Impact of Aging on Urinary Natriuretic Peptides in Nocturia and Nocturnal Polyuria

Lakshay Khosla,Joseph U. Boroda,Joshua Salama,Syed N. Rahman,Danielle J. Gordon,Matthew W. Moy,Yonatan Akivis,Alla Akivis,Jason M. Lazar,Jeffrey P. Weiss,Lori A. Birder 대한배뇨장애요실금학회 2022 International Neurourology Journal Vol.26 No.2

Purpose: The pathophysiology of nocturia and nocturnal polyuria (NP), conditions that become more prevalent with aging, may in part be explained by changes in hormones involved in water homeostasis. The purpose of this study was to analyze the impact of aging on urinary natriuretic peptides in nocturia and NP. Methods: Patients aged ≥18 years completed 24-hour bladder diaries for assessment of nocturia and NP. They were divided into subgroups of ≥65 years old and <65 years old. Urine samples were collected and analyzed for natriuretic peptide (NTproANP, NT-proBNP, and NT-proCNP) levels. Peptide levels were compared between patients with and without nocturia/NP and within age subgroups; correlation to the NP index (NPi) was determined. Results: Compared to patients without nocturia (N=15), patients with nocturia (N=36) had higher median levels of urinary NT-proANP (15.8 pmol/mmol Cr vs. 10.9 pmol/mmol Cr, P=0.016) and NT-proBNP (6.3 pmol/mmol Cr vs. 4.5 pmol/mmol Cr, P=0.021), but showed no differences in NT-proCNP (2.4 pmol/mmol Cr vs. 2.5 pmol/mmol Cr, P=0.967). Patients ≥65 years old with nocturia had higher NT-proANP (29.8 pmol/mmol Cr vs. 11.0 pmol/mmol Cr, P<0.001) and NT-proBNP (9.6 pmol/mmol Cr vs. 5.0 pmol/mmol Cr, P<0.001) than patients <65 years old. Additionally, patients with NP (N=30) showed higher urinary NT-proANP (19.6 pmol/mmol Cr vs. 10.5 pmol/mmol Cr, P<0.001) and NT-proBNP (6.7 pmol/mmol Cr vs. 4.7 pmol/mmol Cr, P=0.020) compared to patients without NP (N=21). NP patients ≥65 years had higher NT-proANP (29.8 pmol/mmol Cr vs. 12.5 pmol/mmol Cr, P<0.001) and NT-proBNP (9.6 pmol/mmol Cr vs. 4.4 pmol/mmol Cr, P=0.004) than patients <65 years old. NPi positively correlated with urinary NT-proANP (RS=0.417, P=0.002) and NT-proBNP (RS=0.303, P=0.031), but not with NT-proCNP (RS=-0.094, P=0.510). Conclusions: Since urinary NT-proANP and NT-proBNP were greater in aged patients with nocturia and NP, natriuretic peptides may contribute to the pathophysiology of these conditions and further research should aim to explore them as targets for management.

Application of the Sleep C.A.L.M. Tool for Assessing Nocturia in a Large Nationally Representative Cohort

Joseph U. Boroda,Benjamin De Leon,Lakshay Khosla,Muchi D. Chobufo,Syed N. Rahman,Jason M. Lazar,Jeffrey P. Weiss,Thomas F. Monaghan 대한배뇨장애요실금학회 2024 International Neurourology Journal Vol.28 No.-

Purpose: Nocturia significantly impacts patients’ quality of life but remains insufficiently evaluated and treated. The “Sleep C.A.L.M.” system categorizes the factors thought to collectively reflect most underlying causes of nocturia (Sleep disorders, Comorbidities, Actions [i.e., modifiable patient behaviors such as excess fluid intake], Lower urinary tract dysfunction, and Medications). The purpose of this study was to assess the association of nocturia with the Sleep C.A.L.M. categories using a nationally representative dataset. Methods: Retrospective analysis of the National Health and Nutrition Examination Survey from 2013/14–2017/18 cycles was conducted. Pertinent questionnaire, laboratory, dietary, and physical examination data were used to ascertain the presence of Sleep C.A.L.M. categories in adults ≥20 years of age. Nocturia was defined as ≥2 nighttime voids. Results: A total of 12,274 included subjects were included (51.6% female; median age, 49.0 years [interquartile range, 34.0–62.0 years]; 27.6% nocturia). Among subjects with nocturia, the prevalence of 0, ≥1, and ≥2 Sleep C.A.L.M. categories was 3.5% (95% confidence interval [CI], 2.8%–4.4%), 96.5% (95% CI, 95.6%–97.2%), and 81.2% (95% CI, 78.9%–83.3%), respectively. Compared to those with 0–1 Sleep C.A.L.M. categories, the adjusted odds of nocturia in subjects with 2, 3, and 4–5 Sleep C. A.L.M. categories were 1.77 (95% CI, 1.43–2.21), 2.33 (1.89–2.87), and 3.49 (2.81–4.35), respectively (P<0.001). Similar trends were observed for most age and sex subgroups. When assessed individually, each of the 5 Sleep C.A.L.M. categories were independently associated with greater odds of nocturia, which likewise persisted across multiple age and sex subgroups. Conclusions: Sleep C.A.L.M. burden is associated with increased odds of nocturia in a dose-dependent fashion, and potentially a relevant means by which to organize the underlying etiologies for nocturia among community-dwelling adults.

Clinical and biochemical outcomes of men undergoing radical prostatectomy or radiation therapy for localized prostate cancer

Schreiber, David,Rineer, Justin,Weiss, Jeffrey P.,Safdieh, Joseph,Weiner, Joseph,Rotman, Marvin,Schwartz, David The Korean Society for Radiation Oncology 2015 Radiation Oncology Journal Vol.33 No.1

Purpose: We analyzed outcomes of patients with prostate cancer undergoing either radical retropubic prostatectomy (RRP) +/- salvage radiation or definitive radiation therapy (RT) +/- androgen deprivation. Materials and Methods: From 2003-2010 there were 251 patients who underwent RRP and 469 patients who received RT (${\geq}7,560cGy$) for prostate cancer. Kaplan-Meier analysis was performed with the log-rank test to compare biochemical control (bCR), distant metastatic-free survival (DMPFS), and prostate cancer-specific survival (PCSS) between the two groups. Results: The median follow-up was 70 months and 61.3% of the men were African American. For low risk disease the 6-year bCR were 90.3% for RT and 85.6% for RRP (p = 0.23) and the 6-year post-salvage bCR were 90.3% vs. 90.9%, respectively (p = 0.84). For intermediate risk disease the 6-year bCR were 82.6% for RT and 59.7% for RRP (p < 0.001) and 82.6% vs. 74.0%, respectively, after including those salvaged with RT (p = 0.06). For high risk disease, the 6-year bCR were 67.4% for RT and 41.3% for RRP (p < 0.001) and after including those salvaged with RT was 67.4% vs. 43.1%, respectively (p < 0.001). However, there were no significant differences between the two groups in regards to DMPFS or PCSS. Conclusion: Treatment approaches utilizing RRP +/- salvage radiation or RT +/- androgen deprivation yielded equivalent DMPFS and PCSS outcomes. Biochemical control rates, using their respective definitions, appeared equivalent or better in those who received treatment with RT.

Clinical and biochemical outcomes of men undergoing radical prostatectomy or radiation therapy for localized prostate cancer

David Schreiber,Justin Rineer,Jeffrey P. Weiss,Joseph Safdieh,Joseph Weiner,Marvin Rotman,David Schwartz 대한방사선종양학회 2015 Radiation Oncology Journal Vol.33 No.1

Purpose: We analyzed outcomes of patients with prostate cancer undergoing either radical retropubic prostatectomy (RRP) +/– salvage radiation or definitive radiation therapy (RT) +/– androgen deprivation. Materials and Methods: From 2003–2010 there were 251 patients who underwent RRP and 469 patients who received RT (≥7,560 cGy) for prostate cancer. Kaplan-Meier analysis was performed with the log-rank test to compare biochemical control (bCR), distant metastatic-free survival (DMPFS), and prostate cancer-specific survival (PCSS) between the two groups. Results: The median follow-up was 70 months and 61.3% of the men were African American. For low risk disease the 6-year bCR were 90.3% for RT and 85.6% for RRP (p = 0.23) and the 6-year post-salvage bCR were 90.3% vs. 90.9%, respectively (p = 0.84). For intermediate risk disease the 6-year bCR were 82.6% for RT and 59.7% for RRP (p < 0.001) and 82.6% vs. 74.0%, respectively, after including those salvaged with RT (p = 0.06). For high risk disease, the 6-year bCR were 67.4% for RT and 41.3% for RRP (p < 0.001) and after including those salvaged with RT was 67.4% vs. 43.1%, respectively (p < 0.001). However, there were no significant differences between the two groups in regards to DMPFS or PCSS. Conclusion: Treatment approaches utilizing RRP +/– salvage radiation or RT +/– androgen deprivation yielded equivalent DMPFS and PCSS outcomes. Biochemical control rates, using their respective definitions, appeared equivalent or better in those who received treatment with RT.

Oxidative Stress Biomarkers in Age-Related Lower Urinary Tract Disorders: A Systematic Review

Lakshay Khosla,Susan Gong,Jeffrey P. Weiss,Lori A. Birder 대한배뇨장애요실금학회 2022 International Neurourology Journal Vol.26 No.1

Purpose: To conduct a systematic review of preclinical and clinical peer-reviewed evidence linking alterations in oxidative stress biomarkers or outcome measures that were also prevalent in specific age-related lower urinary tract (LUT) disorders. Methods: PubMed, Scopus, CINAHL, and Embase were searched for peer-reviewed studies published between January 2000 and March 2021. Animal and human studies that reported on the impact of oxidative stress in age-related LUT disorders through structural or functional changes in the LUT and changes in biomarkers were included. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) protocol was followed. Results: Of 882 articles identified, 21 studies (13 animal; 8 human) met inclusion criteria. Across LUT disorders, common structural changes were increased bladder and prostate weights, ischemic damage, nerve damage and detrusor muscle hypertrophy; common functional changes included decreased bladder contraction, increased bladder sensation and excitability, decreased perfusion, and increased inflammation. The disorders were associated with increased levels of biomarkers of oxidative stress that provided evidence of either molecular damage, protective mechanisms against oxidative stress, neural changes, or inflammation. In all cases, the effect on biomarkers and enzymes was greater in aged groups compared to younger groups. Conclusions: Increased oxidative stress, often associated with mitochondrial dysfunction, plays a significant role in the pathogenesis of age-related LUT disorders and may explain their increasing prevalence. This systematic review identifies potential markers of disease progression and treatment opportunities; further research is warranted to evaluate these markers and the mechanisms by which these changes may lead to age-related LUT disorders.

Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

Joseph J. Safdieh,David Schwartz,Joseph Weiner,Jeffrey P. Weiss,Justin Rineer,Isaac Madeb,Marvin Rotman,David Schreiber 대한방사선종양학회 2014 Radiation Oncology Journal Vol.32 No.3

Purpose: To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. Materials and Methods: The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003–2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. Results: The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). Conclusion: In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.

Long-term tolerance and outcomes for dose escalation in early salvage post-prostatectomy radiation therapy

Safdieh, Joseph J.,Schwartz, David,Weiner, Joseph,Weiss, Jeffrey P.,Rineer, Justin,Madeb, Isaac,Rotman, Marvin,Schreiber, David The Korean Society for Radiation Oncology 2014 Radiation Oncology Journal Vol.32 No.3

Purpose: To study the long-term outcomes and tolerance in our patients who received dose escalated radiotherapy in the early salvage post-prostatectomy setting. Materials and Methods: The medical records of 54 consecutive patients who underwent radical prostatectomy subsequently followed by salvage radiation therapy (SRT) to the prostate bed between 2003-2010 were analyzed. Patients included were required to have a pre-radiation prostate specific antigen level (PSA) of 2 ng/mL or less. The median SRT dose was 70.2 Gy. Biochemical failure after salvage radiation was defined as a PSA level >0.2 ng/mL. Biochemical control and survival endpoints were analyzed using the Kaplan-Meier method. Univariate and multivariate Cox regression analysis were used to identify the potential impact of confounding factors on outcomes. Results: The median pre-SRT PSA was 0.45 ng/mL and the median follow-up time was 71 months. The 4- and 7-year actuarial biochemical control rates were 75.7% and 63.2%, respectively. The actuarial 4- and 7-year distant metastasis-free survival was 93.7% and 87.0%, respectively, and the actuarial 7-year prostate cancer specific survival was 94.9%. Grade 3 late genitourinary toxicity developed in 14 patients (25.9%), while grade 4 late genitourinary toxicity developed in 2 patients (3.7%). Grade 3 late gastrointestinal toxicity developed in 1 patient (1.9%), and grade 4 late gastrointestinal toxicity developed in 1 patient (1.9%). Conclusion: In this series with long-term follow-up, early SRT provided outcomes and toxicity profiles similar to those reported from the three major randomized trials studying adjuvant radiation therapy.