Frailty increases the risk for developing urinary tract infection among 79,887 patients with diabetic mellitus and chronic kidney disease

Abstract

Background Patients with diabetic mellitus (DM) and chronic kidney disease (CKD) are at an increased risk of urinary tract infection (UTI) due to their altered immunological integrity. These patients are similarly prone to developing frailty, a state of cumulative health deficits involving multiple domains and leading to adverse outcomes. Whether frailty predisposes affected individuals to UTI among patients with DM and CKD remains unclear. Methods A population-based cohort of patients with DM and CKD (n = 79,887) were assembled from the Longitudinal Cohort of Diabetes Patients, with their baseline frailty status measured by a modified FRAIL scale. We analyzed their risk of developing UTI depending on their severity of frailty, after accounting demographic profiles, lifestyle factors, comorbidities, concurrent medications, and major interventions. A secondary analysis focused on the risk of urosepsis related to frailty. Results Among all participants, 36.1 %, 50.3 %, 12.8 %, and 0.8 % did not have or had 1, 2, and ≥ 3 FRAIL items, respectively, at baseline. After 3.51 years, 11,175 UTI events occurred. Kaplan-Meier analysis showed that participants with DM, CKD and an increasing number of FRAIL items had successively higher incidence of UTI than those without any FRAIL items (log rank p < 0.001). Cox proportional hazard modeling revealed that after accounting for all confounders, those with more severe frailty exhibited a significantly higher risk of incident UTI (for groups of 1, 2, and ≥ 3 FRAIL items, hazard ratio 1.19, 1.24, and 1.43, respectively; all p < 0.001) than those without. An 11 % risk elevation for UTI could be observed for every FRAIL item increase. Participants with more severe frailty exhibited a trend of having higher risk of urosepsis as well. Conclusions Having frailty predicted a higher risk of developing UTI in the future in patients with DM and CKD. It would be prudent to screen for frailty in these patients and provide optimal frailty-directed management to attenuate their risk of UTI and improve their outcomes.

Systematic Review of Literature Examining Bacterial Urinary Tract Infections in Diabetes

“…Multiple studies have shown that diabetes increases the risk for UTI complications such as recurrent UTI, bacteremia, requiring hospitalization for UTI treatment, and 30-day mortality: (i) In elderly individuals with diabetes-associated chronic kidney disease (CKD; N = 79,887; mean age = 59.6 years), the presence of age-associated frailty was a significant risk factor of UTI and urosepsis [ 63 ]; (ii) in a study from Greece, diabetic individuals (DM = 19; no DM = 81; median age = 60 years) were more susceptible to recurrent UTI (defined as ≥3 UTI in one year) with an OR of 5.5 ( P = 0.006) [ 64 ]; (iii) in an Australian study (DM = 396; no DM = 2391; overall mean age = 37.1 years), diabetic individuals were more likely to be hospitalized for UTI treatment (OR calc = 2.8; P < 0.001) requiring ~1.5 days longer hospital stay ( P = 0.04) compared to nondiabetics [ 65 ]; (iv) in a matched control study from the US ( N = 179,580; mean age = 56 years), compared to nondiabetics, the UTI recurrence within three months of first diagnosis of T2DM was ~3-times ( P < 0.0001) more common [ 66 ]; (v) in a prospective study of hospitalized diabetic patients with advanced CKD (glomerular filtration rate< 30 ml/min; N = 88; mean age = 68 years), individuals with higher fasting glucose showed slower (> 9 days) renal recovery after an episode of UTI and ~ 3 times higher susceptibility to developing Gram negative bacteremia [ 67 ]; (vi) in a study of elderly Dutch individuals, compared to nondiabetic controls ( N = 718, median age = 64 years), diabetic individuals ( N = 140; median age = 73 years) were at higher risk of recurrent UTI (OR (adjusted for age and cardiovascular disease) = 2.2; P = 0.017, higher risk for bacteremia (OR = 1.2; P = 0.037), and higher risk of 30-day mortality (OR = 2.0; P = 0.007) [ 40 ]; (vii) in a retrospective study from Taiwan, diabetic patients with late-stage CKD (glomerular filtration rate ≤ 30 ml/min; N = 225; mean age = 63.5 years) had an increased risk of acute kidney injury following an episode of UTI [ 68 ]; (viii) in a cohort of Japanese patients requiring hospitalization for the treatment of bacteremia resulting from UTI ( N = 70; mean age = 68 years), 17.1% were diabetic [ 69 ]; (ix) compared to nondiabetic controls ( N = 81; mean age = 66 years), diabetic patients with E. coli UTI ( N = 190; mean age = 69 years) showed a 1.2-fold higher incidence of urosepsis [ 57 ]; (x) in a cohort of elderly hospitalized for UTI treatment ( N = 251, mean age = 65.3 years), DM significantly increased the risk for death (OR = 22.66; P < 0.01) in a 30-day period following hospitalization [ 70 ]; and (xi) in a cohort of Dutch women, compared to nondiabetic controls ( N = 6958; mean age = 51 years), diabetic subjects ( N = 340; mean age = 65.5 years) were at a higher risk of recurrent UTI (OR (adjusted for age) = 2.0; P < 0.001) [ 71 ]. In summary, it is evident from clinical data that diabetes significantly increased risk of UTI complications such as recurrent UTI, bacteremia, and for requiring hospitalization for UTI treatment, with an important caveat that in majority of studies examining association between DM and UTI complications, diabetic subjects are ≥60 years of age.…”

“…The results from such analyses reveal that both age and female sex increase the risk of UTI independent of DM, although diabetic women are at >3-fold increased risk of ASB and UTI in comparison to men as shown in Table 5 and that the magnitude of UTI risk is different at each age category [ 66 , 76 , 77 , 96 – 99 ]. Moreover, among diabetic individuals, old age and age-associated frailty increase UTI risk by ~2-fold and the need for hospitalization for the treatment of UTI by 1.45-fold [ 63 , 96 , 100 ].…”

COVID-19 prevalence and mortality in longer-term care facilities

“…Frailty has been linked to elevated COVID-19 mortality among LTCF residents, reflecting a combination of increased incidence of infection as well as more adverse consequences—the same combination that has been observed for other infectious diseases. [ 62 , 63 ] Individuals with severe frailty or cognitive deficiencies require extensive assistance with daily routines and hence greater exposure if a staff person becomes infected. Moreover, frailty has a strong association with immune dysregulation that is likely to exacerbate vulnerability to COVID-19 as with other infectious diseases.…”

Association between indoor microbiota, home environment characteristics, and frailty status of elderly residents

“…Lodderomyces and Trichoderma are widespread fungi occurring in nature and are potential opportunistic pathogens associated with in ammation and infection in immunocompromised hosts [37,38]. Moreover, frail individuals are at a higher risk of developing urinary tract infections due to an immunocompromised status [39], and infectious arthritis compared to younger adults [40,41]. Brevibacterium and Aerococcus are common pathogens in urinary tract infections [42], of which Aerococcus is also a common pathogen causing joint infections [43].…”