High-resolution and highly accelerated MRI T2 mapping as a tool to characterise renal tumour subtypes and grades.

BACKGROUND: Clinical imaging tools to probe aggressiveness of renal masses are lacking, and T2-weighted imaging as an integral part of magnetic resonance imaging protocol only provides qualitative information. We developed high-resolution and accelerated T2 mapping methods based on echo merging and using k-t undersampling and reduced flip angles (TEMPURA) and tested their potential to quantify differences between renal tumour subtypes and grades. METHODS: Twenty-four patients with treatment-naïve renal tumours were imaged: seven renal oncocytomas (RO); one eosinophilic/oncocytic renal cell carcinoma; two chromophobe RCCs (chRCC); three papillary RCCs (pRCC); and twelve clear cell RCCs (ccRCC). Median, kurtosis, and skewness of T2 were quantified in tumours and in the normal-adjacent kidney cortex and were compared across renal tumour subtypes and between ccRCC grades. RESULTS: High-resolution TEMPURA depicted the tumour structure at improved resolution compared to conventional T2-weighted imaging. The lowest median T2 values were present in pRCC (high-resolution, 51 ms; accelerated, 45 ms), which was significantly lower than RO (high-resolution; accelerated, p = 0.012) and ccRCC (high-resolution, p = 0.019; accelerated, p = 0.008). ROs showed the lowest kurtosis (high-resolution, 3.4; accelerated, 4.0), suggestive of low intratumoural heterogeneity. Lower T2 values were observed in higher compared to lower grade ccRCCs (grades 2, 3 and 4 on high-resolution, 209 ms, 151 ms, and 106 ms; on accelerated, 172 ms, 160 ms, and 102 ms, respectively), with accelerated TEMPURA showing statistical significance in comparison (p = 0.037). CONCLUSIONS: Both high-resolution and accelerated TEMPURA showed marked potential to quantify differences across renal tumour subtypes and between ccRCC grades. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03741426 . Registered on 13 November 2018. RELEVANCE STATEMENT: The newly developed T2 mapping methods have improved resolution, shorter acquisition times, and promising quantifiable readouts to characterise incidental renal masses.

A murine monoclonal antibody against H5N1 avian influenza virus cross-reacts with human kidney cortex cells.

To investigate the biological characteristics of monoclonal antibodies (mAbs) against avian influenza virus (AIV) and the possible mechanism of AIV-related kidney injury. BALB/c mice were immunized with inactivated H5N1 AIV to prepare monoclonal antibody H5-32, and its subtype, titer and cross-reactivity with other influenza viruses were identified. The reactivity of monoclonal antibody with normal human tissue was analyzed by immunohistochemistry. Immunofluorescence and confocal laser scanning technique were used to detect the binding sites between mAb and human renal cortical cells, and Western blotting was used to detect the size of binding fragments. Immunohistochemical analysis confirmed that monoclonal antibody H5-32 cross-reacted with normal human kidney tissue. In human kidney, mAb H5-32 was localized in the cytoplasm of human renal tubular epithelial cells, and its binding fragment size was about 43 kDa. H5N1 AIV appears to bind to human renal tubular epithelial cells, which may be one of the mechanisms of kidney injury caused by AIV infection.

Relationship between cortical and medullary thickness and glomerular filtration rate among living kidney donors.

The relationship between the kidney cortex and medulla is not well understood in healthy populations. This study characterised the relationship between cortical/medullary thickness and measured glomerular filtration rate (GFR) in 390 living kidney donors. A positive relationship was observed between medullary, but not cortical, thickness and GFR. We propose that this reflects a correlation between juxtamedullary nephron number and GFR.

Developmental Characteristics of the Glomerular and Tubular Portion of the Nephron in the Human Foetal Kidney Cortex: Morphometrical and Immunohistochemical Analysis.

This study aimed to morphometrically examine the development of glomeruli and tubules in the kidney cortex of human foetuses at different gestational ages (GAs). We also investigated the expression of the proliferation marker Ki-67 and apoptosis-related markers Bcl-2 and Bax during nephrogenesis using immunohistochemistry. Kidney samples from 38 human foetuses of both sexes with GA ranging from 13 to 40 weeks were analysed. The samples were divided into 7 groups based on GA, each corresponding to 1 lunar month. Foetal kidneys showed a spatiotemporal gradient of nephron differentiation with the transient stages of nephron anlage located in the nephrogenic zone and immature nephrons located in the subjacent maturation zone. In the inner cortex, nephrons establish the morphological characteristics of definitive nephrons. The average area, perimeter, and Feret's diameter of the glomeruli formed within the kidney cortex gradually decreased up to a period of 29-32 weeks of gestation and subsequently increased until a period of 37-40 weeks. There was a weak negative correlation with GA. In contrast, the areal density of glomeruli increased up to a period of 21-24 weeks and then gradually decreased until a period of 37-40 weeks, showing a moderate negative correlation with GA. The average area of renal tubules slightly decreased until a period of 21-24 weeks of gestation and then gradually increased until a period of 36-40 weeks, showing a moderate positive correlation with GA. The average areal density of renal tubules increased significantly until a period of 21-24 weeks of gestation, remained relatively constant until a period of 33-36 weeks, and then increased significantly at 36-40 weeks. There was a strong positive correlation with GA. Our results showed that Ki-67 was expressed in numerous cells of the metanephric mesenchyme, pretubular aggregates, renal vesicles, comma-shaped bodies, and early S-shaped bodies. During subsequent development and the spatial expansion of nephrons towards the mature zone, the expression of Ki-67 was markedly reduced. Similarly, Bcl-2 was strongly expressed in induced nephrogenic progenitor cells, pretubular aggregates, renal vesicles, and comma-shaped bodies. As vascularisation and maturation of the nephron proceeded, Bcl-2 staining became less intense and limited to the parietal layer of the Bowman's capsule and renal tubules. Weak Bax expression was observed in individual scattered cells within segments of the nephrons at all developmental stages. In the mature zone, more intense Bax staining was observed in the renal tubules.

The Extracellular Matrix Environment of Clear Cell Renal Cell Carcinoma.

The extracellular matrix (ECM) of tumors is a complex mix of components characteristic of the tissue of origin. In the majority of clear cell renal cell carcinomas (ccRCCs), the tumor suppressor VHL is inactivated. VHL controls matrix organization and its loss promotes a loosely organized and angiogenic matrix, predicted to be an early step in tumor formation. During tumor evolution, cancer-associated fibroblasts (CAFs) accumulate, and they are predicted to produce abundant ECM. The ccRCC ECM composition qualitatively resembles that of the healthy kidney cortex in which the tumor arises, but there are important differences. One is the quantitative difference between a healthy cortex ECM and a tumor ECM; a tumor ECM contains a higher proportion of interstitial matrix components and a lower proportion of basement membrane components. Another is the breakdown of tissue compartments in the tumor with mixing of ECM components that are physically separated in healthy kidney cortex. Numerous studies reviewed in this work reveal effects of specific ECM components on the growth and invasive behaviors of ccRCCs, and extrapolation from other work suggests an important role for ECM in controlling ccRCC tumor rigidity, which is predicted to be a key determinant of invasive behavior.

Associations between nephron number and podometrics in human kidneys.

Podocyte loss and resultant nephron loss are common processes in the development of glomerulosclerosis and chronic kidney disease. While the cortical distribution of glomerulosclerosis is known to be non-uniform, the relationship between the numbers of non-sclerotic glomeruli (NSG), podometrics and zonal differences in podometrics remain incompletely understood. To help define this, we studied autopsy kidneys from 50 adults with median age 68 years and median eGFR 73.5 mL/min/1.73m2 without apparent glomerular disease in a cross-sectional analysis. The number of NSG per kidney was estimated using the physical dissector/fractionator combination, while podometrics were estimated using model-based stereology. The number of NSG per kidney was directly correlated with podocyte number per tuft and podocyte density. Each additional 100,000 NSG per kidney was associated with 26 more podocytes per glomerulus and 16 podocytes per 106 µm3 increase in podocyte density. These associations were independent of clinical factors and cortical zone. While podocyte number per glomerulus was similar in the three zones, superficial glomeruli were the smallest and had the highest podocyte density but smallest podocytes. Increasing age and hypertension were associated with lower podocyte number, with age mostly affecting superficial glomeruli, and hypertension mostly affecting juxtamedullary glomeruli. Thus, in this first study to report a direct correlation between the number of NSG and podometrics, we suggest that podocyte number is decreasing in NSG of individuals losing nephrons. However, another possible interpretation may be that more nephrons might protect against further podocyte loss.

Sexual dimorphism in renal heme oxygenase-1 and arachidonic acid metabolizing enzymes in spontaneously hypertensive rats versus normotensive Wistar Kyoto rats.

Numerous studies have demonstrated a sexual dimorphism in blood pressure (BP) control in spontaneously hypertensive rats (SHR), however the mechanisms remain to be further elucidated. Based on the established role of arachidonic acid metabolites and heme oxygenase (HO) in BP control, we hypothesize that higher BP in male SHR is associated with differential expression in renal HO and arachidonic acid metabolizing enzymes vs. female SHR. Higher BP in male SHR coincided with significant increases in renal cortical superoxide production and thiobarbituric acid reactive substances (TBARs) levels as measures of oxidative stress compared to normotensive female WKY and female SHR. The elevations in BP and oxidative stress in male SHR were also associated with a decrease in cortical heme oxygenase-1 (HO-1) expression when compared to normotensive female WKY. Although there was no sex or strain differences in cortical expression of the epoxyeicosatrienoic acids (EETs) producing enzyme, cytochrome P450 epoxygenase (CYP2C23), in male and female SHR and WKY, SHR had greater expression of the EETs metabolizing enzyme, soluble epoxide hydrolase (sEH) vs. WKY. Cortical expression of the 20-hydroxyeicosatetraenoic acid (20-HETE) producing enzyme, cytochrome P450 hydroxylase (CYP4A), was less in female WKY and SHR compared to strain-matched males and cortical 20-HETE levels were also less in female SHR vs. male SHR. Cortical cyclooxygenase-2 (COX-2) expression was significantly greater in female SHR and WKY vs. males and cortical prostaglandin E2 (PGE2) levels in female SHR was significantly greater than male WKY. In conclusion, our data suggest that sex differences in renal oxidative stress, HO-1 and arachidonic acid metabolizing enzymes could contribute to sexual dimorphism in hypertension in young SHR.

Automated Segmentation of Kidney Cortex and Medulla in CT Images: A Multisite Evaluation Study.

BACKGROUND: In kidney transplantation, a contrast CT scan is obtained in the donor candidate to detect subclinical pathology in the kidney. Recent work from the Aging Kidney Anatomy study has characterized kidney, cortex, and medulla volumes using a manual image-processing tool. However, this technique is time consuming and impractical for clinical care, and thus, these measurements are not obtained during donor evaluations. This study proposes a fully automated segmentation approach for measuring kidney, cortex, and medulla volumes. METHODS: A total of 1930 contrast-enhanced CT exams with reference standard manual segmentations from one institution were used to develop the algorithm. A convolutional neural network model was trained (n=1238) and validated (n=306), and then evaluated in a hold-out test set of reference standard segmentations (n=386). After the initial evaluation, the algorithm was further tested on datasets originating from two external sites (n=1226). RESULTS: The automated model was found to perform on par with manual segmentation, with errors similar to interobserver variability with manual segmentation. Compared with the reference standard, the automated approach achieved a Dice similarity metric of 0.94 (right cortex), 0.90 (right medulla), 0.94 (left cortex), and 0.90 (left medulla) in the test set. Similar performance was observed when the algorithm was applied on the two external datasets. CONCLUSIONS: A fully automated approach for measuring cortex and medullary volumes in CT images of the kidneys has been established. This method may prove useful for a wide range of clinical applications.

Castleman Disease of the Kidney in Computed Tomography Urography.

BACKGROUND: Castleman Disease (CD) of the kidney is extremely rare. In this study, we have presented a case of CD of the left kidney and comprehensively described the findings of computed tomography urography. CASE PRESENTATION: The case involved unusual imaging characteristics of the focal central cystic area. CONCLUSION: The small and regular cyst-like structures and the hyperdense mass relative to the renal parenchyma in plain scans might help distinguish the CD of the kidney from other hypervascular tumors.

Impact of passive smoking on renal vascular morphology

ABSTRACT Objective To determine whether passive smoking causes morphological and structural changes in the arcuate arteries of rats exposed for 7 to 28 days. Methods Wistar rats aged eight weeks and weighing 260g on average were allocated to a Control or a Smoker Group. Groups were further divided into 4 groups containing 5 animals each. Morphological-functional analysis of the right kidneys was carried out after 7 and 28 days of exposure to the smoke of 40 cigarettes per day. Cigarettes were burned at set times using automated cigarette-burning equipment ("Smoking Machine" - SM-MC-01). At the end of each exposure period, the kidneys were dissected and submitted to histological processing for morphological and quantitative analysis. Results Exposure to cigarette smoke for 7 days led to a decrease in inner vascular diameter. Decreased thickness of the vascular tunica media was observed after exposure for 28 days. Increased thickness of the tunica adventitia, increased total vascular wall thickness, increased total vascular diameter and qualitative increase in collagen deposition were observed. Vascular volume increased after 28 days of exposure. Conclusion Passive smoking has a negative impact on renal vasculature.

Asymmetric Opening of Mitochondrial Permeability Transition Pore in Mouse Brain Hemispheres: A Link to the Mitochondrial Calcium Uniporter Complex

Abstract The prolonged entry of large amounts of calcium into the mitochondria through the mitochondrial calcium uniporter complex (MCUC) may cause the permeability transition pore (mPTP) to open, which contributes to the pathogenesis of several diseases. Tissue-specific differences in mPTP opening due to variable expression of MCUC components may contribute to disease outcomes. We designed this study to determine differential mPTP opening in mitochondria isolated from different regions of mouse brain and kidney and to compare it with the expression of MCUC components. mPTP opening was measured using mitochondria isolated from the left/right brain hemispheres (LH/RH, respectively) and from kidney cortex/medulla, while the expression level of MCUC components was assessed from total cellular RNA. Interestingly, LH mitochondria showed less calcium-induced mPTP opening as compared to RH mitochondria at two different calcium concentrations. Conversely, mPTP opening was similar in the renal cortex and renal medulla mitochondria. However, the kidney mitochondria demonstrated bigger and faster mPTP opening as compared to the brain mitochondria. Furthermore, asymmetric mPTP opening in the LH and RH mitochondria was not associated with the expression of MCUC components. In brief, this study demonstrates thus far unreported asymmetric mPTP opening in mouse brain hemispheres that is not associated with the mRNA levels of MCUC components.

DHEA-pretreatment attenuates oxidative stress in kidney-cortex and liver of diabetic rabbits and delays development of the disease.

In view of reported discrepancies concerning antioxidant activity of dehydroepiandrosterone (DHEA), a widely used dietary supplement, the current investigation was undertaken to evaluate the antioxidant properties of DHEA in both kidney-cortex and liver of alloxan (ALX)-induced diabetic rabbits, as this diabetogenic compound exhibits the ROS-dependent action. ALX was injected to animals following 7 days of DHEA administration. Four groups of rabbits were used in the experiments: control, DHEA-treated control, diabetic and DHEA-treated diabetic. Our results show for the first time, that in kidney-cortex DHEA resulted in normalization of hydroxyl free radicals (HFR) levels and restoration of catalase (CAT) and glutathione peroxidase (GPx) activities to near the control values, while in liver DHEA prevented the malondialdehyde (MDA) accumulation and normalized glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH) activities. Moreover, in both kidney-cortex and liver DHEA supplementation prevented GSSG elevation accompanied by a decrease in GSH/GSSG ratio. Although DHEA attenuated oxidative stress in both kidney-cortex and liver of ALX-induced diabetic rabbits and significantly delayed the onset of diabetes in time, it did not protect against the final development of diabetes. In conclusion, the current investigation underscores the complexity of the antioxidant action of DHEA. The data are of clinical interest since DHEA supplementation could prevent the deleterious effects of ROS and delay, or even prevent the onset of many diseases. However, in view of the reported pro-oxidant effects of high DHEA doses, the potential use of this agent as a supplement needs a careful evaluation.

Morphofunctional study on the effects of passive smoking in kidneys of rats / Estudo morfofuncional sobre os efeitos do tabagismo passivo em rins de ratos

ABSTRACT Objective To analyze whether passive inhalation of cigarette smoke causes morphological, structural, and functional changes in kidneys of rats. Methods Wistar rats, aged eight weeks, weighing on average 260g, were divided into Control Group and Smoking Group. Each group was subdivided into four groups of ten animals for morphofunctional analysis, in a period of seven and 28 days. The Smoking Group was exposed to smoke of 40 cigarettes per day, at certain times and in automated equipment for cigarette burning, called smoking machine (SM-MC-01). After the exposure period, urine and blood samples were collected for the functional analyses, and the kidneys were dissected and submitted to histological procedures for morphoquantitative analyses. Results After exposure of animals of the Smoking Group, the following were observed: lower weight gain; lower water and feed intake; decreased renal weight, diameter, and volume; reduction in cortical thickness and glomerular volume density; decrease in glomerular and capsular diameter; increase in mesangial density; decreased urine volume; increased levels of glucose, serum creatinine and microalbuminuria; decreased urinary creatinine levels and creatinine clearance rate. Conclusion Passive smoking negatively influences renal morphology and glomerular filtration rate, with effects similar to those described in the literature regarding active smoking.

RESUMO Objetivo Analisar se a inalação passiva da fumaça do cigarro proporciona alterações morfológicas, estruturais e funcionais nos rins de ratos. Métodos Ratos Wistar, com oito semanas de idade, pesando, em média, 260g, foram divididos em Grupo Controle e Grupo Tabagista. Cada grupo foi subdividido em quatro grupos de dez animais para análise morfofuncional, em um período de sete e 28 dias. O Grupo Tabagista foi exposto à fumaça de 40 cigarros por dia, em horários determinados e equipamento automatizado de queima de cigarros, denominado smoking machine (SM-MC-01). Após o período de exposição, foram coletadas amostras de urina e sangue para as análises funcionais, e os rins foram dissecados e submetidos a procedimentos histológicos para análises morfoquantitativas. Resultados Após a exposição dos animais do Grupo Tabagista, observou-se menor ganho de peso; menor consumo de água e ração; menor peso, diâmetro e volume renal; redução em espessura cortical e densidade de volume glomerular; diminuição no diâmetro glomerular e capsular; aumento na densidade mesangial; volume urinário diminuído; níveis aumentados de glicose, creatinina sérica e microalbuminúria; níveis reduzidos de creatinina urinária e redução da taxa de depuração da creatinina. Conclusão O tabagismo passivo influencia negativamente na morfologia renal e na taxa de filtração glomerular, com efeitos semelhantes aos descritos na literatura em relação ao tabagismo ativo.

The effect of long-term dehydration and subsequent rehydration on markers of inflammation, oxidative stress and apoptosis in the camel kidney.

BACKGROUND: Dehydration has deleterious effects in many species, but camels tolerate long periods of water deprivation without serious health compromise. The kidney plays crucial role in water conservation, however, some reports point to elevated kidney function tests in dehydrated camels. In this work, we investigated the effects of dehydration and rehydration on kidney cortex and medulla with respect to pro-inflammatory markers, oxidative stress and apoptosis along with corresponding gene expression. RESULTS: The cytokines IL-1ß and IL-18 levels were significantly elevated in the kidney cortex of dehydrated camel, possibly expressed by tubular epithelium, podocytes and/or mesangial cells. Elevation of IL-18 persisted after rehydration. Dehydration induced oxidative stress in kidney cortex evident by significant increases in MDA and GSH, but significant decreases in SOD and CAT. In the medulla, CAT decreased significantly, but MDA, GSH and SOD levels were not affected. Rehydration abolished the oxidative stress. In parallel with the increased levels of MDA, we observed increased levels of PTGS1 mRNA, in MDA synthesis pathway. GCLC mRNA expression level, involved in GSH synthesis, was upregulated in kidney cortex by rehydration. However, both SOD1 and SOD3 mRNA levels dropped, in parallel with SOD activity, in the cortex by dehydration. There were significant increases in caspases 3 and 9, p53 and PARP1, indicating apoptosis was triggered by intrinsic pathway. Expression of BCL2l1 mRNA levels, encoding for BCL-xL, was down regulated by dehydration in cortex. CASP3 expression level increased significantly in medulla by dehydration and continued after rehydration whereas TP53 expression increased in cortex by rehydration. Changes in caspase 8 and TNF-α were negligible to instigate extrinsic apoptotic trail. Generally, apoptotic markers were extremely variable after rehydration indicating that animals did not fully recover within three days. CONCLUSIONS: Dehydration causes oxidative stress in kidney cortex and apoptosis in cortex and medulla. Kidney cortex and medulla were not homogeneous in all parameters investigated indicating different response to dehydration/rehydration. Some changes in tested parameters directly correlate with alteration in steady-state mRNA levels.

Diagnostic performance of renal ultrasonography in detecting chronic kidney disease of various severity.

Background: Association between early diagnosis of chronic kidney disease (CKD) and low morbidity and mortality rate has been proven. Thus, tools for early CKD diagnosis are vital. Ultrasonography has been widely used to diagnose and monitor the progression of CKD. Objectives: To determine the performance of selected renal ultrasonographic parameters for the diagnosis of early CKD. Methods: In a cohort of patients diagnosed with CKD (n = 100), diagnostic performance of ultrasonographically measured renal length (RL), renal cortical thickness (RCT), and parenchymal thickness (PT) was determined using receiver operating curve analysis; correlation of each parameter with the associated comorbidities and serum creatinine (Scr) levels was also determined. Severity of CKD was graded with estimated glomerular filtration rates (eGFR). Results: Of all patient participants, 85 had severity grades 2 or 3. Mean (standard deviation) Scr was 1.88 (0.60) mg/dL; eGFR was 43.3 (11.85) mL/min/1.73 m2. RL was 9.01 (0.83) cm, PT was 1.32 (0.22) cm, and RCT was 6.0 (0.10) mm. PT and RCT were positively correlated with eGFR (P = 0.01 and 0.002, respectively). Early CKD was better predicted by PT (area under the curve (AUC) 0.735; 82% sensitivity; 30% specificity; 68% positive predictive value (PPV)) and RCT (AUC 0.741; 82% sensitivity; 48% specificity; 51% PPV); severe CKD was better predicted by RL (AUC 0.809; 67% sensitivity; 26% specificity, 45% PPV; 13% negative predictive value). Conclusion: Index ultrasonic parameters show a diagnostic role in different stages of CKD. The index ultrasound and biochemical parameters showed a complementary role in predicting renal dysfunction.

A model of mitochondrial O2 consumption and ATP generation in rat proximal tubule cells.

Oxygen tension in the kidney is mostly determined by O2 consumption (Qo2), which is, in turn, closely linked to tubular Na+ reabsorption. The objective of the present study was to develop a model of mitochondrial function in the proximal tubule (PT) cells of the rat renal cortex to gain more insight into the coupling between Qo2, ATP formation (GATP), ATP hydrolysis (QATP), and Na+ transport in the PT. The present model correctly predicts in vitro and in vivo measurements of Qo2, GATP, and ATP and Pi concentrations in PT cells. Our simulations suggest that O2 levels are not rate limiting in the proximal convoluted tubule, absent large metabolic perturbations. The model predicts that the rate of ATP hydrolysis and cytoplasmic pH each substantially regulate the GATP-to-Qo2 ratio, a key determinant of the number of Na+ moles actively reabsorbed per mole of O2 consumed. An isolated increase in QATP or in cytoplasmic pH raises the GATP-to-Qo2 ratio. Thus, variations in Na+ reabsorption and pH along the PT may, per se, generate axial heterogeneities in the efficiency of mitochondrial metabolism and Na+ transport. Our results also indicate that the GATP-to-Qo2 ratio is strongly impacted not only by H+ leak permeability, which reflects mitochondrial uncoupling, but also by K+ leak pathways. Simulations suggest that the negative impact of increased uncoupling in the diabetic kidney on mitochondrial metabolic efficiency is partly counterbalanced by increased rates of Na+ transport and ATP consumption. This model provides a framework to investigate the role of mitochondrial dysfunction in acute and chronic renal diseases.

Direction of the Biopsy Needle in Ultrasound-Guided Renal Biopsy Impacts Specimen Adequacy and Risk of Bleeding.

INTRODUCTION: Although medical factors such as hypertension and coagulopathy have been identified that are associated with hemorrhage after renal biopsy, little is known about the role of technical factors. The purpose of our study was to examine the effects of biopsy needle direction on renal biopsy specimen adequacy and bleeding complications. METHODS: Two hundred and forty-two patients who had undergone ultrasound-guided renal biopsies were included. A printout of the ultrasound picture taken at the time of the biopsy was used to measure the biopsy angle ("angle of attack" [AOA]) and to determine if the biopsy needle was aimed at the upper or lower pole and if the medulla was targeted or avoided. RESULTS: Of the 3 groups of biopsy angle, an AOA of between 50°-70° yielded the most glomeruli per core (P = .001) and the fewest inadequate specimens (4% vs 15% for > 70°, and 9% for < 50°, P = .038). Biopsy directed at a pole vs an interpolar region resulted in fewer inadequate specimens (8% vs 23%, P = .005), while biopsies that were medulla-avoiding resulted in fewer inadequate specimens (5% vs 16%, P = .004) and markedly reduced bleeding complications (12% vs 46%, P < .001) compared to biopsies where the medulla was entered. DISCUSSION: An AOA of approximately 60°, aiming at the poles, and avoiding the medulla were each associated with fewer inadequate biopsies and bleeding complications. While biopsy of the medulla is necessary for some diagnoses, the increased bleeding risk emphasizes the need for communication between nephrologist, pathologist, and radiologist.

Multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney: CT and MRI findings and clinical characteristic.

PURPOSE: The aim of this study was to clarify the radiologic and clinical characteristics of multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney. METHOD: Fourteen patients with unique and characteristic multiple hemorrhagic subcapsular cortical cysts of the kidney, not categorized in any existing renal cystic diseases, were retrospectively reviewed. The clinical information including age, sex, symptom, family history of renal or renal cystic disease, and laboratory data were collected. CT and MRI findings including distribution, number and size of cysts, and CT attenuation and signal intensity on T1- and T2-weighted MRI of cysts were analyzed. RESULTS: All patients except one were young and none had a family history of renal or renal cystic disease. Common clinical symptoms were flank or abdominal pain and hematuria. In all cases, only the left kidney was involved at initial presentation. Cysts were small (median cyst size, 4-15 mm), numerous, and distributed mainly along the subcapsular cortex of the kidney. Cysts were hyper-attenuated on unenhanced CT, extremely hypointense on T2-weighted MRI, and mildly hyperintense on T1-weighted MRI. All patients except one had normal renal function. Imaging follow-up revealed stable or mildly progressive disease in seven patients. Two patients developed several hemorrhagic subcapsular cortical cysts in the right kidney at follow-up. Three of five patients with a renal pathology specimen showed concurrent IgA nephropathy. CONCLUSION: We have identified a unique renal cystic disease with multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney that has a characteristic manifestation both radiologically and clinically. KEY POINTS: • Multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney is a unique non-familial renal cystic disease with a characteristic manifestation both radiologically and clinically. • Most cases of multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney are stable or slowly progressive, and do not require invasive intervention.

Dynamic changes in histone deacetylases following kidney ischemia-reperfusion injury are critical for promoting proximal tubule proliferation.

Deranged histone deacetylase (HDAC) activity causes uncontrolled proliferation, inflammation, fibrosis, and organ damage. It is unclear whether deranged HDAC activity results in acute kidney injury in the renal hypoperfusion model of bilateral ischemia-reperfusion injury (IRI) and whether in vivo inhibition is an appropriate therapeutic approach to limit injury. Male mice were implanted with intraperitoneal osmotic minipumps containing vehicle, the class I HDAC inhibitor, MS275, or the pan-HDAC inhibitor, trichostatin A (TSA), 3 days before sham/bilateral IRI surgery. Kidney cortical samples were analyzed using histological, immunohistochemical, and Western blotting techniques. HDAC-dependent proliferation rate was measured in immortalized rat epithelial cells and primary mouse or human proximal tubule (PT) cells. There were dynamic changes in cortical HDAC localization and abundance following IRI including a fourfold increase in HDAC4 in the PT. HDAC inhibition resulted in a significantly higher plasma creatinine, increased kidney damage, but reduced interstitial fibrosis compared with vehicle-treated IRI mice. HDAC-inhibited mice had reduced interstitial α-smooth muscle actin, fibronectin expression, and Sirius red-positive area, suggesting that IRI activates HDAC-mediated fibrotic pathways. In vivo proliferation of the kidney epithelium was significantly reduced in TSA-treated, but not MS275-treated, IRI mice, suggesting class II HDACs mediate proliferation. Furthermore, HDAC4 activation increased proliferation of human and mouse PTs. Kidney HDACs are activated during IRI with isoform-specific expression patterns. Our data point to mechanisms whereby IRI activates HDACs resulting in fibrotic pathways but also activation of PT proliferation and repair pathways. This study demonstrates the need to develop isoform-selective HDAC inhibitors for the treatment of renal hypoperfusion-induced injury.

Multiparameter diffusion-weighted imaging for characterizing pathological patterns in lupus nephritis patients: A preliminary study.

BACKGROUND: Microstructural changes of lupus nephritis (LN) kidney such as inflammatory cell infiltration or fibrosis could influence water molecular movement or diffusion, which indicates that diffusion-weighted imaging (DWI) may become a valuable tool in evaluation of this disease. PURPOSE: To explore whether multiparameter diffusion-weighted imaging (mDWI) could contribute to characterize pathological patterns in LN patients. STUDY TYPE: Retrospective. POPULATION: Twenty-two patients with LN. FIELD STRENGTH/SEQUENCE: Multi-b value DWI was performed with a 3.0 T scanner. ASSESSMENT: Apparent diffusion coefficient (ADC)m , perfusion-related diffusion coefficient (Df ), molecular diffusion coefficient (Ds ), perfusion fraction (f), ADCs , α, ADCk , and mean kurtosis (MK) were calculated by monoexponential, biexponential, stretched-exponential, and kurtosis models fits, respectively. STATISTICAL TESTS: Independent sample t-test, Pearson analysis and receiver operating characteristic (ROC). RESULTS: In the whole group, the activity index (AI) correlated significantly with alpha values in the medulla (rho = -0.54, P = 0.03). The chronicity index (CI) correlated significantly with Ds values in the medulla (rho = -0.61, P = 0.02). No significant association was found between any other diffusion parameter and histologic grade with all P > 0.05. For differentiating proliferative LN (Class III or IV) from Class V, the area under the ROC curve (AUC) of alpha in the medulla was 0.833 (P = 0.023). DATA CONCLUSION: mDWI might be used for the characterization of pathological patterns in LN patients. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1075-1084.