Partial nephrectomy in elderly patients: a systematic review and analysis of comparative outcomes.

PURPOSE: The management of renal masses in the elderly population is particularly challenging, as these patients are often more frail and potentially more susceptible to surgical morbidity. This review aims to provide a comprehensive analysis of the outcomes of partial nephrectomy (PN) for treating renal masses in elderly individuals. METHODS: A systematic electronic literature search was conducted in May 2024 using the Medline (via PubMed) database by searching publications up to April 2024. The population, intervention, comparator, and outcome (PICO) model defined study eligibility. Studies were deemed eligible if assessing elderly patients (aged 70 years or older) (P) undergoing PN (I) with or without comparison between a different population (non-elderly) or a different treatment option (radical nephrectomy, ablation or active surveillance) (C) evaluating surgical, functional, and oncological outcomes (O). RESULTS: A total of 23 retrospective studies investigating the role of PN in elderly patients were finally included. PN emerged as a safe procedure also for older patients, demonstrating good outcomes. Preoperative evaluation of frailty status emerged to be paramount. Age alone was discredited as the sole reason to reject the use of PN. The main limitation is the retrospective nature of included studies and the lack of the assessment of elderly patients' frailty. CONCLUSIONS: The surgical treatment of renal masses in older patients is a challenging scenario. PN should be chosen over RN whenever possible since it can better preserve renal function. The use of minimally invasive techniques should be favored in this extremely fragile group of patients.

Single Port Robotic Nephrectomy via lower anterior retroperitoneal approach: feasible, safe and effec-tive option in surgically complex patients.

PURPOSE: Minimally invasive radical nephrectomy is often preferred for larger renal tumours not suitable for partial nephrectomy (1). When performed with a multiport robot, the procedure is routinely performed with a transperitoneal approach, with recent studies highlighting important factors for surgical outcomes, including predictive factors (2), segmental artery unclamping techniques (3), and comparisons of robotic techniques (4). This video shows that SP Robot-Assisted Radical Nephrectomy (RARN) via a lower anterior approach is valuable in challenging cases. MATERIALS AND METHODS: We performed SP-RARN on two complex patients using a retroperitoneal lower anterior approach. The first patient, a 54-year-old female with a BMI of 36.8 kg/m², had a ventral hernia and bowel obstruction history, with a 9 cm right middle kidney mass. The second patient, a 58-year-old male with a BMI of 31.19 kg/m², had ESRD and was on peritoneal dialysis for 8 years, with a 3.4x3.7 cm mass in the right superior pole, suspected to be RCC. The surgical technique is detailed in the video. RESULTS: Both procedures were successful, with operative times of 173 and 203 minutes and blood loss of 150 mL. No complications occurred. Patients were discharged after 31 and 38 hours, respectively. Histopathology confirmed RCC. At the 3-month follow-up, no complications or readmissions were reported. Second patient continued peritoneal dialysis without issues. CONCLUSION: Retroperitoneal SP-RARN via the lower anterior approach avoids the peritoneal cavity, making it suitable for certain patients. In these patients, more so than in others, this procedure is feasible, safe, and less morbid than the standard multiport approach.

Urachal Carcinoma: Insights From a National Database.

INTRODUCTION: Urachal carcinoma (UrC) is a rare, nonurothelial malignancy, comprising less than 1% of all bladder cancers. It usually affects males in their fifth to sixth decade and is often diagnosed at an advanced stage with metastasis. This study examines UrC population characteristics and management. METHODS: We identified UrC patients from bladder biopsies or TURB in the PearlDiver Mariner database (2010-2022). Descriptive statistics detailed patient characteristics. Student's T-Tests compared ages for partial vs. radical cystectomy, and Fisher's exact test compared SDOH presence. Significance was set at P < .05. Analyses used R version 3.6.0 within PearlDiver's software. RESULTS: Among 2475 UrC patients (mean age 69.2 ± 9.2 years, 73.1% men), most were in the south (36.5%), outpatient settings (84.5%), and privately insured (65.3%). A total of 418 (16.2%) had at least 1 SDOH. Imaging before diagnosis was used in 65.74% of patients, primarily ultrasound. Smoking was present in 54.5%, diabetes in 42.9%, and obesity in 25.2%. After diagnosis, 1246 (50.34%) had localized disease; 407 underwent radical cystectomy and 330 partial cystectomy. Patients undergoing radical cystectomy were older (66.74 ± 8.13 years) compared to those undergoing partial cystectomy (60.55 ± 12.92 years) (P < .001), with SDOH factors more prevalent in the partial cystectomy group (P = .03). CONCLUSION: UrC is a rare, often advanced-stage cancer predominantly affecting older men. Our study shows a trend towards partial cystectomy for localized UrC. Further research is needed to personalize surgery and integrate multidisciplinary approaches for better outcomes.

Contemporary management of ischemic priapism: A 12-year population-based analysis from a large US database.

BACKGROUND: Priapism is a urological condition characterized by a persistent erection. The management varies based on its subclassifications. Despite established clinical guidelines for ischemic priapism, there is a lack of large-scale research focused on patient characteristics and management strategies. OBJECTIVES: To analyze the contemporary management of ischemic priapism in the US, exploring patient demographics and clinical characteristics, as well as predictors of erectile dysfunction (ED) and penile prosthesis implantation (PPI). MATERIALS AND METHODS: We performed a retrospective analysis of the PearlDiver Mariner database, reviewing records from 2010-2021. Adult males diagnosed with ischemic priapism were included. Data analysis covered demographic, clinical variables, and management strategies. Predictors of de novo ED and PPI were evaluated using multivariable logistic regression analysis. RESULTS: Of 36,120 patients, most (93%) received only medical management, and a minority underwent surgical interventions (penile shunt surgery [PSS], PPI or both). Medical management was typically effective, as 67.08% of the patients in this group experienced only one episode of priapism. However, de novo ED occurred in 16.57% of these patients. The majority of patients undergoing PPI had an inflatable prosthesis (81%). Older age (odds ratio, OR 1.02), the presence of metabolic diseases (OR 1.39), neurogenic disorders (OR 1.72), solid pelvic malignancies (OR 1.09), and multiple episodes of priapism were identified as significant predictors of de novo ED (all p < 0.05). Similarly, age (OR 1.03), the presence of metabolic diseases (OR 1.23), solid pelvic malignancies (OR 1.99), and multiple episodes of priapism were associated with higher likelihood of PPI (all p < 0.05). CONCLUSION: Most cases of ischemic priapism are managed with the medical therapy. Less than 3% of patients with ischemic priapism receive PPI, and when this occurs an inflatable prosthesis is favored. Age, specific comorbidities, and multiple episodes of priapism appear to be significant predictors of ED and PPI.

Incidence, Timing, and Pattern of Atypical Recurrence after Minimally Invasive Surgery for Urothelial Carcinoma.

The management of urothelial carcinoma has evolved with the introduction of minimally invasive techniques such as laparoscopic or robotic procedures, challenging the traditional approach of open surgery, and giving rise to atypical recurrences (ARs). ARs include port-site metastasis and peritoneal carcinomatosis, yet discrepancies persist among authors regarding their precise classification. Incidence rates of ARs vary widely across studies, ranging from less than 1% to over 10% in both muscle-invasive bladder cancer (MIBC) and upper tract urothelial tumor (UTUC). Peritoneal metastases predominate as the most common ARs in patients with MIBC, while retroperitoneal metastases are prevalent in those with UTUC due to differing surgical approaches. The timing of AR presentation and survival outcomes closely mirror those of conventional recurrences, with which they are frequently associated. Pneumoperitoneum has progressively been regarded less as the cause of ARs, while surgical-related risk factors have gained prominence. Current major surgical-related causes include tumor spillage and urinary tract violation during surgery, avoidance of endo bag use for specimen extraction, and low surgical experience. Factors such as tumor stage, histological variants, and lympho-vascular invasion correlate with the risk of ARs, suggesting a close association with tumor biology. Further studies are required to better understand the incidence, risk factors, characteristics, and outcomes of ARs.

The mitochondrial aspartate/glutamate carrier does not transport GABA.

É£-aminobutyric acid (GABA) is a four­carbon amino acid acting as the main inhibitory transmitter in the invertebrate and vertebrate nervous systems. The metabolism of GABA is well compartmentalized in the cell and the uptake of cytosolic GABA into the mitochondrial matrix is required for its degradation. A previous study carried out in the fruit fly Drosophila melanogaster indicated that the mitochondrial aspartate/glutamate carrier (AGC) is responsible for mitochondrial GABA accumulation. Here, we investigated the transport of GABA catalysed by the human and D. melanogaster AGC proteins through a well-established method for the study of the substrate specificity and the kinetic parameters of the mitochondrial carriers. In this experimental system, the D. melanogaster spliced AGC isoforms (Aralar1-PA and Aralar1-PE) and the human AGC isoforms (AGC1/aralar1 and AGC2/citrin) are unable to transport GABA both in homo- and in hetero-exchange with either glutamate or aspartate, i.e. the canonical substrates of AGC. Moreover, GABA has no inhibitory effect on the exchange activities catalysed by the investigated AGCs. Our data demonstrate that AGC does not transport GABA and the molecular identity of the GABA transporter in human and D. melanogaster mitochondria remains unknown.

Early and late post-procedural complications in different orthotopic neobladder surgical approaches: A systematic review.

Bladder cancer (BCa) represents the second most common malignancy of the genitourinary tract. The major risk factors include age, gender, smoking attitude, and occupational exposure, while the exact etiopathogenesis is still uncertain. Patients diagnosed with a BCa showing invasion of the muscle layer below the submucosa must undergo radical cystectomy (RC) with urinary diversion (UD). Many different surgical approaches to UD have been developed. Packaging an orthotopic neobladder (ON) with a bowel tract represents the gold standard when certain patient selection criteria are satisfied. Using PRISMA guidelines, we performed a systematic review assessing early (within 90 days) and late (beyond 90 days) post-procedural complications of different ON surgical approaches. A comprehensive systematic search was conducted in PubMed, Scopus, and Google Scholar databases to identify papers starting from 2012 using dedicated keywords ("neobladder", "orthotopic neobladder", "complications'' and "outcomes"). A total of 27 articles were found to satisfy the inclusion criteria and selected. Although the ON is a safe procedure that guarantees the patient the best quality of life (QoL), it is not free from risks. Many complications could occur during and after the surgical time which imposes the necessity of strict follow-up and careful checks over time, which should be properly discussed with patients before.

The detection rate for prostate cancer in systematic and targeted prostate biopsy in biopsy-naive patients, according to the localization of the lesion at the mpMRI: A single-center retrospective observational study.

OBJECTIVE: Evaluate the detection rates of systematic, targeted and combined cores at biopsy according to tumor positions in biopsy-naïve patients. MATERIAL AND METHODS: A retrospective analysis of a single-center patient cohort (n = 501) that underwent transrectal prostate biopsy between January 2017 and December 2019 was performed. Multi-parametric MRI was executed as a prebiopsy investigation. Biopsy protocol included, for each patient, 12 systematic cores plus 3 to 5 targeted cores per lesion identified at the mpMRI. Pearson and McNemar chi-squared tests were used for statistical analysis to compare tumor location-related detection rates of systematic, targeted and combined (systematic + targeted) cores at biopsy. RESULTS: Median age of patients was 70 years (IQR 62-72), with a median PSA of 8.5 ng/ml (IQR 5.7-15.6). Positive biopsies were obtained in 67.7% of cases. Overall, targeted cores obtained higher detection rates compared to systematic cores (54.3% vs. 43.1%, p < 0.0001). Differences in detection rates were, however, higher for tumors located at the apex (61.1% vs. 26.3%, p < 0.05) and anteriorly (44.4% vs. 19.3%, p < 0.05). Targeted cores similarly obtained higher detection rates in the posterior zone of the prostate gland for clinically significant prostate cancer. A poor agreement was reported between targeted and systematic cores for the apex and anterior zone of the prostate with, respectively κ = 0.028 and κ = -0.018. CONCLUSION: A combined approach of targeted and systematic biopsy delivers the highest detection rate in prostate cancer (PCa). The location of the tumor could however greatly influence overall detection rates, indicating the possibility to omit (as for the base or posterior zone of the gland) or add (as for the apex or anterior zone of the gland) further targeted cores.

Ischemia-Reperfusion Injury in Kidney Transplantation: Mechanisms and Potential Therapeutic Targets.

Kidney transplantation offers a longer life expectancy and a better quality of life than dialysis to patients with end-stage kidney disease. Ischemia-reperfusion injury (IRI) is thought to be a cornerstone in delayed or reduced graft function and increases the risk of rejection by triggering the immunogenicity of the organ. IRI is an unavoidable event that happens when the blood supply is temporarily reduced and then restored to an organ. IRI is the result of several biological pathways, such as transcriptional reprogramming, apoptosis and necrosis, innate and adaptive immune responses, and endothelial dysfunction. Tubular cells mostly depend on fatty acid (FA) ß-oxidation for energy production since more ATP molecules are yielded per substrate molecule than glucose oxidation. Upon ischemia-reperfusion damage, the innate and adaptive immune system activates to achieve tissue clearance and repair. Several cells, cytokines, enzymes, receptors, and ligands are known to take part in these events. The complement cascade might start even before organ procurement in deceased donors. However, additional experimental and clinical data are required to better understand the pathogenic events that take place during this complex process.

Ablative Treatments for Small Renal Masses and Management of Recurrences: A Comprehensive Review.

This review focuses on ablative techniques for small renal masses (SRMs), including radiofrequency ablation (RFA), cryoablation (CA), microwave ablation (MWA), and irreversible electroporation (IRE), and discusses recurrence management. Through an extensive literature review, we outline the procedures, outcomes, and follow-up strategies associated with each ablative method. The review provides a detailed examination of these techniques-RFA, CA, MWA, and IRE-elucidating their respective outcomes. Recurrence rates vary among them, with RFA and CA showing comparable rates, MWA demonstrating favorable short-term results, and IRE exhibiting promise in experimental stages. For managing recurrences, various strategies are considered, including active surveillance, re-ablation, or salvage surgery. Surveillance is preferred post-RFA and post-CA, due to slow SRM growth, while re-ablation, particularly with RFA and CA, is deemed feasible without additional complications. Salvage surgery emerges as a viable option for larger or resistant tumors. While ablative techniques offer short-term results comparable to surgery, further research is essential to understand their long-term effects fully. Decisions concerning recurrence management should consider individual and tumor-specific factors. Imaging, notably contrast-enhanced ultrasounds, plays a pivotal role in assessing treatment success, emphasizing the necessity of a multidisciplinary approach for optimal outcomes. The lack of randomized trials highlights the need for further research.

Unlocking Precision Medicine: Liquid Biopsy Advancements in Renal Cancer Detection and Monitoring.

Renal cell carcinoma (RCC) remains a formidable diagnostic challenge, especially in the context of small renal masses. The quest for non-invasive screening tools and biomarkers has steered research towards liquid biopsy, focusing on microRNAs (miRNAs), exosomes, and circulating tumor cells (CTCs). MiRNAs, small non-coding RNAs, exhibit notable dysregulation in RCC, offering promising avenues for diagnosis and prognosis. Studies underscore their potential across various biofluids, including plasma, serum, and urine, for RCC detection and subtype characterization. Encouraging miRNA signatures show correlations with overall survival, indicative of their future relevance in RCC management. Exosomes, with their diverse molecular cargo, including miRNAs, emerge as enticing biomarkers, while CTCs, emanating from primary tumors into the bloodstream, provide valuable insights into cancer progression. Despite these advancements, clinical translation necessitates further validation and standardization, encompassing larger-scale studies and robust evidence generation. Currently lacking approved diagnostic assays for renal cancer, the potential future applications of liquid biopsy in follow-up care, treatment selection, and outcome prediction in RCC patients are profound. This review aims to discuss and highlight recent advancements in liquid biopsy for RCC, exploring their strengths and weaknesses in the comprehensive management of this disease.

Upper Tract Urothelial Cancer: Guideline of Guidelines.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare disease with a potentially dismal prognosis. We systematically compared international guidelines on UTUC to analyze similitudes and differences among them. METHODS: We conducted a search on MEDLINE/PubMed for guidelines related to UTUC from 2010 to the present. In addition, we manually explored the websites of urological and oncological societies and journals to identify pertinent guidelines. We also assessed recommendations from the International Bladder Cancer Network, the Canadian Urological Association, the European Society for Medical Oncology, and the International Consultation on Bladder Cancer, considering their expertise and experience in the field. RESULTS: Among all the sources, only the American Urologist Association (AUA), European Association of Urology (EAU), and the National Comprehensive Cancer Network (NCCN) guidelines specifically report data on diagnosis, treatment, and follow-up of UTUC. Current analysis reveals several differences between all three sources on diagnostic work-up, patient management, and follow-up. Among all, AUA and EAU guidelines show more detailed indications. CONCLUSIONS: Despite the growing incidence of UTUC, only AUA, EAU, and NCCN guidelines deal with this cancer. Our research depicted high variability in reporting recommendations and opinions. In this regard, we encourage further higher-quality research to gain evidence creating higher grade consensus between guidelines.

The Role of MUC1 in Renal Cell Carcinoma.

Mucins are a family of high-molecular-weight glycoproteins. MUC1 is widely studied for its role in distinct types of cancers. In many human epithelial malignancies, MUC1 is frequently overexpressed, and its intracellular activities are crucial for cell biology. MUC1 overexpression can enhance cancer cell proliferation by modulating cell metabolism. When epithelial cells lose their tight connections, due to the loss of polarity, the mucins become dispersed on both sides of the epithelial membrane, leading to an abnormal mucin interactome with the membrane. Tumor-related MUC1 exhibits certain features, such as loss of apical localization and aberrant glycosylation that might cause the formation of tumor-related antigen epitopes. Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and it is the most common kidney cancer. The exact role of MUC1 in this tumor is unknown. Evidence suggests that it may play a role in several oncogenic pathways, including proliferation, metabolic reprogramming, chemoresistance, and angiogenesis. The purpose of this review is to explore the role of MUC1 and the meaning of its overexpression in epithelial tumors and in particular in RCC.

Sacral Neuromodulation: Device Improvement and Current Applications in Urology.

Sacral neuromodulation (SNM) offers a therapeutic approach to urological patients suffering from idiopathic overactive bladder (OAB) syndrome, with or without incontinence and non-obstructive urinary retention (NOR), who are not responding to or are not compliant with conservative or medical therapies. The exact mechanism of action of SNM is not fully understood but modulation of the spinal cord reflexes and brain networks by peripheral afferents is regarded as the main pathway. Over the years, surgical techniques improved, leading to the development of the modern two-stage implantation technique. The quadripolar lead is positioned percutaneously under fluoroscopy guidance through the third sacral foramen following the trajectory of S3. The procedure can be performed under local or general anesthesia with the patient in prone position. Current applications of sacral neuromodulation in urology are increasing thanks to the recent improvements of the devices that make this a valuable option not only in conditions such as overactive bladder and non-obstructing urinary retention but also neurogenic lower urinary tract dysfunction.

A mitochondrial NADPH-cholesterol axis regulates extracellular vesicle biogenesis to support hematopoietic stem cell fate.

Mitochondrial fatty acid oxidation (FAO) is essential for hematopoietic stem cell (HSC) self-renewal; however, the mechanism by which mitochondrial metabolism controls HSC fate remains unknown. Here, we show that within the hematopoietic lineage, HSCs have the largest mitochondrial NADPH pools, which are required for proper HSC cell fate and homeostasis. Bioinformatic analysis of the HSC transcriptome, biochemical assays, and genetic inactivation of FAO all indicate that FAO-generated NADPH fuels cholesterol synthesis in HSCs. Interference with FAO disturbs the segregation of mitochondrial NADPH toward corresponding daughter cells upon single HSC division. Importantly, we have found that the FAO-NADPH-cholesterol axis drives extracellular vesicle (EV) biogenesis and release in HSCs, while inhibition of EV signaling impairs HSC self-renewal. These data reveal the existence of a mitochondrial NADPH-cholesterol axis for EV biogenesis that is required for hematopoietic homeostasis and highlight the non-stochastic nature of HSC fate determination.

Transcriptional and metabolic effects of aspartate-glutamate carrier isoform 1 (AGC1) downregulation in mouse oligodendrocyte precursor cells (OPCs).

Aspartate-glutamate carrier isoform 1 (AGC1) is a carrier responsible for the export of mitochondrial aspartate in exchange for cytosolic glutamate and is part of the malate-aspartate shuttle, essential for the balance of reducing equivalents in the cells. In the brain, mutations in SLC25A12 gene, encoding for AGC1, cause an ultra-rare genetic disease, reported as a neurodevelopmental encephalopathy, whose symptoms include global hypomyelination, arrested psychomotor development, hypotonia and seizures. Among the biological components most affected by AGC1 deficiency are oligodendrocytes, glial cells responsible for myelination processes, and their precursors [oligodendrocyte progenitor cells (OPCs)]. The AGC1 silencing in an in vitro model of OPCs was documented to cause defects of proliferation and differentiation, mediated by alterations of histone acetylation/deacetylation. Disrupting AGC1 activity could possibly reduce the availability of acetyl groups, leading to perturbation of many biological pathways, such as histone modifications and fatty acids formation for myelin production. Here, we explore the transcriptome of mouse OPCs partially silenced for AGC1, reporting results of canonical analyses (differential expression) and pathway enrichment analyses, which highlight a disruption in fatty acids synthesis from both a regulatory and enzymatic stand. We further investigate the cellular effects of AGC1 deficiency through the identification of most affected transcriptional networks and altered alternative splicing. Transcriptional data were integrated with differential metabolite abundance analysis, showing downregulation of several amino acids, including glutamine and aspartate. Taken together, our results provide a molecular foundation for the effects of AGC1 deficiency in OPCs, highlighting the molecular mechanisms affected and providing a list of actionable targets to mitigate the effects of this pathology.

Outcomes and Techniques of Robotic-Assisted Partial Nephrectomy (RAPN) for Renal Hilar Masses: A Comprehensive Systematic Review.

Background: Robot-assisted partial nephrectomy (RAPN) is increasingly being employed in the management of renal cell carcinoma (RCC) and it is expanding in the field of complex renal tumors. The aim of this systematic review was to consolidate and assess the results of RAPN when dealing with entirely central hilar masses and to examine the various methods used to address the surgical difficulties associated with them. Methods: A thorough literature search in September 2023 across various databases focused on RAPN for renal hilar masses, adhering to PRISMA guidelines. The primary goal was to evaluate RAPN's surgical and functional outcomes, with a secondary aim of examining different surgical techniques. Out of 1250 records, 13 full-text manuscripts were reviewed. Results: Evidence is growing in favor of RAPN for renal hilar masses. Despite a predominance of retrospective studies and a lack of long-term data, RAPN shows positive surgical outcomes and preserves renal function without compromising cancer treatment effectiveness. Innovative suturing and clamping methods are emerging in surgical management. Conclusions: RAPN is a promising technique for managing renal hilar masses in RCC, offering effective surgical outcomes and renal function preservation. The study highlights the need for more long-term data and prospective studies to further validate these findings.

Management of Pediatric Urolithiasis in an Italian Tertiary Referral Center: A Retrospective Analysis.

Background and Objectives: In recent years, the prevalence of pediatric urolithiasis has increased in North America and Western countries, though it is endemic in developing countries. The aim of this study is to describe the experience of a tertiary pediatric referral center in the surgical management of pediatric urolithiasis. Materials and Methods: We retrospectively reviewed the experience of patients ≤ 16 years old affected by urinary stones who underwent surgery. Results: From April 2021 to September 2023, 31 pediatric patients underwent surgical procedures for stone diseases at our department: 13 preschool-aged (1-5 years) and 18 school-aged (6-16 years) children. During this period, 12 URSs, 17 RIRSs, and 2 PCNLs were recorded. Five patients had residual fragments at first, so three of them underwent a second endourological lithotripsy (2 RIRSs and 1 URS). Complete clearance was finally achieved in 27 patients. The stone composition was evaluated in 25 cases. Conclusions: Numerous innovations in the surgical treatment of pediatric urolithiasis have resulted from the development of smaller devices and new technology. Our results show how, in experienced centers, retrograde and percutaneous lithotripsy are safe and effective procedures for use in pediatric populations.

Complement System and the Kidney: Its Role in Renal Diseases, Kidney Transplantation and Renal Cell Carcinoma.

The crosstalk among the complement system, immune cells, and mediators of inflammation provides an efficient mechanism to protect the organism against infections and support the repair of damaged tissues. Alterations in this complex machinery play a role in the pathogenesis of different diseases. Core complement proteins C3 and C5, their activation fragments, their receptors, and their regulators have been shown to be active intracellularly as the complosome. The kidney is particularly vulnerable to complement-induced damage, and emerging findings have revealed the role of complement system dysregulation in a wide range of kidney disorders, including glomerulopathies and ischemia-reperfusion injury during kidney transplantation. Different studies have shown that activation of the complement system is an important component of tumorigenesis and its elements have been proved to be present in the TME of various human malignancies. The role of the complement system in renal cell carcinoma (RCC) has been recently explored. Clear cell and papillary RCC upregulate most of the complement genes relative to normal kidney tissue. The aim of this narrative review is to provide novel insights into the role of complement in kidney disorders.