Healthy Kidney Research Articles

Visualizing filtration: a hands-on model for understanding Starling forces in glomerular filtration rate.

Understanding complex physiological processes is a cornerstone of medical education, and one such fundamental concept is the regulation of the glomerular filtration rate (GFR) by Starling forces. Therefore, developing a physiologically sound educational model to demonstrate these forces can significantly enhance the learning experience for students, providing them with a clear and comprehensive understanding of renal filtration. Starling forces include the glomerular capillary hydrostatic pressure, which drives plasma filtration; the plasma colloid osmotic pressure (also referred to as the oncotic pressure within the capillary), which opposes filtration; and the Bowman's capsule hydrostatic pressure, which resists fluid influx. Bowman's capsule oncotic pressure is typically considered negligible in healthy kidneys and, therefore, does not usually influence the glomerular filtration process. It is crucial for future clinicians to understand these Starling forces in order to monitor and manage kidney function effectively. To aid in understanding these concepts, we present a simple yet effective physical model of GFR. This model uses pressurized air and a serological pipette setup to simulate the filtration process, with a ping-pong ball's height representing GFR. Various perturbations demonstrate changes in Starling forces, allowing students to visualize the impact of different physiological and pathological conditions on GFR. This hands-on approach aims to simplify the complex interplay of factors affecting GFR, making it an invaluable educational tool for medical students.NEW & NOTEWORTHY Physical models enhance the understanding of complex physiological concepts. This Illumination introduces a hands-on model using pressurized air and a serological pipette to simulate glomerular filtration rate (GFR), with a ping-pong ball indicating filtration rate. The model demonstrates how Starling forces, glomerular capillary hydrostatic pressure, plasma colloid osmotic pressure, Bowman's capsule oncotic pressure, and Bowman's capsule hydrostatic pressure, affect GFR, providing a clear and comprehensive learning experience for students.

Oxygen sensing in the kidney.

The kidneys fulfil several essential homeostatic functions for the body. One of them is the maintenance of sufficient oxygen supply to the organs. For this purpose, the kidneys control the formation of red blood cells by the production of the hormone erythropoietin. This control of red cell formation is not only relevant to prevent states of oxygen deficiency but also to prevent an unwanted increase of red cell numbers causing thromboembolic risks. The adequate production of erythropoietin requires a sensing of the arterial oxygen content and transduction to hormone production. This oxygen sensing is a two-step process which includes a translation of the arterial oxygen content to respective oxygen tension in the tubulointerstitium and a perception of the resulting local interstitial oxygen tension to translate them into specific cellular responses such as the production of erythropoietin. This contribution will describe these steps of oxygen sensing for the healthy kidney and for the changes occurring during states of chronic renal disease, which are commonly associated with anemia. In this context a special focus will also be set on intrarenal hypoxia and oxygen sensing in the diabetic kidney including the treatment with tubular glucose transport (SGLT-2) inhibitors which might influence the oxygen sensing in the kidney. Finally, we will consider the effects of prolylhydroxylase inhibitors (PHD-I), which fundamentally interfere with the cellular oxygen sensing and which are meanwhile treatment options in renal anemia.

Hypoxia-Induced Differences in the Expression of Pyruvate Dehydrogenase Kinase 1-Related Factors in the Renal Tissues and Renal Interstitial Fibroblast-like Cells of Yak (Bos Grunniens).

Hypoxia is one of the factors severely affect renal function, and, in severe cases, it can lead to renal fibrosis. Although much progress has been made in identifying the molecular mediators of fibrosis, the mechanisms that govern renal fibrosis remain unclear, and there have been no effective therapeutic anti-fibrotic strategies to date. Mammals exposed to low oxygen in the plateau environment for a long time are prone to high-altitude disease, while yaks have been living in the plateau for generations do not develop kidney fibrosis caused by low oxygen. It has been suggested that metabolic reprogramming occurs in renal fibrosis and that pyruvate dehydrogenase kinase 1 (PDK1) plays a crucial role in metabolic reprogramming as an important node between glycolysis and the tricarboxylic acid cycle. The aim of this study was to investigate the effects of hypoxia on the renal tissues and renal interstitial fibroblasts of yaks. We found that, at the tissue level, HIF-1α, PDK1, TGF-β1, Smad2, Smad3, and α-SMA were mainly distributed and expressed in tubular epithelial cells but were barely present in the renal mesenchymal fibroblasts of healthy cattle and yak kidneys. Anoptical density analysis showed that in healthy cattle kidneys, TGF-β1, Smad2, and Smad3 expression was significantly higher than in yak kidneys (p < 0.05), and HIF-1α and PDK1 expression was significantly lower than in yak kidneys (p < 0.05). The results at the protein and gene levels showed the same trend. At the cellular level, prolonged hypoxia significantly elevated PDK1 expression in the renal mesangial fibroblasts of cattle and yak kidneys compared with normoxia (p < 0.05) and was proportional to the degree of cellular fibrosis. However, PDK1 expression remained stable in yaks compared with renal interstitial fibroblast-like cells in cattle during the same hypoxic time period. At the same time, prolonged hypoxia also promoted changes in cellular phenotype, promoting the proliferation, activation, glucose consumption, lactate production, and anti-apoptosis in the both of cattle and yaks renal interstitial fibroblasts The differences in kidney structure and expression of PDK1 and HIF-1α in kidney tissue and renal interstitial fibroblasts induced by different oxygen concentrations suggest that there may be a regulatory relationship between yak kidney adaptation and hypoxic environment at high altitude. This provides strong support for the elucidation of the regulatory relationship between PDK1 and HIF-1α, as well as a new direction for the treatment or delay of hypoxic renal fibrosis; additionally, these findings provide a basis for further analysis of the molecular mechanism of hypoxia adaptation-related factors and the adaptation of yaks to plateau hypoxia.

Identification and validation of key extracellular proteins as the potential biomarkers in diabetic nephropathy

ObjectiveAccumulation of extracellular matrix (ECM) proteins in the glomerular mesangial region is a typical hallmark of diabetic nephropathy (DN). However, the molecular mechanism underlying ECM accumulation in the mesangium of DN patients remains unclear. The present study aims to establish a connection between extracellular proteins and DN with the goal of identifying potential biomarkers for this condition.MethodsDifferentially expressed genes (DEGs) between DN kidney tissue and healthy kidney tissue were analyzed using the public data GSE166239. Two gene lists encoding extracellular proteins were then utilized to identify extracellular protein-differentially expressed genes (EP-DEGs). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed on these EP-DEGs. A protein–protein interaction (PPI) network was established to identify key EP-DEGs. Furthermore, the diagnostic ability, immune cell infiltration, and clinical relevance of these EP-DEGs were investigated. Immunohistochemistry (IHC) staining of paraffin-embedded renal tissues was performed to validate the accuracy of the bioinformatic results.ResultsA total of 1204 DEGs were identified, from which 162 EP-DEGs were further characterized by overlapping with extracellular protein gene lists. From the PPI network analysis, five EP-DEGs (e.g., TNF, COL1A1, FN1, MMP9, and TGFB1) were identified as candidate biomarkers. TNF, COL1A1, and MMP9 had a high diagnostic accuracy for DN. Assessment of immune cell infiltration revealed that the expression of TNF was positively associated with resting dendritic cells (DCs) (r = 0.85, P < 0.001) and M1 macrophages (r = 0.62, P < 0.05), whereas negatively associated with regulatory T cells (r = − 0.62, P < 0.05). Nephroseq v5 analysis demonstrated a negative correlation between the estimated glomerular filtration rate (eGFR) and TNF expression (r = − 0.730, P = 0.025). Gene set enrichment analysis (GSEA) revealed significant enrichment of glycosaminoglycan (GAG) degradation in the high-TNF subgroup. IHC staining of renal tissues confirmed significantly elevated TNF-a expression and decreased hyaluronic acid (HA) levels in the DN group compared to controls (both P < 0.05), with a negative correlation observed between TNF-a and HA (r = − 0.691, P = 0.026).ConclusionOur findings suggest that TNF may play a pivotal role in the progress of DN by driving ECM accumulation, and this process might involve GAG degradation pathway activation.

The relation between dietary polysaccharide intake and urinary excretion of tetraglucoside.

The urinary metabolite tetraglucoside (Glc4) is a potential biomarker for hepatic glycogen storage diseases (GSDs). Glc4 is believed to reflect body glycogen content and/or turnover. However, dietary polysaccharide intake may influence Glc4 excretion, potentially limiting the utility of Glc4 as a monitoring biomarker in hepatic GSDs. We aimed to investigate the association of dietary polysaccharide intake with Glc4 excretion. Urinary Glc4 excretion (mmol/mmol creatinine and mmol/24 h) was analyzed using a validated LC-MS/MS method. Data was analyzed from 65 kidney transplant recipients and 58 healthy kidney donors in the TransplantLines cohort study. Spearman's correlation and multivariable linear regression analyses were performed. In the multivariable analysis, dry lean body mass (DLBM), dietary polysaccharide intake, transplantation status, age, sex, and glycated hemoglobin (HbA1c) served as independent variables. Daily variation was examined in 21 healthy individuals of urinary Glc4 excretion in 2-h collections over a 24-h period. Mixed generalized additive models were built to study the association of prior polysaccharide intake with Glc4 excretion. No (univariate) associations were found between polysaccharide intake and Glc4 excretion. However, a significant interaction between DLBM and polysaccharide on 24 h Glc4 excretion was observed in the multivariate analysis. Glc4 excretion throughout the day exhibited no relationship to prior polysaccharide intake. Our findings suggest an indirect effect of polysaccharide intake on Glc4 excretion, potentially due to changes in muscle glycogen content and/or turnover. We have found no evidence that dietary polysaccharides under normal intakes increase urinary Glc4 directly.

Skeletal muscle size and quality in healthy kidney donors, normal range and clinical associations

The gold standard to estimate muscle mass and quality is computed tomography (CT) scan. Lower mass and density (intramuscular fat infiltration) of skeletal muscles are markers of sarcopenia, associated with increased mortality risk, impaired physical function, and poorer prognosis across various populations and medical conditions. We aimed to describe standard reference values in healthy population, prospective kidney donors, and correlate clinical parameters to muscle mass and density. Included in the cohort 384 consecutive kidney donors. Mean age was 44.6 ± 11.5 (range 18.4–74.2), 46% were female and mean BMI was 25.6 ± 3.8 kg/m2. Our quantified reference values for psoas cross -sectional area (CSA) index at L3 level (males/females respectively) were 6.3 ± 1.8 and 4.8 ± 1.9 cm2 /m2, and density was 46.1 ± 5 and 41 ± 5 HU at that level. Older age (standardized beta coefficient − 0.12, p = 0.04), sex (− 0.32, p < 0.001) and BMI (0.17, p = 0.002) were significantly associated with CSA index of psoas at L3. Density, however, was associated with triglycerides level (− 0.21, p < 0.001), in addition to age (− 0.22, p < 0.0001), sex (− 0.27, p < 0.001) and BMI (− 0.1, p = 0.05). Our study validates the normative values of psoas muscle mass and density in healthy individuals and suggests correlations with clinical parameters. We demonstrate the significance of measuring not only the mass of the muscle, but also its density, as it has a valid association with metabolic parameters, including BMI and lipid level, even in healthy individuals and in the normal range of the tests.

Tremor after solid organ transplantation: Results from the TransplantLines Biobank and Cohort Study.

Tremor is a frequent complaint of solid organ transplant recipients. We report on the largest population investigated with clinical neurophysiological methods. Our aim is to objectively establish the tremor prevalence and syndrome in the largest population of solid organ transplant recipients. Tremor was measured in heart, kidney, liver, and lung recipients, using accelerometers during rest, postural, and weight-loaded conditions. The 95th percentile of healthy kidney donors' tremor amplitude was used as the cutoff to determine the presence of tremor in transplant recipients. Tremor frequency, frequency variability, and effect of loading were used to investigate enhanced physiological tremor as the likely tremor syndrome. Impact on activities of daily life was assessed, and correlations with tacrolimus blood levels were investigated. Tremor was present in 52% of 246 transplant recipients, typically in postural positions. Mean tremor frequency was 6.1 (±2.0) Hz; mean tremor variability was 2.6 (±1.8) Hz. A frequency decrease upon loading was found in 83% of patients with tremor. Sixty-five percent of patients met formal clinical neurophysiological criteria for enhanced physiological tremor. Tremor-related impairment was present in 55% and correlated with tremor amplitude (ρ = 0.23, p ≤ 0.001). In a binominal regression analysis, tacrolimus blood levels were independently associated with tremor prevalence (p = 0.009). More than half of solid organ transplant recipients experience a tremor that best fits the syndrome of enhanced physiological tremor. This is the first objective study on tremor that has established a better understanding of the neurophysiological mechanisms of tremor in a large population of solid organ transplant recipients.

Risk factors of renal function deterioration after radical nephroureterectomy for upper tract urothelial carcinoma.

To investigate the risk factors of renal function deterioration after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). A total of 153 patients with UTUC who underwent radical surgery at a high-volume center in China from January 2015 to December 2019 were included in this study. The renal function of all patients was evaluated during follow-up. Besides, these patients were grouped according to postoperative renal function. The risk factors of renal function deterioration included age, sex, body mass index (BMI), T stage, tumor location and size, lymph node invasion, lymph node dissection (LND), surgical margin, tumor histology, lymphovascular invasion (LVI), hypertension, diabetes, hematuria, blood transfusion, hydronephrosis on the affected side, urine specific gravity, creatinine, uric acid, and preoperative glomerular filtration rate (GFR) on the healthy and affected sides. The correlation between risk factors and inclusion indexes was analyzed using univariate and multivariate analyses. A total of 153 patients were enrolled in this study, and the follow-up continued for 14 (11, 24) months. Acute kidney injury (AKI) was diagnosed in 65 patients in the short-term follow-up after RNU, and renal function deterioration was diagnosed in 52 patients in the long-term follow-up after RNU. The univariate analysis of 65 patients with short-term AKI revealed that there were statistically significant differences in preoperative hydronephrosis, hypertension, urinary protein, tumor size, preoperative Hb, preoperative creatinine, blood transfusion, and preoperative GFR of the healthy kidney. The multivariate Logistic regression analysis results showed that preoperative creatinine, GFR of the healthy kidney, and blood transfusion were independent risk factors for AKI. Moreover, The multivariate Logistic regression analysis of 52 patients with long-term renal insufficiency after surgery indicated that there were statistically significant differences in preoperative hydronephrosis, tumor size, preoperative GFR of the healthy kidney, and postoperative AKI. For patients with UTUC, the preoperative creatinine level is high, blood transfusion was given during or after procedure and the GFR of the healthy kidney is low, it is easy to have AKI in the short term after operation. In addition, there was no hydronephrosis before operation, the tumor size was small, the GFR of the healthy kidney was low before operation, AKI occurred after operation, the renal function was easy to deteriorate for a long time after operation. The above risk factors may aggravate renal function deterioration of these patients after surgery, resulting in the loss of the opportunity to continue treatment.

Expression and Distribution of Different Protein Kinase A Isoforms in Healthy and Diseased Kidneys

Expression and Distribution of Different Protein Kinase A Isoforms in Healthy and Diseased Kidneys

Sex-Specific Differences in Branched Chain Amino Acid (BCAA) Catabolism and Mitochondrial Respiration in Healthy and Injured Kidneys

Sex-Specific Differences in Branched Chain Amino Acid (BCAA) Catabolism and Mitochondrial Respiration in Healthy and Injured Kidneys

Primary Cultures from Injured and Healthy Mouse Kidneys: A Comparative Transcriptomic Analysis

Primary Cultures from Injured and Healthy Mouse Kidneys: A Comparative Transcriptomic Analysis

Near-Infrared Microscopy Reveals Diabetic Nephropathy in ob/ob Mice

Diabetic nephropathy (DN) is a major cause of global kidney failure. While histological kidney biopsy is the gold standard for diagnosis, it primarily reveals tissue morphology. In contrast, near-infrared (NIR) microscopy offers a label-free method for detailed molecular characterization of kidney tissue. Hematoxylin and eosin-stained kidney tissue samples from 17 ob/ob mice with DN and 14 healthy mice were examined using Fourier transform-NIR microscopy. Four different spectra were obtained from both the mesangium and tubulus. NIR spectral analysis unveiled distinct differences in wavenumbers between DN-affected and healthy kidneys, notably in the carbohydrate and protein-associated region (5500-4200cm-1). In the mesangium, DN tissue samples exhibited higher median values at 4235cm-1, 4659cm-1, 4844cm-1, 4906cm-1, and 5222cm-1 compared to controls (P<0.05, P<0.01, P<0.05, P<0.05 and P<0.001, respectively). In tubular spectra, higher median values were found at 4258cm-1, 4659cm-1, 5222cm-1, and 5346cm-1 in the DN group (P<0.01, P<0.05, P<0.05 and P<0.01, respectively). These spectral differences strongly correlated with metabolic, histologic, and urinary parameters, providing valuable DN progression insights. The classification model achieved a visible clustering between the control and DN group for both the mesangial and tubular measurements. NIR microscopy demonstrated significant spectral differences between DN and healthy kidney tissues in mice, hinting at its potential for providing chemical insights, aiding in more accurate diagnoses, and offering a foundation for further clinical exploration and potential therapeutic advancements in DN.

Renal sinus adipose tissue: exploratory study of metabolic features and transcriptome compared with omental and subcutaneous adipose tissue.

The objective was to study metabolic characteristics and transcriptome of renal sinus adipose tissue (RSAT) located around renal arteries and veins. Adipose tissue biopsies from RSAT, omental (OAT), and subcutaneous (SAT) depots were obtained from healthy kidney donors (20 female, 20 male). Adipocyte glucose uptake rate and cell size were measured, and gene expression analyses using transcriptomics were performed. RSAT adipocytes were significantly smaller, with a higher basal glucose uptake rate, than adipocytes from SAT and OAT. Transcriptomic analyses revealed 29 differentially expressed genes between RSAT and OAT (RSAT: 23 lower, 6 higher) and 1214 differentially expressed genes between RSAT and SAT (RSAT: 859 lower, 355 higher). RSAT demonstrated molecular resemblance to OAT, both exhibiting lower metabolic gene expression and higher expression of immune-related pathways, including IL-17, TNFα, and NF-κB signaling than SAT. Weighted gene coexpression network analysis associated RSAT with immune response and nucleic acid transport processes. Despite its location near the renal hilum, RSAT closely resembled OAT and there was a lack of expression in the classical brown adipose tissue genes. Gene enrichment analyses suggest an inflammatory environment in RSAT compared with SAT and, to some extent, OAT. The findings suggest specific RSAT functions that could impact renal function and, possibly, the development of renal and cardiometabolic disorders.

Multiparametric MRI based assessment of kidney injury in a mouse model of ischemia reperfusion injury

Kidney diseases pose a global healthcare burden, with millions requiring renal replacement therapy. Ischemia/reperfusion injury (IRI) is a common pathology of acute kidney injury, causing hypoxia and subsequent inflammation-induced kidney damage. Accurate detection of acute kidney injury due to IRI is crucial for timely intervention. We used longitudinal, multi-parametric magnetic resonance imaging (MRI) employing arterial spin labelling (ASL), diffusion weighted imaging (DWI), and dynamic contrast enhanced (DCE)-MRI to assess IRI induced changes in both the injured and healthy contralateral kidney, in a unilateral IRI mouse model (n = 9). Multi-parametric MRI demonstrated significant differences in kidney volume (p = 0.001), blood flow (p = 0.002), filtration coefficient (p = 0.038), glomerular filtration rate (p = 0.005) and apparent diffusion coefficient (p = 0.048) between the injured kidney and contralateral kidney on day 1 post-IRI surgery. Identification of the injured kidney using principal component analysis including most of the imaging parameters demonstrated an area under the curve (AUC) of 0.97. These results point to the utility of multi-parametric MRI in early detection of IRI-induced kidney damage suggesting that the combination of various MRI parameters may be suitable for monitoring the extent of injury in this model.

Ex Vivo Simultaneous H215O Positron Emission Tomography and Magnetic Resonance Imaging of Porcine Kidneys-A Feasibility Study.

Pig kidneys (n = 7) were connected to a NMP circuit. PET/MRI was performed at two different pump flow levels: a blood-oxygenation-level-dependent (BOLD) MRI sequence performed simultaneously with a H215O PET sequence for determination of RBP. RBP was measured using H215O PET in all kidneys (flow 1: 0.42-0.76 mL/min/g, flow 2: 0.7-1.6 mL/min/g). We found a linear correlation between changes in delivered blood flow from the perfusion pump and changes in the measured RBP using PET imaging (r2 = 0.87). Our study demonstrated the feasibility of combined H215O PET/MRI during NMP of isolated porcine kidneys with tissue oxygenation being stable over time. The introduction of H215O PET/MRI in nephrological research could be highly relevant for future pre-transplant kidney evaluation and as a tool for studying renal physiology in healthy and diseased kidneys.

An in vitro study for reducing the cytotoxicity and dose dumping risk of remdesivir via entrapment in nanostructured lipid carriers

The aim of this study was to synthesize and evaluate nanostructured lipid carriers (NLCs) loaded with Remdesivir (RDV) to control its side effects in COVID-19 patients. Due to the low solubility and short half-life of RDV in the blood, an injectable formulation was prepared using sulphobutylether-beta-cyclodextrin. However, it can accumulate in the kidney and cause renal impairment. NLCs improve the parenteral delivery of hydrophobic drugs such as RDV by increasing drug solubility and bioavailability. For the synthesis of RDV-NLCs, the aqueous phase containing Tween 80 was injected into the lipid phase under rapid stirring and was sonicated. The experimental conditions were optimized using Box-Behnken design and Design Expert software. The optimum formulation contained a total lipid of 2.13%, a total surfactant of 1%, and a hot bath time of 71 min. The optimum formulation showed particle size, polydispersity index, zeta potential, and entrapment efficiency values of 151.0 ± 1.7 nm (from 149.1 to 152.1), 0.4 ± 0.1 (from 0.3 to 0.5), −43.8 ± 1.2 mV (from −42.4 to −44.7), and 81.34 ± 1.57% (from 79.52 to 82.33%), respectively. RDV-NLCs showed acceptable stability for 30 days at 25 ℃ and were compatible with commonly used intravenous infusion fluids for 48 h. FE-SEM images of RDV-NLC showed spherical particles with a mean diameter of 207 nm. The NLC-RDV formulation showed a sustained release of RDV with a low risk of dose-dumping, minimizing potential side effects. In addition, RDV in the form of RDV-NLC causes less cytotoxicity to healthy normal kidney cells, which is expected to reduce renal impairment in COVID-19 patients.

Calciprotein particle counts associate with vascular remodelling in chronic kidney disease.

Calciprotein particles (CPPs) are circulating calcium and phosphate nanoparticles associated with development of vascular calcification (VC) in chronic kidney disease (CKD). Although recent studies have been focusing on associations of CPPs with presence of VC in CKD, insights in the underlying processes and mechanisms by which CPPs might aggravate VC and vascular dysfunction in vivo are currently lacking. Here, we assessed overall burden of abdominal VC in healthy kidney donors and CKD patients, and subsequently performed transcriptome profiling in vascular tissue obtained from these subjects, linking outcome to CPP counts and calcification propensity. Calcification scores were quantified in renal arteries, iliac arteries and abdominal aorta, using computed tomography (CT) scans of kidney donors and CKD patients. Vascular tissue was collected from kidney donors (renal artery) and CKD patients (iliac artery), after which bulk RNA sequencing and gene set enrichment analysis (GSEA) was performed on a subset of patients. Calcification propensity (crystallization time, T50) was measured using nephelometry, and CPP counts with microparticle flow cytometric analysis. Increased calcification scores (based on CT) were found in CKD patients compared to kidney donors. Transcriptome profiling revealed enrichment for processes related to endothelial activation, inflammation, extracellular matrix (ECM) remodelling and ossification in CKD vascular biopsies compared to kidney donors. Calcification propensity was increased in CKD, as well as CPP counts, of which the latter significantly associated with markers of vascular remodelling. Our findings reveal that CKD is characterized by systemic VC with increased calcification propensity and CPP counts. Transcriptome profiling showed altered vascular gene expression with enrichment for endothelial activation, inflammation, ECM remodelling and ossification. Moreover, we demonstrate for the first time that vascular remodelling processes are associated with increased circulating CPP counts. Interventions targeting CPPs are promising avenues for alleviating vascular remodelling and VC in CKD.

Histopathological-Based Analysis of Human Kidney Spatial Transcriptomics Data: Toward Precision Pathology

The application of spatial transcriptomics (ST) technologies is booming and has already yielded important insights across many different tissues and disease models. In nephrology, ST technologies have helped to decipher the cellular and molecular mechanisms at work in kidney diseases and have allowed the recent creation of spatially anchored human kidney atlases in healthy and diseased kidney tissues. During ST data analysis, the obtained computationally annotated clusters are often superimposed on a histologic image without their initial identification being based on the morphologic and spatial analyses of the tissues and lesions. In this study, we conduct a histopathologic-based analysis of ST data on a human kidney sample corresponding as closely as possible to the reality of the interpretation of a kidney biopsy sample in a health care or research context. This study shows the feasibility of a morphology-based approach to interpreting ST data, helping to improve our understanding of the lesion phenomena at work in chronic kidney disease at both the cellular and the molecular level. Finally, we show that our newly identified pathology-based clusters can be accurately projected onto other slides from nephrectomy or needle biopsy samples. They thus serve as a reference for analyzing other kidney tissues, paving the way for the future of molecular microscopy and precision pathology.

Single-cell multi-omic and spatial profiling of human kidneys implicates the fibrotic microenvironment in kidney disease progression.

Kidneys are intricate three-dimensional structures in the body, yet the spatial and molecular principles of kidney health and disease remain inadequately understood. We generated high-quality datasets for 81 samples, including single-cell, single-nuclear, spot-level (Visium) and single-cell resolution (CosMx) spatial-RNA expression and single-nuclear open chromatin, capturing cells from healthy, diabetic and hypertensive diseased human kidneys. Combining these data, we identify cell types and map them to their locations within the tissue. Unbiased deconvolution of the spatial data identifies the following four distinct microenvironments: glomerular, immune, tubule and fibrotic. We describe the complex organization of microenvironments in health and disease and find that the fibrotic microenvironment is able to molecularly classify human kidneys and offers an improved prognosis compared to traditional histopathology. We provide a comprehensive spatially resolved molecular roadmap of the human kidney and the fibrotic process, demonstrating the clinical utility of spatial transcriptomics.

AI-based segmentation of renal enhanced CT images for quantitative evaluate of chronic kidney disease

To quantitatively evaluate chronic kidney disease (CKD), a deep convolutional neural network-based segmentation model was applied to renal enhanced computed tomography (CT) images. A retrospective analysis was conducted on a cohort of 100 individuals diagnosed with CKD and 90 individuals with healthy kidneys, who underwent contrast-enhanced CT scans of the kidneys or abdomen. Demographic and clinical data were collected from all participants. The study consisted of two distinct stages: firstly, the development and validation of a three-dimensional (3D) nnU-Net model for segmenting the arterial phase of renal enhanced CT scans; secondly, the utilization of the 3D nnU-Net model for quantitative evaluation of CKD. The 3D nnU-Net model achieved a mean Dice Similarity Coefficient (DSC) of 93.53% for renal parenchyma and 81.48% for renal cortex. Statistically significant differences were observed among different stages of renal function for renal parenchyma volume (VRP), renal cortex volume (VRC), renal medulla volume (VRM), the CT values of renal parenchyma (HuRP), the CT values of renal cortex (HuRC), and the CT values of renal medulla (HuRM) (F = 93.476, 144.918, 9.637, 170.533, 216.616, and 94.283; p < 0.001). Pearson correlation analysis revealed significant positive associations between glomerular filtration rate (eGFR) and VRP, VRC, VRM, HuRP, HuRC, and HuRM (r = 0.749, 0.818, 0.321, 0.819, 0.820, and 0.747, respectively, all p < 0.001). Similarly, a negative correlation was observed between serum creatinine (Scr) levels and VRP, VRC, VRM, HuRP, HuRC, and HuRM (r = − 0.759, − 0.777, − 0.420, − 0.762, − 0.771, and − 0.726, respectively, all p < 0.001). For predicting CKD in males, VRP had an area under the curve (AUC) of 0.726, p < 0.001; VRC, AUC 0.765, p < 0.001; VRM, AUC 0.578, p = 0.018; HuRP, AUC 0.912, p < 0.001; HuRC, AUC 0.952, p < 0.001; and HuRM, AUC 0.772, p < 0.001 in males. In females, VRP had an AUC of 0.813, p < 0.001; VRC, AUC 0.851, p < 0.001; VRM, AUC 0.623, p = 0.060; HuRP, AUC 0.904, p < 0.001; HuRC, AUC 0.934, p < 0.001; and HuRM, AUC 0.840, p < 0.001. The optimal cutoff values for predicting CKD in HuRP are 99.9 Hu for males and 98.4 Hu for females, while in HuRC are 120.1 Hu for males and 111.8 Hu for females. The kidney was effectively segmented by our AI-based 3D nnU-Net model for enhanced renal CT images. In terms of mild kidney injury, the CT values exhibited higher sensitivity compared to kidney volume. The correlation analysis revealed a stronger association between VRC, HuRP, and HuRC with renal function, while the association between VRP and HuRM was weaker, and the association between VRM was the weakest. Particularly, HuRP and HuRC demonstrated significant potential in predicting renal function. For diagnosing CKD, it is recommended to set the threshold values as follows: HuRP < 99.9 Hu and HuRC < 120.1 Hu in males, and HuRP < 98.4 Hu and HuRC < 111.8 Hu in females.