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Chronic kidney disease (CKD) is a widespread condition often resulting from multiple factors, including maternal influences. These risk factors not only heighten the likelihood of developing CKD but increase the risk of a preterm birth. Adverse events during nephrogenesis can disrupt kidney development, leading to a reduced number of nephrons. As survival rates for preterm infants improve, more individuals are living into adulthood, thereby elevating their risk of CKD later in life. This review aims to explore the connections between preterm birth, kidney development, and the increased risk of CKD, while proposing practical solutions for the future through a multidisciplinary approach. We examine human studies linking preterm birth to negative kidney outcomes, summarize animal models demonstrating kidney programming and reduced nephron numbers, and consolidate knowledge on common mechanisms driving kidney programming. Additionally, we discuss factors in the postnatal care environment that may act as secondary insults contributing to CKD risk, such as acute kidney injury (AKI), the use of nephrotoxic drugs, preterm nutrition, and catch-up growth. Finally, we outline recommendations for action, emphasizing the importance of avoiding modifiable risk factors and implementing early CKD screening for children born preterm. Together, we can ensure that advancements in kidney health keep pace with improvements in preterm care. [ABSTRACT FROM AUTHOR]

Endoscopic and biopsy findings have identified two distinct phenotypes among individuals with calcium oxalate (CaOx) kidney stones. The first type has normal renal papillae but shows interstitial mineral deposition, known as Randall's plaque. The other phenotype presents with collecting duct plugging and a higher incidence of loss of papilla tissue mass. With Randall's plaque, renal papilla injury involves the loss of small patches of calcified tissue (Randall's plaque detaching with the stone), which likely results in damage to only a few nephrons. In contrast, collecting duct mineral plugs are very large, causing obstruction to tubular flow. Since each terminal collecting duct drains thousands of nephrons, ductal plugs could lead to the degeneration of many nephrons and a significant loss of renal glomeruli. New visualization techniques for immune cells in papillary biopsies have revealed that the Randall's plaque phenotype is marked by the accumulation of macrophages around the plaque regions. In contrast, preliminary data on the plugging phenotype shows collecting duct damage with mineral plugs and increased T-lymphocytes throughout the papilla. These regions also show tubulitis, i.e., T-cell infiltration into nearby collecting duct epithelium. This suggests that while some CaOx stone formers may have some papillary inflammation but with minimal damage to nephrons, others suffer from obstruction to flow for many nephrons that may also include destructive inflammation in the renal tissue. We propose that CaOx stone formers with the plugging phenotype will have a higher long-term risk for loss of renal function. [ABSTRACT FROM AUTHOR]

Objective • Clear renal cell carcinoma (ccRCC) is a common and deadly urinary system tumor. The TNM system determines treatment and prognosis based on cancer advancement. While nephron-sparing surgery is an option for localized ccRCC, advanced cases are challenging, and molecular-targeted therapy is crucial. Methods • Here, we implemented microarray datasets to identify a total of 119 differentially expressed genes (DEGs) and ten hub genes by a protein-protein interaction network (PPI) and performed module analysis through STRING and Cytoscape. Results • Data from this analysis shed light on a positive correlation between SLC12A3 (solute carrier family 12 member 3) and tumor-correlated cells. SLC12A3 can predict prognosis and immune infiltration levels in KIRC patients. Conclusion • Our findings demonstrated that SLC12A3 expression accounts for favorable prognosis and increased immune infiltration of various cell types. This could lead to potential therapeutic aims and biomarkers for KIRC (kidney renal clear cell carcinoma). [ABSTRACT FROM AUTHOR]

Organ‐on‐a‐chip (OOC) models based on microfluidic technology are increasingly used to obtain mechanistic insight into (patho)physiological processes in humans, and they hold great promise for application in drug development and regenerative medicine. Despite significant progress in OOC development, several limitations of conventional microfluidic devices pose challenges. First, most microfluidic systems have rectangular cross sections and flat walls, and therefore tubular/ curved structures, like blood vessels and nephrons, are not well represented. Second, polymers used as base materials for microfluidic devices are much stiffer than in vivo extracellular matrix (ECM). Finally, in current cell seeding methods, challenges exist regarding precise control over cell seeding location, unreachable spaces due to flow resistances, and restricted dimensions/geometries. To address these limitations, an alternative cell seeding technique and a corresponding workflow is introduced to create circular cross‐sectioned tubular OOC models by pre‐wrapping cells around sacrificial fiber templates. As a proof of concept, a perfusable renal proximal tubule‐on‐a‐chip is demonstrated with a diameter as small as 50 µm, cellular tubular structures with branches and curvature, and a preliminary vascular‐renal tubule interaction model. The cell pre‐wrapping seeding technique promises to enable the construction of diverse physiological/pathological models, providing tubular OOC systems for mechanistic investigations and drug development. [ABSTRACT FROM AUTHOR]

Most biological fluids contain extracellular vesicles (EVs). EVs are surrounded by a lipid bilayer and contain biological macromolecules such as proteins, lipids, RNA, and DNA. They lack a functioning nucleus and are incapable of replicating. The physiological characteristics and molecular composition of EVs in body fluids provide valuable information about the status of originating cells. Consequently, they could be effectively utilized for diagnostic and prognostic applications. Urine contains a heterogeneous population of EVs. To date, these urinary extracellular vesicles (uEVs) have been ignored in the standard urinalysis. In recent years, knowledge has accumulated on how uEVs should be separated and analyzed. It has become clear how uEVs reflect the expression of each molecule in cells in nephron segments and how they are altered in disease states such as glomerular/tubular disorders, rare congenital diseases, acute kidney injury (AKI), and chronic kidney disease (CKD). Significant promise exists for the molecular expression signature of uEVs detected by simple techniques such as enzyme-linked immunosorbent assay (ELISA), making them more applicable in clinical settings. This review presents the current understanding regarding uEVs, emphasizing the potential for non-invasive diagnostics, especially for childhood kidney diseases. [ABSTRACT FROM AUTHOR]

• Collagen XVIII isoforms differ in their expression during nephrogenesis, where the short isoform is expressed in the early phases of nephron development and the two longer forms are detected only in more mature stage of nephrogenesis. • The lack of collagen XVIII isoforms leads to distinct congenital ultrastructural defects of nephrons. • Collagen XVIII deficient fetuses show decreased nephron progenitor cell numbers and changes in nephron progenitors' cell cycle progression. • Altered Sall1 expression and increased macrophage influx in the developing kidney might play a role in the detected defects in the nephron progenitor cell population in collagen XVIII deficient fetuses. Renal development is a complex process in which two major processes, tubular branching and nephron development, regulate each other reciprocally. Our previous findings have indicated that collagen XVIII (ColXVIII), an extracellular matrix protein, affects the renal branching morphogenesis. We investigate here the role of ColXVIII in nephron formation and the behavior of nephron progenitor cells (NPCs) using isoform-specific ColXVIII knockout mice. The results show that the short ColXVIII isoform predominates in the early epithelialized nephron structures whereas the two longer isoforms are expressed only in the later phases of glomerular formation. Meanwhile, electron microscopy showed that the ColXVIII mutant embryonic kidneys have ultrastructural defects at least from embryonic day 16.5 onwards. Similar structural defects had previously been observed in adult ColXVIII-deficient mice, indicating a congenital origin. The lack of ColXVIII led to a reduced NPC population in which changes in NPC proliferation and maintenance and in macrophage influx were perceived to play a role. The changes in NPC behavior in turn led to notably reduced overall nephron formation. In conclusion, the results show that ColXVIII has multiple roles in renal development, both in ureteric branching and in NPC behavior. [ABSTRACT FROM AUTHOR]

A detailed knowledge of the lipid composition of components of nephrons is crucial for understanding physiological processes and the development of kidney diseases. However, the lipidomic composition of kidney tubular segments is unknown. We manually isolated the proximal convoluted tubule (PCT), the cortical thick ascending limb of Henle's loop, and the cortical collecting duct from 5 lean and obese mice and subjected the samples to shotgun lipidomics analysis by high-resolution mass spectrometry acquisition. Across all samples, more than 500 lipid species were identified, quantified, and compared. We observed significant compositional differences among the 3 tubular segments, which serve as true signatures. These intrinsic lipidomic features are associated with a distinct proteomic program that regulates highly specific physiological functions. The distinctive lipidomic features of each of the 3 segments are mostly based on the relative composition of neutral lipids, long-chain polyunsaturated fatty acids, sphingolipids, and ether phospholipids. These features support the hypothesis of a lipotype assigned to specific tubular segments. Obesity profoundly impacts the lipotype of PCT. In conclusion, we present a comprehensive lipidomic analysis of 3 cortical segments of mouse kidney tubules. This valuable resource provides unparalleled detail that enhances our understanding of tubular physiology and the potential impact of pathological conditions. Graphical Abstract [ABSTRACT FROM AUTHOR]

Blood ultrafiltration in nephrons critically depends on specialized intercellular junctions between podocytes, named slit diaphragms (SDs). Here, by studying a homologous structure found in Drosophila nephrocytes, we identify the phospholipid scramblase Scramb1 as an essential component of the SD, uncovering a novel link between membrane dynamics and SD formation. In scramb1 mutants, SDs fail to form. Instead, the SD components Sticks and stones/nephrin, Polychaetoid/ZO-1, and the Src-kinase Src64B/Fyn associate in cortical foci lacking the key SD protein Dumbfounded/NEPH1. Scramb1 interaction with Polychaetoid/ZO-1 and Flotillin2, the presence of essential putative palmitoylation sites and its capacity to oligomerize, suggest a function in promoting SD assembly within lipid raft microdomains. Furthermore, Scramb1 interactors as well as its functional sensitivity to temperature, suggest an active involvement in membrane remodeling processes during SD assembly. Remarkably, putative Ca2+-binding sites in Scramb1 are essential for its activity raising the possibility that Ca2+ signaling may control the assembly of SDs by impacting on Scramb1 activity. [ABSTRACT FROM AUTHOR]

Complex interactions of the branching ureteric bud (UB) and surrounding mesenchymal cells during metanephric kidney development determine the final number of nephrons. Impaired nephron endowment predisposes to arterial hypertension and chronic kidney disease. In the kidney, extracellular matrix (ECM) proteins are usually regarded as acellular scaffolds or as the common histological end-point of chronic kidney diseases. Since only little is known about their physiological role in kidney development, we aimed for analyzing the expression and role of fibronectin. In mouse, fibronectin was expressed during all stages of kidney development with significant changes over time. At embryonic day (E) 12.5 and E13.5, fibronectin lined the UB epithelium, which became less pronounced at E16.5 and then switched to a glomerular expression in the postnatal and adult kidneys. Similar results were obtained in human kidneys. Deletion of fibronectin at E13.5 in cultured metanephric mouse kidneys resulted in reduced kidney sizes and impaired glomerulogenesis following reduced cell proliferation and branching of the UB epithelium. Fibronectin colocalized with alpha 8 integrin and fibronectin loss caused a reduction in alpha 8 integrin expression, release of glial-derived neurotrophic factor and expression of Wnt11, both of which are promoters of UB branching. In conclusion, the ECM protein fibronectin acts as a regulator of kidney development and is a determinant of the final nephron number. [ABSTRACT FROM AUTHOR]

The urinary collecting system (UCS) consists of organized ducts that collect urine from the nephrons and transport it to the ureter and bladder. Understanding the histogenesis of the UCS is critical. Thirty human embryos between the Carnegie stages (CS) 18 and 23 were selected from the Congenital Anomaly Research Center, Kyoto, Japan. Epithelia of the UCS, ureter, and bladder of each sample were randomly selected. Histological findings of the epithelia were analyzed according to the following criteria: type of epithelium, presence or absence of glycogen, percentage of migrated nuclei, percentage of cells in mitosis, and the surrounding mesenchyme. A thickened epithelium lining a narrow luminal cavity was observed in the pre-expanded pelvic specimens at CS18-CS23. At CS23, after pelvic expansion, the UCS showed a thin epithelium with a large luminal cavity mainly located on the early branches, whereas the epithelium covering the subsequent branches had medium thickness. Histological characteristics differed depending on the UCS part and sample stage. The degree of differentiation was evaluated, revealing that in CS18-CS23 pre-expanded pelvis specimens, the undifferentiated epithelium was found in the zeroth to third/fifth generation, whereas at CS23, after pelvic expansion, a differentiated epithelium covered the UCS zeroth to seventh generation. In a comparison of the urothelial epithelium between the UCS, ureter, and bladder, we found that urinary tract differentiation may be initiated in the bladder, followed by the ureter, UCS zeroth to seventh generations, and finally, UCS eighth to end generations. An understanding of the histogenesis of embryonic stage UCS can aid in the clinical management of congenital urinary tract defects and other diseases. [ABSTRACT FROM AUTHOR]

Kidney disease is a devastating condition affecting millions of people worldwide, where over 100,000 patients in the United States alone remain waiting for a lifesaving organ transplant. Concomitant with a surge in personalized medicine, single-gene mutations, and polygenic risk alleles have been brought to the forefront as core causes of a spectrum of renal disorders. With the increasing prevalence of kidney disease, it is imperative to make substantial strides in the field of kidney genetics. Nephrons, the core functional units of the kidney, are epithelial tubules that act as gatekeepers of body homeostasis by absorbing and secreting ions, water, and small molecules to filter the blood. Each nephron contains a series of proximal and distal segments with explicit metabolic functions. The embryonic zebrafish provides an ideal platform to systematically dissect the genetic cues governing kidney development. Here, we review the use of zebrafish to discover nephrogenesis genes. [ABSTRACT FROM AUTHOR]

The central question of nephron-sparing surgery in unilateral non-syndromic Wilms tumour sits at a crossroads between surgery, oncology, and nephrology. There has been a significant paradigm shift in paediatric oncology towards reducing toxicity and addressing long-term treatment-related sequalae amongst childhood cancer survivors. After paediatric nephrectomy and 30–50 years of follow-up, 40% of patients will have chronic kidney disease, including 22% with hypertension and 23% with albuminuria. It is difficult to predict which patients will progress to develop hypertension, reduced glomerular filtration rate, albuminuria, and a higher cardiovascular risk. For these reasons, nephron-sparing surgery when it is technically feasible must be considered. To decrease the incidence of positive surgical margins (viable tumour present at a resection margin), incomplete lymph node sampling, and complications, these procedures should be performed at specialist and experienced reference centres. Based on the impacts of individual treatment pathways, survivors of childhood WT need to be followed through adulthood for early detection of chronic kidney disease, hypertension, and prevention of cardiovascular events. [ABSTRACT FROM AUTHOR]

Background: The kidneys manage body fluids and electrolytes in addition to performing osmoregulation and metabolic waste disposal. The goal of the present study was to investigate the structural characteristics of the kidneys of two tetrapod species; Ptychadena mascarenensis (Mascarene frog) and Chalcides ocellatus ocellatus (Ocellated skink) concerning their habitat, which could be linked to unique structural renal differences. Methods: During December 2020, four specimens of each species were obtained from various locations in Egypt. The animals were captured alive and were suffocated by inhaling chloroform. There kidneys were removed and processed for morphological, histological and electron microscopy examinations. Result: Ptychadena mascarenensis and Chalcides ocellatus ocellatus have groups of nephrons in their kidneys and each nephron consists of a renal corpuscle, an intermediate segment, a proximal tubule, a distal tubule and a collecting duct system. The renal corpuscles and tubules were dispersed throughout the cortex and medulla of both species so the cortex and medulla were not differentiated. In the two tetrapod classes Amphibia (Ptychadena mascareniensis) and Reptilia (Chalcides ocellatus ocellatus), some differences in the morphological, histological and ultrastructural features of the kidney have been identified. Animals use each of these structures to help them adapt to their surroundings. [ABSTRACT FROM AUTHOR]

The kidney is a highly complex organ equipped with a multitude of miniscule filter-tubule units called nephrons. Each nephron can be subdivided into multiple segments, each with its own morphology and physiological function. To date, conventional manual approaches to isolate specific nephron segments are very laborious, time-consuming, often limited to only a specific segment, and typically have low yield. Here, we describe a novel, unconventional method that is superior in many aspects to previous protocols by combining low-cost fluorophore-conjugated lectins or agglutinins (Flaggs) with flow sorting. This allows the simultaneous separation of different nephron segments with preserved 3D morphology from mouse or human samples in under 3 h. Using a 200-µm nozzle and 5 psi, glomeruli, proximal, or distal convoluted tubules are sorted with Cy3-labeled Sambucus Nigra agglutinin (SNA-Cy3), Fluorescein-labeled Lotus Tetragonolobus lectin (LTL-FITC), or Pacific Blue-labeled soybean agglutinin (SBA-PB), respectively. Connecting tubules and collecting ducts are sorted by double-positive SBA-PB and SNA-Cy3 signals, while thick ascending limb segments are characterized by the absence of any Flaggs labeling. From two mouse kidneys, this yields 37–521 ng protein/s or 0.71–16.71 ng RNA/s, depending on the specific nephron segment. The purity of sorted segments, as assessed by mRNA expression level profiling of 15 genes, is very high with a 96.1-fold median enrichment across all genes and sorted segments. In summary, our method represents a simple, straightforward, cost-effective, and widely applicable tool yielding high amounts of pure and morphologically largely intact renal tubule materials with the potential to propel nephron segment-specific research. [ABSTRACT FROM AUTHOR]

Modeling is a core practice in science and is a meaningful way to learn the subject. This article introduces a modeling-based approach that highlights the idea that modeling is an iterative process and integrates the fundamental parts of scientists' work and key suggestions for teaching through modeling. The lesson "The Structure and Function of Kidneys" from a middle school biology course serves as an example of how to conduct the suggested modeling-based approach. By the end of the lesson, almost all students demonstrated a scientific understanding of the structure of nephrons and their functions. On the basis of the implementation of this lesson, we also provide further suggestions for modeling-based teaching. [ABSTRACT FROM AUTHOR]

Excessive salt intake raises blood pressure, but the implications of this observation for human health have remained contentious. It has also been recognized for many years that potassium intake may mitigate the effects of salt intake on blood pressure and possibly on outcomes such as stroke. Recent large randomized intervention trials have provided strong support for the benefits of replacing salt (NaCl) with salt substitute (75% NaCl, 25% KCl) on hard outcomes, including stroke. During the same period of time, major advances have been made in understanding how the body senses and tastes salt, and how these sensations drive intake. Additionally, new insights into the complex interactions between systems that control sodium and potassium excretion by the kidneys, and the brain have highlighted the existence of a potassium switch in the kidney distal nephron. This switch seems to contribute importantly to the blood pressure–lowering effects of potassium intake. In recognition of these evolving data, the United States Food and Drug Administration is moving to permit potassium-containing salt substitutes in food manufacturing. Given that previous attempts to reduce salt consumption have not been successful, this new approach has a chance of improving health and ending the 'Salt Wars'. [ABSTRACT FROM AUTHOR]

The endogenous capacity of the kidney to repair is limited, and generation of new nephrons after injury for adequate function recovery remains a need. Discovery of factors that promote the endogenous regenerative capacity of the injured kidney or generation of transplantable kidney tissue represent promising therapeutic strategies. While several encouraging results are obtained after administration of stem or progenitor cells, stem cell secretome, or extracellular vesicles in experimental kidney injury models, very little data exist in the clinical setting to make conclusions about their efficacy. In this review, we provide an overview of the cutting-edge knowledge on kidney regeneration, including pre-clinical methodologies used to elucidate regenerative pathways and describe the perspectives of regenerative medicine for kidney patients. [ABSTRACT FROM AUTHOR]

In the evolving landscape of nephrology and kidney transplants, assessing renal functional reserve (RFR) in living kidney donors is essential for ensuring donor safety and successful transplantation. This study explores the use of the Intra-Parenchymal Renal Resistive Index Variation (IRRIV) test, a novel non-invasive method, to measure RFR in living donors. Our observational study included 11 participants undergoing living kidney donations, evaluated using the IRRIV-based Renal Stress Test (RST) before and 12 months post-nephrectomy. The study demonstrated significant changes in creatinine and eGFR CKD-EPI levels post-donation, with an average creatinine rise from 69 to 97 µmol/L and a reduction in eGFR from 104 to 66 mL/min/1.73 m2. These variations align with the expected halving of nephron mass post-nephrectomy and the consequent recruitment of RFR and hyperfiltration in the remaining nephrons. This pilot study suggests that the IRRIV-based RST is a practical, safe, and reproducible tool, potentially revolutionizing the assessment of RFR in living kidney donors, with implications for broader clinical practice in donor eligibility evaluation, even in borderline renal cases. Furthermore, it confirms the feasibility of RST in living kidney donors and allows us to assess the sample size in 48 donors for a future study. [ABSTRACT FROM AUTHOR]

Purpose: The distal nephron of kidney plays a pivotal role in advancing acute kidney injury (AKI). Understanding the role of distal nephrons in AKI and identifying markers of injured distal nephrons are critical to comprehending the mechanism of renal injury and identifying novel therapeutic targets.Methods: We analyzed single-cell RNA sequencing (scRNA-seq) data from mice with AKI induced by ischemia-reperfusion (IR), unilateral ureteral obstruction (UUO), cisplatin (CP), sodium oxalate (SO) and lipopolysaccharide (LPS). Additionally, we analyzed renal transcriptomics samples for AKI. Subsequently, we validated the effectiveness of targeting the biomarker Gclc in vitro and in vivo through metabolomics and immunofluorescence.Results: The LOH-Inj and DCT-Inj subtypes were identified through scRNA-seq. Compared to normal distal nephrons, the injured distal nephrons exhibited higher levels of ferroptosis, pro-inflammation, and fibrosis. The expression of ferroptosis-related gene Gclc were high in various AKI models. Furthermore, Gclc was exclusively expressed in the distal nephron and upregulated in the injury subtype. To confirm our findings, we suppressed GCLC expression in the kidneys, resulting to aggravated IR-induced AKI. Inhibition of Gclc promoted damage to primarily renal tubular epithelial cells by promoting inflammatory infiltration, inhibiting glutathione metabolism and exacerbating oxidative stress.Conclusion: Our research findings suggest that Gclc is a potential marker for injured distal nephron. [ABSTRACT FROM AUTHOR]

Background: Focal segmental glomerulosclerosis (FSGS) is a histological pattern of glomerular damage that includes idiopathic conditions as well as genetic and non-genetic forms. Among these various etiologies, different phenotypes within the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT) have been associated with FSGS. Summary: Until recently, the main pathomechanism of how congenital kidney and urinary tract defects lead to FSGS was attributed to a reduced number of nephrons, resulting in biomechanical stress on the remaining glomeruli, detachment of podocytes, and subsequent inability to maintain normal glomerular architecture. The discovery of deleterious single-nucleotide variants in PAX2, a transcription factor crucial in normal kidney development and a known cause of papillorenal syndrome, in individuals with adult-onset FSGS without congenital kidney defects has shed new light on developmental defects that become evident during podocyte injury. Key Message: In this mini-review, we challenge the assumption that FSGS in CAKUT is caused by glomerular hyperfiltration alone and hypothesize a multifactorial pathogenesis that includes overlapping cellular mechanisms that are activated in both damaged podocytes as well as nephron progenitor cells. [ABSTRACT FROM AUTHOR]

Background: During kidney organogenesis, metanephric mesenchyme (MM) and ureteric bud (UB) interact reciprocally to form nephrons. Signaling stimuli involved in these interactions include Wnts, growth factors and nano/micro particles. How UB and MM are interacting is not completely understood. Our study investigated the signaling and communication via extracellular vesicles (EVs) during nephrogenesis. Embryonic day (E) 11.5 mouse kidney UB and MM produce very low number of primary cells that have limited ability for proliferation in culture. Such limitations obstruct studying the role of EVs in induction of nephrogenesis. These issues necessitate to generate a nephrogenesis model allowing to study the comprehensive role of EVs during nephrogenesis. Results: Our study generated a UB derived cell line-based in vitro flexible model of nephrogenesis allowing expandable cell culturing, in addition to performing characterization, tracking and blocking of EVs. UB cell line aggregation with E11.5 MM cells induced the formation of segmented nephrons. Most efficient nephrogenesis was obtained by the co-culturing of 30,000 cells of UB cell line with 50,000 MM cells. Results revealed that both the UB and the MM secrete EVs during nephrogenesis. UB cell line derived EVs were characterized by their size, morphology and expression of markers (CD63, TSG101, CD9 and CD81). Furthermore, proteomics data of UB cell line-derived EVs revealed large number of proteins involved in nephrogenesis-related signaling pathways. Palmitoylated GFP-tagged EVs from UB cell line were found in the nephron formation zone in the developing kidney organoid. UB cell line derived EVs did not induce nephrogenesis in MM cells but significantly contributed to the survival and nephrogenesis-competency of MM cells. The secretion of EVs was continuously inhibited during the ongoing nephrogenesis by the knockdown of RalA and RalB gene expression using short hairpin RNAs. This inhibition partially impaired the ability of UB cell line to induce nephrogenesis. Moreover, impaired nephrogenesis was partially rescued by the addition of EVs. Conclusion: Our study established a novel in vitro flexible model of nephrogenesis that solved the limitations of primary embryonic kidney cells and mouse embryonic stem cell kidney organoids for the EV research. EVs were found to be an integral part of nephrogenesis process. 7F9YfcJgNbSGEsBfhqoDc7 Video Abstract [ABSTRACT FROM AUTHOR]

The intricate vascular system of the kidneys supports body fluid and organ homeostasis. However, little is known about how vascular architecture is established during kidney development. More specifically, how signals from the kidney influence vessel maturity and patterning remains poorly understood. Netrin 1 (Ntn1) is a secreted ligand that is crucial for vessel and neuronal guidance. Here, we demonstrate that Ntn1 is expressed by Foxd1+ stromal progenitors in the developing mouse kidney and conditional deletion (Foxd1GC/+; Ntn1fl/fl) results in hypoplastic kidneys with extended nephrogenesis. Wholemount 3D analyses additionally revealed the loss of a predictable vascular pattern in Foxd1GC/+;Ntn1fl/fl kidneys. As vascular patterning has been linked to vessel maturity, we investigated arterialization. Quantification of the CD31+ endothelium at E15.5 revealed no differences in metrics such as the number of branches or branch points, whereas the arterial vascular smooth muscle metrics were significantly reduced at both E15.5 and P0. In support of our observed phenotypes, whole kidney RNA-seq revealed disruptions to genes and programs associated with stromal cells, vasculature and differentiating nephrons. Together, our findings highlight the significance of Ntn1 to proper vascularization and kidney development. [ABSTRACT FROM AUTHOR]

Nephrons are generally not distributed in the head kidney of teleost. Nonetheless, in this study, the nephron structure was identified in the head kidney of three species of Sebastes (Sebastes inermis, Sebastes schlegelii and Sebastes thompsoni). The kidney is Y shaped, with the development in the head kidney. The nephron structure was confirmed in the head kidney and body kidney. In addition, the nephron consisted of renal corpuscles and tubules, and the renal corpuscle consisted of the Bowman's capsule and glomerulus. Histologically, previous studies reported that the nephron structure is similar to that of other marine teleost. The renal tubule is a simple columnar epithelial layer with microvilli and cilia on the free surface, which is observed as a brush border. The Rrk (relative area ratio of kidney to body surface) was 5.14%, 7.58% and 5.17% in S. inermis, S. schlegelii and S. thompsoni, respectively. The Gar (glomerular area ratio of the head kidney) was higher in the central area than in the peripheral area, and species, which showed significant difference (P < 0.05), were in the following order: S. thompsoni (1.60%) > S. schlegelii (0.90%) > S. inermis (0.66%). [ABSTRACT FROM AUTHOR]

Nephrons are the basic filtering units of the kidneys. Progression of chronic kidney disease (CKD) destroys nephrons permanently. Although there are many computing schemes suggested in recent years to identify CKD stages, no computing method has been suggested for identifying the nephron loss within kidney regions during CKD progression. In this paper, a novel pattern matching-based computation scheme is proposed to detect nephron loss in the kidney regions during CKD progression. We consider image registration (IR) with different transforms and a structural similarity index algorithm (SSIM) to match patterns of ultrasound images of kidney regions to identify the nephron loss. Simulation results show that the proposed scheme based on IR and SSIM algorithms detects almost 34% and 51% and almost 35% and 56% of the nephron damage in the cortex and medulla relative to a normal kidney, respectively. We extend the pattern matching scheme to identify CKD stages, as well. The proposed scheme based on IR and the SSIM algorithm can identify CKD stage with accuracy of 96% and 88%, respectively. The prediction accuracy of the proposed scheme for identifying CKD stage is comparable to that of the gray level co-occurrence matrix-based method, which is the best among the existing computing methods. However, the proposed scheme has advantages over the preexisting scheme, such as: the proposed method can be used to identify both CKD stage and the nephron loss in different kidney regions, and it identifies CKD stage without using a classifier. Therefore, the proposed pattern matching-based computing method is a better alternative to existing computing schemes for CKD stage identification. [ABSTRACT FROM AUTHOR]

Oxidative stress is a well-known cause of chronic kidney disease (CKD). In this study, renal oxidative damage in azotaemic and non-azotaemic aged cats with naturally occurring CKD was investigated using immunohistochemistry for 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE) as markers of oxidative tissue damage. Kidneys were obtained from aged (>10 years old) azotaemic (n = 13) and non-azotaemic (n = 7) cats. Immunoreactivity for 8-OHdG was found in the nuclei of glomeruli, proximal and distal tubules, loops of Henle and collecting ducts, whereas 4-HNE-positive signals were detected in the cytoplasm of distal nephrons in azotaemic and non-azotaemic cats. Quantitative analysis did not identify any significant differences between the azotaemic and non-azotaemic groups for any of the parameters examined. These results indicate that renal oxidative damage occurs in the kidneys of aged cats with CKD, regardless of whether they are azotaemic or non-azotaemic, emphasizing the importance of oxidative stress during early-stage CKD in senior and geriatric cats. [ABSTRACT FROM AUTHOR]

Kidney organoids have shown promise as evaluation tools, but their in vitro maturity remains limited. Transplantation into adult mice has aided in maturation; however, their lack of urinary tract connection limits long-term viability. Thus, long-term viable generated nephrons have not been demonstrated. In this study, we present an approachable method in which mouse and rat renal progenitor cells are injected into the developing kidneys of neonatal mice, resulting in the generation of chimeric nephrons integrated with the host urinary tracts. These chimeric nephrons exhibit similar maturation to the host nephrons, long-term viability with excretion and reabsorption functions, and cisplatin-induced renal injury in both acute and chronic phases, as confirmed by single-cell RNA-sequencing. Additionally, induced human nephron progenitor cells differentiate into nephrons within the neonatal kidneys. Collectively, neonatal injection represents a promising approach for in vivo nephron generation, with potential applications in kidney regeneration, drug screening, and pathological analysis. Chimeric kidneys are generated by injecting exogenous renal progenitor cells into neonatal mouse kidneys which form connections to the host urinary tract and remain viable for an extended period, making them useful for evaluating acute and chronic nephrotoxicity. [ABSTRACT FROM AUTHOR]

The paired kidneys play a significant role in the human body due to the multitude of physiological tasks. Complex biochemical processes keep the sensitive electrolyte and water balance stable and thus ensure the organism's ability to adapt to exogenous and endogenous factors, which is essential for survival. The drug class of diuretics includes substances with very differing pharmacological characteristics. The functioning of the nephron is therefore indispensable for a deeper understanding of the pharmacodynamics, pharmacokinetics and side effect profile of diuretics. In the treatment of acute heart failure with pulmonary congestion, certain diuretics represent an important therapeutic option to counteract hypervolemia and thus an increase in preload. According to current data, diuretics have no proven benefits in the treatment or prevention of acute kidney injury but they can counteract hypervolemia and under certain conditions even reduce the use of renal replacement procedures. [ABSTRACT FROM AUTHOR]

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BACKGROUND: The expression of NGAL/lcn2 (neutrophil gelatinase-associated lipocalin) is directly modulated by mineralocorticoid receptor activation but its role in blood pressure control is unclear. METHODS: a potential relationship between NGAL plasma levels, systolic blood pressure and urinary Na excretion was assessed in the STANISLAS cohort. The specific role of NGAL/lcn2 in salt-sensitive hypertension was studied using lcn2- knockout mice (lcn2 KO) fed with low-Na diet (0Na). RESULTS: we show that NGAL plasma levels positively correlate with systolic blood pressure, whereas they negatively correlate with urinary Na excretion in subjects of the STANISLAS cohort. Prolonged feeding of lcn2 KO mice with a 0Na diet induced lower systolic blood pressure than that of the control group (wildtype), suggesting a role for NGAL/lcn2 in Na-balance homeostasis. Short-term or prolonged 0Na increased Na-Cl cotransporter (NCC) phosphorylation in the cortex of wildtype mice, which was prevented in lcn2 KO mice. Recombinant mouse lcn2 injections in lcn2 KO mice induced NCC phosphorylation in the kidney cortex, associated with decreased urinary Na excretion. Ex vivo experiments using kidney slices from lcn2 KO mice showed increased NCC phosphorylation by recombinant murine lcn2. In addition, recombinant murine lcn2 induced activation of CamK2ß (calcium/calmodulin-dependent protein kinase II ß subunit) phosphorylation in lcn2 KO mice and in kidney slices, providing an underlying mechanism involved in lcn2-induced NCC phosphorylation. Indeed, the inhibition of CamK2ß prevented NCC phosphorylation induced by recombinant lcn2 in kidney slices. CONCLUSIONS: we highlight a novel role of NGAL/lcn2 as a modulator of the activity of the renal sodium transporter NCC affecting salt-sensitive blood pressure. [ABSTRACT FROM AUTHOR]

The PAX2 gene is a transcription factor that is essential for the development of the urinary system among other transcription factors. The role of PAX2 is highlighted from the seventh week of gestation, when it is involved in development processes and the emergence of nephrons and collecting tubes. Being an important factor in renal development, mutations of this gene can produce severe alterations in the development of the urinary tract, namely congenital anomalies of the kidneys and urinary tract. The first reported cases described with the PAX2 mutation included both renal anomalies and the involvement of other organs, such as the eyes, producing renal coloboma syndrome. Over the years, numerous cases have been reported, including those with only renal and urinary tract anomalies. The aim of this review is to present a summary of pediatric patients described to have mutations in the PAX2 gene to contribute to a better understanding of the genetic mechanism causing anomalies of the kidneys and urinary tract. In this review, we have included only pediatric cases with renal and urinary tract disorders, without the involvement of other organs. From what we know so far from the literature, this is the first review gathering pediatric patients presenting the PAX2 mutation who have been diagnosed exclusively with renal and urinary tract disorders. [ABSTRACT FROM AUTHOR]

Copyright of Revista Habanera de Ciencias Médicas is the property of Universidad de Ciencias Medicas de La Habana and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Kidney size and glomerular filtration rate (GFR) often increase with the onset of diabetes, and elevated GFR is a risk factor for the development of diabetic kidney disease. Hyperfiltration mainly occurs in response to signals passed from the tubule to the glomerulus: high levels of glucose in the glomerular filtrate drive increased reabsorption of glucose and sodium by the sodium-glucose cotransporters SGLT2 and SGLT1 in the proximal tubule. Passive reabsorption of chloride and water also increases. The overall capacity for proximal reabsorption is augmented by growth of the proximal tubule, which (alongside sodium-glucose cotransport) further limits urinary glucose loss. Hyperreabsorption of sodium and chloride induces tubuloglomerular feedback from the macula densa to increase GFR. In addition, sodium-glucose cotransport by SGLT1 on macula densa cells triggers the production of nitric oxide, which also contributes to glomerular hyperfiltration. Although hyperfiltration restores sodium and chloride excretion it imposes added physical stress on the filtration barrier and increases the oxygen demand to drive reabsorption. Tubular growth is associated with the development of a senescence-like molecular signature that sets the stage for inflammation and fibrosis. SGLT2 inhibitors attenuate the proximal reabsorption of sodium and glucose, normalize tubuloglomerular feedback signals and mitigate hyperfiltration. This tubule-centred model of diabetic kidney physiology predicts the salutary effect of SGLT2 inhibitors on hard renal outcomes, as shown in large-scale clinical trials.

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. [ABSTRACT FROM AUTHOR]

The paper proposes a multiresolution cross-correlation analysis (MCCA) combining cross-correlation analysis of complex signals with multiresolution wavelet analysis, which provides decomposition of datasets at several resolution levels and processing of the obtained sets of detail wavelet coefficients. Such an approach can improve the interpretation of changes in the dynamics of the system under study, associating the occurring phenomena with the mechanisms responsible for them. The possibilities of MCCA are illustrated by the example of synchronous and asynchronous dynamics of the model of two interacting nephrons providing oscillations with two different time scales. [ABSTRACT FROM AUTHOR]

The main structural and functional element of the kidneys is the nephron, which consists of a glomerulus (branching of renal capillaries) located inside the double-walled Shumliansky-Bowman capsule (capsula glomeruli), which extends into a system of renal tubules flowing into the urinary tubes. Nephrons are divided into superficial (surface), intracortical and juxtamedullary. [ABSTRACT FROM AUTHOR]

Kidney xenotransplantation has been attracting attention as a treatment option for end-stage renal disease. Fetal porcine kidneys are particularly promising grafts because they can reduce rejection through vascularization from host vessels. We are proposing xenogeneic regenerative medicine using fetal porcine kidneys injected with human nephron progenitor cells. For clinical application, it is desirable to establish reliable methods for the preservation and quality assessment of grafts. We evaluated the differentiation potency of vitrified porcine fetal kidneys compared with nonfrozen kidneys, using an in vivo differentiation model. Fetal porcine kidneys connected to the bladder were frozen via vitrification and stored in liquid nitrogen. Several days later, they were thawed and transplanted under the retroperitoneum of immunocompromised mice. After 14 days, the frozen kidneys grew and differentiated into mature nephrons, and the findings were comparable to those of nonfrozen kidneys. In conclusion, we demonstrated that the differentiation potency of vitrified fetal porcine kidneys could be evaluated using this model, thereby providing a practical protocol to assess the quality of individual lots. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the predictive factors for perioperative and long-term renal functions after nephron-sparing surgery (NSS). Materials and Methods: The clinical records of 379 patients who underwent NSS for a single renal tumor with a normal contralateral kidney between 2009 and 2016 were retrospectively analyzed. After surgery, the occurrence of acute kidney injury (AKI) within 7 days and the progression of chronic kidney disease (CKD) 5 years later were assessed using serum creatinine (S-Cr) levels. Perioperative AKI was defined as an increase in the S-Cr level by ≥ 0.3 mg/dL or 1.5–1.9 times the baseline value. CKD was defined as the estimated glomerular filtration rate (eGFR) decreasing from > 60 mL/min/1.73 m2 to < 60 mL/min/1.73 m2. Results: Changes in the eGFR were assessed during 5 years after surgery. Among 379 patients, 81 (21.4%) patients presented diabetes mellitus (DM), and 30 (7.92%) experienced uncontrolled DM. The AKI occurrence and CKD progression were observed in 50 (13.2%) patients and 79 (20.8%) patients, respectively. Multivariable analyses revealed that female gender (95% confidence interval [CI]: 0.16–0.91, odds ratio [OR] = 0.39, P = 0.029), uncontrolled DM (95% CI: 1.05–6.60, OR = 2.63, P = 0.039), and intermediate NePhRO score (95% CI: 1.07–3.80, OR = 2.02, P = 0.03) were associated with perioperative AKI. In addition, old age (95% CI: 1.10–1.18, OR = 1.14, P < 0.001) and uncontrolled DM (95% CI: 1.84–11.4, OR = 4.57, P = 0.001) were associated with long-term CKD progression. Conclusion: Uncontrolled DM is the only predictive factor for perioperative and long-term renal functions after nephron-sparing surgery. [ABSTRACT FROM AUTHOR]

Nephrons are the functional units which comprise the kidney. Each nephron contains a number of physiologically unique populations of specialized epithelial cells that are organized into discrete domains known as segments. The principles of nephron segment development have been the subject of many studies in recent years. Understanding the mechanisms of nephrogenesis has enormous potential to expand our knowledge about the basis of congenital anomalies of the kidney and urinary tract (CAKUT), and to contribute to ongoing regenerative medicine efforts aimed at identifying renal repair mechanisms and generating replacement kidney tissue. The study of the zebrafish embryonic kidney, or pronephros, provides many opportunities to identify the genes and signaling pathways that control nephron segment development. Here, we describe recent advances of nephron segment patterning and differentiation in the zebrafish, with a focus on distal segment formation. [ABSTRACT FROM AUTHOR]

A letter to the editor discusses a study on the treatment of coraliform kidney stones using retrograde intrarenal surgery (RIRS) with thulium fiber laser (TFL) lithotripsy. The study found that RIRS with TFL laser lithotripsy was feasible, effective, and safe for treating staghorn stones. However, the study reported a relatively low stone-free rate and a high complication rate. The authors suggest that RIRS may not be the best method for treating coraliform stones with current technology and propose alternative methods such as ECIRS or mini-percutaneous nephrolithotomy (PNL) as potentially more effective options. [Extracted from the article]

Simple Summary: Beckwith–Wiedemann Syndrome (BWS) is one of the five most frequent syndromes predisposing to Wilms tumor (WT). BWS can be underdiagnosed if the phenotype is mild, and WT can be the presenting symptom. The purpose of this review is to summarize the available data in the current literature on the diagnosis, surveillance, treatment strategies, and outcome of WT in the presence of BWS. The awareness of clinical and pathological features of WT suggestive of BWS-associated WT can lead to prompt genetic counselling and, consequently, to the most appropriate treatment. Beckwith–Wiedemann Syndrome (BWS) is a pediatric overgrowth disorder involving a predisposition to embryonal tumors. Most of the tumors associated with BWS occur in the first 8–10 years of life, and the most common is Wilms tumor (WT). BWS clinical heterogeneity includes subtle overgrowth features or even silent phenotypes, and WT may be the presenting symptom of BWS. WT in BWS individuals exhibit distinct characteristics from those of sporadic WT, and the management of these patients needs a peculiar approach. The most important feature is a higher risk of developing bilateral disease at some time in the course of the illness (synchronous bilateral disease at diagnosis or metachronous recurrence after initial presentation with unilateral disease). Accordingly, neoadjuvant chemotherapy is the recommended approach also for BWS patients with unilateral WT to facilitate nephron-sparing surgical approaches. This review emphasizes the importance of early BWS recognition, particularly if a WT has already occurred, as this will result in an urgent consideration of first-line cancer therapy. [ABSTRACT FROM AUTHOR]

We aimed to investigate expression of the novel susceptibility genes for CAKUT, DLG1 and KIF12, proposed by a systematic in silico approach, in developing and postnatal healthy human kidneys to provide information about their spatiotemporal expression pattern. We analyzed expression of their protein products by immunohistochemistry and immunofluorescence and quantified relative mRNA levels by RT-qPCR. Statistically significant differences in expression patterns were observed between certain developmental stages. Strong expression of DLG1 was observed in the developing kidney, with a gradual decrease from the first phase of kidney development (Ph1) until the third phase (Ph3), when most nephrons are formed; at later stages, the highest expression was observed in the tubules. KIF12 was highly expressed in the developing structures, especially in Ph1, with a gradual decrease until the postnatal phase, which would indicate a significant role in nephrogenesis. Co-localization of DLG1 and KIF12 was pronounced in Ph1, especially on the apical side of the tubular epithelial cells. Thereafter, their expression gradually became weaker and was only visible as punctate staining in Ph4. The direct association of DLG1 with KIF12 as control genes of normal kidney development may reveal their new functional aspect in renal tubular epithelial cells. [ABSTRACT FROM AUTHOR]

Background: Cryoablation is a promising minimally invasive, nephron-sparing treatment of small renal carcinoma (RCC) in co-morbid patients. Purpose: To assess the safety, efficacy, and cancer-specific outcomes of computed tomography (CT)-guided cryoablation of stage T1 (RCC). Material and Methods: A retrospective evaluation of 122 consecutive patients with 128 tumors treated with cryoablation during 2016–2017. All patients had biopsy-verified T1 RCC. Results: Median age was 69 years (IQR=59–76); 69% were male. Median tumor size was 26 mm (± 20–33); 9% were stage T1b. Mean follow-up time was 36.3±12.0 months. In total, 14 (11%) procedures led to complications, of which 4 (3%) were intraoperative, 5 (4%) appeared ≤30 days and 5 (4%) >30 days after treatment. Major complications arose after 4 (3%) procedures. Statistically significant associations were found between major complications and stage T1b (P = 0.039), RENAL score (P = 0.010), and number of needles used in cryoablation (P = 0.004). Residual tumor was detected after 4 (3%) procedures and 5 (4%) tumors had local tumor progression. Of 122 patients, 3 (2%) advanced to metastatic disease. Significant statistical associations were found between local tumor progression and T1b stage tumors and number of needles used in cryoablation (P = 0.05 and P = 0.004, respectively). For patients with T1a tumors, the one- and three-year disease-free survival was 98% and 95%, respectively, and for T1b 100% after one year and 75% after three years. Conclusions: This study showed that cryoablation is a safe and effective treatment of stage T1 RCC and suggests that in selecting candidates for cryoablation of RCC, the tumor characteristics are more critical than patients' baseline health status. [ABSTRACT FROM AUTHOR]

Copyright of Yeni Üroloji Dergisi is the property of Ali Ihsan Tasci and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Polycystic kidney disease (PKD) is a common genetic disorder arising from developmental and postnatal processes. Defects in primary cilia and their signaling (eg, mTOR) underlie the pathogenesis. However, how mTOR regulates tubular integrity remains unclear. The paucity of faithful models has limited our understanding of pathogenesis and, therefore, the refinement of therapeutic targets. To understand the role of mTOR in early cystogenesis, we studied an in-house mouse model, Cd79a-Cre;Tsc1ff. (Cd79a-Tsc1 KO hereafter), recapitulating human autosomal-dominant PKD histology. Cre-mediated Tsc1 depletion driven by the promoter for Cd79a, a known B-cell receptor, activated mTORC1 exclusively along the distal nephron from embryonic day 16 onward. Cysts appeared in the distal nephron at 1 weeks of age and mice developed definite PKD by 4 weeks. Cd79a-Tsc1 KO tubule cells proliferated at a rate comparable to controls after birth but continued to divide even after postnatal day 14 when tubulogenesis is normally completed. Apoptosis occurred only after 9 weeks. During postnatal days 7–11, pre-cystic Cd79a-Tsc1 KO tubule cells showed cilia elongation, aberrant cell intercalation, and mitotic division, suggesting that defective cell planar polarity (PCP) may underlie cystogenesis. mTORC1 was activated in a portion of cyst-lining cells and occasionally even when Tsc1 was not depleted, implying a non-autonomous mechanism. Our results indicate that mTORC1 overactivation in developing distal tubules impairs their postnatal narrowing by disrupting morphogenesis, which orients an actively proliferating cell toward the elongating axis. The interplay between mTOR and cilium signaling, which coordinate cell proliferation with PCP, may be essential for cystogenesis. [ABSTRACT FROM AUTHOR]

While coronavirus disease 2019 (COVID-19) begins as a respiratory infection, it progresses as a systemic disease involving multiorgan microthromboses that underly the pathology. SARS-CoV-2 enters host cells via attachment to the angiotensin-converting enzyme 2 (ACE2) receptor. ACE2 is widely expressed in a multitude of tissues, including the lung (alveolar cells), heart, intestine, kidney, testis, gallbladder, vasculature (endothelial cells), and immune cells. Interference in ACE2 signaling could drive the aforementioned systemic pathologies, such as endothelial dysfunction, microthromboses, and systemic inflammation, that are typically seen in patients with severe COVID-19. ACE2 is a component of the renin–angiotensin system (RAS) and is intimately associated with the plasma kallikrein-kinin system (KKS). As many papers are published on the role of ACE and ACE2 in COVID-19, we will review the role of bradykinin, and more broadly the KSS, in SARS-CoV-2-induced vascular dysfunction. Furthermore, we will discuss the possible therapeutic interventions that are approved and in development for the following targets: coagulation factor XII (FXII), tissue kallikrein (KLK1), plasma kallikrein (KLKB1), bradykinin (BK), plasminogen activator inhibitor (PAI-1), bradykinin B1 receptor (BKB1R), bradykinin B2 receptor (BKB2R), ACE, furin, and the NLRP3 inflammasome. Understanding these targets may prove of value in the treatment of COVID-19 as well as in other virus-induced coagulopathies in the future. [ABSTRACT FROM AUTHOR]

Nephron-sparing surgery (partial nephrectomy) has provided multiple benefits, mainly in patients with small kidney lesions or concomitant diseases that affect overall kidney function in long term, also in patients with a single functional kidney, either congenital or by surgery, end-stage renal disease, bilateral renal tumors or with chromosomal diseases that affects the renal function. The case of a 52-years-old male patient is presented with a 10-cm right kidney tumor in the interpolar region, with not functional left kidney exclusion due to an obstructive process by congenital ureteropyelic stenosis. Right nephron-sparing nephrectomy was performed despite the location and size of the tumor, obtaining excellent oncological and functional results. Follow-up at twelve months of postoperative evolution showed no data of tumor activity, presenting renal function with creatinine of 1.6 mg/dl, with satisfactory evolution. Conclusions: Partial nephrectomy is the standard management for small-volume renal tumors located in the renal cortex and polar areas, or not functional contralateral kidney; but there is the dilemma, when patients appear with impaired renal function or tumors located near the renal hilum by > 5 cm of diameter, the risk of performs this procedure must be taken, the laparoscopic approach is an excellent option. with great results, and minor bleeding than open surgery. [ABSTRACT FROM AUTHOR]

Multiloculated cystic renal masses are uncommon in the pediatric population. The presentation may be as an asymptomatic incidental finding on imaging, abdominal mass, abdominal pain, or urinary tract infection. The differentiation between benign and malignant causes of a cystic lesion by clinical and radiological examination is difficult. Tru-cut biopsy is not recommended due to fear of upgrading a malignant tumor. A definitive diagnosis is confirmed histopathologically only after surgery. Based on certain imaging characteristics, benign nature can be suspected and a conservative approach to surgery can be contemplated to save the kidney. Frozen section biopsy is useful in ruling out malignancy while doing nephron-sparing surgery (NSS) in these patients. NSS may be done by an open or minimally invasive approach. After histological confirmation of cystic nephroma, no other adjuvant treatment is necessary, but long-term surveillance is strongly recommended. [ABSTRACT FROM AUTHOR]

Background The progression of chronic kidney disease (CKD), a global public health burden, is accompanied by a declining number of functional nephrons. Estimation of remaining nephron mass may improve assessment of CKD progression. Uromodulin has been suggested as a marker of tubular mass. We aimed to identify metabolites associated with uromodulin concentrations in urine and serum to characterize pathophysiologic alterations of metabolic pathways to generate new hypotheses regarding CKD pathophysiology. Methods We measured urinary and serum uromodulin levels (uUMOD, sUMOD) and 607 urinary metabolites and performed cross-sectional analyses within the German Chronic Kidney Disease study (N  = 4628), a prospective observational study. Urinary metabolites significantly associated with uUMOD and sUMOD were used to build weighted metabolite scores for urine (uMS) and serum uromodulin (sMS) and evaluated for time to adverse kidney events over 6.5 years. Results Metabolites cross-sectionally associated with uromodulin included amino acids of the tryptophan metabolism, lipids and nucleotides. Higher levels of the sMS [hazard ratio (HR) = 0.73 (95% confidence interval 0.64; 0.82), P  = 7.45e-07] and sUMOD [HR = 0.74 (95% confidence interval 0.63; 0.87), P  = 2.32e-04] were associated with a lower risk of adverse kidney events over time, whereas uUMOD and uMS showed the same direction of association but were not significant. Conclusions We identified urinary metabolites associated with urinary and serum uromodulin. The sUMOD and the sMS were associated with lower risk of adverse kidney events among CKD patients. Higher levels of sUMOD and sMS may reflect a higher number of functional nephrons and therefore a reduced risk of adverse kidney outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Cats are highly susceptible to chronic kidney disease (CKD); however, the pathophysiological mechanisms of feline CKD have not been fully elucidated. To understand the mechanisms of CKD, it is important to clarify the changes in glycosylation of diseased renal cells. Lectins are specific probes used to explore changes in the carbohydrate moiety of cellular components. No study has yet demonstrated lectin binding patterns in normal feline kidneys. In the present study, we performed a lectin histochemical analysis of normal feline kidneys and evaluated the lectin-binding pattern in each nephron segment. Eight lectins, WGA, s-WGA, RCA-I, ConA, PNA, SBA, DBA, and UEA-I, were used as probes in the present study. The lectin binding pattern in each nephron segment was determined for each lectin, and a feline-specific lectin-binding pattern was established in the normal kidney. The present study provides a basis for future glycopathological studies of feline CKD. Lectins have a strict binding specificity to carbohydrate moieties of cellular components, and can thus indicate changes in the glycosylation of cells in diseases. However, lectin-binding patterns in nephron segments of feline kidneys have not been fully surveyed. The present study reported lectin-binding patterns in normal feline kidneys by histochemical investigations of eight commercially available lectin detection kits. Kidneys from four normal cats (intact males, 23–27 months old) were fixed in 4% paraformaldehyde, and embedded in paraffin; lectin histochemistry was performed for WGA, s-WGA, RCA-I, ConA, PNA, SBA, DBA, and UEA-I lectins. WGA, RCA, and ConA binding was observed from Bowman's capsule to the collecting ducts, while only WGA was detected in the glomerular capillary. s-WGA was observed from the proximal tubules to the collecting ducts, showing discriminative heterogeneous binding. PNA and SBA were detected in the distal nephrons, such as the thin limbs of the loops of Henle, distal tubules, and collecting ducts. UEA-I binding was observed in the thick ascending limbs of the loops of Henle, especially in the macula densa regions. DBA lectin showed no positive labeling in nephrons. The observed binding patterns may prove beneficial for the analysis of changes in glycosylation in feline kidney diseases. [ABSTRACT FROM AUTHOR]