Does hormonal therapy affect the bladder or the kidney in postmenopausal women with and without nocturnal polyuria: Results of a pilot trial?

AIM: To observe the impact of hormonal treatment (HT) on voiding patterns and renal circadian rhythms in postmenopausal women with and without nocturnal polyuria (NP). MATERIAL AND METHODS: A prospective, observational study was executed at the menopause clinic of a tertiary hospital. HT was based on patients' choice and was in the form of either oral and transdermal oestrogen. Participants completed a 72-hour bladder diary, completed the ICIQ-FLUTS questionnaire, recorded a renal function profile and gave a blood sample. This set of tests was done before and after 3 months of HT. RESULTS: 32 postmenopausal women with a median age of 52.5 (49.3-56.0) years were enroled in this study. Three months of HT resulted in a significant decrease in fluid intake (p < 0.001) and daytime voiding frequency (p = 0.019). No impact on nocturnal parameters was observed. Observations drawn from the questionnaires did not differ between the baseline and three-month assessments. HT led to a disappearance of the circadian rhythm of the diuresis rate and sodium clearance in patients without NP, as no significant difference between daytime and night-time values was observed (diuresis rate p = 0.3; sodium clearance p = 0.08). In patients with NP at baseline, HT did not induce a circadian rhythm of the diuresis rate and sodium clearance (p = 0.2; p = 0.7). In contrast, free water clearance did change to a clear circadian rhythm (p = 0.02). CONCLUSION: HT led to a significant reduction in both fluid intake and daytime frequency. In women without NP, HT led to a disruption of the circadian rhythms of water and salt diuresis. In patients with NP, a limited normalisation of the circadian rhythm of free water clearance was observed after three months of HT. CLINICAL TRIAL REGISTRATION NUMBER FROM CLINICALTRIALS.GOV: NCT04891926.

The effect of a multidisciplinary weight loss program on renal circadian rhythm in obese adolescents.

Adolescent obesity is a serious health problem associated with many comorbidities. Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is also disrupted in obesity, though this has not yet been investigated. This study aimed to examine renal circadian rhythm in obese adolescents before and after weight loss.In 34 obese adolescents (median age 15.7 years) participating in a residential weight loss program, renal function profiles and blood samples were collected at baseline, after 7 months, and again after 12 months of therapy. The program consisted of dietary restriction, increased physical activity, and psychological support. The program led to a median weight loss of 24 kg and a reduction in blood pressure. Initially, lower diurnal free water clearance (- 1.08 (- 1.40-- 0.79) mL/min) was noticed compared with nocturnal values (0.75 (- 0.89-- 0.64) mL/min). After weight loss, normalization of this inverse rhythm was observed (day - 1.24 (- 1.44-1.05) mL/min and night - 0.98 (- 1.09-- 0.83) mL/min). A clear circadian rhythm in diuresis rate and in renal clearance of creatinine, solutes, sodium, and potassium was seen at all time points. Furthermore, we observed a significant increase in sodium clearance. Before weight loss, daytime sodium clearance was 0.72 mL/min (0.59-0.77) and nighttime clearance was 0.46 mL/min (0.41-0.51). After weight loss, daytime clearance increased to 0.99 mL/min (0.85-1.17) and nighttime clearance increased to 0.78 mL/min (0.64-0.93).Conclusion: In obese adolescents, lower diurnal free water clearance was observed compared with nocturnal values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity. Both before and after weight loss, clear circadian rhythm of diuresis rate and renal clearance of creatinine, solutes, sodium, and potassium was observed.What is Known:• Obesity-related alterations in circadian rhythm have been described for nocturnal blood pressure and for metabolic functions. We believe renal circadian rhythm is disrupted in obesity, though this has not been investigated yet.What is New:• In obese adolescents, an inverse circadian rhythm of free water clearance was observed, with higher nighttime free water clearance compared with daytime values. Weight loss led to a normalization of this inverse rhythm, suggesting a recovery of the anti-diuretic hormone activity.• Circadian rhythm in diuresis rate and in the renal clearance of creatinine, solutes, sodium, and potassium was preserved in obese adolescents and did not change after weight loss.

An exploratory pilot study with copeptin as a biomarker for individualizing treatment for nocturnal polyuria.

OBJECTIVE: The aim of the present study was to investigate the use of random copeptin concentrations as possible biomarkers for the differential diagnosis of nocturnal polyuria (NP). METHODS: In all, 111 patients with and without nocturia were enrolled in the study. Patients with a neurogenic bladder and/or those who had undergone bladder or urethral surgery were excluded from the study. All patients completed a 72-hour frequency-volume chart and a renal function profile. A random blood sample was obtained during the day for measurement of plasma copeptin concentrations, osmolality, and serum sodium and creatinine concentrations. The effect of the use of different definitions for NP was evaluated. RESULTS: The median age of the study participants was 61 years, and 48% were female. Copeptin was significantly correlated with urinary and plasma osmolality, as well as free water clearance (r=0.43, 0.56 and -0.38 respectively; P < .001 for all). Study participants were divided into 3 groups: controls (n = 51), those with NP (n = 41), and those with global polyuria (n = 19). Copeptin concentrations were significantly lower in subjects with global polyuria than in those with NP and the control group (2.96 vs 3.97 and 3.94 pM, respectively; P = .008 and .005). There was no significant difference in random daytime copeptin concentrations between the NP and control groups (P = .972). The results differed when other definitions for NP were used (e.g. NPi33 or NUP10). CONCLUSIONS: We could not confirm our hypothesis that patients with NP have lower copeptin concentrations, although random blood sampling is not ideal. Further research is required to determine the use of copeptin in NP, perhaps in the identification of the desmopressin response.

Development of a multivariate prediction model for nocturia, based on urinary tract etiologies.

PURPOSE: The main objective of our study was to determine which combination of modifiable and non-modifiable parameters that could discriminate patients with nocturia from those without nocturia. This was a post-hoc analysis of 3 prospective, observational studies conducted in Ghent University. Participants completed frequency volume chart (FVC) to compare characteristics between patients with and without nocturia. METHOD: This was a post hoc analysis of three prospective, observational studies conducted in Ghent University. Participants completed frequency volume chart (FVC) to compare characteristics between adults with and without nocturia. Study 1: adults with and without nocturia (n = 148); Study 2: patients ≥65 years with and without nocturnal LUTS (n = 54); Study 3: menopausal women before and after hormone replacement therapy (n = 43). All eligible patients (n = 183) completed a FVC during 24 hours (n = 13), 48 hours (n = 30) or 72 hours (n = 140). The combination of algorithms and number of determinants obtaining the best average area under the receiver operating curve (AUC-ROC) led to the final model. Differences between groups were assessed using the AUC-ROC and Mann- Whitney-Wilcoxon tests. Holm corrections were applied for multiple statistical testing. Also, the stability of the feature selection was evaluated. RESULTS: The best discrimination was obtained when 13 determinants were included. However, a logistic regression model based on seven determinants selected with random forest had comparable discrimination including an optimal signature stability. It was able to discriminate almost perfectly between nights with and without nocturia. CONCLUSION: Relevant information to accomplish the excellent predictability of the model is; functional bladder capacity, 24 hours urine output, nocturnal output, age, BMI. The multivariate model used in this analysis provides new insights into combination therapy as it allows simulating the effect of different available treatment modalities and its combinations.

Pitfalls and opportunities in multidisciplinary research about nocturia in adults.

OBJECTIVES: Describe current shortcomings in clinical research on the treatment of nocturia in adults, and suggest new directions for future studies in this field. METHODS: A literature search was conducted using the keywords 'nocturia,' 'nocturnal polyuria,' 'sleep,' and 'hypertension.' RESULTS: Nocturia, or waking up at night to void, is a highly prevalent and bothersome lower urinary tract symptom (LUTS) affecting up to 40% of adults. Since the majority of patients are diagnosed with nocturnal polyuria (NP) as one of the underlying causes, it is not surprising that the effect of treatments for overactive bladder (OAB) and bladder outlet obstruction (BOO) are disappointing with regard to nocturia. Therefore, we suggest to conduct studies in which nocturic patients are treated according to the underlying pathophysiology: (1) antimuscarinics or ß3-agonists for OAB symptoms, (2) α-blockers or 5α-reductase inhibitors in men with BOO caused by enlarged prostates, (3) desmopressin or diuretics for NP, (4) continuous positive airway pressure in nocturic patients with obstructive sleep apnea, and (5) all its combinations in case of combined pathophysiology. Not only the effect on treatment efficacy or side effects needs to be assessed, but also the impact on related comorbidities such as sleep disorders, hypertension, and endocrine functions such as blood glucose regulation. CONCLUSION: Future research needs to subtype nocturic patients in order to adapt treatment according to the underlying cause.

Isolated Male Epispadias: Anatomic Functional Restoration Is the Primary Goal.

Background. Isolated male epispadias (IME) is a rare congenital penile malformation, as often part of bladder-exstrophy-epispadias complex (BEEC). In its isolated presentation, it consists in a defect of the dorsal aspect of the penis, leaving the urethral plate open. Occurrence of urinary incontinence is related to the degree of dorsal displacement of the meatus and the underlying underdevelopment of the urethral sphincter. The technique for primary IME reconstruction, based on anatomic restoration of the urethra and bladder neck, is here illustrated. Patients and Methods. A retrospective database was created with patients who underwent primary IME repair between June 1998 and February 2014. Intraoperative variables, postoperative complications, and outcomes were assessed. A descriptive statistical analysis was performed. Results and Limitations. Eight patients underwent primary repair, with penopubic epispadias (PPE) in 3, penile epispadias (PE) in 2, and glandular epispadias (GE) in 3. Median age at surgery was 13.0 months [7-47]; median follow-up was 52 months [9-120]. Complications requiring further surgery were reported in two patients, while further esthetic surgeries were required in 4 patients. Conclusion. Anatomical restoration in primary IME is safe and effective, with acceptable results given the initial pathology.