ABSTRACT
Parietal epithelial cells (PECs) are kidney progenitor cells with similarities to a bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become activated and contribute to extracellular matrix deposition. Colony stimulating factor-1 (CSF-1), a hematopoietic growth factor, acts via its specific receptor, CSF-1R, and has been implicated in several glomerular diseases, although its role on PEC activation is unknown. Here, we found that CSF-1R was upregulated in PECs and podocytes in biopsies from patients with FSGS. Through in vitro studies, PECs were found to constitutively express CSF-1R. Incubation with CSF-1 induced CSF-1R upregulation and significant transcriptional regulation of genes involved in pathways associated with PEC activation. Specifically, CSF-1/CSF-1R activated the ERK1/2 signaling pathway and upregulated CD44 in PECs, while both ERK and CSF-1R inhibitors reduced CD44 expression. Functional studies showed that CSF-1 induced PEC proliferation and migration, while reducing the differentiation of PECs into podocytes. These results were validated in the Adriamycin-induced FSGS experimental mouse model. Importantly, treatment with either the CSF-1R-specific inhibitor GW2580 or Ki20227 provided a robust therapeutic effect. Thus, we provide evidence of the role of the CSF-1/CSF-1R pathway in PEC activation in FSGS, paving the way for future clinical studies investigating the therapeutic effect of CSF-1R inhibitors on patients with FSGS.
Subject(s)
Glomerulosclerosis, Focal Segmental , Hyaluronan Receptors , Macrophage Colony-Stimulating Factor , Podocytes , Glomerulosclerosis, Focal Segmental/pathology , Glomerulosclerosis, Focal Segmental/metabolism , Glomerulosclerosis, Focal Segmental/genetics , Animals , Humans , Podocytes/metabolism , Podocytes/pathology , Macrophage Colony-Stimulating Factor/metabolism , Macrophage Colony-Stimulating Factor/genetics , Hyaluronan Receptors/metabolism , Hyaluronan Receptors/genetics , Mice , Cell Proliferation/drug effects , Epithelial Cells/metabolism , Epithelial Cells/pathology , Epithelial Cells/drug effects , Receptor, Macrophage Colony-Stimulating Factor/metabolism , Receptor, Macrophage Colony-Stimulating Factor/genetics , Kidney Glomerulus/pathology , Kidney Glomerulus/metabolism , Male , Disease Models, Animal , Cells, Cultured , Female , Up-Regulation , Cell Movement/drug effects , MAP Kinase Signaling System/drug effects , Signal Transduction , Mice, Inbred C57BL , Receptors, Granulocyte-Macrophage Colony-Stimulating FactorABSTRACT
BACKGROUND: To maximize the availability of suitable grafts and ensure effective management, several reports have demonstrated successful outcomes when using kidney grafts with urolithiasis. This multicenter study reports on the management and long-term outcomes of kidney transplantation using renal grafts with lithiasis. METHODS: Retrospective data from three Spanish hospitals were analyzed for kidney transplants involving grafts with nephrolithiasis performed between December 2009 and August 2023. The study included adult patients, excluding those with incomplete records. It evaluated stone characteristics, complications, and outcomes in recipients and in living kidney donors. RESULTS: Out of 38 analyzed kidney transplants, 57.9% were cadaveric and 42.1% were from living kidney donors. Most diagnoses were incidental during donor evaluation, with an average stone size of 7.06 mm. After follow-up (median 26 months), all recipients but one had functioning grafts, and there were no stone recurrences in both recipients and living kidney donors. Conservative management was adopted in 28 cases, while 10 cases required ex-vivo flexible ureterorenoscopy for stone removal. Following conservative management, 5 patients needed additional treatments for stone-related events. CONCLUSIONS: Kidneys with lithiasis can be considered for transplantation in selected cases, resulting in good functional outcomes with no stone recurrence in recipients or living donors.
ABSTRACT
BACKGROUND AND OBJECTIVE: Orthotopic kidney transplantation (KT) has been proposed as an option for patients ineligible for heterotopic KT. In this scenario, orthotopic robot-assisted KT (oRAKT) represents a novel, minimally invasive alternative to the open approach. Here we describe the largest oRAKT series of patients, with a focus on the surgical technique, perioperative surgical outcomes, and functional results. METHODS: We queried prospectively maintained databases from three referral centers to identify patients who underwent oRAKT and evaluated surgical and functional outcomes. KEY FINDINGS AND LIMITATIONS: Overall, 16 oRAKT procedures were performed between January 2020 and August 2023. These involved four donors after cardiovascular death, five donors after brain death, and seven living donors. All oRAKT procedures were carried out in the left renal fossa. The indication for oRAKT was extensive calcification of the external iliac vessels (100%), frequently associated with prior KT (31%). The median operative time was 295 min (interquartile range [IQR] 268-360) and the median rewarming time 48 min (IQR 40-54). Conversion to open surgery occurred in two cases (12%), and delayed graft function was observed in two cases (12%). Postoperative complications occurred in 11 patients (69%) and three (18%) experienced Clavien-Dindo grade >II complications. At median follow-up of 9 mo (IQR 7-17), 14 patients had a functioning graft and median creatinine of 1.49 mg/dl (IQR 1.36-1.72). CONCLUSIONS AND CLINICAL IMPLICATIONS: Although oRAKT is a challenging procedure, it represents a feasible option for individuals ineligible for heterotopic KT and yields favorable perioperative and mid-term functional outcomes. PATIENT SUMMARY: We evaluated outcomes of orthotopic robot-assisted kidney transplantation (KT), in which the native kidney is removed and the donor kidney is transplanted into its place, in patients who are not eligible for heterotopic KT, in which the native kidney is left in place and the donor kidney is transplanted into a new location. We found that robot-assisted surgery is a safe and feasible alternative to traditional open surgery for orthotopic KT.
Subject(s)
Kidney Transplantation , Robotic Surgical Procedures , Humans , Robotic Surgical Procedures/methods , Kidney Transplantation/methods , Male , Middle Aged , Female , Treatment Outcome , Adult , Retrospective Studies , Aged , Postoperative Complications/etiologyABSTRACT
La utilización de las biopsias renales tantopreimplantacional como en el seguimiento de los pacientes trasplantados está dentro de la práctica habitual. La principal indicación para realizar la biopsia renal enel donante es para la valoración de los injertos de do-nantes con criterios expandidos, lo que ha demostradosu utilidad para decidir si un injerto es apto o no paraser trasplantado. Otras indicaciones incluyen la valoración de donantescon fracaso renal agudo, la valoración de lesiones dudosas a nivel del parénquima renal o como informaciónbasal necesaria en ensayos clínicos. La forma en que labiopsia de realiza tiene importancia en su valoración, y la valoración de las lesiones glomerulares, túbulointersticiales y vasculares del donante condicionan laevolución del injerto renal, tanto en la supervivencia delinjerto, como en el daño renal crónico que presenten enel seguimiento. La principal indicación para realización de biopsias enel receptor es el despistaje de rechazo tanto cuandoexiste sospecha clínica o en los casos de alto riesgoinmunológico donde resulta fundamental el diagnósticode rechazo subclínico. En los pacientes de alto riesgo, como son los pacientes sensibilizados o los receptores de trasplante devivo ABO incompatible, se plantea la planificación debiopsias de protocolo, sin existir un claro consenso entre diferentes centros. Para el procedimiento se utilizauna pistola automática con una aguja de 16 Gauge,y se relaciona con un porcentaje muy bajo de complicaciones.(AU)
Renal biopsy procedure is used prior toinsertion and at follow-up on a daily basis. The maindonor renal biopsy indication is for evaluation of renalgraft with expanded criteria, which have demonstratedtheir utility for renal transplant decisions. Other indications include evaluation of donors on acuterenal failure; indeterminate lesions evaluation on renalparenchyma or evaluation prior to clinical trial evaluation. How the renal biopsy is performed is also important on its evaluation, and evaluation of glomerularlesions, tubule-interstitial and vascular lesions. All thosedetermine renal graft evaluation, survival and chronicrenal disease during follow-up. The main indication for renal biopsy on the recipientis the differential diagnosis of rejection when clinically suspicious or on patients with high- immunologicalrisk where subclinical reject is important. In high0riskpatients, such as sensitized patients or living-donor recipients with ABO incompatibility, protocol biopsies areevaluated without guideline consensus. For that procedure, an automatic punch 16G needle is used, generally associated with low complication rates.(AU)
Subject(s)
Humans , Kidney Transplantation , Histology , Biopsy , Tissue Donors , Kidney/injuries , Kidney/surgery , Urology , Urologic DiseasesABSTRACT
OBJETIVO: El objetivo de este estudio es describir la experiencia inicial en nuestro centro de las primeras 94 Biopsias de Próstata dirigidas (BD) con fusión de imagen ecografía/Resonancia magnética (US/RMmp) y comparar la tasa de detección de CaP con las biopsias sistemáticas. MATERIAL Y MÉTODOS: Se realizó un estudio retrospectivo, descriptivo y comparativo de los primeros 94 pacientes sometidos a BD por fusión de imagen US/RMmp en nuestro centro desde febrero de 2017 hasta marzo de 2018. Todos los pacientes fueron sometidos a un protocolo de 6-12 cilindros de biopsias sistemáticas (BS) (menos 9) y de 2-6 cilindros dirigidos a las lesiones diana visualizadas en la RMmp. Se utilizó el equipo Hitachi/HiVision Preirus con software RVS (Real-time virtual sonography) y un transductor biplanar para la fusión de imagen. Se definió como CaP clínicamente significativo un GS ≥ 3 + 4 en, al menos, 1 de los cilindros realizados. RESULTADOS: La proporción de detección de CaP fue mayor en las BD que en las BS (p = 0,035) y el número de cilindros realizados para su diagnóstico fue menor en las BD comparado con las BS (p < 0,001). Se observó una clara tendencia a una mayor identificación de CaP clínicamente significativo (CaPcs) en las BD comparado con las BS (p = 0,063). CONCLUSIONES: Comparado con las BS, las BD por fusión de imagen US/RMmp presentaron una mayor tasa de detección de CaP y una tendencia a una mayor identificación de CaPcS con una necesidad menor de cilindros realizados
OBJECTIVE: To describe the initial experience in our center on targeted prostate biopsies (TB) using Magnetic Resonance imaging/ultrasonography (MRI/US) fusion and to compare PCa detection with systematic biopsies (SB). PATIENTS AND METHODS: A retrospective, descriptive and comparative study was conducted on the first 94 men who underwent TB using MRU/US fusion in our center since February 2017 to March 2018. All patients underwent a protocol of 6-12 cores of systematic biopsies (SB) (except 9) and 2-6 targeted cores on the MRI index lesion. The Hitachi/HiVision Preirus equipment was used with RVS software (Real-time virtual sonography) and a biplane transducer for the fusión imaging procedure. Clinically significant PCa (csPCa) was defined as: at least one core with a Gleason score of 3+4. RESULTS: The proportion of patients diagnosed with PCa was higher in TB compared with SB (p = 0.035) and the mean of core performed for diagnosis was lower in TB compared with SB (p < 0.001). A trend towards an improved detection of csPCa in TB compared to SB was observed (p = 0.063). CONCLUSIONS: The MRI/US fusion targeted biopsies (TB) showed a higher detection rate of PCa, with les cores taken for diagnosis and a tendency to better identification of csCaP compared to SB
Subject(s)
Humans , Male , Middle Aged , Aged , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Biopsy , Prostate/pathology , Magnetic Resonance Imaging , Retrospective Studies , Prospective Studies , Prostate-Specific Antigen , Prostatic Neoplasms/therapyABSTRACT
La cirugía protésica de pene es el tratamiento definitivo para aquellos pacientes con disfunción eréctil refractaria al tratamiento médico. A pesar de que asocia tasas de satisfacción > 90%, se sabe que los hombres con enfermedad de Peyronie, índice de masa corporal > 30 kg/m2 o aquellos intervenidos previamente de prostatectomía radical presentan tasas de satisfacción menores que la población general. Los motivos principales de insatisfacción son la pérdida subjetiva de longitud del pene y la flacidez del glande. Ante esta circunstancia, se han descrito múltiples técnicas quirúrgicas adyuvantes para mejorar los resultados estéticos y funcionales tras el implante. En nuestro artículo de revisión hemos querido analizar las diferentes maniobras utilizadas en pacientes con enfermedad de Peyronie, las usadas para evitar la disminución de la longitud del pene y aquellas utilizadas para evitar el floppy glans síndrome
Penile prosthetic surgery is the definitive treatment for those patients with erectile dysfunction refractory to medical treatment. Although it associates satisfaction rates > 90%, it is known that men with Peyronie's disease, body mass index > 30kg/m2 or those previously operated on radical prostatectomy have lower satisfaction rates than the general population. The main reasons for dissatisfaction are the subjective loss of penile length and glans'flaccidity. Given such circumstance, several adjuvant surgical techniques have been described to improve aesthetic and functional outcomes after the implant. In our review, we wanted to investigate the different maneuvers used in patients with Peyronie's disease, those used to avoid the reduction of penile length and those used to avoid the floppy glans syndrome