HIV and kidney transplantation in Romania: The index case.

INTRODUCTION: Human immunodeficiency virus (HIV) is no longer considered a contraindication for kidney transplantation (KT). KT management in HIV patients is a complex process with challenges, such as drug interactions between immunosuppression and antiretroviral (ARV) therapy. In our country, no KT has been performed thus far in this category of patients. CASE PRESENTATION: We present the case of a 29-year-old female patient with HIV and end-stage renal disease (ESRD) who performed a KT from a related living donor in March 2022. KT immediate evolution was favorable. No transplant-related complications were reported. HIV viral load remained undetectable and CD4+ T cells were constantly > 500 cell/ µL, during the 18 months of follow-up. The main challenge in our case was the drug interaction between the protease inhibitor-based regimen and tacrolimus. This led to tacrolimus overdose, and, subsequently, change in ARV therapy. ARV switching was performed on a regimen based on integrase inhibitor and nucleoside reverse transcriptase inhibitors. After the ARV change, the therapeutic level of tacrolimus was easily reached and maintained. Kidney graft function remained normal during follow-up, despite tacrolimus overexposure, and no rejection or anti-HLA antibodies were observed. Another challenge was related to the donor's hepatitis C virus status (positive antibodies, negative nucleic acid test). The recipient did not develop seroconversion or detectable viremia at 3-, 6-, 12- and 18-months post-KT. CONCLUSION: We reported the first case of a successful KT in an ESRD patient with HIV in Romania, in whom the post-transplant evolution was favorable.

Robotic-assisted vs. open ureteral reimplantation: a multicentre comparison.

PURPOSE: Open ureteral reimplantation is considered the standard surgical approach to treat distal ureteral strictures or injuries. These procedures are increasingly performed in a minimally invasive and robotic-assisted manner. Notably, no series comparing perioperative outcomes and safety of the open vs. robotic approach are available so far. METHODS: In this retrospective multi-center study, we compared data from 51 robotic ureteral reimplantations (RUR) with 79 open ureteral reimplantations (OUR). Both cohorts were comparatively assessed using different baseline characteristics and perioperative outcomes. Moreover, a multivariate logistic regression for independent predictors was performed. RESULTS: Surgery time, length of hospital stay and dwell time of bladder catheter were shorter in the robotic cohort, whereas estimated blood loss, postoperative blood transfusion rate and postoperative complications were lower than in the open cohort. In the multivariate linear regression analysis, robotic approach was an independent predictor for a shorter operation time (coefficient - 0.254, 95% confidence interval [CI] - 0.342 to - 0.166; p < 0.001), a lower estimated blood loss (coefficient - 0.390, 95% CI - 0.549 to - 0.231, p < 0.001) and a shorter length of hospital stay (coefficient - 0.455, 95% CI - 0.552 to - 0.358, p < 0.001). Moreover, robotic surgery was an independent predictor for a shorter dwell time of bladder catheter (coefficient - 0.210, 95% CI - 0.278 to - 0.142, p < 0.001). CONCLUSION: RUR represents a safe alternative to OUR, with a shorter operative time, decreased blood loss and length of hospital stay. Prospective research are needed to further define the extent of the advantages of the robotic approach over open surgery.

Current role of intraoperative cell salvage techniques in the management of renal tumors with level III and IV inferior vena cava thrombus extension.

Background: En bloc removal of the kidney with tumor thrombus excision in a multidisciplinary team remains the standard treatment for renal cell carcinoma (RCC) with tumor thrombus extension. In order to minimize the hemodynamic impact of the surgical blood loss, intraoperative cell salvage (IOCS) techniques can decrease the need for allogeneic blood and prevent blood transfusion related complications. Objective: In this article, we evaluated the safety of IOCS during radical nephrectomy with inferior vena cava thrombectomy under cardiopulmonary bypass with or without deep hypothermic circulatory arrest. Design and method: In this retrospective comparative multicenter analysis, clinical characteristics of 27 consecutive patients who underwent surgery with or without IOCS between 2012 and 2022 in three referral care units were collected into a database. The need for an allogenic blood transfusion (ABT) was also recorded, defined as any transfusion that occurred either intraoperatively or during the hospital stay. Results: The need for ABT in the cell saver arm was significantly smaller due to the reinfusion of rescued blood (p < 0.015). In multivariate analysis, no cell saver usage was an independent predictor for complications ⩾3 Clavien 3a [odds ratio (OR) 18.71, 95% CI 1.056-331.703, p = 0.046]. No usage of IOCS was an independent predictor for a lower risk of death (OR 0.277, 95% CI 0.062-0.825, p = 0.024). During follow-up, patients who received salvaged blood did not experience an increased risk for developing local recurrence or distant metastases. Conclusion: Transfusion of autologous blood is safe and can be using during nephrectomy and thrombectomy for advanced RCC.

Role of intraoperative cell salvage techniques in the management of renal tumors with advanced caval extension En bloc removal of the kidney with tumor thrombus excision in a multidisciplinary team remains the standard treatment for RCC with tumor thrombus extension. Intraoperative cell salvage techniques (IOCS) can decrease the need for allogeneic blood and prevent blood transfusion related complications. In this article we demonstrated that transfusion of autologous blood is safe and can be using during nephrectomy and thrombectomy for advanced renal cell carcinoma.

How to Integrate Prostate Cancer Biomarkers in Urology Clinical Practice: An Update.

Nowadays, the management of prostate cancer has become more and more challenging due to the increasing number of available treatment options, therapeutic agents, and our understanding of its carcinogenesis and disease progression. Moreover, currently available risk stratification systems used to facilitate clinical decision-making have limitations, particularly in providing a personalized and patient-centered management strategy. Although prognosis and prostate cancer-specific survival have improved in recent years, the heterogenous behavior of the disease among patients included in the same risk prognostic group negatively impacts not only our clinical decision-making but also oncological outcomes, irrespective of the treatment strategy. Several biomarkers, along with available tests, have been developed to help clinicians in difficult decision-making scenarios and guide management strategies. In this review article, we focus on the scientific evidence that supports the clinical use of several biomarkers considered by professional urological societies (and included in uro-oncological guidelines) in the diagnosis process and specific difficult management strategies for clinically localized or advanced prostate cancer.

The Role of the Cardiac Biomarkers in the Renal Cell Carcinoma Multidisciplinary Management.

Renal cell carcinoma, an aggressive malignancy, is often incidentally diagnosed. The patient remains asymptomatic to the late stage of the disease, when the local or distant metastases are already present. Surgical treatment remains the choice for these patients, although the plan must adapt to the characteristics of the patients and the extension of the neoplasm. Systemic therapy is sometimes needed. It includes immunotherapy, target therapy, or both, with a high level of toxicity. Cardiac biomarkers have prognosis and monitoring values in this setting. Their role in postoperative identification of myocardial injury and heart failure already have been demonstrated, as well as their importance in preoperative evaluation from the cardiac point of view and the progression of renal cancer. The cardiac biomarkers are also part of the new cardio-oncologic approach to establishing and monitoring systemic therapy. They are complementary tests for assessment of the baseline toxicity risk and tools to guide therapy. The goal must be to continue the treatment as long as possible with the initiation and optimisation of the cardiological treatment. Cardiac atrial biomarkers are reported to have also antitumoral and anti-inflammatory properties. This review aims to present the role of cardiac biomarkers in the multidisciplinary management of renal cell carcinoma patients.

AKI3-Risk Predictors and Scores in Radical Nephrectomy with High Thrombectomy under Extracorporeal Circulation for Renal Cell Carcinoma with Supradiaphragmatic Inferior Vena Cava/Right Atrial Thrombus: A Single-Centre Retrospective Study.

Background and Objectives: The recommended therapeutic management in renal cell carcinoma (RCC) with supradiaphragmatic inferior vena cava/right atrial thrombus (IVC/RA) is surgery. Extracorporeal circulation is required. Acute kidney injury (AKI), a frequent complication after nephrectomy and cardiac surgery is associated with long-term kidney disease. This study aims to identify the risk factors involved in the occurrence of the severe postoperative AKI (AKI3) and to analyse various preoperative validated risk scores from cardiac and noncardiac surgery in predicting this endpoint. Materials and Methods: The medical data of all patients with RCC with supradiaphragmatic IVC/RA thrombus who underwent radical nephrectomy with high thrombectomy, using extracorporeal circulation, between 2004-2018 in the Prof. C. C. Iliescu Emergency Institute for Cardiovascular Diseases, Bucharest, were retrospectively analysed. The patients who died intraoperatively were excluded from the study. The predefined study endpoint was the postoperative AKI3. Preoperative, intraoperative and postoperative data were collected according to the stratification of study population in two subgroups: AKI3-present and AKI3- absent patients. EuroSCORE, EuroSCORE II, Logistic EuroSCORE, NSQIP any-complications and NSQIP serious-complications were analysed. Results: We reviewed 30 patients who underwent this complex surgery between 2004-2018 in our institute. Two patients died intraoperatively. Nine patients (32.14%) presented postoperative AKI3. Age (OR 1.151, CI 95%: 1.009-1.312), preoperative creatinine clearance (OR 1.066, CI 95%: 1.010-1.123) and intraoperative arterial hypotension (OR 13.125, CI 95%: 1.924-89.515) were risk factors for AKI3 (univariable analysis). Intraoperative arterial hypotension emerged as the only independent risk factor in multivariable analysis (OR 11.66, CI 95%: 1.400-97.190). Logistic EuroSCORE (ROC analysis: AUC = 0.813, p = 0.008, CI 95%: 0.633-0.993) best predicted the endpoint. Conclusions: An integrated team effort is essential to avoid intraoperative arterial hypotension, the only independent risk factor of AKI3 in this highly complex surgery. Some risk scores can predict this complication. Further studies are needed.

Focal therapy for primary tumor and metastases in de novo or recurrent oligometastatic prostate cancer: current standing and future perspectives.

PURPOSE: Focal therapy (FT) is gaining increasing acceptance in the management of localized prostate cancer particularly due to its favorable safety. Preliminary evidence suggests advantageous utilization of local treatment in the field of oligometastatic prostate cancer (OMPC). Since data on the utilization of FT in OMPC are scarce, we sought to summarize available evidence. METHODS: For this narrative comprehensive review, we employed PubMed®, Web of Science™, Embase®, Scopus®, and clinicaltrial.gov databases and Google web search engine to seek peer-reviewed articles, published abstracts from international congresses, and ongoing trials in the English language using the terms "prostate cancer", "oligometastatic", "hormone-sensitive", "focal therapy", "focal treatment", "cryotherapy", "ablation", "cancer" as well as "metastasis-directed therapy. We focused on relevant publications on FT utilized in OMPC targeting the primary or metastatic sites as well as completed and ongoing clinical trials. RESULTS: Growing evidence points to distinct differences in the biologic behavior and molecular signaling processes of OMPC as compared to polymetastatic disease (PMPC). No established biomarkers are available to accurately identify OMPC yet, while several candidates are currently under investigation. The evolution of molecular imaging is set to aid in selecting patients benefitting most from local management. Differences between OMPC and PMPC should be considered when designing the optimal therapeutic strategy. While efficacy data for FT in comparison to standard care in OMPC are scarce, longer progression-free survival and time to castration resistance have been demonstrated for bone metastatic prostate cancer with the primary tumor treated by cryosurgery followed by androgen deprivation therapy (ADT) compared to ADT alone. CONCLUSION: Ongoing research efforts are eagerly awaited to better characterize OMPC and establish customized strategies for patients with this condition.

Mycobacterium Tuberculosis Infection after Kidney Transplantation: A Comprehensive Review.

Tuberculosis (TB) in kidney transplant (KT) recipients is an important opportunistic infection with higher incidence and prevalence than in the general population and is associated with important morbidity and mortality. We performed an extensive literature review of articles published between 1 January 2000 and 15 June 2022 to provide an evidence-based review of epidemiology, pathogenesis, diagnosis, treatment and outcomes of TB in KT recipients. We included all studies which reported epidemiological and/or outcome data regarding active TB in KT, and we approached the diagnostic and treatment challenges according to the current guidelines. Prevalence of active TB in KT recipients ranges between 0.3-15.2%. KT recipients with active TB could have a rejection rate up to 55.6%, a rate of graft loss that varies from 2.2% to 66.6% and a mortality rate up to 60%. Understanding the epidemiological risk, risk factors, transmission modalities, diagnosis and treatment challenges is critical for clinicians in providing an appropriate management for KT with TB. Among diagnostic challenges, which are at the same time associated with delay in management, the following should be considered: atypical clinical presentation, association with co-infections, decreased predictive values of screening tests, diverse radiological aspects and particular diagnostic methods. Regarding treatment challenges in KT recipients with TB, drug interactions, drug toxicities and therapeutical adherence must be considered.

Challenges in Diagnosis of Uretero-Arterial Fistulas after Complex Pelvic Oncological Procedures-Single Center Experience and Review of the Literature.

Introduction: Uretero-arterial fistula (UAF) represents a rare condition that manifests as massive or intermittent hematuria and requires collaboration between a urologist, vascular surgeon and interventional radiologist. In this article, we present our experience with UAF diagnosis, treatment pathways and the results of a nonsystematic review of the literature published in the last decade regarding modern diagnostic procedures. Material and method: We analyzed the clinical data of nine consecutive patients from our institution diagnosed with UAF in the interval of 2012-2022 who underwent open or endovascular surgical treatment. We reviewed patient characteristics, diagnoses and treatment pathways. The literature search resulted in 14 case series, published from 2012 to 2022, describing a total of 670 cases of UAF. Results: The mean age of patients in our cohort was 65.3 years (IQR: 51-79). UAFs were more common in women (77.7%). All patients presented a history of surgical intervention and ir-radiation for pelvic malignancy with permanent ureteric stenting. Overall, 88.8% of patients had urinary diversion, either via ileal conduit or cutaneous ureterostomy. The most common clinical manifestation of UAF was gross hematuria with or without clots accompanied by flank pain due to stent obstruction, while three patients presented with hypovolemic shock. Angiography represents the best option for diagnosis, followed by angioCT, with a sensitivity of 59.83% and 47.01%, respectively. There is no definitive imaging modality associated with high accuracy in detecting UAF and negative findings do not exclude the disease. In emergency cases with massive bleeding, surgical exploration remains the most appropriate management option for both diagnosis and treatment. Endovascular stent graft placement is preferred over open surgery in stable hemodynamic patients. Conclusions: Uretero-arterial fistulas represent a life-threatening complication and must be treated with great awareness. Angiography represents the best modality for diagnosis, followed by computed tomography. However, there is no definitive imaging modality and, in some cases, open approach remains the only option for diagnosis and treatment.

Non-HLA Antibodies in Kidney Transplantation: Immunity and Genetic Insights.

The polymorphic human leukocyte antigen (HLA) system has been considered the main target for alloimmunity, but the non-HLA antibodies and autoimmunity have gained importance in kidney transplantation (KT). Apart from the endothelial injury, secondary self-antigen exposure and the presence of polymorphic alloantigens, respectively, auto- and allo- non-HLA antibodies shared common steps in their development, such as: antigen recognition via indirect pathway by recipient antigen presenting cells, autoreactive T cell activation, autoreactive B cell activation, T helper 17 cell differentiation, loss of self-tolerance and epitope spreading phenomena. Both alloimmunity and autoimmunity play a synergic role in the formation of non-HLA antibodies, and the emergence of transcriptomics and genome-wide evaluation techniques has led to important progress in understanding the mechanistic features. Among them, non-HLA mismatches between donors and recipients provide valuable information regarding the role of genetics in non-HLA antibody immunity and development.

Tumor Lysis Syndrome: An Endless Challenge in Onco-Nephrology.

Tumor lysis syndrome (TLS) is a common cause of acute kidney injury in patients with malignancies, and it is a frequent condition for which the nephrologist is consulted in the case of the hospitalized oncological patient. Recognizing the patients at risk of developing TLS is essential, and so is the prophylactic treatment. The initiation of treatment for TLS is a medical emergency that must be addressed in a multidisciplinary team (oncologist, nephrologist, critical care physician) in order to reduce the risk of death and that of chronic renal impairment. TLS can occur spontaneously in the case of high tumor burden or may be caused by the initiation of highly efficient anti-tumor therapies, such as chemotherapy, radiation therapy, dexamethasone, monoclonal antibodies, CAR-T therapy, or hematopoietic stem cell transplantation. It is caused by lysis of tumor cells and the release of cellular components in the circulation, resulting in electrolytes and metabolic disturbances that can lead to organ dysfunction and even death. The aim of this paper is to review the scientific data on the updated definition of TLS, epidemiology, pathogenesis, and recognition of patients at risk of developing TLS, as well as to point out the recent advances in TLS treatment.

Multicentric comparative analysis of Retzius versus Retzius sparing robotic assisted simple prostatectomy in the management of large prostate glands.

AIM: Robot-assisted simple prostatectomy (RASP) is a minimally invasive alternative to open simple prostatectomy in the management of patients with large prostate glands suffering from moderate-to-severe lower urinary tract symptoms (LUTS). Our study aimed to evaluate two transvesical robotic approaches in order to compare functional outcomes and postoperative complications. MATERIALS AND METHODS: Clinical data from 111 consecutive patients from three tertiary robotic centers were retrospectively collected. Patients were divided into two groups depending on the surgical approach: 58 Retzius sparing and 53 Retzius approach RASP. We evaluated peri-operative outcomes (operating time, blood loss, transfusion rate, length of hospital stay), as well as intra-operative and early complications using a Clavien Dindo scale. Fisher's exact test, chi-square test and Mann-Whitney U test were applied for statistical analyses. A p-value <0.05 was considered statistically significant. RESULTS: Neither subgroup differed significantly in age (p = 0.104), Charlson comorbidity index (p = 0.088) or prostate volume (p = 0.507), total IPSS score (0.763) and Qmax (p = 0.651). Total complication rates were lower for the Retzius approach subgroup (19 vs 11.9%) without reaching statistical significance in multivariate analysis (HR = 1.21, 95% CI = 0.17 - 8.44, p = 0.84). No significant differences based on IPSS total score and Qmax could be observed between the two subgroups during follow-up. CONCLUSIONS: Both RASP approaches provide similar results in terms of functional outcomes and present a good safety profile in the management of large prostatic adenomas. Larger trials are needed in order to establish the indications for each robotic technique.

Molecular Mechanisms Related with Oligometastatic Prostate Cancer-Is It Just a Matter of Numbers?

During the last decade, the body of knowledge regarding the oligometastatic state has increased exponentially. Several molecular frameworks have been established, aiding our understanding of metastatic spread caused by genetically unstable cells that adapt to a tissue environment which is distant from the primary tumor. In the current narrative review, we provide an overview of the current treatment landscape of oligometastatic cancer, focusing on the current biomarkers used in the identification of true oligometastatic disease and highlighting the impact of molecular imaging on stage shift in different scenarios. Finally, we address current and future directions regarding the use of genetic and epigenetic targeting treatments in oligometastatic prostate cancer.

Immunosuppression as a Risk Factor for De Novo Angiotensin II Type Receptor Antibodies Development after Kidney Transplantation.

(1) Background: Angiotensin II type I receptor antibodies (AT1R-Ab) represent a topic of interest in kidney transplantation (KT). Data regarding the risk factors associated with de novo AT1R-Ab development are lacking. Our goal was to identify the incidence of de novo AT1R-Ab at 1 year after KT and to evaluate the risk factors associated with their formation. (2) Methods: We conducted a prospective cohort study on 56 adult patients, transplanted between 2018 and 2019. Recipient, donor, transplant, treatment, and complications data were assessed. A threshold of >10 U/mL was used for AT1R-Ab detection. (3) Results: De novo AT1R-Ab were observed in 12 out of 56 KT recipients (21.4%). The median value AT1R-Ab in the study cohort was 8.5 U/mL (inter quartile range: 6.8-10.4) and 15.6 U/mL (10.8-19.8) in the positive group. By multivariate logistic regression analysis, induction immunosuppression with anti-thymocyte globulin (OR = 7.20, 95% CI: 1.30-39.65, p = 0.02), maintenance immunosuppression with immediate-release tacrolimus (OR = 6.20, 95% CI: 1.16-41.51, p = 0.03), and mean tacrolimus trough level (OR = 2.36, 95% CI: 1.14-4.85, p = 0.01) were independent risk factors for de novo AT1R-Ab at 1 year after KT. (4) Conclusions: De novo AT1R-Ab development at 1 year after KT is significantly influenced by the type of induction and maintenance immunosuppression.

The early impact of preformed angiotensin II type 1 receptor antibodies on graft function in a low immunological risk cohort of kidney transplant recipients.

Intruduction and aim: Angiotensin II type 1 receptor antibodies (AT1R-Ab) are associated with graft rejection and poor graft outcomes in kidney transplantation (KT). We aimed to assess the frequency of preformed AT1R-Ab and their impact on graft function and survival at 1 year after KT in a low immunological risk cohort. METHODS: We performed a prospective, observational cohort study in 67 adult KT recipients, transplanted between 2018 and 2019. A cut-off value >10 U/ml was used for AT1R-Ab detection. RESULTS: The frequency of preformed AT1R-Ab was 10.4% and the median value of their level was 8.4 U/ml (IQR: 6.8-10.4). Donor-specific anti-human leukocyte antigen antibodies (HLA-DSA) were absent, no case of biopsy-proven rejection was reported and the incidence of graft failure was 7.5%. Estimated glomerular filtration rate (eGFR) was significantly reduced in the AT1R-Ab group [35 (29.8-55.2) vs 56.1 (41.3-66.5) ml/min, p = 0.02] at 1 year after KT. After multivariate linear regression analysis, preformed AT1R-Ab were found as an independent determinant of eGFR at 1 year after KT (ß: -15.395; 95% CI: -30.49 - -0.30; p = 0.04). By Cox multivariate regression analysis, preformed AT1R-Ab were not associated with graft failure (HR: 1.36; 95% CI:0.10-14.09; p = 0.80). CONCLUSION: Preformed AT1R-Ab are an independent determinant of graft function but do not impact graft survival at 12 months after transplantation in a prospective low immunological risk cohort of KT recipients.

Angiotensin II type 1 receptor antibodies in kidney transplantation: An evidence-based comprehensive review.

Angiotensin II type 1 receptor antibodies (AT1R-Ab) are among the most investigated types of non-HLA antibodies in kidney transplantation. Our aim is to provide an update regarding the clinical relevance of AT1R-Ab by outlining their prevalence, testing methodology, mechanism of graft injury and the association with graft rejection phenotypes, the relationship with HLA-donor specific antibodies (DSA) and some therapeutic aspects. To accomplish these, we performed a literature review between 2005 and 2019, identifying 27 relevant studies for inclusion. The reported prevalence of these antibodies is widely variable in part related to testing variability and lack of a standardized threshold for positivity. Data available suggest that both pre-formed and de novo antibodies are associated with negative graft outcomes. The pathogenesis of AT1R-Ab mediated graft injury seems to be complement-independent. Different phenotypes of antibody-mediated, T-cell-mediated and vascular rejection have been described in patients with AT1R-Ab. The relationship between HLA-DSA and AT1R-Ab is mutual in terms of their development, including a complex process between alloimmunity, autoimmunity, inflammation, endothelial damage and antigen expression. Antibody double positivity had a synergistic negative effect associated with detrimental effects on graft outcomes. Understanding the complexity of AT1R-Ab mediated graft injury and the relationship with HLA-DSA in kidney transplantation could provide a complementary, integrated assessment of immunological risk, help stratify the risk of graft rejection and dysfunction and may guide the treatment approach.

Kidney Involvement in Hypocomplementemic Urticarial Vasculitis Syndrome-A Case-Based Review.

Hypocomplementemic urticarial vasculitis syndrome (HUVS), or McDuffie syndrome, is a rare small vessel vasculitis associated with urticaria, hypocomplementemia and positivity of anti-C1q antibodies. In rare cases, HUVS can manifest as an immune-complex mediated glomerulonephritis with a membranoproliferative pattern of injury. Due to the rarity of this disorder, little is known about the clinical manifestation, pathogenesis, treatment response and outcome of such patients. We describe here three cases of HUVS with severe renal involvement. These patients had a rapidly progressive form of glomerulonephritis with severe nephrotic syndrome against a background of a membranoproliferative pattern of glomerular injury with extensive crescent formation. Therefore, these patients required aggressive induction and maintenance immunosuppressive therapy, with a clinical and renal response in two patients, while the third patient progressed to end-stage renal disease. Because of the rarity of this condition, there are few data regarding the clinical presentation, pathology and outcome of such patients. Accordingly, we provide an extensive literature review of cases reported from 1976 until 2020 and place them in the context of the current knowledge of HUVS pathogenesis. We identified 60 patients with HUVS and renal involvement that had adequate clinical data reported, out of which 52 patients underwent a percutaneous kidney biopsy. The most frequent renal manifestation was hematuria associated with proteinuria (70% of patients), while one third had abnormal kidney function on presentation (estimated glomerular filtration (GFR) below 60 mL/min/1.73 m2). The most frequent glomerular pattern of injury was membranoproliferative (35%), followed by mesangioproliferative (21%) and membranous (19%). Similar to other systemic vasculitis, renal involvement carries a poorer prognosis, but the outcome can be improved by aggressive immunosuppressive treatment.

Budesonide versus systemic corticosteroids in IgA Nephropathy: A retrospective, propensity-matched comparison.

IgA Nephropathy (IgAN) is characterized by mesangial deposition of dominant, polymeric, galactose-deficient IgA1 molecules of gut-associated lymphoid tissue origin. We sought to evaluate the efficacy of targeting the mucosal immune system dysregulation underlying IgAN pathogenesis with a pH-modified formulation of budesonide with a maximum release of active compound in the distal ileum and proximal colon.We did a retrospective study evaluating the efficacy of budesonide (Budenofalk) in the treatment of IgAN. From a retrospective cohort of 143 patients with IgAN followed in our department we identified 21 patients that received treatment with budesonide. These patients received budesonide at a dose of 9 mg/d in the first 12 months, followed by a dose reduction to 3 mg/d for the subsequent period. Only patients that received a 24-month treatment with budesonide were included in the analysis (n = 18). We matched the budesonide-treated cohort to 18 patients with IgAN treated with systemic steroids from the same retrospective cohort. Efficacy was measured as change in proteinuria, hematuria and estimated glomerular filtration rate over a 24-month period.Treatment with budesonide was associated with a 24-month renal function decline of -0.22 (95%CI, -8.2 to 7.8) ml/min/1.73m, compared to -5.89 (95%CI, -12.2 to 0.4) ml/min/1.73m in the corticosteroid treatment group (p = 0.44, for between group difference). The median reduction in proteinuria at 24-month was 45% (interquartile range [IQR]: -79%; -22%) in the budesonide group and 11% (IQR: -39%; 43%) in the corticosteroid group, respectively (P = .009, for between group difference). The median reduction in hematuria at 24-month was 72% (IQR: -90%; -45%) in the budesonide group and 73% (IQR: -85%; 18%) in the corticosteroid group, respectively (P = .22, for between group difference). Treatment with budesonide was well tolerated with minimal side effects.Budesonide (Budenofalk) was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria, hematuria and preserving renal function over 24 months of therapy.

Systemic treatment options for metastatic hormone-sensitive prostate cancer: making sense of the data.

PURPOSE OF REVIEW: Systemic treatment options for metastatic hormone-sensitive prostate cancer (mHSPC) have recently shifted from the traditional androgen deprivation therapy (ADT) monotherapy to multidrug approaches incorporating drugs initially approved for castration-resistant state and ADT. However, clinicians have difficulties in choosing the adequate combination therapy for individualized patient care, because of the lack of consensus regarding disease risk factors, differences in study design of the major clinical trials and lack of direct comparisons between drugs. The aim of this review is to provide an update of the current treatment options for this heterogenous group of patients. RECENT FINDINGS: Current oncological guidelines strongly recommend that patients with newly diagnosed mHSPC and high-volume disease (CHAARTED criteria) should receive docetaxel and ADT, whereas those with high-risk disease (LATITUDE criteria) abiraterone and ADT. Recently, the Food and Drug Administration approved apalutamide and enzalutamide for mHSPC. Moreover, new data support the efficacy of docetaxel and abiraterone in patients with mHSPC, regardless of metastatic burden. SUMMARY: Today, the combination approach should be recommended for newly diagnosed mHSPC over ADT monotherapy, but treatment initiation must be personalized based on disease, drug and patient characteristics. Thanks to continuous efforts and progress in patient and disease-related outcomes, mHSPC could become a chronic disease.

Treatment of the primary in metastatic prostate cancer.

PURPOSE OF REVIEW: The standard treatment in metastatic prostate cancer (mPCa) is systemic, based on androgen deprivation therapy recommended in different forms, alone or combined with abiraterone acetate or docetaxel. The aim of this review is to synthesize the available data from literature regarding the optimal treatment of the primary in patients diagnosed with metastatic prostate cancer. RECENT FINDINGS: Multimodal treatments offer the best chance for survival for these patients, but the optimal strategy lacks consensus. Using retrospective studies as an argument, recent articles sustain the clinical and oncological benefits of local therapies in hormone-naïve metastatic prostate cancer, represented by radical prostatectomy or radiotherapy. Through these procedures, local control of disease can be achieved, thus avoiding potential complications and further surgical interventions. Even if the current results are not evenly relevant, the treatment of the primary along with metastasis-directed therapy could improve survival and even cure-selected patients. SUMMARY: This article emphasizes important aspects regarding a feasible management of mPCa, with possible impact on subsequent guidelines. The expected results from ongoing trials may provide another perspective in treatment of these cases.