked by H-7, a PKC inhibitor. These results indicated that intracellular signaling pathways of cAMP and PKC modulate free radical-mediated nephrotoxicity induced by CER.

The role of endothelin in early renal cortical reperfusionin renal transplantation.

The role of specific endothelin receptors in the early renal reperfusion and long-term survival in renal transplantation was investigated in Lewis rats. Left renal transplantation was performed following 2 h cold ischaemia without and with ET(A) receptor antagonism and following 16 h cold ischaemia with no treatment, with ET(A) receptor antagonism and with ET(B) receptor antagonism. The ET(A) and ET(B) receptor antagonists, BQ-610 and A-192621 respectively, were added to the preservation solution. Renal cortical perfusion (RCP) was measured postoperatively using laser Doppler flowmetry. All rats in the 2-hour groups survived for 15 days. Animals in the untreated 16-hour group or in the A-192621-treated group died between days 3 and 6 after surgery. Fifty percent of the rats in the 16-hour and BQ-610-treated group died between days 4 and 7 after surgery while the other 50% survived for 15 days. Survival rates correlated well with both the postoperative serum creatinine and the recovery of RCP. We conclude that addition of an ET(A) receptor antagonist to the preservation solution improves renal reperfusion and long-term survival following prolonged ischaemia, whereas ET(B) receptor antagonism does neither.

Material characterization of the pig kidney in relation with the biomechanical analysis of renal trauma.

The objective of this study was an investigation of the material properties of the fresh pig kidney and parametric characterization of its elastic and inelastic material behavior. The material investigation included density measurements, uniaxial as well as three-dimensional compression tests, tensile tests. and shear tests on the samples extracted from the fresh pig kidney. For comparison, density measurements on a number of soft synthetic materials were also performed. Compression tests on the radial and the tangential specimens from the cortex tissue were performed at various loading rates. Three-axial compression tests were performed on the cortex tissues placed in a compression chamber. Shear tests were performed by punching a cylinder into a slice of the cortex. Tensile tests were carried out on the outer capsule. For characterization of the material behavior, a non-linear theoretical simulation based on a two parameter Blatz model was used. For characterization of the time-dependent behavior of the pig kidney cortex, a four-parameter linear viscoelastic model was employed. From the present experimental and theoretical studies, a number of conclusions were derived: (1) The general behavior of the pig kidney cortex samples under compression showed the general non-linear features typical of the soft tissues; the stress strain diagram was composed of a very flat part at very low stress level to about 30% relative deformation which was followed by a steeply rising stiffening leading to the radial rupture of samples marked by a maximum nominal rupture strain of about 50%. (2) The uniaxial compression tests on the radial and the tangential samples from the cortex tissue showed an increase of the rupture stress with the increase in the loading rate, but a decrease in the related rupture strain. (3) The long-term uniaxial compression tests on the cortex specimens under sustained constant load showed an instantaneous deformation followed by a creep response which eventually approached an asymptote. (4) Simulation of the non-linear material behavior of the cortex tissue under uniaxial compression by the Blatz model gave two pairs of material parameters for the cortex in the radial and the tangential directions. Furthermore, fitting of the assumed four-parameter linear viscoelastic model with the experimental data resulted in the viscoelastic material parameters.

Na+,K(+)-ATPase activity of rabbit kidney cortex membranes in ischemia and reperfusion.

The activity of Na+,K(+)-ATPase in the microsomal fraction of rabbit kidney cortex was strongly decreased by ischemia and increased slightly, but not significantly, after reperfusion. These changes were correlated with a dramatic increase in lipid peroxidation in microsomes isolated from both ischemic and reperfused kidneys. This correlation may point to irreversible impairment of the enzymatic function under the influence of either oxygen free radicals or lipid peroxidation.

Attempted nonoperative management of blunt renal lacerations extending through the corticomedullary junction: the short-term and long-term sequelae.

A total of 50 patients who sustained a renal laceration extending through the corticomedullary junction following blunt trauma underwent an attempt at nonoperative (expectant) management of the urological injury. Of the patients 18% could not be stabilized and they subsequently underwent emergency laparotomy. Among our stabilized patients 2 major categories existed: 1) 30 patients with vascularized renal fragments and 2) 11 in whom a fragment of the kidney was devascularized. A statistically significant difference in the length of hospital stay (p equals 0.01) and the need for delayed surgical intervention (p less than 0.001) was noted between the 2 groups. We recommend that the physician must have a heightened awareness of probable complications in patients with major renal lacerations associated with devitalized fragments and suggest that early surgical management should be considered.

Dosimetry study of Nd:YAG laser damage to canine renal cortex.

A dosimetry study of factors affecting the extent of tissue damage inflicted upon the canine renal cortex by the Neodymium:Yttrium Aluminum Garnet (Nd:YAG) laser was undertaken. Laser parameters and renal tissue conditions were varied independently in duplicate in the following manner: (1) power - 5, 10, 20, 50, 75, 100 watts with a spot size of 1.2 mm; (2) exposure duration - 1, 2, and 4 seconds; (3) kidney perfusion and temperature--renal artery unclamped (perfused) without cooling; renal artery clamped (non-perfused) without cooling; and renal artery clamped with cooling. Five days following application of the laser, the animals were sacrificed and serial sections of the renal cortex were examined for maximum depth and width of tissue damage and ablation. Multiple linear regression analysis of the data indicated a direct linear relationship between the joules (watts X seconds) of energy delivered to the renal cortex and the depth and width of tissue damage and ablation (p less than 0.001 for joule regression coefficient for each variable). Seconds and/or watts alone were not major predictors of the outcome after accounting for joules. Clamping the main renal artery significantly reduced the depth and width of laser damage when compared to the perfused kidney (p less than 0.001 for each variable). The depth of damage was similar in the cooled and the non-cooled non-perfused kidney. These data suggest that increased laser energy and kidney perfusion significantly increase renal cortical laser induced damage. Adjustment of these parameters may permit controlled tumor ablation or tissue incision with minimal damage to adjacent normal tissue.