Urology

Lower urinary tract symptoms and metabolic disorders: ICI-RS 2014

Denys M-A, Anding R, Tubaro A, Abrams P, Everaert K. Lower urinary tract
symptoms and metabolic disorders: ICI-RS 2014. Neurourol Urodyn 2016; 35(2): 278–282

An overview of metabolic disorder impact on lower urinary tract symptoms

Neurology and Urodynamics has published an overview of the 2014 International Consultation on Incontinence Research Society (ICI-RS) congress in Bristol, highlighting the potential links between lower urinary tract symptoms (LUTS) and metabolic disorders.1

Global estimates of metabolic syndrome (MetS) prevalence range from <10–84%.1

LUTS and MetS share common pathophysiological determinants:1

• Impaired glucose handling
• Central obesity
• Arterial hypertension
• Microalbuminuria
• Dyslipidaemia.

Previous studies have shown a positive association between MetS, arterial hypertension and LUTS. Furthermore, the risk of developing LUTS is correlated with increased body mass index, waist size and weight gain.1

Modifiable lifestyle factors offer the opportunity to influence the development of LUTS.1

Circadian rhythm

Desynchronisation of the behavioural sleep-wake cycle and the biological circadian clock may increase the risk of both LUTS and MetS, according to recent animal and clinical studies.1

A master circadian clock in the hypothalamus regulates our daily rhythms of sleep, feeding behaviour, hormonal secretion and tissue metabolism. Light signals, conducted via the retino-hypothalamic tract, synchronise the master circadian clock with the daily sleep-wake cycle.1

Nocturnal polyuria can be caused by glycosuria. Glucose tolerance and risk of diabetes can be elevated by circadian rhythm disorders. During sleep, the brain is less aroused, urine production is decreased and the functional capacity of the bladder is increased compared with the awake period. Disruption of these circadian patterns is also associated with nocturnal LUTS.1

Furthermore, healthy adults show a 10–20% reduction in blood pressure during sleep; in patients with nocturia, the drop in sleep systolic blood pressure is significantly reduced.1

Areas of research highlighted as important for future study included:1

• Identification of the molecular mechanisms controlling the local circadian rhythms in the bladder and kidney.

Absence of a dip in sleep systolic blood pressure is predictive of overall mortality, cardiovascular mortality and cardiovascular events.1

Sleep

Deficiencies in sleep have been associated with metabolic diseases including obesity, hypertension and diabetes mellitus. Similarly, patients with poor baseline sleep quality and sleep restriction are at increased risk of LUTS, including nocturia and urinary incontinence. It is hypothesised that nocturia is a result rather than a cause of sleep disorders, as behavioural therapy for insomnia reduces nocturnal voiding.1

In patients with obstructive sleep apnoea syndrome, levels of atrial natriuretic peptide are elevated due to negative intrathoracic pressure, resulting in nocturnal enuresis and incontinence.1

Also suggested as areas for future study were:1

• The effect of sleep disorders/deprivation on LUTS
• The potential need to screen for/treat sleep disorders in patients with LUTS.

Renal function

Limited information is available on the relationship between MetS and urine production, and how this may impact LUTS.1

In obese patients, overactivity of the renin-angiotensin-aldosterone system, combined with sympathetic nervous system stimulation and physical compression of the kidneys, results in increased sodium reabsorption in the renal tubules leading to hypertension.1

Elevated glomerular pressure and renal plasma flow increases the filtration fraction, and may lead to proteinuria and ultimately, renal failure.1

In this area, potential future studies could include:1

• The association between diuresis and LUTS
• The mechanisms linking MetS, diuresis rate and LUTS.

Bladder function

Bladder capacity is modulated by levels of the gap junction protein, connexin-43, which sensitises the responsiveness of bladder smooth muscle to cholinergic stimulation. Increasing levels of connexin-43 reduces bladder capacity and increases urination frequency in rats. Levels of connexin-43 are controlled by a peripheral circadian clock in the bladder, altering bladder capacity to avoid disturbing sleep at night.1

Obesity-associated reductions in levels of physical activity may be associated with increased sympathetic activity and the development and progression of benign prostatic hyperplasia.1

Testosterone levels in obese men may be low compared with normal-weight men due to increased conversion to oestradiol in adipose tissue. Oestrogens play an important role in activating M3-muscarinic receptors, and this can lead to detrusor muscle overactivity and symptoms of an overactive bladder.1

In this field,  future studies could include:1

• The role of lifestyle modifications on LUTS incidence and severity
• Molecular mechanisms of local circadian rhythms in the bladder.

Conclusions

The authors conclude that research into the mechanisms linking LUTS and MetS will build towards new therapeutic strategies for prevention and treatment of these multifactorial conditions.1

Report on: Lower urinary tract symptoms and metabolic disorders: ICI-RS 2014. Denys M-A, Anding R, Tubaro A, Abrams P, Everaert K. Neurourol Urodyn 2016; 35(2): 278–282.