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1.
BMC Urol ; 24(1): 197, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39252077

ABSTRACT

BACKGROUND: Open partial nephrectomy (OPN) has previously been considered the gold standard procedure for treatment of T1 localized renal tumors. After introduction of robot assisted partial nephrectomy (RAPN) as an alternative method to OPN, OPN was gradually abandoned at our department. The aim of the study was to retrospectively compare the results of patients treated with either OPN or RAPN for suspected renal carcinoma. METHODS: Patients who underwent either open or robotic assisted partial nephrectomy between January 1st 2010 and December 31st 2020 were retrospectively included in the study. Each tumor subjected to surgery was scored preoperatively by the RENAL nephrometry score. Complications within 30 days were assessed according to the Clavien-Dindo classification system. RESULTS: A total of 197 patients who underwent partial nephrectomy were identified; 75 were subjected to OPN and 122 were treated with RAPN. There were no significant differences between the groups with respect to age (OPN: 63 years ± 11, RAPN: 62 years ± 10), gender (OPN: 71/29%, RAPN: 67/33%), body mass index (OPN: 28 ± 5, RAPN: 28 ± 5), ASA score (OPN: 2.4 ± 0.6, RAPN: 2.2 ± 0.5), or nephrometry score (OPN: 6.6 ± 1.7, RAPN: 6.9 ± 1.7, p = 0.2). The operative time was significantly shorter in the OPN group (81 min) compared to the RAPN group (144.5 min, p < 0.001). Mean perioperative blood loss was 227 ± 162 ml in the OPN group compared to 189 ± 152 ml in the RAPN group (p = 0.1). Mean length of stay was shorter in the RAPN group (3 days) compared to the OPN group (6, days, p < 0.001). Positive surgical margin rate was significantly higher in the OPN group (21.6%) compared to the RAPN group (4.2%, p < 0.001). There were no differences in the number of Clavien-Dindo graded complications between the groups (p = 0.6). CONCLUSIONS: The introduction of RAPN at our department resulted in shorter length of stay and fewer positive surgical margins, without increasing complications.


Subject(s)
Kidney Neoplasms , Nephrectomy , Robotic Surgical Procedures , Humans , Nephrectomy/methods , Robotic Surgical Procedures/methods , Middle Aged , Female , Male , Retrospective Studies , Kidney Neoplasms/surgery , Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Carcinoma, Renal Cell/surgery , Treatment Outcome
2.
Development ; 151(18)2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39250420

ABSTRACT

In vivo and in vitro studies argue that concentration-dependent Wnt signaling regulates mammalian nephron progenitor cell (NPC) programs. Canonical Wnt signaling is regulated through the stabilization of ß-catenin, a transcriptional co-activator when complexed with Lef/Tcf DNA-binding partners. Using the GSK3ß inhibitor CHIR99021 (CHIR) to block GSK3ß-dependent destruction of ß-catenin, we examined dose-dependent responses to ß-catenin in mouse NPCs, using mRNA transduction to modify gene expression. Low CHIR-dependent proliferation of NPCs was blocked on ß-catenin removal, with evidence of NPCs arresting at the G2-M transition. While NPC identity was maintained following ß-catenin removal, mRNA-seq identified low CHIR and ß-catenin dependent genes. High CHIR activated nephrogenesis. Nephrogenic programming was dependent on Lef/Tcf factors and ß-catenin transcriptional activity. Molecular and cellular features of early nephrogenesis were driven in the absence of CHIR by a mutated stabilized form of ß-catenin. Chromatin association studies indicate low and high CHIR response genes are likely direct targets of canonical Wnt transcriptional complexes. Together, these studies provide evidence for concentration-dependent Wnt signaling in the regulation of NPCs and provide new insight into Wnt targets initiating mammalian nephrogenesis.


Subject(s)
Nephrons , Stem Cells , Wnt Signaling Pathway , beta Catenin , Animals , Nephrons/metabolism , Nephrons/cytology , beta Catenin/metabolism , Mice , Stem Cells/metabolism , Stem Cells/cytology , Pyrimidines/pharmacology , Pyridines/pharmacology , Gene Expression Regulation, Developmental , Cell Proliferation , Glycogen Synthase Kinase 3 beta/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Organogenesis/genetics , Transcription, Genetic
3.
ACS Appl Bio Mater ; 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39241192

ABSTRACT

In this work, we develop recombinant human cationic ferritin (rHCF) as a contrast agent to detect glomeruli in the kidney using positron emission tomography (PET). We first expressed recombinant human ferritin (rHF) in E. coli and then functionalized and radiolabeled it with Copper-64 (64Cu) to form 64Cu-rHCF. Intravenously injected 64Cu-rHCF bound to kidney glomeruli and was detected by PET. A subchronic toxicity study after an intravenous injection of rHCF revealed no significant toxicity. The development of rHCF is an important step toward the potential clinical translation of CF to detect the nephron number in humans.

4.
Development ; 151(18)2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39344436

ABSTRACT

In the developing mammalian kidney, nephron formation is initiated by a subset of nephron progenitor cells (NPCs). Wnt input activates a ß-catenin (Ctnnb1)-driven, transcriptional nephrogenic program and the mesenchymal to epithelial transition (MET) of NPCs. Using an in vitro mouse NPC culture model, we observed that activation of the Wnt pathway results in the aggregation of induced NPCs, which is an initiating step in the MET program. Genetic removal showed aggregation was dependent on ß-catenin. Modulating extracellular Ca2+ levels showed cell-cell contacts were Ca2+ dependent, suggesting a role for cadherin (Cdh)-directed cell adhesion. Molecular analysis identified Cdh2, Cdh4 and Cdh11 in NPCs, and the ß-catenin directed upregulation of Cdh3 and Cdh4 accompanying the MET of induced NPCs. Mutational analysis of ß-catenin supported a role for a Lef/Tcf-ß-catenin-mediated transcriptional response in the cell aggregation process. Genetic removal of all four cadherins, and independent removal of α-catenin or of ß-catenin-α-catenin interactions, abolished aggregation, but not the inductive response to Wnt pathway activation. These findings, and data in an accompanying article highlight the role of ß-catenin in linking transcriptional programs to the morphogenesis of NPCs in mammalian nephrogenesis.


Subject(s)
Cadherins , Cell Aggregation , Epithelial-Mesenchymal Transition , Nephrons , Stem Cells , Wnt Signaling Pathway , beta Catenin , Animals , Cadherins/metabolism , Cadherins/genetics , Nephrons/metabolism , Nephrons/cytology , Stem Cells/metabolism , Stem Cells/cytology , beta Catenin/metabolism , beta Catenin/genetics , Mice , Epithelial-Mesenchymal Transition/genetics , Cell Adhesion , Wnt Proteins/metabolism , Wnt Proteins/genetics , Cells, Cultured
5.
Environ Pollut ; 360: 124645, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39095001

ABSTRACT

Microplastics (MPs) have emerged as a pervasive environmental pollutant of global concern. Their detection within the human placenta and fetal organs has prompted apprehension regarding the potential hazards of MPs during early organogenesis. The kidney, a vital multifunctional organ, is susceptible to damage from MPs in adulthood. However, the precise adverse effects of MP exposure on human nephrogenesis remain ambiguous due to the absence of a suitable model. Here, we explore the potential impact of MPs on early kidney development utilizing human kidney organoids in vitro. Human kidney organoids were subjected to polystyrene-MPs (PS-MPs, 1 µm) during the nephron progenitor cell (NPC) stage, a critical phase in early kidney development and patterning. We delineate the effects of PS-MPs on various stages of nephrogenesis, including NPC, renal vesicle, and comma-shaped body, through sequential examination of kidney organoids. PS-MPs were observed to adhere to the surface of cells during the NPC stage and accumulate within glomerulus-like structures within kidney organoids. Moreover, both short- and long-term exposure to PS-MPs resulted in diminished organoid size and aberrant nephron structure. PS-MP exposure heightened reactive oxygen species (ROS) production, leading to NPC apoptosis during early kidney development. Increased apoptosis, diminished cell viability, and NPC reduction likely contribute to the observed organoid size reduction under PS-MP treatment. Transcriptomic analysis at both NPC and endpoint stages revealed downregulation of Notch signaling, resulting in compromised proximal and distal tubular structures, thereby disrupting normal nephron patterning following PS-MP exposure. Our findings highlight the significant disruptive impact of PS-MPs on human kidney development, offering new insights into the mechanisms underlying PS-MP-induced nephron toxicity.


Subject(s)
Induced Pluripotent Stem Cells , Kidney , Microplastics , Organoids , Humans , Organoids/drug effects , Kidney/drug effects , Induced Pluripotent Stem Cells/drug effects , Microplastics/toxicity , Organogenesis/drug effects , Reactive Oxygen Species/metabolism , Apoptosis/drug effects , Nephrons/drug effects , Environmental Pollutants/toxicity
6.
J Robot Surg ; 18(1): 313, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39112829

ABSTRACT

Exploration of surgical precision in robotic procedures is extensive, yet lacks a unified framework for comparability. This study examines tissue handling precision by comparing the per-minute blood loss rate between robotic and open partial nephrectomy. A literature search from August 2022 to June 2024 identified 43 relevant studies providing data on estimated blood loss and procedure duration. The expected values and standard errors of these variables were used to compute the per-minute blood loss rate (Q). Meta-analytical methods estimated pooled and subgroup-level mean differences, favoring robotic surgery (MDQ = - 1.043 ml/min, CI95% = [- 1.338; - 0.747]). Subgroup analyses by publication year, patient matching, referral center count, and ROBINS-I status consistently supported this advantage. Sensitivity analyses confirmed the above benefit in studies with increased accuracy in reported results (MDQ = - 0.957 ml/min, CI95% = [- 1.269; - 0.646]), low risk of bias involving matched comparisons (MDQ = - 0.563 ml/min, CI95% = [- 0.716; - 0.410]), large sample sizes and increased statistical power (MDQ = - 0.780 ml/min, CI95% = [- 1.134; - 0.425]), and multicenter analyses with patient matching (MDQ = - 0.481 ml/min, CI95% = [- 0.698; - 0.263]). The subsequent analysis of correlation between the original variables suggested a slight reduction in the robotic advantage when the latter were proportionally related. Multilevel meta-regression at both temporal and qualitative scales consistently indicated a comparative benefit of the robotic approach. Potentially, lower per-minute blood loss compared to open surgery suggests that robotic partial nephrectomy demonstrates enhanced precision in tissue handling.


Subject(s)
Blood Loss, Surgical , Nephrectomy , Robotic Surgical Procedures , Robotic Surgical Procedures/methods , Nephrectomy/methods , Humans , Blood Loss, Surgical/statistics & numerical data , Operative Time
7.
Diagnostics (Basel) ; 14(15)2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39125455

ABSTRACT

The aim of our study is to evaluate the effectiveness and safety of a sutureless off-clamp robot-assisted partial nephrectomy (sl-oc RAPN), particularly its impact on renal function. A multicenter study was conducted from April 2021 to June 2022. Patients diagnosed with a renal mass of >2 cm and a PADUA score of ≤6 consecutively underwent an sl-oc RAPN procedure. Tumor features, patients characteristics, and intraoperative outcomes were assessed. An evaluation of renal function was performed preoperatively, and again at 1 and 3 months after surgery by measuring the creatinine and blood urea nitrogen levels. The renal function of the two separate kidneys was assessed by a sequential renal scintigraphy performed before and at least 30 days after surgery. A total of 21 patients underwent an sl-oc RAPN. The median age was 64 years (IQR 52/70), the median tumor diameter was 40 mm (IQR 29/45), and the median PADUA score was 4 (3.5/5). The intraoperative outcomes included operative time (OT), 90 (IQR 74/100) min; estimated blood loss (EBL), 150 (IQR 50/300) mL; and perioperative complications, CD > 3 1(5%); only two patients presented positive surgical margins in their final histology (2/21, 10%). Compared to the preoperative value, a decrease in renal function was highlighted with a statistically significant median decrease of 10 mL/min (p < 0.01). The renal scintigraphy showed an overall decrease in renal function compared to the preoperative value, with a range in the operated kidney that varied from 0 to 15 mL/s and from 0% to 40%, with a median value of 4 mL/s and 12%. sl-oc RAPN is a safe procedure, with a minimal impact on kidney function alteration. This technique has proven effective in preserving renal function and maintaining optimal oncological outcomes with limited complications.

9.
Front Med (Lausanne) ; 11: 1461879, 2024.
Article in English | MEDLINE | ID: mdl-39211339

ABSTRACT

Immunoglobulin A nephropathy (IgAN) often has a poor outcome, with many patients reaching kidney failure within their lifetime. Therefore, the primary goal for the treatment of IgAN should be to reduce nephron loss from the moment of diagnosis. To achieve this, IgAN must be recognized and treated as both a chronic kidney disease and an immunological disease. Agents that have received US Food and Drug Administration and European Medicines Agency approval for the treatment of IgAN include modified-release/targeted-release formulation budesonide (Nefecon) and sparsentan, a selective dual endothelin-A and angiotensin II receptor type 1 antagonist. Other agents, including selective endothelin receptor antagonists, selective or combined APRIL and BAFF antagonists, and a vast array of complement inhibitors are being investigated for the treatment of IgAN. Furthermore, treatment combinations are also being studied, including sodium-glucose cotransporter-2 inhibitors with endothelin receptor antagonists. Due to the complexity of IgAN, combination treatment, rather than a single-agent approach, may provide maximum benefit. With the number of treatments for IgAN likely to increase, combinations allowing safe and effective treatment to halt progression to kidney failure seem within grasp. While trials evaluating combinations are ongoing, more are needed to pave the way for a comprehensive IgAN treatment strategy. Furthermore, an approach to IgAN treatment in which agents are combined early to achieve rapid induction of remission and prevent unnecessary and irreversible nephron loss is required. Following remission, treatments may be adjusted and stripped back as necessary in the maintenance phase with close monitoring. This review discusses the current status of IgAN treatment and explores future strategies to improve outcomes for patients with IgAN.

10.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(4): 661-666, 2024 Aug 18.
Article in Chinese | MEDLINE | ID: mdl-39041562

ABSTRACT

OBJECTIVE: To analyze the clinicopathological characteristics and prognosis of patients with multilocular cystic renal neoplasm of low malignant potential and compare the clinicopathological characteristics of patients with multilocular cystic renal neoplasm of low malignant potential who underwent different surgical methods. METHODS: Clinicopathological data and prognosis of patients admitted to Peking University Third Hospital from January 2010 to September 2023 were collected. Patients who underwent radical nephrectomy or nephron-sparing surgery and were pathologically diagnosed with multilocular cystic renal neoplasm of low malignant potential were identified. Based on the surgical methods, the patients were divided into radical nephrectomy group and nephron-sparing surgery group. The clinicopathological characteristics of the two groups were compared. RESULTS: A total of 35 patients were enrolled in this study. The median age at diagnosis was 53.0 (39.0-62.0) years. Among the 35 patients, 23 were males (65.7%) and 12 were females (34.3%). Nine patients underwent radical nephrectomy (25.7%), while 26 patients underwent nephron-sparing surgery (74.3%). The clinical T-stage of 35 patients did not exceed T2a stage. The median operation time was 145.0 min, and the median estimated intraoperative blood loss was 20.0 mL. The median postoperative hospitalization days was 6.0 d. The postoperative pathological results did not indicate renal sinus invasion, sarcomatous change, adrenal invasion or lymph node invasion. Based on the surgical methods, the patients were divided into a radical nephrectomy group and a nephron-sparing surgery group. There was no significant difference in clinicopathological charac-teristics between the two groups. Except for one patient who was lost to the follow-up, all the other patients were followed up for 8-111 months, with a median follow-up time of 70.5 months. Only one patient died from non-cancer-specific reasons, other patients had no tumor metastasis or recurrence. CONCLUSION: Patients with multilocular cystic renal neoplasm of low malignant potential have a good prognosis. There is no significant difference in clinicopathological characteristics of patients between nephron-sparing surgery group and radical nephrectomy group for multilocular cystic renal neoplasm of low malignant potential.


Subject(s)
Kidney Neoplasms , Nephrectomy , Humans , Male , Female , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Middle Aged , Adult , Prognosis , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/surgery , Nephrons/pathology , Operative Time , Retrospective Studies
12.
Anat Rec (Hoboken) ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39016436

ABSTRACT

The article presents a study of the mesonephros ultrastructure of Baikal omul Coregonus migratorius, Baikal whitefish Coregonus baicalensis, and a cross between Baikal whitefish and humpback whitefish (C. baicalensis × Coregonus pidschian). The mesonephros ultrastructure was studied using electron microscopy methods. The results of the study show that the number of mature granulocytes is a systematic feature and does not depend on the ecology of fish. The quantitative characteristics of blood cells and the ultrastructural features of leukocytes in the mesonephros are associated with the functioning of the nonspecific defence system in fish. Morphological diversity of epithelial cells in nephron tubules is the ancestral characteristic of the modern omul population, associated with geological and climatic events in the history of Lake Baikal. The development of haematopoietic tissue in the mesonephros, the ultrafine structure of ion-transporting interstitial cells, as well as some ultrastructural features found in the nephron, reflect the adaptive capabilities of the species to live in the ultra-deep Lake Baikal.

13.
Cell Syst ; 15(7): 649-661.e9, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38981488

ABSTRACT

Organoids derived from human stem cells are a promising approach for disease modeling, regenerative medicine, and fundamental research. However, organoid variability and limited control over morphological outcomes remain as challenges. One open question is the extent to which engineering control over culture conditions can guide organoids to specific compositions. Here, we extend a DNA "velcro" cell patterning approach, precisely controlling the number and ratio of human induced pluripotent stem cell-derived progenitors contributing to nephron progenitor (NP) organoids and mosaic NP/ureteric bud (UB) tip cell organoids within arrays of microwells. We demonstrate long-term control over organoid size and morphology, decoupled from geometric constraints. We then show emergent trends in organoid tissue proportions that depend on initial progenitor cell composition. These include higher nephron and stromal cell representation in mosaic NP/UB organoids vs. NP-only organoids and a "goldilocks" initial cell ratio in mosaic organoids that optimizes the formation of proximal tubule structures.


Subject(s)
Organoids , Organoids/cytology , Organoids/metabolism , Humans , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Nephrons/cytology , Cell Differentiation/physiology , Stem Cells/cytology
14.
Pediatr Blood Cancer ; 71(9): e31172, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38956810

ABSTRACT

INTRODUCTION: Children with WAGR (Wilms tumor, aniridia, genitourinary anomalies, and range of development delays) syndrome are predisposed to Wilms tumor (WT) and intrinsic kidney disease. Using the comprehensive International WAGR Syndrome Association (IWSA) survey of children with WAGR syndrome, we analyzed tumor characteristics, treatment and congenital risk factors, and kidney function in children with WAGR and WT. METHODS: Descriptive statistics were utilized including demographics, treatment strategies, and patient outcomes. Comparisons were made between patients with WAGR and WT to those with WAGR alone. A multivariable logistic regression was completed for risk of developing WT and to identify predictors of chronic kidney disease (CKD). RESULTS: Sixty-four of 145 children with WAGR developed WT (44.1%). Three relapsed and one died. CKD developed in five children with WAGR without WT (5/81, 6.2%), and in 34 with WAGR and WT (34/64, 28.3%). Children with WAGR and WT were younger (p = .017), and had a greater association with CKD than WAGR children without WT (p < .0001). Two children with WT required hemodialysis, and one underwent kidney transplantation. By univariate analysis, CKD at any stage was associated with complete nephrectomy for the WT surgery (p < .0001), chemotherapy duration greater than 12 months, and three-drug therapy. Upon multivariate analysis, prior nephrectomy was the only significant variable (p = .0002). CONCLUSIONS: Epidemiological analysis of children with WAGR demonstrated favorable oncologic outcomes, but high rate of early CKD in those who developed WT. Further study of the use of nephron-sparing surgery in children with WAGR and strategies to delay or treat early CKD are needed.


Subject(s)
Kidney Neoplasms , Renal Insufficiency, Chronic , WAGR Syndrome , Wilms Tumor , Humans , Wilms Tumor/surgery , Wilms Tumor/pathology , Wilms Tumor/complications , Male , Female , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/pathology , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , WAGR Syndrome/pathology , Child, Preschool , Child , Infant , Adolescent , Nephrectomy , Risk Factors , Prognosis , Follow-Up Studies
15.
BMC Urol ; 24(1): 141, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977987

ABSTRACT

BACKGROUND: The literature on nephron-sparing surgery (NSS) in children with bilateral Wilms' tumors (BWT) involving the collection system is mostly comprised of case reports. The present study aimed to summarize the clinical characteristics, treatments, and prognosis of children with BWT involving the collecting system admitted to our pediatric surgery center compared with those whose tumors did not involve the collecting system. A secondary aim was to discuss how to preserve more kidney parenchyma and prevent long-term renal failure under the premise of preventing tumor recurrence. METHODS: Patients with BWT admitted to our pediatric surgery center between January 2008 and June 2022 were reviewed. All included patients were grouped according to the relationship between the tumor and collecting system according to the intraoperative findings. Group I included children with tumor infiltrating the collecting system, group II included children with tumor growing into the collecting system, and group III included children whose tumor did not involve the collecting system. The clinical features, treatments and prognosis of the patients were analyzed. RESULTS: Seventy patients were enrolled, including 20 patients with 25 sides of tumors infiltrating the collecting system in group I,10 patients with 13 sides of tumors growing into the collecting system in group II, and 40 patients in group III. There was no significant difference in patients age and gender between group I and group II. In total, 20 patients in group I and 9 patients in group II had partial response (PR) after neoadjuvant chemotherapy. In group I, 22 of 25 sides of tumors underwent NSS; in group II, 11 of 13 sides of tumors underwent NSS. During an average follow-up of 47 months, in group I, 6/20 patients relapsed and 2/20 patients died; in group II, 3/10 patients relapsed and 1/10 patient died. There was no significant difference in 4-year overall survival (OS) rate among groups I, II and III (86.36% vs. 85.71%vs. 91.40%, P = 0.902). CONCLUSIONS: To preserve renal parenchyma, NSS is feasible for children with BWT involving the collecting system. There was no significant difference in postoperative long-term OS between patients with BWT involving the collecting system and not involving the collecting system.


Subject(s)
Kidney Neoplasms , Wilms Tumor , Humans , Wilms Tumor/pathology , Wilms Tumor/surgery , Male , Kidney Neoplasms/pathology , Kidney Neoplasms/surgery , Female , Prognosis , Child, Preschool , Retrospective Studies , Infant , Child , Kidney Tubules, Collecting/pathology , Neoplasm Invasiveness , Organ Sparing Treatments/methods
16.
bioRxiv ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39026757

ABSTRACT

The spatial organization of biophysical and biochemical cues in the extracellular matrix (ECM) in concert with reciprocal cell-cell signaling is vital to tissue patterning during development. However, elucidating the role an individual microenvironmental factor plays using existing in vivo models is difficult due to their inherent complexity. In this work, we have developed a microphysiological system to spatially pattern the biochemical, biophysical, and stromal cell composition of the ECM along an epithelialized 3D microchannel. This technique is adaptable to multiple hydrogel compositions and scalable to the number of zones patterned. We confirmed that the methodology to create distinct zones resulted in a continuous, annealed hydrogel with regional interfaces that did not hinder the transport of soluble molecules. Further, the interface between hydrogel regions did not disrupt microchannel structure, epithelial lumen formation, or media perfusion through an acellular or cellularized microchannel. Finally, we demonstrated spatially patterned tubulogenic sprouting of a continuous epithelial tube into the surrounding hydrogel confined to local regions with stromal cell populations, illustrating spatial control of cell-cell interactions and signaling gradients. This easy-to-use system has wide utility for modeling three-dimensional epithelial and endothelial tissue interactions with heterogeneous hydrogel compositions and/or stromal cell populations to investigate their mechanistic roles during development, homeostasis, or disease.

17.
Kidney Int ; 106(3): 496-507, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39046396

ABSTRACT

Glomerulomegaly and focal segmental glomerulosclerosis are histopathological hallmarks of obesity-related glomerulopathy (ORG). Podocyte injury and subsequent depletion are regarded as key processes in the development of these glomerular lesions in patients with ORG, but their impact on long-term kidney outcome is undetermined. Here, we correlated clinicopathological findings and podocyte depletion retrospectively in patients with ORG. Relative (podocyte density) and absolute (podocyte number per glomerulus) measures of podocyte depletion were estimated using model-based stereology in 46 patients with ORG. The combined endpoint of kidney outcomes was defined as a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure. Patients with lower podocyte density were predominantly male and had larger body surface area, greater proteinuria, fewer non-sclerotic glomeruli, larger glomeruli and higher single-nephron eGFR. During a median follow-up of 4.1 years, 18 (39%) patients reached endpoint. Kidney survival in patients with lower podocyte density was significantly worse than in patients with higher podocyte density. However, there was no difference in kidney survival between patient groups based on podocyte number per glomerulus. Cox hazard analysis showed that podocyte density, but not podocyte number per glomerulus, was associated with the kidney outcomes after adjustment for clinicopathological confounders. Thus, our study demonstrates that a relative depletion of podocytes better predicts long-term kidney outcomes than does absolute depletion of podocytes. Hence, the findings implicate mismatch between glomerular enlargement and podocyte number as a crucial determinant of disease progression in ORG.


Subject(s)
Glomerular Filtration Rate , Obesity , Podocytes , Humans , Podocytes/pathology , Male , Female , Retrospective Studies , Middle Aged , Obesity/complications , Adult , Glomerulosclerosis, Focal Segmental/pathology , Glomerulosclerosis, Focal Segmental/etiology , Glomerulosclerosis, Focal Segmental/complications , Kidney Glomerulus/pathology , Disease Progression , Proteinuria/etiology , Proteinuria/pathology , Cell Count , Time Factors , Prognosis , Proportional Hazards Models
18.
Biochem Biophys Rep ; 39: 101736, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38910872

ABSTRACT

The three-dimensional (3D) kidney organoid is a breakthrough model for recapitulating renal morphology and function in vitro, which is grown from stem cells and resembles mammalian kidney organogenesis. Currently, protocols for cultivating this model from induced pluripotent stem cells (iPSCs) and patient-derived adult stem cells (ASCs) have been widely reported. In recent years, scientists have focused on combining cutting-edge bioengineering and bioinformatics technologies to improve the developmental accuracy of kidney organoids and achieve high-throughput experimentation. As a remarkable tool for mechanistic research of the renal system, kidney organoid has both potential and challenges. In this review, we have described the evolution of kidney organoid establishment methods and highlighted the latest progress leading to a more sophisticated kidney transformation research model. Finally, we have summarized the main applications of renal organoids in exploring kidney disease.

19.
Arch Esp Urol ; 77(4): 418-425, 2024 May.
Article in English | MEDLINE | ID: mdl-38840286

ABSTRACT

BACKGROUND: Kidney stones, a common urinary system ailment, often necessitate surgical intervention. Endoscopic combined intrarenal surgery (ECIRS) and multi-channel percutaneous nephron lithotripsy (MPCNL) are key modalities for treating complex renal stones, prompting the need for a comparative analysis to enhance clinical decision-making. METHODS: Patients undergoing surgical treatment for complex kidney stones from April 2018 to April 2022 were divided into the control (MPCNL) and observation (ECIRS) groups. Propensity score matching was used to balance baseline data, and t-tests and chi-square tests were employed to compare the perioperative indicators between the two groups. RESULTS: A total of 210 patients were enrolled in this study for pre-observational comparison, and they were divided into the control group (110 patients) and observation group (100 patients). Following matching, each group comprised 85 patients. Pre-observational comparison revealed significant differences between the groups in age, disease duration, and stone diameter (p < 0.05). However, after matching, baseline data comparison showed no statistically significant differences (p > 0.05). Surgery-related parameters, including operation time, intraoperative blood loss, postoperative activity duration and hospital stay, did not significantly differ between the groups (p > 0.05). The observation group exhibited a significantly higher stone retention-free rate after initial treatment compared with the control group (p < 0.05), although overall stone clearance rates did not significantly differ between the groups (p > 0.05). We found no significant differences in perioperative complications between the two groups (p > 0.05). Moreover, the observation group experienced significantly lower postoperative pain levels at 6, 24 and 48 h compared with the control group (p < 0.001). CONCLUSIONS: Conclusively, ECIRS and MPCNL are viable options for treating complex renal calculi, with similar operation times, complication rates and stone clearance rates. ECIRS may offer advantages including lower postoperative pain and higher initial stone clearance rates than MPCNL. However, large-scale studies with long follow-up times are needed for validation.


Subject(s)
Kidney Calculi , Lithotripsy , Humans , Kidney Calculi/surgery , Male , Retrospective Studies , Female , Middle Aged , Lithotripsy/methods , Treatment Outcome , Adult , Endoscopy , Urologic Surgical Procedures/methods , Aged , Nephrons
20.
Curr Oncol ; 31(6): 2985-2993, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38920711

ABSTRACT

Few data are available on survival outcomes of partial nephrectomy performed for cystic renal tumors. We present the first long-term oncological outcomes of cystic (cystRCC) versus pure clear cell renal cell carcinoma (ccRCC) in a propensity score-matched (PSM) analysis. Our "renal cancer" prospectively maintained database was queried for "cystRCC" or "ccRCC" and "off-clamp robotic partial nephrectomy" (off-C RPN). The two groups were compared for age, gender, tumor size, pT stage, and Fuhrman grade. A 1:3 PSM analysis was applied to reduce covariate imbalance to <10% and two homogeneous populations were generated. Student t- and Chi-square tests were used for continuous and categorical variables, respectively. Ten-year oncological outcomes were compared between the two cohorts using log-rank test. Univariable Cox regression analysis was used to identify predictors of disease progression after RPN. Out of 859 off-C RPNs included, 85 cases were cystRCC and 774 were ccRCC at histologic evaluation. After applying the PSM analysis, two cohorts were selected, including 64 cystRCC and 170 ccRCC. Comparable 10-year cancer-specific survival probability (95.3% versus 100%, p = 0.146) was found between the two cohorts. Conversely, 10-year disease-free survival probability (DFS) was less favorable for pure ccRCC than cystRCC (66.69% versus 90.1%, p = 0.035). At univariable regression analysis, ccRCC histology was the only independent predictor of DFS probability (HR 2.96 95% CI 1.03-8.47, p = 0.044). At the 10-year evaluation, cystRCC showed favorable oncological outcomes after off-C RPN. Pure clear cell variant histology displayed a higher rate of disease recurrence than cystic lesions.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Nephrectomy , Propensity Score , Robotic Surgical Procedures , Humans , Nephrectomy/methods , Female , Male , Carcinoma, Renal Cell/surgery , Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/surgery , Kidney Neoplasms/pathology , Kidney Neoplasms/mortality , Middle Aged , Robotic Surgical Procedures/methods , Aged , Treatment Outcome
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