Number Of Glomeruli Research Articles

Mapping single-nephron filtration in the isolated, perfused rat kidney using magnetic resonance imaging.

The kidney has an extraordinary ability to maintain glomerular filtration despite natural fluctuations in blood pressure and nephron loss. This is partly due to local coordination between single-nephron filtration and vascular perfusion. An improved understanding of the three-dimensional (3-D) functional coordination between nephrons and the vasculature may provide a new perspective of the heterogeneity of kidney function and could inform targeted therapies and timed interventions to slow or prevent the progression of kidney disease. Here, we developed magnetic resonance imaging (MRI) tools to visualize single-nephron function in 3-D throughout the isolated perfused rat kidney. We used an intravenous slow perfusion of a glomerulus-targeted imaging tracer [cationized ferritin (CF)] to map macromolecular dynamics and to identify glomeruli in 3-D, followed by a bolus of a freely filtered tracer (gadolinium diethylenetriamine penta-acetic acid) to map filtration kinetics. There was a wide intrakidney distribution of CF binding rates and estimated single-nephron glomerular filtration rate (eSNGFR) between nephrons. eSNGFR and CF uptake rates did not vary significantly by distance from the kidney surface. eSNGFR varied from ∼10 to ∼100 nL/min throughout the kidney. Whole single-kidney GFR was similar across all kidneys, despite differences in the distributions eSNGFR of and glomerular number, indicating a robust adaptive regulation of individual nephrons to maintain constant single-kidney GFR in the presence of a natural variation in nephron number. This work provides a framework for future studies of single-nephron function in the whole isolated perfused kidney and experiments of single-nephron function in vivo using MRI.NEW & NOTEWORTHY We report MRI tools to measure and map single-nephron function in the isolated, perfused rat kidney. We used imaging tracers to identify nephrons throughout the kidney and to measure the delivery and filtration of the tracers at the location of the glomeruli. With this technique, we directly measured physiological parameters including estimated single-nephron glomerular filtration rate throughout the kidney. This work provides a foundation for new studies to simultaneously map the function of large numbers of nephrons.

Prediction of Renal Function in Living Kidney Donors and Recipients of Living Donor Kidneys Using Quantitative Histology.

Living kidney donors (LKDs) are at increased risk of chronic kidney disease, whereas transplant recipients experience progressive reduction of graft function. We examined the predictive value of quantitative stereology on renal function in LKDs and recipients of living donor kidneys, based on perioperative biopsies from the donated kidney. Cortex volume of both donor kidneys was determined by contrast-enhanced computed tomography and single-kidney glomerular filtration rate (GFR) by 51 chrome-EDTA clearance together with renography. Glomerular density was used to estimate total glomeruli number in addition to glomerular volume, glomerular sclerosis, kidney fibrosis, and arteriole dimensions. GFR measurements were repeated 1 y after transplantation in both LKDs and recipients. Associations between GFR at follow-up and cortex volume and histomorphometric parameters after adjustment of age, gender, body mass index, smoking status, 24-h blood pressure, and single-kidney GFR were examined. We included 49 LKDs (age, 51 ± 12 y) and 51 recipients (age, 44 ± 13 y). At follow-up, GFR was 71 ± 16 mL/min in LKDs and 61 ± 18 mL/min in recipients with hyperfiltration being more prominent in LKDs (30.4%) as compared to recipients (16.4%; P < 0.05). One-year GFR in donors correlated to cortex volume ( P < 0.001) but not to any histological parameters, whereas GFR in recipients correlated to the amount of interstitial fibrosis ( P < 0.01) but not to other histological parameters or cortex volume. Kidney cortex volume, but not renal histology parameters, predicts 1-y renal outcome in LKDs. In contrast, the amount of interstitial fibrosis, but not cortex volume, predicts 1-y graft function in recipients.

Clinical and pathological investigation of oligomeganephronia.

Oligomeganephronia (OMN) is a rare congenital anomaly involving the kidney and urinary tract, characterized by decreased number and compensatory hypertrophy of the nephron. It is caused by abnormal kidney development during the embryonic period, especially in patients with low birth weight; however, the actual etiology and clinical features remain unknown. We aim to reveal the clinical and pathological characteristics, treatment, and outcome. Ten patients diagnosed with OMN between 2013 and 2020 were retrospectively investigated. The data were presented as the median ± interquartile range, and statistical significance was set at p < 0.05. The age at diagnosis was 14.1years, the male-to-female ratio was 6:4, and only four cases were born with low birth weight. The estimated glomerular filtration rate (eGFR) was 62.2mL/min/1.73 m2. The glomerulus diameter of OMN patients was significantly larger (217 vs. 154µm, p < 0.001) in OMN patients, and the number of glomeruli of OMN patients was lower (0.89 vs. 2.05/mm2, p < 0.001) than the control group. Eight of the ten cases were identified by urinary screening. Nine patients were treated with renin-angiotensin system (RAS) inhibitors, following which proteinuria successfully decreased or disappeared. Their median eGFR was also stable, 53.3mL/min/1.73 m2. As few symptoms can lead to OMN discovery, most patients were found during urine screening at school. Kidney dysfunction was observed in all patients at the time of kidney biopsy. Proteinuria has been significantly reduced and the decline rate of eGFR might be improved by RAS inhibitors. "A higher resolution version of the Graphical abstract is available as Supplementary information".

Convolutional Neural Networks for the Evaluation of Chronic and Inflammatory Lesions in Kidney Transplant Biopsies

In kidney transplant biopsies, both inflammation and chronic changes are important features that predict long-term graft survival. Quantitative scoring of these features is important for transplant diagnostics and kidney research. However, visual scoring is poorly reproducible and labor intensive. The goal of this study was to investigate the potential of convolutional neural networks (CNNs) to quantify inflammation and chronic features in kidney transplant biopsies. A structure segmentation CNN and a lymphocyte detection CNN were applied on 125 whole-slide image pairs of periodic acid-Schiff- and CD3-stained slides. The CNN results were used to quantify healthy and sclerotic glomeruli, interstitial fibrosis, tubular atrophy, and inflammation within both nonatrophic and atrophic tubuli, and in areas of interstitial fibrosis. The computed tissue features showed high correlation with Banff lesion scores of five pathologists (A.A., A.Dend., J.H.B., J.K., and T.N.). Analyses on a small subset showed a moderate correlation toward higher CD3+ cell density within scarred regions and higher CD3+ cell count inside atrophic tubuli correlated with long-term change of estimated glomerular filtration rate. The presented CNNs are valid tools to yield objective quantitative information on glomeruli number, fibrotic tissue, and inflammation within scarred and non-scarred kidney parenchyma in a reproducible manner. CNNs have the potential to improve kidney transplant diagnostics and will benefit the community as a novel method to generate surrogate end points for large-scale clinical studies.

Efficacy and safety of percutaneous renal biopsy performed using 18G needle versus 16G needle: a single-center retrospective study

BackgroundAt present, both 16G and 18G needles are used for percutaneous renal biopsy in China. This study aimed to compare the efficacy and safety of biopsy performed with the 18G needle vs. the 16G needle.MethodsThe data of patients who underwent percutaneous renal biopsy at our hospital between January 2015 and December 2019 were retrospectively analyzed. The number of glomeruli obtained by puncture and postoperative complications were compared between patients undergoing biopsy with the 16G and 18G needles. Continuous variables were compared by the t test or the Mann–Whitney U test, and categorical variables by the chi-square test. Correlation analysis was used to examine the relationship of different variables with hematoma size.ResultsOf the total 3138 kidney biopsies, 2526 were performed with the18G needle and 612 with the 16G needle. The number of glomeruli obtained was not significantly different between the two groups (P = 0.078). Large hematomas were significantly more common the 16G group than in the 18G group (9.31% vs. 5.98%, P = 0.003). Arteriovenous fistula was also more common in the 16G group (1.14% vs. 0.23%, P = 0.005). Other complications were rare, with similar incidence in the two groups.ConclusionThe 18G needle is as effective as the 16G needle for percutaneous renal biopsy. The risk of large hematoma and arteriovenous fistula appear to be lower with the 18G needle.

Urinary Podocyte Excretion Predicts Urinary Protein Selectivity and Renal Prognosis.

Background Urinary podocyte excretion is related to a reduction in glomerular podocyte numbers, glomerulosclerosis, and urinary protein selectivity. To elucidate the role of urinary podocytes in proteinuria and renal prognosis and to identify the factors that cause podocyte detachment, we examined urinary podocytes in 120 renal biopsy patients. Methods Podocytes were identified in urinary sediments stained with fluorescent-labeled anti-podocalyxin antibodies in ten high power fields. The amounts of protein bands, separated by SDS-polyacrylamide gel electrophoresis, were calculated using an image software program and the correlation with urinary podocytes was analyzed. Podocyte surface pores were observed using a low-vacuum scanning electron microscope. The renal prognosis, including induction of hemodialysis or 30% reduction in eGFR, was investigated. Results Urinary podocyte excretion showed a higher positive correlation with albumin excretion compared to IgG, prealbumin, and transferrin. There were no significant correlations between urinary podocyte count and low molecular weight proteins, including β2-microglobulin and α1-microglobulin. The number of podocyte surface pores was positively correlated with proteinuria, suggesting enhanced albumin transcytosis. The hemodynamic pressure on the glomerular capillary wall, including products of pulse pressure and pulse rate (water hammer pressure), was positively correlated with urinary podocyte excretion. Urinary podocyte excretion and Tamm–Horsfall protein (THP) were independent risk factors for renal prognosis but were not related to response to treatment. Conclusion Urinary podocyte excretion was correlated with urinary albumin excretion, indicating specific albumin transport by podocytes. Podocytes were detached from the glomerular capillaries by water hammer pressure and THP was involved in the renal prognosis.

ShenKang Injection Attenuates Renal Fibrosis by Inhibiting EMT and Regulating the Wnt/β-Catenin Pathway

Shenkang Injection (SKI) is a traditional Chinese medicine injection commonly used in the clinical treatment of chronic kidney disease. Although it has been confirmed that SKI has anti-kidney fibrosis effects, the underlying mechanism remains unclear. To investigate the effects of SKI on epithelial-mesenchymal transition (EMT) and Wnt/β-catenin pathway and explore its potential anti-fibrosis mechanism. A unilateral ureteral obstruction (UUO) model was induced by ligating the left ureter of male SD rats. A total of 24 rats were randomly divided into the following four groups: sham group, model group, SKI group, and benazepril group. The rats in each group were treated for 28 days, and renal function was evaluated by blood urea nitrogen (BUN) and serum creatinine (Scr). The degree of renal fibrosis was assessed by hematoxylin and eosin (HE) and Masson staining. Extracellular matrix (ECM) deposition was evaluated by immunohistochemistry. Real-time fluorescent quantitative PCR (RT-qPCR) and western blotting were used to detect the expression of genes and proteins in the Wnt/β-catenin signaling pathway. Further studies were performed in vitro using HK-2 cells treated with TGF-β1. At 28 days postoperation, the levels of BUN and Scr expression were significantly increased in the UUO group. SKI and benazepril reduced the levels of BUN and Scr, which displayed protective renal effects. Pathological staining showed that compared with the sham operation group, the renal parenchymal structure was severely damaged, the number of glomeruli was reduced, and a large amount of collagen was deposited in the kidney tissue of the UUO group. SKI treatment reduced morphological changes. Immunohistochemistry showed that compared with the sham operation group, the content of collagen I and FN in the kidney tissue of the UUO group were significantly increased, whereas the SKI content was decreased. In addition, compared with the UUO group, the levels of Wnt1, active β-catenin, Snail1, and PAI-1 expression were reduced in the SKI group, suggesting that SKI may reduce renal fibrosis by mediating the Wnt/β-catenin pathway. Further in vitro studies showed that collagen I, FN, and α-SMA levels in HK-2 cells were significantly increased following stimulation with TGF-β1. SKI could significantly reduce the expression of collagen I, FN, and α-SMA. A scratch test showed that SKI could reduce HK-2 migration. In addition, by stimulating TGF-β1, the levels of Wnt1, active β-catenin, snail1, and PAI-1 were significantly upregulated. SKI treatment could inhibit the activity of the Wnt/β-catenin signaling pathway in HK-2 cells. SKI improves kidney function by inhibiting renal fibrosis. The anti-fibrotic effects may be mediated by regulation of the Wnt/β-catenin pathway and EMT inhibition.

The evolution of performing a kidney biopsy: a single center experience comparing native and transplant kidney biopsies performed by interventional radiologists and nephrologists

BackgroundKidney biopsy is the most vital tool guiding a nephrologist in diagnosis and treatment of kidney disease. Over the last few years, we have seen an increasing number of kidney biopsies being performed by interventional radiologists. The goal of our study was to compare the adequacy and complication rates between kidney biopsies performed by interventional radiology versus nephrology. Methods We performed a single center retrospective analysis of a total of all kidney biopsies performed at our Institution between 2015 and 2021. All biopsies were performed using real-time ultrasound. Patients were monitored for four hours post biopsy and repeat ultrasound or hemoglobin checks were done if clinically indicated. The entire cohort was divided into two groups (Interventional radiology (IR) vs nephrology) based on who performed the biopsy. Baseline characteristics, comorbidities, blood counts, blood pressure, adequacy of the biopsy specimen and complication rates were recorded. Multivariable logistic regression was used to compare complication rates (microscopic hematuria, gross hematuria and need for blood transfusion combined) between these two groups, controlling for covariates of interest. ANCOVA (analysis of variance, controlling for covariates) was used to compare differences in biopsy adequacy (number of glomeruli per biopsy procedure) between the groups.Results446 kidney biopsies were performed in the study period (229 native and 147 transplant kidney biopsies) of which 324 were performed by IR and 122 by nephrologist. There was a significantly greater number of core samples obtained by IR (mean = 3.59, std.dev. = 1.49) compared to nephrology (mean = 2.47, std.dev = 0.79), p < 0.0001. IR used 18-gauge biopsy needles while nephrologist exclusively used 16-gauge needles. IR used moderate sedation (95.99%) or general anesthesia (1.85%) for the procedures more often than nephrology, which used them only in 0.82% and 0.82% of cases respectively (p < 0.0001). Trainees (residents or fellows) participated in the biopsy procedures more often in nephrology compared to IR (97.4% versus 69.04%, p < 0.0001). The most frequent complication identified was microscopic hematuria which occurred in 6.8% of biopsies. For native biopsies only, there was no significant difference in likelihood of complication between groups, after adjustment for covariates of interest (OR = 1.01, C.I. = (0.42, 2.41), p = 0.99). For native biopsies only, there was no significant difference in mean number of glomeruli obtained per biopsy procedure between groups, after adjustment for covariates of interest (F(1,251) = 0.40, p = 0.53).ConclusionOur results suggest that there is no significant difference in the adequacy or complication rates between kidney biopsies performed by IR or nephrology. This conclusion may indicate that kidney biopsies can be performed safely with adequate results either by IR or nephrologists depending on each institution’s resources and expertise.

MO053: Are Renal Prognostic Markers Different in Patients with Exostosin 1/2 Positive or Negative Membranous Lupus Nephritis? A Single Center Experience in Turkey

Abstract BACKGROUND AND AIMS Recently, prognostic importance of antibodies in primary membranous nephropathy is well defined. However, knowledge about antibodies related to disease activity in membranous lupus nephritis (MLN) is limited. Exostosin1 and exostosin2 (EXT1/2) are novel antibodies detected in MLN, and further studies are needed for the prognostic significance of them as a marker. The aim of this study is to determine whether renal prognostic markers differ between EXT1/2 positive and negative MLN patients. METHOD This is a single-center, retrospective and observational study. Class 5 MLN patients aged 18 or older were included in the study. Clinical characteristics, results of biochemical analysis and histopathological examination were recorded from 6 to 18 months. The end-point of the study was determined as complete remission, partial remission, need for renal replacement therapy (RRT) and exitus. Group 1: EXT1/2 positive patients. Group 2: EXT1/2 negative patients. Light, immunofluorescent and electron microscopy findings and laboratory parameters were evaluated in EXT1/2 positive and negative patients. RESULTS Group 1: n = 11 patients. Group 2: n = 7 patients. The main demographic, biochemical and histopathological characteristics of the groups were shown in Table 1. EXT1/2 negative patients, a higher number of sclerotic glomeruli, interstitial fibrosis and a higher amount of proteinuria were present than positive patients (P &amp;lt; 0.05). EXT1/EXT2 negative patients had significantly lower C3 and C4 levels than positive patients (P &amp;lt; 0.05). EXT1/EXT2 negative patients had a higher RRT or exitus rate within 18 months than positive patients (P &amp;lt; 0.05). In contrast, EXT1/EXT2 positive patients had a higher rate of achieving complete or partial remission within 18 months than negative patients (P &amp;lt; 0.05). The effect of immunosuppressive drug use other than steroids and glomerulosclerosis remission was statistically significant (P = 0.04 and P = 0.011). CONCLUSION EXT1/2 negative class 5 LMN patients have more poor renal prognostic indicators than positive patients. RRT or exitus rate is higher in EXT1/EXT2 negative patients than positive patients. However, more randomized controlled studies are needed.

MO074: SGLT2 Inhibition Promotes Intrinsic Kidney Regeneration by Cells of the Renin Lineage

Abstract BACKGROUND AND AIMS With chronic kidney disease (CKD) prevalence rapidly increasing, the need for novel therapies is rising. Sodium glucose co-transporter-2 (SGLT2) inhibitors were originally developed to treat hyperglycemia in patients with type 2 diabetes mellitus. Clinical trials with the SGLT2 inhibitor empagliflozin revealed a marked attenuation of the slope of kidney function decline, also in patients with non-diabetic CKD. The exact mechanism of this kidney sparing effect still remains to be clarified. Interestingly, cells of renin lineage (CoRL), residing in the juxtaglomerular apparatus to regulate blood pressure and fluid balance, have been demonstrated to harbor a stem cell like potential. CoRL have the ability to replenish glomerular cell number by dedifferentiating, migrating and subsequently replacing various glomerular cell types in different kidney injury mouse models. Considering that empagliflozin treatment affects renin plasma levels and electrolyte balance in patients, we hypothesized that empagliflozin could have an effect on CoRL-induced glomerular regeneration. METHOD Experiments were performed in a Ren1cre; tdTomato lineage-trace mouse strain that expresses a tomato fluorescent label in all cells derived from renin lineage. Two kidney injury mouse models were applied; bilateral ischemia reperfusion injury (bIRI) and 5/6 nephrectomy (5/6NTx). Empagliflozin (10 mg/kg) was administered daily via oral gavage for 14 days. Subsequently, mice were sacrificed and kidneys were harvested for histological analysis. RESULTS In both the bIRI and 5/6NTx model, empagliflozin intake led to an increase (&amp;gt;2-fold) of CoRL found in the intraglomerular regions compared with vehicle control littermates. These CoRL seemed to selectively differentiate towards different glomerular cell types per model: bIRI combined with empagliflozin administration resulted in an increase of claudin- (10-fold) and integrin-α8- (1.5-fold) tomato double positive cells, suggesting favored differentiation from CoRL to respectively a parietal epithelial or mesangial cell type. In contrast, in the empagliflozin treated 5/6NTx model, an increase (1.5-fold) in tomato-podocyn double positive cells was observed, implying more restocking of glomerular podocytes by CoRL in this model. CONCLUSION SGLT2 inhibition by empagliflozin treatment leads to increased CoRL-mediated intrinsic regeneration potential and provides the kidney with different replenished cell types in different kidney disease models. Our findings demonstrate a novel mechanism via which SGLT2 inhibition might protect against kidney injury.

MO122: Bleeding Complications after Allograft Kidney Biopsy and Role of Antiplatelet Therapy

Abstract BACKGROUND AND AIMS Percutaneous biopsy is an important tool for monitoring renal allograft and early diagnosis when dysfunction occurs. Bleeding is the most dangerous adverse event, even if it is rare (risk of 0.5%). Cardiovascular (CV) disease affects 2/3 of elderly with CKD and antiplatelet therapy is taken for primary and secondary prevention of CV events. A systematic review on aspirin discontinuation among 50 279 patients at risk for coronary disease shows a 3-fold risk of adverse CV event. The aim of this study is to compare bleeding complications of antiplatelet administration within 5 days from renal biopsy versus absence of therapy. METHOD We conducted a 10-year (2010–2020) single-centre retrospective study on 285 consecutive ultrasound assisted percutaneous allograft kidney biopsy. We collected information about demographic, laboratory (eGFR, platelets, haemoglobin pre/post biopsy, proteinuria) data, biopsy indication (elective/urgent), clinical presentation [acute kidney injury (AKI)/nephrotic syndrome], needle gauge, use of antiplatelet or anticoagulant, diagnosis and complications (categorized as minor and major, according to the need for intervention). We divided patients in two groups: antiplatelet therapy within 5 days versus therapy discontinuation or absence. Bivariate logistic regression was used to analyse possible risk factors associated with complications. RESULTS Among the 285 patients: 173 patients received antiplatelet agents (low-dose aspirin in &amp;gt;90% of cases) within 5 days from biopsy and 112 patients were not on antiplatelet therapy. Diastolic hypertension, AKI and proteinuria were statistically greater in the group without antiplatelet therapy. Histologic diagnoses were evenly present in the two groups, and no differences were observed in the rate of complications. Major complications were diagnosed in 0/112 patients without antiplatelet therapy and 1/173 patients with therapy within 5 days. Minor complications were documented in 14/112 and in 15/173 patients, respectively. There were no statistically significant differences in terms of complications between antiplatelet therapy within 5 days and absence of therapy (Table 1). Furthermore, there were no differences between taking antiplatelet within 48 h or stopping it within 48 h of the procedure (Table 2). No deaths were attributed to procedure and all events occurred within 24 h from biopsy, irrespective of their severity. The univariate logistic regression model (dependent variable: major complication) documented a lower BMI as a significant risk factor; indeed, this was not confirmed at multivariate regression. The analysis did not find a significant difference between 16-G and 18-G biopsy needle in terms of major/minor complications; however, the use of the latter was associated with a significant lower number of glomeruli in the sample. CONCLUSION Our study suggests that the use of antiplatelet agents within 5 days from procedure does not increase the bleeding risk, so it should be safe to continue the therapy in patients at risk for CV events. However, this is a weak evidence that needs prospective studies to be validated. Our data also suggest that 16-G biopsy needle may be safely used to obtain enough tissue for histologic diagnosis.

Macula densa cells control glomerular immune cell homing

Circulating and kidney resident immune cells preferentially home in and around the glomerulus compared to other vascular beds in both normal and inflammatory states, suggesting the presence of unique antimicrobial mechanisms in the glomerular microcirculation that protect the kidney filter. However, the underlying cell and molecular mechanisms are largely unknown. Macula densa (MD) cells are localized at the glomerular vascular entrance as a unique juxtaglomerular cell type and are known to control glomerular hemodynamics, and more recently, glomerular tissue remodeling. This study addressed the hypothesis that MD cells control glomerular immune cell homing by the release of paracrine‐acting pro‐inflammatory factors including opsonins, cytokines, and lymphokines. Bulk and single cell RNA sequencing and transcriptomic analysis of MD vs. control cells isolated from MD‐GFP mouse kidneys identified the high MD‐enrichment of several pathways and genes in the inflammatory response and cellular infiltration by leukocytes (Lcn2, Fga, Fgg, Casp4, Ptgs2, Ptges, Anxa1, Spns2, Spp1, Clu, Ccn1, Cxcl14, Mif). Mice with MD‐specific gain‐of‐function of mTOR (MD‐mTORgof) were developed by intercrossing nNOS/Cre and TSC2/fl mice, and feature globally increased MD cell protein synthesis. Immunoblotting of kidney cortex homogenates confirmed the significant increase in the expression of MD‐specific Ccn1, Cxcl14, Ptgs2, and Ptges in MD‐mTORgof vs. control mice. Intravital multiphoton imaging of the kidney cortex and endogenous circulating and kidney resident immune cell populations (labeled with anti‐CD44‐Alexa680 and F4/80‐Alexa488 antibodies) observed the significantly increased glomerular number, transit time, and migration of circulating CD44+ immune cells and tissue macrophages in MD‐mTORgof vs. control mice. NZM.2328 lupus mice featured significantly increased MD‐centric glomerular density and migration of CD8+ T cells. These results suggest the new role of MD cells and several MD‐derived paracrine‐acting molecular factors as important control mechanisms of glomerular inflammation in health and disease conditions. These newly identified MD mechanisms may be targeted in future anti‐inflammatory therapeutic strategies.

A case of congenital capillary proliferation of the kidney (CCPK)

We report a case of congenital capillary proliferation of the kidney (CCPK) along with the multimodality imaging findings. Four-day-old boy who had managed due to his mother's gestational diabetes underwent abdominal ultrasound and a mass was detected in the right kidney. On gray scale ultrasound, the mass exhibited a hyperechoic, slight lobulated shape and a circumscribed margin. On Doppler mode, the mass showed hypervascularity in its peripheral to central zones. On MRI, the mass was hyperintense on the T2-weighted image, and no diffusion restriction was noted on DWI/ADC. On computed tomography, strong enhancement was shown at center of the mass at the post-contrast early phase; homogeneous enhancement at the entirety of the mass was observed at the delayed phase. We suspected hemangioma but did not rule out the possibility of malignancy. Surgery was performed. Pathologically, the specimen showed a proliferation of capillaries which were positive for vascular endothelial markers and negative for GLUT1 in immunohistochemistry. A small number of entrapped tubules and glomeruli were also observed. After an intensive pathological examination, the diagnosis of CCPK was finally considered. CCPK was recently described as an extremely rare childhood renal vascular lesion, and to our knowledge, only five other cases have been reported. Our patient's multimodality imaging findings well reflected the characteristics of a vascular lesion.

Kidney biopsy adequacy and complications in children — does technique matter?

Kidney biopsy is part of the diagnostic workup of many children with renal disease. Traditionally, a perpendicular approach to the biopsy has been used, but more recently, some proceduralists have favoured a tangential approach. It is not clear if one technique is superior with regards to tissue adequacy or complication rates. In our centre, interventional radiologists (IR) use general anaesthetic and a tangential approach, whereas paediatric nephrologists (PN) use sedation and a perpendicular approach. We examined consecutive native kidney biopsies performed between January 2008 and December 2017 for adequacy (sufficient tissue for light and electron microscopy and immunofluorescence) and examined the electronic medical records for data regarding technique and complications. IR performed 72 (29%) of the 245 native kidney biopsies, obtaining more total glomeruli (median 39 vs 16, p < 0.001) and more glomeruli per tissue core (median 13 vs 8, p < 0.001) than PN. No differences in specimen adequacy were observed between the two groups (79% IR vs 81% PN, p = 0.75) and a diagnosis could be made in 99% and 94% respectively (p = 0.1). A statistically lower rate of peri-nephric haematoma (28% vs 42%, p = 0.04) was detected in the IR group, but there were no significant differences in other complications. One patient required a blood transfusion (PN) and another required surgical intervention for a perinephric haematoma (IR).Conclusion: IR obtained larger samples and number of glomeruli, but the overall adequacy for native kidney biopsies was good using both perpendicular and tangential techniques, with low rates of significant complications.What is Known:• Kidney biopsy is integral to the diagnostic work-up of many children with kidney disease.• Kidney biopsy is a safe procedure with well-established complications in a minority of children.What is New:• Interventional radiologists had higher biopsy yield than paediatric nephrologists, possibly due to the tangential approach.• Biopsy adequacy rates are high using both techniques and provided a diagnosis in over 95% of cases.

The effect of vitamin E on the histological structure of kidney in rats treated with cyclophosphamide

Cyclophosphamide (CP) is a cytotoxic alkylating drug that is commonly used to treat autoimmune disorders and cancer. CP causes nephrotoxicity by producing highly reactive radicals devoid of oxygen. A fat-soluble vitamin E that interacts as a free radical scavenger, inhibiting nitrosamine production and blocking lipid peroxidation from polyunsaturated fatty acids. The aim of this research was to see if vitamin E may help combating CP induced nephrotoxicity. Thirty-two adult albino female Westar rats were randomly divided into four groups (n=8) and received daily treatment for thirty days. Group A considered as control group, receiving normal saline IP at dose of 0.3 ml, group B given 15 mg/kg b.w. of cyclophosphamide IP, while group C received cyclophosphamide with vitamin E at dose 200 mg/kg, oral administration of vitamin E one hour before injection of cyclophosphamide, in group D they received vitamin E orally at dose of 200 mg kg body weight mixed with olive oil daily by oral gavage. In group B the cyclophosphamide causes highly significant reduction in body weight and histologically showed atrophy of most glomeruli, distention in bowman’s space, tubular degeneration and luminal hyaline cast material, while in group C showed most of the glomeruli normal except atrophy of few number of glomeruli and focal epithelial degeneration of renal tubules. Our study found that one of the primary mechanisms induced by cyclophosphamide may be nephrotoxicity due to oxidative stress, and pretreatment with vitamin E reduces cyclophosphamide-induced nephrotoxicity.

Pathological and sonographic review of early isolated severe lower urinary tract obstruction and implications for prenatal treatment.

To identify favorable renal histology in fetuses with early severe lower urinary tract obstruction (LUTO) and determine the best timing and selection criteria for prenatal surgery. This multicenter, retrospective study included male fetuses with severe LUTO which died before 24 weeks of gestation during the period January 2000 to December 2018. Age-matched controls were used as reference standard for renal histology. Prenatal ultrasound features and fetal serum and/or urine β2microglobulin level were retrieved and kidney histology slides (hematein-eosin-safran and α-smooth-muscle-actin (αSMA) immunostaining) were prepared and reviewed. αSMA-positive staining of the blastema is due to its aberrant differentiation into myofibroblastic cells. Cases were sorted into histopathologic groups (favorable or unfavorable) according to the blastema's morphology and αSMA labeling and the data of these groups were compared. Included in the study were 74 fetuses with a median gestational age at outcome of 17 + 6 (range, 13 + 0 to 23 + 5) weeks. Parenchymal organization was preserved in 48% of the kidneys. A blastema was present in 90% of the kidneys, but it was morphologically normal in only 9% and αSMA-negative in only 1% of them. Most (82%) fetuses had an unfavorable prognosis, and 36% of fetuses died ≤ 18 weeks and had severe renal lesions detected on histology (early unfavorable prognosis). A favorable renal prognosis was associated with an earlier gestational age (P = 0.001). Fetuses with LUTO had a significantly lower number of mature glomeruli (P < 0.001) compared with controls. However, there was no significant difference in the number of glomeruli generations between the early-unfavorable-prognosis group (≤ 18 weeks) and the group with a favorable prognosis (P = 0.19). A comparison of prenatal ultrasound features and biochemical markers between groups could not identify any prenatal selection criteria. Before 18 weeks, around 30% of fetuses with severe LUTO still have potential for kidney development. Identification of these cases would enable them to be targeted for prenatal therapy. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Administration of retinoic acid to pregnant mice increases the number of fetal mouse glomeruli

The prevalence of chronic kidney disease (CKD) is increasing worldwide, and CKD is a serious global health problem. Low glomerular number is one of the risk factors for CKD; therefore, the glomerular number is associated with the risk of CKD. Increasing the glomerular number above normal levels may reduce the risk of CKD. It has been reported that, in vitro, the addition of retinoic acid (RA) to the culture medium increases the glomerular number. However, there is no report of an increase in glomerular number above normal levels with the addition of RA in vivo. In this study, RA (20 mg/kg) was administered intraperitoneally to pregnant mice once at embryonic day (E) 10.5, E12.5, E14.5, or E16.5. The fetuses were harvested at E18.5 and fetal mouse kidneys were evaluated. Fetal kidney volume and weight were significantly increased in the E16.5 group compared to the control group. The total glomerular number in the E16.5 group was also approximately 1.46 times higher than that in the control group. In summary, we established a method to increase the glomerular number in the fetal kidney by administration of RA to pregnant mice at E16.5. These results will facilitate the investigation of whether CKD risk is reduced when the glomerular number increases above normal.

Moringa oleifera Seed at the Interface of Food and Medicine: Effect of Extracts on Some Reproductive Parameters, Hepatic and Renal Histology.

The lipid-rich Seed of Moringa oleifera has been promoted as an effective water clarifier. Aside its vital nutritional application as an emerging food additive, the seed has continued to gain a wider acceptance in various global ethnomedicines for managing several communicable and lifestyle diseases, howbeit, its potential toxic effect, particularly on fertility and pregnancy outcomes has remained uninvestigated; the effect of Moringa oleifera seed (MOSE) aqueous-methanol extracts on fertility and pregnancy outcome, was investigated in vivo using female Wistar rats that were divided into 50, 100, 300 and 500 mg per kilogram body weight. Group six was given Moringa oleifera seed treated water ad-libitum (ad-libitum group). Organs harvested for histological assessment included ovary, uterus, liver and kidney. In addition to HPLC fingerprint and a preliminary peptide detection, we determined the physico-chemical characteristics and mineral content of MOSE using standard methods. Data were analyzed with significance at p ≤ 0.05. There was no significant difference in the estrus cycle, mating index, gestation survival index, gestation index, fertility index and sex ratio among all groups. Gestation length was reduced in some groups. While the male pup birth weight was comparable among the different groups, female pups birth weights were significantly reduced in 50 and 100 mg groups. Anogenital distance indices of female pups in ad libitum group were significantly increased. Pathologies were observed in liver and kidneys of dams while kidneys of pups presented a dose dependent reduction in the number of glomeruli. There were no observed pathological changes in the ovary and uterus. This study showed for the first time in rodents, that the lipid-rich MOSE is unsafe to the kidney of rodents while the lipid-free MOSE appears to be safe at doses up to 300 mg/kg body weight. Findings from this study suggested that the female pups were masculinized. In conclusion, the lipid-rich seed extracts of MOSE appear to be unsafe during pregnancy, induce hepatic and renal toxicity while the lipid-free MOSE excludes inherent toxicity as the hydrophobic part has been linked to toxicity as observed in this study due to the developmental programming effect on female offspring in rodents.

Deletion of STAT3 from Foxd1 cell population protects mice from kidney fibrosis by inhibiting pericytes trans-differentiation and migration.

Signal transduction and activator of transcription 3 (STAT3) is a key transcription factor implicated in the pathogenesis of kidney fibrosis. Although Stat3 deletion in tubular epithelial cells is known to protect mice from fibrosis, vFoxd1 cells remains unclear. Using Foxd1-mediated Stat3 knockout mice, CRISPR, and inhibitors of STAT3, we investigate its function. STAT3 is phosphorylated in tubular epithelial cells in acute kidney injury, whereas it is expanded to interstitial cells in fibrosis in mice and humans. Foxd1-mediated deletion of Stat3 protects mice from folic-acid- and aristolochic-acid-induced kidney fibrosis. Mechanistically, STAT3 upregulates the inflammation and differentiates pericytes into myofibroblasts. STAT3 activation increases migration and profibrotic signaling in genome-edited, pericyte-like cells. Conversely, blocking Stat3 inhibits detachment, migration, and profibrotic signaling. Furthermore, STAT3 binds to the Collagen1a1 promoter in mouse kidneys and cells. Together, our study identifies a previously unknown function of STAT3 that promotes kidney fibrosis and has therapeutic value in fibrosis.

Relationship between glomerular number in fresh kidney biopsy samples and light microscopy samples.

On-site evaluation of fresh kidney biopsy (FKB) samples at the time of biopsy is useful to verify that adequate specimens are acquired. However, some cases present poor correlation between glomerular number in FKB samples and light microscopy (LM) samples. We examined the usefulness of such on-site evaluation. We conducted a retrospective cross-sectional observational study (n = 129) to assess the correlation between glomerular number in FKB samples and LM samples and the associated factors hindering the evaluation. There was a significant positive correlation between glomerular number in FKB samples and LM samples. The median ratio of glomerular number (LM samples/FKB samples) was 0.74. According to this ratio, cases were divided into three groups: reasonable estimation (65 cases), underestimation (32 cases), and overestimation (32 cases). Comparing the reasonable and underestimation groups, significant differences were detected in the extent of interstitial fibrosis and tubular atrophy (IFTA) and interstitial inflammation. Logistic regression analysis demonstrated that IFTA and interstitial inflammation were significantly associated with the underestimation. Moreover, the cortex length of FKB samples correlated with glomerular number in LM samples regardless of tubulointerstitial lesions. Glomerular number determined during on-site evaluation can be a reference for the actual number of glomeruli in LM samples. Since tubulointerstitial lesions make it difficult to recognize glomeruli in FKB samples, the possibility of underestimation for cases with possibly severe tubulointerstitial lesions should be considered. In such cases, evaluation of cortex length of FKB samples may substitute for evaluating glomeruli on-site.