Asymptomatic Bacteriuria, Hyponatremia and Geri-atric Syndrome

Study Overview
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Brief Summary
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The population is aging. Aged people are more prown to develop frailty. The causes of frailty are multifactorial and are being investigated in research settings. Cardiovascular diseases, inflammaging and changes in microbiota have been associated with frailty and geriatric syndrome. The prevalence of asymptomatic bacteriuria and SIADH-related hyponatremia is also important in aging and associated with inflammaging. The aim of this study is to examine, if asymptomatic bacteriuria and SIADH-related hyponatremia could be markers for frailty and geriatric syndrome.

Detailed Description
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The demographic evolution represents a challenge for the general public health. The global population, especially in the developed countries, is aging. Aging is associated with a decrease of physio-logical functions leading to frailty. Frailty is an important concept in geriatric medicine: it is a biological syndrome of decreased reserve and resistance to stressors resulting from cumulative decline across multiple physiological systems (like osteopenia, sarcopenia, dysregulation of hypothalamic axis …). Factors that lead to frailty influence each other and can be self-perpetuating. Frailty is a geriatric syndrome but there are a lot of other geriatric syndrome such as falls, undernutrition,… When young people are sick, they present mostly more than one symptom who can be referred to one disease or one cause. In contrast, geriatric patients will present one symptom, such as confusion, fall, undernutrition,… which can be referred to multifactorial causes or diseases. This is the concept of geriatric syndrome. Frailty or geriatric syndrome has been related to inflammaging. Inflammaging, characterized by an increase of circulating cytokines such as interleukin (IL)-6 and acute phase proteins, is a feature of immunosenescence. This process of immunosenescence is suggested to participate in the pathogene-ses of frailty and geriatric syndromes. The possible origins of inflammaging are multifactorial and controversies still exist: cardiovascular (CV) diseases, depression and chronic cytomegalovirus (CMV) infections are associated with this pro-inflammatory state. These comorbidities are highly prevalent in geriatric patients and could therefore contribute to the association between low-grade inflammation, frailty and geriatric syndromes. The intestinal barrier and microbiota are associated with frailty and inflammaging. Multiple potential pathways exist through which the gut microbiota can provoke inflammaging (through TLR, stimulation of immune cells, translocation, endotoxines et cetera). In the same way of thinking, asymptomatic bacteriuria could also be responsible of inflammaging and frailty. The prevalence of asymptomatic bacteriuria is increased with aging and in patient with diabetes. It has also been shown to be associated with chronic inflammation (sTNFR and TNFα), increased WBCC and neutrophils. To our knowledge, it is unknown if asymptomatic bacteriuria is associated with frailty. Hyponatremia is highly prevalent in hospitalized patients. SIADH-related hyponatremia represents 1/3 of the causes of hyponatremia. The incidence of SIADH related hyponatremia is believed to be higher in older people. It is associated with an increased risk of falls, confusion and mortality. The physiological balance between water and salt changes with aging. SIADH is classified as an euvo-lemic status; however, it is caused by an excess of water. The inappropriate secretion of vasopressin( ADH=anti-diuretic hormone) increases the expression of the aquaporins in the renal tubules. These aquaporines increase the reabsorption of water resulting in an altered ratio of reabsorption of water and Salt, leading to hyponatremia. SIADH-related hyponatremia is also associated with inflammation. IL-6 and IL-1β are able to stimulate the pituitary-hypothalamic axis to secrete vasopressin. SIADH related hyponatremia could be also a sign of inflammaging and related with frailty.

Official Title
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Asymptomatic Bacteriuria, Hyponatremia and Geri-atric Syndrome

Conditions
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Asymptomatic Bacteriuria, Frailty, Geriatric Syndrome, SIADH

Intervention / Treatment
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* Diagnostic Test: urine sample
* Diagnostic Test: Blood and urine sample


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 70 years old Informed consent Presence of the geriatric syndrome (dementia, depression, frailty, dependence, fall, undernu-trition, incontinence…) or not in function of the group Exclusion Criteria: Symptoms of urinary tract infection Confusion CRP > 5 mg/L Previous urological history Intake of antibiotics Intake of diuretics Intake of SSRI

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: academic, prospective study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Frailty or more<br>patients with the geriatric syndrome who will be recruited at the geriatric out patient clinic | Diagnostic Test: urine sample<br>* Each participant will give a urine sample for diagnose of asymptomatic bacteriuria<br>Diagnostic Test: Blood and urine sample<br>* Each participant will give a urine and blood sample for diagnose of SIADH<br>|
| Placebo Comparator: healthy<br>healthy aged people defined as in the modified SENIEUR protocol who will be recruited by an extern call thanks UZ Brussel website of thanks to staff's knowledge | Diagnostic Test: urine sample<br>* Each participant will give a urine sample for diagnose of asymptomatic bacteriuria<br>Diagnostic Test: Blood and urine sample<br>* Each participant will give a urine and blood sample for diagnose of SIADH<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| asymptomatic bacteriuria | If the presence of an asymptomatic bacteriuria is associated with frailty or the geriatric syn-drome | At baseline | 
| SIADH | If the presence of SIADH-related hyponatremia is associated with frailty or geriatric syn-drome | At baseline | 
| SIADH and inflammaging | If the presence of SIADH-related hyponatremia is associated with a low grade chronic in-flammation as demonstrated by a raised c-reactive protein (CRP). | At baseline |