In human nephrectomy specimens, the kidney level of tubular transport proteins does not correlate with their abundance in urinary extracellular vesicles.

Human urinary extracellular vesicles (uEVs) contain proteins from all nephron segments. An assumption for years has been that uEVs might provide a noninvasive liquid biopsy that reflect physiological regulation of transporter protein expression in humans. We hypothesized that protein abundance in human kidney tissue and uEVs are directly related and tested this in paired collections of nephrectomy tissue and urine sample from 12 patients. Kidney tissue was fractioned into total kidney protein, crude membrane (plasma membrane and large intracellular vesicles)-enriched, and intracellular vesicle-enriched fractions as well as sections for immunolabeling. uEVs were isolated from spot urine samples. Antibodies were used to quantify six segment-specific proteins [proximal tubule-expressed Na+-phosphate cotransporters (NaPi-2a), thick ascending limb-expressed Tamm-Horsfall protein and renal outer medullary K+ channels, distal convoluted tubule-expressed NaCl cotransporters, intercalated cell-expressed V-type H+-ATPase subunit G3 (ATP6V1G3), and principal cell-expressed aquaporin 2] and three uEV markers (exosomal CD63, microvesicle marker vesicle-associated membrane protein 3, and ß-actin) in each fraction. By Western blot analysis and immunofluorescence labeling, we found significant positive correlations between the abundance of CD63, NaCl cotransporters, aquaporin 2, and ATP6V1G3, respectively, within the different kidney-derived fractions. We detected all nine proteins in uEVs, but their level did not correlate with kidney tissue protein abundance. uEV protein levels showed higher interpatient variability than kidney-derived fractions, indicating that factors, besides kidney protein abundance, contribute to the uEV protein level. Our data suggest that, in a random sample of nephrectomy patients, uEV protein level is not a predictor of kidney protein abundance.

Cytoreductive Nephrectomy in Select Primary Metastatic Renal Cell Carcinoma Patients: A Comprehensive Nationwide Outcome Analysis.

(1) Background: The role of cytoreductive nephrectomy (CN) is controversial in patients with primary metastatic renal cell carcinoma (mRCC). (2) Methods: We evaluated the impact of CN, or no CN, followed by first-line targeted therapy (TT) in a nationwide unselected cohort of 437 consecutive patients with primary mRCC over a two-year period with a minimum of five years of follow-up. Data sources were national registries supplemented with manually extracted information from individual patient medical records. Cox proportional hazards estimated the hazard ratio (HR) of overall death and cancer-specific death after one and three years. (3) Results: 210 patients underwent CN and 227 did not. A total of 176 patients (40%) had CN followed by TT, 160 (37%) had TT alone, 34 (8%) underwent CN followed by observation, and 67 (15%) received no treatment. After adjustments in Model 2, patients treated with TT alone demonstrated a worsened overall survival (OS) compared to those treated with CN + TT, HR 0.63 (95% CI: 0.19-2.04). (4) Conclusions: In this nationwide study, CN was associated with enhanced outcomes in carefully selected patients with primary mRCC. Further randomized trials are warranted.

Lifestyle and Clinical Factors in a Nationwide Stage III and IV Renal Cell Carcinoma Study.

BACKGROUND: The aim was to investigate whether patient-related or clinical risk factors present at the diagnosis of advanced stage renal cell carcinoma (RCC) had an impact on the overall mortality, cancer-specific mortality, and recurrence risk in a national cohort. METHODS: Patients registered with stage III and IV RCC in the Danish Renal Cancer Database (DaRenCa) in 2014-2016 were included in the study and followed up until recurrence or death. We conducted a Cox Proportional Hazard Model to examine the association between several variables and the development of RCC. These variables included BMI, hypertension, smoking status, symptoms at diagnosis, performance status, multidisciplinary team (MDT) discussion, surgical margin, and primary metastasis. Separate analyses were performed for cc-RCC and non-ccRCC patients. RESULTS: In our cohort of 929 patients, 424 individuals died from RCC during the follow-up period, with a median follow-up time of 4.1 (95% CI: 0.8-5.0) years for ccRCC and 2.0 (95% CI: 0.1-5.0) years for non-ccRCC. A multivariate analysis demonstrated that a positive surgical margin (HR 1.53 and 1.43), synchronous metastasis (HR 2.06 and 3.23), and poor performance status (HR 4.73 and 5.27) were significantly associated with a decreased 5-year overall and cancer-specific survival, respectively. Furthermore, a positive surgical margin was associated with a higher risk of recurrence in ccRCC. MDT discussion was found to reduce mortality risk in non-ccRCC. CONCLUSION: Clinical- and disease-related variables have a greater impact on RCC mortality and recurrence than the selected lifestyle-related factors. The inclusion of MDT discussion in the diagnosis and management of advanced RCC should be further evaluated for its potential to improve patient outcomes.

Circulating Tumor DNA in Patients with Renal Cell Carcinoma. A Systematic Review of the Literature.

CONTEXT: Over the past decade there has been increasing interest in the potential of liquid biopsies and systematic biomarkers in the diagnosis and management of kidney cancer, as they may provide a tool for early detection of disease and monitoring of treatment response. OBJECTIVE: To identify and summarize relevant published data on circulating tumor DNA (ctDNA) in patients with renal cell carcinoma (RCC). EVIDENCE ACQUISITION: We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement of studies identified in PubMed, MEDLINE, EMBASE, and Cochrane Library up to January 15, 2021. Two reviewers independently screened all articles and performed the data extraction. EVIDENCE SYNTHESIS: Nineteen studies investigating ctDNA in RCC (1237 patients) were included and analyzed in the final review. The study size and design varied widely, and the studies were divided into five groups according to the method used for ctDNA detection. The outcome data included (1) the sensitivity/specificity if available; (2) the method used for ctDNA detection; and (3) the main findings in the studies. CONCLUSIONS: The studies highlight that the level of ctDNA in RCC appears to be low. Studies using multiple methods for ctDNA detection indicate that tumor-guided analysis improves the ctDNA detection rate and suggest that cell-free methylated DNA immunoprecipitation and high-throughput sequencing may be a very sensitive method for ctDNA detection in RCC. PATIENT SUMMARY: We systematically reviewed the literature to identify all relevant studies investigating circulating tumor DNA in patients with kidney cancer to investigate its use and potential in this highly malignant disease. We found that the level of circulating tumor DNA is low in kidney cancer and that very sensitive methods have to be used for detection in this disease.

Incidence and Associated Risk Factors of Venous Thromboembolism After Open and Laparoscopic Nephrectomy in Patients Administered Short-period Thromboprophylaxis: A Danish Nationwide Population-based Cohort Study.

OBJECTIVE: To report the incidence of venous thromboembolism (VTE) after nephrectomy in Denmark and explore associated risk factors. MATERIALS AND METHODS: A nationwide population-based retrospective cohort study was performed. All nephrectomies from January 2010 to August 2018 were assessed for postoperative VTE events. Univariable and multivariable analyses were used to evaluate the odds ratio (OR) of clinical variables' effect on postoperative VTEs, within 4 weeks and 4 months after nephrectomy. RESULTS: In 5213 nephrectomized patients, postoperative VTE incidence was 1% and 2% within 4 weeks and 4 months, respectively. Multivariable analyses revealed that predictors of postoperative VTE within 4 months were: open nephrectomy (OR 2.5, P = .001), history of VTE (OR 13.3, P <.001), length of hospital stay (OR 0.98, P = .02), and lymph node dissection (OR 2.0, P = .04). Limitations included the retrospective and registry-based study design and absence of individual patient data on patient body mass index and length of surgery. CONCLUSION: For nephrectomy, postoperative VTE is rare. Open nephrectomy, history of VTE, length of hospital stay, and lymph node dissection are important risk factors which should be evaluated when tailoring VTE prophylaxis regimens.

Cutaneous metastases in renal cell carcinoma: a systematic review and a case report.

Objective: Cutaneous metastases of renal cell carcinoma (C.M.R.C.C.) are rare and associated with a poor prognosis. The aim of this study is to evaluate the incidence and the prognosis of C.M.R.C.C. with a relevant case report. Materials and methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (P.R.I.S.M.A.) of existing literature in English and Scandinavian languages was used in t​​he period 1902-2017 with a literature search in PubMed, Embase, and Cochrane Library. Results: Nine original articles were found where the incidence of a C.M.R.C.C. was 3.3% (168/5017). In order to estimate the prognosis of C.M.R.C.C., 161 articles were found with a total of 334 cases. Survival was described in 40% of all cases (132/334). In 31% (102/334) of the cases the final time of death was stated and in this group the mean survival was 10.9 months. Ninety-six per cent died within 36 months after being diagnosed with C.M.R.C.C. Conclusion: C.M.R.C.C. are rare with an incidence of 3.3%. The prognosis is poor with a high mortality. It is suggested that the skin should be examined in the diagnostic evaluation and follow-up for patients with renal cell carcinoma.

[Metastasis in testis from prostate cancer].

We present a case of an 89-year-old male diagnosed with a prostatic adenocarcinoma. He developed a metastasis to his left testis and was treated with bilateral orchiectomy. Histology showed a ductal adenocarcinoma with positive immunohistochemical markers for PSA and p501. Testicular metastases from prostate cancer are rare and are assumed to be associated with progressed disease and poor prognosis. Ductal adenocarcinomas may be associated with a higher risk of dissemination to the testis.