Renal cortex microperfusion evaluated by laser speckle contrast imaging in an ex vivo perfused kidney model-A proof-of-concept study.

BACKGROUND: Validated quantitative biomarkers for assessment of renal graft function during normothermic machine perfusion (NMP) conditions are lacking. The aim of this project was to quantify cortex microperfusion during ex vivo kidney perfusion using laser speckle contrast imaging (LSCI), and to evaluate the sensitivity of LSCI when measuring different levels of renal perfusion. Furthermore, we aimed to introduce LSCI measurements during NMP in differentially damaged kidneys. METHODS: Eleven porcine kidneys were nephrectomized and perfused ex vivo. Cortex microperfusion was simultaneously monitored using LSCI. First, a flow experiment examined the relationship between changes in delivered renal flow and corresponding changes in LSCI-derived cortex microperfusion. Second, renal cortical perfusion was reduced stepwise by introducing a microembolization model. Finally, LSCI was applied for measuring renal cortex microperfusion in kidneys exposed to minimal damage or 2 h warm ischemia (WI). RESULTS: Cortex microperfusion was calculated from the LSCI-obtained data. The flow experiment resulted in relatively minor changes in cortex microperfusion compared to the pump-induced changes in total renal flow. Based on stepwise injections of microspheres, we observed different levels of cortex microperfusion that correlated with administrated microsphere dosages (r2 = 0.95-0.99). We found no difference in LSCI measured cortex microperfusion between the kidneys exposed to minimal damage (renal cortex blood flow index, rcBFI = 2090-2600) and 2 h WI (rcBFI = 2189-2540). CONCLUSIONS: Based on this preliminary study, we demonstrated the feasibility of LSCI in quantifying cortex microperfusion during ex vivo perfusion. Furthermore, based on LSCI-measurements, cortical microperfusion was similar in kidneys exposed to minimal and 2 h WI.

Predictive value of contrast-enhanced ultrasonography for the early diagnosis of renal dysfunction after kidney transplantation: A systematic review and meta-analysis.

OBJECTIVES: We aimed to evaluate the changes in renal cortical microperfusion and quantitative contrast-enhanced ultrasonography (CEUS) parameters after kidney transplantation, and to determine the evidence-based value of CEUS in predicting renal dysfunction. METHODS: The Embase, MEDLINE, Web of Science, and Cochrane Library databases were searched for relevant studies published from 2000 to 2023 on the use of CEUS to assess the renal cortical microcirculation after kidney transplantation. Subject terms and related keywords were combined, and a meta-analysis and systematic review were performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. RESULTS: The search yielded six studies involving 451 patients with moderate to high overall quality. The peak intensity (standardized mean difference [SMD]: -0.64, 95% confidence interval [CI] -1.13 to -0.15, p = 0.01) of CEUS was significantly lower in patients with renal dysfunction than in those with stable renal function. However, the time to peak (SMD: 0.28, 95% CI 0.04 to 0.52, p = 0.02) was significantly shorter in patients with renal dysfunction than in those with stable renal function. The total renal cortical microperfusion and renal cortical perfusion intensity were decreased, and the perfusion time was prolonged, in patients with renal dysfunction after kidney transplantation. CONCLUSION: CEUS parameters can reflect real-time changes in renal cortical microperfusion, thus providing a basis for the early diagnosis of renal dysfunction after kidney transplantation.

Ultrasonographic quantitative evaluation of acute and chronic renal disease using the renal cortical thickness to aorta ratio in dogs.

The renal cortical thickness (RCT) has been correlated with renal function. Previous studies have also reported that the RCT:Abdominal aorta(Ao) ratio is constant in normal dogs with various physical factors. This multi-center, retrospective, analytical study aimed to determine if there are differences between actual RCT and predicted value of RCT considering physical factors in dogs with acute or chronic renal disease. We also aimed to demonstrate whether the RCT and Ao ratio index would be useful for evaluating renal pathology. A total of 54 dogs with acute or chronic renal disease and 30 normal healthy dogs were included in this study. The RCT was measured at the center of the renal pyramid as the shortest distance perpendicular to the renal capsule from the base of the renal medullary pyramid at three points. The diameter of the Ao was measured just caudal to the branch of the left renal artery in the sagittal plane in systole. The RCT:Ao ratio of chronic kidney disease (CKD) patients was 0.50 ± 0.11 (mean ± standard deviation). The RCT:Ao ratio in normal dogs was 0.67 ± 0.07. The RCT:Ao ratio in patients with acute kidney injury (AKI) was 0.83 ± 0.05. There was a statistically significant difference between normal dogs and dogs with CKD (P < 0.001) and between normal dogs and dogs with AKI (P < 0.001). In conclusion, findings from the current study supported using the RCT:Ao ratio as a non-invasive quantitative method for characterizing kidney pathology in dogs with acute or chronic renal disease.

A mathematical model of the rat kidney. IV. Whole kidney response to hyperkalemia.

The renal response to acute hyperkalemia is mediated by increased K+ secretion within the connecting tubule (CNT), flux that is modulated by tubular effects (e.g., aldosterone) in conjunction with increased luminal flow. There is ample evidence that peritubular K+ blunts Na+ reabsorption in the proximal tubule, thick ascending Henle limb, and distal convoluted tubule (DCT). Although any such reduction may augment CNT delivery, the relative contribution of each is uncertain. The kidney model of this laboratory was recently advanced with representation of the cortical labyrinth and medullary ray. Model tubules capture the impact of hyperkalemia to blunt Na+ reabsorption within each upstream segment. However, this forces the question of the extent to which increased Na+ delivery is transmitted past the macula densa and its tubuloglomerular feedback (TGF) signal. Beyond increasing macula densa Na+ delivery, peritubular K+ is predicted to raise cytosolic Cl- and depolarize macula densa cells, which may also activate TGF. Thus, although the upstream reduction in Na+ transport may be larger, it appears that the DCT effect is critical to increasing CNT delivery. Beyond the flow effect, hyperkalemia reduces ammoniagenesis and reduced ammoniagenesis enhances K+ excretion. What this model provides is a possible mechanism. When cortical [Formula: see text] is taken up via peritubular Na+-K+([Formula: see text])-ATPase, it acidifies principal cells. Consequently, reduced ammoniagenesis increases principal cell pH, thereby increasing conductance of both the epithelial Na+ channel and renal outer medullary K+ channel, enhancing K+ excretion. In this model, the effect of aldosterone on principal cells, diminished DCT Na+ reabsorption, and reduced ammoniagenesis all provide relatively equal and additive contributions to renal K+ excretion.NEW & NOTEWORTHY Hyperkalemia blunts Na+ reabsorption along the nephron, and increased CNT Na+ delivery facilitates K+ secretion. The model suggests that tubuloglomerular feedback limits transmission of proximal effects past the macula densa, so that it is DCT transport that is critical. Hyperkalemia also reduces PCT ammoniagenesis, which enhances K+ excretion. The model suggests a mechanism, namely, that reduced cortical ammonia impacts CNT transport by raising cell pH and thus increasing both ENaC and ROMK conductance.

Coadministration of Melatonin and Insulin Improves Diabetes-Induced Impairment of Rat Kidney Function.

INTRODUCTION: The present study was designed to evaluate the therapeutic efficacy of melatonin and insulin coadministration in diabetes-induced renal injury in rats. RESEARCH DESIGN AND METHODS: Diabetes was achieved by giving streptozotocin (15 mg/kg) for 6 consecutive days. The diabetic condition was confirmed by assessing the blood glucose level; animals having blood glucose levels above 250 mg were considered as diabetic. Following the confirmation, animals were randomly divided into different experimental groups, viz group I served as the control (CON), group II diabetic (D), group III D+melatonin (MEL), group IV D+insulin (INS), group V D+MEL+INS, group VI D+glibenclamide (GB), group VII CON+MEL, group VIII CON+INS, and group IX CON+GB. Following the completion of the experimental period, animals were sacrificed, blood was collected via a retro-orbital puncture, and kidneys were harvested. Diabetic rats exhibited a significant increment in blood glucose and biochemical indexes of renal injury (tubular disruption, swollen glomeruli with loss of glomerular spaces, and distortion of the endothelial lining) including augmented levels of serum creatinine, urea, uric acid, Na+, and K+, and inhibition/suppression of the activity of glutathione (GSH) peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase, and GSH-S-transferase in the renal cortex. RESULTS: By examining thiobarbiturate reactive substances, reduced GSH, superoxide dismutase activity, and catalase activity in the renal cortex of control and diabetic rats, it was documented that treatment with melatonin or insulin alone or in combination showed a significant ad integrum recovery of GSH-dependent antioxidative enzymatic activities. Melatonin and insulin coadministration caused greater reductions in circulating tumor necrosis factor-α, tumor growth factor-ß1, interleukin (IL)-1ß, and IL-6 levels in diabetic rats, whereas IL-10 levels increased, as compared to each treatment alone. Diabetic rats showed a significant increase in the expression of both MT1 and MT2 melatonin receptor genes. Melatonin or insulin treatment alone or in combination resulted in significant restoration of the relative expression of both melatonin receptors in the renal cortex. CONCLUSION: The coadministration of exogenous melatonin and insulin abolished many of the deleterious effects of type 1 diabetes on rat renal function.

Ameliorative role of alpha-lipoic acid in renal cortical structural damage, induced by limb ischemia-reperfusion injury in the rat.

Ischemia-reperfusion injury is related to kidney dysfunction due to bilateral lower limb ischemia. This kidney injury may lead to acute kidney failure and mortality. Alpha-Lipoic Acid, a known antioxidant, can ameliorate kidney dysfunction and histopathology related to several etiologies. Ischemia was performed in adult male rats by bilateral femoral artery occlusion, then ischemia-reperfusion was done for 1 day and 7 days. Lipoic acid was administered to rats that had undergone ischemia-reperfusion for 7 days. The renal cortices of the kidneys of the tested groups were processed for light and electron microscopic examination. Immunohistochemical evaluation was performed using the following markers: cleaved caspase 3, inducible nitric oxide synthase, and tumor necrosis factor-alpha. There was damage to the renal cortical tubules and degeneration of podocytes and thickening of the glomerular basement membrane. Additionally, there was an increase in apoptosis and the inflammatory markers' immunoreactivity. Administration of alpha-lipoic acid resulted in improvement of the structural and immunohistochemical changes of the renal cortex. This may suggest a therapeutic rule of it and promising application for variable kidney injuries.

Effects of body parameters on renal cortical stiffness measured by shear-wave elastography in patients with kidney transplantation. / 人体参数对剪切波弹性成像定量移植肾皮质硬度的影响.

OBJECTIVES: The results of elastic imaging in evaluating the function and histopathological changes of allogeneic renal transplantation are contradictory, one of the important reasons may be that there are differences in human parameters related to kidney transplantation among individuals. The purpose of this study is to explore the related human body parameters on shear-wave elastography (SWE) effects on quantitative stiffness of graft cortex. METHODS: From March 2021 to November 2021, a total of 63 patients with allogeneic kidney transplantation in the Department of Ultrasonography, Third Xiangya Hospital, Central South University, were selected to collect the parameters of two-dimensional, color Doppler and SWE. The subjects were divided into a <20% group and a 20%-30% group according to the variation of cortical hardness measurement. Mann Whitney U test was used to compare the differences in relevant human parameters, and Spearman rank correlation was used to analyze the correlation between relevant human parameters and cortical hardness of transplanted kidney. RESULTS: There was no significant difference between the 2 groups in age, sex, postoperative time, resistance index of interlobar artery, SCr, blood uric acid, ratio of fat layer to muscle layer, and BMI (all P>0.05). Compared with the <20% group, the patients in the 20%-30% group had smaller cortical hardness of the transplanted kidney, greater total distance between the transplanted kidney and the skin surface, and thicker fat layer or muscle layer in front of the transplanted kidney (all P<0.05). The age of patients, the total distance from the transplanted kidney to the skin surface, the thickness of fat layer and muscle layer, the ratio of fat layer to muscle layer, BMI, and the variation of cortical hardness were significantly negatively correlated with the cortical hardness of the transplanted kidney (all P<0.05). CONCLUSIONS: Human parameters relevant to kidney transplantation affect the accuracy of SWE in measuring the cortical hardness of the transplanted kidney. It is very important to obtain the highly stabile elastic measurement value and interpret the elastic measurement results according to different levels of human body related parameters in combination with individual conditions.

A mathematical model of the rat kidney. III. Ammonia transport.

Ammonia generated within the kidney is partitioned into a urinary fraction (the key buffer for net acid excretion) and an aliquot delivered to the systemic circulation. The physiology of this partitioning has yet to be examined in a kidney model, and that was undertaken in this work. This involves explicit representation of the cortical labyrinth, so that cortical interstitial solute concentrations are computed rather than assigned. A detailed representation of cortical vasculature has been avoided by making the assumption that solute concentrations within the interstitium and peritubular capillaries are likely to be identical and that there is little to no modification of venous composition as blood flows to the renal vein. The model medullary ray has also been revised to include a segment of proximal straight tubule, which supplies ammonia to this region. The principal finding of this work is that cortical labyrinth interstitial ammonia concentration is likely to be several fold higher than systemic arterial ammonia. This elevation of interstitial ammonia enhances ammonia secretion in both the proximal convoluted tubule and distal convoluted tubule, with uptake by Na+-K+-ATPases of both segments. Model prediction of urinary ammonia excretion was concordant with measured values, but at the expense of greater ammoniagenesis, with high rates of renal venous ammonia flux. This derives from a limited capability of the model medulla to replicate the high interstitial ammonia concentrations that are required to drive collecting duct ammonia secretion. Thus, renal medullary ammonia trapping appears key to diverting ammonia from the renal vein to urine, but capturing the underlying physiology remains a challenge.NEW & NOTEWORTHY This is the first mathematical model to estimate solute concentrations within the kidney cortex. The model predicts cortical ammonia to be several fold greater than in the systemic circulation. This higher concentration drives ammonia secretion in proximal and distal tubules. The model reveals a gap in our understanding of how ammonia generated within the cortex is channeled efficiently into the final urine.

Inducible nitric oxide synthase (iNOS) mediates ethanol-induced redox imbalance and upregulation of inflammatory cytokines in the kidney.

Overexpression of the inducible isoform of the enzyme nitric oxide synthase (iNOS) has been associated to pathological processes in the kidney. Ethanol consumption induces the renal expression of iNOS; however, the contribution of this enzyme to the deleterious effects of ethanol in the kidney remains elusive. We examined whether iNOS plays a role in the renal dysfunction and oxidative stress induced by ethanol consumption. With this purpose, male C57BL/6 wild-type (WT) or iNOS-deficient (iNOS-/-) mice were treated with ethanol (20% v/v) for 10 weeks. Treatment with ethanol increased the expression of Nox4 as well as the concentration of thiobarbituric acid reactive substances and the levels of tumor necrosis factor α in the renal cortex of WT but not iNOS-/- mice. Augmented serum levels of creatinine and increased systolic blood pressure were found in WT and iNOS-/- mice treated with ethanol. WT mice treated with ethanol showed increased production of reactive oxygen species and myeloperoxidase activity, but these responses were attenuated in iNOS-/- mice. We concluded that iNOS played a role in ethanol-induced oxidative stress and pro-inflammatory cytokine production in the kidney. These are mechanisms that may contribute to the renal toxicity induced by ethanol.

Regulation of NKCC2B by TNF-α in response to salt restriction.

We have previously shown that TNF-α produced by renal epithelial cells inhibits Na+-K+-2Cl- cotransporter (NKCC2) activity as part of a mechanism that attenuates increases in blood pressure in response to high NaCl intake. As the role of TNF-α in the kidney is still being defined, the effects of low salt intake on TNF-α and NKCC2B expression were determined. Mice given a low-salt (0.02% NaCl) diet (LSD) for 7 days exhibited a 62 ± 7.4% decrease in TNF-α mRNA accumulation in the renal cortex. Mice that ingested the LSD also exhibited an ~63% increase in phosphorylated NKCC2 expression in the cortical thick ascending limb of Henle's loop and a concomitant threefold increase in NKCC2B mRNA abundance without a concurrent change in NKCC2A mRNA accumulation. NKCC2B mRNA levels increased fivefold in mice that ingested the LSD and also received an intrarenal injection of a lentivirus construct that specifically silenced TNF-α in the kidney (U6-TNF-ex4) compared with mice injected with control lentivirus. Administration of a single intrarenal injection of murine recombinant TNF-α (5 ng/g body wt) attenuated the increases of NKCC2B mRNA by ~50% and inhibited the increase in phosphorylated NKCC2 by ~54% in the renal cortex of mice given the LSD for 7 days. Renal silencing of TNF-α decreased urine volume and NaCl excretion in mice given the LSD, effects that were reversed when NKCC2B was silenced in the kidney. Collectively, these findings demonstrate that downregulation of renal TNF-α production in response to low-salt conditions contributes to the regulation of NaCl reabsorption via an NKCC2B-dependent mechanism.

Key genes differential expressions and pathway involved in salt and water-deprivation stresses for renal cortex in camel.

BACKGROUND: Camels possess the characteristics of salt- and drought-resistances, due to the long-time adaption to the living environment in desert. The camel resistance research on transcriptome is rare and deficient, especially reabsorption in renal cortex. Non-coding RNAs are normally considered as the RNA molecules that are not translated into proteins, their current roles remain mostly in regulation of information flux from DNA to protein, further on normal life activities and diseases. In order to reveal the mysterious veil of the post-transcriptional regulation of ncRNAs in renal cortex for the first time as far as we know, we designed and carried out the experiment of salt stress and water-deprivation stress in camel. RESULTS: By means of RNA-seq in renal cortex of Alxa Bactrian Camel (Camelus bactrianus), we identified certain significantly differential RNAs, including 4 novel lncRNAs, 11 miRNAs and 13 mRNAs under salt stress, 0 lncRNAs, 18 miRNAs and 14 mRNAs under water-deprivation stress. By data analysis, the response pathway of post-transcriptional regulation concerning salt and water-deprivation stresses was put forward, involving preventing sodium from entering the cell, purifying of water and compensating neutral amino acids by miR-193b, miR-542-5p interaction with SLC6A19 mRNA. CONCLUSION: Based on the resistance-related lncRNAs, miRNAs, and mRNAs, we proposed the post-transcriptional regulation pathway to explain how camels respond to salt and water-deprivation stresses in the ncRNAs regulation level of renal cortex for the first time, thus hoping to provide a theoretical basis for therapy of disease that is similar to high blood pressure in humans.

A Computer Model of Oxygen Dynamics in the Cortex of the Rat Kidney at the Cell-Tissue Level.

The renal cortex drives renal function. Hypoxia/reoxygenation are primary factors in ischemia-reperfusion (IR) injuries, but renal oxygenation per se is complex and awaits full elucidation. Few mathematical models address this issue: none captures cortical tissue heterogeneity. Using agent-based modeling, we develop the first model of cortical oxygenation at the cell-tissue level (RCM), based on first principles and careful bibliographical analysis. Entirely parameterized with Rat data, RCM is a morphometrically equivalent 2D-slice of cortical tissue, featuring peritubular capillaries (PTC), tubules and interstitium. It implements hemoglobin/O2 binding-release, oxygen diffusion, and consumption, as well as capillary and tubular flows. Inputs are renal blood flow RBF and PO2 feeds; output is average tissue PO2 (tPO2). After verification and sensitivity analysis, RCM was validated at steady-state (tPO2 37.7 ± 2.2 vs. 36.9 ± 6 mmHg) and under transients (ischemic oxygen half-time: 4.5 ± 2.5 vs. 2.3 ± 0.5 s in situ). Simulations confirm that PO2 is largely independent of RBF, except at low values. They suggest that, at least in the proximal tubule, the luminal flow dominantly contributes to oxygen delivery, while the contribution of capillaries increases under partial ischemia. Before addressing IR-induced injuries, upcoming developments include ATP production, adaptation to minutes-hours scale, and segmental and regional specification.

An equation to estimate the renal cortex volume in chronic kidney disease patients.

BACKGROUND: The renal cortex volume is associated with the kidney function and chronic kidney disease (CKD) risk factors, and it may also be a prognostic factor. We aimed to create an equation to estimate the renal cortex volume of CKD patients in day-to-day clinical practice. METHODS: The subjects included 116 ethnic Japanese CKD patients who were ≥ 18 years of age. The renal size (length, width and thickness) was measured by ultrasound. The body height, weight, year of age, sex, birth weight, gestational age, diabetes status, hypertension status, family history of CKD and dialysis and estimated glomerular filtration rate (eGFR) were collected as expected dependent variables. We made models for the equation regarding the renal cortex volume measured by non-contrast magnetic resonance imaging as a true renal cortex volume. Stepwise multiple linear regression analyses were performed with the log-transformation of dependent and independent variables. The accuracy of the models was compared using the leave one out cross-validation method. RESULTS: The estimated volume of the renal cortex (cm3) = 0.012 × renal length (cm)0.92 × width (cm)0.53 × body weight (kg)0.40 × body height (cm)0.67 × eGFR (ml/min/1.73 m2)0.22 × 1.12 if diabetes. The adjusted R 2 value and the accuracy within 30 and 50% were 0.73, 0.94 and 0.99, respectively. CONCLUSIONS: This study provided a new method for estimating the renal cortex volume in day-to-day clinical practice.

Methods in renal research: Measurement of autophagic flux in the renal cortex ex vivo.

The role of autophagy in the kidney and many nephrological diseases has gained prominence in recent years. Much of this research has been focused on markers of autophagy that are static and reveal little about the state of this dynamic pathway. Other mechanistic investigations are limited to in vitro studies, that often provide circumstantial evidence of autophagic flux. Here we describe a method for measuring autophagic flux ex vivo that allows more direct observations to be made in situ regarding the state of autophagic flux within the renal cortex of a single animal.

Increased Renal Echogenicity in Children With Appendicitis.

OBJECTIVES: Ultrasound (US) is an important modality for the detection of acute appendicitis in children but has limited sensitivity and specificity. Therefore, additional US findings may contribute to the diagnosis. In our experience, children with acute appendicitis often have increased renal cortical echogenicity on US imaging. The purpose of this study was to examine the association of increased renal cortical echogenicity with appendicitis. METHODS: This study included 240 consecutive pediatric patients with no renal or liver disease who underwent US examinations for suspected appendicitis between February 2014 and January 2016. Ultrasound images of the liver and right kidney were retrospectively reviewed, and the echogenicity of the renal cortex was classified as less than the liver, equal to the liver, or greater than the liver. RESULTS: The renal cortex was abnormally hyperechoic in 38 (50%) of all of the patients who had appendicitis according to US (P < .001) and in 47% of patients who underwent appendectomy (P = .002). Overall, 36% of patients with increased renal cortical echogenicity had a diagnosis of appendicitis. After correction for variables, patients with renal hyperechogenicity had a 2.5 times chance of appendicitis (odds ratio, 2.5). CONCLUSIONS: There is a statistically significant association between increased renal cortical echogenicity and appendicitis. In the absence of hepatic or renal disease, this finding may increase the accuracy of the US diagnosis of appendicitis. Increased renal cortical echogenicity may be added to the list of US findings accompanying acute appendicitis in children.

Accounting for oxygen in the renal cortex: a computational study of factors that predispose the cortex to hypoxia.

We develop a pseudo-three-dimensional model of oxygen transport for the renal cortex of the rat, incorporating both the axial and radial geometry of the preglomerular circulation and quantitative information regarding the surface areas and transport from the vasculature and renal corpuscles. The computational model was validated by simulating four sets of published experimental studies of renal oxygenation in rats. Under the control conditions, the predicted cortical tissue oxygen tension ([Formula: see text]) or microvascular oxygen tension (µPo2) were within ±1 SE of the mean value observed experimentally. The predicted [Formula: see text] or µPo2 in response to ischemia-reperfusion injury, acute hemodilution, blockade of nitric oxide synthase, or uncoupling mitochondrial respiration, were within ±2 SE observed experimentally. We performed a sensitivity analysis of the key model parameters to assess their individual or combined impact on the predicted [Formula: see text] and µPo2 The model parameters analyzed were as follows: 1) the major determinants of renal oxygen delivery ([Formula: see text]) (arterial blood Po2, hemoglobin concentration, and renal blood flow); 2) the major determinants of renal oxygen consumption (V̇o2) [glomerular filtration rate (GFR) and the efficiency of oxygen utilization for sodium reabsorption (ß)]; and 3) peritubular capillary surface area (PCSA). Reductions in PCSA by 50% were found to profoundly increase the sensitivity of [Formula: see text] and µPo2 to the major the determinants of [Formula: see text] and V̇o2 The increasing likelihood of hypoxia with decreasing PCSA provides a potential explanation for the increased risk of acute kidney injury in some experimental animals and for patients with chronic kidney disease.

Automated renal cortical volume measurement for assessment of renal function in patients undergoing radical nephrectomy.

BACKGROUND: Renal volume change greatly affects renal function after nephrectomy. Although various measuring techniques were reported, no standard measuring method is available. In this study, we examined the computational automated volumetric method, and evaluated the volumetric change to assess the functional outcome in patients undergoing radical nephrectomy. We developed the predictive equation for postoperative renal function from volume alternation and validated the performance. METHODS: Thirty-two patients undergoing radical nephrectomy participated in this study. Renal volume was calculated using three different methods [ellipsoid method, conventional manual voxel count method for renal parenchyma (manual RPV), and automated voxel count method for renal cortex (automated RCV)] through newly developed imaging software. Statistical analysis was performed to evaluate the correlation between renal functional alternation 7 days after the nephrectomy and renal volumetric change. A simple predictive equation for the postoperative renal function by renal volume loss was developed and externally validated through another 12 cases. RESULTS: The automated RCV method had the strongest correlation between renal function alternation and RCV change (R = 0.82), than manual RPV (R = 0.69) and ellipsoid method (R = 0.50). Subsequently, a simple equation for postoperative renal function by renal volume alternation was developed: predicted postoperative estimated glomerular filtration rate (eGFR) from renal volume change = preoperative eGFR × (postoperative renal volume / preoperative renal volume). In the external validation cohort, automated RCV demonstrated the predictive performance of the constructed equations for renal function (R = 0.77). CONCLUSIONS: The computational automated RCV measurements is a simple estimation of renal functional outcome for patients undergoing radical nephrectomy.

Mechanism of grape seeds extract protection against paracetamol renal cortical damage in male Albino rats.

OBJECTIVE: The aim of the study was to assess the possible protective role of grape seeds extract (GSE) in ameliorating the toxic effects of paracetamol overdose on the rat renal cortical tissue. BACKGROUND: Paracetamol is one of the widely used non-steroidal anti-inflammatory drugs (NSAIDs). Unfortunately, it was reported as the most common cause of toxic ingestion in the world. Grape seeds extract (GSE) is known to have a strong antioxidant and anti-inflammatory properties. METHODS: The rats were divided into 4 groups; control group, GSE group, paracetamol group and GSE with paracetamol group. Kidney specimens were processed for biochemical, histological and immunohisto-chemical studies. RESULTS: The study showed marked biological changes in the form of significant increase in serum urea and creatinine levels with significant decrease in renal superoxide dismutase with paracetamol group. Furthermore, Proximal (PCT) and distal convoluted tubules showed marked degeneration, dense nuclear staining, cytoplasmic vacuolization, and partial loss of the brush borders. Most tubules were dilated, irregular and were filled with hyaline casts. PCT and DCT showed less PAS reaction and more COX-2 and caspase expression if compared with the control and the GSE groups. Concomitant administration of grape seeds extract with paracetamol revealed a noticeable amelioration of these biochemical and histological changes. Proximal and distal convoluted tubules showed less PAS reaction and more COX2 and caspase expression if compared with the control and the GSE. Concomitant administration of GSE with paracetamol revealed a noticeable amelioration of these biochemical and histological changes. CONCLUSION: Grape seeds extract provided biochemical and histo-pathological improvement in paracetamol induced renal cortical toxicity. These findings revealed that this improvement was associated with a decrease in oxidative damage and apoptosis (Tab. 1, Fig. 7, Ref. 55).

Therapeutic efficacy of bone marrow derived mesenchymal stromal cells versus losartan on adriamycin-induced renal cortical injury in adult albino rats.

BACKGROUND: Renal disease is a major health problem. Recent studies have reported the efficacy of stem cell therapy in nephropathy animal models. AIM OF THE WORK: This study was designed to investigate the therapeutic effectiveness of bone marrow-derived mesenchymal stromal cells (MSCs) versus losartan in the treatment of renal alterations induced by adriamycin (ADR). MATERIALS AND METHODS: Thirty-five adult male albino rats were divided into four groups. Group I was the control group. Group II (adriamycin-treated group),which included ten rats that were injected with a single dose of adriamycin (15 mg/kg) intraperitoneally, was subdivided into subgroup IIa and IIb and they were sacrificed 1 week and 5 weeks after adriamycin injection, respectively. Group III was the adriamycin + losartan-treated group and 1 week after adriamycin injection five rats received 10 mg/kg of losartan orally and daily for 4 weeks. Group IV was the adriamycin + MSC-treated group); five rats were injected with adriamycin as group II then supplied with MSCs at a dose of 1 × 10(6) cells suspended in 0.5 mL of phosphate-buffered saline (PBS) per rat in the tail vein 1 week after adriamycin injection. Rats of this group were sacrificed 4 weeks after the stem cell injection. Blood urea nitrogen and serum creatinine were measured. Samples from renal cortex were processed for light and electron microscope examination. As regards light microscope, sections were stained with hematoxylin and eosin (H-E), periodic acid-Schiff (PAS), masson trichrome, proliferating cell nuclear antigen (PCNA) and Caspase-3 immunohistochemical stains. Morphometrical and statistical analyses were also conducted. RESULTS: Examination of adriamycin-treated group revealed deterioration of renal functions and various degrees of renal structural alterations as vacuolated cytoplasm, dark nuclei and detached epithelial lining. Administration of losartan partially improved ADR-induced kidney dysfunction, whereas MSCs denoted a more ameliorative role evidenced by structural and functional recovery. CONCLUSION: MSCs have a relevant therapeutic potential against ADR-induced renal damage. MSCs may accomplish this role by decreasing caspase-3 expression and increasing proliferating cell nuclear antigen staining which influence the regeneration of the kidney.

Determinants of renal shape in chronic kidney disease patients.

BACKGROUND: The determinants of renal shape are not well established. The purpose of this study was to investigate the relationship between the renal shape, as measured by ultrasound, and the clinical characteristics in chronic kidney disease (CKD) patients. METHODS: The study included 121 CKD patients who had undergone kidney biopsy. The renal shape was defined by: (1) the renal shape index: renal length/(renal width + renal thickness) and (2) the renal width/length. IgA nephritis patients (excluding patients with diabetes), comprised the largest subgroup (n = 49) and were analyzed separately. RESULTS: The correlation analyses and two-sample Student's t test results showed that age, eGFR, BMI, cortex volume fraction measured by MRI (cortex volume/renal volume), percentage of global sclerosis, weight, sex, hypertension and diabetes were significantly correlated with the renal shape in both kidneys. In a stepwise multiple linear regression analysis, old age and high BMI were independently associated with plump kidney. As for the left renal shape index, low cortex volume fraction was also independently associated with plump kidney. In the IgA nephritis patient subgroup, the cortex volume fraction was the most significant factor contributing to the left renal shape index (r = 0.50, p < 0.01) and the width/length (r = -0.47, p < 0.01). CONCLUSION: Age and BMI were stronger determinants of renal shape than renal function in CKD patients. The left renal cortex volume fraction was also an independent determinant and a more important factor in IgA nephritis patients.