Key Points. PIEZO1 activation reduces cystogenesis: Yoda1 activates PIEZO1, raising calcium and lowering cAMP, reducing cyst growth in autosomal dominant polycystic kidney disease models.
Context-dependent role of PIEZO1: PIEZO1 knockout in mice with or without polycystic kidneys does not affect cyst formation, suggesting redundancy in mechanosensitive pathways.
Therapeutic potential: Findings support PIEZO1 activation as a part of combination therapy to slow cyst growth in autosomal dominant polycystic kidney disease, needing more in vivo studies.
Background. The disruption of calcium signaling associated with polycystin deficiency is a key factor in abnormal epithelial growth in autosomal dominant polycystic kidney disease. Calcium homeostasis can be influenced by mechanotransduction. The mechanosensitive cation channel PIEZO1 has been implicated in sensing intrarenal pressure and regulating urinary osmoregulation, but its role in kidney cystogenesis is unclear.
Methods. We hypothesized that altered mechanotransduction contributes to cystogenesis in autosomal dominant polycystic kidney disease and that activation of mechanosensitive cation channels could be a therapeutic strategy.
Results. We demonstrate that Yoda1, a PIEZO1 activator, increases intracellular calcium and reduces forskolin-induced cAMP levels in mouse inner medullary collecting duct (mIMCD3) cells. Notably, knockout of polycystin-2 attenuated the efficacy of Yoda1 in reducing cAMP levels in mIMCD3 cells. Yoda1 also reduced forskolin-induced mIMCD3 cyst surface area in vitro and cystic index in mouse metanephros ex vivo in a dose-dependent manner. However, collecting duct–specific PIEZO1 knockout neither induced cystogenesis in wild-type mice nor altered cystogenesis in the Pkd1RC/RC mouse model.
Conclusions. These findings support the potential role of PIEZO1 agonists in mitigating cystogenesis by increasing intracellular calcium and reducing cAMP levels, but the unaltered in vivo cystic phenotype after PIEZO1 knockout in the collecting duct suggests possible redundancy in mechanotransductive pathways.
Background Secondary hyperparathyroidism (SHPT) is a prevalent chronic complication in patients undergoing hemodialysis. Parathyroidectomy (PTX) is crucial for reducing mortality and improving the prognosis in the treatment of refractory hyperparathyroidism. However, it is often associated with a number of postoperative complications such as postoperative hypotension, hyperkalemia, and hungry bone syndrome. A previous study demonstrated that low blood pressure influences the patency of autogenous arteriovenous fistulas (AVF). Few studies have examined AVF dysfunction following PTX. This study aimed to identify and describe the risk variables associated with AVF dysfunction after PTX.Methods Cases of AVF dysfunction after PTX between 2015 and 2021 were studied. Four controls were identified for each patient and were matched for sex and age. Biochemical parameters and blood pressure of the patients before and after PTX were recorded. Risk factors for AVF dysfunction after PTX were identified using conditional logistic regression analysis.Results Sixteen patients and 64 controls were included in this study. Baseline demographic and laboratory data were compared. Patients in the AVF dysfunction group had lower levels of postoperative calcium than the controls. After surgery, calcium levels decreased more in patients with AVF dysfunction than in the control group. The decrease in systolic blood pressure (ΔSBP) after PTX was greater in the AVF dysfunction group than that in the control group. For each 1 mmHg increment in ΔSBP, the risk of AVF dysfunction after surgery increased by 11.6% (OR = 1.116, 95% CI, 1.005–1.239, p = .040). The likelihood of developing AVF dysfunction after surgery was twelvefold higher in diabetic patients than in non-diabetic patients (OR = 12.506, 95% CI, 1.113–140.492, p = .041). Among patients with ΔSBP > 5.8 mmHg after PTX, the AVF failure rate was significantly greater in patients with diabetes than in those without diabetes. Patients with a history of AVF failure had a nine-fold higher risk of developing AVF dysfunction (OR = 9.143, 95% CI, 1.151–72.627, p = .036). Serum albumin, hemoglobin, ΔiPTH, and age were not independent predictors of AVF dysfunction. The cutoff value for SBP was 5.8 mmHg, as determined by the Youden index of the receiver operating characteristic curve.Conclusion Decreased systolic blood pressure (ΔSBP) after PTX, diabetes, and AVF failure history were risk factors for AVF dysfunction following PTX in patients with SHPT. Diabetes patients with ΔSBP > 5.8 mmHg were more prone to AVF dysfunction after PTX.
Abstract Objectives To establish a predictive model for sepsis after percutaneous nephrolithotomy (PCNL) using machine learning to identify high-risk patients and enable early diagnosis and intervention by urologists. Methods A retrospective study including 694 patients who underwent PCNL was performed. A predictive model for sepsis using machine learning was constructed based on 22 preoperative and intraoperative parameters. Results Sepsis occurred in 45 of 694 patients, including 16 males (35.6%) and 29 females (64.4%). Data were randomly segregated into an 80% training set and a 20% validation set via 100-fold Monte Carlo cross-validation. The variables included in this study were highly independent. The model achieved good predictive power for postoperative sepsis (AUC = 0.89, 87.8% sensitivity, 86.9% specificity, and 87.4% accuracy). The top 10 variables that contributed to the model prediction were preoperative midstream urine bacterial culture, sex, days of preoperative antibiotic use, urinary nitrite, preoperative blood white blood cell (WBC), renal pyogenesis, staghorn stones, history of ipsilateral urologic surgery, cumulative stone diameters, and renal anatomic malformation. Conclusion Our predictive model is suitable for sepsis estimation after PCNL and could effectively reduce the incidence of sepsis through early intervention.
Zohreh Gholizadeh Ghozloujeh, Tripti Singh, Kenar D. Jhaveri
et al.
Lupus nephritis (LN), a severe complication of systemic lupus erythematosus (SLE), leads to significant kidney inflammation and damage and drastically increases mortality risk. Predominantly impacting women in their reproductive years, LN poses specific risks during pregnancy, including pre-eclampsia, growth restrictions, stillbirth, and preterm delivery, exacerbated by lupus activity, specific antibodies, and pre-existing conditions like hypertension. Effective management of LN during pregnancy is crucial and involves carefully balancing disease control with the safety of the fetus. This includes pre-conception counseling and a multidisciplinary approach among specialists to navigate the complexities LN patients face during pregnancy, such as distinguishing LN flare-ups from pregnancy-induced conditions. This review focuses on exploring the complex dynamics between pregnancy and LN, emphasizing the management difficulties and the heightened risks pregnant women with LN encounter.
Anoop Sheshadri, Jessica R. Elia, Gabriel Garcia
et al.
Rationale & Objective: Despite guidelines calling to improve physical activity in older adults, and evidence suggesting that prekidney transplant physical function is highly associated with posttransplant outcomes, only a small percentage of older patients treated with dialysis are engaged in structured exercise. We sought to elucidate barriers and facilitators of exercise among older adults treated with dialysis awaiting transplant and their care partners. Study Design: Individual, in-depth, cognitive interviews were conducted separately for patients and care partners through secure web-conferencing. Setting & Participants: Twenty-three patients (≥50 years of age, treated with dialysis from the University of San Francisco kidney transplantation clinic, with a short physical performance battery of ≤10) and their care partners. Analytical Approach: All audio interviews were transcribed verbatim. Three investigators independently coded data and performed qualitative thematic content. The interview guide was updated iteratively based on the Capability Opportunity Motivation Behavior model. Results: Patients’ median age was 60 years (57 ± 63.5) and care partners’ median ages was 57 years (49.5 ± 65.5). Thirty-nine percent of patients and 78% of care partners were female, 39% of patients and 30% of care partners self-identified as African American, and 47% of dyads were spouse or partner relationships. Major themes for barriers to pretransplant exercise included lack of understanding of an appropriate regimen, physical impairments, dialysis schedules, and safety concerns. Major facilitators included having individualized or structured exercise programs, increasing social support for patients and care partners, and motivation to regain independence or functionality or to promote successful transplantation. Limitations: Participants geographically limited to Northern California. Conclusions: Although patients and care partners report numerous barriers to pretransplant exercise and activity, they also reported many facilitators. An individualized, structured, home-based exercise program could circumvent many of the reported barriers and allow older patients to improve pretransplant physical function. Plain-Language Summary: Although exercise can improve the fitness of older adults treated with dialysis for kidney transplantation and reduce posttransplant complications, many such individuals do not exercise. We sought to elicit perspectives on barriers and facilitators to prekidney transplant exercises from older adults treated with dialysis and their care partners. We found that although patients and care partners had unique perspectives, they shared many barriers (such as physical and/or cognitive impairment, difficulty scheduling around dialysis, lack of guidance on exercise, and reduced exercise motivation related to dialysis) and several facilitators (such as desire to regain functionality and participate in life and motivation for successful transplantation). A shared interest among patients and care partners in joint participation in structured and home-based exercise may represent a tool to overcome barriers to pretransplant exercise.
Moni Roy MD, FACP, Joseph Y. Kim MD, PhD, Rone-Chun Lin MD
Multiple simultaneous opportunistic infections in Human Immunodeficiency virus-1/Acquired immunodeficiency syndrome (HIV-1/AIDS) is a known and dreaded occurrence that often leads to poor outcomes. We present a case of disseminated aspergillosis and active Hepatitis-B virus (HBV) infection in such a host, where cell free DNA (cfDNA) next generation sequencing (NGS) of plasma was used to expedite diagnosis. Bronchoscopy was avoided and treatment was started expeditiously. In this case report we discuss the interpretation of the cfDNA NGS, and its potential role for early diagnosis and avoidance of invasive testing.
Michele Scialpi, Antonio Improta, Danilo Delli Carpini
et al.
Computed tomography has been considered the preferred imaging modality for the surveillance of patients with testicular tumors (TTs) following radical orchiectomy. However, because of the concerns of frequent radiation exposure and intravenous iodinated contrast, biparametric magnetic resonance imaging (bpMRI) is a valid and safer alternative in the surveillance of patients with TT, instead of multiparametric magnetic resonance imaging. In this review article, we propose a protocol algorithm that utilizes bpMRI in the evaluation of patients after radical orchiectomy for TTs.
Cite this article as: Scialpi M, Improta A, Carpini DD, Tonto M, Nicola R, Mancioli F. Biparametric magnetic resonance imaging in the surveillance of testicular tumors following radical orchiectomy. Turk J Urol 2020; 46(6): 436-41.
AbstractThe present review provides an update about the major achievements and recent advances of immunotherapy in renal cell carcinoma, urothelial carcinoma, and prostate cancer. Although the treatment strategy for renal cell carcinoma and urothelial carcinoma includes traditional cancer immunotherapies, such as interleukin‐2 and interferon‐alfa, the clinical outcomes of these therapies are unsatisfactory. In recent years, the development of immune checkpoint inhibitors has drastically changed the treatment strategy for various cancers, including genitourinary cancer. The present review summarizes the approved cancer immunotherapies for renal cell carcinoma, urothelial carcinoma and prostate cancer. Furthermore, we review the response evaluation and biomarkers for immune checkpoint inhibitors with a distinctive mode of action that is different from cytotoxic agents. Finally, future perspectives for cancer immunotherapy are discussed.
Our previous study found that plate factor-4 variant (CXCL4L1) was downregulated in the serum of patients with prostate cancer (PCa). The aim of the present study was to investigate the prognostic value of CXCL4L1 in PCa. In total, 213 PCa patients treated with radical prostatectomy were enrolled and peripheral blood samples of all patients were collected. Expression of serum CXCL4L1 in patients with different tumor stages and grades were measured by enzyme-linked immunosorbent assay (ELISA). The Kaplan–Meier method was applied to estimate the progression to castration-resistant prostate cancer (CRPC), metastasis, biochemical recurrence (BCR)-free survival, and overall survival (OS). Prognostic factors for BCR-free survival and OS were determined by univariate and multivariate analyses using the Cox proportional hazards regression model. The expression of CXCL4L1 was significantly lower in PCa patients with advanced pathological tumor stage, high-grade Gleason score, and metastasis. Moreover, downregulation of CXCL4L1 not only strongly correlated with aggressive clinicopathological features, but also predicted tumor progression and unfavorable outcomes. Finally, multivariate Cox regression analyses identified CXCL4L1 as an independent prognostic factor for both BCR-free survival (hazard ratio [HR]: 2.03, 95% confidence interval [CI]: 1.26–3.27; P = 0.004) and OS (HR: 2.26, 95% CI: 1.07–4.79; P = 0.033). In conclusion, our results indicate that CXCL4L1 might serve as a novel and promising prognostic biomarker for patients with PCa and potential therapeutic target in the future.
Jonathan W. Goldman, Basmah Abdalla, Melody A. Mendenhall
et al.
Abstract Background The management of malignancy post kidney transplantation includes reduction in immunosuppression and referral to an oncologist management of their malignancy. Recent advances in oncology have resulted in the approval of several classes of drugs with immune-modulatory activity. However, activation of the immune system against malignant cells may precipitate allograft rejection in solid organ transplant recipients. Case presentation Herein we present a case of acute kidney allograft rejection in a 50 year old man following administration of the novel immune-modulatory agent nivolumab for the treatment of metastatic squamous cell carcinoma. Conclusion The management of malignancy in solid organ transplant recipients requires a heightened awareness of the potential for allograft rejection in this new era of cancer therapeutics.
Abstract Background End stage renal disease (ESRD) is on the rise globally. Varicella infection among adult patients with ESRD has been reported to lead to multiple complications and even death. While varicella vaccination has been recommended in paediatric renal patients; recommendation on varicella vaccination among adult patients with ESRD remained sparse. This review is aimed at evaluating the impact of varicella infection among adult patients with ESRD and make a recommendation for vaccination. Methods Three databases (PubMed, Embase and Cumulative Index to Nursing and Allied Health Literature (CINAHL)) were searched in April 2018 with keywords ‘varicella, chronic kidney failure, chronic kidney disease, renal replacement therapy, kidney transplantation, end stage renal disease, end stage renal failure, chicken pox, vaccine, vaccination and complications’. Results 29 articles were selected for review. The studies were mainly case reports, and they included measured outcomes: prevalence of seronegativity, impact (morbidity, length of stay, and mortality) of varicella among patients with ESRD, seroconversion rates and safety of varicella vaccination. The prevalence of seronegativity among varicella-infected ESRD adults was found to be at 42 to 100%. Nineteen deaths were reported. At least 54 patients have had complications from varicella infection. Seroconversion rate post vaccination was found to be around 64–94%. Conclusion Varicella is associated with significant morbidity and mortality rates in adult patients with ESRD. Varicella vaccination should be considered for the vulnerable, seronegative patients.
The aim of this study was to define the clinical significance of transurethral resection of the prostate (TURP) in patients with benign prostate hyperplasia (BPH) and an elevated prostate-specific antigen (PSA) level.
Methods:: We retrospectively evaluated patients with BPH, lower urinary tract symptoms (LUTS; International Prostate Symptom Score [IPSS] ≥ 8), an elevated serum PSA level (≥ 4 ng/mL), and previous negative transrectal ultrasonography (TRUS) guided prostate biopsy. The PSA level after TURP was monitored by long-term follow-up. The tumor detection rate on resected prostate tissue, IPSS, maximal urinary flow rate (Qmax), and postvoid residual urine (PVR) were analyzed.
Results: One-hundred and eighty-six patients were enrolled. Histological examination of resected tissue by TURP revealed prostate cancer in 12 of these patients (6.5%). Among 174 patients without prostate cancer, the mean PSA level and the PSA normalization rate in 112 patients followed up at postoperative day (POD) 3 months were 1.26 ± 0.13 ng/mL and 94.6%, respectively. The mean PSA level and the PSA normalization rate were 1.28 ± 1.01 ng/mL and 95.7% in 47 patients at 1st year, 1.17 ±0.82 ng/mL and 97.1% in 34 patients at second years, and 1.34 ± 1.44 ng/mL and 97.2% in 36 patients at third years of TURP. One patient showed a dramatic increase in the PSA level was diagnosed with prostate cancer at 7 years after TURP. IPSS, quality of life, Qmax, and PVR were improved significantly at POD 3 months compared to baseline (P <0.05), respectively.
Conclusions: TURP significantly reduced the serum PSA level, which was maintained for at least 3 years. This could be helpful to screen the prostate cancer using PSA value in the patient with previous negative biopsy and elevated PSA. In addition, TURP improves IPSS, Qmax, and PVR in patients with BPH, moderate LUTS, and an elevated PSA level.
Shingo Hatakeyama, Hayato Yamamoto, Akiko Okamoto
et al.
The oral adsorbent AST-120 has the potential to delay dialysis initiation and improve survival of patients on dialysis. We evaluated the effect of AST-120 on dialysis initiation and its potential to improve survival in patients with chronic kidney disease. The present retrospective pair-matched study included 560 patients, grouped according to whether or not they received AST-120 before dialysis (AST-120 and non-AST-120 groups). The cumulative dialysis initiation free rate and survival rate were compared by the Kaplan-Meier method. Multivariate analysis was used to determine the impact of AST-120 on dialysis initiation. Our results showed significant differences in the 12- and 24-month dialysis initiation free rate (P<0.001), although no significant difference was observed in the survival rate between the two groups. In conclusion, AST-120 delays dialysis initiation in chronic kidney disease (CKD) patients but has no effect on survival. AST-120 is an effective therapy for delaying the progression of CKD.
Shashikant Mishra, Rajan Sharma, Chandra Prakash Garg
et al.
Background : There are no Indian data of high-intensity focused ultrasound (HIFU). Being an alternative, still experimental modality, reporting short-term safety outcome is paramount.
Aims : This study was aimed at to assess the safety and short-term outcome in patients with prostate cancer treated by HIFU.
Settings and Design : A retrospective study of case records of 30 patients undergoing HIFU between January 2008 to September 2010 was designed and conducted.
Materials and Methods : The procedural safety was analyzed at 3 months. Follow-up consisted of 3 monthly prostate-specific antigen (PSA) levels and transrectal biopsy if indicated. All the patients had a minimum follow-up of 6 months.
Results : A mean prostate volume of 26.9 ± 8.5 cm 3 was treated in a mean time of 115 ± 37.4 min. There was no intraoperative complication. The postoperative pain visual analogue score at day 0 was 2.1 ± 1.9 and at day 1 was 0.4 ± 0.8 on a scale of 1-10. Mean duration of perurethral catheter removal was 3.9 days. The complications after treatment were: LUTS in seven patients, stress incontinence in two, stricture in two, and symptomatic urinary tract infection in five. Average follow-up duration was 10.4 months (range, 6-20 months). Mean time to obtain PSA nadir was 6 ± 3 months with a median PSA nadir value of 0.3 ng/ml. Two patients had positive prostatic biopsy in the localized (high risk) group.
Conclusions : HIFU was safe in carcinoma prostate patients. The short-term results were efficacious in localized disease. The low complication rates and favorable functional outcome support the planning of further larger studies.